THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES Digitized by the Internet Archive in 2014 https://archive.org/details/systematicorganiOOcumm_0 / SYSTEMATIC ORGANIC CHEMISTRY MODERN METHODS OF PREPARATION AND ESTIMATION / SYSTEMATIC ORGANIC CHEMISTRY MODERN METHODS OF PREPARATION AND ESTIMATION BY WILLIAM M. CUMMING B.Sc, F.l.C. Lecturer on Organic Chemistry in The Royal Technical College Glasgow ; late of British Dyestuffs Corporation, Ltd. I. VANCE HOPPER B.Sc, A.R.C.Sc.I., F.l.C. Lecturer on Organic Chemistry in The Royal Technical College^ Glasgow ; late of British Dyestuffs Corporation, Ltd. AND T. SHERLOCK WHEELER B.Sc, A.R.C.Sc.I, A.l.C. Chemist, Research Department, Royal Arsenal, Woolwich ; late of The Royal Technical College, Glasgow. * * 1 D to ■■> t 1 3 1 NEW YORK D. VAN NOSTRAND COMPANY EIGHT WARREN STREET 1926 86395 PRINTED IN GREAT BRITAIN R v m PREFACE The present work is intended as a complete laboratory guide to the preparations and estimations of organic chemistry for undergraduate and post-graduate students. ' An endeavour has been made to introduce J up-to-date methods, some of which are. new, having been developed by j the authors. In all cases sufficient practical details are given to enable a o beginner, with the aid of the sections on apparatus and methods, to carry out the necessary operations for himself. The research student, it is hoped, will often find within, the preparations required. To meet the needs of the many students whose ultimate interests are likely to be industrial, several manufacturing methods are described on a laboratory scale. An industrial experience which has been invaluable to the authors in their duties as teachers, has led them to include a few notes on costing, since they feel that this subject, of such vital importance in industry, is neglected in our technical institutions. ^ References to the original literature have been given after almost every ^ preparation, thus affording a means of amplifying, if desired, the practical ^details. Stress has been laid on the value of consulting original papers through the media of the lexicons of Bichter, Beilstein and Stelzner. Lists of suggested preparations have been included. It is believed that greater interest is developed when the student works through a a sequence of preparations which are more or less intimately connected. *L The authors have striven to make the book something more than a ^ collection of recipes. Owing to deficiencies in the teaching of the subject, there is to : day a tendency for the student to think that there is a lecture- room and a laboratory variety of organic chemistry. To such an extent does this division exist that a student who in the lecture-room knows the general method for the preparation of, say, anhydrides, in the laboratory is quite at sea when asked to prepare any anhydride other than that of acetic acid. To combat this, the preparations of several compounds of a ^ given type have been included in most sections of the book. Many reactions of purely theoretical interest have been incorporated, so that the student may gain some real idea of the possibilities of his subject, and that he may feel his practical and theoretical text-books to be very near akin. Indeed, the authors trust that from a theoretical standpoint alone the student may find the book useful in that it will enable him to view his subject from an angle different to the usual, and in this way to gain perspective. The better to accomplish this, they have introduced a new classification of organic reactions in which reaction follows reaction on a definite plan. They hope that the student who carefully reads through this book will not only have acquired much varied vi PREFACE theoretical and practical knowledge, but also that his purely theoretical books will take on a new meaning, and that even their current jargon of " reducing A with HI " and " distilling B with lime " will be for him ) something more than a form of words. Identifications have not been dealt with beyond including some few tests and tables of reactions. A section has been included dealing with the preparation of such inorganic compounds as are largely used in organic chemistry, and on the correct preparation of which much may depend. The authors would here emphasise th e importance of introducing "oleum" of all strengths into the teaching laboratories of this country. It is of great industrial importance, cheap, and not dangerous when properly handled. The section on estimations is rather more comprehensive than is given in most text-books of this kind, and is composed entirely of examples found to give good results in practice. The authors beg to acknowledge assistance received directly and indirectly from well-known text-books by the following authors — Adams \ and others, Barnett, Barrowcliff and Carr, Cain, Cain and Thorpe, Cohen, Elbs, Fiertz-David, Fischer, Grattermann, Henderson, Knecht and Hibbert, Lassar-Cohn, Hans Meyer, Meyer- Jacobson, Meyer-Tingle, Perkin F. M., Sudborough and James, and Ullmann. They wish to express their thanks to Professor F. J. Wilson ior his kindly interest and valuable suggestions ; to Professor I. M. Heilbron for useful advice ; to Mr. A. B. Crawford, B.Sc., A.R.T.C., A.I.C., and Mr. E. C. Pickering, B.Sc, A.I.C., for reading the proofs ; and to Messrs. Constable & Co. for the way in which they have carried out their share of the work. They desire to acknowledge specially the assistance rendered by Mr. , James Connell, B.Sc, A.I.C., in drawing the illustrations for the book. The authors will be grateful for any suggestions or for notification of any errors. The Royal Technical College, Glasgow. W. M. C. AND I. V. H. Research Department, Royal Arsenal, T. S. W. Woolwich. ! ABBREVIATIONS A. T ,ipnirr « Atitiq lfn r I or* t homi'o -LiltJUlg b -rillllcLlcIl U-ci V^IltJIIlltJ. A. Spl. Ssn t^t^I pm on "f" T ,i d Ki rr a A nriQ Ion r1or» Pnomm oupjjitjiutJiiu, xjifDuiQ b i^.iiiiciit;ii u.(3i v^neiiiie. A. Ch. a nn£i ma rip ^Viotyiio ot - T-^Vn7CJir*no xxllXlctltJo Lit? VyllcIIllt? t?L Jt Iiy biqUt?. A m Sr*r* Journal of the American Chemical Society. B. JL>C-1 l^llLO JL/tJU. LoOlltJIl dltJJlllbL-IltJll V^Ubt;llbCIl<*l L. B.P. "Roilinor T^riin'f" Bi. '. rvfi 1 Ifvtii n Hp 1^, SsriPipf",p pniminnp hp "Paimo. C. fIVi pm iqpVi pa f Ipti t~t*£1 1 nl a T"f WlidllibOIlcb v^t>ll LI ct l U let it, C. N. Chemical News. C. r. '. Comptes rendus de l'-Academie des Sciences. C. T. (IVi omi P£i 1 r F 1 T'Qflp .T<~»n i*n ti 1 d z. ! ! Chemiker Zeitung. D. SsTIPPlri P (nrT*£l VI kj L/C'V^J.IH-' V^ld V 11 y • D.R.P. nprmfln T-^si+pn'f V.7 Ul illctll JT d L/Ollt. E.P. "Rti^igIi Pafprrl" JJIIUOU X dlClll, F.P. G. V-TdZjiiCLtaj dllllllL-ct 1 Lctllctllct. J. .Ta Tirp^lipriplif, Hpt* plnpmip J. c. s. OOU.Lli.cli. VI tilt? v^lltulllbcll QOCloty. J. Eng. UOUIllctl Ol XIllAUbLllctl dllU. XLill^lllct^lllli^ V^IlcIIllb LI V • J. pr. T T? P Q U. JLV. V/. o. O OUIIlctl Ol LIlc XvUbblctll vyllt?11110) Action of Heat on the Compound formed by treating Grignard Reagent with a Ketone in absolute Ethereal -Solution . . 62 (c) Action of Dimethyl Sulphate on Magnesium Alkyl or Aryl Halide (Grignard) . . . . . . .63 | Reaction X. — Action of Zinc Alkyl on Alkyl Halides ... 64 CHAPTER IV Hydroxy Compounds Reaction XI. — Intramolecular Elimination of Water from certain Molecules .......... 65 Reaction XII. — Reduction of Aldehydes and Ketones to Pinacones . 65 Reaction XIII. — Condensation of a Phenol with Formaldehyde . . 66 Reaction XIV. — (a) Action of Magnesium Alkyl or Aryl Halide on Aldehydes and Ketones (Grignard) ..... 67 (b) Action of Magnesium Alkyl or Aryl Halide on Esters, Acyl Chlorides and Acid Anhydrides . . . . 70 Reaction XV. — Action of Zinc Alkyl on Aldehydes, on certain Ketones, •and on Acyl Chlorides . . . . . . .71 Reaction XVI. — Action of certain Oxidising Agents on a- and (3- Naphthols ......... 72 7 CHAPTER V Oxy Compounds Reaction XVII. — Intramolecular rearrangement of the Glycols (Pinacoline Transformation) ...... 74 Reaction XVIII. — Ring Formation by Elimination of Water from certain Molecules . . . . . . . .75 Reaction XIX. — (a) Condensation of Anthranol Derivatives with Glycerol . . . . . . . 78 (b) Condensation of Anthranol Derivatives with Formaldehyde . 79 Reaction XX. — (a) Action of Metallic Zinc on a Mixture of an Aromatic Hydrocarbon and a Derivative of Phthalyl Chloride . . 79 (b) Action of certain Anhydrous Metallic Halides on a Mixture of an Aromatic Hydrocarbon or certain Derivatives and an Acyl Halide (Friedel-Crafts) 80 (c) Action of a Mixture of Aluminium and Mercuric Chloride on a Mixture of an Aromatic Hydrocarbon and an Alkyl Halide . 84 (d) Combined Action of Carbon Monoxide and Hydrogen Chloride on an Aromatic Hydrocarbon in presence of a Mixture of Anhydrous Aluminium and Cuprous Chlorides (Gattermann- * Koch) . . . 85 Reaction XXI. — (a) Dry Distillation of the Barium or Calcium Salt of a Fatty Acid with Barium or Calcium Formate . . 86 (b) Dry Distillation of the Barium or Calcium Salts of Fatty Acids 86 (c) Action of Acetic Anhydride on Carboxylic Acids and subsequent y Distillation ..... v ... 87 (d) Catalytic Action of its Manganese Salt on the Vapour of a Fatty Acid 88 xii CONTENTS Reaction XXII. — {a) Action of Magnesium Alkyl or Aryl Halide on (i.) excess of Ethyl Formate, (ii.) Ethyl Orthoformate, (iii.) di -substituted Formamide and other Derivatives of Formic Acid (Grignard) ....... 89 (b) Action of Magnesium Alkyl or Aryl Halide on (i.) Nitrites, fii.) Amides (Grignard) ....... 89 (c) Action of Zinc Alkyl on Acyl Chlorides in certain proportions . 90 Reaction XXIII. — (a) Condensation of Ethyl Formate with certain Oxy Compounds under the influence of Sodium Ethoxide (Claisen) 90 (b) Condensation of Esters other than Ethyl Formate with certain Ketones under the influence of Sodium E thy late, Metallic Sodium, or Sodamide (Claisen) . . . . . .91 Reaction XXIV. — Condensation of certain Oxy Compounds with one another under the influence of Dehydrating Agents . . 93 Reaction XXV. — Action of an Alkyl Halide on the Sodio -derivative of certain Ketones. ........ 94 CHAPTER VI Hydroxy-oxy Compounds Reaction XXVI. — (a) Condensing Action of Potassium Cyanide, Potassium Carbonate, or other substances on Aliphatic (Claisen), and Aromatic Aldehydes (Liebig) . . . .95 (6) Condensing Action of Potassium Cyanide on a Mixture of an Aliphatic Aldehyde and a Ketone ..... 97 Reaction XXVII. — Condensation of Chloroform with Phenols and simultaneous Hydrolysis of the Product (Reimer-Tiemann) . 98 Reaction XXVIII. — Formation of an Aldime by the action of Hydrogen Chloride and Hydrogen Cyanide (HCN.HC1) on a Phenol or a Phenol Ether in the presence of Anhydrous Aluminium Chloride, and the Hydrolysis of the Aldime so formed (Cattermann) . 100 Reaction XXIX. — (a) Condensation of a Phenol with Phthalic Anhydride to form a Phthalein . . . . .100 (b) Condensation of a Phenol with Phthalic Anhydride to a deriva- tive of Anthraquinone . . . . . . .102 (c) Condensation of Meta-hydroxy- and Di-meta-dihydroxy-benzoic Acids with themselves and with Benzoic Acid under the action of hot Sulphuric Acid . . . . . .103 Reaction XXX. — Condensation of a Mtrile with a Phenol or a Phenol Ether and Hydrolysis of the resulting Ketimine Hydrochloride to a Ketone . . . . . . . . .103 Reaction XXXI. — Action of Heat on Sodium Formate . . .105 Reaction XXXII. — Action of Alkalis on certain a-di-ketones . . 105 Reaction XXXIII. — (a) Condensation of an Aromatic Carboxylic Acid with Formaldehyde (Lederer-Manasse) .... 106 (b) Condensation of Malonic Acids with Aldehydes or some Ketones under the influence of Primary and Secondary Amines 106 (c) Condensation of Aldehydes with Malonic Acid in the presence of Alcoholic Ammonia . . . . . . 107 (d) Condensation of Aldehydes with the Sodium Salts of certain Acids in the presence of Acid Anhydrides (Perkin) . 107 (e) Condensation of the Dichlorides of Aromatic Aldehydes with the Sodium Salts of certain Acids ..... 109 CONTENTS xiii Reaction XXXIV. — {a) Condensation of Carbon Dioxide with a Phenol (Kolbe-Schmitt) . . . . . . .110 (b) Action of Carbon Dioxide on an Organo -magnesium Halide . 112 (c) Action of Carbon Dioxide on Sodium Acetylides in Dry Ether 115 Reaction XXXV. — (a) Condensation of Phthalic Anhydride with Aromatic Hydrocarbons in the presence of Anhydrous Alumi- nium Chloride (Friedel-Crafts) . . . . . .115 (b) Condensation of Phthalic Anhydride with Phenols in the presence of Anhydrous Aluminium Chloride, s-tetrachloroethane being used as a Solvent . . . . . . .117 Reaction XXXVI. — Condensation of Carbon Tetrachloride with Phenols and simultaneous Hydrolysis . . . . .117 Reaction XXXVII. — Action of finely divided Metals on Halogen Acids 117 Reaction XXXVIII. — {a) Action of Aqueous or Alcoholic Potassium or Sodium Cyanide on Aliphatic Halogen Compounds and Hydrolysis of the Nitriles so formed . . . . .118 General Methods of Isolating Organic Acids from their Salts. . 121 (b) Action at 200° of Aqueous or Aqueous-alcoholic Potassium Cyanide in presence of Cuprous Cyanide on Aromatic Halogen Compounds, and Hydrolysis of the Nitriles so formed . . 121 (c) Action of Halogen Cyanide on Aldehydes and Ketones, and Hydrolysis of the Cyanhydrins so formed . . . .121 Reaction XXXIX. — Fusion of the Salts of Aromatic Sulphonic Acids with Sodium Formate . . . . . . .124 Reaction XL. — Condensation of a Phenol with a " Methane Carbon Atom " . . 124 CHAPTER VII Oxide-oxy Compounds Reaction XLI. — Elimination of Water from o-Phenoxy-benzoic Acids 126 Reaction XLII. — Prolonged action of Heat on Ethyl Aceto-acetate . 127 Reaction XLIII. — (a) Formation of Esters by the action of Acid Anhydrides or of Acid Chlorides on an Alcohol in the presence of Magnesium Alkyl Halide (Crignard) . . . .128 (b) Formation of Ethyl Esters by the action of Ethyl Chloro- formate on Magnesium Alkyl Halide in Dry Ethereal Solution 128 (c) Condensation of a-Halogen Fatty Acid Esters with Aldehydes and Ketones by means of Zinc or Magnesium (Reformatsky- Grignard) . . . . . . . . .128 (d) Condensation of Di-ethyl Oxalate with Alkyl Halides in the presence of Zinc (Frankland-Duppa) ..... 130 Reaction XLIV. — (a) Condensation of Alkyl and Aryl Halides with Ethyl Sodio-malonate and its Homologues .... 130 (b) Condensation of Alkyl and Aryl Halogen Compounds with the Sodio- and other Metallo- derivatives of Aceto -acetic Ester and its Homologues ......... 132 (c) Condensation of Alkyl and Acyl Halides with the Sodio -deriva- tives of Cyanacetic Ester . . . . . . .137 Reaction XLV. — Condensation of Aldehydes and Ketones with certain Esters under the influence of Acetic Anhydride, Hydro- chloric Acid, Sodium Ethoxide or certain Bases . . . 137 Reaction XL VI. — Condensation of an Ester with itself or with another Ester by means of Sodium Ethoxide or Sodamide (Claisen) . 140 Reaction XL VII. — Condensation of an Ester with itself by the action of Iodine on its Sodio -derivative . . . . . .144 XIV CONTENTS CHAPTEE VIII Nitrogen Compounds page Keaction XLVIII. — (a) Action of Alkali Cyanides on Alkyl and Acyl Halides .......... 146 (b) Action of Alkali Cyanides on Alkyl Halogen Sulphates . .147 (c) Action of di-methyl Sulphate on Potassium Cyanide . . 148 Keaction XLIX. — {a) Action of Cuprous Potassium Cyanide on Aromatic Diazonium Compounds (Sandmeyer) . . . 149 (b) Action of finely divided Copper and Alkali Cyanides on Aromatic Diazonium Compounds . . . . . . .150 Keaction L. — (a) Addition of Hydrogen Cyanide to Aldehydes or Ketones .......... 150 (b) Condensation of an Aldehyde with Ammonia and Hydrogen Cyanide ... . . . . . . . 152 (e) Action of Hydrogen Cyanide on Quinones . . . .154 Reaction LI. — {a) Action of Acids on the non-para substituted Hydrazo compounds ......... 155 (b) Molecular rearrangement of Di-benzanilides . . . ' .156 Keaction LIL — (a) Action of Copper Powder on 2- and 4-mono-nitro- and 2 : 4-di-nitro-chloro- and bromo -benzenes and their Homologues . . . . . . . . . 157 (b) Action of Cuprous Chloride on Nitro -diazonium Compounds . 157 Reaction LIII. — Action of Aceto-acetic Ester on Aldehyde Ammonias 158 Reaction LIV. — (a) Condensation of Non-di-ortho-substituted Primary Aromatic Amines with Acrolein (Skraup) . . . . 159 (b) Condensation of Primary Aromatic Amines other than Ortho- substituted with two Molecules of certain Aldehydes (con- taining the group — CH 2 CHO) under the influence of Sulphuric or Hydrochloric Acid . . . . . . .162 (c) Condensation of o-Amino-benzaldehydes with aldehydes, ketones, aceto-acetic ester, etc., under the influence of a trace of Sodium Hydroxide, to give quinoline derivatives . .163 Reaction LV. — Intramolecular condensation of Phenyl Hydrazones of Aldehydes, Ketones, and Ketonic Acids by heating with Hydrochloric Chloride or Zinc Chloride . . . .164 THE LINKING OF HYDROGEN TO GABBON CHAPTER IX Hydrogen Compounds Reaction LVI. — Action of Water on certain Metallic Carbides . .166 Reaction LVII. — Action of Hydrogen in the presence of finely divided Nickel on Aromatic Compounds . . . . . .167 Reaction LVIII. — (a) Reduction of Phenols and Quinones by Distilla- tion with Zinc Dust . . . . . . . .170 Purification of Crude Anthracene . . . . . .171 (b) Reduction of Aromatic Ketones to the corresponding Hydro- carbons by treatment with Hydriodic Acid or with Sodium in Alcoholic Solution . . . . . . . .171 Reaction LIX. — Reduction of a Primary Aryl Hydrazine to the corresponding Hydrocarbon by the action of Copper Sulphate or Ferric Chloride . . . . . . . . 172 Reaction LX. — Action of Water on Magnesium Alkyl or Aryl Halides 173 Reaction LXI. — Reduction of Diazonium Compounds to the corre- sponding Hydrocarbon . . . . . . .174 CONTENTS xv Keaction LXII. — Direct reduction of Halogen Compounds . 17.-) Purification by Fractional Liquefaction or Evaporation . 176 CHAPTER X Hydroxy Compounds (Alcohols and Phenols) , Reaction LXIII. — Combined Oxidation and Reduction of Aromatic Aldehydes under the influence of Caustic Alkalis . . .178 Reaction LXIV. — (a) Reduction of Aldehydes and Ketones to the corresponding Alcohols by the use of Alkaline Reducing Agents 179 (b) Reduction of Aldehydes and Ketones to the corresponding Alcohols by the use of Acid Reducing Agents . . .180 (c) Reduction of Quinones . . . . . .181 CHAPTER XI oxy and hydpvoxy-oxy compounds (aldehydes, ketones and Acids) Reaction LXV. — (a) Reduction of Phenolic Acids to the corresponding Aldehydes by the action of Sodium Amalgam and Boric Acid in the presence of a Primary Aromatic Amine . . .183 (b) Reduction of Lactones to the corresponding Hydroxy Aldehydes by the action of Sodium Amalgam in faintly Acid Solution . 184 Reaction LXVI. — {a) Reduction of Unsaturated Acids by means of Sodium Amalgam in Alkaline Solution . . . .185 (b) Reduction of Hydroxy Acids by the action of Hydriodic Acid. 186 Reaction LXVII. — (a) Ketonic Hydrolysis of Alkyl Derivatives of Aceto-acetic Ester . . . . . . . .187 (b) Acid Hydrolysis of Alkyl Derivatives of Aceto-acetic Ester . 188 , CHAPTER XII Halogen Compounds Reaction LXVIII. — Simultaneous reduction and Halogenation of Polyhydric Alcohols . . . . . . . . 190 Reaction LXIX. — Partial reduction of Tri-halogen to Di-halogen Compounds . . . . . . . . 19^ THE LINKING OF OXYGEN TO CARBON CHAPTER XIII Hydroxy Compounds (Alcohols and Phenols) Reaction LXX. — Oxidation of certain Hydrocarbons . . .193 Reaction LXXI. — Replacement of Halogen by Hydroxyl . . .194 Reaction LXXII. — Replacement of the Diazo Group by Hydroxyl . 198 Reaction LXXIII. — Direct replacement of the Aromatic Ammo-group by Hydroxyl 201 Reaction LXXIV. — Action of Mineral Acids on Phenyl-hydroxylamine 203 Reaction LXXV. — Fusion of Aromatic Sulphonic Acids with Caustic Alkalis 213 Reaction LXXVI. — Addition of Hydroxyl to Ethvlenic Bonds. . 205 Purification of Methyl Alcohol 206 Purification of Ethyl Alcohol 207 xvi CONTENTS CHAPTER XIV 1 Oxide Compounds (Ethers) page ( Reaction LXXVIL— Action of Sulphuric Acid on an Alcohol or a Mixture of Alcohols ........ 208 Purification of Commercial Ether ...... 209 • Reaction LXXVIII. — Action of Alkyl Halides on Alkali Alcoholates or Phenates . . . . . . ... - . . 209 Reaction LXXIX. — Action of Dimethyl Sulphate on Hydroxy Com- pounds . . . . . . . . . .211 Reaction LXXX. — Action of very Dilute Methyl Alcoholic Hydrogen Chloride on the Sugars . . . . . . 214 ' Reaction LXXXI. — Action of Hydrogen Chloride on a Mixture of an Aldehyde and an Alcohol . . . . . . .215, Reaction LXXX II. — Condensation of an Aldehyde with itself under the action of Mineral Acids or of Calcium Chloride . . 215 Reaction LXXX III. — Action of Caustic Alkali on a, /3-chlorhydrins . 216 a Reaction LXXXI V. — Addition of Phenols to Quinones . . .217 CHAPTER XV Oxy Compounds (Aldehydes, Ketones and Quinones) « Reaction LXXXV. — Simultaneous Oxidation and Hydrolysis of Mono -halogen Compounds .... . . 219 ^, Reaction LXXX VI. — Hydrolysis of certain Di-halogen Compounds . 219 Reaction LXXX VI I. — Hydrolysis of certain Anils .... 220 Reaction LXXX VIII. — Action of Nitrous Acid on the Monoximes of ^ o-Di-ketones . . . . . . . . .221 Reaction LXXXIX. — Hydrolysis of Nitriles to Amides . . . 222 Reaction XC. — Hydrolysis of the Di-saccharoses .... 223 Reaction XCI. — (a) Oxidation of Aromatic Hydrocarbons to Aldehydes by the action of Chromyl Chloride in Carbon Disulphide Solution (Etard) 224 f (b) Oxidation of Aromatic Hydrocarbons to Aldehydes by the action of Chromic Acid in Acetic Anhydride Solution . . 225 (c) Oxidation of Aromatic Hydrocarbons to Aldehydes by the action of Cerium Dioxide in presence of Concentrated Sulphuric Acid 225 Reaction XCII. — Action of Oxidising Agents on Methylene Groups in Aromatic Compounds ....... 226 Reaction XCIII. — Oxidation of Aromatic Hydrocarbons to Quinones . 227 Reaction XCIV. — Oxidation of Primary Aromatic Amines and their ;para-substituted Derivatives to Quinones ..... 228 CHAPTER XVI Hydeoxy-oxy Compounds (Acids) Reaction XCV.— Hydrolysis of Nitriles 232 Reaction XCVI. — Hydrolysis of Esters to Acids .... 234 Reaction XCVII. — Hydrolysis of Amides, Acyl Chlorides and Acid Anhydrides 236 Reaction XCVIIL — Simultaneous Oxidation and Hydrolysis of Benzyl and Benzal Chlorides and their Derivatives . . 236 Reaction XCIX. — Oxidation of certain Carbon Compounds to less Complex Compounds ........ 237 CONTENTS xvii PAGE Eeaction C. — Oxidation of the Side Chain in Aromatic Compounds . 237 Reaction CI. — (a) Oxidation of Primary Alcohols to the corresponding Carhoxylic Acids . . . . . . . .241 (b) Oxidation of Aldehydes to Carboxylic Acids . . . 242 CHAPTER XVII Oxide-oxy Compounds (Esters and Acid Anhydrides) Reaction CII. — Direct Action of an Acid on an Alcohol . . . 246 Reaction CIII. — Continual removal of Water in a suitable Apparatus. 248 Reaction CIV. — Use of Concentrated Sulphuric Acid or of Hydrogen Chloride to promote Esterification . . . . . 249 Reaction CV. — Action of Acid Anhydrides on Alcohols and Phenols . 251 Reaction CVI. — Action of Acyl Chlorides on Alcohols . . . 253 Reaction CVII. — Action of an Alkyl Iodide on the Silver Salt of an Acid . .256 Reaction CVIII. — Polymerisation of an Aldehyde to an Ester . . 257 Reaction CIX. — Action of Heat on certain Dibasic Acids . . . 257 Reaction CX. — Action of an Acyl Chloride on the Sodium Salt of an Acid 258 Reaction CXI. — Action of Dehydrating Agents on a Free Acid . . 259 Reaction CXII. — Action of certain Bases on Acyl Chlorides . . 260 THE LINKING OF NITROGEN TO CAEBON CHAPTER XVIII Nitro Compounds Reaction CXIII. — Action of Dilute Nitric Acid on some Organic Compounds . . . . . . . . .261 Reaction CXIV. — Action of Concentrated Nitric Acid on Aromatic Compounds . . . . . . . . .261 Reaction CXV. — Action of a Mixture of Concentrated Nitric and Concentrated Sulphuric Acids (mixed acid) on Aromatic Compounds ......... 262 Rules of Nitration 263 Analysis of a Mixed Acid ........ 263 The Isolation of Nitro Compounds ...... 264 Reaction CXVI. — Action of Nascent Nitric Acid on Aromatic Com- pounds in presence of Concentrated Sulphuric Acid . . 269 Reaction CXVII. — Action of Nitrous Fumes on certain Organic Com- pounds . . . . . . . • . .271 Reaction CXVIII. — Action of Nitrous Acid on Aromatic Amines in presence of Cuprous Salts (Sandmeyer) . . . .273 Reaction CXIX. — Action of Silver Nitrite on Alkyl Halides . . 273 Reaction CXX. — Action of Concentrated Nitric Acid on certain Sulphonic Acids 274 . Reaction CXXI. — Action of Tetranitromethane on Bases . . . 274 CHAPTER XIX Reaction CXXII. — Action of Phenols and Primary Aromatic Amines on Diazonium Compounds ....... 275 Reaction CXXIII. — Action of Nitrous Acids on Phenols, and Tertiary Aromatic Amines . . . . . . . .276 s.o.c. b xviii CONTENTS PAGE I Reaction CXXIV. — Action of Nitrous Acid on Secondary Amines, and subsequent Eearrangement of the Products. . . . 278 Eeaction CXXV.— Action of Alkyl Halides on Phthalimide (Potassium Salt) 279 Eeaction CXXVI. — Action of Hydroxylamine on Aldehydes and Ketones 279 ' Eeaction CXXVII. — Action of Acids. Acid Chlorides, Anhydrides and Phosphorus Pentachloride on Oximes (Beckmann) . .281 Eeaction CXXVIII. — Action of Phenylhydrazine, etc., on Aldehydes and Ketones ......... 282 Eeaction CXXIX. — Action of Semicarbazide on Aldehydes and Ketones 284 * Eeaction CXXX. — Formation of Amino Gruanidine Derivatives . 285 Eeaction CXXXI. — Formation of Semioxamazones .... 285 c Eeaction CXXXII. — Action of Aliphatic Halogen Compounds on Aliphatic or Aromatic Primary Amines . . . .286 Eeaction CXXXIII. — Action of Aromatic Halogen Compounds on t Ammonia or Amino Compounds . . . . . .289 Eeaction CXXXIV.— Action of Silver Cyanide on Alkyl Halides . 290 Eeaction CXXXV. — Action of Chloroform and Alcoholic Potash on Aliphatic and Aromatic Primary Amines .... 290 Eeaction CXXXVI. — Action of the Hydrochloride of a Primary Aromatic Base on the Base ...... 290 1 Eeaction CXXXVII. — Action of Bromine (or Chlorine) and Alkali on certain Amides and Imides (Hofmann) . . . . 291 i Eeaction CXXXVIIL— Action of Heat of Ammonium Salts . . 292 Eeaction CXXXIX. — Action of Ammonia on Esters, Acid Chlorides or Anhydrides . . . . . . . . . 293 Eeaction CXL. — Action of Ammonia on Phenols and Sulphonic Acids 294 Eeaction CXLI. — Action of Acids, Acid Anhydrides and Chlorides on Primary and Secondary Amines ...... 296 i Eeaction CXLII. — Action of Primary Aromatic Amines on Alcohols . 298 Eeaction CXLIII. — Condensation of Aromatic Aldehydes with Primary Aromatic Amines ........ 299 j Eeaction CXLIV. — Action of Ammonia on Aldehydes . . . 300 Eeaction CXLV. — Action of Nitrous Acid on certain Ketones . t . 301 THE LINKING OF SULPHUR TO CARBON CHAPTEE XX Sulphonic Acids Eeaction CXLVI. — Action of Concentrated Sulphuric Acid on Hydro- carbons or Substituted Hydrocarbons ..... 302 Isolation of Sulphonic Acids . . . . . . 302 Tests for Complete Sulphonation . . . . .303 Apparatus Used in Sulphonation . . . . . . 303 Eeaction CXLVII. — Action of Fuming Sulphuric Acid (oleum) on Hydrocarbons or Substituted Hydrocarbons . . . 305 Estimation of S0 3 in Oleum . . . . . . .305 Preparation of Oleum of a given Strength ..... 306 Eeaction CXLVII I. — Action of Chloro -sulphonic Acid on Hydro - *• carbons or Substituted Hydrocarbons . . . . 309 Eeaction CXLIX. — Intramolecular Eearrangement of Aromatic Amine Sulphates. . . . . . . . . .311 CONTENTS xix PAGE Reaction CL. — Action of Sulphites and Bisulphites on Substituted Hydrocarbons . . . . . . . . .312 (a) Replacement of Halogen . . . . . . 312 (b) Simultaneous Reduction and Sulphonation . . . .312 (c) Alkyl Sulphonic Acids . 312 (d) Olefinic Compounds . . ■ . . . . . .312 Reaction CLI. — Action of Poly-sulphates on certain Hydrocarbons . 316 Reactions of the Sulphonic Croup . . . . . • 316 CHAPTER XXI Reaction CLII. — Action of Sulphur and Sodium Sulphide on Aromatic Bases . . . . . . . . . \ 317 Reaction CLIII. — Action of Sulphur Dioxide on Aromatic Hydro- carbons in presence of Aluminium Chloride or Mercuric Chloride 318 Reaction CLIV. — Action of Sulphur Dioxide on a Diazonium Com- pound in presence of finely divided Copper . . . .319 Reaction CLV. — Action of Potassium Xanthate on Diazonium Com- pounds with Subsequent Hydrolysis and Oxidation . . 320 Reaction CLVI. — Action of Hydrogen Sulphide on Diazonium Com- pounds . . . . . . . . . . 320 Reaction CLVII. — Action of Hydrosulphides on Alkyl Halides or Sulphates, or on certain Aromatic Halogen Derivatives . 321 Reaction CLVIII. — Action of Phosphorus Pentasulphide on Acids or Alcohols 322 Reaction CLIX. — Action of Sulphonyl Chlorides on Hydrocarbons in presence of Aluminium Chloride . . . . . .322 Reaction CLX. — Action of Phosphorus Pentasulphide on Ethers . 322 Reaction CLXI. — Action of Sodium or Potassium Sulphide on Alkyl Halides or Alkyl Sulphates . . ■ . . . . 322 THE LINKING OF HALOGEN TO CARBON CHAPTER XXII Reaction CLXII. — Replacement of Oxygen and Hydroxyl by Halogens 323 Reaction CLXIII. — Addition of Halogen or Halogen Hydride to Unsaturated Compounds . . . . . . .331 Reaction CLXIV. — Replacement of Hydrogen by Nascent Halogen . 335 Reaction CLXV. — Replacement of Hydrogen by Use of Halogen Compounds ......... 336 Reaction CLXVL — Replacement of the Amino Croup by Halogen . 338 Reaction CLXVII. — Replacement of Halogen by Halogen. . . 340 Reaction CLXVIII. — Replacement of Hydrogen by Molecular Halogen 341 THE LINKING OF HYDROGEN TO NITROGEN CHAPTER XXIII Amino Compounds Reaction CLXIX. — Action of Metals on Nitro Compounds in Acid Solution 350 Reaction CLXX. — Action of Metals on Nitro Compounds in Alkaline Solution .......... 355 XX CONTENTS PAGE Reaction CLXXI. — Action of Alkali Sulphides and Hydrosulphides on Nitro Compounds . . . . . . . 357 Reaction CLXXII. — Action of Reducing Agents on Azo Compounds. 359 Reaction CLXXIII. — Action of Reducing Agents on Nitroso Com- pounds . . . . . . . . . 360 Reaction CLXXIV. — Reduction of Oximes to Amines with Metallic Sodium or Sodium Amalgam . . . . . .360 CHAPTER XXIV Reaction CLXXV. — Action of Metallic Zinc on Nitro Compounds in Neutral Solution 363 Reaction CLXXVI. — Action of Reducing Agents on Diazonium Com- pounds .......... 363 THE LINKING OF NITROGEN TO NITROGEN CHAPTER XXV Reaction CLXXVII. — Action of Nitrous Acid on Primary Aromatic Amines .......... 365 Preparation of Diazonium Compounds . . . . .366 Reactions of Diazonium Compounds . . . . . .369 Reaction CLXXVIII. — Action of Alkaline Reducing Agents on Aromatic Nitro Compounds . . . . . .371 CHAPTER XXVI Dyes Azo Dyes 372 Di- and Tri-Aryl Methane Dyes . . . •.' . 374 Pyrone or Phthalein Dyes ....... 378 Nitro Dyes . . . . . . ..." 379. Thiazine Dyes .......... 380 Indigoid Dyes . . . . . . . . . . 382 Anthraquinone Dyes ... . . . . . . 384 CHAPTER XXVII Drugs 386 CHAPTER XXVIII Electrolytic Preparations . . . . . • .391 CHAPTER XXIX Products from Natural Sources ...... 394 CHAPTER XXX Stereochemical Reactions ........ 399 CHAPTER XXXI Decompositions . . . . . . . • • 403 CONTENTS CHAPTER XXXII Miscellaneous Preparations PART III CHAPTER XXXIII Detection of Elements present in Carbon Compounds . . 435 CHAPTER XXXIV Quantitative Estimation of Carbon and Hydrogen . . . 438 Modifications of the Method and other Notes .... 446 Combustion of Substances containing Nitrogen .... 448 Combustion of Substances containing Sulphur or Halogen . . 449 Combustion of Substances containing Metallic Radicles . . 449 CHAPTER XXXV Quantitative Estimation of Nitrogen . . . . . 450 Dumas Method — (a) Closed Tube . r . . . . .450 (b) Open Tube . . . . . 454 Further Notes ......... 455 Kjeldahl Method . . .456 CHAPTER XXXVI Quantitative Estimation of Halogens and Sulphur . . . 458 Carius Method (for halogens) ..... . 458 Pira and Schiff Method (for halogens) 460 Robertson Method (for halogens) .... . .461 Carius Method (for sulphur) ....... 463 Fusion Method (for sulphur) ....... 463 Simultaneous Determination of Halogens and Sulphur. . . 464 xxi PAG E 415 * CHAPTER XXXVII Molecular Weight Determination ...... 465 Victor Meyer Method • .465 Freezing Point Method 466 Boiling Point Method . ... . . . . 469 CHAPTER XXXVIII Determination of the Equivalent of an Acid ... . . 472 Determination of the Equivalent of a Base .... 474 xxii CONTENTS CHAPTER XXXIX Group Estimations PAGE Estimation of Primary or Secondary Amines by Acetylation . 475 Estimation of the Number of Hydroxyl Groups in a Compound . 475 Estimation of Acyl Derivatives ...... 476 Estimation of Methoxyl or Ethoxyl Groups .... 476 Estimation of Esters ......... 479 Estimation of Amides . . . . . . . 1 . 479 Estimation of Aldehydes (other than Formaldehyde) . . 479 Estimation of Formaldehyde . . . . . . 480 CHAPTER XL Estimations based on the Use of Titanous Chloride . . ' . 482 Estimation of Nitro Compounds ...... 483 Estimation of Nitroso Compounds ..... . 484 Estimation of Dyes ......... 485 CHAPTER XLI Estimations based on Diazotisation or Coupling . . .487 Preparation of Standard Reagents . . . . . .487 Estimation of Amines . . . . . . . .489 Estimation of Phenolic Compounds . . . . . 490 Estimation of H Acid . . . . ... . 490 CHAPTER XL 1 1 Miscellaneous Estimations ........ 492 Estimation of j9-Phenylenediamine . . . • • 492 Estimation of Thioph en in Benzene . ... . . . 493 Estimation of Enol Modification . . . . . . 493 Estimation of Anthracene ....... 494 Estimation of Acetone . . . . . . . 494 , Estimation of Glucose or Cane Sugar . . . . . . 496 PART IV CHAPTER XLIII Inorganic Section ......... 498 Reagents . . . . . . ... . 498 4 Test Papers and Solutions ....... 500 Preparations .... . . . . . . 502 Tables . . . 509 CHAPTER XLIV Tests for the Common Organic Acids . . . . .512 Tests for Alkaloids . . . . . . . . .519 Tests for Carbohydrates . . . . . . . . 523 Index 525 SYSTEMATIC ORGANIC CHEMISTRY PART 1 CHAPTER I INTRODUCTORY Cautions. 1. Fire. — (a) Fire extinguishers should always be at hand in the laboratory, and should be applied at once. (b) Great care is necessary in the use of ether, light petroleum, carbon disulphide, acetone, alcohol, benzene, etc., as the vapours of these are highly inflammable. They should always be distilled from a water bath and be collected in the apparatus shown on p. 18. Special care is necessary with carbon disulphide, as its vapour inflames in contact with a warm surface, even in the absence of a flame. (c) If the liquid in a beaker or flask catches fire, the source of heat should be removed, and the flame extinguished by placing a watchglass on the opening of the vessel. (d) A blanket should be at hand in case the clothes catch fire. 2. Poison. — (a) All operations in which fumes or noxious vapours are evolved must be carried out in a good fume cupboard. (b) Special care must be taken not to breathe vapours of the following : strong or fuming acids, cyanogen, hydrogen cyanide, carbon monoxide, halogens, phosgene, alkyl sulphates, acyl chlorides, nitro compounds, etc. (c) The hands should be immediately washed after using poisonous substances such as alkaloids, potassium or sodium cyanide, arsenious oxide, phosphorus. This precaution could be extended to the majority of organic compounds. 3. Accidents. — (a) A First- Aid outfit should be kept in each laboratory. j (6) For burns by heat, cover with carron oil or paint with solution of picric acid. Carron oil = linseed oil + lime water (equal parts). (c) For acid burns (1) on the skin ; wash with much water and with dilute ammonia, or bicarbonate solution ; apply carron oil when dry. (2) in the eye ; use much saturated solution of borax. (d) For alkalis (1) on the skin ; wash with much water, then with 1% acetic acid. (2) in the eye ; use much saturated boric acid solution and then drop in castor oil. (e) For acid on the clothes wash with ammonium carbonate solution. (/) For alkali on the clothes, wash with dilute acetic or boric acids, and remove remaining acid with ammonium carbonate solution. (g) For bromine on the skin, wash with alcohol, then with carron oil. S.O.C. 1 B 2 SYSTEMATIC ORGANIC CHEMISTRY All these remedies should be kept on a special shelf in the laboratory. Sodium Residues. — These should not be dropped into the sink or waste box, but should be added in small portions to alcohol, and when all action has ceased, the solution poured into the sink. Scheme of Arrangement of Reactions. The reactions in this book are grouped in sections determined by the linking of elements that occurs in the reaction to form the product. The order of the sections depends on the Richter alphabet— C, H, 0, N, CI, Br, I, S, etc. A complete classification by this method would take the following form ; — I. Reactions in which C, H, 0, N, CI, Br, I, S, etc., II. Reactions in which H, 0, N, CI, Br, I, S, etc., III. Reactions in which H, 0, N, CI, Br, I, S, etc., j > are linked to C. are linked to 0. are linked to N. and so on. Small sections as III. are not further subdivided in practice. Large sections are subdivided to give a separate subsection for the linking of each separate element to the main one, so to speak, of the section ; and each subsection is further subdivided according to the type of compounds necessarily obtained in the various reactions. An examination of the table of contents and of the C to C section will make all the details clear. In the various sections the reactions follow one another so that related reactions come together as much as possible. Of course in practice points arise which have to be settled arbitrarily. Some reactions can be placed under two or more headings, e.g., C 6 H 5 SH — > C 6 H 5 S0 3 H might be put under S to 0 or 0 to S. In this case it is more natural to put it in the latter section, but in analogous cases the doubtful reaction is classified under the section first occurring. No linkings to H are considered, H is always supposed to be linked to the other element. Some sections do not appear in the book because so few reactions fall within them. Decomposition reactions in which links are broken rather than made, electrolytic preparations and some others are placed in a separate section. INTRODUCTORY 3 The name in brackets above some preparations is the structural name as far as one exists. In the many cases where no definite structural name exists, an alternative name, simply, is given. Hints to Students. 1. Before commencing a course on practical organic chemistry, become familiar with the chapter on apparatus and methods. This chapter must be continually referred to as the course proceeds, so that facility in manipulative detail may be gained. 2. Before beginning any individual preparation read carefully the entire method and also obtain a clear idea of the theory as well as the practice of the operation. Know the reason for every step in the process. 3. Work on a definite plan, never omitting anything essential for the sake of speed. 4. Procure suitable and sufficient apparatus. This applies especially to the use of vessels appropriate to the quantities to be used. 5. Clean, and if necessary, dry all apparatus before use. 6. Fit up the apparatus carefully and compactly, paying particular attention to the boring and fitting of corks. 7. Follow exactly the instructions given. Definite times, temperatures and weights are not specified for nothing. 8. Cultivate a habit of observation ; observe all changes and record them. This is one of the essentials of successful research. 9. Whenever possible control the course of the reaction by testing samples. This will in many cases enable the end point to be determined exactly (see Acetanilide, Benzenesulphonic Acid). 10. Remember that the criterion of practical work is the yield of pure substance obtained, and if this differs by more than 10% from the yield stated, seek the cause of this difference, and then repeat the experiment. 11. After the experiment expand the notes already taken, giving par- ticulars of the yield, physical characteristics (M.P., B.P., D. } and micro- scopic examination for crystalline form) of the product. The ratio of the yield obtained to the theoretical yield also should be recorded as a per- centage. 12. Cost the preparation (see p. 5) and compare the price with the current value if quoted. 13. A sample of each stable product should be kept in a specimen bottle, and details of physical characteristics and the yield placed on the label. 14. Above all, keep the bench neat and clean. Use separate dusters for it and for the apparatus. The Use of the Library. The references given in this book to the reactions and preparations should be. consulted where possible by the student. A knowledge of the literature is of fundamental importance. Richter's Lexicon must be used where a reference for a preparation is not available, the method of using which is given fully in the preface to that book. To b 2 4 SYSTEMATIC ORGANIC CHEMISTRY facilitate the use of this lexicon, molecular formula) have been given in this book. Richter also gives references to Beilstein which should afterwards be consulted, and the latter book always gives an indication of the scope of the reference. Cultivate a habit of reading the current journals, especially J. C. S., J. S. C. I., Berichte and Am. Soc. Do not forget that organic chemistry is not the only branch of the subject. Suggested Lists of Preparations. Before commencing a course in practical organic chemistry, the student should have a definite list of preparations to follow. These should be arranged in increasing order of difficulty, and in such a way that, as far as possible, each preparation leads naturally to the next. Where several students are working in the laboratory, the best results are obtained when each works through a different list and compares notes with his neighbour. The following lists are suggested : — I. II. III. IV. 1 X No 196 No. 141 No. 320 No. 478 2 55 263, 266 5 5 320 ,5 181 5, 310 3 55 33, 35 5 5 215 „ 192 5, 215 "i 55 408, 479 55 195, 197 55 158 55 440 5 55 73 55 99 „ 482 55 223 6 55 181 55 374 „ 337 „ 359 ,7 *> 246 55 425 ,5 271 5, 384 8 )i 225 55 221 5, 227 55 184 9 9i 360 5 5 358 5, 286 5, 214 10 5 5 291 55 290 „ 363 „ 268 ]1 55 383 5J 385 5, 275 „ ' 186, 262 12 5* 222 5 5 282 „ 240 „ 486 INTRODUCTORY 5 I. IT. III. IV. 13 No. 370 No. 138 No. 290 No. 375 14 368 55 238 ,5 382 5 1 457 15 5 5 129 11 338 „ 106 1 1 287 16 1 1 242 1 1 28, 34 „ 44 55 397 17 55 245 292 „ 24, 164 11 136 18 1 1 342 1 1 345 ,5 204 1 1 269 19 1 1 390 11 275 „ 344 55 41 20 55 389 55 20, 55 55 155 55 441 21 1 1 19, 54 5 5 392 „ 20 5 5 49, 50 More advanced students should work through a synthesis involving several steps, e.g., Collidine, and should also attempt the preparation of homologues of some of the substances given in detail. In the lists given above, several preparations of industrial importance are included. Note on Costing. The student should always acquaint himself with the cost of the materials he uses in a preparation. He should therefore consult the price-list of some well-known manufacturer or retailer. In fact, a copy of such a price-list should be on the wall of every laboratory. Having ascertained such prices, he should also, after finishing his preparation, ascertain the price of his final product from the price-list to see if he is making the pro- duct economically. Of course, many other factors influence the market prices, such as labour, recovery of by-products, etc., and so on, but it is a good exercise to see in how far his estimated price agrees with the price- list. For example, there is a well-known reaction by which aromatic amines can be converted into the corresponding hydrocarbons. It would be little short of a crime, however, except for academic purposes, to attempt to prepare toluene from toluidine in this way, since the value of the finished product is half of that of the starting material, apart altogether from the cost of the other reagents required ; often such reactions can well be studied in a test-tube. This practical application of a very interesting and important reaction is cited merely to show the importance of having some idea of the cost of materials. 6 SYSTEMATIC ORGANIC CHEMISTRY This should be done in all the simpler preparations which are likely to be included in any price-list. In this way the student will become ac- quainted with the elements of costing which will play an important part in his after life in the factory, where economic considerations are of prime importance. Even should he not take up the manufacturing side of his profession, he should be acquainted with the relative costs of the more common products, and trained to decide for himself whether, for example, it would be more economical to extract with ether or benzene, taking into consideration the relative efficiencies of the two processes. Moreover, he should not use chemically pure products for his pre- parations, unless for research purposes. The ordinary technical qualities are quite suitable for most preparations, and are, of course, much cheaper. It should be remembered that the facilities for the purification of many organic products are much greater on the large scale, than in the laboratory. It is, however, a good exercise to purify for himself a technical product of poor quality (see Purification of Crude Anthracene, p. 171). CHAPTER II APPARATUS AND METHODS Practical Hints. Softening of Corks. — Corks should always be softened before inserting in any flask and the boring performed after softening. Several methods are available. The cork may be softened in the ordinary eccentric iron press between the two rollers. It may also be rolled on the floor under- neath the foot. A convenient way is to place the cork in hot or boiling water ; the cork swells somewhat and becomes quite soft so that it can be made to fit various tubes or flasks. An excellent method of reducing the size of a cork is to rotate it in a flame until the outer coating has charred ; it is then rolled, and cleaned : a cork thus treated may be used for vacuum distillations as the layer of carbon forms a good seal. Rubber stoppers should be occasionally rubbed with a little toluene, which prevents hardening and keeps them clean. A trace of vaseline smeared on a rubber stopper affords considerable protection from the action of halogens. Rubber stoppers should always be removed from vessels while the latter are still warm, to prevent sticking to the glass. Boring of Corks. — Sharp borers should always be used. The end of the cork is placed against some solid object and bored half-way through from one end. The boring should then be completed from the other end. The boring of rubber stoppers may be greatly facilitated by moistening the borer with caustic soda. Removing fixed Stoppers. — Hot water should be run on to the neck of the bottle and the stopper gently tapped with another glass stopper. The neck of the bottle may be inverted in hot water for a minute and after- wards gently tapped. If these methods fail, and if the contents of the bottle are not easily inflammable, the neck of the bottle may be rotated in a flame prior to tapping. Similar methods may be applied to fixed stop-cocks. Crystallisation. The solid product obtained from a chemical reaction is seldom pure, being contaminated with various impurities and by-products. For purification, the process of crystallisation is generally employed. As the process is of such frequent occurrence, the student should early in his course acquire proficiency in it. When dealing with products obtained in plenty, the utmost care should be taken to obtain the maximum yield of pure crystallised compound, as only by doing so can the manipulative skill be acquired which is necessary to obtain a satisfactory yield of pure compound from a product obtained in meagre quantities. 7 8 SYSTEMATIC ORGANIC CHEMISTRY Crystallisation by Cooling. — The ideal solvent is one in which the com- pound to be obtained in pure crystalline form is insoluble in the cold, but readily soluble in the hot. Further, the impurities should either be insoluble or else very soluble. In practice such a solvent is seldom obtained, but the nearest approach to it should be selected. The solvents most commonly employed are : — Water. Alcohol. Ether. Benzene. Petroleum ether. Acetone. Glacial acetic acid. or mixtures of — Water and alcohol. Water and acetic acid. Ether and petroleum ether. Benzene and petroleum ether. The following are frequently used : chloroform, carbon disulphide, car- bon tetrachloride, ethyl acetate, pyridine, hydrochloric acid, sulphuric acid, nitrobenzene, aniline, phenol, epichlorhydrin, ethylene dichloride. Selection of Solvent. — In order to select a suitable solvent small quanti- ties (each about 0-1 gm.) of the finely pulverised product are placed in several test tubes and treated with a few drops of single solvents of the above class. Where the substance dissolves easily in the cold on shaking, or does not dissolve appreciably on boiling, the solvents in question may be regarded as unsuitable. Where the substance dissolves on heating or boiling, and separates out again on cooling, the solvents are suitable ; that solvent should be selected which gives good crystals in the greatest abundance. At times crystallisation does not take place owing to super- cooling ; in such cases the side of the test tube should be rubbed with a glass rod, or the solution should be " seeded " by the addition of a small portion of the crude product, since such operations frequently induce crystallisation. If necessary, the solution should also be cooled in ice or in a freezing mixture. With substances which are sparingly soluble in the common solvents, solvents of high boiling point such as toluene, nitro- benzene, etc., should be used. Where no single solvent is found suitable, a mixture of two miscible solvents, in one of which the product is soluble and in the other insoluble, may be employed with advantage. Substances which are very soluble in cold alcohol or cold acetic acid are frequently but slightly soluble in water, and many substances which are very soluble in benzene are sparingly soluble in petroleum ether. From the preliminary investigation with single solvents it can generally be deduced which are suitable to serve as mixed solvents. The substance is dissolved in a small quantity of one solvent and heated ; the second solvent is then gradually added to the hot solution until a turbidity appears ; heat is again applied until com- APPARATUS AND METHODS 9 plete solution, takes place, and the solution is set aside to cool. Many substances separate in an amorphous or sticky form from an alcohol- water solvent. It is important that the crystals should be sufficiently well defined that their crystalline form as well as the presence of other crystals or impurities can be detected with the aid of a lens. The crystals obtained from these preliminary tests should be preserved, to serve, if needed, to " seed " the solution containing the main bulk of the substance. Preparation of Solution. — If the substance is readily soluble the heating is generally carried out in a flask (conical or ordinary) on a water bath. If considerable heating is necessary, a reflux condenser should be provided to avoid loss of solvent or danger of fire. Should the vapour catch fire, the flame should be withdrawn and the mouth of the vessel covered with a damp cloth or with a watch glass. When the solvent is neither very volatile nor easily inflammable (i.e., water or acetic acid), the heating may be performed in a beaker over a flame. Small quantities of such liquids as alcohol or benzene may be heated in a similar manner by an experienced operator. Where the resulting solution does not require filtration, a conical flask should always be used (see next section). During the heating, the contents of the vessel should be fre- quently shaken or stirred, since crystals, especially when they melt to a heavy oil on the bottom of the vessel, render the latter liable to crack. In preparing the solution an excessive amount of sol- vent should not be employed at first ; successive small quantities should be added to the boiling or nearly boiling solution until the substance just completely dissolves, or until nothing but impurity remains undissolved. With fig. 1. substances of low melting point care should be taken that concentrated solutions from which the substance commences to separate at temperatures above its melting point, are not used. When using mixed solvents, the procedure is similar to that described for the pre- liminary tests ; if on the addition of the second liquid (i.e., water or petroleum ether) resinous impurities separate, these should be filtered off before proceeding further. Filtration of Hot Solution (see also Filtration).— This operation is usually necessary in order to remove insoluble impurities, filter fibres, etc. When the substance does not separate rapidly from the hot solution, and the liquid filters quickly, the solution may be filtered through an ordinary funnel with a short stem, fitted with a folded filter paper (Fig. 1). Both funnel and paper should previously be warmed in a steam bath. Or, the solution may be filtered with suction, using suitable types of apparatus (Figs. 26, 27). The funnel and filtering medium should be previously warmed. When the filtrate is collected in a thick glass suction flask, the latter should be warmed beforehand by immersion in warm water. The bell-jar form of filtering apparatus (Fig. 28) is recommended, as the hot solution can be collected in a conical flask of suitable size. For " crystallisation by cooling " a rather wide-mouthed conical flask should be used to contain the hot filtered solution — a filter flask serves equally 10 SYSTEMATIC ORGANIC CHEMISTRY well for large volumes ; with vessels of this conical type the crystals do not creep up the sides, as may occur when beakers or the so-called " crystal- lisation dishes " are used ; after separation, the crystals can easily be removed with the aid of a glass rod over the end of which a short piece of rubber tube has been drawn. If the substance crystallises rapidly from the hot solution, a hot filter should be used. Figs. 2 and 3 show steam jacketed and hot- water jacketed filters. With a volatile and easily inflammable solvent the flame should be removed from the jacket immediately before filtering, danger of fire being thereby avoided ; Fig. 2. in such an instance the steam funnel is preferable when the steam is generated at a safe distance. After nitration the conical flask is covered with a watch-glass and set aside. If large crystals are required, the rate of cooling should be as slow as possible, and the flask should not be disturbed. The rate of cooling may be lessened by immersing the flask in a bath of warm water and allowing the bath [j ! | and its contents to cool. If the substance separates in large coarse crystals on slow cooling, or if small pure crystals are required, it is expedient to cool quickly in cold water or in ice water, and to stir or agitate the solution at the same time. Small crystals are generally free from mother liquor which is liable to be occluded in large crystals. When the substance is very soluble at ordinary temperature, the cooling should be continued in a freezing mixture. Cooling Mixtures. Temp. Temp. Mixture in gms. falls from Mixture in gms. falls from 15° to 15° to 14 alum + 100 aq. . 14° 25 amm. chloride + 100 ice —15° 36 sodium chloride + 100 aq. 13° 45 amm. nitrate + 100 ice —17° 12 pot. sulphate + 100 aq. 12° 50 sod. nitrate + 100 ice —18° 14 sod. phosphate + 100 aq. 11° 33 sod. chloride + 100 ice —20° 75 amm. sulphate + 100 aq. 9° 1 pot. sulphocyanate + 1 aq. . —24° 20 sod. sulphate cryst. + 100 aq. 8° 52 amm. nitrate + 55 "] —26° 85 mag. sulphate cryst. + 100 aq. 7° sod. nitrate 40 sod. carbonate cryst. + 100 aq. 6° 100 dil. H 2 S0 4 66% . . —31° 16 pot. nitrate + 100 aq. . 5° 13 amm. chloride + 38 } +100 30 amm. carbonate + 100 aq. 3° sod. nitrate . . 1 ice. —31° 30 calcium chloride + 100 aq. . 2° 2 pot. nitrate + 112 | 20 sod. carbonate + 100 ice 2° pot.sulphocyanate J —34° 30 amm. chloride + 100 aq. —3° 3 calcium chloride cryst. + 2 ice —49° 110 sod. thiosulphate + 100 aq. . —4° Solid C0 2 + ether —100° 250 calcium chloride cryst. + 100 aq . —8° 30 pot. chloride + 100 ice —11° 100 cone. HC1 + 100 ice . — 15° 8 sod. sulphate + 5 cone. HC1 . —12° 50 cone. HC1 + 100 ice . -18° From Erdrnann-Kothner — N aturkonstanten (1905). APPARATUS AND METHODS 1 1 Separation of Crystals.— This is generally effected by filtration with suction, vessels of size suitable to the quantities dealt with being selected. The crystals left on the funnel should be well pressed down and then washed a few times with small quantities of the pure solvent in order to remove the last traces of mother liquor. If the substance is easily soluble, too large quantities of solvent must not be employed for washing. When a solvent which is not readily volatile has been used (e.g., nitrobenzene, acetic acid, etc.), it must be removed from the crystals by washing with an easily volatile solvent with which it is miscible. After being thoroughly drained on the funnel, the crystals are dried (see also p. 33). They may be placed on filter paper or porous plate, covered to protect from dust, and allowed to dry in the air, or left in a desiccator over a suitable substance to absorb the solvent ; the operation may be hastened by evacuating the desiccator. If the crystals have a high melting point, the drying may be effected in a bath at temperatures below the fusion point. In this connection it should be noted that the presence of small quantities of solvent may produce a considerable lowering of the melting point — to avoid this a test portion should first be dried. Often further crops of crystals can be obtained by concentrating the mother liquor ; generally these are less pure and require to be recrystallised. In some cases the first crop has to be recrystallised before the crystals are pure (determined by M.P.). It is often convenient, in order to separate a second crop, to dilute the mother liquor with a liquid in which the dis- solved substance is sparingly soluble. Crops separated in this w T ay generally require recrystallisation. Crystals which are very soluble in the solvent at laboratory temperature, and which have been obtained by cooling the solution in a freezing mixture, should be filtered through an ice-jacketed funnel (Fig. 4). In all cases the process of crystallisation must be continued until no change in melting point occurs on further crystallisation, or until the product obtained by evaporating a sample of the mother liquor has the same melting point as the crystals separated from it. Crystallisation by Evaporation. — This method is employed when the substance is so easily soluble in all solvents (hot and cold) that it will only separate after partial evaporation. The solvent is allowed to evaporate spontaneously in the air or in a desiccator ; if in the latter the evaporation is greatly hastened by using a suitable absorbent as well as evacuating the desiccator. The type of vessel employed depends on the volatility of the solvent ; obviously the conical flask already recommended for " crystal- lisation by cooling " is not suitable for spontaneous evaporation, while a beaker or shallow " crystallising dish " is. When the latter type of vessel is used, " crusts " often form on the sides above the surface of the liquid. Such crusts seldom consist of pure substance, and they should be carefully removed with a spatula before attempting to filter off the crystals. Since the purifying effect of crystallisation depends on the fact that the 12 SYSTEMATIC ORGANIC CHEMISTRY impurities remain dissolved in the mother liquor — except in cases where the impurities being insoluble are first filtered of! — the solvent should never be completely evaporated, but the crystals should be filtered of! while still covered with mother liquor. Special Methods. — With some substances it is difficult to obtain good crystals by the methods already described. A method which frequently gives excellent results, consists in dissolving the substance in some solvent, then adding a second solvent, miscible with the first, but in which the substance is sparingly soluble. The first solvent is then gradually removed and the substance separates out — usually in the crystalline form. If the first solvent is the more volatile in air, spontaneous evaporation in air may diminish its concentration in the solution. The solution may be placed in a desiccator over some substance which absorbs the first solvent but not the second ; in this way water may be removed from a water-alcohol solution by solid caustic potash or quicklime. Another method — applicable when the substance is soluble in alcohol and in ether, but insoluble in water — consists in making a saturated solu- tion in cold alcohol, adding water until considerable precipitation has taken place, then adding ether until the precipitate has redissolved, and finally allowing the ether to diminish by spontaneous evaporation. When a substance is soluble without change in concentrated sulphuric acid, but insoluble in water, a saturated solution in the former medium when left exposed to water- vapour — say, side by side with a vessel of water under a bell- jar — gradually absorbs water, and the substance frequently separates out in crystalline form. The purification of many products can be facilitated by distillation, prior to crystallisation, provided they distil without decomposition. Generally it is preferable to conduct the distillation under reduced pressure. Fractional Crystallisation. The process of fractional crystallisation is employed to separate two or more substances, all of which are soluble in the solvent used. When only two substances are present, it is often possible to find, by preliminary tests, a solvent which, when used in suitable quantity, will dissolve the whole of the more soluble compound, but only a small quantity of the less soluble. In such a case, a preliminary separation may be effected by shaking the mixture with a quantity of solvent (hot or cold — as found suitable by trial), and filtering the solution from the residue remaining undissolved. For extracting a mixture of this nature with a hot solvent the Soxhlet apparatus (Fig. 29) is specialty useful ; in fact this apparatus should be employed for all extractions where a residue remains undissolved, since filtration as well as extraction is accomplished ; also only a relatively small quantity of solvent is required (see p. 31). When commencing a fractional crystallisation, preliminary tests similar to those described under "Crystallisation" are first carried out, and the crystals which separate during such tests examined with a lens. The crystals which form first are either the least soluble or most abundant constituent of the mixture. If a second or further type of crystal appears, APPARATUS AND METHODS L3 its shape and time of formation relative to cooling should be noted ; it is often necessary to filter off the first crop while the mixture is still warm. When dealing with a finely-powdered or amorphous mixture, it is often useful to examine a small portion placed on a watch-glass under the microscope. The action of a few drops of various solvents (hot or cold) can be examined in this position, and valuable information — which might not be obvious to the naked eye — perhaps gained concerning the solubility or insolubility of some constituent in a particular solvent. No definite plan can be given which will suit all examples of fractional crystallisation. The scheme outlined in " Text-book of Inorganic Chemistry," Vol. IV., p. 324 (J. Newton Friend), when applicable, affords a convenient method of marking and recording the various fractions involved in a fractional crystallisation ; it also avoids the accumulation of a vast number of small crops and mother liquors : — The mixture is dissolved with the aid of heat in a solvent to give solu- tion (1). From this solution on cooling, crystals separate which are filtered off, and solution (1) is thereby divided into crop (2) and mother liquor (3). Crop (2) is dissolved in the minimum quantity of hot solvent, and from the resulting solution after cooling, crop (4) and mother liquor (5) are obtained. Mother liquor (3) is concentrated, and from the concen- trated solution after cooling, crop (6) and mother liquor (7) are obtained. Crop (6) and mother liquor (5) are united to form a single fraction, and after being heated to dissolve and subsequently cooled give rise to crop (10) and mother liquor (11). Crop (4) is dissolved in a small portion of pure solvent by heating and after cooling is divided into crop (8) and mother liquor (9). Mother liquor (7) after concentration and cooling yields crop (12) and mother liquor (13). (9) and (10), likewise (11) and (12), are united to give single fractions. Proceeding in this way, the least soluble 14 SYSTEMATIC ORGANIC CHEMISTRY compound goes to the left in the diagram, while the most soluble goes to the right, and compounds of intermediate solubility lie between these extremes. Each crop should be tested for purity. If, when examined with the aid of a lens, two or more types of crystals are present, the crop must be recrystallised. When a crop appears uniform, a small portion should be withdrawn, dried by exposure on porous porcelain or on filter paper, and its melting point taken. In the above scheme if crop (2), say, is pure it takes no further part in the recrystallisation ; mother liquor (3) is then worked up. When the principal product is moderately soluble in the hot solvent, but not very soluble in the cold solvent, the following method might be serviceable. The product is divided into three (say) equal por- tions, A, B and C. A is recrystallised from the minimum quantity of pure solvent, yielding crop A v The mother liquor from A x and small quantity of washings are used to recrystallise B, yielding crop B x . The mother liquor from B 1 is similarly used to recrystallise C. In this way the mother liquor from C x should be more or less saturated with the impurities present, while it contains but little more of the principal product than was contained in the mother liquor from A r If crop A x is impure, it is recrystallised from fresh solvent yielding crop A 2 . Crops B x and C x are recrystallised from mother liquors A 2 and B 2 , and mother liquors C x and C 2 are united. The process is continued after this fashion until the crop under A is pure. The crop under B then becomes the first fraction, and the mother liquors from the C's are combined and evaporated so as to give a crop D, which becomes the new end-fraction and enters into the recrystallisations : — A B C Ai Bi Ci An Bn Cn D Bm Cm Dm— n E This method was found very useful for the purification of ^-a-phenyl- ethylamine Z-malate (p. 401). When the product separates from the solvent in compact crystalline masses, the mother liquor may be decanted on to the next fraction, and thus filtration, which is always attended with some slight loss of material, is avoided. It sometimes happens that after a fractional crystallisation has been continued for some time, a solution is obtained from which two products crystallise side by side, the solution being apparently saturated with regard to each product. In such a case a separation might be effected by evaporating off the solvent and proceeding with a different solvent in which the ratio of the solubilities of the two compounds differs from the corresponding ratio in the first solvent. In some such cases mechanical APPARATUS AND METHODS 15 means of separation might be effective ; if one set of crystals is heavier than the other, the lighter set may be separated by stirring the super- natant liquor (or by rotating the vessel) and rapidly decanting. The mother liquor after nitration from the lighter crystals may be agitated a second time over the heavier crystals in order to remove any of the lighter which still remain. If one or both sets of crystals separate in fairly large form, a separation may be effected by hand picking. Determination o£ Melting Point. In order to identify a substance, or to test its purity, the melting point of the substance is determined, a process which can be rapidly carried out. If a substance does melt at all, it should, if pure, melt sharply at a definite temperature. If the aim is one of final identification of the compound, this figure should agree with the figure given in the literature. If the figure is considerably lower than the one given, one must suspect impurity or else a different compound from that stated. In every case, however, the melting point should be verified by reference to Beilstein or Richter's Lexicon or Stelzner. If the melting point is higher than the figure given, the compound may be a different one, or the melting point may have been carelessly taken, for example, by heating too quickly. In general, a pure substance melts within 1° of the figure given. If the melting point is not sharp, the substance should be recrystalHsed from a suitable solvent before a further determination is made. From this it is obvious that great care should be observed in making this simple determination, and the following points should be carefully observed. The choice of a thermometer is an important one. In the first place it should have a small bulb, and the range should be suitably chosen. For example, if it is known that a substance has a low melting point, a ther- mometer of range 0° — 100° should be used. If the substance has a high melting point, a range of say 200° — 300° should be chosen and so on. All thermometers used for the determination of melting points should be standardised against a standard thermometer. The preparation of the capillary tube requires a little practice. A piece of thin- walled glass tubing or a test tube is heated in an ordinary Bunsen flame or blow-pipe until it softens, when it is withdrawn from the flame and carefully drawn out for 2 or 3 feet. Draw slowly at first, then quicker as the glass cools and hardens. The central part, consisting of the capillary tube, is then cut into sections of about 8 — 10 cms. in length, and one end of each section fused in the flame. A supply of melting point tubes should always be in readiness. The substance of which the melting point has to be taken should be perfectly dry. A sample is ground to a fine powder on a watch-glass with a clean glass rod, introduced into the capillary tube and shaken to the bottom, light scratching of the tube with a file often brings this about. The tube is then ready for fixing to the thermometer. The liquid used in the melting point apparatus is usually concentrated sulphuric acid (vaseline may also be used). After being reheated several times, sulphuric 16 SYSTEMATIC ORGANIC CHEMISTRY acid is apt to become discoloured. It may be rendered water-white again by adding a crystal of potassium nitrate and heating. For melting points above 250° sulphuric acid should not be employed alone. For melting points ranging between 250° — 350° C, about 30% of potassium sulphate should be added to the sulphuric acid. Higher temperatures may be obtained by increasing the quantity of potassium sulphate. This sulphate mixture is solid at ordinary temperature, but it is not so easily discoloured. For temperatures above 370° fused zinc chloride may be used in place of sulphuric acid or the sulphate mixture. The melting point apparatus consists of a small beaker or a large-sized Fig. 5. Fig. 6. test tube containing sulphuric acid up to a convenient level. The ther- mometer can be held in position with its bulb well immersed in the acid, by means of a clamp in the former case, or by means of a cork in the latter. It is advisable to have some kind of mechanical agitation in the sulphuric acid (see sketch) although if the heating is carefully done, this may be dispensed with. Figs. 5 and 6 show the arrangement in the two cases where a glass rod is used as a stirrer, the stirring being maintained while the acid is slowly heated. The cork at A in Fig. 6 should be as thin as possible so as to obscure the minimum amount of the scale, and if no agitator is used passing through the cork, then a slit should be made in the cork to allow exit to the vapours on heating. The thermometer is first dipped in the sulphuric acid, and then the drop APPARATUS AND METHODS 17 of acid which clings to the bulb is smeared on the side of the capillary tube containing the substance. The capillary tube is then made to adhere to the thermometer (Fig. 6) by capillary attraction, so that the substance in the tube is just opposite the bulb of the thermometer. This method is much better than using a rubber band, which is apt to perish in the sulphuric acid fumes, and gives rise generally to a speedy discoloration of the acid. A cloth should be placed on the bench below the apparatus when heating is commenced, so as to protect the observer should an accident occur. The Bunsen burner should be held in the left hand and the stirrer worked with the right. The heating should be moderated on approaching the melting point, and the Bunsen lowered to give a flame about 2 cms. in length. The temperature at which the substance shows the "first sign of melting is taken as the melting point of the substance. Correction. — Melting points are usually given as " uncorrected " ; for correction the following formula is employed : — T c = T 0 + 0-000156Z(T o - T m ) T c = corrected temperature. T 0 = observed temperature. 0-000156 = apparent coefficient of expansion of mercury in glass. I = length of mercury column in degrees above surface of liquid. T m = mean temperature of mercury column, i.e., the temperature of the middle point of the mercury column, taken by another thermometer. Some Corrected Melting Points for Standardising Thermometers. — p-Toluidine ... 45° Salicylic acid . . . 159-8° a-Naphthylamine . . 50° Anthracene . . . 216° Naphthalene . . . 80-8° Carbazole . . . 246° Benzoic acid . . . 122-5° Anthraquinone . . 285° "Mixed" Melting Points. — Impurities generally lower the melting point of a substance. To determine whether two substances of the same melting point are one and the same, a convenient method is to mix equal quantities of the two and take a melting point of the mixture. If the melting point is not lowered the two substances are identical. Setting Point. — When a large quantity of the substance is available a very speedy determination of its setting point (freezing point) may be made as follows. The method is used largely on the technical scale, and is specially suitable for controlling chemical operations. The substance is placed in a large test tube and melted. A thermometer reading fifths or tenths of a degree is used, and is placed in the melted substance which is stirred by means of the thermometer. The mercury in the thermometer gradually falls as the liquid cools, until it reaches a point when it jumps up suddenly (due to the heat liberated on the appear- ance of the solid phase). The stirring is continued, and the highest temperature to which it reaches after this upthrust is taken as the setting point or freezing point. This figure should, of course, agree with the melting point. 18 SYSTEMATIC ORGANIC CHEMISTRY Distillation and Determination of Boiling Point. The apparatus for the ordinary distillation of a liquid and for deter- mining its boiling point is the same. A pure liquid should boil at a {a) For low B.P. liquids. (6) For medium B.P. liquids, (c) For high B.P. liquids. Fig. 7. constant temperature, and the whole should pass over within a very small range. The liquid to be distilled, or of which the boiling point is to be obtained. Fig. 8. is placed in a suitable round-bottomed flask, fitted with a side tube. The flask chosen should be of suitable capacity, e.g., one should not use a 500-c.c. distilling flask to distil 10 c.cs. of a liquid. Figure 7 above shows the position the side tube should hold in particular cases. APPARATUS AND METHODS L9 This is important, and a proper choice will well repay the trouble taken. The liquid should half fill the bulb of the distilling flask. Determination of Boiling Point. — After the liquid has been placed in the distilling flask, the thermometer which is chosen to suit the substance, as in the determination of melting points, is fixed in the neck of the flask by Fig. 9. means of a thin cork, so that the bulb of the thermometer is opposite the exit tube. The flask is then fixed to a condenser by means of a cork placed as near as possible to the neck of the flask. The condenser is attached to an adapter at its lower end to deliver the condensed liquid into a receiver. This cork should be placed as far as possible from the end of the condenser tube. The sketch. (Fig. 8) shows how the complete apparatus should appear. The ordinary Liebig condenser should be replaced by an air condenser for liquids boiling over 160° (see Fig. 9). When inflammable liquids are distilled, the receiver, as shown, should take the form of a Buchner flask, with a rubber tube connected to the side tube, and dipping over the side of the bench. In this way inflammable vapours are removed from the region of the Bunsen burner. Before heating is commenced, a small piece of unglazed porcelain or magnesite is introduced into the flask in order to prevent " bumping " or j too vigorous boiling. Heat is applied very gradually, and the temperature raised very slowly at first, until it reaches a point at which the liquid distils regularly and there remains constant. , This temperature is the boiling point of the liquid. When there is only a very small quantity of liquid available, two methods may be applied : — 1. A very small distilling flask, preferably pear-shaped, may be used. The sketch (Fig. 10) shows a very useful type of flask for this purpose. c 2 20 SYSTEMATIC ORGANIC CHEMISTRY These flasks can be obtained of capacity down to 1 c.c. The hood prevents condensed liquid returning to the bulb. 2. This jnethod_ may be employed for even one drop of liquid. The latter is placed in a narrow tube which has been sealed at one end, and this tube is attached to a thermometer by means of a rubber band in such a position that the liquid is opposite the bulb of the thermometer. Into the liquid is now placed the open end of a sealed melting point tube ;■ the whole is fixed in the melting point apparatus. The sketch (Fig. 11) shows the arrangement. At first bubbles of air are expelled from the end of the capillary tube due to expansion as soon as heat is applied to the acid ; the heating should be very carefully carried out. Ultimately a point will be reached at which there is a regular I stream of bubbles emitted from the tube. This temperature is the boiling point. At least two observations should be Fig. 11. niade by this method, a new capillary tube being used each time. The mean is taken as the true boiling point. These boiling points are " uncorrected " — the " corrected " figure is obtained as with melting points. Corrections. — {a) Thermometer Reading. T c = T 0 + 0-000156Z(T o - T m ) T 0 = observed boiling point. T c = corrected boiling point. I = length of mercury column not heated by the vapours. T m = mean temperature of mercury column (see Melting Point). (b) Barometric Pressure. T c = T G + 0-043 (760 - P) P = atmospheric pressure in millimetres. Some Corrected Boiling Points for Standardising Thermometers.— Chloroform . . . 61-3° Nitrobenzene . . . 210-9° Benzene . . . 80-2° Quinoline . . . 237-5° Chlorobenzene . . 131-2° Benzophenone . . 305-9° Aniline . . . 184-4° Mercury . . . 356-8° Fractional Distillation. Fractional distillation, using the ordinary distillation apparatus, is employed for separating substances whose boiling points differ by at least 40° C. The mixture is distilled slowly and the distillates are collected in i separate receivers. For example, a mixture of benzene (B.P. 80-2°) and 1 nitrobenzene (B.P. 210-9°) can be separated by collecting the distillate i which came over at about 80° in one receiver and the distillate which came 1 over at about 210° in another receiver. By repeating this process carefully, \ the two receivers will ultimately contain pure benzene and pure nitro- r APPARATUS AND METHODS 2) benzene respectively. It is always necessary to repeat the process when the boiling points of the liquids are fairly close. When the boiling points lie near one another the same method can be used, but before a separation can be obtained the process may have to be repeated ten or twenty times, and even then the separation will probably not be complete. By using still-heads or fractionating columns this difficulty can be obviated. Fig. 12 indicates the types of still-heads most commonly used in the laboratory for this purpose. The principle of all is similar ; they offer a large cooling surface to the rising vapours which are always in contact with the falling condensed liquid. In this way only Fig. 12. Fig. 13. the more volatile liquid passes over to the condenser. Fig. 13 shows a column attached to a flask. Such an apparatus could be used for separat- ing, say, a mixture of benzene (B.P. 80-2°) and toluene (B.P. 110°). It is always necessary to repeat the process at least once until the constituents of the mixture give definite boiling points. In some cases liquids, even with different boiling points, cannot be separated in this way, owing to the formation of constant boiling mixtures, which behave like pure substances. The boiling point of such a mixture is a function of the pressure. Such mixtures cannot, therefore, be separated by distillation. The excess of each constituent beyond the constant boiling proportion would, of course, pass over, until the composition reached that of the constant boiling mixture, which has either a maximum 22 SYSTEMATIC ORGANIC CHEMISTRY or minimum boiling point compared with any other mixture of the substances. The tables given below, which are taken from " A Laboratory Course of Organic Chemistry " (A. W. Titherley), show the boiling point and com- position of some such constant boiling mixtures, consisting of two sub- stances, A and B. Constant Boiling Mixtures. Minimum B.P. Type I. A. B. B.P. of constant mixture . % of A. in constant mixture. B.P. B.P. Methyl alcohol . 65-5° Acetone 56-6° 55-95° 13-5 Water 100° Ethyl alcohol 78-3° 78-15° 4-43 Water 100° Isopropyl alcohol . 82-45° 80-35° 12-10 Water 100° n -Propyl alcohol . 97-2° 87-7° 28-31 Water 100° Butyric acid 159-5° 99-2° 80 Benzene . 80-2° Ethyl alcohol 78-3° 68-25° 67-64 Benzene . 80-2° Methyl alcohol 65-5° 58-35° 60-45 Pyridine . 115° Water . 100° 92-5° 59 laximum B.P. Type II. Water 100° Formic acid . 99-9° 1071° 23 Water 100° HC1 . . about -80° 110° 79-76 Water 100° HBr . . „ -73° 126° 52-5 Water 100° HI . „ -35° 127° 43 Water 100° HN0 3 . 86° 120-5° 32 Chloroform 61-2° Acetone 56-6° 64-7° 80 The boiling points are given for 760 mms. pressure. In Type I. the boil- ing point of the constant boiling mixture is below that of either con- stituent, while in Type II. the boiling point of the constant boiling mixture is above that of either constituent. References. — For theoretical considerations of this subject the student is referred to : — Walker, " Introduction to Physical Chemistry" (1919), p. 83. Smith, " Introduction to Inorganic Chemistry," pp. 587, 609, 211, 273, 279. Noyes and Warfel, Am. Soc, 23 (1901), 468. Young, " Stoichiometry " (1918), p. 252. A very simple and ingenious type of still-head, and one which is very effective, was patented by Dufton (see J. S. C. L, 38, 45). Steam Distillation. Steam distillation is sometimes employed for separating substances of high boiling point which have an appreciable vapour pressure at 100°. It APPARATUS AND METHODS 23 consists in passing a current of steam through the mixture. The sketch (Fig. 14) shows the apparatus usually employed. The steam is generated in a tin canister or a glass flask which is provided with a long glass safety Fig. 14. tube dipping below the surface of the water. The distilling flask should be large and should be sloped to prevent the liquid splashing up into the condenser. The steam delivery tube should be slightly bent, as shown. Rubber stoppers should not be used. In order to prevent excessive condensation of steam the distilling flask should be directly heated, and a soluble salt may be added to raise the tempera- ture. The distillate may consist of a solution in water (acetic acid — see p. 476), or of two layers (aniline — see p. 351), or a solid may separate (o-nitro- phenol — see p. 272). If the last tends to choke the condenser the cooling water should be turned off occasionally. Steam may be substituted by alcohol or ether vapour in particular cases. Control tests should be made occasionally to determine the completion of the distillation ; these tests may be physical or chemical, depending on the nature of the substance. For theoretical discussion see " Outlines of Physical Chemistry," Senter, p. 90. Superheated Steam. — This is used for distilling substances which are difficultly volatile. The steam from the generator is passed through a copper spiral (Fig. 15) which is heated by a Bunsen flame, and which has Fig. li 24 SYSTEMATIC ORGANIC CHEMISTRY a side tube attached for a thermometer. This tube is placed on the exit tube, and as far away as possible from the flame. Continuous Steam Distillation. — The appa- ratus (Fig. 16) is very convenient when this process has to be carried on for some time. The substance to be steam distilled is placed in the round-bottomed flask A along with water if none is present. To the flask is attached through a cork a tube delivering to a vertical tube B, and with a small side tube C. A condenser is fitted to the top of the vertical tube and a receiver D of the type shown, or a flask with a two-holed stopper. The small side tube C is attached to a delivery tube E fixed to the receiver by means of a rubber tube. When the flask is boiled the vapour is condensed in the con- denser and the liquid falls into the receiver. When this process has been continued for some time, the top layer of water in the receiver gradually rises, and when it reaches the level of the small side tube C passes back automatically into A. The process is now con- tinuous. The liquid in the receiver can be separated when desired by opening the tap on the bottom of the receiver. When the liquid to be steam-distilled is lighter than water, the small glass tube E is extended to the bottom of the receiver. Fig. 16. Dry Distillation. This is a process which is occasionally used in the laboratory ; it is usual to perform the distillation in an iron or copper vessel as glass will not stand the heat. In order to prevent a cake forming, and thus secure uniform heating, it is advisable to mix the substance to be distilled with iron turnings which conduct the heat into the interior of the mass, pro- vided, of course, that the iron turnings have no chemical action on the substance. Vacuum Distillation. Some liquids decompose when distilled in the ordinary way ; these can generally be distilled under reduced pressure. The apparatus used is shown in the sketch (Fig. 17) and may be of glass, provided large vessels are not used. It is usual to heat the distilling flask in a bath and not by direct heat. The distilling flask, which may be of the ordinary type or, better, having two necks as shown (Fig. 18), should be wrapped in asbestos cloth, which acts as a protection as well as a preventative of loss of heat by radiation. To the flask is attached a glass tube drawn out to a fine capillary APPARATUS AND METHODS 25 which dips below the surface of the liquid. By the passage of small quantities of air, or some other gas if air is unsuitable, regular boiling is maintained, and this is of extreme importance. A. rubber tube with screw Fig. 17. clip may be connected to the top of the capillary tube so as to regulate the air supply. Provided the liquid has no action on rubber, rubber stoppers should be used ; they should be smeared with vaseline before inserting. Good corks, however, are quite satisfactory if covered with collodion after Fig. 18. (Claisen). Fig. 19. insertion, or charred as described on p. 7. Between the receiving flask and the pump is placed a manometer for reading the pressure. If the ordinarv water pump is used a water trap (Fig. 19) must be inserted between the pump and the manometer to prevent water sucking back into the apparatus. When the distillation is to be discontinued the flame 26 SYSTEMATIC ORGANIC CHEMISTRY should be extinguished and air allowed to enter by carefully opening the tap attached to the water trap. Vacuum distillation may be used in fractionating liquids. The apparatus is similar except that facilities are provided in the receiving vessel for collecting different fractions. Two sketches (Figs. 17, 20) show suitable types of receivers for use in fractionating under reduced pressure. The desiccator type is shown in Fig. 17, and contains six or seven small receivers into which the distillate Can be run, different fractions being obtained by turning the handle on the top, thus bringing another receiver into position. This avoids breaking the vacuum. Fig. 20 shows a single 4 Fig. 20. receiver which can be emptied without breaking the vacuum. While a fraction is being collected, A and B are closed while C is open. The receiver is emptied by closing C and opening A and B. While the next fraction is being collected the receiving flask may be removed. It sometimes happens that a liquid " bumps " violently even with the addition of a few porcelain clips and the passage of a fine gas current through the flask. The best plan in such cases is to immerse the flask so far into the heating bath (see p. 35) that the level of the latter is above the level of the liquid in the flask. In this way the vapour is super- heated, and bumping does not occur. A convenient apparatus for distilling liquids of high boiling point under reduced pressure is shown in Fig. 21, in which the receiver is an ordinary APPARATUS AND METHODS 27 distilling flask, and is kept cool by a current of cold water (for another type of receiver see Fig. 22). As with glass flasks there is a risk that they may collapse under a vacuum, especially when heated to high temperatures, the eyes should be protected by goggles when using them as above. Pumps. — The lowest pressure obtainable by a water pump is the vapour pressure of water at the temperature of the water (usually 10 — 15 mms.). For pressures below this a mechani- cal pump must be employed, which in some cases reduces the pressure to less than 1 mm. Note. — The boiling points of high boiling point liquids are reduced by about 100° at 10 — 15 mms. A Receiver for Distillation in a Current of Gas or under Reduced Pressure. — The receiver shown in Fig. 22 can be used to fractionate liquids in a current of gas or under reduced pressure. . The condensing liquid is first collected in A, the tap B being turned so as to connect tubes b and c. The gas current meanwhile passes from A into C where it displaces air and prepares C for the recep- tion of the fraction. The tubes d and e are shown as for a heavy gas, e.g., C0 2 ; for a light gas the relative depths to which they enter the flask must be reversed. To isolate the fraction, B is turned to put c in communication with A. The liquid, helped by the gas-current, passes into C, B is turned through 180°, and the tube c swept out by gas passing from b. Taps D and E are closed, and the ground- glass joint F opened. A new flask is put on at the joint, and when the air in it has been swept out, the next fraction can be collected. If it is necessary to collect the fractions at very short intervals, several flasks can be swept out simultaneously by connecting them in series to /. If glass joints are unnecessary throughout, pieces of rubber tubing can be used for connecting the flasks together. Fig. 22. 28 SYSTEMATIC ORGANIC CHEMISTRY Fig. 23. As shown, the apparatus is adapted for the collection of very readily oxidisable liquids. In many cases it will not be necessary to have taps D and E ; and F can be replaced by a rubber connection. The apparatus can also be used for fractionation in vacuo. The vacuum pump is con- nected at/, and while a fraction is collecting, exhaustion takes place from b to c. The fraction, after being sucked into C by turning B through 180°, is isolated by closing B by a right-angle turn, closing E and disconnecting at /. Air or other gas can then be admitted through E, and F discon- nected. If preferred, E can conveniently be a three-way tap. Another flask is then fitted on, and when exhausted, b and c are put in communica- tion. To save time, several flasks can be kept exhausted by attaching them in series to/ and to the pump (J. S. C. L, 41, 59 (T.) ). Sublimation. Sublimation is a process used for the purification of some compounds, especially when the quantity of substance is small. The first point to determine is that the substance does actually sublime. This is done by heating a little of the substance in a dry test tube held in an almost horizontal position. The sublimate, if any, will collect on the colder parts of the tube. Several types of apparatus are available for sub- limation. If the substance sublimes readily, the fol- lowing apparatus is convenient. It consists of two watch-glasses clamped together by a brass clip, the substance being placed in the lower glass and a perfo- rated filter paper between them. The sketch (Fig. 23) shows the arrangement. This is heated on a sand bath. The sublimate collects in the upper glass, and the filter paper prevents the sublimate from falling into the residue. The upper watch-glass may be kept cool by covering it with several pieces of damp filter paper and wetting these from time to time. The upper watch- glass may be replaced by an inverted glass filter funnel with a plug of cotton wool in its stem (Fig. 24). When the substance is difficult to sublime, it may be heated m a crucible placed in a round hole in a piece of asbestos board. The crucible is covered with a large clock-glass and a small flame is used so that the heat is directed only on to the crucible, as shown in Fig. 25. Filtration (see also p. 9). Filtration by means of suction is generally employed where possible in the operations of organic chemistry, since more rapid and more complete Fig. 24. Fig. 25. APPARATUS AND METHODS 21) separation of the mother liquor is in this way effected. For this purpose several types of apparatus are in use. For large quantities of material the Buchner funnel and flask (Fig. 26) is used, the filter paper being cut so as to cover the perforations. If filter paper is attacked by the liquor, cloth, such as flannel or cotton, might be used instead. For highly corrosive liquids, a layer of fibrous asbestos should be employed as filtering medium ; this is prepared by boiling asbestos wool with hydrochloric acid, then pouring on to the Buchner funnel and washing thoroughly with water while suction is applied. If neces- sary, the asbestos is then dried by washing successively with alcohol and ether. In al] cases the filtering medium should be moistened with the solvent used, and well pressed down on the perforated plate. An ordinary funnel in which is placed a perforated disc (Fig. 27a) may be used instead of the Buchner funnel, and this form is very convenient for separating small quantities of solids. The paper should be cut slightly larger than the disc, and should be carefully placed in position, and pressed down after moistening. For separating small quantities of liquid the apparatus (Fig. 27b) is very Fig. 27. suitable ; the liquid is received in a test tube placed inside the Buchner flask. The apparatus (Fig. 28) shows the most convenient arrangement when the filtrate is further required. It consists of a bell jar cemented with vase- line to a ground-glass plate ; the double-holed rubber stopper carries the filter funnel and a tube for connecting to pump. The liquid is collected in a receiver placed inside the bell jar. The great advantage of the apparatus is that any type of receiver may be employed. If the filter funnel has a long stem, it may be used in conjunction with a hot-water jacket (Fig. 3) or an ice jacket (Fig. 4). 30 SYSTEMATIC ORGANIC CHEMISTRY In order to separate as much liquid as possible from a large bulk of solid, the solid, after being filtered in the ordinary way by means of a Buchner funnel and well pressed, is removed from the funnel, placed in a stout piece of cloth and tightly wrapped. It is then placed in a press of the ledger type and pressure gradually applied (of. Drying). Decolorisation. It often happens that the com- pound prepared in a particular pre- paration is discoloured ; various methods are used to remove traces of colouring and of tarry matter. The most common is to boil up the sub- stance in solution with animal char- coal — added in the cold — and then to filter and recover the compound from the filtrate by crystallisation or distillation. Very little of good Fig. 28. decolorising carbon is necessary as a rule, and that may be re-vivified by impregnating with a concentrated zinc chloride solution, igniting, and washing with acid. It should be remembered that animal charcoal contains only about 10% of carbon, the remainder being phosphates of different metals, iron, etc. ; this should be considered especially when decolorising in acid solution. If any of these substances are likely to be harmful, the animal charcoal should be boiled up with .hydrochloric acid, filtered, washed and dried. Sometimes a solution remains cloudy after filtration. As a rule this cloudiness can be removed by adding very small equivalent quantities in solution of calcium chloride and sodium phosphate. The calcium phosphate pre- cipitated usually brings down all gelatinous matter and may then be removed by filtration. Decoloration is sometimes due to oxidation, and the colouring matter may often be removed by passing S0 2 gas through the solution, always provided that this has no action on the substance in solution. Salting Out. Some substances which are soluble in water are not soluble or only slightly soluble in solutions of certain salts, such as sodium chloride, calcium chloride, sodium acetate, sodium sulphate. The salt may be added in the solid form or as a saturated solution. By this means alcohol and acetone can be separated from their solutions in water. The process is used very largely on the technical scale for the separation of dyestufis (see pp. 373, 374). APPAKATUS AND METHODS 3] Extraction of Solids. When it is required to separate a solid from an impurity, it is desirable to carry out the extraction in a Soxhlet apparatus, a sketch of which is shown (Fig. 29). The substance to be extracted is placed in a paper thimble A which is set in position in the main Soxhlet tube, a loose plug of cotton wool being placed in the top of the thimble. The Soxhlet is attached to a flask which contains a small amount of a solvent; the solvent chosen should be such that either the desired substance or the impurity is insoluble, or nearly so. A condenser is attached to the Soxhlet tube ; the ball condenser C shown in sketch is the most convenient. When the solvent is boiled, the vapour passes through side tube D to the condenser, from which liquid drops back to the thimble. When this liquid reaches the top of the side tube E, it automatically syphons back into the flask B with the extracted matter in solution. The process is continuous. It is advisable to use a minimum quantity of solvent at the beginning and, if necessary, to add more solvent through the condenser. More rapid extraction can be brought about if the substance is inti- mately mixed with some inert substance, such as glass or sand. When the extraction is judged to be complete, the Soxhlet is removed and the substance crystallised from the solution remaining in the flask. Separation of two Immiscible Liquids. Fig. 29. For this purpose, funnels of the types Fig. 30 are used. The liquids to be separated are run into the funnel, and after standing for some time, the stopper at the top is removed and the more dense liquid is run off through the tap at the bottom. If the upper layer is required, it is poured out through the top of the funnel after running off the bottom layer ; this is to prevent contamination with the liquid in the stem ■ and tap of the funnel. In all cases a funnel of convenient size should be chosen. If the volume of liquids is small, separation can be effected by the use of a small pipette to which Is attached a length of rubber tubing ; the Fig. 30. 32 SYSTEMATIC ORGANIC CHEMISTRY rubber tubing is held in the mouth, gentle suction is applied, and the eye kept on a level with the common surface of the liquids. Separation by Extraction. — Separating funnels are again used for this purpose. The substance to be extracted is generally in solution or sus- pension in water. A solvent which is immiscible with water and in which j the substance is soluble is added— in small quantities at first. The funnel is stoppered and agitated, holding the tap and stopper closed, after which it is set aside in a vertical position until the liquids separate. Separation is then effected as above. The solvent most commonly employed is ether, but benzene, chloroform, ligroin and amyl alcohol are used in special circumstances. In all cases extraction should be carried out more than once, the extracts 1 being added together. The amount of substance which goes into solution in ether, etc., depends on the distribution coefficient, that is, the ratio of the concentrations in the two solvents after equilibrium is attained. This ratio is constant for any given temperature, provided the molecular weight of the solute does not vary in either solvent (see " Outlines of Physical Chemistry," Senter, p. 177). It follows then that extraction may have to be repeated several times, and also that it is more efficient to extract a number of times with suc- cessive small quantities of solvent rather than once with a large quantity. When a quantity of the substance separates from the solution as an oil, this oil should be separated before extraction is attempted. In extraction with ether the following points should be noticed : — 1. All burners in the immediate vicinity should be extinguished. 2. After shaking, the funnel should be inverted and the pressure released by gradually opening the stopcock. 3. If an emulsion persists after standing, this may frequently be" destroyed by agitating the ethereal layer with a glass rod. Addition of a few drops of alcohol is sometimes effective. In special cases filtration may be useful. If the funnel be held in a stream of warm water for a time, separation may be facilitated. 4. Extraction is complete when a sample of the ether layer when evaporated to dryness leaves no residue. 5. Ether is soluble in water to the extent of 8%. If the aqueous volume to be extracted is large, it should be saturated with common salt, in which solution ether is much less soluble. 6. Water is soluble in ether to the extent of 1-5%. It follows, therefore, that the ether extract must be dried (see p. 34) before removing the ethei by evaporation. 7. The ether is generally removed by distillation. A moderate sized flask should be used and more solution added from time to time. The apparatus shown in Fig. 31 enables the additions to be made without APPAKATUS AND METHODS 33 interruption of the distillation. The flask is fitted with a two-holed stopper carrying a dropping-funnel and a glass tube. By means of a piece of rubber tubing and a second short piece of glass tubing inserted through a cork, the top of the funnel is connected through the first piece of glass tubing with the interior of the flask ; the rubber tubing on this connection carries a spring clip. The ethereal solution — a portion at a time — is placed in the funnel and the cork inserted in the neck of the funnel. The stop- cock of the funnel and the spring clip are then opened simultaneously, and the ether flows into the flask without interruption, since the pressure above the ether in the funnel and the pressure inside the flask have been equalised by the opening of the spring clip. When the ether has run in, the tap and the clip are closed. 8. Salts are generally insoluble in ether. Ferric chloride, mercuric chloride, mercuric iodide, stannous chloride and chromic anhydride, however, are fairly soluble. Drying. Drying of Solids.— (a) At Ordinary Temperature. — When the solid is insoluble in a volatile solvent, such as ether or petroleum ether (40° — 60°), and this solvent is miscible with the solvent from which the solid was crystallised, drying may be greatly facilitated by washing the substance while still on the filter with such a volatile solvent. The usual method of drying at ordinary temperature consists in spreading the solid on several layers of filter paper or on a porous plate, and leaving until dry. It is necessary, however, to pro- tect the solid from dust contamination by covering with filter paper or watch-glass in such a manner that free access of air is per- mitted. The drying may be more quickly carried out by placing the solid on a porous tile in a vacuum desiccator. Desiccators. — These are of two types, the ordinary and the vacuum (see Fig. 32). The drying in the latter is generally 6 — 7 times quicker than in the former. The Fig. 32. desiccator is charged, according to the nature of the substance to be absorbed, with one or other of the following substances — Cone. H 2 S0 4 : to absorb water, basic substances. Granular calcium chloride : to absorb water, alcohols, some basic substances. Solid sodium or potassium hydroxide : to absorb water, acids, phenols, alcohols, esters. Quicklime : to absorb water, acids. S.O.C. D SYSTEMATIC OKGANIC CHEMISTKY Soda lime : to absorb water, acids. Paraffin wax : to absorb carbon disulphide, ether, chloroform, benzene. It is obvious from the foregoing list that impurities as well as solvent may be removed from a solution by exposure in a desiccator containing a suitable absorbent. It is essential that the absorbent does not react with the substance to be dried. Of drying agents, cone. H 2 S0 4 , P 2 0 5 and solid KOH are equal in drying power and most effective for ordinary purposes. Solid NaOH and CaCl 2 are likewise nearly equivalent in drying power. N.B. — A suction flask should always be inserted between a vacuum desiccator and a water pump when the latter is used, as slight varia- tions in water pressure may result in water being sucked back into the desiccator. (b) At Higher Temperature. — If it is desired to dry a solid at a tempera- ture higher than ordinary, a test should first be made with a small portion. This is necessary since many substances decompose at relatively low temperatures and such temperatures should be noted. Moreover, the presence of slight impurities or of solvent may considerably lower the melting point of the solid. Other changes — decomposition, loss of solvent of crystallisation, etc. — may take place on heating, and these should be noted. For drying at temperatures up to 100°, the water bath or steam oven is generally used. For drying at higher temperatures the air oven is em- ployed, but here a thermometer should be inserted and particular care taken that the substance is not over-heated. A very convenient form of drying apparatus is the toluene bath (p. 35). Drying of Liquids. — (a) At Ordinary Temperature. — Liquids are usually dried by the addition of some solid dehydrating agent, such as granular calcium chloride, solid caustic potash or soda, anhydrous sodium sulphate, anhydrous potassium carbonate, anhydrous cupric sulphate, phosphorus pentoxide, metallic sodium. It is essential that the drying agent should have no action on the liquid to be dried, or any substance dissolved in it, and great care should be exercised in the choice of a drying agent. For example, calcium chloride should not be used for drying alcohols or amines. Caustic potash or soda should not be employed for drying acids, phenols, esters, certain halides, etc. The minimum quantity of drying agent should be used, otherwise liquid is lost by absorption. After standing some time, the liquid is separated by decantation or filtration. The drying of ethereal solutions is an operation frequently met with in the laboratory, for in most cases it is advisable to dry an ethereal extract before evaporating off the ether. Again, to dry a moist solid, it is often convenient to dissolve it in ether and to dry the ethereal solution with a dehydrating agent. The dry solid is then obtained on evaporation of the ether. (b) At Higher Temperatures. — This method is seldom employed, and is only effective when the liquid has a high boiling point and is not volatile in steam. APPARATUS AND METHODS 35 Baths. Baths are used for heating, drying, etc. ; the heating can be thus carried out more uniformly than is possible with a direct name. A judicious selection of the type of bath required for any operation should be made — an air bath should not be used if a water bath suits the purpose. In all cases a means of ascertaining the temperature should be provided, either by taking the temperature of the bath, or of the sub- stance heated on the bath. Water Bath. — This is employed for heating or drying up to 100°. For tem- peratures below 100° the vessel should be immersed in the water ; for 100° the vessel should be so far immersed as to be largely surrounded by steam. When a water bath is to be used for many hours or days, a constant-level arrangement should be attached (Fig. 33). Salt Solutions.— Temperatures above 100° can be attained by the addition of salts to the water. The boiling points of a few saturated solutions is appended : Fig. 33. Sodium chloride Magnesium sulphate Potassium nitrate . Sodium nitrate Calcium chloride . B.P. 109° 108° 116° 121° 180° Toluene Bath (Fig. 34), — This bath consists of a double-walled enclosure access to which is obtained by a hinged door carrying a stout rubber joint. The door is fastened by thumb-screws. Any suit- able liquid can be placed in the outer jacket to which is attached a con- denser ; the liquid, how- ever, most generally used is toluene (B.P. 110°). The inner compartment is fitted with an exit tube carrying a vacuum gauge, and this may be attached to a vacuum pump. This offers a very convenient method of drying sub- stances at a temperature — slightly above 100° and under reduced pressure. Air Bath. — A convenient form of air bath is made of sheet iron, and Fig. 34. 36 SYSTEMATIC ORGANIC CHEMISTRY completely lined on the outside with asbestos. Air ovens are generally used for temperatures above 100°. In no case should the substance be placed on the lower shelf ; the bulb of the thermometer should reach close to the shelf on which the substance is placed. Sand Bath— This form of bath is used for temperatures well above 100°. A thermometer should always be placed in the substance being heated. It is important that the layer of sand should only be just thick enough to protect the vessel from excessive heat. Oil Bath— Suitable oils may be used such as higher boiling paraffins, melted paraffin wax, glycerine, etc. The oil should not be heated to its flash point, and the surface of oil exposed should be as small as possible. Fig. 35. Metal Bath.— This type of bath is the most suitable for heating to high temperatures. Before heating, the vessel to be heated should be held in a luminous flame until covered with a deposit of carbon which prevents the fused metal from adhering to the flask ; it also renders the vessel less liable to crack. The following metals and alloys may be used : — M.P. Bi (4), Cd (1), Pb (2), Sn (1) .... 65° Bi (4), Cd (2), Pb (1), Sn (2) .... 80° Bi (3), Pb (2), Sn (2) 95° Bi(l),Pb(l),Sn(l) . . . . . 122° Sn . MM • • 232° Pb . . . . . • • 327° Zn , . • • • 419° APPARATUS AND METHODS 37 Mechanical Agitation. The importance of mechanical agitation cannot be over-estimated. In some preparations a yield cannot be obtained at all unless efficient agitation is provided ; mechanical agitation should be used, there- fore, wherever continuous agitation is essential. A suitable vessel should first be chosen, and an agitator made, usually of glass rod, to suit this par- ticular vessel. The rela- tive densities of the sub- stances to be mixed must be borne in mind ; obvi- ously it will require much more vigorous agitation to sulphonate benzene, or to reduce nitrobenzene with, say, iron, than to fuse a sulphonic acid with caustic soda, or to reduce dinitrobenzene with sodium sulphide solution — due to the much greater differences in the specific gravities of the reacting substances. The propeller type of agi- tator is always service- able provided the speed is high. The driving force may be electric or hydraulic, but various simple devices can be adopted depending on the nature of the chemical reaction. For example, air or other gas may be passed into the mixture, etc. Where active boiling is taking place in a mixture, mechanical agitation is usually unnecessary. The sketch (Fig. 35) shows a battery of agitators driven by an electric motor and employing different types of agitators. By changing the driving belt to different pairs of pulleys, different speeds of agitator can be obtained. It is always wise to have some idea of the speed of agitation. Fig. 37. 86395 38 SYSTEMATIC ORGANIC CHEMISTRY Sulphonation Pot. — The most satisfactory method, however, of using mechanical agitation is in conjunction with a specially constructed piece of apparatus. Various types can now be procured and some are very effective. Fig. 36 shows one such. It consists of a cast-iron pot with a lid carrying the brass bearing and gear wheels of the central shafts. The large driving pulley drives the outer shaft in one direction and the inner shaft in the opposite direction, a suitable form of iC blade " being attached to each. The lid is attached to the pot by thumb -screws, suitable jointing matter being used, such as rubber. Openings are provided in the lid for reflux condenser, thermometer, and addition tube. The apparatus, which may be driven from an electric motor, is admirably suited for sulphona- tions, nitrations, and reductions. When such an apparatus cannot be obtained the apparatus (Fig. 37) in glass is recommended. Heating under Pressure. When a mixture of substances is heated in an enclosed space no volatile matter can escape, and hence, at a certain period in the heating, pressure begins to develop. Substances or solutions may thus be heated to a temperature above the boiling point of any or all of them without incur- ring the loss of reacting substances or reaction products ; and the method has the advantage that many reactions which cannot be brought about by boiling substances in open vessels can be easily brought about by heating under pressures above atmospheric. If it is desired to heat two substances under pressure, but not to a temperature above the I boiling point of either, a third substance of lower boiling point which has I no chemical action on either of them is introduced. Heating under pressure is generally done in — (a) Sealed Tubes, or (6) Autoclaves. (a) Sealed Tubes. — As only small quantities of substance can be dealt with, the method is only applicable for small scale experiments or quantita- tive work {e.g., Estimation of Halogens — Carius). Generally soft glass tubes j about 50 cms. long, 18 — 20 mms. outside diameter, and walls 2-5 — 3 mms. thick, are used, but if the contents attack soft glass, or if large quantities of gas are evolved on heating, or if the temperature of heating is high, tubes of difficultly fusible potash glass should be employed, since these are more resistant to chemical action and do not crack so readily. As glass deteriorates with age, a piece of new glass should be selected for sealed tube work. A suitable length is cut (see p. 440), thoroughly washed, and after being allowed to drain for some time is dried by warming with a 4 moving flame while a current of air is blown through it. To seal one end of the tube, about two inches of the tube at this end is heated by revolving it in the smoky flame of a blowpipe for a few minutes. The blast is then turned on slowly, and the tube, while held in one hand j at an angle of 45°, heated at the end until softening takes place, when a previously warmed glass rod held in the other hand is fused on to it. The ; blast flame is adjusted so that it will heat a zone of glass about as broad as the diameter of the tube to be sealed, and is directed at a point about 3 cms. j APPARATUS AND METHODS 39 from the end of the tube, which is slowly brought into the flame with constant rotation. When the glass begins to thicken the ends are slowly pulled asunder, taking care not to pull out the softened glass too much, but to allow the sides to fall together, as shown at A (Fig. 38). When this occurs, the narrow part is heated till it melts and the ends pulled asunder. The closed end should present the appearance shown at D If a considerable mass of glass be left at d, it may be removed by heating it to redness, touching it with the pointed end of a cold glass tube, to which it will adhere, and by which it may be pulled away. Any blob of glass remaining is heated in a small blowpipe flame, and by gently blowing with the mouth into the open end of the tube, and re-heating and blowing again, the blob can be removed, and finally, by using a rather larger flame, heating and blowing alternately, the end is neatly rounded — 1 \ H 1 P E 1 > =— a Fig. 38. shown at E. After cooling slightly the hot end of the tube is annealed by holding it for a few minutes in a luminous flame. Hard glass is much more easily worked in the oxygen- coal gas flame, obtained by attaching a cylinder of oxygen in place of the air blast to the lamp. Filling the Tube. — Since the tube is afterwards sealed at the open end, it is necessary when filling the tube to take care that none of the ingredients come into contact with it near that end. The tube should be clamped in a vertical position beside the working bench, and a funnel tube, having a stem as wide as the tube will admit, is inserted in the open end ; through this the substances are added. In analytical work (see Estimation of Halogens) the weighed substance should be introduced in a container of its own. When fuming liquids are employed (see Preparation of Para- nitrobenzyl Bromide) these should be placed in test tubes stoppered with glass wool or asbestos ; obnoxious fumes during the sealing process are thus largely avoided. When withdrawing the funnel tube, care is taken to avoid bringing it into contact with the walls of the tube. The amount of substance which may be introduced depends on the conditions ; the tube should never be more than half filled, and if much gaseous products 40 SYSTEMATIC ORGANIC CHEMISTRY is formed, or if the temperature of heating be high, a lesser quantity should be introduced. Sealing. — The tube is held at an angle of 45°, and in a manner already described ; the open end is warmed in a smoky flame, then heated to softening, and a glass rod sealed on to it. Likewise, as described before, the tube is heated at a point about 3 cms. from the end by rotating it in a blast flame. The glass is evenly heated and not drawn out, but when the apparent inside diameter of the tube is reduced to about 3 mms., the tube is quickly withdrawn from the flame and a capillary formed by slowly drawing out the thickened part (Fig. 38). In order to secure a thick end to the point of the capillary a, about 2 cms. of the tube at the shoulder is warmed a little at the moment of finally sealing it ; the con- traction of the air in the tube, in consequence of its cooling, ensures the Sealing of Hard Glass.— For this a slightly different method of sealing is employed. As soon as the glass is sufficiently soft, it is not thickened, but is drawn out at once to a wide capillary. By directing the flame on the shoulder of the tube and continuing to draw out, the capillary is then lengthened to about 3 cms. It is then thickened by revolving in the flame and finally sealed off. The sealing of hard glass' requires at least a first-class blowpipe ; and the sealing may be facilitated by placing a brick or tile near the flame in such a position that the heat is reflected on to the tube. As soon as the tube is sealed and annealed, it is clamped in a vertical position, with capillary uppermost, and left to cool. Tube Furnace or Bomb Furnace- Heating. — When cold, the tube is trans- ferred to the removable metallic cylinder of the tube furnace (Fig. 39). The cap of the cylinder is screwed on and the latter placed in position in the furnace. Various forms of furnace are used : the common forms are heated by a series of pinhole gas-jets, and are easily regulated. The Fig. 39. glass at a running together to a solid end when it is melted in the fl a m e. If it is desired to collect a gas produced during the chemi- cal reaction, the capillary is made several inches long, and is bent into the form of a delivery tube. It is then possible to break the tip of this under a cylin- der in a trough of liquid. APPARATUS AND METHODS 41 removable cylinder is not supplied with all furnaces, but it is advisable to have it for the following reasons : (a) The furnace may be approached without fear of glass splinters, and (b) in case the tube bursts, the glass fragments and contents (of the sealed tube) remaining in the cylinder can be easily removed. When a removable cylinder with screw cap is not available, the sealed tube is placed in the fixed cylinder of the furnace, the capillary end pointing towards a wall of the furnace room so that no damage will accrue in case of an explosion. At the commencement of the heating, small flames are used and the temperature raised gradually to the desired point. The temperature is indicated by a thermometer, inserted through a cork in the opening at the top of the furnace, the bulb of the thermometer being about 1 cm, from the bottom of the iron tube. The danger of the bursting of sealed tubes may be diminished in many cases by interrupting the heating after a certain length of time, opening the capillary after the tube has completely cooled, and allowing the generated gases to escape. The tube is then resealed and heated again. Or, to take an example of bromination, one half the necessary quantity of bromine may be added at first, the tube sealed and heated to the desired temperature ; the tube is then allowed to cool, after which the capillary is opened, the second instalment of bromine added through a long capillary tube, and the tube after being resealed is heated as before. Opening Sealed Tubes. — The greatest possible care must be observed in handling an unopened tube. It must never be removed from its pro- tecting case for examination or for any other purpose. It must not be opened until perfectly cold, and when opening it is held in such a position that no one can be injured should it burst. When cold, the protecting case of iron is withdrawn from the furnace and held in one hand. The cap (if present) is unscrewed, and while the iron tube is held in a slightly inclined position so that the capillary is somewhat higher than the other end, the capillary is made to project beyond the iron case by giving the cylinder a slight jerk. The part of the iron cylinder near the open end and which is gripped with the hand, is wrapped round with a cloth. The extreme end of the capillary is then gradually heated in a Bunsen flame. If pressure exists inside, the end of the capillary is blown open on softening, provided there is no obstruction in the capillary. If there is obstruction it may be removed by heating. Under certain conditions, as, for instance, when the tube contains an explosive mixture of gases (which sometimes happens when phosphorus and hydriodic acid are used) or when it is desired to collect the gaseous products, the end of the capillary is carefully broken off with pincers or tongs — in the latter case inside a piece of pressure tubing connected with a suitable gas receiver. After the capillary is opened, the tube is removed from the iron case, and the conical end broken off in the following manner. A deep file mark is made across the tube about 1 cm. below the shoulder, and the scratch is touched with the pointed end of a drawn-out glass rod which has been 42 SYSTEMATIC ORGANIC CHEMISTRY previously heated to redness in a blowpipe flame. In the majority of cases a crack forms at the file mark, and this may be led round the tube by touching the glass immediately in front of the crack with the heated point of the glass rod. If the thick end of a glass rod is used in these operations, the crack may form longitudinally on the tube. A piece of wire, bent to the shape of the tube and heated to redness, may be employed in place of the heated glass rod. Another method which is not so liable to cause splintering at the cut is the following. The file mark is made as before. Two pieces of wet filter paper are rolled round the tube, one on each side of the file mark and about 0-5 cm. apart. The space between the papers is then heated by gradually bringing it into a pointed blow- pipe flame, the tube being rotated the while. If the tube does not crack at once, it is given a few turns in the flame, after which the heated portion is moistened with a few drops of water, when the breaking off follows with certainty. In ana- lytical work this latter method of opening should be employed, as it is important to avoid the mixing of frag- ments of glass with the contents of the tube. The tube is then emp- tied of its contents. (b) Autoclaves. — These are closed vessels made of iron, bronze or copper. Those in common use are made from cast steel, and hence are capable of standing great pressure. Such vessels are not suited for heating mixtures of a resultant acid reaction, but may be used for mixtures which are of neutral or alkaline reaction. When acidic substances are being dealt with, autoclaves covered on the interior with a resistant enamel are used, but unfortunately few enamels are very durable and in consequence the vessel has to be re-enamelled at intervals. Of the special alloys which are used for autoclaves, those containing 1 — 3% of Ni which are highly resistant to alkalis, and those containing 12% Si and 4 — 6% Al (Tantiron) which are practically unattacked by acids, are the most important. Fig. 40 Fig. 40. APPARATUS AND METHODS 43 represents a form of autoclave which is commonly used for experi- mental purposes. The body B of the autoclave is immersed in an oil or metal bath. Along the flange of the body there runs a circular groove of rectangular section which is filled with lead (molten lead run in and allowed to solidify). On the lower surface of the flange of the lid there is a projecting ring which fits neatly into the lead-filled groove, and when the screws between the body and lid are tightened, a pressure-tight joint is formed at the lead ring. In order to secure a proper joint, judicious tightening of the screws (these should run easily at first) is necessary. To begin with, one nut is screwed home with the hand, the nut diametrically opposite is similarly treated, these are then alternately given a few turns with a wrench until they are moderately tight. The intervening nuts are then screwed home, each one a little at a time so as to maintain as far as possible a uniform pressure over the whole surface of the lead ring. This done, a further tightening — which may be repeated a few times — is given to all the nuts, going round them in circular fashion. During the heating, the nuts should be tested from time to time, and tightened if necessary. The lid of the autoclave is provided with two openings — one for a ther- mometer tube, and another for a pressure gauge, each of which is fixed by a screw pressure-tight joint ; sometimes there is a third opening for a safety valve, but with a tested autoclave bought from a reliable firm, a safety valve is unnecessary, and often an encumbrance. Such autoclaves should, however, be frequently tested by engineers. It is often convenient to place inside the body of an autoclave a neat fitting pot of lead or enamelled metal. The space between the two vessels may be filled with molten solder or molten lead, but in many cases no such filling is used. The inner vessel serves to protect the main body of the apparatus, and its easy removability (when no filling is used) — on the small experimental scale at any rate — can be utilised in the charging and the emptying of the apparatus. During the operation of heating, oil or mercury sufficient to cover the bulb of a thermometer is placed in the thermometer tube. Autoclaves are made in various sizes with capacities ranging from half a litre up to a few thousand litres. Those which are provided with stirring gear are, of course, the more efficient, and details of these may be obtained from the catalogues of well-known manufacturers. The limits of temperature and pressure are about 300° C. and 60 atmo- spheres, and the greatest charge should not be more than about 75% of the volume of the vessel. Temperature of the outer bath, in which a ther- mometer is kept immersed, should be about 30° higher than the internal temperature. The screws must not be loosened so long as there is any pressure indicated on the gauge. When a charge contains ammonia or develops ammonia on heating, a manometer fitted with an iron and not with a bronze tube, must be used, since ammonia vapours rapidly destroy copper or bronze tubes. Density of Liquids. The density of a liquid is most easily determined by means of vessels known as pyknometers, the volume of which need not exceed 1 c.c. 44 SYSTEMATIC ORGANIC CHEMISTRY Fig. 41. Perkin's modification (Fig. 41) of the Sprengel pyknometer is well adapted for small quantities of liquid and also for volatile liquids. The apparatus which usually has a volume of 2 — 10 c.cs. consists of a U-tube, the limbs of which are drawn out to capillaries and bent as shown. On limb A a small bulb is blown, and below this a ring is etched round the capillary. The ends of the capillaries are fitted with loose glass caps. The apparatus is cleaned and dried by washing successively with water, alcohol, and ether, and then drawing air through the tube. The apparatus is first weighed empty, being suspended from the beam of a balance by a piece of platinum wire. Liquid is then drawn into the vessel through B until the bulb on A is half full. The apparatus is immersed in a bath at constant temperature— ice and water serves for 0°, while a thermostat should be used for higher temperatures. After standing in the bath for some time, the apparatus is inclined until limb B assumes a horizontal position ; a piece of filter paper applied to the end of this limb is allowed to absorb liquid until the meniscus on limb B sinks to the etched mark. The apparatus is then returned to a vertical position, the glass caps are replaced on the limbs, and after removing from the bath the whole is carefully dried with a good cloth and weighed. Afterwards the apparatus is cleaned and dried, and the operation repeated, using distilled water. , If both operations are carried out at the same temperature — W The approximate density == — where W = weight of liquid, and W x = weight of water. W The absolute density ( D x D, 4/ Wj where D = density of water at 4°, temperature of operations. ^nd The Polarimeter. The polarimeter is used for determining the specific rotations of optically active substances and also for determining concentrations of solutions of optically active substances of known specific rotation. The polarimeter con- is sists of two Nicol prisms I N and N x (Fig. 42) set J at a distance from one another and on a common axis. N x is the polariser and N the analyser. The polarimeter tube T, containing a definite 0 ID S P N, Fig. 42. APPARATUS AND METHODS 45 length — usually 10 or 20 cms. — of liquid is placed between the two Nicols. Monochromatic light must be used, generally that from a sodium flame F being employed. The light from F passes first through a bichro- mate cell C in order to give the pure sodium D light, then through a lens to the polariser. In the Laurent polarimeter a thin quartz plate P is inserted to cover half the field. In the Lippich type a small Nicol prism or two Nicol prisms are used instead of a quartz plate to cover part of the field ; and this instrument possesses the advantage that it can be used with light of any wave length. Light vibrating in only one plane passes through the polarimeter tube to the analyser N, which can be rotated about the main axis. The eyepiece at E consists of a system of lenses for focussing. The sodium flame produced from common salt or borax is adjusted to give a maximum of light, the tube T being removed for the time being. The polariser N x is fixed in position. The illuminated split disc is then focussed from the eyepiece E, and the analyser rotated until the whole field is of uniform intensity. The reading as indicated on a circular disc fitted with a vernier attached to the eyepiece is taken as the zero reading. This reading should be determined before every experiment. The substance of which the specific rotation is to be determined is placed in a clean dry polarimeter tube in the form of liquid or of solution so as to completely nil the tube. The tube is then placed in position in the polarimeter ; the analyser is again turned until the intensity of illumination on each half of the disc is equal. The angle is again read on the scale, and this reading, minus the zero reading, gives the angle of rotation, a D . The temperature at which the observation is made should be noted ; in some cases a jacketed polarimeter tube, through which water at a definite temperature is circulated, is used. The specific rotation — J ^ — at temperature t of a pure liquid is calculated from the formula : — a = angle of rotation. I = length in decimetres of liquid in polarimeter tube. d = density of liquid at t°. The specific rotation of an optically active compound in a pure solvent may be calculated from the formula : — c = gms. of active compound in 100 c.cs. of solvent. p = percentage of solute by weight. If the substance turns the plane of polarisation to the right, i.e., clock- wise, it is said to be dextro-rotatory, and if to the left, laevo-rotatory. (See Findlay, " Practical Physical Chemistry," p. 112.) Hi SYSTEMATIC ORGANIC CHEMISTRY Fig. 43. Apparatus for certain Catalytic Preparations. The following apparatus (Fig. 43) serves for such a large number of catalytic preparations that it may be considered general apparatus (see acetaldehyde, acetone and hexahydro-phenol). The catalyst, generally distributed over some bulky material (e.g., pumice, etc.), is placed in a combustion tube which is ins ert ed through two holes in the ends of a long cylin- drical air bath made of tin or light sheet iron. The air bath is of such a length (about 75 cms.) that it fits on an ordin- ary combustion furnace by which it is heated ; its diameter is usually about 20 cms., and there are two openings in the top for the insertion of thermometers. Nitrogen-filled thermometers or thermo-couples are necessary for temperatures of 400° and above. When a liquid is used in the reaction it may be led into the tube in the following ways, the method selected depending on the requirements of the reaction : — 1. A distilling flask is attached to the inlet end of the tube and the liquid distilled over, or it may be evaporated over in a current of gas. 2. A silica distilling flask surrounded by an air bath (a tin or iron box covered with a card of asbestos) is connected to the tube, the bath being heated to a high temperature, say 300° — 400°. The liquid is dropped into the silica flask from a dropping funnel inserted through a cork in the neck of the flask ; by this means the rate of passage of vapours over the catalyst may be controlled, and further, the vapours are at a high temperature before coming into contact with the catalyst. 3. A bent dropping funnel is inserted through a cork in the inlet end of the combustion tube, the first 15 cms. of which is loosely packed with asbestos and is kept outside the air bath. The liquid is allowed to drop in slowly from the funnel. A small flame is lighted under the tube where the liquid drops, and the flames gradually increase in size as the catalyst is approached ; this precaution is to prevent breakage. A solid, if easily volatile, may be treated as for a liquid. In some cases it may be steam distilled over the catalyst. Most experiments of this kind require efficient apparatus for condensing the products of reaction ; owing to the high temperature it is generally Fig. 44. APPARATUS AND METHODS 17 advisable to pass these first through an empty flask and then through some efficient type of condenser. The condensing apparatus may be attached to the exit end of the combustion tube by means of a cork and delivery tube, or the exit end of the combustion tube may be bent and drawn out after the shape of an adapter. Addition Tube. The Y-shaped tube (Fig. 44) is a most convenient apparatus through which to make additions to a mixture which is being heated under a reflux condenser. It is particularly useful for the addition of solids (for example, sodium — see p. 361). For the addition of liquids a dropping funnel is introduced through a cork in the upright limb. PART II CHAPTER III the linking of carbon to carbon , Hydrogen Compounds In this section are described those preparations in which carbon atoms are caused to unite with one another. It is this property whereby carbon atoms unite to form molecules of seemingly unlimited com- plexity, which has led to the study of the carbon compounds being made a special branch of chemistry, and these reactions are, theoretically at any rate, the most important of all those discussed. They are often known as " nucleus syntheses." Reaction I. Passage of the Vapour of certain Hydrocarbons through a red-hot Tube. (A., 230, 5.) — A large number of hydrocarbons condense to form hydrocarbons of higher molecular weight when their vapour is passed through a red-hot tube. The method, however, is only of theoretical importance for the yield is in most cases small owing to incomplete con- version, and to the formation of a large number of by-products. Benzene has been obtained from acetylene in this way ; benzene itself, and diphenyl methane treated in a similar manner give diphenyl and nuorene respec- tively. Heat R.H. + H.R. > R.R. + H 2 , where R.H. is a hydrocarbon. Preparation 1. — Diphenyl (Phenyl-benzene). C 6 H 5 .C 6 H 5 . C 12 H 10 . 154. Method I. — In this experiment the apparatus shown in Fig. 45 is used. The flask, of about 1J litres capacity, contains 500 gms. of benzene kept boiling by means of a water bath. The flask is provided with a cork having two perforations, through one of which the tube a passes while < the second accommodates the tube b. This leads to the iron tube R (a wrought-iron gas pipe of 1 metre length, and 20 mms. internal diameter), which is filled with pieces of pumice, and heated by means of a com- bustion furnace or a Fletcher's gas furnace to a bright red heat. From the flask the benzene vapour passes into the glowing tube, and is here partially converted into diphenyl, hydrogen, and other products. The unchanged benzene and the volatile diphenyl pass through the tube e into the con- I denser K and flow from it through a back into the flask. The tube a dips 48 THE LINKING OF CARBON TO CARBON 49 below the level of the liquid, and at d has a tube sealed on for the escape of the hydrogen. The operation is carried on for from 6 to 10 hours, the apparatus acting auto- matically. The flask now contains a fairly concentrated solution of diphenyl in ben- zene. The latter is removed on a water bath, and the residue is fractionated. The part passing over above 150° solidifies in the receiver, and consists of almost pure diphenyl. It may be purified by crystalli- sation from alcohol. The yield is greatly dependent on the tem- perature of the iron tube. With a low gas pressure the ordinary p IG> 45> combustion furnace is almost useless ; in that case it is better to substitute a Fletcher's gas furnace or a charcoal furnace for it. 2CJL C 6 H 5 .C 6 H 5 + H 2 Yield.— Up to 20% theoretical (100 gms.). D. f 0-9845. (Z. Ch., 1866, 707 ; A., 230, 5.) This " thermal condensation " can also be brought about by exposing the vapour of benzene to the action of a wire or filament kept at red heat by an electric current. Method II. — The apparatus is as follows : — Two copper wires pass tight-fitting through the cork in the neck of a flask, and are connected together above the benzene in the flask by a coiled platinum wire, 25 cms. long and -2 mm. in diameter. A reflux condenser is fitted to the side tube of the flask. 50 gms. of benzene are boiled on a water bath in the flask. After fifteen minutes' boiling the air in the flask will have been expelled, and the current is switched on and regulated by means of a variable resistance so that the platinum spiral glows red (4 — 4-5 amps. ; 8 — 10 volts). A battery of accumulators can be used as a source of current, or the latter can be obtained from an alternating service supply at 110 or 220 volts, the necessary reduction in current and voltage being brought about by a rheostat or a bank of lamps. In the latter case it is more economical to use the thread of a carbon lamp instead of a platinum wire. After five hours a portion of the benzene will have been converted into diphenyl under the action of red heat. The unaltered benzene is removed 50 SYSTEMATIC ORGANIC CHEMISTRY on a water bath, and the residual liquid fractionated from a small flask, the portion 240°— 270° being collected separately, and recrystallised from alcohol or from a mixture of benzene and petroleum ether — 2C 6 H 6 = C 6 H 5 .C 6 H 5 + 2H. Yield.— 22% theoretical (11 gms.) Colourless leaflets ; soluble in ben- zene ; M.P. 71° ; B.P. 254° ; D. f 0-9845. (Z. e., 7, 903.) Fig. 46. Reaction II. Reduction under certain Conditions of Aromatic Ketones. (A., 194, 310.) — When aromatic ketones are reduced by zinc dust in the presence of glacial acetic acid pinacones are formed (see p. 65). 2C 6 H 5 .CO.C 6 H 5 + 2H = (C 6 H 5 ) 2 C.(OH).C(OH).(C 6 H 5 ) 2 . If hydrochloric acid is added the reduction goes to the corresponding hydrocarbon ; e.g., from benzophenone s-tetraphenylethane is obtained. 2C 6 H 5 .CO.C 6 H 5 + 6H > (C 6 H 5 ) 2 .CH.CH.(C 6 H 5 ) 2 . Reaction III. Oxidation under certain Conditions of Lower Hydro- carbons. (B., 32, 432.) — In this reaction two molecules of a hydrocarbon are condensed together by eliminating hydrogen by means of an oxidising agent. Two neutral oxidising agents, potassium persulphate, and lead oxide, are especially useful in this type of reaction. The former is used in dilute aqueous solution, at a temperature of about 100° ; to obtain results with the latter much higher temperatures are necessary. The substance is mixed with the lead oxide and heated to over 250°, or it is distilled over heated lead oxide. The results obtained vary with the temperature and the amount of lead oxide used, e.g., fluorene can be oxidised to either THE LINKING OF CARBON TO CARBON 51 bidiphenylene- ethane or bidiphenylene-ethylene. With potassium per- sulphate the first stage only is reached. C 6 H 4 C 6 H 4 \ r, / C 6 H 4 C 6 H 4 \ \ / / C fi H 4 CH - CH C 6 H 4 C 6 H 4 C 6 H 4 It is to be noted that to obtain practicable yields this reaction must be confined to aromatic hydrocarbons. In the aliphatic series it only takes place in a few cases, and then gives but a yield of the order of 1%. Preparation 2. — Dibenzyl (1-2 Diphenylethane). CfiHriCHo.CHo.CRH, C 1d H n 182. 90 grns. potassium persulphate (1 mol.) are dissolved in a litre of water, and to this is added 60 gms. (2 mols.) of toluene. The mixture is heated on a water bath for 4 hours in a flask fitted with good agitation and a reflux condenser (see Fig. 37). The oily layer is then separated, dried over calcium chloride and fractionally distilled, the fraction 270° — 280° con- sisting of dibenzyl and benzoic acid being separately collected. The earlier fractions consist of toluene and benzaldehyde. The dibenzyl fraction is dissolved in ether and the benzoic acid removed by shaking with dilute caustic soda solution. The ether is then removed on the water bath, and the residue recrystallised from dilute alcohol. 4C 6 H 5 .CH 3 + 0 2 ^2C 6 H 5 CH 2 CH 2 C 6 H 5 + 2H 2 0. Yield. — 15% theoretical (9 gms.). Colourless monoclinic needles ; M.P. 51°— 52° ; B.P. 248° ; D.g 0-9752. (B., 32, 432, 2531.) Preparation 3. — Bi-diphenylene-ethane (l-2-Di-(2-2 1 -diphenylene)- ethane). CH i CH C26 H 18 . 330. 10 gms. (2 mols.) of fluorene, and 15 gms. (excess) of lead oxide are E 2 52 SYSTEMATIC OKGANIC CHEMISTRY thoroughly mixed and heated with slow stirring in a metal crucible in a bath till the temperature of the latter reaches 270°, where it is kept for 2 hours. The crucible is cooled to 150°, wiped clean, and plunged into cold water. The contents, which are by this means loosened, are ground up, extracted with boiling benzene, and the extract concentrated to small bulk. The crystals which separate are recrystallised from benzene, or glacial acetic acid. The mother liquors contain unaltered fluorene. + H 2 0 Yield. — 50% theoretical (5 gms.). Colourless crystals ; slightly soluble in alcohol and ether ; soluble in hot benzene and glacial acetic acid ; M.P. 246°. (A., 291, 6.) Reaction IV. (a) Action of Dehydrating Agents on a Mixture of an Aromatic Hydrocarbon and an Aromatic Alcohol. (B. 6, 964.) — This reaction, which was discovered by Baeyer, gains importance from its similarity to the methods used in preparing such substances as phenol- phthalein and fluorescein (see pp. 100, 378). Various dehydrating agents — concentrated sulphuric acid, zinc chloride, phosphorus pentoxide — can be used. Sulphuric acid, although perhaps the most convenient, has the disadvantage that it tends to sulphonate the aromatic substances employed. At a low temperature, however, diphenylmethane can be obtained from benzyl alcohol and benzene. At 140° phosphorus pentoxide condenses benzene and diphenylcarbinol to triphenylmethane (see B., 7, 1204). Not only substituted benzyl alcohols, but even mandelic acid can be brought within the scope of the reaction, while in place of benzene its nitro, amino or phenolic derivatives may be used. REjCH ;OH + HI R n = RRjCHRu + H 2 0. Preparation 4. — Diphenylmethane. (Benzyl-benzene.) CH 2 .(C 6 H 5 ) 2 . C 13 H 12 . 168. A mixture of equal weights of concentrated sulphuric acid and glacial acetic acid is run into a mixture of 10 gms. (1 mol.) of benzyl alcohol (q.v.), 27 gms. (excess) of benzene and 100 gms. of glacial acetic acid until most of the benzene has separated on the surface. After 12 hours, 500 gms. of concentrated sulphuric acid are added under constant cooling, and the THE LINKING OF CARBON TO CARBON 53 mixture again allowed to stand for 6 hours. The mass is then poured into water, extracted with ether, the extract dried over calcium chloride, and the residue, after removing the ether on a water bath, fractionated under reduced pressure, the fraction 174° — 176° at 30 mms. being separately collected. C 6 H 5 .CH 2 OH + C 6 H 6 = C 6 H 5 .CH 2 .C 6 H 5 + H 2 0. Yield. — 25% theoretical (4 gms.). Colourless oil ; on cooling solidifies to needle-shaped crystals ; orange-like odour ; M.P. 26° ; B.P. 760 263° ; B.P. 30 175° ; D. 1 1-0056. (B., 6, 964.) Reaction IV. (b) Action of Dehydrating Agents on Certain Ketones. (J. pr., 15, 129). — This is a reaction of historical interest, for it was by its preparation from acetone by distillation with fairly strong sulphuric acid that the symmetry of mesitylene was deduced, and from it the orientation of such compounds as m-xylene was established. It will be noted that though a high temperature is used, steric hindrance prevents any sul- phonation of the mesitylene formed. Besides its dehydrating action, the purely condensing capabilities of sulphuric acid should not be overlooked. Thus methyl acetylene con- denses in the presence of sulphuric acid to mesitylene. 3CH 3 C ■ CH = C 6 H 3 (CH 3 ) 3 . Compare the action of heat on acetylene. Preparation 5— Mesitylene. (s-Trimethylbenzene.) C 6 H 3 (CH 3 ) 3 [1:3:5]. 120. 400 gms. of clean dry sand are placed in a 2-litre retort connected with a condenser. 250 gms. (3 mols.) of acetone are added, and then a cooled mixture of 560 gms. of concentrated sulphuric acid and 150 gms. of water are run in, in a slow continuous stream, the retort being meantime cooled in cold water. After 24 hours' standing, the mixture is slowly distilled, directly or in steam. When oily drops appear in the neck of the retort, the receiver is changed and the distillate collected until only very small quantities of the oil appear. Meanwhile the colour of the liquid in the retort changes to deep brown, and finally to black, sulphur dioxide is evolved, and the mass froths up considerably. The upper yellowish layer of the distillate is separated from the lower aqueous layer, washed with caustic soda and water, and dehydrated over calcium chloride. It is then fractionated, the fraction 100° — 200° being redistilled four times over thin slices of metallic sodium, when about two-thirds of it is obtained as pure mesitylene coming over at 161° — 166°. 3CH 3 .CO.CH 3 = C 6 H 3 (CH 3 ) 3 + 3H 2 0. Yield. — -Variable, about 25% theoretical (40 gms.). Colourless, strongly refracting liquid ; B.P. 760 1 63° ; D.J 0-881 ; D. 1 , 0 0-8694. (J. pr., 15, 129 ; A., 147, 143 ; 278, 260 ; Bl., 40, 267 ; Am. Soc, 15, 256 ; 20, 807.) Acetophenone condenses in a manner similar to acetone if it is heated 54 SYSTEMATIC OBGANIC CHEMISTEY with phosphorus pentoxide, or better if saturated with dry hydrogen chloride at ordinary temperatures. s-Triphenylbenzene is deposited after standing for several days in a warm place ; by resaturating the mother liquors, yields of up to 50% can be obtained. Two isomeric s-triphenyl- benzenes are known (B., 7, 1123 ; 23, 2533 ; C., 1900, II., 255.) C 6 H 5 HC m o i CgH; 0 CH C — C fi H, CH CfiH, CH — C 6 H 5 C H 2 CH H Reaction V. Cinnamic Condensation and Elimination of Carbon Dioxide. (Am. Soc, 1, 313.) — This is an extension of Perkin's reaction, and depends on the fact that when benzaldehyde and phenyl-acetic acid are condensed in the usual way, the unsaturated acid thus formed is unstable, and loses carbon dioxide, giving stilbene. C 6 H 5 .CHO + H 2 C.(C 6 H 5 )COOH -> C 6 H 5 CH : C(C 6 H 5 )COOH -> C 6 H 5 CH : CH.C 6 H 5 . Technically this method is of no importance, as the hydrocarbon is obtained from coal-tar. Reaction VI. (a) Action of certain Anhydrous Metallic Halides on a Mixture of an Aromatic Hydrocarbon and an Akyl Halide. (Friedel-Crafts.) (C. r., 1877, 1450.)— The " Friedel-Crafts " reaction, of which the above illustrates one phase, is one of the most important condensing reactions known to organic chemistry. Applied to the production of aromatic hydrocarbons and their derivatives, the action consists in the catalytic use of anhydrous aluminium chloride for condensing an aromatic hydro- carbon or its derivatives with a chlorine or bromine compound. Halogen acid is always evolved, and the product is a compound with aluminium chloride which decomposes, yielding the required compound on addition of water. Not only does the reaction proceed without the Use of heat in most cases, but frequently it must be moderated by using a large excess of the hydrocarbon, or better by diluting with some neutral solvent, such as ligroin, carbon disulphide, or nitrobenzene. The two former diluents automatically keep down the temperature to their boiling points; the latter has the especially useful property of dissolving anhydrous alu- minium chloride. If a hydrocarbon derivative is used, coupling takes place in the para position, or, if that is occupied, in the ortho, but the yield suffers. In place of aluminium chloride, in some cases aluminium THE LINKING OF CARBON TO CARBON 55 bromide (D.R.P., 126421), aluminium foil and hydrogen chloride (B., 28, 1136), or mercuric chloride (see Reaction VI. (b) ), ferric chloride, zinc chloride (B., 30, 1766), or the aluminium-mercury couple (Reaction VI. (c) ) can be used. (See also C. r., 84, 1392 ; B., 18, 2402 ; 33, 815. For other uses of this reaction, see pp. 80, 115.) The methods employed vary but little. The aluminium chloride is slowly added to a mixture of the hydrocarbon and the alkyl halide, or the alkyl halide is added to a mixture of the other two. The latter process is most used in the case of volatile halides which are led in gaseous form into the mixture of the other two components, for a time which varies as the number of alkyl groups it is desired to introduce. EC1 + A1C1 3 = E.CIAICI3 R.C1.A1CI 3 + RJi = RI^AlClg + HC1 RRjAlClg + H 2 0 = RR X + A1C1 3 -f H 2 0. Note. — Bottles filled with aluminium chloride have frequently a high internal pressure and must, therefore, be opened with great care, being covered with a cloth while so doing. For some anomalies in the behaviour of aluminium chloride as compared with that of aluminium bromide, see A. ? 225, 155. Preparation 6. — Triphenylmethane. (Methenyl-triphenyl.) CH.(C 6 H 5 ) 3 . C 19 H 16 . 244. 40 gms. (1 mol.) of chloroform which has stood for 12 hours over calcium chloride is mixed with 200 gms. (excess) of similarly treated benzene in a retort connected to an upright condenser. The operation is carried out in a fume cupboard. 30 gms. of anhydrous aluminium chloride (see p. 503) are added in 5-gm. lots every 5 minutes with constant shaking. The reaction is completed by boiling for half an hour on a water bath, the retort cooled, and its contents very cautiously poured into an equal volume of ice-cold water. The upper layer of triphenylmethane dissolved in benzene is separated, dried over calcium chloride, the benzene removed on a water bath, and the residue fractionated to 200°. It is then distilled under reduced pressure from a retort without a condenser. Impure triphenylmethane first distils and then the distillation slackens. The retort is more strongly heated till the distillate no longer solidifies on cooling. The crude triphenylmethane in the receiver is twice recrystallised from hot benzene, heated on a water bath to remove " benzene of crystallisa- tion " and finally recrystallised from hot alcohol. CHCI3 + 3C 6 H 6 = CH(C 6 H 5 ) 3 + 3HC1. Yield. — 33% theoretical (25 gms.). Colourless rhombic plates ; M.P. 92° ; B.P. 760 350° ; D. g 1-0568. The compound with benzene has the formula C 9 H 16 .C 6 H 6 . Note. — The aluminium chloride used must be recently made and of good quality, otherwise it must be resublimed from a retort, as it is essential it should be perfectly anhydrous. (C. r., 1877, 1450; B., 26, 1961 ; BL, 37, 6 ; A., 197, 252.) 56 SYSTEMATIC ORGANIC CHEMISTRY Reaction VI. (b) Action under certain conditions of Aluminium and Mercuric Chloride on a Mixture of an Aromatic Hydrocarbon and an Alkyl Halide. (J. C. S., 117, 1335.)— This is a development of the Friedel-Crafts reaction which has lately yielded some very interesting results. As far back as 1895 an attempt to use a mixture of aluminium powder and mercuric chloride in the ordinary Friedel-Crafts reaction ended in failure (B., 28, 1139). Later (B., 37, 1560), it was proved that mercuric chloride and aluminium in benzene or toluene formed compounds of the type C 6 H 6 .AlCl 3 .HgCl. It was by the use of these double compounds that the secondary reactions, which caused the failure of the earlier attempts, were avoided and some very interesting condensations brought about. In the formation of the catalyst the following reaction occurs : C 6 H 6 + Al + 2HgCl 2 ^ C 6 H 6 .AlCl 3 .HgCl + Hg. An excess of mercuric chloride must be used to prevent the mercury iberated amalgamating with the aluminium, for the couple so formed would act concurrently with, but in a different manner to, the double compound (see the next reaction). Applied to the synthesis of hydrocarbons the following results have been obtained by this new method. 9 : 10-Diphenyl-9 : 10-dihydroanthracene is formed by the condensation of benzene and chloroform, whilst in the ordinary Friedel-Crafts reaction (A., 194, 254 ; 227, 107) triphenyl- methane (Preparation 6) is the main product, traces of chloraryl- methanes and tetraphenylethane (B., 26, 1952) being also formed. The same compound was also obtained from benzal chloride and benzene. Carbon tetrachloride and benzene give 9:9 : 10 : 10-tetraphenyl-9 : 10- dihydroanthracene as do also phenylchloroform and benzene. In the older reaction triphenylchloromethane (p. 425) is the chief product. Chloroform and toluene yield by this process dimethyl-9 : 10-ditolyl- 9 : 10-dihydroanthracene ; using aluminium chloride, tetratolylethane has been prepared (B., 14, 1530). Finally benzal chloride and toluene yield dimethyl-9 : 10-diphenyl-9 : 10-dihydroanthracene. EH + , C1 2 CH K \ I \ I C 6 H 5 CH C 6 H 5 + C 6 H 4 C 6 H CHCL + CH RH | I R For other applications of this reaction see pp. 84, 115. THE LINKING OF CARBON TO CARBON 57 Preparation 7. - 9 : 10-Diphenyl - 9 : 10 - dihydroanthracene (y 1 - y 2 Diphenylanthracene hydride). CH 332. | CH C 6 H 5 . To prepare the catalyst, 13 gms. (excess) of dry benzene and 20 gms. (excess) of mercuric chloride are treated, gradually, in a flask fitted with a reflux condenser, with 1 gm. of aluminium powder, the flask being mean- while vigorously shaken and occasionally cooled in ice-water. A green crystalline mass separates, and the reaction is completed by immersing the flask in tepid water for half an hour. The mercury liberated in the ' reaction is removed, and the catalyst is then ready for use. 9 gms. (2 mols.) of chloroform are added drop by drop through the con- j denser, and the flask left at ordinary temperature for 2 hours, heated for an hour at 40° and then for an hour at 40° — 50°. During the whole course of the reaction the contents of the flask are well agitated by a mechanical stirrer (see the apparatus shown on p. 37). On cooling, the product is decomposed with ice and filtered. From the filtrate a deep-red oil separates, from which all unchanged benzene is evaporated, and the residue extracted with boiling acetic acid containing a little water. The compound which separates on cooling is recrystallised from dilute alcohol, and then repeatedly from acetone. The same compound can be prepared from 8 gms. (2 mols.) of benzal chloride, 13 gms. (excess) of benzene, and the above quantities of alu- minium and mercuric chloride. The reaction is completed at 50° — 55°. Otherwise the details are as already described. C 6 H 6 + CHC1 3 CeHe + + + C 6 H 6 CHCI3 + C 6 H 6 C 6 H 5 I CH /\ C 6 H / ^C 6 H 4 + 6HC1 Yh C 6 H 5 . Colourless crystals ; soluble in alcohol ; M.P. 159° (J. C. S., loc. cit.) ; M.P. 164-2° (Am. Soc, 13, 556). Oxidised with chromium trioxide in glacial acetic acid solution, yields anthraquinone ; gives a diacetyl 58 SYSTEMATIC ORGANIC CHEMISTEY derivative on heating with acetic anhydride and pyridine (J. C. S., 117, 1335). Reaction VI. (c) Action of the Aluminium — Mercury Couple, or of certain finely divided Metals on a Mixture of an Aromatic Hydrocarbon and an Alkyl Halide. (J. C. S., 67, 826.) — The action of the couple is analogous to that of anhydrous aluminium chloride. Zinc dust or finely divided copper can also be used. Preparation 8. — Diphenylmethane. (Benzyl-benzene.) C 6 H 5 .CH 2 .C 6 H 5 . C 13 H 12 . 168. 1 gm. of freshly prepared aluminium-mercury couple (see p. 503) is added to 65 gins, (excess) of benzene in a flask attached to an upright condenser, the whole being placed in a fume cupboard. 32 gms. (1 mol.) of benzyl chloride are slowly dropped in from a tap-funnel, during an hour, through the top of the condenser. The flask is then heated on a water bath for 15 minutes, its contents shaken with a very dilute solution of caustic soda, and the benzene solution separated. The aqueous portion is again extracted with benzene, and the whole benzene solution dehydrated over calcium chloride, the benzene removed on a water bath, and the residue distilled under reduced pressure, the fraction, 174° — 176° at 80 mms., being retained. C 6 H 5 CH 2 C1 + C 6 H 6 + (Al/Hg) = C 6 H 5 .CH 2 .C 6 H 5 + HC1 + (Al/Hg). Yield. — 33% theoretical (14 gms.). Properties (see p. 53). (J. C. S., 67, 826.) Reaction VI. (d) Action of Anhydrous Aluminium Chloride on a Mixture of an Aromatic Hydrocarbon and a Diazonium Compound. (B., 26, 1994.) — The solid diazonium salt is warmed with an aromatic hydro- carbon and anhydrous aluminium chloride. As a by-product, the chlor- derivative of the hydrocarbon is formed. The reaction proceeds thus :— C 6 H 5 .N 2 .C1 + C 6 H 6 (A1C1 3 ) = C 6 H 5 .C 6 H 5 + N 2 + HC1.(A1C1 3 ). Diphenyl can also be obtained from diazobenzene chloride by treatment with stannous chloride. (J. pr., [2], 40, 97.) 2C 6 H 5 .N 2 .C1^C 6 H 5 .C 6 H 5 + 2N 2 + Cl 2 . SnCl 2 + Cl 2 ~> SnCl 4 . See also Reaction VIII. Reaction VII. (a) Action of Sodium on Halogen Compounds (Wiirtz, Fittig, and Freund). (A., 131, 303.) — The application of this reaction to the synthesis of paraffins by Wiirtz was of great importance to chemical theory, as it afforded strong evidence of the chain linking of carbon atoms, and enabled the structure of many hydrocarbons to be determined by their syntheses. Fittig applied the reaction to aromatic hydrocarbons. In this latter case a second side-chain may be introduced from a di-halogen derivative, simultaneously with the first or subsequently in a second reaction. All the possibilities of the reaction are illustrated in the synthesis of anthra- THE LINKING OF CARBON TO CARBON 59 cene hydride and phenanthrene simultaneously from o-bromobenzyl bromide. CH 9 Br Br C 6 H 4 < + 4Na + ^>C 6 H 4 CH 2 Br BrCH 2 C 6 H 4X / + 4NaBr CH 9 Br BrCIL CH 2 .CH 2 / \ <\ S II, + 4Na ^CeH, = C 6 H 4 C 6 H 4 Br Br + 4NaBr The reaction does not occur with the same readiness in all cases, the yields obtained varying greatly. j9-Bromotoluene gives a good yield of ^-xylene, the ortho-compound a poor yield of the corresponding hydrocarbon, whilst the meta-compound gives none whatever. If the reaction is sluggish, it may be promoted in many cases by raising the temperature or by adding a little ethyl acetate. If the reaction is too vigorous, on the other hand, an indifferent solvent, e.g., toluene, ether, or - ligroin, is added to moderate it. Since the discovery of the Friedel-Crafts reaction its very wide and varied application has led to its supplanting the Fittig method, than which in most cases it gives better yields. Freund applied the method to the synthesis of cycloparamns. From trimethylenedibromide, trimethylene was prepared, whilst hexamethylene- dibromide vielded hexamethylene in a similar manner. (M., 3, 626 ; A. Ch., [5], 14, 488.) CH 2 +2Na = /\ + 2NaBr. CH 2 Br CH 2 CH 2 In the Fittig reaction it is to be noted that bromo- andiodo-compounds ? give better yields than chloro-compounds. Preparation 9. — Ethyl Benzene. (Phenylethan.) t C 6 H 5 .C 2 H 5 . C 8 H 10 . 106. 30 gms. (excess) of metallic sodium in the form of small pieces of wire are slowly added to 120 c.cs. of anhydrous ether prepared from commercial ether as described on p. 209. The ether is contained in a round flask tf (1 litre) which when the evolution of hydrogen has ceased, is attached to an upright condenser and immersed in a vessel of ice-water. A mixture i of 78 gms. (2 mols.) of bromobenzene and 70 gms. (excess) of ethyl bromide, both carefully dehydrated, is added and the mixture left to stand over- night. The liquid is then decanted from the sodium bromide, which has a blue colour, and the latter washed twice with dry ether. The ether is removed on a water bath, and the residue fractionated from a small I distilling flask, the fraction 132° — 135° being collected separately. C 6 H 5 Br + C 2 H $ Br + 2Na = C 6 H 5 .C 2 H 5 + 2NaBr. 60 SYSTEMATIC ORGANIC CHEMISTRY Yield.— 60% theoretical (30 gms.). Colourless liquid ; B.P. 134° ; D. 2 f 0-8664. (A., 131, 303.) Note.— The residue in the flask contains unaltered sodium. This must be destroyed by adding the residue in small portions to alcohol, and allowing to stand till all action ceases. Preparation 10. — Dibenzyl. (1-2-Diphenylethan.) C 6 H 5 .CH 2 .CH 2 .C 6 H 5 . C 14 H 14 . 182. 12 gms. (slightly more than 2 mols.) of sodium wire are added to 50 gms. (2 mols.) of benzyl chloride, the whole refluxed on a water bath until no further change takes place, extracted with dry ether, and the extract fractionated, the fraction 244° — 254° being retained, and recrystallised from alcohol. The reaction goes best in the absence of a solvent, but toluene can be added to lower the refluxing temperature. 2C 6 H 5 CH 2 C1 + 2Na = C 6 H 5 .CH 2 .CH 2 .C 6 H 5 + 2NaCl. Colourless needles ; soluble in benzene and in hot alcohol ; M.P. 51°— 52° ; B.P. 248° ; D. g> 0-9752. (A., 121, 250 ; 137, 258.) Reaction VII. (b) Action of Metals other than Sodium on Iodo-com- pounds. (B., 34, 2176.) — This reaction can be applied in both the aliphatic and aromatic series. In the latter, chloro- or bromo -compounds can also be used if nitro-groups are present in the ortho- or ^ra-positions. The reaction is carried out by heating the iodo compound with zinc if aliphatic, or with copper if aromatic, to a high temperature in a sealed tube. In this way n-octane (di-w-butyl) has been obtained from w-primary-butyl iodide, and diphenyl from iodobenzene. 2RI + 2Cu = KR + Cu 2 I 2 . The reaction is only suited for the preparation of symmetrical com- pounds from one halogen compound. Attempts to prepare unsymmetrical ones by using two halogen compounds, give mixtures difficult to separate, because the two halogen compounds used must be both aromatic or both aliphatic, and hence condense with themselves under the same conditions as they condense with one another. Fittig's method is free from this drawback. Preparation 11. — Diphenyl. (Phenylbenzene.) C 6 H 5 .C 6 H 5 . C 12 H 10 . 154. 20 gms. (2 mols.) of iodobenzene are heated with 20 gms. (excess) of copper powder for 3 hours in a sealed tube (see p. 38) to 230°. The contents of the tube are extracted with ether, and the filtered extract fractionated, the ether being removed on a water bath and the fraction, 245° — 255°, retained and recrystallised from alcohol. 2C 6 H 5 I + 2Cu = C 6 H 5 .C 6 H 5 + Cu 2 I 2 . Yield. — 80% theoretical (6 gms.). Colourless leaflets ; soluble in hot alcohol ; M.P. 70°— 71° ; B.P. 254° ; D. * 2 0 9845. (B., 34, 2176.) THE LINKING OF CARBON TO CARBON 6] Reaction VIII. Action of certain finely divided Metals on diazonium compounds in Alcohol or Acetic Anhydride Solution. — This reaction is limited to the preparation of s-diaryl compounds. Copper, zinc, or iron powder may be used, but the former is, on the whole, the most satisfactory, especially when it has been freshly prepared according to Gattermann's recipe. As with other " finely divided metal " reactions of this type, there is a Sandmeyer analogue, but except in the case of nitro-compounds, the reaction then for the most part takes a different course (see Reaction CLXVL). The reaction proceeds smoothly in aqueous or absolute alcoholic, or in acetic anhydride solutions. (B., 23, 1226 ; 28, 2049.) Its exact course has not been worked out, but it may be formulated as follows : — ENH 2 -> EN 2 S0 4 H 2EN 2 .S0 4 H + Cu -> EE + 2N 2 + CuS0 4 + H 2 S0 4 . Peepakation 12. — Diphenyl (Phenylbenzene). C 6 H 5 .C 6 H 5 . C 12 H 10 . 154. 31 gms. (2 mols.) of aniline dissolved in 150c.cs. of water and 40 gms. (slight excess) of concentrated sulphuric acid are diazotised in the usual way (see p. 366) with 23 gms. (2 mols.) of sodium nitrite in 10% solution. The diazo solution is treated with 100 gms. of 98% alcohol, and 50 gms. (excess) of copper powder (see p. 504) are added while the whole is well stirred (see p. 37). A vigorous evolution of nitrogen occurs, and by the end of the reaction the temperature has risen to 30° or 40°. The stirring is continued for an hour, and then the mixture is steam distilled. The distillate at first consists chiefly of alcohol with small amounts of an oil insoluble in water. Small portions of it are tested from time to time by dilution with water. When a solid precipitate is thus obtained, the distillate is separately collected until no more solid comes over. The distillate is then heated to 71° to melt the solid diphenyl ; on cooling, the liquid may be easily poured off. The product is almost pure, but may be recrystallised from alcohol. 100 gms. of zinc powder may be used instead of the copper. With it the best results are obtained by adding, first, 10 c.cs. of a cold saturated solution of copper sulphate, and then the zinc as above. Care must be taken in this case not to let the temperature rise above 30° — 40°. Iron powder can also be employed. Yield. — In each case 25% theoretical (6 gms.). Properties (see p. 60). (B., 23, 1226 ; 28, 2049.) Diphenyl can also be obtained from diazobenzene sulphate by treating it with warm benzene (B., 26, 1997), but the method is not of much im- portance, except in so far as it illustrates the well-known reactivity of diazo-compounds. Reaction IX. (a) Action of Magnesium Alkyl or Aiyl Halide on certain Alkyl or Aryl Halides in the presence of Absolute Ether (Grignard). (C. 1906, II., 748.)— The Grignard reaction has perhaps a wider application than even the Friedel* Crafts or the diazo reaction. When an alkyl or aryl 62 SYSTEMATIC ORGANIC CHEMISTRY bromide or iodide is treated with magnesium powder in presence of absolute ether, a magnesium alkyl or aryl halide is formed. Mg + EI = RMgl. The substance so formed can be treated with a large variety of reagents to give a correspondingly large number of compounds, provided there is no moisture present, the smallest trace of which completely inhibits reaction. There are various theories to account for the action of the ether or the other solvents which can be used in its place. These will be found discussed in any large text-book on organic chemistry. When alkyl halides act on an absolute ethereal solution of magnesium alkyl or aryl halide, hydrocarbons are formed. RMgl + UJ. = RRj + Mgl 2 . The same type of reaction occurs when magnesium acts on an excess of an alkyl or aryl halide in the presence of absolute ether. n-Hexyl bromide in this way yields n-dodecane. C 6 H 13 Br + Mg = C 6 H 13 .MgBr. C 6 H 13 .MgBr + C 6 H 13 Br = C 12 H 26 + MgBr 2 . Further apnlications of the Grignard reaction are given under Reactions XIV., XXII., XXXIV., XLIIL, LX. Reaction IX. (b) Action of Heat on the Compound formed by treating Magnesium Alkyl or Aryl Halide with a Ketone in absolute Ethereal Solution (Grignard). (B. 5 35, 2647.)— When the Grignard reagent is treated with a ketone, the following reaction occurs : — BRjCO + E n MgI = RB 1 !R 11 C.OMgI. This latter compound when treated with water is hydrolysed to a ter- tiary alcohol RRjRjjCOH. If, however, the anhydrous reaction mixture be heated for a long time on the water bath, an olefine is formed with the splitting-off of magnesium hydroxyiodide. CH 3 I + Mg = CH 3 .Mg.I. CH 3 .Mg.I. + C 6 H 6 .CO.CH s = (C e H 6 )(CH 8 ) a C.O.Mg.I. CH 3 (C 6 H 5 )(CH 3 )C l .O.Mg.I = (C 6 H 5 )(CH 3 ).C : CH 2 + Mg(OH)I. Acetophenone and magnesium methyl iodide yield 2-phenyl-l-propene. As can be seen from the equation one at least of the radicals R, R 1? R 1]L , must have a non-tertiary carbon linked in the intermediate compound to the " hydroxy-magnesium-iodide " carbon. Preparation 13— 1.1-Diphenyl-methyl-ethylene. (C 6 H 5 ) 2 C:CH.CH 3 . C 15 H 14 . 194. The Grignard reagent is prepared from 6 gms. (2 mols.) of dry mag- nesium, and 39 gms. (2 mols.) of ethyl iodide (redistilled), as described in Preparation 18, 120 c.cs. of anhydrous ether being used. 23 gms. (1 mol.) of dry, finely divided benzophenone are added, the flask being cooled THE LINKING OF CARBON TO CARBON 63 if the reaction becomes too vigorous. The mixture is then heated 6 hours on a water bath, treated with dilute acid, extracted with ether, the ether removed on a water bath, and the residue fractionated under reduced pressure, the fraction 169° — 170° at 18 mms. being separately collected and recrystallised from petroleum ether. C 2 H 5 I + Mg-*C 3 H 5 .Mg.I. C 2 H 5 .Mg.I + (C 6 H 5 ) 2 CO -> (C 6 H 5 ) 2 C(OMgI)CH 2 CH 3 . (C 6 H 5 ) 2 C(OMgI)CH 2 CH 3 -^(C 6 H 5 ) 2 C-CH.CH 3 + Mg(OH)I. Colourless crystals ; M.P. 52° ; B.P. 18 169°— 170°. (B., 35, 2647.) Reaction IX. (c) Action of Dimethyl Sulphate on Magnesium Alkyl or Aryl Halide (Grignard). — When a Grignard compound is treated with dimethyl sulphate, methylation of the alkyl or aryl group takes place, the metal-halogen residue being split off. (B. 36, 2116.) E.Mg.Br + (CH 3 ) 2 S0 4 = R.CH 3 + Br.Mg.(CH 3 )S0 4 . Diethyl sulphate reacts similarly. (Am. Soc, 44, 2621.) The yields are good, as is to be expected from the components of the reaction. It will be noted that in the Grignard reactions so far described, only bromo- or iodo-compounds are mentioned. Chlorine compounds do not enter so readily into this reaction ; to induce them to react it is usually necessary to add a crystal of iodine (B., 38, 2759), or mercuric chloride (C, 1907, I., 872), or a previously prepared magnesium solution (B., 38, 1746 ; C, 1907, I, 455). By the method above outlined, toluene has been prepared from bromo- benzene, and ^-xylene from ^-bromotoluene. Prepakation i4.— ^-Xylene (1.4-Dimethylbenzene). CH./ ^>CH 3 . C 8 H 10 . 106. The Grignard reagent is prepared, as in Preparation 18, by heating 67 gms. (1 mol.)_p-bromotoluene, 10 gms. (1 mol.) of dry magnesium and 200 c.cs. of anhydrous ether. When almost all the magnesium has disappeared, a solution of 50 gms. (1 mol.) of dimethyl sulphate (caution !) in anhydrous ether is added. A vigorous reaction takes place, and after it subsides, the reaction product is poured on to ice. The ether is removed by distillation, and the residue is steam distilled. The oil is separated from the distillate and fractionated, the fraction, 136° — 140°, being collected. CH 3 C 6 H 4 Br -> CH 3 C 6 H 4 MgBr -> CH 3 .C 6 H 4 .CH 3 . Yield. — 75% theoretical (40 gms.). Colourless oil ; characteristic odour ; B.P. 138° ; D. 2 4 ° 0-869. (B., 36, 2116.) Owing to the closeness of the boiling points of the three xylenes they cannot be readily separated one from the others ; so that a method such as the above, by which one isomer can be obtained free from the others, in a good yield, is of importance. For some details on magnesium aryl halides see B., 36, 2898. 64 SYSTEMATIC ORGANIC CHEMISTRY Note. — Dimethyl sulphate is extremely poisonous ; on no account must its vapour be inhaled. All work with it should be carried out in a good fume cupboard ; it must be added to mixtures by means of a tap-funnel, i for if spilled on the hands it is readily absorbed through the skin. Should any fall on the clothes, they must be changed at once. Reaction X. Action of Zinc Aikyl on Alkyl Halides. — The action of zinc alkyl on various types of compounds is much the same as that of magnesium alkyl or aryl halide. Before the discovery of the latter, zinc alkyl was widely used as a general synthetic reagent, but its spontaneous inflammability led to its replacement by the more conveniently prepared Grignard reagent ; it does not form aryl compounds ; even in alkyl syntheses it is not nearly so widely applicable, its one advantage being that 4 the reactions it does bring about go somewhat more smoothly than the corresponding magnesium reactions. Zn(CH 3 ) 2 + 2CH 3 I = Znl 2 + 2C 2 H 6 . CHAPTER IV carbon to carbon Hydroxy Compounds The condensations now to be considered include all those in which the reaction is such that there is of necessity a hydroxyl group in the final product. Reaction XI. Intramolecular Elimination of Water from certain Mole- cules. (A., 227, 242.) — When phenyl isocrotonic acid is heated, water is eliminated and a-naphthol is formed. This synthesis which is of theo- retical interest, was discovered by Fittig. It is one of the proofs of the structure of naphthalene. CH CH Reaction XII. Reduction of Aldehydes and Ketones to Pinacones. (B., 27, 456.) — When ketones are reduced to secondary alcohols, some intermolecular condensation usually also occurs, and a pinacone is formed. 2RR 1 CO + 2H = RR 1 C(OH).C(OH).RR 1 . This side reaction cannot be avoided when reducing aliphatic ketones, but in the aromatic series either product can be obtained by varying the conditions of the reduction. An alkaline reduction favours ketone pro- duction ; pinacones are formed when acid reducing agents are employed (see Preparation 15). Pinacones can also be obtained by using suitable electrolytic reductions. Aldehydes, too, have been brought within the scope of the reaction. Thus hydrobenzoin (s-diphenyl-ethan-diol) has been prepared from benzalde- hyde by an acid reduction. 2C 6 H 5 .CHO -> C 6 H 5 .CH(OH).CH(OH).C 6 H 5 . Acetone, the simplest ketone, gives the simplest pinacone. 2(CH 3 ) 2 CO -> (CH 3 ) 2 C(OH)C(OH)(CH 3 ) 2 . The pinacones formed from acetophenone, benzophenone, and many s.o.c. 65 r 66 SYSTEMATIC OKGANIC CHEMISTEY other ketones are exactly similar in structure (C, 1906, II., 148 ; B., 27, 454 ; G, 1900, II., 794 ; C., 1903, II., 23). Preparation 15— Benzpinacone (s-Diphenyl-ethan-diol). (C 6 H 5 ) 2 .C(OH).C(OH).(C 6 H 5 ) 2 . C 26 H 22 0 2 . 366. 5 gms. (2 mols.) of benzophenone are boiled for J hour with 50 gms. of 85% acetic acid and 10 gms. of zinc foil, the whole being well shaken throughout. The liquid is decanted from the zinc residues, cooled, and filtered ; the filtrate is again boiled up with zinc, and this process repeated a third time, the same filter being used each time. The benzpinacone remaining on the filter is then washed with 85% acetic acid, and recrystallised from 13 parts of boiling glacial acetic acid. 2(C 6 H 5 ) 2 CO + H 2 = (C 6 H 5 ) 2 C(OH).C(OH)(C 6 H 5 ) 2 . Yield — 90% theoretical (4-5 gms.). Colourless crystals ; M.P. (with decomposition) 168°. (C, 1881, 150 ; A., 133, 26 ; B., 10, 1473.) For the " pinacoline transformation " undergone by pinacones, see p. 74. Reaction XIII. Condensation of a Phenol with Formaldehyde (Lederer- Manasse). (B., 27, 2411.)— This reaction can take three different courses according to conditions. (i.) With the more powerful condensing agents, e.g., caustic alkalis or hydrochloric acid, a diphenyl methane compound is usually formed. 2C 6 H 5 OH + H.CHO = HO.C 6 H 5 .CH 2 .C 6 H 4 OH + H 2 0. (ii.) The less powerful condensing agents, e.g., alkali carbonates, alkaline earth oxides, lead oxide, or dilute acids or alkalis, give a benzyl alcohol or sometimes a di-(hydroxy-methyl) compound. C 6 H 5 OH + H.CHO = OH.C 6 H 4 .CH 2 OH C 6 H 4 (CH 3 )(OH)[l : 4] + 2H.CHO = C 6 H 2 (CH 3 )(OH)(CH 2 OH) 2 [l : 4 : 3 : 5]. (lii.) Hydrochloric acid sometimes gives a benzyl chloride derivative, the benzyl alcohol first formed being chlorinated by the acid. Such chlorides are easily hydrolysed to the alcohol (see Preparation 124). 0HC 6 H 4 .C1[1 : 2] + H.CHO -> C 6 H 3 (OH)(Cl)(CH 2 OH)[l : 2 : 4] ~> C 6 H 3 (0H)(C1)(CH 2 C1)[1 : 2 : 4]. In all three cases the ^ara-position to the hydroxyl group is preferred ; if it is occupied, condensation takes place, but less readily, in the ortho-. The above rules as to which condensation a given reagent will bring about are only general, in no particular case can it be foretold with certainty how far the reaction will go. The reaction is of importance, especially when as in (ii.) it is used for the production of phenolic methanols. Lately formaldehyde has been con- densed at higher temperatures with phenol to give substances resembling celluloid, and articles made from this synthetic celluloid are now on the market (Bakelite, etc.). For other formaldehyde condensations, see Keactions XIX. (6), XXXIIL (a), XLV. CARBON TO CARBON 07 Pkeparation 16. — o- and j9-Hydroxybenzyl Alcohols (1:2- and 1 : 4- Methylolhydroxybenzene). C 6 H 4 .(OH)(CH 2 OH). C v H 8 0 2 . 124. 30 gms. (1 mol.) of phenol are dissolved in 150 c.c. (a slight excess) of 10% caustic soda ; 35 gms. (excess) of 40% formaldehyde solution are added, and the whole allowed to remain at room temperature for 6 days. It is neutralised with hydrochloric acid, extracted repeatedly with ether, and the latter removed on a water bath. If necessary the residue is steam-distilled to remove unchanged phenol, and the benzyl alcohols which are left are then shaken for some time with cold benzene until nothing further dissolves. The or^o-compound which is much the more soluble, is thus separated from the para-. C 6 H 5 (OH) + H.CHO = OH.C 6 H 4 .CH 2 OH. Yield. — Including both compounds 80% theoretical (32 gms.). o-Hydroxybenzyl alcohol (saligenin) forms colourless crystals ; M.P. 82° ; the ^ara-compound melts at 112°. (B., 27, 2411.) Preparation 17. — 3 : 5 : 3' : 5'-Tetramethyl-2-2'-Dihydroxy-Diphenyl- methane (Di-(3 : 5-Dimethyl-2-Hydroxyphenyl-(l) ) -Methane). CH, CH 3 /\ CH /\ -CH 2 OH C 17 H 20 O 2 . 256. 10 gms. (2 mols.) of xylenol (1 : 3-dimethyl-4-hydroxybenzene) are dis- solved in 300 c.cs. (excess) of 1-5% caustic soda solution ; 5 gms. (excess) of 40% formaldehyde solution are added, and the mixture allowed to stand for 4 days. It is then acidified with acetic acid and extracted with ether, the solvent removed on a water bath, and the residual oil left in a vacuum over sulphuric acid until at length it becomes almost a solid. The latter is recrystallised several times from ligroin. 2C 6 H 3 (CH 3 ) 2 (OH)[l : 3 : 4] + CH 2 0 = [3:5: 6]C 6 H 2 (CH 3 ) 2 (OH).CH 2 .C 8 H a — (CH 3 ) 2 (OH)[3- : 5': 6'] + H 2 0. Long colourless needles ; easily soluble in alcohol, ether, chloroform, acetic acid, benzene ; sparingly soluble in cold ligroin ; M.P. 145° — 146° ; when boiled for 1 hour with acetic anhydride a diacetate is obtained which, when recrystallised from dilute alcohol, forms fine needles, M.P. 86°. (B., 40 ; 2526.) Reaction XIV. (a) Action of Magnesium Alkyl or Aryl Halide on Alde- hydes and Ketones (Grignard). (B., 31, 1003.)— This phase of the Grig- nard reaction can be utilised for the preparation of all types of alcohols (C, 1901, L, 725 ; II, 622 ; 1902, I, 414). (i.) Primary alcohols can be obtained from formaldehyde, or rather from its polymer trioxymethylene, which has to be used in place of the usual aqueous solution. Magnesium phenyl iodide and trioxymethylene F 2 68 SYSTEMATIC ORGANIC CHEMISTRY yield benzyl alcohol for example, the usual Grignard intermediate com- pound being formed. C 6 H 5 MgI + CH 2 0 -> H 2 C(C 6 H 5 )OMgI -> C 6 H 5 CH 2 OH. (ii.) Other aldehydes yield in the same way secondary alcohols. Acetaldehyde and methyl iodide give isopropyl alcohol. CH3CHO + MgCH 3 I (CH 3 )C(CH 3 )OMgI (CH 3 ) 2 CHOH. Benzaldehyde and magnesium phenyl bromide or iodide give diphenyl carbinol. C 6 H 5 CHO + MgC 6 H 5 I -> (C 6 H 5 ) 2 CHOMgI -> (C 6 H 5 ) 2 CHOH. (C. r., 130, 1322 ; B., 31, 1003). (hi.) Tertiary alcohols are formed from ketones. The simplest tertiary alcohol is prepared from acetone and magnesium methyl iodide. Mg(CH 3 )I + (CH 3 ) 2 CO -> (CH 3 ) 2 C(CH 3 )OMgl -> (CH 3 ) 3 C(OH). Methyl ethyl ketone and methyl iodide give tertiary amyl alcohol. CH 3 COC 2 H 5 + CH 3 MgI = (CH 3 ) 2 .COH.C 2 H 5 + Mg(OH)I. Coming to the aromatic series, acetophenone and methyl iodide, for example, yield phenyldimethyl carbinol. An important step in the synthesis of 'i-terpineol is the preparation of ethyl-S-hydroxy-hexahydro jo-toluate from ethyl-S-ketohexahydrobenzoate and magnesium methyl iodide. CO H 9 C CH, CIL C(CH 3 )OH. H,C /\ CH 2 + MgCH 3 I = HaC CH, HC CH COOEt. COOEt. + Mg(OH)I. The usual precautions must be taken in all these reactions, to guard against the possibility of moisture being present. The technique of the method will be apparent from the following. Preparation 18.— (1) Phenylmethyl Carbinol (l-Phenyl-ethanol-(l) ). HC(CH 3 )(C 6 H 5 )OH. C 8 H 10 O. 122. All reagents used must be thoroughly dry. (1.) 36 gms. (1 mol.) of methyl iodide which have been allowed to stand for 12 hours over calcium chloride and then redistilled, are mixed with 50 c.cs. of ether purified and dried as described on p. 209. 20 c.cs. of this mixture are run into a flask fitted with a dropping funnel and long reflux condenser. The flask contains 6 gms. (1 mol.) of magnesium ribbon, which has been cleaned with emery paper and dried in the air oven at CARBON TO CARBON 69 110° — 1:20° for several hours. If necessary, the reaction is started by adding a crystal of iodine. When the first reaction has subsided, 70 c.cs. of dry ether are added, and the remainder of the mixture of alkyl iodide and ether run in drop by drop from the tap-funnel. The contents of the flask are then boiled on the water bath until all (or nearly all) of the magnesium has dissolved. (2.) The flask is now disconnected, and under cooling by ice- water, 26 gms. (1 mol.) of freshly distilled benzaldehyde mixed with an equal volume of dry ether are dropped in from a tap-funnel with constant shaking, and the whole allowed to stand for 12 hours. (3.) Just sufficient hydrochloric acid to dissolve the precipitate is added with constant shaking and cooling. The aqueous layer is separated, and the ether washed first with sodium bicarbonate solution, then with sodium bisulphite (to remove free iodine) and again with sodium bicarbonate. The extract is dried over potassium carbonate and the ether removed on a water bath. The carbinol which remains is fractionated under reduced pressure. (1) CH 3 I + Mg = CH a MgL (2) C 6 H 5 CHO + CH 3 MgI = C 6 H 5 (CH 3 )CH(OMgI). (3) (C 6 H 5 )(CH 3 )CH(OMgI) + H 2 0 = (C 6 H 5 )(CH 3 )CHOH + (OH)Mgl. Yield. — 56% theoretical (20 gms.). Colourless liquid ; insoluble in water ; B.P. 15 100° ; B.P. 28 110°— 111° ; B.P. 10 118° ; B.P. 760 203° ; D. \ 5 1-013. (C. r., 130, 1322 ; B., 31, 1003.) The same method may be used for phenylethyl carbinol taking 39 gms. (1 mol.) of ethyl iodide. The compound is obtained as a colourless liquid ; B.P. 760 221° ; D. 1 ! 0-9900. Peeparation 19. — Tertiary Butyl Alcohol (2-Methyl-2-propanol). (CH 3 ) 3 C(OH). C 4 H 10 O. 74. The Grignard compound is prepared as described in Preparation 18 from 36 gms. (1 mol.) of dry methyl iodide, 120 c.c. of sodium-dried ether, and 6 gms. (1 mol.) of dry magnesium ribbon or powder. 14 gms. (1 mol.) of dry acetone dissolved in 30 c.c. of dry ether are slowly added from a tap funnel with constant shaking and under cooling by ice-water. A white bulky precipitate of the magnesium compound separates. After standing overnight, just sufficient dilute sulphuric acid to dissolve the precipitate is added with constant shaking and cooling. The ether solution of the alcohol separates and is withdrawn and distilled. (CH 3 ) 2 CO + Mg.CH 3 .I = (CH 8 ) a C(CH 8 ).OMgI. (CH 3 ) 3 C(OMgI) + H 2 0 = (CH 3 ) 3 C(OH) + Mg(OH)I. Colourless crystals ; soluble in water ; M.P. 25° ; B.P. 83° ; D. 3 4 ° 0-7788. In an exactly similar manner, using 39 gms. (1 mol.) of ethyl iodide, dimethylethyl carbinol may be prepared. It is obtained as a colourless liquid, soluble in water ; B.P. 762 102° ; D. 1 * 0-8144. The following shows the method of preparing and using magnesium aryl halides in this synthesis. I 70 SYSTEMATIC OBGANIC CHEMISTRY Preparation 20. — Triphenyl Carbinol (Triphenylmethanol). (C 6 H 5 ) 3 C(OH). C 19 H 16 0. 260. 1-2 gms. (1 mol.) of bright magnesium ribbon is dried in the air oven at 110°, cut into 1 cm. pieces, and treated in a well-dried round-bottomed 300-c.c. flask with a solution of 8 gms. (1 mol.) of bromobenzene in 40 gms. of sodium-dried ether to which a crystal of iodine has been added. The flask is now warmed on a water bath, under a reflux condenser in a current of dry hydrogen (caution ! no flame must approach the end of the con- denser.) Light flocculse appear in the liquid ; they are due to unavoidable moisture, but they soon disappear, and then the magnesium begins to dissolve. When the magnesium has completely dissolved, except for traces of impurities — this should not take more than 2 hours — the heating is stopped, and the liquid is treated at ordinary temperatures with 9-1 gms. (1 mol.) of benzophenone dissolved in 25 gms. of sodium-dried ether. The liquid becomes red, then a thick tough precipitate separates, which, when the heating is renewed, reacts vigorously, and solidifies in the course of half an hour. The reaction mixture is then allowed to cool, and treated with pieces of ice and sulphuric acid. When decomposition is complete, steam is passed through until the distillate is clear. This removes ether and all by-products (benzene, diphenyl) ; almost pure triphenyl carbinol remains, and is recrystallised from benzene. C 6 H 5 .Br + Mg = C 6 H 5 .Mg.Br. C 6 H 5 .MgBr + C 6 H 5 .CO.C 6 H 5 = (C 6 H 5 ) 2 C(C 6 H 5 )OMgBr. (C 6 H 5 ) 2 C(C 6 H 5 )(OMgBr) + H 2 0 = (C 6 H 5 ) 3 C.OH + OH.Mg.Br. Yield. — 75% theoretical (10 gms.). Colourless crystals ; soluble in ether and hot benzene ; gives a deep red solution in strong sulphuric acid ; in glacial acetic acid it is colourless, but addition of a drop of concentrated hydrochloric acid gives a deep yellow coloration ; M.P. 159°. Diphenylmethyl carbinol is prepared in the same way from 6 gms. of acetophenone. Reaction XIV. (b) Action of Magnesium Alkyl or Aryl Halide on Esters, Acyl Chlorides, and Acid Anhydrides. (C, 1901, I., 725 ; II., 622 ; 1902, I., 1414.) — In all the above cases tertiary alcohols are obtained, except, of course, in the case of formic esters when secondary alcohols are formed. Using esters the reaction has a wide application, as the examples given below show ; the use of the acyl chlorides and anhydrides is only of theoretical interest. The reactions in all cases take the usual " Grignard " course. RCO.OEt + 2MgR 1 Br — >■ EC.OMgBr + Mg(OEt)Br. K R(B, 1 ) 2 C(OH) + OH.MgBr. RC(R 1 ) 2 OMgBr + MgBr.Cl. R(R 1 ) 2 C.OH + Mg(OH)Br. 2R(R 1 ) 2 C.OMgBr + 0(MgBr) 2 . - 2R(R 1 ) 2 COH. RCfR^OMgBr + H 2 0 -> RCO.C1 + 2MgRjBr -> RfR^aOMgBr + H 2 0 = (RCO) 2 0 + 4MgR!Br = 2R(R 1 ) 2 COMgBr — ; CARBON TO CARBON 71 The yields are in most cases good, and the reactions smooth. A great advantage of the Grignard reaction is that it can be applied to complicated derivatives of the reacting substances. This renders it valuable in the synthesis of substances such as, e.g., terpenes. The following list should give some idea of the scope of the reaction. (i.) Ethyl formate and magnesium ethyl iodide give diethyl carbinol. (ii.) Methyl acetate and magnesium methyl iodide give tertiary butyl alcohol (cf. Reaction XIV. (a) (iii.) ). (iii.) Ethyl A'-tetrahydro-jo-toluate, see p. 68, and magnesium methyl iodide give i-terpineol (l-(2-methyl-2-ethylol)-4-methyl-3-cyclo- hexene). (iv.) Ethyl chloracetate and magnesium phenyl bromide give diphenyl- chlorhydrin. (v.) Methyl benzoate and magnesium phenyl bromide give triphenyl carbinol. (vi.) Acetyl chloride and magnesium methyl iodide give trimethyl carbinol. (vii.) Acetic anhydride and magnesium ethyl iodide give diethylmethyl carbinol. The equations of the above reactions should be written out. An interesting application of the method such as contained in (iii.) should be looked up first-hand in the literature. It may be mentioned that the " Grignard " reaction can also be applied to the production of primary alcohols by the interaction of ethylene oxide and magnesium alkyl halide. (C, 1907, I., 1102 ; 1908, II., 105.) CH 2 CH 2 — OMgBr CH 2 — OH ^>0 +MgBrC 2 H 5 -> | -> | CH 2 CH 2 — CH 2 — CH 3 CH 2 CH 2 — CH 3 . Preparation 21. — Triphenyl Carbinol (Triphenylmethanol). (C 6 H 5 ) 3 C(OH). C 19 H 16 0. 260. The Grignard reagent — magnesium phenyl bromide — is prepared as described in Preparation 20 from 1-2 gms. (1 mol.) of dry magnesium and 8 gms. (1 mol.) of dry bromobenzene. 6-8 gms. (1 mol.) of dry methyl benzoate dissolved in 25 gms. of sodium-dried ether are added to the cold solution, slowly, and with constant shaking. The liquid is then heated on a water bath until no further change takes place. Ice and dilute sulphuric acid are added to the cold reaction mixture, which, when the precipitate has dissolved, is steam-distilled. The triphenyl carbinol which remains is recrystallised from benzene. C 6 H 5 COOCH 3 + 2C 6 H 5 MgBr -> (C 6 H 5 ) 3 C.O.MgBr -> (C 6 H 5 ) 3 C(OH). See p. 70. Reaction XV. Action of Zinc Alkyl on Aldehydes, on certain Ketones, and on Acyl Chlorides. (A., 223, 162.)— As with other " zinc alkyl " reactions the corresponding Grignard reaction described in Reaction XIV. 72 SYSTEMATIC ORGANIC CHEMISTRY lias replaced it almost completely, so that the following is only of more or less historical and theoretical interest. (a) With all aldehydes except formaldehyde, secondary alcohols are formed (A., 213, 369 ; B., 14, 2557). H 2 0 CH3CHO (CH 3 ) 2 CHOZnCH 3 > (CH 3 ) 2 CHOH. This reaction only occurs with zinc methyl and zinc ethyl ; with the higher zinc alkyls the aldehydes are reduced to the corresponding alcohols (B., 17, R., 318 ; A., 223, 162). (b) In general ketones do not react with zinc alkyl. Exceptions are certain ketones which do not contain a methyl group attached to the carbonyl group, e.g., diethyl ketone, ethylpropyl ketone. These with zinc methyl or ethyl yield the usual zinc-oxy-alkyl compounds which, treated with water, give tertiary alcohols (B., 19, 60 ; 21, R., 55). H 2 0 (C 2 H 5 ) 2 CO -> (C 2 H 5 ) 3 COZnC 2 H 5 > (C 2 H 5 ) 3 C(OH). (c) With acid chlorides the reaction takes place in three stages (Z. ch., 1864, 385 ; 1865, 614). (i.) One molecule of the zinc alkyl reacts and the usual type of addition compound is formed. CI. / CH 3 COCl + Zn(CH 3 ) 2 -> (CH 3 ) 2 COZnCH 3 . If water be now added, a ketone is obtained. (ii.) If a second molecule of the zinc alkyl act upon the new com- pound, another reaction takes place. (CH 3 ) 2 C(Cl)(OZnCH 3 ) + Zn(CH 3 ) 2 -> (CH 3 ) 3 COZnCH 3 + Zn(CH 3 )(Cl). (iii.) Addition of water yields now a tertiary alcohol. H 2 0 (CH 3 ) 3 C(O.Zn.CH 3 ) > (CH 3 ) 3 C(OH). If in the second stage another zinc alkyl be used, tertiary alcohols con- taining two or three different alkyl groups can be prepared (A., 175, 374 ; 188, 110, 122 ; C, 1910, II., 1201). Only zinc methyl and zinc ethyl thus furnish tertiary alcohols ; zinc propyl produces only those of the secondary type (B., 16, 2284 ; 24, R., 667). The historical importance of the acid chloride method lies in the fact that in 1864 it led to the discovery of tertiary alcohols. Reaction XVI. Action of certain Oxidising Agents on a- and ^-Naph- thols. (J. R. C. S., 6, 183.) — If to an aqueous solution of a naphthol a few drops of a neutral aqueous solution of ferric chloride be added, a green coloration is produced, and after a time, a flocculent precipitate of dinaphthol. Performed in this way on the " test-tube " scale, the xeaetion is very useful for identification purposes. CARBON TO CARBON -]iihy<3 73 Pkepakation 22. — a-a-Dinaphthol (^'-Dihydroxydinaphthyl). OH OH C 20 H 14 O 2 . 286. 10 gms. (2 mols.) of a-naphthol are dissolved in the minimum quantity of boilin^bater, and ferric chloride solution is gradually added on cooling, until the precipitate formed is a bright reddish- violet. The latter is filtered off, and is boiled once with water, and twice with benzene. The residue is recrystallised from alcohol. 2C 10 H 7 OH. + 0 = OH.C 10 H 6 .C 10 H 6 .OH + H 2 0. Yield. — 35 — 40% theoretical (7 — 8 gms.). Shining rhombic crystals ; insoluble in water ; soluble in alcohol and ether ; slightly soluble in chloroform and benzene ; M.P. 300°. (J. R. C. S., 6, 183.) A solution of a-naphthol in very dilute alcohol can also be used in the above preparation. Preparation 23. — /3-j6-Dinaphthol (o-o'-Dihydroxy-m-m'-dinaphthyl) , OH HO C 20 H 14 O 2 . 286. 10 gms. (2 mols.) of /3-naphthol are dissolved in an excess of ether, and 16 gms. (excess) of anhydrous ferric chloride are gradually added to the solution in a flask fitted with a reflux condenser. Much heat is evolved during this operation. The mixture is then refluxed on a water bath until most of the naphthol is oxidised. (To test this a small portion of the ethereal solution is treated with an excess of dilute hydrochloric acid, and the ether evaporated. The dinaphthol separates out even in the warm as an oil while /3-naphthol crystallises out on cooling.) When this is the case, the ether is removed on a water bath, water and powdered calcium carbonate are added to the residue, and the whole well shaken. Excess caustic soda is then added, the solution is filtered, and precipitated with dilute sulphuric acid. The precipitate is washed with boiling water or boiling ligroin, and recrystallised from benzene. 2C 10 H 7 OH + 2FeCl 3 = OH.C 10 H 6 .C 10 H 6 .OH + 2FeCl 2 + 2HC1. Yield. — 40% theoretical (8 gms.). Colourless needles from alcohol, prisms from a mixture of carbon disulphide and alcohol ; insoluble in water ; slightly soluble in chloroform ; soluble in alcohol and ether ; M.P. 216° ; M.P. (corr.) 218° ; Forms a picrate. (J. R. C. S., 6, 187 ; B., 15, 2166.) CHAPTER V carbon to carbon Oxy Compounds In the following section are discussed the more important of those con- densations which give rise to oxy compounds — aldehydes, ketones, and quinones. The reactions in this section, as in all, may be divided into two classes — those in which the product is an oxy compound, because oxy compounds only undergo the reaction — the oxy group playing, so to speak, a catalytic part, e.g., Reaction XX. (6) ; and those in which an oxy com- pound is actually formed during the action from non-oxy starting sub- stances, e.g. Reaction XVII. Owing to the peculiar activating properties of the oxy group, the former class looms large in the following, more so than in the reactions discussed in the previous section. Reaction XVII. Intramolecular rearrangement of the Glycols (Pinacoline Transformation). (B., 36, 2016.) — Di-primary, primary-secondary, pri- mary-tertiary, and di-secondary glycols yield aldehydes by withdrawal of water and rearrangement, when heated with hydrochloric or sulphuric acids, or with certain dehydrating agents. Ethylene oxide derivatives may be considered to be intermediate compounds, for the ethylene oxide compounds themselves undergo the same change. Hydrobenzoin yields diphenylacetaldehyde. C 6 H 5 .CH(OH).CH(OH).C 6 H 5 — > C 6 H 5 .CH.CH.C 6 H 5 -> (C 6 H 5 ) 2 .CH.CHO. 0 (C, 1907, I, 15 ; B., 36, 2016 ; C, 1905, II., 237.) Secondary-tertiary and di-tertiary glycols change into ketones in the same way, similar elimination of water and migration of an alkyl group occurring. The di-tertiary glycols — known as " pinacones " — undergo this reaction with great readiness, yielding ketones — ■" pinacolines." The simplest of the di-tertiary glycols is tetramethyl glycol or pinacone, and this, by the transformation, gives pinacoline. (C, 1906, II., 670.) (CH 3 ) 2 :C(OH) (CH 3 ) 2 :C I i/° (CH 3 ) 2 : C(OH) (CH 3 ) 2 : CT -> (CH 3 ) 3 C.CO.CH 3 The reaction itself is called the " pinacoline transformation." Ethers of the glycols also behave similarly, in some cases with particular ease 74 CARBON TO CARBON 75 (B., 39, 2288 ; A., Ch., [8], 9, 484). For a corresponding reaction among ketones, see p. 105. Reaction XVIII. Ring Formation by Elimination of Water from certain Molecules. (B., 41, 3632 ; A., 311, 178.)— Many important syntheses of ring compounds come under this heading. Only a few can be mentioned. (i.) 1 : 2-Diketones containing a CH 2 group together with the CO group can be condensed to quinone derivatives — -diacetyl, for example, readily yields dimethyl quinone — under the action of alkalis, ketols are inter- mediately formed. CH3.COCO.CH3 CH 8 C(OH).CO.CH s CH3.CO.CO.CH3 CH 2 .CO.CO.CH 3 CH 3 C(OH)CO.CH 2 CH3C.CO.CH I I "> II II CH 2 CO. 0(OH)CH 3 CH.CO.C.CH3. (B., 22, 2215 ; 28, 1845.) (ii.) The o-benzoylbenzoic acids give anthraquinone derivatives on heating with dehydrating agents. This synthesis is very similar to that of a-naphthol from phenyl-^o-crotonic acid (Reaction XI.), but there is no rearrangement of the primary product. (Z., a Ch., 19, 669.) COx CO H : ! C 6 H 4 i 'fC 6 H 4 -> C 6 H 4 / yC 6 H, o-Benzoylbenzoic acid (Reaction XXXV. (a) ) itself yields anthraquinone, and 2-j9-toluoylbenzoic acid gives 2-methyl-anthraquinone. These syn- theses are, at present, mostly of theoretical interest in throwing light on the structure of anthraquinone and hence of anthracene, but there is some probability of their becoming industrially important (see Reaction XX. (a), also Preparation 24). (iii.) When ethylidene bisacetoacetic ester is refluxed with cone, sulphuric acid, simultaneous condensation to a ring compound, hydrolysis, and elimination of carbon dioxide take place, and a cyclic ketone is ob- tained. All compounds which, like ethylidene bisacetoacetic ester, contain 1 : 5-carbonyl groups, and in addition a methyl group attached to one of them, undergo the same condensation with acids or alkalis, so that there exists here a very general method of passing from open-chain to ring com- pounds. To take the most general case— X-CH-CO X-CH-CO H 2 CH -> RC 6 H 4 C 14 H 8 0 2 . 208. 10 gins. (1 mol.) of o-benzoylbenzoic acid are mixed with 60 gms. of cone, sulphuric acid, heated to 150° for 1 hour, cooled and poured on to ice. The precipitated anthraquinone is collected and thoroughly washed, first with hot water then with warm dilute (5N) caustic soda and finally with warm water. It is dried in a steam oven, and completely purified by sublimation, at 250° (see p. 28). CO CO \/ \ :H CO; OH CO Yield. — Theoretical (9 gms.). Yellow needles ; insoluble in water ; somewhat soluble in benzene and the usual organic solvents ; soluble in glacial acetic acid ; M.P. 277° ; sublimes at 250° ; B.P. 382°. (Z. a., 19, 669.) In the above preparation phosphorus pentoxide can equally well be used instead of sulphuric acid. 2-Methyl anthraquinone can be prepared by heating 2-£>-toluoyl- benzoic acid with about 9 times its weight of oleum containing 20% S0 3 . On dilution with water, and re crystallising from dilute acetic acid, pale yellow needles are obtained, M.P. 177°. (B., 41, 3632; J. pr. [ii], 33, 318; A,, 311, 178). Preparation 25. — Dimethylcyclohexenone (l-3-Dimethyl-5-on-6-cyclo- hexen). CH,CH CH 2 CO A CH 2 C.CH 3 CJL,0. 124. Crude ethylidinebisacetoacetic ester as prepared in Preparation 72 is melted on the water bath and poured into 500 c.cs. 20% sulphuric acid in a round-bottomed flask attached to a reflux condenser. A few pieces of porcelain chips are added, and the whole vigorously boiled for 7 hours. It is then steam distilled until the distillate measures about 100 c.cs. The distillate is then set aside for 24 hours in a well-stoppered bottle. The residue is again refluxed for 7 hours and again steam distilled, 100 c.cs. of distillate being again collected. The process is repeated a third time, and then steam is blown into the mixture until no oil, or only a trace, separates from a test portion when treated with solid caustic potash. To the three 78 SYSTEMATIC ORGANIC CHEMISTRY united distillates is now added pure anhydrous solid caustic potash until the solution is saturated. A reddish-brown oil separates, and is removed by means of a separating funnel. The alcohol is distilled off using a column, and the residue dried over anhydrous sodium sulphate. The dimethylcyclohexenone is then recovered from the residue by fractional distillation, the fraction 200° — 215° being retained. C 2 H 5 OOCCH — CO C 2 H 5 OOC.CH — CO / I / CH 3 CH 3 CH C,H,OOC— CH— COCH. / CH,CH C 2 H 5 OOCC CC!H- 2C0 2 + 2C 2 H 5 OH + CH 3 CH CH CH, \ CH / -C.CH -CO\ \CH,~- CH / -C.CH. Yield— 75— 90% theoretical (15—18 gms.). Colourless liquid, B.P. 211°. (A., 281, 25.) Reaction XIX. (a) Condensation of Anthranol Derivatives with Glycerol. (B., 44, 1666.)— This condensation gives rise to the benz- anthrones which are used as intermediates in the dye industry. The reaction may be assumed to go as follows — CHOH / / / \ ! > H 2 COH; HO; . CH.i / V " \ Hi H 2 C^ C CH CH C(OH) CH C(OH) /\ / HC / xx CH C CO CARBON TO CARBON 79 1 Sulphuric acid is the condensing agent used. The reaction might be compared with the preceding reaction and with Skraup's quinoline synthesis (see p. 159). Preparation 26.— Benzanthrone. C = CoH, C 6 H 4 X \C 6 H 3 C 17 H 10 O. 230. CO 10 gms. (1 mol.) of anthranol are dissolved or suspended in 150 gms. of sulphuric acid (80%), and 10 gms. (excess) of glycerol are added. The mixture is carefully heated to 120°, when S0 2 is evolved, and kept there till the reaction is complete (4 hours). The cooled mass is poured into water, and the product which separates is collected, washed, boiled for 30 minutes with 13 times the quantity of 1% sodium hydroxide solution, pressed and dried. It is recrystallised from alcohol. /C(0H) X ! ' C,H,^ )> C eH 4 + C 3 H 5 (0H) 3 C 6 H 4 / \C 6 H, N - CU - / CO Pale yellow needles ; insoluble in cold alcohol and in dilute acids and alkalis ; soluble in cone, sulphuric acid with a reddish-brown colour, and deep orange fluorescence ; M.P. 170°. (D.R.P. 176018 ; see also B., 44, 1666.) Reaction XIX. (b) Condensation of Anthranol Derivatives with Formaldehyde. (A., 420, 134.) — The anthranols can also give rise to other intermediates by condensation with formaldehyde. Methylene anthra- quinone is thus obtained from anthranol. CH. + CH 2 0 C(.OH) Reaction XX. (a) Action of Metallic Zinc on a Mixture of an Aromatic Hydrocarbon and a Derivative of Phthalyl Chloride. — This is a method of synthesising anthraquinone and its derivatives, and hence a method of elucidating their structure, and also the structure of anthracene. Other- wise the method is not of importance, but it may be in the future, since anthraquinone is in great and increasing demand for the production of the new vat-dyes, such as indanthrene ; phthalyl chloride can be 80 SYSTEMATIC ORGANIC CHEMISTRY obtained cheaply from naphthalene (see also Reaction XVIII. (ii.), and p. 115). CO . CO . CI + . CO . CI The action of zinc in this case resembles that of anhydrous aluminium chloride in the Friedel-Craft reaction. If the structure of anthraquinone is accepted, this reaction helps to support the formula of phthalyl chloride as given above against the alternative formula. \-CO > y CC1 2 for which there is also evidence (A., 238, 329 ; see Reaction XX. (6) (vi.) ). Reaction XX. (6) Action of certain Anhydrous Metallic Halides (Aluminium Chloride, Aluminium Bromide, Aluminium and Hydrogen Chloride, Ferric Chloride) on a mixture of an Aromatic Hydrocarbon or certain derivatives, and an Acyl Halide. (Friedel-Crafts). (A. Ch., [6], 1, 518.) — This is an even more important application of the Friedel-Crafts synthesis than the methods of synthesising hydrocarbons (pp. 54, 56). The reactions involved are more readily controlled since the products, in presence of aluminium chloride, do not undergo further condensations. Usually these products have also the advantage of being more easily separated, for as shown below in (hi.), the formation of isomers can be avoided. What has been said under Reaction VI. covers the general experi- mental methods of the synthesis, the same solvents and considerations applying in all cases. The following will give some idea of the scope of the reaction. (i.) Both aliphatic and aromatic acyl chlorides can be used (A. Ch., [6], 1, 503 ; 14, 455). C 6 H 6 + CHgCOCl = C 6 H 5 .CO.CH 3 + HC1. C 6 H 6 + C 6 H 5 C0C1 = C 6 H 5 .CO.C 6 H 5 + HC1. (ii.) Homologues of both the reacting substances may be employed. C 6 H 6 + CH 3 CH 2 COCl = C 6 H 5 .CO.CH 2 .CH 3 + HC1. C 6 H 6 + C 6 H 5 CH 2 C0C1 = C 6 H 5 .CO.CH 2 .C 6 H 5 + HC1. C 6 H 5 CH 3 + C 6 H 5 C0C1 = p-CH 3 C 6 H 4 COC 6 H 5 + HC1. (A., 189, 84 ; B., 12, 2299.) (iii.) The acid radical always enters the joara-position to the alkyl radical ; if that is occupied, it goes to the ortho-. A little of the ortho- compound is formed along with the para- in all cases, so that in preparing, CARBON TO CARBON 81 for instance, phenyl-jo-tolyl-ketone, the method given in the last equation should not be used, but it should be made from benzene and £>-toluoyl chloride, when it is the only compound formed. (A., 189, 84 ; B., 12, 2299.) C 6 H 6 + ^-CH 3 C 6 H 4 C0C1 = jp-CH 8 C 6 H 4 COC 6 H 5 + HCL The pure o- and m-compounds can be prepared in a similar manner, (iv.) Instead of the hydrocarbons the phenol ethers which react with great ease can be employed ; the same rules as to position apply. C 6 H 5 .O.CH 3 + C 6 H 5 .C0.C1 = ^-CH 3 O.C 6 H 4 .COC 6 H 5 + HCL (v.) Substituted acid chlorides may be used to obtain substituted ketones. C 6 H 6 + ^-Br.C 6 H 4 .COCl = p-BrC 6 H 4 COC 6 H 5 + HCL C 6 H 6 + i?-N0 2 C 6 H 4 COCl = ^)-N0 2 C 6 H 4 COC 6 H 5 + HC1. (vi.) The chlorides of the dibasic acids react in two ways : (a) With 1 mol. of hydrocarbon they give acid chlorides, (b) With 2 mols. of hydrocarbon di-ketones are formed, except in the case of phosgene. COCl 2 + 2C 6 H 6 = CO.(C 6 H 5 ) 2 + 2HC1. (B., 10, 1854.) C0C1 2 + 2C 6 H 5 CH 3 = CO.(C 6 H 4 .CH 3 ) 2 [4 : 4'] + 2HC1. (A., 312, 92 ; B., 7, 1183 ; 10, 2173 ; J. pr., [2], 35, 466.) C0C1 2 + C 6 H 5 N(CH 3 ) 2 = CO(C 6 H 4 N(CH 3 ) 2 ) 2 [4 : 4'] + 2HC1. (B., 19, 109 ; B., 24, 3198.) The last compound 4 : 4 / -tetramethyl-di-amino-benzophenone is also known as " Michler's ketone," and is an important intermediate in the preparation of dyestuffs of the fuchsine series, e.g., crystal violet. As to di-ketones, the following examples will suffice — CH 2 . CO . CI CH 2 .CO.C 6 H 5 + 2C 6 H 6 = | + 2HC1. CH 2 . CO . CI CH 2 .CO.C 6 H 5 (B., 13, 320.) C 6 H 5 C^ 2 J C *H \ / C \ C 6 H 4 / )0 + 2 C 6 H 6 = C 6 H 4 / \ Q \co/ \co/ 00 + 2HC1 With phthalyl chloride " diphenylphthalide," important on account of its relation to the fluorescein dyes, is formed (B., 14, 1865). Comparing with' Reaction XX. (a) it will be seen that phthalyl chloride is probably tautomeric. Succinyl chloride is also considered to be simi- larly tautomeric, a number of facts supporting this view. Unlike phthalyl chloride, however, it reacts symmetrically, as has been seen, with benzene and aluminium chloride. 82 SYSTEMATIC ORGANIC CHEMISTRY (vii.) Naphthalene reacts in a manner similar to benzene. C 10 H 8 + C 6 H 5 C0C1 = «-C 10 H 7 COC 6 H 5 + HC1. It will be noted in the following examples that the quantities of alu- minium chloride used are larger than in the case of the hydrocarbons synthesised by this reaction. This is necessary owing to the stability of the addition compounds aluminium chloride forms with the product. So stable are these compounds that the aluminium chloride is unable to exert its catalytic action, and molecular quantities of the condensing agent have to be taken. (J. C. S., 83, 1470.) Preparation 27 .— Acetophenone (l-Phenyl-l=Ethanon). C 6 H 5 .CO.CH 3 . C 8 H 8 0. 120. 50 gms. (1 mol.) of freshly prepared finely powdered anhydrous alu- minium chloride (see p. 503) are placed in a 500-c.c. flask attached to an upright condenser, 30 gms. (1 mol.) of dry benzene are immediately added, and then, while cooling the flask by ice-water, 35 gms. (excess) of acetyl chloride are slowly dropped in from a tap-funnel fitted to the top of the condenser. A brown viscid mass is formed which, after standing for 1 hour, is poured on to ice and extracted with a little benzene. The extract is washed with dilute caustic soda and with water, dehydrated over calcium chloride, filtered and distilled. The fraction 190° — 205° is redistilled. C 6 H 6 + CHgCOCl + AICI3 = C 6 H 6 C0CH 3 [A1C1 3 ] + HC1. C 6 H 6 C0CH 3 [A1C1 3 ] + 3H 2 0 = C 6 H 6 COCH 3 + Al(OH) 3 + 3HC1. Yield. — 50% theoretical (20 gms.). Colourless plates ; sweetish odour ; insoluble in water ; soluble in benzene ; M.P. 20° ; B.P. 202° ; D. J 1-032. (A. Ch., [6], 1, 507 ; 14, 455.) Note. — In all these experiments the aluminium chloride must be weighed out in a dry test-tube closed by a cork. Preparation 28. — Benzophenone (Diphenyl-methanon). C 6 H 5 .CO.C 6 H 5 . C 13 H 10 O. 182. 30 gms. (excess) of dry benzene, 30 gms. (1 mol.) of pure benzoyl chloride, and 130 gms. of dry carbon disulphide are placed in a dr}^ flask and 29 gms. (1 mol.) of freshly prepared, finely powdered, anhydrous aluminium chloride are added. The flask is then connected with a long reflux condenser, and heated on a water bath kept at 50°, until only small amounts of hydrogen chloride are evolved (about 2 J hours). The carbon disulphide is then distilled off on a water bath (caution) and the still warm residue is carefully poured into a large flask containing 300 c.cs. of ice-water. The reaction flask is then washed out into the ice-water flask with 100 c.cs. of wa'ter, 10 c.cs. of cone, hydrochloric acid are added, and the whole steam distilled for 15 minutes. The cold residue is extracted with ether, the ethereal solution is repeatedly washed with water, filtered, and three times washed with dilute caustic soda solution. It is dehydrated over calcium chloride, filtered and CARBON TO CARBON 83 distilled from a "high boiling point" distilling flask (see p. 18), the fraction 209°— 305° being retained. C 6 H 6 + C 6 H 5 C0C1 + A1C1 3 = C e H 6 .CO.C 6 H 6 [AlCl 8 ] + HC1. C 6 H 5 C0C 6 H 5 [A1C1 3 ] + 3H 2 0 = C 6 H 5 .CO.C 6 H 5 + Al(OH) 8 + 3HC1. Yield. — 80% theoretical (30 gms.). Colourless crystals ; insoluble in water ; soluble in benzene ; M.P. 48° ; B.P. 763 297° ; B.P. 12 162° ; a labile modification (M.P. 26°) also exists ; it transforms to the stable modification on boiling or on touching with a little of the latter. (B., 26, R., 380 ; A. Ch., [6], 1, 518.) The effect of carbon disulphide on the velocity of the action, and on the yield should be noted by comparing the above preparation with the preceding. Preparation 29. — Acetylmesitylene (1:3: 5 - Tri-methyl - 2-acetyl - benzene). . CH 3 \cOCH3 C n H 14 0 162. CH CH, 25 gms. (1 mol.) of mesitylene (see p. 53), 75 gms. of carbon disul- phide and 30 gms. (excess) of freshly distilled acetyl chloride are placed in a flask provided with a reflux condenser, and 33 gms. mols.) of finely powdered, freshly prepared, anhydrous aluminium chloride are added, gradually. The mixture is finally warmed for 15 minutes on a water bath and poured on to ice, 10 c.cs. of cone, hydrochloric acid are added, and the whole is steam-distilled until no more oily drops pass over t The distillate is extracted with benzene and the extract washed with dilute caustic soda solution and with water, dried over calcium chloride and distilled, the fraction 230° — 240° being retained. C 6 H 3 (CH 3 ) 3 [1 : 3 : 5] + CH 3 .CO.Cl = C 6 H 2 (CH 3 ) 3 (CO.CH 3 )[l : 3 : 5 : 2] -f HC1. Yield.— 60% theoretical (36 gms.). Colourless liquid ; B.P. 235°. (B.. 24, 3542.) Preparation 30. — p-p' -Dimethyl Benzophenone. [4']CH 8 .C 6 H 4 .CO.C 6 H 4 CH 8 [4']. C 15 H 14 0. 210. This preparation must be conducted in a good draught cupboard. 100 gms. of toluene, containing 20% of carbonyl chloride (see p. 509), are placed in a flask to which is attached by a two-holed stopper a reflux con- denser and a wide-stemmed glass filtering funnel. To the end of the con- denser is attached a delivery tube leading to a fume duct. The flask is surrounded by a freezing mixture, and 50 gms. of finely powdered anhy- drous aluminium chloride are gradually added through the funnel during 4 hours, the funnel being closed by a cork after each addition. When all has been added, the flask is very gently warmed for a short time, and the contents slowly poured into ice-water (caution). It is then steam- g 2 84 SYSTEMATIC ORGANIC CHEMISTRY distilled until nothing further passes over. The aqueous layer of the distillate is removed and a 1% solution of hydrochloric acid added to the solid matter, which is again steam-distilled for about 30 minutes. The solid matter in the distillate is filtered off, washed and recrystallised several times from dilute alcohol. 2C 6 H 5 CH 3 + COCl 2 -^CO(C 6 H 4 .CH 3 [4]) 2 + 2HC1. Yield. — 50% theoretical (22 gms.). Colourless needles ; insoluble in water ; soluble in benzene and alcohol ; M.P. 95° ; B.P. 333°. (B., 10, 2173 ; A., 312, 92 ; J. pr„ [2], 35, 466.) Note. — Carbonyl chloride is extremely poisonous, and special care must be taken in its use. Reaction XX. (c) Action of a Mixture of Aluminium and Mercuric Chloride on a Mixture of an Aromatic Hydrocarbon and an Alkyl Halide. (J. C. S., 117, 1330.) — This modification of the Friedel-Crafts condensation has been fully dealt with under its application to the synthesis of hydro- carbons. In the case of ketones the results obtained are more in accord- ance with the results of the older method than were those discussed in the first hydrocarbon section. Pkeparation 31. — Acetophenone (1 -Phenyl- 1-ethanon). C 6 H 5 .CO.CH 3 . C 8 H 8 0. 120. 20 gms. (1 mol.) of dry benzene, and 20 gms. of mercuric chloride are placed in a flask fitted with a reflux condenser and 1 gm. of aluminium powder is added, gradually, and with vigorous shaking, the ensuing reaction being moderated by occasional cooling in an ice bath. A green, crystal- line mass separates, and the reaction is completed by immersing the flask in tepid water for half an hour. The mercury liberated in the reaction is removed and the preparation of the catalyst is complete. 20 gms. (1 mol.) of acetyl chloride are added in small quantities through the condenser, the reaction mixture being well agitated by a mechanical stirrer. (For a suitable apparatus, see Fig. 37.) The whole is allowed to stand for 2 hours, and then heated to 40° for 1 hour. ,On cooling, water is added to decompose the product, and the liberated oil extracted with benzene. The extract is dried over calcium chloride and fractionated, the fraction 195° — 205° being retained. C 6 H 6 + Al + 2HgCl 2 = C 6 H 6 .AlCl 3 .HgCl + Hg. C 6 H 6 .AlCl 3 .HgCl + CHgCOCl = CH 3 .CO.C 6 H 5 .AlCl 3 .HgCl + HC1. 2CH 3 COC 6 H 5 .AlCl 3 .HgCl + 6H 2 0 = 2CH 3 COC 6 H 5 + 2A1(0H) 3 + Hg 2 Cl 2 + 6HC1. Yield. — 60% theoretical (18 gms.). Colourless plates ; sweetish odour ; soluble in benzene ; insoluble in water ; M.P. 20° ; B.P. 202° ; D. \ 1-032. (J. C. S., 117, 1330.) The yield of acetophenone above is 10% better than that obtained in the ordinary Friedel-Crafts reaction. A similar method can be applied to the preparation of ^>-tolyl-methyl-ketone, 20 gms. (1 mol.) of dry toluene, 2 gms. of aluminium powder, 35 gms. of mercuric chloride, and 17 gms. (1 mol.) of acetyl chloride being used. The yield is 45% theoretical (13 gms.). The ketone is obtained as a low-melting solid, B.P. 224°. CARBON TO CARBON 85 Reaction XX. (d) Combined Action of Carbon Monoxide and Hydrogen Chloride on an Aromatic Hydrocarbon in presence of a Mixture of Anhy- drous Aluminium and Cuprous Chlorides (Gattermann-Koch). (B., 30, 1622 ; 31, 1149 ; A., 347, 347.)— When it was discovered that a mixture of carbon monoxide and hydrogen chloride behaved as the unknown formyl chloride, it became possible to utilise directly the Friedel-Crafts method in the synthesis of aldehydes. The reaction may be expressed by the following equations — HC1 + CO[Cu 2 Cl 2 ] = H.CO.Cl.[Cu a Cl 2 ]. CH 3 .C 6 H 5 + H.C0.C1[A1C1 8 ] = CH 8 .C 6 H 4 .CHO.rAl.Cl 3 ] + HC1. CH 3 .C 6 H 4 .CH0.[A1C1 3 ] + 3H 2 0 = CH 3 .C 6 H 4 .CHO + Al(OH) 3 + 3HC1. Benzene itself does not react — unless hydrobromic acid is used — and can on that account be used as a solvent (D.R.P., 126421). Many other hydrocarbons o- and m-xylene, mesitylene, ethylbenzene, diphenyl, etc., can all be employed to give the corresponding aldehydes. The CHO group enters the jwa-position to the alkyl residue just as in the ketonic synthesis. Thus o-xylene gives 3 : 4-di-methyl-benzaldehyde. Since the Friedel-Crafts reaction when applied to the phenol ethers yields the corresponding ketones far more easily than the same reaction applied to hydrocarbons (see Reaction XX. (b) (iv.) ), it is noteworthy | that the above reaction does not apply to the phenol ethers. To obtain aldehydes from them or from phenols, a modified method must be used (see p. 100). Preparation 32. — ^-Tolylaldehyde (1-4-Methylbenzaldehyde). CH 3 .C 6 H 4 .CHO[l : 4]. C 8 H 8 0. 120. To 30 gms. (1 mol.) of freshly distilled toluene (B.P. 110°) contained in a wide-necked vessel cooled with water, 45 gms. of pulverised, freshly prepared aluminium chloride and 5 gms. of pure cuprous chloride are added. The vessel is closed by a three-holed cork, in the middle hole of which is inserted a glass tube which carries an efficient stirrer ; the other holes are used for the inlet and outlet tubes. After the apparatus has been firmly fastened in a clamp, it is immersed in a jar filled with water at 20°. A current, not too rapid, of carbon monoxide and hydrogen chloride k is led in through a prong-shaped tube while the stirrer is set in motion. The gases are dried by bubbling each through cone, sulphuric acid, their rates of entry being so regulated that the volume of carbon monoxide is about twice that of the hydrogen chloride passing in. The escaping gas is led directly to the hood opening of a draught chamber. In the course of an hour, when about 1 — 2 litres of carbon monoxide have been passed into the mixture, the temperature rises to 25° — 30° ; the remainder of the gas is passed in during 4 — 5 hours. Should the reaction mixture become so viscous before the lapse of this time that the stirrer revolves only with difficulty, the reaction may be stopped. The viscid product is then poured into a large flask containing crushed ice ; the aldehyde formed, and any unattacked toluene is distilled over with steam. The distillate — oil and water — is then shaken up with a sodium bisulphite solution (see p. 506) for a long time, and the toluene which does not dissolve is 8G SYSTEMATIC OKGANIC CHEMISTRY separated in a funnel. If the aldehyde-bisulphite compound should crystallise out, water is added till it dissolves. The filtered aqueous solution is then treated with anhydrous sodium carbonate until it shows a decided alkaline reaction, the aldehyde distilled off in steam, extracted with ether, the extract dried over anhydrous calcium chloride, and the ether removed on a water bath. CH 3 .C 6 H 4 .H + Cl.CO.H = CH 3 .C 6 H 4 .CHO. + HC1. Yield. — 60% theoretical (22 gms.). Colourless liquid ; characteristic odour ; B.P. 204°. (B., 30, 1622 ; 31, 1149 ; A., 347, 347.) Reaction XXI. (a) Dry Distillation of the Barium or Calcium Salt of a Fatty Acid with Barium or Calcium Formate. — This is one of the methods by which aldehydes may be obtained from acids. Like most dry distil- lations, the yields are poor, and the method is seldom used. CH 3 - H.CO. CO.O.Ca.O.i CO — CH 3 i = 2CH 3 .CHO + 2CaC0 3 . O.Ca.O.CO! H Reaction XXI. (b) Dry Distillation of the Barium or Calcium Salts of Fatty Acids. (Z. Ch., 19, 1755.)— This is an old method of preparing ketones, and is still used. Originally calcium salts were employed, but barium salts have been found to give better yields. Mixed ketones can be prepared by distilling an intimate mixture of the salts of two acids, but the symmetrical ketones from the single acids are also formed at the same time. The method is perfectly analogous to that given above for alde- hydes. Almost all of the fatty acids give this reaction, but it is better to distil under reduced pressure when working with the higher members of the series. If the salt of a dibasic acid be used, since the two carboxyls are already linked together, distillation produces a ring compound. This is a very important method of ring-formation, and series for a very large variety of compounds. The following examples will give an idea of the scope of the reaction — (i.) CH 3 .CO. i O.Ca.O.CO. i CH 3 -I- -> 2CH 3 .CO.C 6 H 5 + 2CaC0 3 . C 6 H 5 . | CO.O.Ca.O. | CO.C 6 H 5 . Some (CH 3 ) 2 CO and (C 6 H 5 ) 2 CO are also formed. (ii.) CH 2 — CH 2 — CO i 0\ CH 2 — CH 2 — CO j /Ca | I + CaC0 3 . CH 2 — CH 2 — ! COO / CH 2 — CH 2 (hi.) /CH 2 — CO.O \^ /CH 2X C 8 H 14 — CO.O/ Ca_> C 8 H 14 — —CO + CaC0 3 . (hi.) represents the last step in the synthesis of camphor by heating calcium homo-camphorate in a current of carbon dioxide (Z. Ch., 19, 1755). Preparation 33 —Acetone (2-Propanon). CH 3 COCH 3 . C 3 H 6 0. 58. 100 gms. (2 mols.) of anhydrous calcium or barium acetate are distilled CAEBON TO CARBON 87 from a metal retort attached to a long condenser, some dry iron turnings being previously mixed with the salt to distribute the heat. When no more liquid distils, the distillate is shaken for 5 hours with three volumes of saturated sodium bisulphite solution (see p. 506). The crystalline compound is filtered off, dissolved in the minimum quantity of water. Anhydrous sodium carbonate is added until the solution is alkaline, and the acetone then distilled from a water bath. The distillate is dried over calcium chloride and redistilled, the fraction 55° — 59° being retained. CH 3 CO CH, 0 Ca 0. OC CO . 0 Ca 0 CH 3 Yield. — 20% theoretical (7*5 gms.) from calcium acetate ; 25% theo- retical (10 gms.) from barium acetate. Colourless mobile liquid ; B.P. 56-3° ; D. ^ 0-742 ; soluble in water. The distillate may also be purified by adding an equal volume of water to dissolve the acetone, dehydrating for several hours over quicklime under a reflux, distilling, and dehydrating further over calcium chloride. Preparation 34. — Benzophenone (1-Phenyl-l-ethanon). C 6 H 5 .CO.C 6 H 5 . C 13 H 10 O. 182. 10 gms. (2 mols.) of benzoic acid are heated to boiling with 25 gms. (excess) of slaked lime and ten times the weight of water, until the acid is completely dissolved and the liquid reacts alkaline. It is then filtered hot from the excess of slaked lime. On cooling most of the calcium benzoate separates out from the filtrate in white needles. The remainder is ob- tained on evaporating the mother liquor. The salt is filtered as well as possible at the pump, pressed by means of the press, and completely dried in metal dishes over a free flame. The mass is now introduced into a metal retort (made of iron or copper), which is connected with a long condenser-tube. The retort must not be filled more than two-thirds full. It is heated over a powerful gas burner, so that the dry distillation of the salt proceeds as quickly as possible. A pale brownish coloured mixture of benzene, benzophenone and aromatic products first distils over. The distillation is stopped when the distillate becomes brown and viscous. The distillate is dried with calcium chloride, and then fractionated. The fraction 250° — 310° contains the benzo- phenone. The product sometimes soon solidifies, but more frequently remains syrupy for days. Crystallisation begins, however, at once, when a small quantity of solid benzophenone is added. The crystals are freed from the oily mother liquor by pressing between filter paper, or by spreading on a porous tile, and are recrystallised from ligroin. 2C 6 H 5 COOH -> (C 6 H 5 COO) 2 Ca -> (C 6 H 5 ) 2 CO. Yield. — 30% theoretical (20 gms.) (see p. 83). Reaction XXI. (c) Action of Acetic Anhydride on Carboxylic Acids, and subsequent Distillation. — This method of preparing ketones is worthy of 88 SYSTEMATIC ORGANIC CHEMISTRY note because it was used to obtain S-ketohexahydrobenzoic acid from 4-carboxyl-heptan-di-acid. COOH OOOH CO CH 2 CH 2 CH, CH. CH, CH, CH„ CH., / - CH CH COOH COOH 6-Ketohexahydrobenzoic acid is important, because it is the starting point in one of the methods of synthesising terpenes (see p. 68). Reaction XXI. (d) Catalytic action of its Manganese Salt on the vapour of a Fatty Acid. — When acetic acid vapour is passed over heated manga- nese acetate, acetone is formed. The process is continuous and the method gives better yields than the older distillation method. The cycle of changes which takes place in the action may be formulated somewhat as follows — Mn.(O.OC.CH 3 ) 2 = (CH 3 ) 2 CO + MnC0 3 . MnC0 3 + 2CH 3 COOH = Mn.(O.OC.CH 3 ) 2 + C0 2 + H 2 0, and so on. The principle of this method has been utilised on the industrial scale, and with success for the preparation of acetone. The acetic acid may be prepared from acetylene via acetaldehyde (see p. 426) thus providing a commercial synthesis of acetone from coke. Preparation 35. — Acetone. CH 3 .CO.CH 3 . C 3 H 6 0. 58. About 20 gms. of manganous carbonate are made into a thick paste with water in a basin. This is stirred with an equal bulk of pumice in small pieces, and then placed in an air oven at 110° — 120° until quite dry. When dry it is loosely packed into a combustion tube, sufficient being taken to fill rather more than half (40 cms.), the length of the tube ; two asbestos plugs are used to keep the layer in position. The combustion tube is then placed in a long cylindrical air bath (see Fig. 43). The side tube of a distilling flask containing acetic acid is inserted through an ordinary cork in one end of the combustion tube. The other end of the combustion tube may be bent and drawn out after the fashion of an adapter, or it may be fitted with a cork and delivery tube ; in either case it is connected to an apparatus for condensing the mixture of acetone and acetic acid which passes over (see p. 47 for con- denser arrangement). The air bath is heated to 120°— 130° and main- tained at this while the combustion tube is filled with the vapour of acetic acid by boiling the acetic acid in the distilling flask for a few minutes. The air bath is then raised to 400° — 450°, i.e., until the bottom of the air bath is at a good red heat (N.B., a thermometer should not be used unless it is nitrogen rilled). Shields of thick asbestos paper should be placed over the air bath to conserve heat. The distillate which collects in the receivers (the second receiver should be cooled in ice), consists of acetic acid, acetone CARBON TO CARBON 89 and water. If this distillate is passed a second or third time over the catalyst, the yield of acetone is increased. In this way excellent yields may be obtained. The final distillate is distilled from an apparatus on a water bath, using a thermometer and efficient condenser, collecting what distils up to 80° ; this is dried in contact with solid potassium carbonate and fractionally distilled. B.P. of acetone 56°. CH3COOH + HOOC.CH3 = CH3.CO.CH3 + C0 2 + H 2 0. (See p. 87.) Reaction XXII. (a) Action of Magnesium Alkyl or Aryl Halide on (i.) excess of Ethyl Formate, (ii.) Ethyl Orthoformate, (hi.) di-substituted formamide and other Derivatives of Formic Acid (Grignard). — This is the Grignard method of preparing aldehydes. The same remarks apply to this reaction as to the other " Grignards " dealt with. The equations illustrate its course. (i.) H.COOC 2 H 5 + C 6 H 5 MgI -> C 6 H 5 CHO + C 2 H 6 O.Mg.I. (ii.) H.C(OC 2 H 5 ) 3 + C 6 H 5 MgI -> C 6 H 5 CHO + C 2 H 5 OMgI + H 2 0. + 2C 2 H 5 OH. (iii.) H.CO.N(CH 3 ) 2 + C 6 H 5 MgI -> HC(C 6 H 5 )(OMgI)N(CH 3 ) -> C 6 H 5 CHO + (CH 3 ) 2 NH + Mg(OH)I. The course of the above reaction should be studied carefully, as it is somewhat different from those so far discussed. Reaction XXII. (b) Action of Magnesium Alkyl or Aryl Halide on (i.) Nitriles, and (ii.) Amides (Grignard). — This is the analogous reaction to the foregoing, ketones being obtained in place of aldehydes by using derivatives of acids other than formic. The esters, however, do not figure among the derivatives which can be employed (see p. 70). /* CN C = NMgl I + 2EMgI -> I CN C = NMgl C = NH C = 0 (i.) + 2Mg(OH)I 1 H _^ + 2NH 3- C = NH C = 0 /C 2 H 5 C 6 H 5 CN + C 2 H 5 MgI -> C = NMgl -> C 6 H 5 .CO.C 2 H 5 + NH 3 + Mg(OH)I. (ii.) C 6 H 5 CONH 2 + CH 3 MgI -> C 6 H 5 C(CH 3 )(OMgI)NH 2 -> C 6 H 5 .CO.CH 8 + Mg(OH)I + NH 3 . These reactions are of theoretical rather than of practical interest. 90 SYSTEMATIC ORGANIC CHEMISTRY Reaction XXII. (r) Action of Zinc Alkyl on Acyl Chlorides in certain proportions. — The preparation of alcohols by this method has already been discussed (Reaction XV). By using only 1 mol. of zinc alkyl to 2 mols. of acid chloride, the reaction can be stopped at the inter- mediate ketone stage. In the Grignard reaction with acid chlorides, it has not been found possible to do this owing to the greater reactivity of the Grignard compounds. 2CH3.CO.Cl + Zn(CH 3 ) 2 = 2CH3COCH3 + ZnCl 2 . Reaction XXIII. (a) Condensation of Ethyl Formate with certain Oxy Compounds under the influence of Sodium Ethoxide (Claisen). (A., 283, 306.) — This condensation is undergone by all compounds containing the group — CH 2 — CO—. It follows the same lines as the other ester-ketone condensations (see p. 137 et seq.). COR COR ! I R.CH 2 + C 2 H 5 O.O.C.H -> R.CH.CHO + C 2 H 5 OH COR I -> R.C : CH(OH) + C 2 H 5 OH. The compounds so formed were at first thought to be aldehyde deriva- tives, thus the compound derived from acetophenone was thought to have the formula — C 6 H 5 COCH 2 CHO. Support was lent to this view by the fact that the compound gave an oxime, C 6 H 5 .CO.CH 2 .CH : NOH. On the other hand in many reactions it behaved as if it had the formula C 6 H 5 COCH : CH(OH). It gave a sodium salt, being obtained as such in its preparation ; and a chloro compound, C 6 H 5 COCH : CHC1, when treated with PC1 5 . The view now held is that these " hydroxymethylene " com- pounds are tautomeric ; both oxy and enol forms being present. The enol form is of special interest on account of the great reactivity of the hydroxyl group. The double bond seems to have the same activating effect as the oxy group in carboxyl compounds, the hydroxyl group behaving more like an acid hydroxyl than an alcoholic. The chloride derived from it is nearly as reactive as an acid chloride ; and the corresponding amino compound behaves rather as an amide than as an amine. The compounds separate from the condensation as sodium salts. From the simple ketones, the compound formed is not stable and, undergoes change on precipitation from its sodium salt. The formation of a hydroxymethylene compound is used as proof of the presence of the group — CH 2 — CO — in camphor. The following preparation shows the details of the method. Preparation 36.— Camphor Aldehyde (Hydroxymethylene Camphor). CO /CO and C 8 II , , CH.CHO X C = CH(OH). C 8 H 14 and C 8 H 14 C n H 16 0 2 . 180. CARBON TO CARBON 91 90 gms. (excess) of camphor are dissolved in toluene which has been freed from water by standing over calcium chloride, and to this solution are added 6 gms. of sodium wire. To the well cooled mixture 19 gms. (1 mol.) ethyl formate are added, when it is set aside in an ice chest for 24 hours. It is then poured into ice water, and after vigorous shaking, the aqueous layer removed. After acidifying with acetic acid, and then extracting with ether, the ethereal extract is dried over calcium chloride. The ether is removed by distillation, and the residue, after being placed in a basin, is allowed to evaporate slowly at ordinary temperature. The oil which remains solidifies on standing to colourless crystals. /CO /CO C 8 H 14 j + C 2 H 5 ONa + H.COOC 2 H 5 -> C 8 H 14 | + 2C 2 H 5 OH ^CH 2 ^C = CH(ONa) /CO / co ^ C 8 H 14 ~ > C 8 H 14 | Xx C = CH(OH) \ CH.CHO. Yield.— Theoretical (46 gms.). Soluble in ether ; M.P. 77°. (A., 283, 306.) Reaction XXIII. (b) Condensation o£ Esters other than Ethyl Formate, with certain Ketones under the influence of Sodium Ethylate, Metallic Sodium, or Sodamide (Claisen). (B., 22, 1009 ; 23, R., 40 ; 38, 695.)— This is a similar reaction to that discussed above, and is part of a general condensation undergone by esters with oxy compounds, other phases of which will be found discussed on pp. 137-145. The reaction may be formulated as follows — EiCOOEt + H^CEnCOCEm = E^CO.CEjjCOCEm + Et.OH. where R may be hydrogen or an alkyl or aryl group. It is only these i ketones which possess the group HC — CO — that undergo the reaction. The compound formed is always a 1 : 3-di-ketone. The way in which the condensing agent used brings about the condensation is described under the actual preparations (see Preparation 37). The compounds themselves are di-ketones, but their sodium salts are derived from the corresponding enol compounds (B., 25, 3074). Of the three condensing agents used, sodamide is the most and sodium ethylate the least effective. Prepakation 37. — Benzoyl Acetone (1-Phenyl-l : 3-di-oxybutan). C 6 H 5 .CO.CH 2 .CO.CH 3 . C 10 H 10 O 2 . 162. Method I. — 6 gms. (1 mol.) of fresh dry sodium ethylate (see p. 505) are added to 20 gms. (excess) of dry ethyl acetate under cooling by water. After 15 minutes, 10 gms. (1 mol.) of acetophenone are added ; the separation of the sodium salt of benzoyl acetone immediately begins. A little dry ether is added, and in 4 hours the sodium compound is filtered 92 SYSTEMATIC ORGANIC CHEMISTRY off, washed with, ether, air-dried, dissolved in cold water, and the solution acidified with acetic acid. Benzoyl acetone separates. (1) CH 3 COOEt + C 2 H 5 ONa /ONa = CH 3 C— OC 2 H 5 /ONa (2) CH 3 C — OC 2 H 5 + CH 3 COC 6 H 5 ^OC 2 H 5 = CH 3 C(ONa) : CH.CO.C 6 H 5 .+ 2C 2 H 5 OH. CH 3 C(ONa) : CH.CO.C 6 H 5 + CH 3 .COOH = CH 3 CO.CH 2 CO.C 6 H 5 + CH 3 COO.Na. Yield. — 66% theoretical (10 gms.). Colourless crystals; insoluble in water ; M.P. 61° ; gives a deep violet coloration with ferric chloride and a bluish-green crystalline precipitate of copper benzoyl acetone with alcoholic copper acetate. This shows the compound to be tautomeric, a little of the enol form being present at ordinary temperatures. The acidity of the hydroxyl group in the enol form is not so marked as it is in the case of the hydroxymethylene compounds ; nevertheless, the metallic salts of benzoyl acetone and such di-ketones are remarkably stable, and on account of their great crystallising power have been used for the determination of the valency and atomic weight of the rare elements. They are also of importance in the theory of co-ordinating valencies. (C, 1900, L, 588 ; B., 34, 2584.) Method II. — 25 gms. (excess) of ethyl acetate and 30 gms. of aceto- phenone (1 mol.) are dissolved in 200 c.cs. of anhydrous ether. To this is slowly added with gentle cooling 20 gms. (excess) of powdered sodamide. It is then set aside for 24 hours, when the sodium salt separates, and is poured on to a mixture of ice and water sufficient completely to dissolve it. The aqueous layer is separated, and the ether removed from it by passing air through. Acetic acid is then added until the solution is acid, the precipitated benzoyl acetone being filtered off and washed with water. /ONa CH 3 COOC 2 H 5 + NaNH 2 -> CH 3 C — OC 2 H 5 . X NH 2 /ONa CH 3 C — OCoH 5 + CH 3 COC 6 H 5 -> CH 3 C(ONa) : CH.COC 6 H 5 \ N H 2 + C 2 H 5 OH + NH 3 . CH 3 C(ONa) : CH.COC 6 H 5 + CH 3 COOH -> CH 3 C(OH) : CH.COC 6 H 5 + CH 3 COONa. CH 3 C(OH) : CHCOC 6 H 5 ^ CH 3 COCH 2 COC 6 H 5 . Yield— 75% theoretical (30 gms.). Colourless crystals; M.P. 61°; insoluble in water. (B., 36, 695.) Thus the yield is improved by using ether as a solvent, and by replacing sodium ethylate by sodamide. CARBON TO CARBON 93 Reaction XXIV. Condensation of certain Oxy-Compounds with one another under the influence of Dehydrating Agents. (A., 223, 139.) — Aldehydes and ketones readily condense with one another under the influence of such reagents as zinc chloride, hydrochloric acid, sulphuric acid, alkali hydroxides, sodium acetate solution, etc., to give a-, /3-olefinic aldehydes and ketones : The reaction may be divided into the following : — (i.) Two aldehydes condense to give an olefinic aldehyde. Acetaldehyde by treatment with zinc chloride yields crotonaldehyde. (B., 14, 514 ; 25, R., 372.) CH 3 CHO + CH3CHO -> CH 3 CH(OH)CH 2 CHO -> CH 3 CH = CHCHO. By using condensing agents which are not at the same time dehydrating agents, the intermediate aldol compound can be isolated (see p. 95). A mixture of acetaldehyde and benzaldehyde yields cinnamic aldehyde by the action of hydrogen chloride, sodium hydrate, or sodium ethylate. (B., 17,2117; 20,657.) C 6 H 5 CHO + CH 3 CHO -> C 6 H 5 CH = CHCHO + H 2 0. Piperonyl acrolein is obtained from piper onal and acetaldehyde. This is the initial step in the synthesis of piperine, one of the first alkaloids synthesised. (B., 27, 2958.) 0 /\CHO 0 /\CH : CH.CHO. H 2 CO< + CHg.CHO -> H 2 C < MX > X 0 (ii.) An aldehyde and a ketone or two ketones condense to yield an olefinic ketone. Citral and acetone give pseudo-ionone. (B., 27, R., 768 ; see Reaction XVIII. (iv.) .) (CH 3 ) 2 C : CHCH 2 CH 2 C(CH 3 ) : CHCHO + CH 3 COCH 3 -> (CH 3 ) 2 C : CHCH 2 CH 2 C(CH 3 ) : CHCH : CHCOCH 3 . Acetone yields mesityl oxide. (A., 178, 351.) CH 3 .CO.CH 3 + CH,.CO.CH 3 -> (CH 3 ) 2 C : CHCOCH 3 . Hydrochloric acid is best suited for this condensation ; the acetone being saturated with it in the cold. (hi.) Several molecules of the same ketone may condense to yield di- and poly-olefimc ketones. (B., 36, 2555 ; C, 1903, II., 566.) Three molecules of acetone form phorone. 3CH 3 COCH 3 ->(CH 3 ) 2 C = CH.CO.CH = C(CH 3 ) 2 . Preparation 38. — Benzylidene Acetone (l-Phenyl-3-on-l-buten). C 6 H 5 CH : CH.CO.CH 3 . C 10 H 10 O. 146. 2 gms. (1 mol.) of benzaldehyde and 3-5 gms. (excess) of acetone are heated with 20 c.cs. of 10% caustic soda solution on a water bath for 1 hour. 94 SYSTEMATIC ORGANIC CHEMISTRY The crystals which separate on cooling are filtered of! and fecrystalHsed from a little alcohol. C 6 H 5 .CHO + CH3.CO.CH3 C 6 H 5 CH : CH.CO.CH3 + H 2 0. Yield. — Theoretical (3 gms.). Colourless crystals ; dissolve with an orange red colour in sulphuric acid ; M.P. 42° ; B.P. 262°. (A., 223, 139 ; B., 6, 254.) 0- and jo-nitrobenzylidene acetones can be prepared in the same way from 0- and ^-nitrobenzaldehydes respectively. They melt at 60° and 110°. Peeparation 39 .— Benzylidene Acetophenone (l-3-Diphenyl-3-on-l- propen). C 6 H 5 .CH : CH.CO.C 6 H 5 . C 15 H 12 0. 208. 2-1 gms. (1 mol.) of benzaldehyde and 2-4 gms. (1 mol.) of acetophenone are dissolved in 20 gms. of alcohol, 2 gms. of 10% caustic soda solution are added, and the whole allowed to stand for 24 hours. The precipitate is recrystallised from ligroin. C 6 H 5 CHO + CH 3 COC 6 H 5 = C 6 H 5 CH : CH.CO.C 6 H 5 + H 2 0. Yield.— Theoretical (4 gms.). Colourless crystals ; M.P. 57°— 58° ; B.P. 346°. (B., 20, 657.) Reaction XXV. Action of an Alkyl Halide on the Sodio-derivative of certain Ketones. (B., 21, 1297 ; 23, 2072.)— The fact that two phenyl groups have something of the same acidifying influence as one carbonyl group is shown in the case of desoxybenzoin, C 6 H 5 .CO.CH 2 C 6 H 5 ; one of the two methylene hydrogens in this compound is replaceable by sodium and with the sodium compound, the same kind of synthesis may be effected as with sodio aceto-acetic ester. The methylene group behaves as if it were between two carbonyl groups, except that the second methylene hydrogen is not replaceable. Na C 6 H 5 .CO.CH 2 C 6 H 5 > C 6 H 5 .C : CHC 6 H 5 ONa C 2 H 5 I > C 6 H 5 .CO.CH(C 2 H 5 )C 6 H 5 . Desoxytoluoin CH 3 . C 6 H 4 . CH 2 . CO . C 6 H 4 . CH 3 and desoxyanisoin CH3O . C 6 H 4 . CH 2 CO . C 6 H 4 OCH 3 behave similarly, as do all the phenyl- benzyl ketones. CHAPTER VI carbon to carbon Hydroxy-Oxy Compounds The reactions below are those in which carbon atoms are linked together to give compounds containing both a hydroxyl and an oxy group. In the aliphatic series there are three main divisions of such compounds : — (a) The oxy group is linked to a terminal carbon, and the hydroxyl group to another carbon — aldols. (6) The oxy group is linked to a non-terminal carbon, and the hydroxy] group to another — ketols. (c) The oxy group is linked to the same carbon, necessarily terminal — ■ as the hydroxyl group — acids. The above only applies to the simplest hydroxy-oxy compounds ; acid- ketols, ketaldols, and acid ketaldols also exist. The terms aldol and ketol are not usually applied in the aromatic series, but there is no reason why salicylaldehyde, for instance, should not be termed an aldol — or an aldphenol, if it is desired to restrict " ol " to purely alcoholic hydroxy Is. Reaction XXVI. (a) Condensing Action of Potassium Cyanide, Potas- sium Carbonate, or other substances on Aliphatic (Claisen), and Aromatic Aldehydes (Liebig). (J. S. C, 117, 324.) — With aliphatic and aromatic aldehydes this condensation follows very different lines. In the former the condensation takes place between the aldehydic carbon of one molecule and the a-carbon of another molecule. The same or different aldehydes may be used. 2R 1 RCH.CHO = RR 1 CH.CH(OH).C(RR 1 ).CHO. R.CH 2 .CHO + R^HO = R 1 CH(OH).CH(R).CHO. It will be seen that only an aldehyde with at least one a-hydrogen can condense with itself or with another aldehyde. This latter, however, need have no particular structure. Condensing agents stronger than those mentioned above ehminate water if possible, after condensation. Two a-hydrogen atoms in an aldehyde are necessary for this reaction (see Eeaction XXIV.). It is worth noting that if the aldol condensation takes place in the presence of magnesium amalgam, the aldehydic group is simultaneously reduced and a 1 : 3-dihydric alcohol is formed. When aromatic aldehydes are heated with potassium cyanide in aqueous alcoholic solution, the aldehyde groups condense and a ketol is formed. The reaction was discovered by Liebig for benzaldehyde (A., 3, 276), but was later applied to other aromatic aldehydes (B., 25, 293 ; 95 96 SYSTEMATIC ORGANIC CHEMISTRY 26, 60), and since then some heterocyclic aldehydes have been found to undergo the reaction. (B., 28, R., 992.) Theoretically the reaction is supposed to take place according to the following equations — ■ /OH C 6 H 5 .CHO + KCN + H 2 0 -> C 6 H 5 C — H + KOH. Cyanhy drin. /OH /OH CfiHcC OH — H •CN C 6 H 5 CHO C 6 H 5 C C — — C 6 H 5 C 6 H 5 .CO.CH(OH)C 6 H 5 + HCN. Benzoin. Aldol condensate The action of the potassium cyanide is catalytic, a small quantity being capable of condensing a large quantity of aldehyde. Preparation 40. — Aldol. CH 3 .CHOH.CH 2 .CHO. C 4 H 8 0 2 . 88. 200 c.cs. of ice-cold water are placed in the apparatus (Fig. 47), which is immersed in a cooling bath. 100 gms. of freshly distilled acetaldehyde, in portions at a time, are introduced while the cork is momentarily withdrawn, the bottle being agitated slightly during the addition, and great care being taken that the temperature of the contents does not rise above 0°. A suitable cooling bath for this stage consists of ice, water and a little hydrochloric acid. When all the aldehyde is added, the cooling bath is replaced by one of ice and hydrochloric acid, and when the temperature of the contents of the bottle has fallen to — 12°, 100 c.cs. of a 2-5% solution of potassium cyanide are slowly dropped in while the bottle is rotated ; the temperature must be kept below — 8°. After the cyanide is added, the mixture is kept for 2 hours below —8°, the freezing mixture being renewed if necessary, and then for 30 hours in an ice chest at 0°. The resulting c syrupy solution of pale yellow colour is saturated in the cold with common salt, and then quickly extracted four times with a moderately large volume of ether. The ethereal extracts are dried over anhydrous sodium sulphate, the ether distilled off, and the residue distilled under reduced pressure. Aldol passes over at 80° — 90° and 20 mms. pressure. A suction flask containing cone, sulphuric acid n ) 0 e i 1 ' i) ?u m w Fig. 47. CAKBON TO CARBON 97 should be placed between the receiver and the pump to absorb aldehyde vapours, which would otherwise prevent a high vacuum being obtained. CHg.CHO + CH3CHO -VCH 3 .CHOH.CH 2 .CHO. Yield. — 50% theoretical (50 gms.). Colourless, odourless liquid ; D. J 1-12 ; B.P. 20 75°. On distilling at atmospheric pressure forms acetaldehyde and much crotonaldehyde. (A., 306, 323 ; C, 1907 L, 1400; J. C. S, 117, 324.) Preparation 41. — Benzoin (l-2-Diphenyl-X-on-2-ol-ethan). C 6 H 5 .CO.CH(OH).C 6 H 5 . C 14 H 12 0 2 . 212. 21 gms. (2 mols.) of pure benzaldehyde and 2 gms. of 95% potassium cyanide dissolved in 80 c.cs. of 50% alcohol are refluxed for an hour on a water bath. The crystals of benzoin which separate on cooling are filtered off ; 2 gms. of potassium cyanide are added to the filtrate and a second yield of benzoin obtained as before. The whole is recrystallised from hot alcohol. 2C 6 H 5 CHO -> C 6 H 5 CO.CH(OH).C 6 H 5 . Yield. — 90% theoretical (38 gms.). Colourless prisms ; slightly soluble in water ; soluble in alcohol and ether ; M.P. 137° ; is easily oxidised to benzil (q.v.). (A., 3, 276 ; 34, 187 ; 198, 151.) Reaction XXVI. (b) Condensing Action of Potassium Cyanide on a mixture of an Aliphatic Aldehyde and a Ketone. (A., 306, 324.) — This is a reaction similar to the previous, a ketone and an aldehyde being condensed to give a 1 : 3-ketol. K-CO-CH^ + K n CHO -> R.CO.CHR 1 .CH(OH)K 11 . The ketone undergoing condensation must have at least one oc-H. If it has two, then, on heating, these ketols eliminate water to give olefmic ketones. It is to be noted that no condensation takes place at the oxy- carbon of the ketone. An excess of the ketone must always be used to prevent the condensation of two molecules of the aldehyde to an aldol compound. If the reaction is carried out at a high temperature, and with more powerful condensing agents, the unsaturated ketone is directly obtained (see Reaction XXIV.). (B., 25, 3165 ; C, 1297, I., 1018 ; 1905, II., 752). Preparation 42. — Hydracetyl Acetone (Pentanol-(2)-on-(4) ). CH 3 CH(OH)CH 2 COCH 3 . C 5 H 10 O 2 . 102. 116 gms. (2 mols. ; excess) of pure acetone are cooled to —12° (see p. 96) and treated with a 30% solution of 5 gms. of potassium cyanide. The mixture is then slowly stirred by mechanical means, and 44 gms. (1 mol.) of freshly prepared acetaldehyde dropped in, the temperature being always below —5°. The whole is allowed to stand for half an hour in the freezing mixture and 8 hours in an ice-chest. 1J vols, of alcohol-free ether are added, and the lower layer of potassium cyanide solution removed. Any remaining cyanide solution is extracted by washing twice with 60 c.cs. of saturated brine, and a third time with 30 c.cs. to ensure nothing further being removed. The washing solution is extracted several times with ether and the total ethereal solution dried for 2 hours over anhydrous S.O.O. H 98 SYSTEMATIC ORGANIC CHEMISTRY sodium sulphate (calcium chloride absorbs hydracetyl acetone). The ether is removed under reduced pressure and the residue fractionated three times under a pressure of 20 mms., first from 60° — 110°, second 70° — 90°, and third 77°— 79°. CH 3 CHO + CH 3 COCH3->CH 3 CH(OH)CH 2 COCH3. Yield. — 25% theoretical (25 gms.). Transparent, viscous liquid, mis- cible in all proportions with water or alcohol ; can be salted out of aqueous solution by potassium carbonate; B.P. 76J 176° — 177° (slight decom- position) ; B.P. 20 77°— 78° ; D. \ 8 0-9780. (A., 306, 324 ; B., 34, 2092 ; 37, 504.) Note the use of 2 mols. of acetone to prevent aldol formation. Reaction XXVII. Condensation of Chloroform with Phenols and simultaneous Hydrolysis of the Product (Reimer-Tiemann). (B., 15, 2585.) —This is a well-known method for the preparation of phenolic-aldehydes. The phenol is treated with chloroform and an alkaline hydroxide, when the former enters the ortho- and to a less extent the ^ara-position to the hydroxyl group ; hydrolysis to an aldehyde then takes place. C 6 H 4 ^ONa + C1.CHC1 2 + NaOH -> C 6 H 4 \CHC1. l 2 i -ONa C 6 H 4 ^CH(OH) 2 I /OH C 6 H 4 « \}HO. Di-aldehydes can be obtained from some polyhydric phenols. Phenolic- ethers also react as do hydroxy-aldehydes and hydroxy-acids. Though it has such a wide application, the reaction suffers from many defects. The yields are poor, being of the order of 20% theoretical. This is due to the following causes : — (a) A portion of the phenol does not react at all. (b) Some forms an ester of ortho-formic acid — 3C 6 H 5 ONa + CHCI3 = 3NaCl + CH(OC 6 H 5 ) 3 . An excess of chloroform helps to prevent this. (c) A portion of the aldehyde first formed is lost by condensation with some unattacked phenol to form a derivative of triphenyl methane — yCHO + 2HC 6 H 4 OH C 6 H 4 = H 2 0 + CH(C 6 H 4 OH) 3 . A. non-excess of phenol tends to prevent this. CARBON TO CARBON 99 (d) The alkali tends to resinify the aldehyde formed. Temperature control lessens this. The Reimer reaction is useless with compounds like phloroglucinol, pyrogallol, naphthols, poly-acid phenols of naphthalene, etc. Accordingly, where possible (for the j9-hydroxybenzaldehydes), the aluminium chloride method (Reaction XXVIII.) should be used. The yields are better, the reactions go more smoothly, little resin being formed, while pyrogallols and naphthols, etc., also react. Unfortunately, though the non-formation of other than £>-hydroxyaldehydes is often an advantage, it limits the scope of the reaction and necessitates the use of the Reimer method in many cases. It should be noted that the nitro-phenols do not condense with chloroform (B., 9, 423, 824 ; 10, 1562 ; 15, 2685). Preparation 43. — Salicylaldehyde (1 : 2 Hydroxy-benzaldehyde) and 1 : 4-Hydroxy-benzaldehyde. OH.C 6 H 4 .CHO.[l : 2 and 1 : 4]. C 7 H 6 0 2 . 122. 50 gms. (1 mol.) of phenol and 160 gms. (excess) of caustic soda in 160 c.cs. of water are heated to 50° — 60° in a 1 -litre flask on a water bath under a reflux. A thermometer dipping into the liquid is fitted to the flask. 75 gms. (excess) of chloroform are added, 10 c.cs. at a time, through the top of the condenser, the flask being well shaken after each addition. By alternate heating and cooling the temperature is kept at 65° throughout. The whole is then refluxed for half an hour, the excess of chloroform removed on a water bath, and the residue carefully acidified with dilute sulphuric acid and distilled in steam till no more oily drops pass over. The distillate is extracted with ether, and the extract shaken with twice its volume of a freshly prepared, nearly saturated solution of sodium hydrogen sulphite for a long time till no more crystals separate. (For preparation of bisulphite, see p. 506.) The precipitated bisulphite com- pound is filtered off, washed free from traces of phenol with alcohol and decomposed by heating on a water bath with dilute sulphuric acid. The aldehyde which separates is extracted with ether, the extract washed with water and dehydrated over anhydrous sodium sulphate. The ether is removed on a water bath and the aldehyde distilled. Some ^-hydroxy- benzaldehyde remains in the flask after the steam distillation. Tarry matter is removed by filtering hot through a moistened filter paper. The cold filtrate is extracted with ether, the extract dried over calcium chloride, the ether removed on a water bath, and the residue recrystallised from a small quantity of hot water containing sulphur dioxide. C 6 H 5 .O.Na + 3NaOH + CHC1 3 = C 6 H 4 (ONa)CHO + 3NaCl + 2H 2 0. Yield. — Salicylaldehyde, 20% theoretical (13 gms.) ; 1 : ^-Hydroxy- benzaldehyde, 4% theoretical (3 gms.) ; total, 24% theoretical (16 gms.). Salicylaldehyde. — Colourless fragrant oil, soluble in water ; miscible in all proportions with alcohol and ether ; B.P. 196-5° ; solidifies to large crystals at 0° ; D.^ M72. ip-Hydroxybenzaldehyde — Colourless needles ; soluble in hot water, alcohol and ether ; M.P. 116° ; sublimes. (B., 9, 824 ; 15, 2585.) H 2 100 SYSTEMATIC OKGANIC CHEMISTRY Reaction XXVIII. Formation of an Aldime by the action of the com- pound of Hydrogen Chloride and Hydrogen Cyanide, HCN.HC1, on a Phenol or a Phenol Ether hi the presence of Anhydrous Aluminium Chloride, and the Hydrolysis of the Aldime so formed (Gattermann). (B., 31, 1765 ; 32, 271 ; A., 357, 363.)— As stated in Reaction XX. (d), the Gattermann- Koch reaction does not apply to phenols or phenol ethers. If it is desired to obtain aldehydes from them, hydrogen cyanide is used in place of carbon monoxide, and the mixture of anhydrous hydrogen cyanide and hydrogen chloride is allowed to act in presence of aluminium chloride alone, cuprous chloride being unnecessary. The crystalline compound, HCLHCN, which hydrogen chloride forms with hydrogen cyanide, can also be used directly. z n H.CN + HCI -> C = NH Na. / 0H AJC1 3 / 0H C 6 H/i + ~ > C 6 H 4 \E C1CH : NH \m : NH.HC1. The aldime hydrochloride so formed is very easily hydrolysed by acids to the aldehyde. /OK /OR C 6 H 4 + H 2 0 -> C 6 H 4 + NH 3 . \}H : NH N^HO Combination always takes place in the ^ara-position to the hydroxyl or alkoxyl group. Owing to the difficulty of working with anhydrous hydro- gen cyanide, the method is seldom used in the laboratory. Reaction XXIX. (a) Condensation of a Phenol with Phthalic Anhydride to form a Phthalein. (A., 183, 1 ; 202, 68.)-^-The phthalei'ns result from the condensation of phthalic anhydride (1 mol.) with phenols (2 mols.) on heating with dehydrating agents — sulphuric acid, fused zinc chloride (to 120°) or anhydrous oxalic acid (to 115°). These compounds are particularly important; some are dyes of great technical value. The simplest representative of the class is phenolphthalem. CO /\ 2C 6 H 5 OH + C 6 K 4 / pO CO /C 6 H 4 (OH) [1 : 4] C — C 6 H 4 (OH) [1 : 4] = C 6 H 4 /O \co CAKBON TO CARBON 101 Thus the phthaleins are triphenyl methane derivatives, being all derived from phthalophenone (diphenyl phthalide). >(C 6 H 5 ) 2 C 6 H 4 o (See p. 81.) The free phthaleins are usually colourless crystalline compounds dis- solving with intense colorations in alkalis, but being reprecipitated by acids, even by C0 2 . In very concentrated alkali they give colourless solutions. A quinone structure is assumed for the coloured salts, e.g., for phenolphthalein in alkali solution. C fi H, ,[1]C -C 6 H 4 OH Xc 6 H 4 = 0 COOH The phthaleins derived from di- or polyhydric phenols are all anhydrides formed by the elimination of water from two phenolic hydroxyls, attached to two different benzene rings. These " anhydride phthaleins " are known as pyronines, since they contain, like the pyrones, a six-membered oxygen-containing ring. Even in the preparation of phenolphthalein a little of the simplest pyronine is obtained from an or^o-phthalein first formed. From resorcinol the pyronine fluorescein is the main product (see p. 378). Preparation 44. — Phenolphthalein. >(C 6 H 4 OH[4]) 2 \C 6 H 4 C00[2J 318. 16 gms. cone, sulphuric acid is added to a mixture of 40 gms. (excess) of phenol and 20 gms. (1 mol.) of phthalic anhydride. The mixture is heated for 9 hours at 115° — 120° in an oil bath, and the redoil formed poured into 0Mk SoWdl 1 a 102 SYSTEMATIC OKGANIC CHEMISTKY ^/ jJ - . a litre of water. The phenol is removed by continued boiling, water being added to replace that lost by evaporation. After cooling, the liquid is filtered and the residue washed with water. It is then dissolved in dilute caustic soda solution, and again filtered. The nitrate is acidified with acetic acid and a few drops of hydrochloric acid, and after standing for some time, the precipitate is filtered off and dried. It is then remixed on a water bath with an excess of absolute alcohol, a little animal charcoal being added if necessary. After filtration, the residue is washed with boiling absolute alcohol, and the combined filtrate and washings evaporated to two thirds its bulk. It is diluted with 8 vols, of water and filtered through a wet filter to remove resinous matter. The filtrate is then con- centrated on the water bath until the phenolphthalein crystallises. 2C 6 H 5 OH + C 6 H 4 (CO) 2 0->C(C 6 H 4 COO)(C 6 H 4 OH) 2 + H 2 0. Yield. — 25% theoretical (10 gms.). White crystalline powder ; M.P. 250°- — 253° ; slightly soluble in cold alcohol ; soluble in alkalis to crimson solution. (B., 9, 1230 ; A., 183, 1 ; 202, 68.) Reaction XXIX. (b) Condensation of a Phenol with Phthalic Anhydride to a derivative of Anthraquinone. (A., 212, 10.) — When equimolecular quantities of phthalic anhydride and a phenol react at 180° in the presence of cone, sulphuric acid, the product is not a phthalein, but the action takes a different course, and a derivative of anthraquinone is obtained. CO CO C 6 H 4 / \0 + H 2 C 6 H 3 OH = C 6 H 4 / \C 6 H 3 OH ([1] and [2]) \ / \ / CO CO a - and /3-hydroxyanthraquinone. Alizarin (1 : 2-dihydroxyanthraquinone) and an isomer hystazarin (2 : 3-dihydroxyanthraquinone) are also formed in this way from catechol and phthalic anhydride. Preparation 45. — Quinizarin (1 : 4-Dihydroxyanthraquinone). / co \ C e H 4 C 6 H 2 (OH) 2 [l : 4]. C 14 H 8 0 4 . 240. W 40 gms. (excess) phthalic anhydride and 10 gms. (1 mol.) of pure quinol are heated for 3 hours in a flask in an oil bath at 170° — 180° with 200 gms. pure cone, sulphuric acid and 20 c.cs. of water. It is then heated for 1 hour at 190° — 200°. The hot solution is gently poured into about a litre of cold water in a large basin. The whole is then heated to boiling and filtered hot with suction. The residue is again extracted with boiling water and filtered hot. It is then boiled up with 400 c.cs. glacial acetic acid and filtered hot, to remove carbonaceous matter. The filtrate is diluted with its own volume of hot water and filtered, the residue being CAEBON TO CARBON 103 again extracted with boiling glacial acetic acid and again precipitated with hot water. The crude quinizarin which separates on cooling is filtered, well washed with water and dried on a water bath. It is then quickly distilled from a hard glass retort with a large name, a porcelain mortar being used as receiver. The distillate is then powdered and recrystalhsed from glacial acetic acid and washed with more dilute acetic acid and finally with water. C 6 H 4 '0 + H 2 C 6 H 2 (OH); ,co> C 6 H 2 (OH) 2 + H a O. Yield. — 20% theoretical (4 gms.). Dark red needles from toluene, orange yellow leaves from glacial acetic acid ; M.P. 195° ; insoluble in water. (B, 8, 152 ; A, 212, 10.) Note. — The quinizarin which solidifies in the neck of the retort may be recovered by distilling some glacial acetic acid from the retort, a dis- tilling flask being used as receiver. Acetic acid vapour is inflammable, so that a rubber tube dipping over the side of the bench should be con- nected to the side tube of the flask. Reaction XXIX. (c) Condensation of Meta-hydroxy- and di-meta- dihydroxy-benzoic Acids with themselves and with Benzoic Acid under the action of hot Sulphuric Acid. (B., 18, 2147.) — The products of this action are like the above hydroxyanthraquinones. HCK VX)OH HO HOOCv iOH CO CO CO HOOc/NoB COOH OH K)H OH OH OH CO OH These reactions are of interest as confirming the structure of anthra- quinone and its hydroxy derivatives. Reaction XXX. Condensation of a Nitrile with a Phenol or a Phenol Ether and Hydrolysis of the resulting Ketimine Hydrochloride to a Ketone. (J. C. S., 118, 309.) — This is a new method of synthesising phenolic ketones, and is an extension of the Gattermann method for phenolic aldehydes (Reaction XXVIII.). (B., 43, 1122.) In 1915 Hoesch showed that the condensation of a nitrile with a phenolic compound led to the formation of a ketimine hydrochloride which could be easily hydrolysed to give a ketone. HC1 HO.RH + E X CN > HO.RRj C : NH.HC1 > HO.RRiCO. The phenol and the nitrile are dissolved in dry ether, and anhydrous 104 SYSTEMATIC ORGANIC CHEMISTRY hydrogen chloride led in. On standing, the hydrochloride of the ketimine separates. Addition of fused zinc chloride is sometimes advantageous. The ketone is obtained on heating or boiling the hydrochloride with water. The ketimines themselves have also been isolated in some cases. They are unstable, and are hydrolysed on dissolving in water. C 6 H 5 OH + C 6 H 5 .CH 2 .CN -> [4]0HC 6 H 5 C(NH.HC1)C 6 H 5 -> [4]OH.C 6 H 5 .CO.C 6 H 5 . Condensation takes place in the ^-position to the hydroxyl group. Di- and poly-hydric phenols and phenolic ethers can also be employed, as can hydroxy and methoxy nitriles (J. C. S., 118, 309). CH 3 0 r /\0CH 3 CH 3 0/\0CH + OHCH 2 CN -> ; I \yCOCH 2 OH. oh/\oh + ch 3 o.ch 2 cn -> oh/xoh OH WCO.CH 2 OCH 3 . OH It is interesting to note that if a hydroxy nitrile be condensed with a di- or poly-hydric phenol, cumaron derivatives are obtained by elimination of water. The methoxy group prevents this. OH/\OH -> H0/\0H + OHCH 2 CN 0 HO/\/\CH \yCOCH 2 OH Ico Preparation 46. — w-Methoxyresacetophenone (l-Methoxy-2-oxy-2- (2 : 4-dihydroxy-phenyl-(l) )-ethan). C 9 H 10 O 4 . 182. HO,-" ^OH !cO.CH 2 .OGH 3 . 6-5 gms. (1 mol.) of pure resorcinol are dissolved in 50 c.cs. of anhydrous ether and 5 gms. (1 mol.) of methoxyacetonitrile are added. A current of dry hydrogen chloride is passed through the solution for 2 hours, and the latter is allowed to stand in an ice-chest for 5 days. The ether is then poured off from the yellow crystalline ketimine hydrochloride, which is washed twice with the same solvent and recrystallised from methyl alcohol. It forms a white crystalhne mass (M.P. 205° — 207°). It is dissolved in water and heated at 80° (not more, or tarry matter CARBON TO CARBON 105 i separates) for 30 minutes. The solution becomes of a deep red colour. On cooling, the ketone separates ; it is recrystallised from hot water. C 6 H 4 (OH) 2 [l : 3] + CH 3 OCH 2 CN -> C 6 H 3 (OH) 2 (CO.CH 2 .OCH 3 )[l : 3 : 4]. Yield- -70% theoretical (8 gms.). Plates with nacreous lustre ; soluble in alcohol, ether, benzene ; insoluble in petroleum ether ; reduces Fehling's solution, forming a copper mirror ; M.P. 136°. (J. C. S,, 118, 309.) Resacetophenone can be prepared from resorcinol and acetonitrile in the very same way in 90% yield. 1 gm. of fused zinc chloride can be added in the above reaction either initially or after the passage of the hydrogen chloride. It improves the yield and shortens the time of standing, but unless care is taken, it tends to cause decomposition of the product during its isolation. Reaction XXXI. Action of Heat on Sodium Formate. (B., 15, 4507.)— When sodium formate is rapidly heated above 440°, an unusual reaction takes place. It loses hydrogen and forms sodium oxalate. HCOONa COONa + =1 +H 2 . HCOONa COONa In the presence of sodium hydroxide, carbonates or oxalates, the reaction takes place at 360° and to a greater extent. (C, 1903, II., 777 ; 1905, II., 367.) Oxidation of formic acid with nitric acid similarly yields oxalic acid. (B, 17, 9.) Reaction XXXII. Action of Alkalis on certain a-di-ketones. (A. 25, 25 ; 31, 324 ; B., 14, 326 ; 19, 1868 ; 41, 1644.)— When benzil is fused with potassium hydroxide, or digested with alcoholic potash, or heated for a long time with aqueous potash, a molecular re-arrangement not unlike the pinacoline transformation (q.v.) takes place, and benzilic acid is formed. H 2 0 C 6 H 5 CO.CO.C 6 H 5 -> C 6 H 5 CO.C(OH) 2 C 6 H 5 -> (C 6 H 5 ) 2 : C(OH)CO.OH. The acid can also be obtained directly from benzil by the action of air and caustic potash. 0+H 2 0 C 6 H 5 CH(OH)CO.C 6 H 5 > (C 6 H 5 ) 2 C(OH)COOH. Anisil and cuminil in a similar way yield anisilic and cuminilic acids. Preparation 47. — Benzilic Acid (Diphenyl-hydroxy-ethan acid). (C 6 H 5 ) 2 C(OH).COOH. C 14 H 12 0 3 . 228. 50 gms. (excess) of caustic potash are melted with a small quantity of water in a silver, nickel, or copper crucible. The liquid is allowed to cool to 150° (for combined thermometer and stirrer, and precautions to be taken in alkali fusions, see Fig. 50), and 10 gms. of dry, finely powdered benzil are added with constant stirring. The benzil melts and the whole soon sets to a solid mass of potassium benzilate. When all the oil has dis- appeared, the melt is cooled, dissolved in water, and benzilic acid pre- cipitated by acidifying with hydrochloric acid. The precipitate is cooled with cold water and, to free it from traces of benzoic acid, is boiled in a 106 SYSTEMATIC ORGANIC CHEMISTRY dish with water until the smell of the latter has disappeared. On cooling, benzilic acid separates, and is purified by recrystallisation from hot water. C 6 H 5 CO.CO.C 6 H 5 + KOH = (C 6 H 5 ) 2 C(OH)COOK. Yield.— 80% theoretical (16 gms.). See Preparation 48. (A., 25, 25 ; 31, 329 ; B., 14, 316.) Peeparation 48. — Benzilic Acid. (C 6 H 5 ) 2 C(OH).COOH. C 14 H 12 0 3 . 228. 20 gms. (1 mol.) of benzil, 20 gms. (excess) of solid potassium hydroxide, and 40 c.cs. of water are placed in a flask, and when the potash has dissolved, 50 c.cs. of alcohol are added. The mixture is then boiled for 10 — 12 minutes (not longer) on a boiling water bath ; poured while still boiling into a beaker, and cooled and stirred to accelerate crystallisation. After half an hour's standing in ice, the crystals are filtered off at the pump through hardened filter paper, well pressed, and carefully washed with 4(> — 50 c.cs. of ice-cold alcohol, so that the filtrate is finally almost colourless. The crystals are then dissolved in about 400 c.cs. of water, the solution filtered, brought to the boiling point, and 20 c.cs. of boiling dilute sulphuric acid are added. Part of the benzilic acid precipitates as an oil which, however, at once crystallises ; the rest separates out in colourless needles on cooling the solution. It can be again recrystallised from hot water. C 6 H 5 .CO.CO.C 6 H 5 + KOH = (C 6 H 5 ) 2 C(OH).COOK. Yield. — 90% theoretical (20 gms.). Colourless needles ; scarcely soluble in cold water ; readily in hot water, and in alcohol ; M.P. 150°. (B., 4, 1644.) Reaction XXXIII. (a) Condensation of an Aromatic Carboxylic Acid with Formaldehyde. (Lederer-Manasse). — In the presence of mineral acids formaldehyde condenses to di-phenyl derivatives with aromatic acids in much the same way as with phenols (Reaction XIII.), except that in this case it is in the meta position the condensation takes place. Reaction XXXIII. (b) Condensation of Malonic Acids with Aldehydes or some Ketones under the influence of Primary or Secondary Amines. (B., 35, 1143.) — This is an example of the activating effect of two 1 : 3-oxy groups on a methylene group between them. In the presence of primary " or secondary amines — e.g., ethylamine, di-ethylamine, piperidine — malonic acid condenses with aldehydes and some ketones to give unsatu- rated dicarboxylic acids. It is probable that the amine reacts first with the aldehyde, water being eliminated. E.CHO + H^Rj = R.CH : NRj + H 2 0, or E.CHO + 2HNR n = R.CH : (NR n ) 2 + H 2 0. (R 1]L = a divalent or two monovalent radicals.) The aldehyde derivative then acts on the acid to regenerate the amine, RCH : NR X + CH 2 (COOH) 2 = R.CH : C(COOH) 2 + NH^ or RCH(NR U ) 2 + CH 2 (COOH) 2 = RCH : C(COOH) 2 + 2NHRJJ. CAKBON TO CAKBON 107 In this way cinnamic aldehyde and malonic acid give cinnamylidene malonic acid. C 6 H 5 .CH : CH.CHO + H 2 C(COOH) 2 = C 6 H 5 CH : CH.CH : C(COOH) 2 + H 2 0. This latter, like all malonic acid derivatives, loses carbon dioxide in heating, and yields cinnamylidene acetic acid (see Preparation 426). For another and similar condensation brought about by amines, see Keaction XLV. Reaction XXXIII. (c) Condensation of Aldehydes with Malonic Acid in the presence of Alcoholic Ammonia. (B., 31, 2604.) — When aldehydes are heated on a water bath with 1 mol. of malonic acid and 2 mols. of dilute alcoholic ammonia, condensation takes place as in the previous reaction, but elimination of carbon dioxide simultaneously occurs, so that it is an unsaturated derivative of acetic acid that is formed. NH 3 CH 2 (COOH) 2 C 6 H 5 .CHO > C 6 H 5 .CH : NH > C 6 H 5 CH : C(COONH 4 ) 2 -> C 6 H 5 CH : CHCOONH 4 ->C 6 H 5 CH : CHCOOH. In this way, also, crotonaldehyde yields sorbic acid (B., 33, 2140). CH 3 .CH : CH.CHO -> CH 3 .CH : CH.CH : C(COO.H.) 2 -> CH 3 CH : CH.CH : CHCOOH. Preparation 49. — Cinnamic Acid (3-Phenyl-2-propen acid). C 6 H 5 CH : CH.COOH. C 9 H 8 0 2 . 148. 20 gms. (1 mol.) of benzaldehyde and 80 gms. (2 mols. of NH 3 ) of an 8% solution of ammonia in alcohol, are added to 20 gms. (1 mol.) of malonic acid. The mixture is heated on a water bath until a clear solution is obtained. The alcohol is then removed by evaporation and the heating continued until the evolution of carbon dioxide ceases. The residue is dissolved in water, and cinnamic acid precipitated by adding hydrochloric acid. It is then purified as in Preparation 50. C 6 H 5 CHO + H 2 C.(COOH) 2 ^C 6 H 5 CH : CH.COOH + C0 2 + H 2 0. Yield.— 80% theoretical (22 gms.) (see p. 109). (A., 188, 194 ; B., 31, 2604.) Reaction XXXIII. (d) Condensation of Aldehydes with the Sodium Salts of certain Acids in the presence of Acid Anhydrides (Perkin). (A. 100, 126 ; 227, 48 ; B, 10, 68 ; 14, 1826 ; J. C. S., 21, 53 ; J., 1877, 789.) — This is a reaction of very wide application, and one much used in the preparation of unsaturated aromatic carboxylic acids. It consists in heating together — usually to 180° — an aldehyde, the sodium salt of a fatty acid with at least one a-hydrogen atom, and an acid anhydride. The following series of reactions then occur : — (i.) Condensation takes place between the a-carbon of the acid salt and the aldehydic carbon (cf. the aldol condensation, p. 95). H.CUO + R x .CH 2 .COONa -> R.CH(OH).CHR } .COONa, 108 SYSTEMATIC ORGANIC CHEMISTRY The hydroxy acid so formed is stable if : (a) the a-carbon of the original acid has only one hydrogen atom attached, e.g., C 6 H 5 .CHO + (CH 3 ) 2 .CHCOONa -> C 6 H 5 CH(OH)C.(CH 3 ) 2 COONa. or (b) it is a a-hydroxy acid, and so immediately forms a stable lactone. This occurs when sodium succinate is employed. C 6 H 5 .CHO + CH 2 .COONa -> C 6 H 5 .CH.(OH).CH.(COONa).CH 2 .COONa. CH 2 COONa -> C 6 H 6 .CH(OH).CH(COOH).CH a .COOH -> C 6 H 5 .CH.CH(COOH) CH 2 I 0 — CO Phenyl -par aconic Acid. (ii.) Except in the above cases, elimination of water occurs and an oc, j8 unsaturated acid is formed. E.CHCOHJ.CHEpCOONa -> E.CH : CE^COONa. (iii.) If an or^o-phenolic aldehyde is used, a further loss of water takes place with the formation of a lactone. /\CHO /\CH : CH / \.CH : CH CH,COONa \/OH \/ 0H C00H \/— 0— CO Although the anhydride used need not be that of the acid of which the Na salt is used, it is best to have it so ; otherwise there is a Hability to double decomposition between the sodium salt and the anhydride, giving both sodium salts and both anhydrides, thus leading to a mixture of con- densation products. A low temperature helps to prevent such decom- position. Both substituted aldehydes and acids may be used so that the reaction is capable of numerous modifications. The following equations will illustrate this — C 6 H 5 CHO + CH 2 ClCOONa — > C 6 H 5 .CH : CC1.COOH. C.Hs.CH : CH.CHO + CH 3 COONa -> C 6 H 5 CH : CH.CH : CHCOOH. CH:CH.CH:CHC00H. H C^^l i — — 0^^ 2 \(>l ICH:CH.CHO + CH 3 COONa -> CH 2 I I 0\/ Piperic Acid. A.Uphatic aldehydes may also be used in this reaction, but react with difficulty. C ABB ON TO CARBON 109 h ' Pkeparation 50. — Cinnamic Acid (3-Phenyl-2-propen acid). C 6 H 5 .CH : CH.COOH. C 9 H 8 0 2 . 148. [ 20 gms. (excess) of benzaldehyde, 30 gms. (excess) of acetic anhydride both freshly distilled, and 10 gms. (1 mol.) of freshly prepared powdered anhydrous sodium acetate (see p. 506) are refluxed together for 8 hours in a 250 c.c. round-bottomed flask fitted with a wide vertical air-con- denser about 60 cms. long in an oil bath, kept at 180°. A calcium chloride tube is fitted to the top of the condenser. The experiment need not be completed in 1 day ; when finished, the hot reaction mixture is poured into a 1 -litre round-bottomed flask, sodium carbonate is added till alkaline, and then water until the bulk is 5 times the original. The whole is then steam-distilled until no more benzaldehyde comes over. The residue is filtered hot through a wet, folded filter paper to remove oil and resinous by-products ; cooled, and acidified with dilute hydrochloric acid. The precipitated cinnamic acid is purified by reprecipitation from alkaline solution or by recrystallisation from hot water. C 6 H 5 .CH : 0 + CH 3 .COONa -> C 6 H 5 .CH(OH).CH 2 .COONa -> C 6 H 5 .CH : CH.COONa -> C 6 H 5 .CH : CH.COOH. 7 Yield.— 85% theoretical (15 gms.). Crystallises from hot water in fine needles ; from alcohol in thick prisms ; readily soluble in hot water ; M.P. 133° ; B.P. 760 3 00°. (A., 227, 48 ; J. C. S., 21, 53 ; B., 16, 1436.) Malonic acid condenses especially readily. Even at ordinary tem- peratures, in presence of acetic anhydride, it yields benzalmalonic acid . with benzaldehyde. Better results are obtained, however, by using a less powerful condensing agent — glacial acetic acid — at 100°. This synthesis is interesting as providing a method for the preparation of certain mono- basic acids, since all malonic acids readily lose carbon dioxide on heating (see Preparation 426). Preparation 51. — Benzalmalonic acid (2-Benzylidene-propan-di-Acid). C 6 H 5 CH : C(COOH) 2 . C 10 H 8 O 4 . 192. 4 gms. of glacial acetic acid, 7 gms. (1 mol.) of benzaldehyde and 7 gms J[l mol.) of malonic acid are heated together for 10 hours at 100° under a reflux. On cooling, benzalmalonic acid separates out, is filtered off and washed with chloroform. C 6 H 5 CHO + H 2 C(COOH) 2 -> C 6 H 5 CH : C(COOH) 2 + H 2 0. i Yield.— 40 % theoretical (5—6 gms.). Colourless crystals ; M.P. 196° with decomposition ; insoluble in chloroform ; is converted to cinnamic acid at 200°— 210°. (A., 218, 129.) Reaction XXXIII. (e) Condensation of the Dichlorides of Aromatic Aldehydes with the Sodium Salts of certain Acids. (B., 15, 969.) — This is a modification of the previous reaction used commercially to prepare cinnamic acid, by heating sodium acetate with benzal chloride. The l latter is much cheaper than benzaldehyde. C 6 H 5 .CHC1 2 + CH 3 .COONa = C 6 H 5 .CH : CH.COONa + NaCl + HC1. 110 SYSTEMATIC ORGANIC CHEMISTRY Reaction XXXIV. (a) Condensation of Carbon Dioxide with a Phenol (Kolbe and Schmitt). (J. pr. 5 [2] 10, 89 ; 27, 39 ; 31, 397.)— When carbon dioxide is passed over dry sodium phenolate at 110°, sodium phenylcarbonate is obtained. C 6 H 5 ONa + C0 2 = C 6 H 5 O.CO.ONa. If the temperature be then slowly raised to 190°, intramolecular rearrangement takes place, and monosodium salicylate is formed. This, at ordinary pressures reacts with unchanged sodium phenolate to produce di-sodium salicylate and phenol. /^O.CO.ONa f^ 011 [^J ^/COONa. C 6 H 4 (OH)(COONa) + C 6 H 5 ONa = C 6 H 4 (ONa)(COONa) + C 6 H 5 OH This is " Kolbe's synthesis " of phenoHc acids. It is capable of very wide application. In all cases the carboxyl group primarily seeks the ortho-position ; if that is occupied, some condensation in the para-position occurs. The following are some examples. (i.) Phenolic ethers also react, e.g., sodium guaiocolate gives 3-methoxy- 2-hydroxy-benzoic acid. (ii.) The polyhydric phenols react especially easily. Boiling with an aqueous solution of ammonium carbonate or under pressure with aqueous potassium carbonate is sufficient. (M., 1, 236, 468 ; 2, 448, 458.) C 6 H 4 (OH) 2 + OH.COOK = C 6 H 3 (OH) 2 COOK + H 2 0. (iii.) oc- and j8-naphthols yield each a hydroxy-naphthoic acid. It is an interesting fact that if potassium phenolate is used in the Kolbe synthesis para-hydroxy benzoic acid is obtained, especially at high tem- peratures. Potassium phenyl carbonate is first formed, and heated up to 150° yields salicjdic acid, but if the temperature be further raised, the para-acid is produced in increasing quantities until at 220° potassium jpara- hydroxy-benzoic acid is the sole product. It will have been noted that in the formation of salicylic acid, only one v half of the phenol is converted ; the rest is obtained unchanged. Schmitt (Dingier 's Polytechnisches Journal, 255, 259) succeeded in modifying the synthesis to obviate this defect, and his is the method always used in- dustrially, although the other is more convenient in the laboratory. In Schmitt's synthesis sodium phenyl carbonate is prepared by heating up to 120° — 140° dry sodium phenolate with carbon dioxide in autoclaves under pressure. Complete transformation of the sodium phenyl carbonate first formed to mono-sodium salicylate then occurs on further heating. The carbon dioxide may be led in from a cylinder under pressure, or liquid or solid carbon dioxide may be mixed directly with the sodium phenolate in the autoclave. If preferred, the sodium phenyl carbonate can be prepared at ordinary pressures at 110° and then heated under pressure at 140°. CAEBON TO CARBON 111 Preparation 52. — Salicylic Acid (l-Hydroxy-2-carboxy-benzene). .OH /\C0.0H. I J C 7 H 6 0 3 . 138. (Kolbe's Method.) 1 10 gms. (2 mols.) of pure sodium hydroxide are dissolved in 15 c.cs. of water in a metal basin, and with stirring, 23 gms. (2 mols.) of crystallised phenol are gradually added. The solution is then heated over a small tree flame, with continual stirring, until a crystalline film forms on the surface of the liquid. Evaporation is continued by heating with a luminous flame kept in constant motion. During the process the basin should be securely clamped. A caked mass is obtained which is crushed at intervals with a pestle. When the mass no longer cakes together, it is transferred to a dry warm mortar and pulverised as it cools. The powder while still warm, is quickly returned to the basin, and heated as before with thorough stirring, until it is dry enough to form dust. It is then immediately placed in a 200-c.c. tubulated retort, where it is heated in a bath to 140° in a fairly rapid current of dry hydrogen (caution) obtained from a Kipp generator. * When in about 1 hour no more moisture condenses in the neck of the retort, and the body of the retort appears dry, the mass is allowed to cool in the current of hydrogen and then, while still warm, broken up, removed, quickly powdered in a mortar and replaced. The object of the above operations is to obtain perfectly dry, uncharred, well powdered sodium phenate, for it is on these factors that the success of the whole preparation depends. A moderate stream of carbon dioxide, dried through two wash f bottles of cone, sulphuric acid is passed over the surface of the sodium phenate by means of a bent tube fixed through the tubulus of the retort, and terminating 1 cm. above the substance. The retort is immersed as far as possible in the oil bath, and the temperature gradually raised to - 110° and kept there for 1 hour. The temperature is then raised to 190° in 4 hours, and on to 200°, where it is kept for 2 hours. During the whole operation, the mass is stirred frequently with a glass rod momentarily P inserted through the tubulus, and the retort also shaken from time to time, to ensure that fresh surfaces shall be exposed to the action of the gas. During the heating phenol distils and collects in the neck of the retort while the contents darken in colour. On cooling, the phenol is melted by ^ application of a flame to the outside of the neck and allowed to flow away ; then the crude reaction product is shaken out through the tubulus into a large beaker, and the retort washed out several times with warm water. The whole is boiled, filtered if necessary, and treated with much cone, hydrochloric acid (100 c.cs.), cooled for some hours in ice-water, and pre- cipitation of the crude salicylic acid facilitated by rubbing the sides of the vessel with a glass rod. The precipitate is filtered off at the pump, washed \ with a little cold water, and dried on a porous plate. The filtrate is eva- porated to low bulk, and a little more acid obtained. It may be purified 112 SYSTEMATIC OKGANIC CHEMISTRY by recrystallising from boiling water with the addition of animal charcoal, but it is better to distil the crude acid with superheated steam (see p. 23). The crystals are thoroughly dried, first on a porous plate, and then by heating on a water bath. They are placed in a short-necked flask ^ and heated in an oil bath to 170°. Then connection is made to the steam generator and a moderate current of steam at 175° pressed in. It is I important that the steam generator be not connected to the flask till the oil bath and steam have the same temperature. A wide condenser is % used (width of inner tube 3 cms. ; of outer jacket 6 cms. ; length of latter 80 cms.), otherwise the condensing acid soon blocks it. The connecting tube between the flask and condenser must be 2-5 cms. wide, and as short as possible. The side-piece should be near the bulb. When no more acid distils, the crystals in the condenser are added to the distillate which is 1 boiled and filtered. The acid separates on cooling. C 6 H 5 .O.Na + C0 2 = C 6 H 5 O.CO.ONa. ^ONa C 6 H 5 O.CO.ONa + C 6 H 5 ONa = C 6 H 3 + C 6 H 5 OH. ^CO.ONa • "I Yield. — 60% theoretical, allowing for phenol recovered (10 gms.) Colourless needles ; soluble in alcohol and hot water ; much used in w . industry as an antiseptic and a dye intermediate ; like all or^o-hydroxy benzoic acids, is volatile in steam (cf. Preparation 43) ; yields phenol on heating ; M.P. 158'5°. (B., 8, 537 ; Dingl. Poly. J., (1885), 255, 259 ; D.R.P., 38, 742 ; E.P., 7801/86.) (J. pr., [2], 10, 95 ; 27, 39 ; 31, 397.) Reaction XXXIV. (6) Action of Carbon Dioxide on an Organo-mag- I nesium Halide (Grignard). (B., 35, 2519 ; 39, 634 ; 40, 1584.)— When an alkyl or aryl magnesium bromide or iodide dissolved in dry ether is treated with dry carbon dioxide, the mono-carboxylic acid of the next 9 higher series is formed. Like all " Grignards " (see pp. 61, 67, 89) this reaction is of very general application. It works better with iodides than with bromides, and with aryl rather than alkyl compounds. The general remarks on the other Grignard reactions apply here. Moisture must be ■ absent, iodine can be used as a catalyst and so on. Also the reaction takes place in two stages, the usual intermediate compound being obtained. R.Mg.I + C0 2 = K.COOMgl. E.COOMgl + H 2 0 = R.COOH + OH.Mgl. Either acid or alkali can be used to hydrolyse the intermediate com- pound. The yields in most cases are good, but the reaction can sometimes take another course. (B., 40, 1584.) Before the following preparations are attempted, the methods for the three should be studied and compared. Preparation 53. — Propionic Acid (propan acid). CH 3 .CH 2 .COOH. C 3 H 6 0 2 . 74. All vessels used in this experiment must be absolutely dry. 12 gms. . (1 mol.) of dry bright magnesium turnings (see Preparation 18) are dis- CARBON TO CARBON 113 solved in a solution of 28 gms. (1 mol.) of dry ethyl iodide in 20 c.cs. of dry ether (see p. 209) contained in a flask fitted with a reflux condenser. The action may, if necessary, be started by adding a crystal (0-05 gm.) of iodine ; should it become too vigorous, it is moderated by cooling in water. When all the magnesium has dissolved, a not too rapid stream of carbon dioxide, washed once with sodium carbonate solution, twice with cone, sulphuric acid, and passed then over phosphorus pentoxide, is led in until it ceases to be absorbed, the flask being cooled if required. The ether is removed on a water bath and the residue distilled with dilute sulphuric acid (water is added as required) until the distillate is no longer acid. The propionic acid may be isolated by forming the lead salt, pro- ceeding as in Preparation 473, or the aqueous solution may be treated with excess of sodium carbonate and evaporated to dryness. The powdered residue is then distilled with cone, sulphuric acid until the temperature reaches 155°. The distillate is again distilled, the fraction 137° — 142° being retained. C 2 H 5 I + Mg = C a H 5 .Mg.I. C 2 H 5 .Mg.I + C0 2 = C 2 H 5 .COOMgI. C 2 H 5 .CO.OMgI + H 2 0 = C 2 H 5 .COOH + (OH)MgL Yield. — 50% theoretical (7 gms.). Colourless liquid ; rancid acid odour ; M.P. 24° ; B.P. 141° ; D. J 1-013. How the yield increases with aryl-compounds may be seen from the two following preparations. Preparation 54. — Benzoic Acid (Benzene-mono-carboxylic acid). C 6 H 5 .COOH. C 7 H 6 0 2 . 122. 2-6 gms. (1 mol.) of clean magnesium powder (or thin shavings or ribbon about 2 mms. in width, each piece about 1 cm. long, cleaned with fine emery paper and then with filter paper) are dried in an air oven at 110° for 20 minutes and placed in a dry flask fitted with a reflux. A mixture of 40 c.cs. of dry ether (see p. 209) and 20-4 gms. (1 mol.) of dry iodo- benzene of constant boiling point, and a crystal of iodine are then added. The flask is dipped in hot water or heated on a water bath so that the ether boils gently. In about half an hour a white flocculent precipitate will begin to form, and when the heat of the reaction makes the ether boil vigorously, the water bath is removed. The flask is now wrapped in a dry cloth to con- serve the heat of the reaction, and in the course of 2 hours the magnesium 'will have practically all dissolved. (If this does not occur, traces of moisture are present, and the experiment must be repeated, the ether being distilled off and again dried over sodium.) When the boiling of the ether slackens, the flask is reheated for half an hour as before on a water ♦ bath. The flask is then cooled in ice-water, the condenser removed, and a slow current of carbon dioxide, washed and dried as in the previous experiment, ' is led into the ethereal solution, which may still contain traces of undis- solved magnesium. The cooling must be continued throughout the s.o.c. i 114 SYSTEMATIC ORGANIC CHEMISTRY operation. The reaction mixture forms two layers, an upper layer of ether, and a heavy resinous lower layer of the reaction product. If the gas current is too rapid, only a slight layer of resinous mass will be obtained, but the preparation will still succeed if the cooling be thorough. Pow- dered ice is now added, and then, slowly, 30 c.cs. (excess) hydrochloric acid (1 : 1). The precipitated benzoic acid is extracted with ordinary ether, the latter removed on a water bath, and the residue gently warmed with dilute caustic alkali. The undissolved portion (see B., 49, 1584) is filtered off, and the benzoic acid reprecipitated with hydrochloric acid. More acid is obtained by extracting the mother liquor with ether. The whole is recrystallised from hot water. C 6 H 5 I -> C s H 5 .Mg.I -> C 6 H 5 .CO.O.MgI -> C 6 H 5 .COOH. Yield. — 90% theoretical (11 gms.). Colourless needles ; soluble in hot water, and in alcohol and ether ; volatile in steam ; M.P. 122° ; B.P. 250°. (B, 38, 2759.) C0 2 can also be added directly to benzene in presence of aluminium chloride to yield benzoic acid. Pkeparation 55. — Triphenylacetic Acid (Triphenylethan acid). (C 6 H 5 ) 3 C.COOH. C 20 H 16 O 2 . 288. 10 gms. (1 mol.) of triphenyl chloromethane (see p. 425) and 0-05 — 0-1 gm. of iodine, are dissolved by gentle heating in 50 c.cs. of ether, dried as on p. 209. 2 gms. (2 \ mols.) of clean, dry magnesium powder (see Preparation 18), are added, and the whole boiled under a reflux while a not too rapid current of dry carbon dioxide (see Preparation 52) is led into the liquid. After 3 hours, a lemon-yellow precipitate of the complex magnesium compound has formed. While the carbon dioxide is passing in, the whole is frequently shaken up, and dry ether is added to replace that removed by the carbon dioxide. To decompose the complex mag- nesium compound, 60 c.cs. of water are added to the flask, and the whole well shaken, poured into a basin, gradually treated with 40 c.cs. of cone, hydrochloric acid to dissolve the excess of magnesium, and boiled for 3 minutes, during which it is well shaken. The crude acid is filtered off on cooling, washed and boiled in a porcelain basin with 200 c.cs. (excess) of a 10% caustic soda solution and 100 c.cs. of water, when the greater portion of the acid goes into solution. The mixture is diluted with 300 c.cs. of water, cooled, filtered, and 100 c.cs. of cone, hydrochloric acid added. The liquid is heated to make the somewhat gelatinous precipitate granular, j cooled, the acid filtered off, washed and dried. It is recrystallised from glacial acetic acid. (C 6 H 5 ) 3 CC1 -> (C 6 H 5 ) 3 CMgCl -> (C 6 H 5 ) 3 CCOOMgCl -> (C 6 H 5 ) 3 C.COOH. Yield. — 83% theoretical (8-5 gms.). Long glittering prisms ; sparingly soluble in water, ether or benzene ; M.P. 264°— 265°. (B., 39, 634.) For a resume of some recent applications of the Grignard reagents, see J. S. C. L, 41, 7. CARBON TO CARBON 115 Reaction XXXIV. (c) Action of Carbon Dioxide on Sodium Acetylides in Dry Ether. (B., 12, 853 ; J. pr., [2], 27, 417 ; B., 33, 3586.)— This is an example of the great activating influence of a triple bond, When carbon dioxide is passed into a solution of the sodium derivative of an acetylenic hydrocarbon in dry ether, direct addition takes place to give the sodium salt of the next highest acetylenic carboxylic acid. For example, sodium allylene yields sodium tetrolate — CH 3 C : CNa-^CH. 3 .C ; C.COONa, and sodium phenyl-acetylene gives sodium phenyl-propiolate — C 6 H 5 C ; CNa->C 6 H 5 .C : C.COONa. This reaction should be compared with the preceding one. The fact that the presence of a triple bond attached to a carbon makes a hydrogen attached to that carbon replaceable by a metal should also be noted (cf. Reaction XXIII. (a) ). Reaction XXXV. (a) Condensation of Phthalic Anhydride with Aro- matic Hydrocarbons in the presence of Anhydrous Aluminium Chloride (Friedel-Crafts). (A., 291, 9 ; C. r., 119, 139.)— When the dichloride of phthalic anhydride reacts with an aromatic hydrocarbon in presence of anhydrous aluminium chloride, phthalophenone (diphenylphthalide) is formed (see p. 101). With phthalic anhydride itself the reaction can be made to take the same or a different course. Using an excess of hydro- carbon, condensation and hydrolysis occurs, and o-benzoyl-benzoic acid or its homologues are obtained according to the reacting hydrocarbon. Not only can the latter be varied, but derivatives of phthalic anhydride may be used, so that a great number of compounds can be synthesised in thislway. /CO x A1C1 3 C 6 H 4 <^\0 +C 6 H 6 > /CO.C 6 H 5 H 2 0 y COC 6 H 5 C 6 H 4 < > C 6 H 4 < XJ0.0H(A1C1 3 ) XIOOH. The or^o-benzoyl-benzoic acids readily yield anthraquinone and its derivatives (see p. 77). It may be noted that o-benzoyl-benzoic acid itself, with benzene and aluminium chloride, yields phthalophenone ; the same compound is made directly from phthalic anhydride by increasing the amount of the latter or by adding acetic anhydride. The same holds for ^>-toluoyl-benzoic acid and ditolylphthalide. (Am. Soc, 43, 1965 ; J. C. S., 122, 539.) (For the use of carbomethoxylbenzoyl chlorides and of homophthalic anhydrides in these reactions, see Am. Soc, 43, 1950.) Preparation 56. — o-Benzoyl-benzoic Acid. y COC 6 H 5 [1] C 6 H 4 < C 14 H 10 O 3 . 226. x COOH [2] 175 gms. (excess) of dry benzene are added to 50 gms. (1 mol.) of finely powdered phthalic anhydride. To this is added 90 gms. fresh aluminium 1 2 116 SYSTEMATIC ORGANIC CHEMISTRY chloride and the mixture is gently heated on a water bath in a flask fitted with a good mechanical agitator and a reflux condenser (see Fig. 37). The reaction is moderated by cooling. When the mass becomes viscous, the temperature is raised to 7 0° and kept there till the evolution of hydro- chloric acid ceases. The mechanical agitator is removed and an ordinary condenser attached. Four volumes of cold water are gradually added through ,a tap funnel, and the heat evolved causes most of the unchanged benzene to distil over. Steam is then passed through the mixture to remove the remainder of the benzene, and the residue is boiled for 4 hours, caustic soda solution being added to make slightly alkaline. The pre- cipitated alumina, formed by the decomposition of the aluminium com- pound, is filtered off and washed with boiling water. The filtrate which contains the sodium salt of o-benzoyl-benzoic acid is then acidified with dilute hydrochloric acid, and the free acid filtered off. It is then recrystal- lised from water. /CO v A1C1 3 .CO— C 6 H 5 C 6 H 4 < >0 + C 6 H 6 > C 6 H 4 < Yield.— 95% theoretical (72 gms.). Colourless crystals; M.P. 127° when anhydrous ; contains 1H 2 0 when crystallised from water ; M.P. 94°. (A., 291, 9 ; B., 14, 1865 ; 41, 3631.) Peepakation 57.— 2-^-Toluoyl-benzoic Acid ( (2-Carboxyl-phenyl)- (4-methyl-phenyl)-methanon) . /\COOH /\CH 3 . C 15 H 12 0 3 . 240. — CO— 50 gms. (1 mol.) of finely powdered phthalic anhydride and 200 gms. (excess) of dry redistilled toluene are mixed together, and 100 gms. (excess) of finely powdered, freshly prepared, anhydrous aluminium chloride (see p. 503) are added all at once. Hydrogen chloride is evolved, and the mixture becomes warm. After 10 hours, water is added, and excess of toluene removed by steam-distillation. The aqueous solution is poured off (from it a little phthalic acid may be removed by acidification), and the remaining cake is treated with sodium carbonate till alkaline, steam is passed in for 5 hours to decompose the aluminium compound, the whole filtered, and the filtrate acidified whereby [2-j9-toluoyl-benzoic acid is precipitated. .CO. AICI3 /C 6 H 4 CH 3 C 6 H 4 < >0 + C 6 H 5 .CH 3 > C 6 H 4 < \C(K \COOH(AlCl 3 ) /C 6 H 4 .CH 3 -> c 6 h 4 <; X!OOH. Yield, — 97% theoretical (78 gms.). Colourless crystals ; insoluble in cold water ; M.P. 146°. (B., 41, 3632 ; J. pr., [2], 33, 318 ; A., 311, 178.) CARBON TO CARBON 117 Reaction XXXV. (b) Condensation of Phthalic Anhydride with Phenols in the presence of Anhydrous Aluminium Chloride, s-tetrachloroethane being used as a Solvent. (B., 52, 2098 ; 53, 826.)— This is an extension of the previous reaction to phenols; employment of tetrachloroethane as solvent has enabled satisfactory yields to be obtained. Condensation takes place in the or^o-position to the hydroxyl group. Thus phenol and phthalic anhydride yield 2-(o-hydroxy-benzoyl)-benzoic acid. OH A1C1 3 .CO /\ C^XO+CAOH- ->C 6 H 4Xcooh and j9-chloro-phenol and phthalic anhydride give 2-(2-hydroxy-5-chlor- benzovl)-benzoic acid. OH /CO x AICI3 /CO /\ C 6 H 4 < >0 + C1C 6 H 4 0H > C 6 H 4 < X!(K \COOH CI. This reaction is especially interesting for many of the above compounds readily yield the corresponding anthraquinone derivatives (see p. 77), e.g., 4-chloro-l-hydroxy-anthraquinone has been obtained from j9-chloro- phenol ; substituted anthraquinones of this type are becoming increasingly important. Reaction XXXVI.— Condensation of Carbon Tetrachloride with Phenols and simultaneous Hydrolysis (Tiemann-Reimer). (B., 10, 2185.) — This reaction is perfectly analogous to that of the formation of hydroxy- aldehydes by means of chloroform and caustic alkali (see p. 98). A mixture of a phenol, carbon tetrachloride and caustic soda or caustic potash solution are boiled together. Condensation occurs, chiefly in the ^am-position, but small amounts of the ortho-acids are also formed. The product after the excess of carbon tetrachloride has been removed, is saturated with carbon dioxide and the unchanged phenol extracted with ether. The hydroxy acids are then precipitated by acidification with hydrochloric acid. /OH C 6 H 5 OH + CC1 4 -f 5KOH = C 6 H 4 < + 4KC1 + 3H 2 0. -COOK A variation of this method consists in heating carbon tetrachloride with potassium phenolate under pressure with sufficient alcohol to give a clear solution. The product in this case is mostly the or^o-acid (cf. Reaction XXXIV. {a) ). Reaction XXXVII. — Action of finely divided Metals on Halogen Acids. (B., 2, 720 ; 28, R., 466.) — The use of metals — sodium, copper, silver — to eliminate halogen from halogen compounds, and bring about the con- densation of the carbons to which the halogen atoms are attached has, as is well known, a very wide application. It is employed as a standard 118 SYSTEMATIC ORGANIC CHEMISTRY method with the halogen acids which react readily, to obtain many of the higher dibasic acids. Thus bromacetic acid on heating with finely divided metallic silver yields succinic acid ; /3-iodo-propionic acid in a similar manner gives adipic acid with silver at 140° and with copper at 160°. Ag 2 Br.CH 2 .COOH + 2AgBr + Br.CH 2 .COOH I.CH 2 .CH 2 .COOH + Ag 2 -> 2AgI LCH 2 .CH 2 .COOH CH 9 .C00H CH 2 .COOH. CH 2 .CH 2 .COOH CH 9 .CH 2 .C00H. Of the metals mentioned silver gives the best results, while iodo- and then bromo- give better yields than chloro-acids. This synthesis has one rather anomalous application, when a-brom- isobutyric acid (or its ethyl ester) is heated with silver, some tetramethyl- succinic acid is produced in the ordinary way (B., 23, 297 ; 26, 1458). But there also appears trimethylglutaric acid (A., 292, 220 ; C. (1906), II., 422). To explain the unexpected formation of this acid, it has been assumed that a portion of the a-bromisobutyric acid gives up HBr to form methacrylic acid. This latter then forms /3-bromisobutyric acid, and the silver withdraws bromine from the a- and acids, whereby the residues unite to tri-methylglutaric acid (B., 22, 48, 60). A similar explanation applies to some other syntheses in which tetramethylsuccinic and tri- methylglutaric acids appear together. HOOC.C(Br.; CH< CH 2 Br HBr CH,Br. >HOOC.CC + HBr H OOC.CH< \CH 3 ~ > X CH 3 . HOOC.CH IL Br Ag 2 + ^.COOH / (CH 3 ) 2 ,CH 2 HOOC.CH C.(COOH) CH 3 (CH 3 ) 2 . Trimethylglutaric Acid. (Compare this reaction with Reaction XL VII.) Reaction XXXVIII. (a) Action of Aqueous and Alcoholic Potassium or Sodium Cyanide on Aliphatic Halogen Compounds, and Hydrolysis of the Nitriles so formed. (B., 14, 1965 ; 15, 2318.) — The preparation and hydrolysis of nitriles are dealt with on p. 146 and p. 232 respectively. In many cases, however, it is unnecessary to isolate the nitrile ; it can be directly hydrolysed to the corresponding acid on its formation. Among others, the following syntheses have been carried out in this way : — (i.) w-Valeric acid (pentan acid) from n-butyl bromide (Am. Soc, 42, 310). CARBON TO CARBON 119 (ii.) Methyl succinic acid (methyl-butan di-acid) from propylene di- bromide. (iii.) w-Pimelic acid (heptan di-acid) from penta -methylene di-bromide. (iv.) TricarballyHc acid (3-carboxyl-pentan di-acid) from propeny] tri- bromide (Preparation 60). (v.) Citric acid (3-hydroxyl-3-carboxyl-pentan di-acid) from di-chlor- acetonic acid. Preparation 58. — Malonic Acid (Propan di-acid). CH 2 (COOH) 2 . C 3 H 4 0 4 . 104. 100 gms. (1 mol.) of powdered chloracetic acid are treated with 150 gms. of broken ice and dissolved in 125 gms. (1 mol.) of 33J% caustic soda solution. If the liquid is still acid, it is exactly neutralised with caustic soda solution, and then treated with a solution of 69 gms. (1 mol.) of 98% potassium cyanide in 130 gms. of water which has been warmed to 40° C. After an hour, the mixture is slowly warmed to 100° and kept at this temperature for 1 hour. It is allowed to cool to 25°, 125 gms. (1 mol.) of 33J% caustic soda solution are again added, and the liquid is slowly warmed to 100° and kept at that temperature until no more ammonia is evolved (2 — 3 hours). When a sample of the liquid treated with more sodium hydrate solution gives no further ammonia on boiling, the conversion of the cyanacetic acid into malonic acid is complete. The solution is cooled, acidified with dilute hydrochloric acid and carefully evaporated to complete dryness on a water bath. The residue is pow- dered and repeatedly extracted with ether and the ether removed on a water bath when malonic acid remains. It may be purified by dissolving in just sufficient caustic soda solution, boiling with animal charcoal, acidifying, evaporating to dryness, and extracting with ether as before. NaOH NaCN CH 2 Cl.COOH > CH 2 CLCOONa > CH 2 (CN)COONa NaOH HC1 > CH 2 (COONa) 2 > CH 2 (COOH) 2 . Yield. — 84% theoretical (85 gms.). Colourless crystals ; easily soluble in water, alcohol, and ether ; M.P. 132° ; loses carbon dioxide yielding acetic acid at 140° — 150°. All malonic acid homologues do this (see Reaction XXXIII. (b) ). (A., 204, 125 ; B., 22, [2], 400.) Di- ethyl malonate may be prepared from chloracetic acid by a similar method. The use of ice to keep down the temperature, and at the same time supply the amount of water required as a solvent or otherwise, in a reaction should be noted. Preparation 59.— Succinic Acid (Butan di-acid). COOH.CH 2 .CH 2 .COOH. C 4 H 6 0 4 . 118. 100 gms. (1 mol.) of ethylene dibromide and 75 gms. (excess) of potas- sium cyanide in alcoholic solution are refluxed on a water bath in a 750-c.c. 120 SYSTEMATIC ORGANIC CHEMISTRY round-bottomed flask until potassium bromide ceases to separate out from the solution. The latter is then cooled and filtered ; 60 gms. (2 mols.) of solid caustic potash are added, and the mixture again remixed on a water bath in a fume cupboard until the strong evolution of ammonia gas begins to slacken. The flask is then cooled, and the contents are acidified with dilute hydrochloric acid and carefully evaporated to dryness. The dry powdered residue is repeatedly extracted with absolute alcohol, and the extract distilled on a water bath. The succinic acid remains behind in small crystals ; it is recrystallised from hot water, decolorising if necessary with a little animal charcoal. CH 2 Br.CH 2 Br + 2KCN = CH 2 (CN).CH 2 .CN + 2KBr. (CH 2 CN) 2 + 2KOH + 2H 2 0 = (CH 2 COOK) 2 + 2NH 3 . (CH 2 COOK) 2 + 2HC1 = CH 2 .COOH + 2KC1 CH 2 .COOH Yield. — 80% theoretical (50 gms.). Colourless prisms ; soluble in water, alcohol, and ether ; insoluble in chloroform ; sublime above 100° without decomposition ; M.P. 180° ; at 235° decompose forming the anhydride. (P. R. S., 10, 574; A., 120, 268.) For the isolation of ethylene dicyanide, see p. 146.) Preparation 60. — Tricarballylic Acid (3-Carboxyl-pentan-diacid). CH 2 .COOH. I CH.COOH. C 6 H 8 0 6 . 176. CH 2 .COOH. 50 gms. (1 mol.) of propenyl tribromide are dissolved in excess of alcohol, 36 gms. (1 mol.) of coarsely powdered potassium cyanide are added, and the whole heated for 15 hours in a soda-water bottle with the cork well tied down in a water bath, the bottle being well wrapped in a cloth. A small autoclave can also be used. The bottle is then cooled in a freezing mixture, carefully (use goggles) opened, and the alcoholic liquid filtered from the potassium bromide which has separated out. The filtrate is now refluxed on a water bath with a sufficient quantity (40 gms.) of caustic potash to decompose the cyanide formed until no more ammonia is evolved. The alcohol is distilled off on a brine bath, and the cooled residue evaporated to dryness with excess nitric acid. From it, after being well dried and powdered, the tricarballylic acid may be extracted with absolute alcohol. The dark-coloured substance obtained on evaporating of! the alcohol is recrystallised from hot water with the addition of animal charcoal. C 3 H 5 Br 3 + 3KCN = C 3 H 5 (CN) 3 + 3KBr. CHo(CN).CH(CN).CH 2 CN + 3KOH + 3H 2 0 = CH;(COOH).CH(COOH).CH 2 )COOH) + 3NH 3 Yield. — 70% theoretical (22 gms.). Colourless rhombic plates ; easi y soluble in water and alcohol ; M.P. 158°. (P. R. S., 14, 77.) CARBON TO CARBON 121 General Methods of isolating organic acids from their salts may here be noted. (i.) An insoluble acid can be precipitated from a solution of a soluble salt by addition of dilute hydrochloric sulphuric or nitric acids and filtered off or extracted with a solvent (see Preparations 47, 52, 56, 186, etc.). (ii.) A volatile acid soluble in water can be obtained by treatment of a solution of its alkali salt with sulphuric acid, dilute or strong, according as the acid is more or less volatile, and subsequent distillation (see Pre- parations 53, 175). (iii.) A liquid or volatile acid soluble in water may be isolated by treatment of the lead salt with H 2 S and the draining or evaporating away of the acid as it is liberated (see Preparation 188). (iv.) A soluble non- volatile acid may be obtained by evaporating a soluble salt with dilute hydrochloric or nitric acids to dryness, and extract- ing the residue with a suitable solvent. Hydrochloric acid is usually the better to use, as nitric acid may oxidise the product (see Preparations 58, 59, 60, etc.). (v.) If the metal present be not an alkali metal, and if the acid be soluble, the former may be precipitated by addition of the exact quantity of sulphuric acid, say, or by means of H 2 S or hydrochloric acid ; the filtrate is then evaporated to dryness or distilled. Sulphuric acid is used when calcium, strontium, barium, lead, etc., are present ; hydrochloric acid when silver, lead, or mercury (-ous) are the metals to be dealt with, while H 2 S is advantageous when tin or lead have to be removed (see Pre- parations 62, 488, etc.). It is best to use sulphuric acid where a subse- quent distillation is necessary. Reaction XXXVIII. (6) Action at 200° of Aqueous or Aqueous-alco- holic Potassium Cyanide in presence of Cuprous Cyanide on Aromatic Halogen Compounds, and Hydrolysis of the Nitriles so formed. (B., 52, [B], 1749.) — It is difficult directly to replace nuclear halogen atoms in aromatic compounds, unless these atoms be rendered labile by the presence of nitro- or other negative groups (see p. 194). Lately, however, it has been shown that by the action of aqueous or aqueous-alcoholic potas- sium cyanide at 200°, using cuprous cyanide as catalyst, combined replace- ment of the halogen by CN and hydrolysis of the nitrile so formed occurs. In this way bromo-benzene has been directly converted into benzoic acid, ^)-di-bromo-benzene into terephthalic acid, and j9-bromaniline into p- aminobenzoic acid. Similar transformations have also been effected in the benzene series as well as with derivatives of naphthalene and thiophene. Copper is the unique catalyst in this reaction which compares in some respects with the older Sandmeyer reaction. Reaction XXXVIII. (c) Action of Hydrogen Cyanide on Aldehydes and Ketones and Hydrolysis of the Cyanhydrins so formed. (B., 14, 235; C. Z. (1896), 90; C, (1900), I., 402.)— As is explained under Reaction L (q.v.) aliphatic and aromatic aldehydes and ketones or their bisulphite compounds react with hydrogen cyanide to form cyanhydrins (a-hydroxy -nitriles). These are readily hydrolysed to a-hydroxy-acids for 122 SYSTEMATIC ORGANIC CHEMISTRY the preparation of which, since the isolation of the nitrile is unnecessary, the above reaction is often directly used. In the sugar group it is of especial interest, not only for its value in determining constitution, but also for the synthesis of sugar and other derivatives containing long carbon chains. Thus (Z-glucose yields in this way the lactone of a-^-glucoheptonic acid, which may be reduced to cn-d- glucoheptose — that is to a sugar containing one more secondary-alcohol group than the original sugar (see Reaction LXV. (b), where the subject is further treated). In this way, too, lactic acid has been synthesised from acetaldehyde. CH 3 CHO + HCN -> CH 3 .CH(OH)CN — > CH 3 CH(OH)COOH. Dichloracetonic acid has been prepared from dichloracetone. CH 2 C1 CH 2 C1 .1 I CO -> C(OH)COOH CH 2 (OH)(CHOH) 5 CH(OH)CN -> CH 2 OH.(CHOH) 5 .CHOH.COOH. Yield. — 70% theoretical (90 gms.). Colourless crystals ; soluble in water ; M.P. 140°. (B., 19, 1916 ; 23, 936 ; A., 270, 65, 272, 200.) It is noteworthy that it is often preferable to use the bisulphite compound of the aldehyde rather than the aldehyde itself (see p. 151). The small quantity of ammonia used above to help the reaction may do so by the momentary formation of the ammonia compound of the aldehyde. | | /OH CHO + NH 3 -> HC< NH 2 I /OH | .OH HC< + -> B.C( + NH 3 . X NH 2 HCN \CN Hydrogen cyanide seems to react in this way more readily than it unites directly to the oxy group. I l/ 0H CHO + HCN -> CH \ " \CN. The lactone of a-^-fructose-carboxylic acid, M.P. 130°, is prepared in the same manner from (^-fructose (leevulose). It will be noted that from glucose, four carboxylic acids can be obtained — an a- and /3-acid from 124 SYSTEMATIC ORGANIC CHEMISTRY each of the optical isomers (A., 270, 64). Like many acids containing a y-hydroxy group, all these free acids are unstable, immediately forming lactones on liberation from their salts. Reaction XXXIX. Fusion of the Salts of Aromatic Sulphonic Acids with Sodium Formate. — An important property of sulphonic acids is the behaviour of their salts in certain fusions. Two of these are dealt with on p. 203 and p. 316. The third — fusion with sodium formate to obtain carboxylic acids — is of theoretical rather than commercial import- ance. It is interesting, however, when considered in comparison with the other two fusions. C 6 H 5 .S0 3 Na + H.COONa = C 6 H 5 .COONa + H.S0 3 Na. The aromatic group is as it were transferred from one acid radical to another, interchanging with hydrogen in so doing. Reaction XL. Condensation of a Phenol with a 6 ' Methane Carbon Atom. ' ' (A., 194, 123 ; 196, 77 ; B., 28, R., 743.)— Phenols can be condensed with compounds which can yield a nuclear carbon, to give dyes of the rosalic acid series. The fewco-compound — a-j9 3 -hydroxy-triphenyl-methanol— first formed, is unstable and immediately yields the dyestuff, no oxidising agent being necessary. In this respect these compounds differ from the analogous rosaniline compounds (see p. 376). Aurin, the simplest member of the series, is prepared by heating together phenol, oxalic, and strong sulphuric acids at 130° for 6 hours. H 2 S0 4 y 0 2C 6 H 5 OH (COOH) 2 -> ( + CO) > ,(C 6 H 4 OH) 2 r^( C 6H 4 OH) C 6 H 5 OH [ V OH -J 0 (HOC 6 H 4 ) 2 = C = C 6 H 4 = 0. The methane carbon atom can also be supplied by formaldehyde ; the steps in the synthesis are — H 2 C = 0 + H - C6H4 '° H H 2 C(C 6 H 4 OH) 2 C 6 H 5 0 H + 0 H.C 6 H 4 .OH r C(C 6 H 4 OH) 3 -| |_OH J (HOC 6 H 4 ) 2 C = C 6 H 4 = 0. Rosolic acid (methyl aurin) another important member of this series, is prepared by oxidising a mixture of phenol and o- and 2>-cresols with arsenic acid and sulphuric acid. 1 mol. of each of the cresols and 1 mol. of phenol react, the methyl carbon of the ^-cresol molecule serving as a nuclear carbon. CARBON TO CARBON 125 CJL.OH HC H H:C 6 H 4 .OH H H:C 6 H 3 .OH .CH, 30 /C 6 H 4 OH / HO.O— C 6 H 4 OH \C 6 H 3 (OH)(CH 3 ) /C 6 H 4 OH / -> C = C 6 H 4 = 0 \ \C.H 8 (OH)(CH 8 )[3 : 4]. These compounds dissolve in alkalis, and alcohols with a bright red colour, but they are now little used as dyes. As will be seen, they are assumed to have a quinonoid formula like all the triphenylmethane dyes (see p. 374). \ CHAPTER VII carbon to carbon Oxide-Oxy Compounds In this section those nuclear syntheses of which the product is neces- sarily an ester or some other compound containing both an oxy and an oxide (ether) group are described. Many important reactions are here involved — partly owing to the activating influence of the oxy-group, and partly because the inertness of the oxide-group enables oxy compounds containing it to be used, where the corresponding hydroxy-oxy compound (acid) is inadmissible, owing to the reactivity of its hydroxyl group. On this account, these ester syntheses are very often only undertaken to obtain an acid by an after-hydrolysis. Reaction XLI. Elimination of Water from o-Phenoxy-benzoic Acids (o-Phenyl-salicylic acids). (B., 21, 502; 25, 1652; 26, 71.)— The xanthones (di-benzpyrones) possess a chromogenic nature, and form the basis of some dyestuffs. They are obtained by loss of water from the o-phenoxy -benzoic acids by treating the latter with dehydrating agents- cone, sulphuric acid at 100°, fused zinc chloride, or acetic anhydride. /0\ 0 11 OH \/\CO o-Phenoxy -benzoic acid. 0 Xanthone. They have also been synthesised by condensing salicylic acid with phenols through the agency of sulphuric acid, acetic anhydride, etc. (B., 21, 502 ; 24, 3982 ; 25, 1652 ; 26, 71 ; 27, 1989 ; A., 254, 265.) All four possible mono-hydroxy xanthones have been prepared in this way, as have some of the poly-hydroxy compounds. These latter are the more important. (HO)C 6 H : H OH OH. CO, + oh/ C 6 H 4 HOC fi H, ,CQ 0 The xanthones are allied to the thio-xanthones (J. C. S., 97, 1290) the acridones (B., 25, 1734) and the fluorones (J. C. S., 99, 545). The mother 126 CARBON TO CARBON 127 substance obtained by reduction of xanthone is xanthene (methylene-di- phenylene oxide). (B., 26, 72.) 0 Xanthene. Fluorone. Although the xanthones contain a ketone oxygen atom, they, like the pyrones (see p. 378), do not react with hydroxylamine, or phenyl hydrazine. Reaction XLIL Prolonged action of Heat on Ethyl Aceto-acetate. (A., 273, 186.) — By prolonged boiling of aceto-acetic ester under a reflux con- denser at ordinary pressures, condensation occurs, and dehydracetic acid is formed. The parent acid, a 8-hydroxy-acid, is unstable, and has not yet been isolated. CO.OEt. HO.C.CH3 CO — 0 — C.CH3 I [I -> I II + 2EtOH. CH 3 .CO.CH 2 EtO.CO.CH CH 3 .CO.CH— CO— CH 1 mol. of the keto- reacts with 1 mol. of the enol-form ; it will be noted how the activated methylene group enters into the reaction. The lactone formed is important, because hydriodic acid reduces it to 1 0 [ di-methyl pyrone CH 3 C : CH.CO.CH : C.CH 3 , a certain amount of re- arrangement occurring. This latter compound is, like all the pyrones, of great theoretical interest (see p. 378). Also dehydracetic acid figures in the chemistry of the ketenes, ketene itself polymerising to it, under the influence of zinc bromide or tertiary amines, or even spontaneously. CO 0 = C : CH 2 (C 2 H 5 ) 3 N CO — 0 — C.CH 3 II > I II CH 2 =CO CH 2 0 : C = CH 2 CH 3 .CO.CH— CO— CH. (A., 273, 186 ; C, 1900, II., 625 ; A, 257, 261.) Preparation 63. — Dehydracetic Acid (Methyl-aceto-pyronon) (Feist). CO — 0 — C.CH 3 . I || C 8 H 8 0 4 . 168. CH 3 .CO.CH — CO — CH 20 gms. (2 mols.) of ethyl aceto-acetate are boiled under a reflux for 6 hours, pieces of porous porcelain being added to promote regular ebullition. The liquid is then distilled to 200° ; the distillate may be fractionated in vacuo to recover unchanged aceto-acetic ester (see Preparation 73). The brown residue solidifies on cooling to a crystalline mass. It is boiled with 5N caustic soda solution with the addition of animal charcoal and filtered 128 SYSTEMATIC ORGANIC CHEMISTRY hot. The sodium salt crystallises from the nitrate ; acidification with dilute sulphuric acid precipitates the required lactone. 2CH 3 .CO.CH 2 COOC 2 H 5 = C 8 H 8 0 4 + 2C 2 H 5 OH. Yield. — 80% theoretical, allowing for aceto-acetic ester recovered (5 gms. on each 10 gms. of aceto-acetic ester used). Colourless needles ; insoluble in water ; M.P. 108° ; B.P. 760 2 69° ; K = 0-00053. (A., 257, 261 ; B., 27, R., 417.) Reaction XLIII. (a) Formation of Esters by the action of Acid Anhy- drides or of Acid Chlorides on an Alcohol in the presence of Magnesium Alkyl Halide (Grignard). (B., 39, 1738.)— This application of the Grignard reaction to the preparation of esters is of theoretical rather than practical interest as illustrating the wide applicability of this many-sided reaction. The steps in the synthesis will be clear from the examples given ; they are somewhat different from the usual phases of a Grignard reaction. (i.) RMgl + (CH 3 ) 3 C(OH) = (CH 3 ) 3 COMgI + E.H. 2(CH 3 ) 3 COMgI + (CH 3 CO) 2 0 -> /OMgl CH 3 .C-O.C(CH 3 ) 3 \0 > 2CH 3 .CO.O.C.(CH 3 ) 3 + (IMg) a O. CH 3 .C~OC(CH 3 ) 3 ^OMgl (ii.) (CH 3 ) 3 COMgI + CH 3 COCl = CH 3 CO.O.C(CH 3 ) 3 + MgClI. Iso-amyl acetate has been obtained in this way from isoamyl alcohol and acetyl chloride. The method does not offer any advantages over the more usual esterification reactions. For the general experimental method and precautions necessary in Grignard reactions, see Preparation 18. Reaction XLIII. (b) Formation of Ethyl Esters by the action of Ethyl Chloroformate on Magnesium Alkyl Halide in Dry Ethereal Solution (Grig- nard). — This is another mode of application of the Grignard reaction to the synthesis of esters. It is more direct than the previous method. /OMgCl CH 3 Mg.Cl + Cl.COOC 2 H 5 ->• Cl.C.OC 2 H 5 -> CH 3 .COOC 2 H 5 + MgCl 2 . \CH 3 Reaction XLIII. (c) Condensation of a-Halogen Fatty Acid Esters with Aldehydes and Ketones by means of Zinc or Magnesium (Reformatsky- Grignard). (C, (1901), I., 1196 ; IL,30; (1902), I., 856.)— This is an exten- sion of the Grignard and zinc alkyl reactions which enables a-halogen esters to be condensed with oxy compounds as if they were simple alkyl halogen compounds. The zinc or magnesium alkyl derivative is neither prepared beforehand nor isolated in the reaction, but there is little doubt that some such compound is transitorily formed. Zinc is the metal most usually CARBON TO CARBON 129 employed. The product is a /3-hydroxy ester, and the method is the standard one for obtaining the higher ^-hydroxy acids. The equation below will illustrate this : — ZnBr CH 3 .CHBr.COOC 2 H 5 + Zn -> CH 3 CH(COOC 2 H 5 ). ZnBr CH3.CHO + CH 3 .iH(COOC 2 H 6 ) -> OZnBr I H 2 0 CH 3 .CH(CHCH 3 ).COOC 2 H 5 > OH I CH 3 CH(CH.CH 3 ).COOC 2 H 5 Preparation 64. — Ethyl /^hy BrZn- CH(CH 3 )COOC 2 H 5 . CH 3 I CH 3 CO + BrZnCH(CH 3 )COOC 2 H 5 -> I /OZnBr C \ CH 3 I \CHCH 3 .COOC 2 H 5 CH 3 H 9 0 2' > CH 3 C(OH)CH 3 CH(CH 3 )COOC 2 H 5 . Zn(CH(CH 3 )COOC 2 H 5 ) 2 might also be considered an intermediate com- pound in the reaction. s.o.c. K 130 SYSTEMATIC ORGANIC CHEMISTRY Yield. — 50% theoretical (60 gms.). Colourless oil, insoluble in water ; B.P. 30 , 105°. (C, (1901), L, 1196 ; II., 30 ; (1902), L, 856.) Reaction XLIII. (d) Condensation o£ Di-ethyl Oxalate with Alkyl Halides in the presence of Zinc (Frankland — Duppa). (A., 185, 184.) — This is a type of condensation very similar to those just described. The zinc alkyl is not isolated, and simple halogen compounds are used. The product is a derivative of glycollic acid. ^/OC 2 H 5 Zn ^/OCaHs 2CH 3 I + C = O -> C - CH 3 \C00C 2 H 5 I \0ZnCH 3 Ln + COOC 2 H 5 /CH 3 /CH3 C— CH 3 H 2 0 C — CH 3 | \0ZnCH 3 > | \OH COOC 2 H 5 COOC 2 H 5 . Reaction XLIV. (a) Condensation oi Alkyl and Aryl Halides with Ethyl Sodio-malonate and its Homologues. (B., 7, 1383 ; Am. Soc. (1921), 680.)— The malonic esters are almost as valuable as the aceto-acetic esters (see Reaction XLIV. (b) ) in the synthesis of mono- and poly-carboxylic acids owing to the successive replaceability by sodium of the hydrogen atoms of the methylene group, activated as it is by two neighbouring carbonyl groups. These sodio derivatives are very reactive, and undergo the following changes : — (i.) By the action of alkyl halide on the sodio compound, a mono-alkyl compound is formed. Na RI CH 2 (COOC 2 H 5 ) 2 -> CHNa(COOC 2 H 5 ) 2 -> CHR(COOC 2 H 5 ) 2 . (ii.) By the action of alkyl halide on the sodio derivative of a mono- alkyl malonic ester, a di-alkyl compound is produced. Na RJ CHR(COOC 2 H 5 ) 2 -> CNaR(COOC 2 H 5 ) 2 -> CR 1 R(COOC 2 H 5 ) 2 . From these esters the corresponding dibasic acids can be obtained by hydrolysis, so that the homologues of malonic acid can be synthesised in this way. Again, as all these acids have two carboxyls attached to the same carbon atom, they lose carbon dioxide on heating and pass into mono- basic fatty acids (B., 27, 1177). This affords an important and standard synthesis for these latter acids (see Preparation 426, also Preparations 58 and p. 107). (iii.) Cyclo paraffin derivatives can also be synthesised. Malonic ester and ethylene bromide in the presence of sodium alcoholate yield tri- methylene-di-carboxylic ester and thence a di- and mono-carboxyhc acid. (Am. Soc, 42, 314 ; 43, 680.) CARBON TO CARBON 131 CH 2 Br CH 2 (COOC 2 H 5 ), I + CELBr C 2 H 5 ONa CH, CH 9 > CH— CH(COOC 2 II 5 ) 2 . CH 2 Br (This compound can be isolated by using an excess of the alkylene bromide). CH 2 C(COOC 2 H 6 ) a ;C(COOH)< CH. — > |^CHCOOH. CH 2 C 2 H 5 ONa is more frequently used to obtain the sodio derivatives of the malonic esters, though metallic sodium can also be employed. By using various alkylene dibromides, 4, 5, 6 or 7, membered rings can also be obtained. (A., 284, 197.) (iv.) Simultaneously there is formed in the above reaction butane-tetra- carboxylic ester, and it yields a tetra- and thence a dibasic acid (adipic acid). The tetra-basic ester can also yield ring compounds (Reaction XLVIL). CH 2 Br CH 2 CH(COOC 2 H 5 ) 2 I + 2CHNa(COOC 2 H 5 ) 2 > j CH 2 Br CH 2 CH(COOC 2 H 5 ) 2 CH 2 CH(COOH) 2 (heat) CH 2 CH 2 COOH ~> I > I CH 2 CH(COOH) 2 CH 2 CH 2 COOH. (v.) Also by starting with compounds such as I., ring compounds may be synthesised by intra-molecular condensation. CH(COOC 2 H 5 ) 2 C 2 H 5 ONa CNa(COOC 2 H 5 ) 2 CBr /\ I R -CBr Ri C(COOC 2 H 5 ) 2 R — 1 R n (vi.) Halogen esters react like simple alkyl halides. CH 2 C1C00C 2 H 5 + CH 2 (COOC 2 H 5 ) 2 CH(COOC 2 H 5 ) 2 I CH 2 (COOC 2 H 5 ) Ethane -tricarboxylic Ester. CH.ONa 132 SYSTEMATIC ORGANIC CHEMISTRY (vii.) The acyl malonic esters are produced from the acyl chlorides, and sodio-malonic ester in a manner exactly analogous to the alkyl malonic esters (B., 20, R., 381). Benzoyl chloride, and sodio ethyl malonate yield benzoyl-malonic ester. C 6 H 5 C0C1 + CHNa(COOC 2 H 5 ) 2 -> (C 6 H 5 CO)CH(COOC 2 H 5 ) 2 . The structure of the sodio derivatives of diketomethylene compounds like malonic ester, is dealt with in Reaction XLIV. (b), and an explanation is given as to why only one hydrogen is replaceable at a time. Pkepaeation 65. — Ethyl-malonic Ester. C 2 H 5 CH(COOC 2 H 5 ) 2 . C 9 H 16 0 4 . 188. To 25 gms. of absolute alcohol contained in a flask provided with a reflux condenser, 2-3 gms. of sodium are added, and when the metal has dissolved, 16 gms. of ethyl malonate are added. The sodio-derivative of the ester is precipitated as a white solid. The flask is shaken while 20 gms. of ethyl iodide are slowly run in from a dropping funnel ; the precipitate gradually reacts and sodium iodide is deposited. Heating is conducted on a water bath (1 — 2 hours) until the product ceases to show an alkaline reaction. The alcohol is distilled off, the residue diluted with water and extracted with ether. The extract is dried over calcium chloride, the ether distilled off, and the residue fractionated, when the product passes over at 200°— 210°. CH 2 (COOC 2 H 5 ) 2 -> CHNa(COOC 2 H 5 ) 2 -> C 2 H 5 .CH(COOC 2 H 5 ) 2 . Yield. — 75% theoretical (15 gms.). Colourless oil of fruity odour ; B.P. 207° ; D. l * 1-008. (A., 204, 134.) Methyl, propyl, butyl, etc., malonic esters are also obtained in a similar manner. It is to be observed that aryl halides do not undergo this re- action. The di-alkyl esters are obtained from the mono-alkyl esters in the same way as the latter are obtained from malonic ester. But although di-alkyl compounds are not formed directly in any quantity, yet it frequently happens that a little is obtained in the preparation of the mono-alkyl compound from 1 mol. of sodium ethoxide and 1 mol. of alkyl halide, owing to the product sought for reacting with more sodium and alkyl halide. This may be prevented when necessary by using only half the calculated quantity of sodium and alkyl halide. By this means the yield of benzoyl malonic ester for example is raised from 55% to 85% in its preparation from sodium, benzoyl chloride and malonic ester. (B., 44, 1507.) Reaction XLIV. (6) Condensation of Alkyl and Aryl Halogen Com- pounds with the Sodio- and other Metallo- derivatives of Aceto-acetic Ester and its Homologues. (A., 186, 214 ; 201, 143 ; 213, 143.)— Like malonic ester, aceto-acetic ester contains two 1 : 3-carbonyl groups with a methylene group in position 2. It is only to be expected then that it yields with metallic sodium or sodium alcoholate sodio derivatives from which mono- and di-, alkyl and aryl homologues can be obtained by treat- ment with a suitable halide, including halogen esters. Aceto-acetic acid shows the same property, but its great instability necessitates the use of CARBON TO CARBON 133 its very stable ethyl ester. Other examples of 1 : 3 di-keto-2-methylene compounds, of which all possess similar properties to the esters described in this and the previous reaction will be found on p. 91. Reference may also be made to Reaction XLVI. These compounds are alike in being tautomeric, the keto and enol forms being in an equilibrium which varies both with substance and with temperature— — CO.CH 2 .CO — ~ > — C(OH) : CH.CO— and — CO.CHE.CO — > — C(OH) : CR.CO— It is this equilibrium which renders difficult the explanation of the course of the reactions which take place when metallic sodium or sodium ethoxide and then alkyl or acyl halide are added to these compounds. At first it was thought that the sodio-compound formed with acetoacetic ester was CH 3 .CO.CHNa.COOC 2 H 5 , because the reaction with alkyl and acyl halides always yielded a C-derivative, CH 3 .CO.CHR.COOC 2 H 5 . The first example of a different course of reaction was found in the formation of an O-derivative — j8-carbethoxy-hydroxy-crotonic ester from sodio- aceto-acetic ester and chloroformic ester (J. pr., [2], 37, 473 ; B., 25, 1760 ; A., 277, 64). This could only be explained by assigning an enol formula to the sodium salt — CH 3 C(ONa) : CHCOOC 2 H 5 + C1C00C 2 H 5 -^ CH 3 .C(OCOOC 2 H 5 ) : CHCOOC 2 H 5 . This immediately explained why only one of the methylene hydrogen atoms is replaceable at a time. The formation of C-derivatives could then be looked on as an addition reaction followed by the separation of sodium halide. A I CH 3 C(ONa) II + i — > I -> CH CH 3 CH I . Nil COOC 2 H 5 COOC 2 H, CH.CO CH(CH 3 ) + Nal. I COOC 2 H 5 Some of the C-derivative, acetyl-malonic ester, is also formed in the chloroformic ester condensation quoted above. In the majority of cases the C-derivative is produced to the exclusion of the O-derivative. For an explanation, see J. pr., [2], 37, 473 ; see also equation (4), p. 134. The various alkyl derivatives of aceto-acetic ester are important, because of the hydrolyses they undergo (see p. 182). Some reference to the structure of the acetoacetic ester will be found under Reaction XLVI., p. 140 ; the reactions which it undergoes are discussed in Reactions XLVIL, Lin. 134 SYSTEMATIC ORGANIC CHEMISTRY The following equations will illustrate some extensions of which the reaction is capable : — • (1) C 6 H 5 .CC1 2 .C 6 H 5 + CH 3 C : CH.COOC 2 H 5 (Cu' = ^ 6 Benzophenone Dichloride. Cu' Cuproaceto- acetic Ester. CH 3 COCHCOOC 2 H 5 / (C,H 5 ) a C— CI -> CH 3 C : CCOOC 2 H 5 CH 3 CO.CCOOC 2 H 5 / I "> II Cu'O C(C 6 H 5 ) 2 C(C 6 H 5 ) 2 / Diphenyl-aceto- aery Hie CI Ester. The reaction may be assumed to go as above. The copper derivative of aceto-acetic ester is formed by adding a saturated alcoholic solu- tion of cupric acetate to the ester ; a bluish-green crystalline precipitate (C 6 H 9 0 3 ) 2 Cu is produced (cf. p. 92). rixr \ >C : CHCOOC 2 H 6 /C 1 /O/ (2) CO + Cu \C : CHCOOC 2 H 5 Carbonyl Chloride CH 3 CH 3 COCH.COOC 9 H 5 / CO CH 3 COCH.COOC 2 H 5 . Carbonyl Diaceto -acetic Ester. The latter compound is important in the synthesis of y-pyrone. (3) Attention may also be drawn to the synthesis of ethyl di-keto- camphorate from ethyl di-ketocamphopyrate (see Reaction XL VI. (in.) ). OC CH — COOC 2 H 5 X >»CH 3 ) 2 OC CH OC CH COOC 2 H 5 >C(CH 3 ) OC C COOC 2 H 5 I CH 3 (4) It is of interest to note that while chloroformic ester yields mostly CARBON TO CARBON J 35 the O-derivative, it is only the C-derivative that is obtained from chloro- acetic ester. CH 2 Cl.COOC 2 H 5 + CH 3 C(ONa) : CHCOOC 2 H 5 -* CH 3 COCH(CH 2 C06C a H 5 )COOC 2 H 8 . Acetyl-succinic Ester. On the other hand, chloroformic ester yields the C-derivative with cuproaceto-acetic ester. (B., 37, 3394, 4627 ; 38, 22.) (5) In the previous reaction (v.), ring compounds may be synthesised by intramolecular condensation. COCH 2 COOC 2 H 5 COCHNaCOOC 2 H 5 C 2 H 5 ONa R CBr R CBr t \ / \ Rj R 2 Rj Rc CO — — CHCOOC 2 H 5 c Pw R The following preparations show the experimental methods used. It is to be noted that in all these reactions bromides and iodides give better yields than chlorides. Pkepakation 66. — Ethyl-aceto-acetic Ester (Ethyl ester of 2-ethyl-3-on- butan acid). CH 3 .CO.CH(C 2 H 5 )COOC 2 H 5 . C 8 H 14 0 3 . 158. 32-5 gms. (1 mol.) of aceto-acetic ester are slowly added with cooling to the solution obtained by dissolving 5-7 gms. (1 atom) of clean sodium wire in 70 gms. of absolute alcohol under a reflux. 40 gms. (1 mol.) of ethyl iodide are then slowly added, and the whole refluxed on a water bath until it shows a neutral reaction. If necessary a little more ethyl iodide is added. The alcohol is removed on a water bath and the residual oil shaken with water and extracted with ether. The ethereal extract is dried over anhydrous potassium carbonate, the ether removed on a water bath, and the residue distilled, the portion boiling at 190° — 198° at 760 mms. being collected separately. If preferred, the fractionation can be done under reduced pressure. C 2 H 5 ONa C 2 H 5 I CH 3 .CO.CH 2 .COOEt > CH 3 .CO.CHNa.COOEt > CH 3 .CO.CH(C 2 H 5 )COOEt. Yield. — 80% theoretical (32 gms.). Colourless oil ; insoluble in water ; B.P. 14 84° ; B.P. 760 198° ; D. ? 0-9834. (A., 186, 220 ; 192, 153 ; C, (1904), II., 309.) Other mono-alkyl aceto-acetic esters may be prepared in an exactly analogous manner, using corresponding molecular quantities of the alkyl iodides. 136 SYSTEMATIC ORGANIC CHEMISTRY In the preparation of some of the higher mono-alkyl aceto-acetic esters the yield is sensibly lowered, owing to the formation of di-alkyl compounds due to secondary reactions of the same type as those described on p. 132. This in like manner can be remedied by using only half the calculated quantity of sodium and alkyl halide. The unattacked aceto-acetic ester is recovered by distillation. Preparation 67. — Benzyl Aceto-Acetic Ester. CH 3 COCH(CH 2 C 6 H 5 )COOC 2 H 5 . C 13 H 16 0 3 . 220. To a solution of 6 gms. (1 atom) of sodium in 75 c.cs. (excess) of absolute alcohol are gradually added 65 gms. (2 mols.) of aceto-acetic ester. 32 gms. benzyl chloride are dropped in, and the temperature of the mixture is maintained at 30° for an hour. It is then refluxed for an hour. The product is distilled under reduced pressure, the fraction 164° — 165° at 14 mms. consisting of benzyl aceto-acetic ester being retained. Up to this temperature, the unattacked aceto-acetic ester passes over. CH 3 COCHNaCOOC 2 H 5 + C 6 H 5 CH 2 C1 CH 3 COCH(CH 2 C 6 H 5 )COOC 2 H 5 . Yield.— 85% theoretical (47 gms.). Colourless oil ; B.P. 14 165° ; B.P. 760 2 76° ; insoluble in water. (A., 204, 179.) An equally good yield can be obtained by replacing the ethyl alcohol by 100 c.cs. butyl alcohol. The di-alkyl esters are made from the mono-alkyl esters in a manner exactly similar to that by which the mono-alkyl esters are made from aceto-acetic ester itself. The method of preparation of acyl aceto-acetic esters is exemplified in the following. The reaction goes through phases similar to those described for alkyl compounds, but owing to the greater reactivity of the acyl halides, special precautions have to be taken. Unlike the alkyl chlorides, the acyl chlorides give good yields ; there is no need to use the bromides or the iodides. Preparation 68. — Benzoyl Aceto-Acetic Ester. COC 6 H 5 I CH 3 COCH.COOC 2 H 5 . C 13 H 14 0 4 . 234. To 600 c.cs. of absolute alcohol in a flask attached to a reflux are gradually added 35 gms. (2 atoms) of sodium cut in small pieces. When all the sodium has dissolved, the solution is cooled. To 300 c.cs. of this solution are added 100 gms. (1 mol.) of aceto-acetic ester, and with continual stirring, 45 c.cs. of benzoyl chloride are dropped in from a burette during 15 minutes, the temperature being kept below 10°. After 30 minutes, 150 c.cs. of the original solution and 22 c.cs. benzoyl chloride are added as before. This process is repeated until all the original solution is used up, and 90 c.cs. benzoyl chloride in all. After 12 hours, the sodium salt is filtered off and washed with ether. By acidifying with dilute acetic acid in the presence of ice-water, the ester is liberated, extracted with ether, dried over anhydrous sodium sulphate, and the ether removed. The CARBON TO CARBON 137 residue is then distilled under reduced pressure, the fraction 173°— 177° at 12 mms. being retained. CH 3 CO.CHNaCOOC 2 H 5 + C 6 H 5 C0C1 -> CH 3 COCH(COC 6 H 5 )COOC 2 H 5 . Viscous oil ; insoluble in water ; B.P. 12 , 175°, with slight decomposi- tion ; tautomeric. (B., 18, 2131 ; 44, 1507.) Reaction XLIV. (c) Condensation of Alkyl and Acyl Halides with the Sodio-derivatives of Cyanacetic Ester. (B., 20, R., 477 ; 21, R., 353 ; 27, R., 262 ; C, (1900), II, 38 ; (1905), I, 150 ; J. pr, [2] 51, 186.)— Cyanacetic ester, CH 2 (CN)COOC 2 H 5 has similar properties to malonic and aceto-acetic esters, inasmuch as the methylene hydrogen atoms are successively replacable by sodium and this latter by alkyl and acyl radicals. C : N Na C j N C j N or | C 2 H 5 ONa EI > I > CH 2 CH CHE |/° Na COOC 2 H 5 \QCtfI. The activation of the methylene hydrogens is connected not only with the presence of oxy groups, but also is influenced by other groups con- taining double and multiple linkings. This is somewhat analogous to the activating effect of nitro groups in aromatic compounds. Reference may also be made to the hydroxymethylene compounds, Reaction XXIII. (a). The groups C : O and C \ N resemble one another in many of their reactions. It may be noted that unsaturated groups always tend to give an acid character to any compound in which they occur. The synthesis, like its analogues, may be extended to halogen esters. C 2 H 5 ONa CH 2 COOC 2 H 5 . CH 2 ICOOC 2 H 5 + CN.CH 2 COOC 2 H 5 > C N.CH(COOC 2 H 5 ) Cyano -succinic Ester. Reaction XLV. Condensation of Aldehydes and Ketones with certain Esters under the influence of Acetic Anhydride, Hydrochloric Acid, Sodium Ethoxide or certain bases. (A., 218, 172 ; B., 29, 172 ; 30, 481 ; 31, 735, 2585.) — 1 mol. of an aldehyde can be made to condense with 1 mol. of an ester containing an a-methylene group, thus KiCHO + RCH 2 COOC 2 H 5 - E X CH : CRCOOC 2 H 5 . If hydrochloric acid or acetic anhydride be used, both aliphatic and aromatic aldehydes can be employed, but if sodium ethoxide or small quantities of diethylamine, piperidene, quinoline, etc., be taken, aromatic aldehydes also will react. In these reactions the methyl gives better results than the ethyl ester. 138 SYSTEMATIC ORGANIC CHEMISTRY Esters, such as those of malonic, aceto-acetic or cyanacetic acids, in which the methylene group is doubly activated, will condense even with ketones. By varying the proportion of aldehyde or ketone to ester, 2 mols. of the former can be made to condense with 1 of the latter, using the basic condensing agents only (4, below). The following will illustrate these points : — HClor (CHoCOUO (1) C 6 H 5 .CHO + CH 2 (COOC 2 H 5 ) 2 - > C 6 H 5 CH : C(COOC 2 H 5 ) 2 . Benzal-malonic Ester. (2) CH 3 .CHO + RNH 2 -> CH 3 CH : NR + H 2 0. CH 3 CH : NR + CH 2 (COOC 2 H 5 ) 2 -> CH 3 CH : C(COOC 2 H 5 ) 2 + NH 2 R. Ethylidene-malonic Ester. C 9 H 7 N (3) (CH 3 ) 2 : CO + CH 3 .CO.CH 2 .COOC 2 H 5 (4) (CH 3 ) 2 CO (CH 3 ) 2 C : C(COCH 3 )COOC 2 H 5 . Isopropylidine Aceto-acetic Ester. yCN /CH.COOC 2 H 5 (CH 3 ) 2 : C<^ CH.COOC 2 H 5 \CN. Peeparation 69. — Ethyl Cinnamate (Ethyl ester of 3-phenyl-2-propen acid). C 6 H 5 CH : CH.COOC 2 H 5 . C n H 12 0 2 . 176. To 50 gms. (excess) of pure ethyl acetate (see Preparation 196) are added 23 gms. (excess) of sodium in the form of wire. The flask is cooled in ice, and with slight shaking, 10 gms. (1 mol.) of benzaldehyde are gradually added. When all the sodium has gone into solution, the flask is set aside for 2 hours, when it is acidified with dilute acetic acid. The ester layer which separates is removed, shaken up with dilute sodium carbonate solution, and dried over calcium chloride. It is then distilled, the fraction 265°— 275° being retained. C 2 H 5 ONa C 6 H 5 CHO + CH 3 COOC 2 H 5 > C 6 H 5 CH : CH.COOC 2 H 5 . Colourless liquid ; insoluble in water ; B.P. 271°. (B., 23, 976.) This method of preparation can be applied generally to the esters of the phenyl- olefine acids. Although metallic sodium is used, yet as in the aceto-acetic ester synthesis (see Reaction XL VI.) a trace of alcohol must always be present to form sodium ethoxide. This is usually the case. If necessary, sodium ethoxide itself can be employed. The use of some other condensing agents will be clear from the following preparation. Preparation 70. — Benzalmalonic Ester (2-Benzylidene-propan di-acid.) C 6 H 5 CH : C(COOC 2 H 5 ) 2 . C 14 H 16 0 4 . 248. 8 gms. (1 mol.) of pure drv malonic ester, and 5 gms. (1 mol.) of dry, CARBON TO CAKBON 139 freshly distilled benzaldehyde are mixed. They can be condensed with hydrochloric acid gas or ammonia, according to the following methods : — (i.) Hydrogen Chloride. — The mixture is cooled to — 10° (see p. 10) and saturated with dry hydrogen chloride, the temperature being kept below — 5°. The whole is then allowed to stand at room temperature for 8 days, and the product worked up as described below. (ii.) Ammonia. — The mixture is allowed to stand with 2 gms. of ammonia in alcoholic solution, until all the benzaldehyde has disappeared. The product in each case is washed with much water, with dilute hydro- chloric acid (especially in (ii.) ) and again with water. It is then dried over anhydrous sodium sulphate and distilled under reduced pressure, the fraction 185° — 195° at 12 mms. being retained. Hydrochloric acid acts directly as a condensing agent. With ammonia the reaction may be formulated — C 6 H 5 CHO + NH 3 — > C 6 H 5 CH : NH + H 2 0. C 6 H 5 OH : NH + CH 2 (COOC 2 H 5 ) 2 -> C 6 H 5 CH : C(COOC 2 H 5 ) 2 + NH 3 . Colourless oil ; insoluble in water ; B.P. 13 198°. (A., 268, 156 ; D.R.P. 97734.) Compare this preparation with that of benzal malonic acid (Preparation 51). Preparation 71— Methylene-dimalonic Ester. CH 2 [CH(COOC 2 H 5 ) 2 ] 2 . C 15 H 24 0 8 . 332. 32 gms. of ethyl malonate and 8 gms. of formalin (40%) are placed in a flask, cooled by immersion in ice, and 0-5 gm. of diethylamine added. The flask is then cooled and left to stand for 12 hours at room temperature, after which it is heated on a boiling water bath for 5 — 6 hours. The aqueous layer is separated, and the residue distilled under reduced pres- sure (about 12 mms.). The distillation is conducted slowly, so that all the water passes over below 50°. Methylene-dimalonic ester passes over at 190°— 200°. CH 2 0 + 2HN(C a H 5 ) a -> CH a (NC a H 6 ) 2 + H 2 0. /CH(COOC 2 H 5 ) 2 CH 2 (NC 2 H 5 ) 2 + 2CH 2 (COOC 2 H 5 ) 2 ^ CH 2 < + 2HN(C 2 H 5 ) 2 . \CH(COOC 2 H 5 ) 2 Yield. — 80% theoretical (27 gms.). Colourless oil ; insoluble in water ; B.P. 18 , 205° ; B.P. 12 , 198°. (B., 22, 3294 ; 31, 738, 2585.) Preparation 72. — Ethylidenebisaceto-acetic Ester (4-Methyl-2-6- dioxy-3-5-carbethoxyl-heptan) . CH 3 .CO.CH.CH(CH 3 )CH.(COOC 2 H 5 )CO.CH 3 j COOC 2 H 5 . C 14 H 22 0 6 . 286. 8-5 gms. (1 mol.) of pure freshly distilled acetaldehyde are slowly added to 50 gms. (2 mols.) of pure vacuum distilled cooled aceto-acetic ester con- tained in a thick- walled flask closed by a cork and having a thermometer reaching almost to the bottom. The flask is cooled to — 10° to — 15° in 140 SYSTEMATIC ORGANIC CHEMISTEY a freezing mixture of ice and salt. A few drops of diethylamine are then added by means of a burette. Owing to neutralisation of the first portions of the amine by traces of acids nearly always present as impurities, an increase in the temperature seldom takes place at first. After the addition of about 5 drops an elevation of a few degrees will be noticed, and the liquid becomes turbid. From this point a further 5 drops are added slowly, and the temperature is allowed to rise gradually to 0°. 20 more drops are then slowly added with frequent shaking ; the whole operation should take about 1 hour. In all, 30 drops (=1-5 gms.) of the base are required. The whole is allowed to stand in the freezing mixture for 15 minutes, then removed and allowed to come to room temperature. Should the temperature go up to 20° on account of secondary reactions, the flask is cooled for a short time in ice-water. The reaction product is a viscous bright yellow liquid in which numerous drops of water are suspended. It is allowed to remain until it solidifies to a crystalline mass ; this generally requires from 2 — 3 days. If the pure product is required, the mass is pressed on a porous plate and recrystallised from dilute alcohol. The crude product will serve for the preparation of dimethylcyclohexanone (see p. 77). The solidifica- tion of the crude product may be hastened by seeding it, after one day's standing, with crystals obtained in a previous preparation. This is best done on the upper portion of the flask, which is only moistened by the liquid. CH3.CHO + 2HN(C 2 H 5 ) 2 = CH 3 CH(N(C 2 H 5 ) 2 ) 2 + H 2 0. CH 3 CH3.CO.CHH + CH + HCH.CO.CH3 COOC 2 H 5 /\ I N(C 2 H 5 ) 2 N(C 2 H 5 ) 2 COOC 2 H 5 = CH 3 CH 3 CO CO I CH 3 I + 2NH(C 2 H 5 ) 2 . CH CH CH I I COOC 2 H 5 COOC 2 H 5 Yield.—70% theoretical (40 gms.). Colourless needles ; M.P. 79°— 80°. (A., 323, 83 ; 332, 1 ; B., 36, 2118.) Acetaldehyde and aceto-acetic ester in presence of acetic anhydride, hydrochloric acid, ammonia, diethylamine, piperidine, etc., can also be made to yield ethylidene monoaceto-acetic ester. (A., 218, 172 ; B., 29, 172 ; 31, 735.) With regard to the intermediate compounds of the types RCH : NR and RCH : (NRR X ) 2 postulated in some of the above reactions, it is to be noted that compounds of the type RCH(OH)NHR and RCH(OH)NRR 1 can also be regarded as intermediates. Reaction XLVI. Condensation of an Ester with itself or with another Ester by means of Sodium Ethoxide, or Sodamide (Glaisen). (J. (1868), CARBON TO CARBON 141 323 ; Phil. Mag., 156, 37 ; A., 186, 161, 214 ; 201, 243 ; 213, 137.)- When sodium ethoxide or sodamide acts on acetic or propionic esters, 2 mols. of the esters condense to yield aceto-acetic or propiopropionic esters respectively. In the reaction 1 mol. of alcohol is split off from 2 mols. of ester, the ethoxy group coming from one molecule, and the hydrogen atom from the a-carbon of a second. CH 3 CH 3 CH 2 .COO.C 2 H 5 + | C 2 H 5 ONa HCH.COOC 2 H 3 > CH 3 CH 2 CO.CH(CH 3 )COOC 2 H 5 + C 2 H 5 OH. The reaction can also be extended to condensations between two different esters, it being only necessary that one of the esters should have two a-hydrogen atoms, one to react and one to enable a sodio-derivative to be formed. /3-ketonic compounds always result — this condensation in fact belonging to the same class as those described in Reaction XXIII. (6). The higher esters do not condense in the same manner. When sodium acts on normal butyric ester, ^so-butyric ester, iso- valeric ester, etc., the resulting compounds are not analogous, being hydroxy-alkyl derivatives of higher fatty acids (A., 249, 54). Some di-basic esters in undergoing the condensation yield ring compounds ; this is an especially important feature of the reactions (see p. 142). The mechanism of the process must now be considered. The reaction between metallic sodium and acetic ester only occurs in the presence of a trace of alcohol (B., 3, 305), so sodium ethoxide must be regarded as the condensing agent (cf. Reaction XLV., p. 137). This view is supported by the fact that separately prepared sodium ethoxide gives almost as good a yield as metallic sodium. The first step in the synthesis may be taken to be — x OC 2 H 5 CH 2 CH 3 : CO.OC 2 H 5 + C 2 H 5 ONa -> CH 3 C-ONa or c. 0 C 2 H 5 \OC 2 H 5 ONa I. II. II. results from I. by the loss of alcohol, but I. is more probably the intermediate compound, because methyl benzoate and sodium benzoxide give the same compound — actually isolated — as benzyl benzoate and sodium methoxide. /ONa C 6 H 5 COOCH 3 + C 6 H 5 CH 2 ONa->C 6 H 5 C-OCH 3 y \OCH 2 C 6 H 5 . C 6 H 5 COOCH 2 C 6 H 5 -fCH 3 ONaX I. then reacts with the still unchanged ester or with a molecule of the other ester — CHo v -OC2H5 H\ \c/ + >C(R)COOC 2 H 5 > NaO/ \OC 2 H 5 H/ CH 3 C : C(E)COOC 2 H 5 + 2C 2 H 5 OH. I ONa 142 SYSTEMATIC ORGANIC CHEMISTRY or else a molecule of ester and a molecule of II. unite and then split off alcohol, with rearrangement. OC 2 H 5 CH 2 CH 2 (R)C/' , cqC 2 H 2 XX 5 ONa CH 2 CH 2 (R)C< 0 COC 2 H 5 > x ONa /OC 2 H 5 — C 2 H 6 OH RCH 2 C< CH 2 — COC 2 H 5 > \ONa |i 0 RCHC = CH— COC 2 H 5 . ! II ONa 0 (A., 297, 92 ; B., 36, 3678 ; 38, 714, 1934.) Both assumptions coincide equally well with the fact that fatty acid esters do not condense analogously to the above, with secondary and tertiary alkyl groups. Sodamide can also be employed as condensing agent. The intermediate compound is then — CH 3 v /OC 2 H 5 CH 2 ^ I. >C< or >C— OC 2 H 5 . II. NaCK \NH 2 NaCK It is in favour of II. that it is an intermediate compound independent of the condensing agent. For the influence of solvents on the reaction, see C, (1907), IL, 30. The following examples are of interest : — C 2 H 5 ONa (i.) H.COOC 2 H 5 + CH 3 .COOC 2 H 5 > H.CO.CH 2 COOC 2 H 5 + C 2 H 5 OH. X Formylacetic Ester. (Hydroxym ethylene- acetic Ester). The above reaction goes best in ethereal or benzene solution. COOC 2 H 5 C 2 H 5 O.CO.CO.CH 2 .COOC 2 H 5 . (ii.) | + CH 3 .COOC 2 H 5 -> Oxalacetic Ester COOC 2 H 5 + C 2 H 5 OH. COOC 2 H 5 /CH a COOC a H 5 Ciii.) I + C : (CH 3 ) 2 -> COOC 2 H 5 \H 2 COOC 2 H 5 /3-/3-Di-methylglutaric-di-ethyl-ester. CO CHCOOC 2 H 5 ^>C(CH 3 ) 2 CO CHCOOC 2 H 5 . Di ketocamphopyric Ester. This is an important step in the synthesis of camphor (see Reactions XLIV. (6) (3) ). CARBON TO CARBON 143 Preparation 73. — Aceto-acetic Ester (Ethyl ester of 3-oxy-butan acid). CH 3 COCH 2 COOC 2 H 5 or CH 3 C(OH) : CH.COOC 2 H 5 . C 6 H 10 O 3 . 130. 250 gms. of commercial ethyl acetate are shaken with sodium carbonate solution, separated and allowed to stand for 24 hours over freshly fused calcium chloride, filtered into a distilling flask, and redistilled, care being taken that all parts of the apparatus are perfectly dry. This treatment frees the ethyl acetate from all traces of acetic acid and water, but leaves enough alcohol to allow sodium ethoxide to be formed to bring about the reaction. With too much alcohol the reaction goes too vigorously and the yield is poor, with too little the reaction goes very slowly or not at all. 20 gms. (1 atom) of pure dry sodium in the form of wire are placed in a clean dry J-litre round-bottomed flask. The latter is attached to a long reflux condenser, and 200 gms. (excess) of the purified ethyl acetate are slowly introduced through the top of the condenser. When the first action is over, the whole is heated on a water bath to gentle ebullition for 3 hours, when 150 gms. of 50% acetic acid are added gradually till the mixture is just acid (test with litmus). The whole is well shaken to re- dissolve any deposited solid, and the mixed ethyl acetate and ethyl aceto- acetate separated by adding an equal volume of saturated brine. Should a precipitate separate a little water is added to dissolve it. The upper layer of the mixed esters is fractionally distilled under reduced pressure, the fraction 85° — 95° at 40 mms. separately collected and redistilled under reduced pressure. The residue in the flask contains dehydracetic acid (see Preparation 63). To obtain the best results the experiment must be completed in one day. /OC 2 H 5 C 2 H 5 .ONa + CH 3 .COOC 2 H 5 = CH 3 .C— OC 2 H 5 \O.Na. / OC 2 H 5 CH 3 .C— OC 2 H 5 + CH 3 .COOC 2 H 5 = \ONa CH 3 .C : CHCOOC 2 H 5 + 2C 2 H 5 .OH. O Na CH 3 .C : CHCOOC 2 H 5 + CH 3 .COOH = ONa CH 3 .C : CHCOOC 2 H 5 + CH 3 .COONa OH CH 3 .C : CHCOOC 2 H 5 ->* CH 3 .CO.CH 2 .COOC 2 H 5 . OH Yield. — 40% theoretical (44 gms.). Colourless pleasant-smelling liquid ; slightly soluble in water ; B.P. 760 181° ; B.P. 12 72° ; D. 2 4 ° 1-0256. For the estimation of the amount of keto and enol forms present in the equilibrium mixture, see p. 493. 144 SYSTEMATIC OKGANIC CHEMISTRY For the separation of the keto and enol forms by distillation, see B., 53, 1410. (J., (1863), 323 ; Phil. Trans., 156, 37 ; A., 186, 161, 214.) Reaction XLVII. Condensation of an Ester with itself by the action of Iodine on its Sodio Derivative. (B., 23 ; R., 141 ; A., 201, 144 ; 266, 88.)— When iodine, usually in ethereal solution, acts on the sodio derivatives of esters, such as malonic or aceto-acetic esters, the metal is eliminated, and higher dibasic esters are obtained. As will be seen, the reaction is especially useful for preparing cyclo-paraffins by acting with iodine (or bromine) upon disodio-methylene- and disodio-ethylene-, etc., di-malonic esters. (a) COOC 2 H 5 HC + I 2 + HC -> I! II C.ONa C.ONa I I OC 2 H 5 OC 2 H 5 H H C C : (COOC 2 H 5 ) 2 (COOC 2 H 5 ) 2 Ethane -tetra carboxylie Ester (Di-malonic Ester.) /CNafCOOCgHs), /C(COOC 2 H 5 ) 2 {h) CH 2 +I 2 -> CH 2 J m ^CNafCOOCaHgk , \j(COOC 2 H 5 ) 2 . Disodio-methylene di-malonic Ester Cyclo -propane tetra- (Propane-tetracarboxylic Ester.) carboxylie Ester. / /CH 2 CNa(COOC 2 H 5 ) 2 W CH 2 +I 2 > \CH 2 CNa(COOC 2 H 5 ) 2 Disodio propylene di-malonic Ester (Pentane tetracarboxylic Ester.) /CH 2 .C(COOC 2 H 5 ) 2 CH 2 i \CH 2 .C(COOC 2 H 5 ) 2 . Cyclo -pentane tetracarboxylic Ester. Cf. Reaction XLIV. (a) (3). W 2CH 3 .CO.CHNaCOOC 2 H 5 + I 2 -> CH 3 CO CHCOOC 2 H 5 CH 3 .CO.CH.COOC 2 H 5 . Di-acetosuccinic Ester. The action of methylene and ethylene iodides, etc., on the sodio deriva- tives of the esters dealt with above might have been discussed under Reaction XLIV. (a), but is best dealt with here. The di-iodides react analogously to the iodine molecule ; extra carbon is of course introduced into the reacting molecules. The following will illustrate :— CARBON TO CARBON 145 /HC(COOC 2 H 5 ) 2 (i.) 2CHNa(COOC 2 H 5 ) 2 + CH 2 I 2 -> CH 2 \HC(COOC 2 H 5 ) 2 C(COOC 2 H 5 ) 2 (ii.) NaC(COOC„H 5 ) 2 / IH a C CH, NaC(COOC a H 5 )j CH 2 C(COOC 2 H 5 ) 2 (iii.) 2CH 3 COCHNaCOOC 2 H 5 + CH J 2 -> CH 3 COCHCOOC 2 H 5 CH 8 COCCOOC 2 H 5 i /\ H 2 C C 2 H 5 ONa + CH 2 I 2 H 2 C CH 2 I > CH 3 .COCHCOOC 2 H 5 CH 3 CO C COOC 2 H 5 It will be seen that whereas iodine leads to 1 : 2 tetra- and di-basic esters, methylene, ethylene, etc., iodides yield respectively 1:3, 1:4, etc., esters. The yields in these ring syntheses, as in most others, vary in agreement with Baeyer's " Strain Theory." Preparation 74. — Diethyl Di-acetosuccinate ( 1.2-Dicarbethoxyl-l : 2- diethanoyl ethan). CH 3 .COCH— CH.CO.CH 3 . C 12 H 18 0 6 . 258. I - I C 2 H 5 OOC COOC 2 H 5 . In a stoppered bottle of 500 c.cs. capacity provided with a reflux con- denser, 25 gms. (2 mols.) of aceto-acetic ester are dissolved in 150 gms. of pure ether which has been dried over sodium, and to this solution 5 gms. (2 mols.) of fine sodium wire are added. After 2 hours, the bottle is shaken at intervals, being stoppered while so doing, till no further evolution of hydrogen takes place, and all the metal has been con- verted into sodio-aceto-acetic ester. 20 gms. (excess) of finely powdered iodine are dissolved in pure anhydrous ether, and the solution added in small portions, and with constant shaking to the solution of the sodio- aceto-acetic ester. Sodium iodide is precipitated as soon as the colour of the iodine no longer vanishes at once, the solution is filtered, the ether evaporated off, and the di-acetsuccinic ester allowed to solidify. It is then pressed on a porous tile, and recrystallised from warm 50% acetic acid. 2Na I 2 2CH 3 CO.CH 2 COOC 2 H 5 > 2CH 3 C(ONa) : CHCOOC 2 H 5 > CH 3 .CO.CH — CH.CO.CH 3 C 2 H 5 OOC COOC 2 H 5 . Yield. — 40% theoretical (10 gms.). Colourless crystals ; plates when crystallised slowly ; needles when crystallised rapidly ; soluble in ether ; insoluble in water ; M.P. 88°. (B., 7, 892 ; A., 266, 88.) (Cf. Reaction XXXVII.; which is, so to speak, converse to this reaction.) s.o.c. l CHAPTER VIII carbon to carbon Nitrogen Compounds Nitrogen enters into the constitution of many carbon compounds, and such nitrogen-containing compounds are usually very reactive ; in addition to reacting with other compounds a great number readily undergo intramolecular transformations. Nitrogen also plays an important part in ring formation ; nitrogen-containing rings are very stable, and the condensations which give rise to them many and various. On this account a great many important reactions and preparations come to be dealt with in this section ; of these, however, only a small selection can be given. Reaction XLVIII. {a) Action of Alkali Cyanides on Alkyl and Acyl Halides. (Bl., [2], 50, 214.) — This reaction is capable of very wide application, all the simple alkyl halogen compounds, the acyl halides, and the halogen fatty acids come within its scope. The nitriles so formed yield acids by hydrolysis, so it is frequently the first step in the synthesis of an acid — the preparation and hydrolysis of the nitrile are often com- bined. The preparations of malonic, succinic, tricarballylic and other acids (Preparations 58, 59, 116, 60) illustrate this. The extension of this reaction to acyl halides is important, and should be referred to, as should the interaction of silver cyanide, and alkyl iodides, to give isonitriles. Mercuric and silver cyanides, it may be noted, give with acyl chlorides and bromides better yields of normal acyl nitriles than do the alkali cyanides. In reactions where nitriles are prepared from halogen compounds by double decomposition with alkali cyanide in alcoholic or aqueous alcoholic solution, the latter is usually added in solution or as a powder (cf. Preparations 75, 76, 77), otherwise the alkali halide which separates forms a coating round the cyanide and hinders further action. If the reaction is performed in aqueous solution, as in the preparation of malonic acid (p. 119), this precaution is not so necessary ; the alkali halide, when formed, remains in solution. Preparation 75. — Ethylene Di-Cyanide (Succino-nitril). CH 2 .CN | C 4 H 4 N 2 . 80. CH 2 .CN. The solution of the nitrile prepared as in Preparation 59 from 100 gms. (1 mol.) of ethylene dibromide and 75 gms. (excess) of potassium cyanide, after filtration from the separated potassium bromide, is evaporated on a 146 CARBON TO CARBON 147 water bath under reduced pressure. The residue is extracted with absolute alcohol, the extract evaporated as before, and the residue fractionated under reduced pressure, the fraction 144° — 150° at 10 mms. being retained. CH 2 Br CH 2 CN | + 2KCN = | + 2KBr. CH 2 Br CH 2 CN Yield. — 80% theoretical (34 gms.). Amorphous transparent mass ; readily soluble in water, chloroform and alcohol ; sparingly soluble in ether ; M.P. 54-5° ; B.P. 10 147° ; B.P. 20 159°. (Bl., [2], 50, 214 ; C, (1901), II., 807.) Propenyl tricyanide, the nitrile of tri-carballylic acid, is obtained in a similar manner (see Preparation 60). Prepaeation 76. — Benzyl Cyanide (Phenyl-ethan Acid Nitril). C 6 H 5 .CH 2 .CN. C 8 H 7 N. 117. 60 gms. (slightly more than 1 mol.) of commercial potassium cyanide are dissolved in 55 gms. of water in a f -litre round-bottomed flask fitted with a reflux condenser and placed in a fume cupboard. 100 gms. (1 mol.) of benzyl chloride dissolved in 100 gms. of alcohol are poured slowly into the hot solution of potassium cyanide through the top of the condenser, and the whole gently boiled for 4 hours on a sand bath. The flask is then cooled, and the upper dark brown liquid, consisting of an alcoholic solution of benzyl cyanide, is decanted from the crystalline deposit of potassium chloride and distilled over wire gauze in a fume cupboard, the fraction 210°— 235° being retained. It is crude benzyl cyanide, and can be used for Preparation 173. To prepare the pure substance, this fraction is redistilled and collected at 230°— 235°. C 6 H 5 CH 2 C1 + KCN ■-= C 6 H 5 CH 2 CN + KC1. Yield. — Almost theoretical (55 gms.). Colourless, pungent smelling liquid ; B.P. 232° ; D. l7 4 - 5 1-0171. (A., 96, 247 ; B., 14, 1645 ; 19, 951.) Reaction XLVIII. (b) Action of Alkali Cyanides on Alkyl Halogen Sulphates. (A., 10, 249.) — The alkyl nitriles may also be prepared by dry-distilling alkali cyanides with alkali-alkyl-sulphates. M X CN + S0 2 (OM n )OR = RCN + S0 2 (OM 11 )(OM 1 ). Pkepaeation 77. — Ethyl Cyanide (Propionitril). C 2 H 5 CN. C 3 H 5 N. 55. 50 gms. (excess) of finely powdered (caution!), dry, commercial potas- sium cyanide and 50 gms. (1 mol.) of finely powdered potassium ethyl sulphate dried at 100° are intimately mixed. An iron tube, closed at one end, is one-third filled with the mixture. The tube is tapped while in a horizontal position to form a channel along the upper surface of the mixture, is placed in a combustion furnace so that the open end projects 3 cms. from the furnace, and connected with a condenser and receiver, all L 2 148 SYSTEMATIC ORGANIC CHEMISTRY being set up in a fume cupboard. The mixture is then gradually heated, from the front backwards, to a red heat. The distillate is redistilled to 110°, and the second distillate (propionitril, isopropionitril, alcohol and water) shaken with a small quantity of cone, hydrochloric acid to remove isopropionitril, washed with a small quantity of water, dehydrated over calcium chloride or anhydrous potassium carbonate and fractionated between 97° and 101°. The propionitril dissolved in the washings is separated by adding calcium chloride, and worked up as above. C 2 H 5 .O.S0 2 .OK + KCN = KO.S0 2 .OK + C 2 H 5 CN. 7^.-60% theoretical (10 gms.). Colourless liquid, peculiar ethereal smell ; slightly soluble in water ; B.P. 98° ; D. \ 2 0-789. (A., 10, 249 ; 148,252; 159,79.) A somewhat similar method of cyanide preparation is applicable in the aromatic series ; aromatic sulphonic acid potassium salts, on fusion with potassium cyanide or potassium ferrocyanide, yield aromatic nitriles. The reaction can be extended to derivatives of pyridine. S0 3 K I I CN + KCN =|| + K 2 SO. N N (Nicotino -nitrile.) Reaction XLVTII. (c) Action of di-methyl Sulphate on Potassium Cyanide. (B., 40, 3215.) — This method, which gives excellent yields, is only applicable to the preparation of aceto-nitrile ; dimethyl sulphate is unique in this as in other reactions. Pkepaeation 78. — Methyl Cyanide (Acetonitril). CH 3 CN. C 2 H 3 N. 41. 68 gms. (1 mol.) of finely powdered potassium cyanide are dissolved in 60 c.cs. of water, in a 500-c.c. round-bottomed flask, and after cooling, 126 gms. (1 mol.) of dimethyl sulphate (caution ! see p. 254) are added in three equal portions, the whole being shaken vigorously and cooled under water after each addition. During the shaking, the flask is closed by a one-holed cork carrying a glass tube bent three or four times, so as to form a spiral, having its axis horizontal. This prevents spurting out of any liquid. The milky liquid is distilled on a water bath in a fume cupboard at 82°, a litre flask being used owing to frothing. The residue in the flask is treated on cooling with another 65 gms. (1 mol.) of potassium cyanide, added slowly, in 50% solution as before, and the whole is very cautiously distilled from a water bath. A violent reaction occurs, and when this has slackened, the distillation is continued until the residue in the flask becomes solid and nothing more comes over. The distillate is diluted, and shaken with half its volume of water ; solid potassium car- bonate is added until no more dissolves, the layer of nitrile is separated from the aqueous solution and redistilled over phosphorus pentoxide, the fraction 79° — 83° being retained. CAKBON TO CARBON 149 KCN + (CH 3 ) 2 S0 4 = (CH 3 )KS0 4 + CH 3 CN. CH 3 KS0 4 + KCN = K 2 S0 4 + CH 3 CN. Yield. — 95% theoretical (78 gms.). Colourless liquid ; ethereal odour ; slightly soluble in water ; B.P. 82°. (B., 40, 3215.) Reaction XLIX. (a) Action of Cuprous Potassium Cyanide on Aromatic Diazonium Compounds. (Sandmeyer). (B,, 17, 1633, 2650; 18, 1492, 1496.) — If a diazonium salt is added to a hot solution of cuprous-potassium cyanide, and the whole boiled on a water bath, nitrogen is evolved, and the corresponding nitrile formed. 2R.N 2 C1 + KCN(CuCN) 2 -> 2RCN + 2N 2 + KCN + Cu 2 Cl 2 . As usual in Sandmeyer reactions, the product, if volatile, is separated by distillation in steam ; if non- volatile, extraction or nitration is used. The manner in which the cuprous salt reacts is not exactly known ; it certainly unites at first with the diazonium compound to form a double salt (cf. Reaction CLXVL). The method is widely applicable, and as the yields are usually good, it is a standard method for the preparation of aromatic nitriles. Preparation 79. — Benzo-nitrile (Cyano-benzene). C 6 H 5 .CN. C 7 H 5 N. 103. The details of this preparation are practically the same as those given for j9-tolu-nitrile (Preparation 80) . A cuprous-potassium cyanide solution, prepared as therein described, is warmed to about 70°, and added in small portions to a solution of diazonium-benzene chloride prepared from 18-6 gms. (1 mol.) of aniline as described in Preparation 378. When the addition is complete, the liquid is warmed on a water bath for 15 minutes and distilled in steam ; the distillate is extracted with ether. The ethereal solution is washed repeatedly with dilute caustic soda and with dilute sulphuric acid, dried over anhydrous potassium carbonate, filtered, and the oil which remains on driving off the ether, fractionated. Owing to the evolution of cyanogen and hydrocyanic acid, this preparation must be carried out in a good fume cupboard. HN0 2 Cu 2 CN 2 .KCN C 6 H 5 NH 2 > C 6 H 5 .N 2 .C1 > C 6 H 5 CN. HC1 Yield. — 65% theoretical (13 gms.). Colourless oil ; odour resembling that of benzaldehyde or nitrobenzene ; insoluble in water ; soluble in ether ; B.P. 191°. (B., 17, 2653.) Preparation 80. -^-Tolu-nitrile (l-Methyl-4-cyano-benzene). CH 3 .C 6 H 4 .CN.[1.4.]. C 8 H 7 N. 117. 50 gms. (1 mol.) of copper sulphate crystals are dissolved in 200 c.cs. of water, and 56 gms. (excess) of 96% potassium cyanide added to the warm solution. As cyanogen is evolved, the operation must be carried out in a good fume cupboard, and the fumes must on no account be inhaled. 20 gms. (1 mol.) of ^-toluidine are then diazotised as in Preparation 378, and the diazo solution gradually added in a J hour, from a dropping funnel to the cuprous-potassium cyanide solution at 90°, the mixture being kept 150 SYSTEMATIC ORGANIC CHEMISTRY well shaken. The product is heated on a water bath for a J hour, and distilled in steam in a good fume cupboard, since hydrogen cyanide and a little isocyanide are formed ; the solid distillate is filtered off, dried on a porous plate, and redistilled. CuS0 4 + 2KCN = Cu(CN) 2 + K 2 S0 4 . 2Cu(CN) 2 = Cu 2 (CN) 2 + (CN) 2 . Cu 2 (CN) 2 + KCN 2CuQN.KCN. 2CH 3 .C 6 H 4 N 2 C1 + 2CuCN.KCN = 2CH 3 .C 6 H 4 .CN + 2N 2 + Cu 2 Cl 2 + KCN. Yield— 65% theoretical (14 gms.). Colourless crystals ; insoluble in water; soluble in ether ; M.P. 24° ; B.P. 218°. (B., 17, 2653.) o-Tolu-nitrile is prepared in an exactly similar fashion from o-toluidine. It boils at 205° ; D. ° 4 1-006. Reaction XLIX. (b) Action of finely divided Copper and Alkali Cyanides on Aromatic Diazonium Compounds (Gattermann). (B., 23, 1218.)— This is the Gattermann modification of the preceding Sandmeyer reaction ; as usual, the cuprous salt is replaced by finely divided copper. This method gives better yields of some aromatic nitriles. Preparation 81. — Benzonitrile (Cyanobenzene). C 6 H 5 CN. C 7 H 5 N. 103. (This reaction must be carried out in a good fume cupboard.) 31 gms. (1 mol.) of aniline are dissolved in 40 gms. (excess) of 50% sul- phuric acid, the solution cooled to 0° by addition of ice, and the base diazotised by the addition of 23 gms. (1 mol.) of sodium nitrite as described in Preparation 378. 80 gms. (excess) of 96% potassium cyanide in 50% solution are poured in, and then, with constant stirring, 40 gms. of copper paste (see p. 504) are added in small quantities, and the whole allowed to stand until the evolution of nitrogen ceases and the copper sinks to the bottom of the vessel. The reaction is then over. The product is steam- distilled, and the nitrile extracted and purified as described under Pre- paration 79. C 6 H 5 N 2 S0 4 H + KCN(Cu) = C 6 H 5 CN + KHS0 4 + N 2 (Cu). Yield. — 60% theoretical (20 gms.). Colourless oil ; insoluble in water ; soluble in ether ; odour resembling that of benzaldehyde or nitrobenzene ; B.P. 191°. (B., 23, 1218.) The preparation of o- or ^-tolu-nitrile is exactly similar. Reaction L. (a) Addition of Hydrogen Cyanide to Aldehydes or Ketones. (B., 14, 235 ; 39, 1224, 1857 ; 28, 10 ; C. Z., (1896), 90.)— Hydrocyanic acid adds on to aldehydes and ketones to yield a-hydroxy nitriles (Cyan- hydrins). KI^CO + HCN -> RRiCfOHjCN. Nascent hydrogen cyanide formed by the action of hydrochloric acid on potassium cyanide is usually employed except with sugars, where hydro- cyanic acid and a little ammonia are used. The manner in which am- monia promotes the action as also the better results obtained by the use of the bisulphite compound of the aldehydes and potassium cyanide have been dealt with under Reaction XXXVfll. (c). CARBON TO CARBON 151 Preparation 62 illustrates the importance of this reaction in the sugar group. For the hydrolysis of nitriles, see p. 232. Preparation 82.— Acetone Cyanhydrin (2-Hydroxy-2-cyano-propan). (CH 3 ) 2 C(OH)CN. C 4 H 7 ON. 85. 10 gms. (1 mol.) of acetone are shaken with a saturated sodium bisul- phite solution containing 18 gms. (1 mol.) of NaHS0 3 , and, after cooling, 30 gms. (excess) of a cold 50% solution of 96% potassium cyanide are slowly added. The crystalline bisulphite compound soon dissolves and a fluorescent oil is formed. This is extracted several times with ether, and the ethereal extracts are shaken with saturated bisulphite solution (to remove acetone) and then washed with saturated brine. The ether is removed on a water bath, and the residual oil dried under reduced pressure over cone, sulphuric acid. It is then fractionated under reduced pressure; the fraction 80° — 85° at 23 mms. being retained. OH (CH 3 ) 2 CO + NaHS0 3 = (CH 3 ) 2 C X \OS0 2 Na ATT OTT (CH RR 1 C(OH)S0 3 Na — > RR 1 C(CN)(NHAr). In the following preparation, the amino-nitrile formed is hydrolysed directly to the corresponding amino-acid. These latter are of great importance in the chemistry of the proteins. Preparation 84. — Racemic Leucine (Racemic-4-methyl-2-amino- pentan acid). (CH 3 ) 2 .CH.CH 2 .CH(NH 2 ).COOH. C 6 H 13 0 2 N. 131. (This preparation must he carried out in a good fume cupboard.) 50 gms. (1 mol.) of pure redistilled iso- valeric-aldehyde are dissolved in 100 c.cs. of absolute ether (see p. 209) and the solution cooled in ice and saturated with dry ammonia (see p. 503). The water formed in the reaction is separated by means of a funnel, the ethereal solution is shaken with a little potassium carbonate, filtered, and evaporated under reduced pressure at a temperature not greater than 25°. The oily residue of iso- valeraldehyde-ammonia which usually crystallises rapidly, is at once CARBON TO CARBON 153 suspended in 100 c.cs. of water ; the liquid is cooled, and 36 c.cs. (1 mol. HON) of 50% hydrocyanic acid are gradually added (caution!). The mixture is allowed to stand, with frequent shaking for 12 hours, and then a mixture of 400 c.cs. (excess) of cone, hydrochloric acid (D. 1-19) and 200 c.cs. of water is added. This produces a lumpy precipitate, which is dissolved by prolonged boiling in a flask ; another 200 c.cs. of water are added, and the boiling continued for 2 hours more. The mixture is finally evaporated to dryness on a water bath to remove hydrochloric acid. The residue is warmed with about 60 c.cs. of water and made faintly alkaline with ammonia. When cold, the leucine which has separated is filtered off at the pump and washed with cold water until all the am- monium chloride has been removed. Further purification is effected by recrystallising from hot water with the addition of animal charcoal. The mother liquor is concentrated or treated with absolute alcohol to obtain any leucine remaining dissolved therein. (CH 3 ) 2 : CH . CH 2 .CHO + NH 3 = (CH 3 ) 2 .CH : CH 2 .CH(OH)NH 2 (CH 3 ) 9 : CH.CH 2 CH(OH)(NH 2 ) + HCN = (CH 3 ) 2 : CH.CH 2 .CH(CN)(NH 2 ) + H 2 0. H 2 0 (CH 3 ) 2 : CH.CH 2 .CH(CN)(NH 2 ) > (CH 0 ) 2 : CH.CH 2 CH.(NH 2 )COOH. Yield.— 33% theoretical (25 gms.). Shining leaflets ; slightly soluble in cold water ; very slightly in hot alcohol ; decomposes on heating. (A., 94, 243 ; 316, 145 ; B., 33, 2372.) Preparation 85 . — o-Carboxy-phenamino-acetonitrile (1- (cyanmethyl- amino)-2-carboxy-benzene). C 6 H 4 .(NH.CH 2 CN)(COOH)[l : 2]. C 9 H 8 0 2 N 2 . 176. Method I. — 7 gms. (1 mol.) of finely powdered potassium cyanide and 14 gms. (1 mol.) of finely powdered anthranilic acid are suspended in 50 c.cs. of ether or benzene in a flask fitted with a reflux condenser. The whole is well cooled in a freezing mixture, and 7-5 c.cs. (1 mol. CH 2 0) of 40% formalin are slowly added. A brisk reaction sets in, and two layers are formed, the lower of which solidifies on cooling to a mass of crystals of the potassium salt of the required acid. This is collected, dissolved in water, the free acid precipitated by acidification with acetic or hydro- chloric acids, washed with cold water, and recrystallised from alcohol, benzene, or chloroform. CH 2 0 C 6 H 4 (NH 2 )(COOH)[l : 2] ► CH 2 (OH).NHC 6 H 4 .COOH[l : 2] K.CN HC1 > CH 2 (CN).NH.C 6 H 4 COOK[l : 2] — > CH 2 (CN)NH.C 6 H 4 COOH[l : 2]. Yield. — Theoretical (18 gms.). Method II. — 20 c.cs. (1 mol. NaHS0 3 ) of 40% sodium bisulphite solution, and 7-5 c.cs. (1 mol. CH 2 0) of 40% formalin are mixed, and the mixture kept at 60° — 70° for about 20. minutes until the smell of formaldehyde has vanished. A solution of 14 gms. (1 mol.) of anthranilic acid in 10-3 c.cs. (exactly 1 mol. NaOH) of 30% caustic soda solution is then added, and the whole heated on a water bath until no more anthranilic acid is present 154 SYSTEMATIC ORGANIC CHEMISTRY (about 45 minutes). To test the reaction mixture, a sample is withdrawn at intervals, acidified with an excess of acetic acid, a few drops of sodium nitrite added to the well-cooled mixture, and the whole poured into an alkaline solution of R-salt. Anthranilic acid is absent when no red azo- colour is obtained. When the test is negative, or nearly so, a solution of 7 gms. (1 mol.) of potassium cyanide in 25 c.cs. of water is added, and the whole heated to 7 0° — 80° for 20 minutes. On cooling, an excess of glacial acetic acid is added, and the nitrile filtered off and purified as before. CH 2 (OH)(S0 3 Na) C 6 H 4 (NH 2 )(COONa)[l:2] > CH 2 (S0 3 Na)NH.C 6 H 4 COONa[l:2] KCN CH 3 COOH — »CH 2 (CN)NH.C 6 H 4 COONa[l:2] >CH 2 (CN)NH.C 6 H 4 COOH[l:2] Yield. — Theoretical (18 gms.). Crystallises from alcohol (3 parts) in leaflets ; from benzene or chloroform in long needles ; insoluble in water ; M.P. 183°. (D.R.P., 157909 ; B., 39, 2807.) Reaction L. (c) Action of Hydrogen Cyanide on Quinones. (B., 33, 675 ; D.R.P., 117005.) — Hydrogen cyanide reacts easily with quinones to give di-cyan-di-hydroxy derivatives of the parent hydrocarbons. A molecule of the quinone is simultaneously reduced. O OH I! O O 2HCN = -CN EL -CN OH OH 0 Yh Preparation 86. — benzene). OH /\CN CN OH Dicyanoquinol (1:4- Dihydroxy -2:3- dicyano- C 8 H 4 0 2 N. 160. (This preparation must be carried out in a fume cupboard.) 20 gms. (2 mols.) of ^-benzoquinone are dissolved in 60 c.cs. of alcohol, CARBON TO CARBON 155 and a cold mixture of 25 c.cs. (excess) of cone, sulphuric acid and 50 c.cs. of alcohol are added. The mixture is well cooled in a freezing mixture, and a 50% solution of potassium cyanide (caution !) slowly run in until a green fluorescence appears, and the liquid reacts alkaline. About 110 gms. of solution will be required. The whole is then acidified with sulphuric acid (caution !) and the alcohol removed by distillation under reduced pressure from a water bath. The residue is washed with water, and recrystallised from hot water with the addition of animal charcoal. 2C 6 H 4 0 2 + 2HCN = C 6 H(OH) 2 (CN) 2 [l : 4 : 2 : 3] + C 6 H 4 (OH) 2 [l : 4]. Crystallises in pale yellow leaflets, which contain 2 mols. of water ; slightly soluble in water ; its neutral solution fluoresces blue, its acid solution violet, and its alkaline solution green ; on heating it decolorises at 230°. (B., 33, 675 ; D.P.R., 117005.) Reaction LI. (a) Action of Acids on the non-para substituted Hydrazo Compounds. (A., 270, 330 ; 287, 97 ; B., 26, 681, 688, 699.)— When hydrazobenzene is treated with mineral acids, an intermolecular rearrange- ment to benzidine (^-jOg-diaminodiphenyl) takes place. C 6 H 5 .NH.NH.C 6 H 5 -> H 2 N.C 6 H 4 .C 6 H 4 NH 2 [4 : 4'.] This reaction can be extended to almost all non-para substituted hydrazo compounds ; if one or both joara-positions are substituted, either or^o-benzidine or diphenylamine derivatives known as ortho- or para- semidines are formed. NH NH< NH 2 / NH 2 •NH-A ( V- NH— o-Benzidine. o-Semidine. ^>-Semidine. NH. Benzidine and its homologues are very important intermediates in the dye industry. Preparation 87. — Benzidine (4 : 4'-Diamino-l : l'-di-phenyl). H 2 N./ ^> <^ )NH 2 . C 12 H 12 N 2 . 184. 5 gms. (1 mol.) of hydrazobenzene are shaken with 20 c.cs. of cone, hydro- chloric acid for 10 minutes. The diluted solution is made alkaline with caustic soda, extracted several times with ether, and the latter removed on a water bath. The benzidine which remains is washed with cold water, and recrystallised from boiling water. C 6 H 8 NH.NH.C 6 H 5 -> H 2 N.C 6 H 4 C 6 H 4 NH 2 [4 : 4']. Yield. — Almost theoretical (5 gms.). Lustrous plates when freshly 156 SYSTEMATIC ORGANIC CHEMISTRY crystallised ; darkens in air ; soluble in hot water ; M.P. 127° ; forms a difficultly soluble sulphate. (J. pr., [1], 36, 93.) Reaction LI. (b) Molecular rearrangement of Di-benzanilides.— When dibenzanilide is heated to 230° for 2 days, rearrangement takes place, and 2 and 4-(benzoylamino)-benzophenones are formed. NH(COC 6 H 5 ) NH(COC 6 H 5 ) /\ /^COC 6 H 5 C 6 H 5 N(COC 6 H 5 ) 2 > and COC 6 H 5 If either the o- or ^-position is occupied, only one isomer is obtained ; transformation to the meto-position does not occur. This is a standard method of preparation of acyl-amino-ketones, or by a further hydrolysis, of aminoketones. The tendency, illustrated in this reaction, of groups to wander from the amino group to the nucleus, is also shown in previous reactions and in the preparation of amino-azobenzene from diazoamino- benzene (Preparation 456) of sulphanilic acid from aniline sulphate (Pre- paration 290) of o- and ^-chloracetanilides from acetchloranilide (Pre- paration 327) of o- and j9-toluidine from methylaniline hydrochloride, and of 1 : 2 : 4-aminodimethylbenzene (2 : 4-xyhdine) from dimethylaniline hydrochloride. Preparation 88. — 4-Amino-3-methyl benzophenone (l-Methyl-2- benzoyl-6-amino benzene). NH, CH. COC 6 H 5 . 211. To 26 gms. (2 mols.) of benzoyl chloride are added gradually 10 gms. of o-toluidine (1 mol.) and the mixture is heated for 15 hours in an oil bath at 230°. A brown viscid liquid is formed which solidifies on cooling. In order easily to separate the 4-amino 3-methyl benzophenone, the mass is hydrolysed by boiling for 14 hours with excess of alcohol containing half its bulk of cone, hydrochloric acid. The product thus obtained is steam- distilled when alcohol and then ethyl benzoate pass over. The acid residue which contains the hydrochloride of the base is boiled for some time with water and filtered from tarry matter. The filtrate is then made slightly alkaline, and o-toluidine derived from untransformed dibenzoyl- o-toluidine, removed by steam distillation. A solid separates from the alkaline liquid in the flask, and after cooling this is filtered off and ex- tracted with absolute alcohol. The alcohol is almost completely removed on the water bath, and a few drops of cone, sulphuric acid are added. On adding a little ether, the base crystallises out in the form of colourless needles. CARBON TO CARBON 157 CH 3 .C 6 H 4 .NH 2 [1.2] + 2C 6 H B C0C1 -> CH 3 C 6 H, .N(COC 6 H,) 2 + 2HC1 CH 3 C 6 H 4 N(COC 6 H 5 ) 2 -> CH 3 .C 6 H 3 (COC 6 H 5 )NH(COC 6 H 5 ) [1.5.2J HC1 + C 2 H 5 OH > CH 3 .C 6 H 3 .(COC 6 H 5 )NH 2 .HCl + C 6 H 5 COOC 2 H 5 NaOH > CH 3 .C 6 H 3 .(COC 6 H 5 )NH 2 [1.5.2]. Colourless needles ; soluble in alcohol ; insoluble in ether and in water. (J. C. S., 85, 386, 591.) Reaction LII. (a) Action of Copper Powder on 2- and 4-mono-nitro- and 2 : 4-di-nitro-chloro- and bromo-benzenes and their Homologues. (B., 34, 2172.) — Symmetrical diphenyl derivatives can be prepared by heating aromatic iodo-compounds with copper powder (see Reaction VII. (b) ). Chloro- and bromo-compounds, however, only react when activated by nitro groups in the ortho- or ^am-positions. Di-nitro-di- phenyl derivatives can be obtained from them in good yield by heating with the metallic powder to about 250° in sealed tubes. If both the ortho- and ^ara-positions are occupied by nitro groups, the activation of the halogen atom is such that the corresponding diphenyl derivative can be prepared by boiling with copper powder in nitrobenzene solution. N0 2 . N0 2 NQ 2 >C1 + 2Cu + Cu 2 CL Preparation 89. — o-^-o '-^'-Tetranitro-diphenyl (l-(2' : 4'-Dinitro- phenyl)-2 : 4-dinitrobenzene). [2.4](N0 2 ) 2 C 6 H 3 .C 6 H 3 (N0 2 ) 2 [2'.4'.J. C 12 H 6 0 8 N 4 . 334. 10 gms. (1 mol.) of 2-4-dinitrochlorbenzene (see p. 266), 10 gms. (excess) of copper powder, and 20 c.cs. of nitrobenzene are refmxed for 1 hour and the cooled solution diluted with ether and filtered. Ligroin is slowly added to the filtrate and the oil which separates crystallised by scratching the sides of the vessel. It is recrystallised from benzene. [1:2: 4](N0 2 ) 2 C 6 H 3 C1 + 2Cu + C1C 6 H 3 (N0 2 ) 2 [ 1 : 2 : 4.] = [2.4](NO a ) a C. e H 8 .C 6 H,(N0 2 ) S! [2 / .4'] + Cu 2 Cl 2 . Yield. — 66% theoretical (5-5 gms.). Yellowish prisms ; insoluble in petroleum ether ; M.P. 163°. (B., 34, 2177.) Reaction LII. (6) Action of Cuprous Chloride on Nitro-diazonium Com- pounds. (B., 34, 3802 ; 38, 725.) — Ordinarily when cuprous chloride acts on a diazonium salt in acid solution, a chloro-compound is the chief pro- duct (Sandmeyers reaction, p. 338), and only a small quantity of the corresponding diphenyl compound is formed. But if a nitro-diazonium salt be used, the diphenyl derivative is formed in much larger quantities. The same holds good for Gattermann's modification of the reaction using copper powder (B., 23, 1226). 2C 6 H 4 (N0 2 )N 2 C1 + Cu 2 Cl 2 = (N0 2 )C 6 H 4 .C 6 H 4 (N0 2 ) + 2CuCl 2 + 2N 2 . 158 SYSTEMATIC ORGANIC CHEMISTRY Peeparation 90.— p-p '-Dinitrodiphenyl (l-(4-Nitro-phenyl)-4-nitro- benzene). NO/ > < >N0 2 . C 12 H 8 N 2 0 4 . 244. By-product ^-Chloro-nitro-benzene. (l-Chloro-4-nitro -benzene) C 6 H 4 (C1)(N0 2 )[1 : 4.] C 6 H 4 0 2 NC1. 157-5. A cold solution of 21-6 gms. (1 mol.) of cuprous chloride in 100 c.cs. of cone, hydrochloric acid (see p. 502) is added to the diazo solution prepared from 30 gms. (1 mol.) of j9-nitraniline, 45 gms. (excess) of cone, sulphuric acid, 60 c.cs. of water and 15-3 gms. (1 mol.) of sodium nitrite. During the addition of the copper salt the whole is vigorously stirred. There is a brisk evolution of nitrogen, the mass turns black and a brownish- yellow substance is precipitated. When the liquid becomes green, the reaction is finished. The product is distilled in steam until no more p-chloro-nitro-benzene passes over. There remains in the distilling flask almost pure 4 : 4'-di-nitro-diphenyl. It is filtered off, dried, and recrystallised from benzene. The by-product £>-chloronitrobenzene is worked up by filtering it from the liquid portion of the distillate, drying on a porous plate, and recrystallising from benzene. HNO. % N0 2 C >N 2 C1. --^ NO / \- >N0 2 and NO,< >C1. Yield. — 4 : 4' ' -dinitrophenyl 55% theoretical (14 gms.) ; p-chloronitro- benzene 40% theoretical (13 gms.). 4 : 4' -dinitrodiphenyl is a crystalline solid ; M.P. 237° ; p-chloronitrobenzene is a crystalline solid ; M.P. 83° ; B.P. 238-5°. (B., 38, 726.) In an exactly analogous manner there is obtained from 30 gms. of m-nitraniline, 23 gms. (87%) of 3-3 '-dinitrodiphenyl (yellow needles ; insoluble in cold glacial acetic acid ; M.P. 200°) and 6 gms. (20%) of m-chloronitrobenzene ; (colourless crystals ; insoluble in cold benzene ; M.P. 45° ; if rapidly cooled after fusion, melts at 24°, but in a short time reverts to the stable modification). Similarly 30 gms. of o-nitraniline yield 17-6 gms. (64%) of 2 : 2'-di- nitro-diphenyl (crystalline solid, insoluble in cold benzene ; M.P. 127°) and 9 gms. (30%) of o-nitrochloro-benzene (colourless crystals, insoluble in cold benzene ; M.P. 32-5°). Reaction LIII. Action of Aceto-acetic Ester on Aldehyde-ammonias (Hantzsch). (A., 215, 1.) — When aceto-acetic ester is heated with aldehyde ammonias alkyl derivatives of dimethyl-dihydro-pyridine-di- carboxylic ester are produced. ! CARBON TO CARBON 159 R R I I OCH CH C 6 H 5 O.OC.CH 2 CH 2 .CO.C 2 H 5 /\ | | -> C 2 H 5 O.OCC C.CO.OC 2 H 5 CH3CO CO.CH3 |l || CH 3 — C C— CH 3 HNH 2 \/ N + 3H 2 0 1 H A great many aldehydes can be employed — propionic aldehyde, nitro- benzaldehyde, phenylacetaldehyde, furfurol — so that the reaction is of wide application. For the steps in the conversion of the compounds obtained to alkyl or aryl derivatives of di-methyl-pyridine, see pp. 235, 403,404. Preparation 91. — Diethyl-dihydro-collidine-dicarboxylate (2:4:6- Trimethyl-3 : 5 dicarbethoxyl-piperidine-(2)-(5)-di-en). CH 3 CH C 2 H 5 OOC.C./\C.COOC 2 H 5 . C 14 H 21 0 4 N. 267. II li CH 3 .C\/C.CH 3 NH 13 gms. (slightly more than 1 mol.) of acetaldehy de-ammonia (see p. 300) are covered with 80 gms. (2 mols.) of ethyl aceto-acetate and warmed gently (in a fume cupboard) until ebullition has commenced (100° — 110°, stir with a thermometer). Should the reaction become too violent, the heating is stopped until it subsides. In 5 minutes the reaction is completed, and an equal volume of dilute hydrochloric acid is added with stirring to the hot liquid, the stirring being continued until the oil which separates sets to a white crystalline mass. This latter is powdered, filtered, washed first with diluted hydrochloric acid, and then with water, well pressed and recrystallised from the minimum quantity of hot alcohol. CH 3 I CH 3 0 : CH CH \ -> EtOOC.C/ \C.COOEt. H 3 C.CO 0 : C.CH 3 _j_ 3jj 2 Q H.N.H H 3 C.C\ v /C.CH 3 H NH Yield. — 60% theoretical (30 gms.). Colourless plates with bluish fluorescence ; insoluble in water ; sparingly soluble in alcohol ether and carbon disulphide ; readily soluble in benzene ; M.P. 131°. (A., 215, 1.) Reaction LIV. (a) Condensation of Non-di-ortho-substituted-primary- aromatic Amines with Acrolein (Skraup). (M., 1, 316 ; 2, 141 ; B., 13, 911 ; 160 SYSTEMATIC ORGANIC CHEMISTEY 14, 1002 ; 29, 705.) — When a primary aromatic amine which has a non- substituted carbon in the or^o-position is heated with glycerol and cone, sulphuric acid in the presence of an oxidising agent, the following series of reactions occur : — (i.) The glycerol is dehydrated by the acid to acrolein. -2H 2 0 CH 2 OH.CHOH.CH 2 OH > CH 2 = CH.CHO. (ii.) The aldehyde then condenses with the aromatic amine to form an aldehyde-amine. CH 2 : CH.CHO + KNH 2 -> CH 2 : CH.CH : N.K + H 2 0. (iii.) The latter compound under the influence of the oxidising agent condenses to a derivative of quinoline. CH /\ /\/\CH 0 I I |CH \y x/\/ N : CH.CH : CH 2 N The oxidising agent usually employed is the nitro-compound corre- sponding to the amine, e.g., nitro-benzene when aniline is the base ; for 2?-toluidine, ^-nitro-toluene serves, and so on. Arsenic acid, however, can be generally employed, and gives better results. The reaction is capable of very wide application ; nitro-, halogen-, hydroxy-, carboxy- quinolines can all be obtained from the corresponding amines ; the amino-naphthalenes also react. Diamines yield the so-called phen- anthrolines. (B., 16, 2519 ; 23, 1016.) h 2 n/\/\nh 2 N m-Phenanthroline. Sometimes the amine can be dispensed with, and the corresponding nitro-body used alone. It is reduced by the hydrogen arising in the reaction. Of technical interest is the fact that ^-nitro-alizarin on heating with glycerol and sulphuric acid yields a blue dye — Alizarin Blue. (B., 16, 445 ; 29, 708 ; A., 201, 333.) OH OH CO CO | -OH /\/\/\. -OH CO CO Alizarin Blue. CARBON TO CARBON 161 Preparation 92. — Quinoline (Benz-pyridine). C 9 H 7 N. 129. N 125 gms. of cone, sulphuric acid are gradually added, with shaking to a mixture of 46 gms. (1 mol.) of aniline, 30 gms. of nitrobenzene and 125 gms. (excess) of glycerol contained in a 2-litre round-bottomed flask. The latter is fitted with a long wide reflux condenser, and heated on a sand bath until bubbles of white vapour are evolved. The source of heat is removed until the reaction moderates, when the flask is again heated to gentle ebullition for 3 hours. Water is added, and the unchanged nitro- benzene distilled off in steam. The residue is treated with cone, caustic soda solution until it is strongly alkaline, and the quinoline and aniline present distilled off in steam. The distillate is treated with dilute sul- phuric acid until the bases are both completely dissolved and the solution contains excess of acid. To the cooled solution sodium nitrite solution is added until a drop of the solution gives a blue coloration with potassium- iodide-starch paper (see p. 501). The aniline is thus converted into the diazonium compound, and on boiling on a water bath, the latter passes into phenol. The solution is again made alkaline, and the quinoline distilled off in steam. The distillate is extracted with ether, dehydrated over solid caustic potash, the ether removed on a water bath, and the residue distilled. CH 2 H \CH J CH ^ + H 2 0 Yield. — 70% theoretical (45 gms.). Colourless liquid ; characteristic odour ; insoluble in water ; soluble in alcohol and ether ; B.P. 237° ; D. I 1-108. (B., 13, 911 ; 14, 1002.) Preparation 93. — o-Nitroquinoline (o-nitro-benzpyridine). C 9 H 6 0 2 N 2 . 174. 100 gms. of cone, sulphuric acid and 51-5 gms. of arsenic acid are well shaken in a flask with 110 gms. glycerine and 50 gms. of o-nitraniline — and then carefully heated on a sand bath under a reflux condenser. As soon as the reaction begins, the flask is removed from the sand bath until it has moderated ; it is then boiled for 3 hours. When cold, a large volume of water is added to the contents of the flask, and the whole allowed to stand overnight, and then filtered. Caustic soda is carefully added to the s.o.c. M 162 SYSTEMATIC ORGANIC CHEMISTRY filtrate until a brown precipitate appears, which is filtered off and dis- carded. Caustic soda is then added to the filtrate until alkaline. The nitro-quinoline thus obtained is washed with water, boiled up with alcohol and animal charcoal, and after filtration is precipitated by the addition of water. O : CH 2 /\h \ch CH + H 2 0 NO, N Yield. — 55% theoretical (35 gms.). Colourless monoclinic needles ; insoluble in water ; soluble in alcohol ; M.P. 88°. (B., 29, 705.) Reaction LIV. (b) Condensation of Primary Aromatic Amines, other than Ortho Substituted, with two Molecules of certain Aldehydes (containing the group — CH 2 CHO) under the influence of Sulphuric or Hydrochloric Acid. (B., 16, 2415 ; A., 249, 110.) — Quinolines substituted in the benzene or in both nuclei may be formed, an intermediate stage being an aldehyde- amine. RiNH 2 + OHC.CH 2 .E -> R X N : CH.CH 2 E. Two molecules of the latter then condense to RjN = CHCHE I EjNH.CH CH 2 E which splits off amine and hydrogen to give a quinoline derivative (B., 29, 59). (Ri-H) \n [2] -CH = CE I CCH 9 E. That hydrogen is set free is proved by the reduction of; some of the quinoline derivative to a tetrahydroquinoline derivative. A mixture of two aldehydes, or of an aldehyde and a ketone, may be employed. (B., 20, 1908.) An alkylidene-aniline may be substituted for the primary amine, and the condensation takes place in presence of zinc chloride. C 6 H 5 N : CHCH 3 + CH 3 CHO CARBON TO CARBON ir>3 Peeparation 94. — Quinaldine (a-Methyl-quinoline). C 10 H 9 N. 143. To a mixture of 30 gms. cone, hydrochloric acid and 10 gms. zinc chloride are added 15 gms. (1 mol.) of aniline, and the whole is remixed on a water bath. To this is slowly added during 2 hours, 12| gms. (2 mols.) of acetaldehyde. The whole is boiled on a sand bath for 90 minutes, and after making alkaline with caustic soda, is steam-distilled. The quin- aldine is separated and distilled, the fraction 244°— 250° being collected. CH / CH 2C 2 H 5 NH 2 + 2CH 3 CHO -> 2C 6 H 5 N : CHCH 3 — > C 6 H 4 j X N =C.CH 3 . Yield. — 50% theoretical (10 gms.). Colourless liquid ; characteristic odour ; insoluble in water ; B.P. 247°. (B., 16, 2465 ; D.R.P., 28217.) Reaction LIV. (c) Condensation of o-Amino-benzaldehydes with Alde- hydes, Ketones, Aceto-acetic Ester, etc. under the influence of a trace of Sodium Hydroxide, to give Quinoline Derivatives (B., 16, 1835 ; 25, 1752.) — The first stage is the formation of an o-amino-benzo ketone. CH !NH 2 + CH 3 COCH 3 - > I l NB i 2 I CO.CH3, which, like all such compounds, readily condenses to quinoline derivatives. CH = CH CH=CH C « H < ! > c q r{ I NH 2 OC.CH3 \ I N C.CII3. The reaction usually takes place by gentle warming with a trace of alkali in alcoholic solution. Prolonged heating at 150° is necessary, however, and alcohol and alkali are no longer employed in the condensation to y-hydroxyquinolines of the anthranilic acids and aldehydes, ketones, etc. (B., 28, 2809.) An interesting synthesis of quinoline from o-toluidine is given by con densation with glyoxal (B., 27, 628). CH 3 O.CH /x /CH /v y CH CH > NH 2 O.CH V\ N h 2 OCH (Cf. the synthesis of Carbostryl, B., 14, 1916). CH I N M 2 164 SYSTEMATIC ORGANIC CHEMISTRY Pkepaeation 95. — Quinaldine (a-Methyl-quinoline), C 10 H 9 N. 143. \/\/CH 3 N 20 gms. (1 mol.) of o-amino-benzaldehyde and 9 gms. (1 mol.) of dried and redistilled acetone are dissolved in absolute alcohol, and a few drops of alcoholic caustic soda added. The condensation takes place at the ordinary temperature. The quinaldine is distilled off in steam and washed with water until free from acetone. H 2 CH CH \/\NH 2 0 : C.CIL Yield. — Theoretical (23 gms.). Colourless liquid ; insoluble in water ; B.P. 247°. (B., 16, 1834.) Reaction LV. Intramolecular condensation of Phenyl Hydrazones of Aldehydes, Ketones and Ketonic Acids by heating with Hydrochloric Acid or Zinc Chloride (Fischer). (B., 19, 1563 ; 26, R., 14.)— This is an important preparation-method for the alkylindols. The reactions occurring are somewhat complicated, since both a rearrangement and a splitting off of ammonia takes place. rs- — CH, C 6 H 5 NH.N : CHCH 2 CH 3 - Propylidene-phenyl-hydrazone. C 6 H 5 NHN : C(CH 8 )COOC 2 H, ■> C 6 H 4 CH + NH 3 \ / * NH /3-Methyl-indol. /C H X C.COOC 2 H 5 -> C 6 H 4 Phenylhydrazone of Pyruvic Ester. NH + NH 3 . a-Indol-carboxylic Ester. Preparation 96.— Methyl Ketol (a-Methyl-indol). CH CH CH CH C !H V.U C Q H Q N. 131. C.CH, 30 gms. (1 mol.) of phenylhydrazine are mixed with 18 gms. (slightly more than 1 mol.) of commercial acetone (B.P., 56° — 58°). The mixture becomes very warm and a good deal of water separates. The mixture is heated on a water bath for 15 minutes, a small portion being occasionally CAKBON TO CARBON 165 tested with Fehling's solution. As long as phenylhydrazine is present in excess, the Fehling's solution is reduced ; more acetone is then added from time to time until the reducing action of the mixture has almost ceased. The turbid oil (crude acetone-phenylhydrazone) is placed in a large copper crucible, and the excess of acetone removed by heating on a water bath for \ hour. 200 gms. of dry commercial zinc chloride are next added, and the mixture heated on the bath with frequent stirrmg. The whole is then heated on an oil bath to 180°, and when in a few minutes the mass has acquired a dark colour the crucible is immediately removed from the bath and stirred. The reaction is complete in a short time, and can be followed by the change in colour of the fusion and the evolution of vapours. The dark fused mass is treated with 3 J times its weight of hot water, and distilled in steam after acidification with a little hydro- chloric acid. The methyl ketol distils over, slowly but completely, as a pale yellow oil which soon solidifies. This is filtered off, melted to free it from water and distilled. It must be kept in a well-closed bottle. Yield. — 55% theoretical (20 gms.). Pale yellow crvstals : obnoxious odour ; M.P. 95° ; B.P. 750 , 272°. (A., 234, 126.) CH 3 C 6 H 5 NHNH 2 + OC = C 6 H 5 NHN : C(CH 3 ) 2 + H 2 0. CH 3 CHAPTER IX the linking of hydrogen to carbon Hydrogen Compounds Although neither so numerous nor important as the carbon to carbon reactions discussed in Chapter VIII., yet a number of reactions, more particularly a number of those classed under the heading of reductions have to be dealt with below. Not unnaturally hydrocarbons loom largely among the products ; some of the most important methods of preparing them depend on the reduction of derivatives previously obtained. Reaction LVI. Action of Water on certain Metallic Carbides. (J. C. S., 87, 1232). — This reaction has an important and well-known application in the production of acetylene on an industrial scale. Methane can be obtained in a similar way from aluminium carbide. yC CH Ca<||| + 2H 2 0 = CaO + ||) X C CH. A1 4 C 3 + 12H 2 0 = 3CH 4 + 4Ai(OH) 3 . Preparation 97. — Acetylene (Ethin). CH III C 2 H 2 . 26. CH. 10 gms. (1 mol.) of calcium carbide are placed in a shallow layer over sand in a large conical flask fitted with a two-holed rubber stopper carrying a tap-funnel and a delivery tube. Water is added drop by drop from the tap-funnel. The gas evolved contains among other impurities hydrogen from free calcium, siluretted hydrogen from calcium silicide, phosphoretted hydrogen from calcium phosphide, and acetaldehyde vapour produced by condensation of acetylene with water. The gas is purified by passing it through (i.) dilute sulphuric acid ; this removes ammonia ; (ii.) a tower packed with a mixture of equal parts of bleaching I powder and quicklime ; this removes phosphorus compounds ; (hi.) a solution of cupric chloride acidified with dilute sulphuric acid ; (iv.) a solution of ferric chloride similarly acidified ; (v.) a solution of chromic I acid ; all these remove phosphorus and sulphur compounds ; (vi.) a 50% j aqueous solution of caustic potash. The gas is collected in a gas-holder, over 50% aqueous glycerol, in which it is only very slightly soluble. I Before collecting, care should be taken that all air has been removed r from the apparatus ; during the filling of the holder the rate of flow of I 166 THE LINKING OF HYDROGEN TO CARBON 167 liquid from it should be adjusted so that there is a slightly increased pressure in the apparatus ; this can be seen from the height of liquid in the central tube of the gas-holder. The purity of the gas is tested by explosion analysis (J. C. S., 84, 555) ; the ratio contraction on explosion ; absorption by baryta water after explosion should lie between 0-73 and 0-77 (theoretical 0-75). Great care must be taken that this preparation is carried out in the absence of name, and that neither the apparatus nor the collected gas is exposed to direct sunlight, which decomposes acetylene. Also the cupric chloride solution employed for washing should be kept acid ; if it becomes alkaline the explosive copper acetylide is precipitated. Should this occur the solution is mixed with much water and poured away. CaC 2 + 2H 2 0 = C 2 H 2 + CaO. Colourless gas ; when pure has a garlic-like smell ; at N.T.P. water dissolves 1 volume ; acetone 31 volumes ; explosive limits in air 3 — 52% ; in oxygen 2—92%. (J. C. S., 87, 1232.) Methane is prepared from aluminium carbide and dilute hydrochloric acid in a similar apparatus. It is purified as described on p. 176. Reaction LVTI. Action of jjHydrogen in the presence of finely divided Nickel on Aromatic Compounds (Sabatier-Senderens). (C. r., 132, 210.) — The addition of hydrogen to an aromatic compound by passing its vapour mixed with hydrogen over finely divided nickel at a relatively low tempera- ture is a reaction of wide and important application. Although nickel is the metal most usually employed, other metals can also act as hydrogen carriers. The method is chiefly used for the reduction of the nucleus in aromatic compound^— hydrocarbons, phenols, amines, etc., to the corre- sponding unsaturated and fully-saturated paraffin derivatives. Ethylenic and acetylenic linkings, aldehydes and ketones can also be reduced in this way, and the reaction has been applied on the large sc«le to the removal of the unsaturation (" hardening ") of fats and oils. Preparation 98. — Hexahydrobenzene (cyclohexan). CH 2 H 2 C/\CH 2 H 2 C\^^/CH 2 CH 2 Preparation of the Catalyst, Small pieces of pumice stone of a convenient size are soaked in a con- centrated solution of nickel nitrate in distilled water, and heated in a basin over a free flame until the nitrate has been converted into the oxide. Alternatively the pumice is impregnated with a paste of its own weight of nickel oxide and distilled water, and dried on a water bath. The nickel oxide is reduced by heating in a current of pure, thoroughly dried hydrogen in a combustion tube. The arrangement of the apparatus, and the preparation and purification of hydrogen is the same as for the prepara- C R H 84. 168 SYSTEMATIC ORGANIC CHEMISTRY tion of reduced copper (see p. 410). The pumice is loosely packed into the combustion tube and kept in position by asbestos plugs. The air bath is maintained at about 280° ; it is tilted slightly forwards so that any liquid formed may run down into the receiver. Ordinary corks should be used, and not rubber stoppers in making the connections to the combustion tube. Unpurified hydrogen must not be admitted, as otherwise the catalyst will be poisoned. It is convenient to have a by- pass in the form of a T-piece between the copper gauze and the caustic soda tower. At first the hydrogen escapes through the by-pass. After the air has been expelled (a sample must be collected and tested) as far as the T-piece, the copper gauze tube is heated, and the current of hydrogen is then diverted through the tower into the combustion tube. Some should also be allowed to escape through, the funnel B (Fig. 48) to remove air from its stem. When the air has all been expelled as before, the air bath carrying the combustion tube is heated. Air must not be allowed to enter the combustion tube from now until the end of the experiment. The reduction of the nickel oxide will take at least a week ; the hydrogen is passed at the rate of about 300 c.cs. per minute. The reduction is accom- panied by a colour change from black to a greyish-yellow, and is complete when no more steam is evolved, i.e., when a calcium chloride tube at the exit end of the combustion tube does not gain in weight after passing the exit gas through it for J hour. Hydrogenation of Benzene. The benzene used should first be tested for thiophene with isatin and cone, sulphuric acid, and then redistilled and recrystallised ; traces of sulphur and chlorine compounds completely inhibit the reaction. The benzene is introduced at the rate of about 7 c.cs. per hour into the combus- tion tube by means of a dropping-funnel, B, whose stem, drawn out to a capillary, passes through one hole of the double-holed cork at A (Fig. 48). The quantity of benzene used is obtained by weighing the quantity in the funnel before and after the experiment. The temperature of the air bath should be 180° — 190°, and the hydrogen should be passed at about <= I :.L; H SOU _l Fig. 48. THE LINKING OF HYDROGEN TO CARBON 169 250 c.cs. per minute. When commencing to add the benzene at A, air must not be allowed to enter the tube ; the vapour issuing from the combustion tube is condensed in a flask immersed in a freezing mixture. The liquid obtained which contains a little unchanged benzene, when sufficient has been collected, is treated with a nitrating mixture of sulphuric and nitric acid (see p. 262). Cyclohexane is scarcely affected by this mixture while benzene is rapidly nitrated. It cannot otherwise easily be separated from cyclohexane ; their boiling points and freezing points are almost identical. After standing for 1 hour the top layer of oil is separated, well washed with water, and dried for 24 hours over calcium chloride. It is fractionated, and the fraction 78° — 85° redistilled and collected between 80°— 82°. C 6 H6 + 3H 2 = C 6 H 12 . Yield. — 80% theoretical. Calculated on the benzene volatilised (8-5 gms. cyclohexane per 10 gms. benzene). Almost theoretical allowing for unchanged benzene (11 gms. cyclohexane per 10 gms. benzene). Colourless liquid ; insoluble in water ; B.P. 81°. (C. r, 132, 210.) Preparation 99.— Hexahydrophenol (cyclohexanol). CHOH H 2 C/\CH 2 C 6 H 12 0. 100. CH 2 The apparatus is as in Preparation 98, except that in front of the catalyst tube is inserted a small distilling flask weighed before and after the experi- ment containing 100 gms. of pure redistilled phenol. Hydrogen enters by means of a one-holed cork in the neck of the flask and leaves by the side tube, which fits into a one-holed cork at A (Fig. 48). During the reduction (p. 167) of the nickel oxide the tube by which the hydrogen enters the flask is raised a little above the surface of the phenol. After reduction is complete and the temperature of the catalyst has been reduced to 180° — 190°, the phenol in the flask is heated almost to its boiling point, and the hydrogen delivery tube pushed well down into the liquid. Care must be taken that phenol does not condense in the tube, and that only the vapour passes over. When sufficient liquid has con- densed in the receiver, it is shaken with caustic soda solution to remove unchanged phenol, extracted with ether, and the extract dried over anhydrous potassium carbonate for 24 hours. The ether is removed on a water bath, and the residue distilled ; the fraction 166° — 174° is collected and refractionated between 169° — 171°. C 6 H 5 OH + 3H 2 = C 6 H u OH. Yield. — Almost theoretical (10-5 gms. of hexahydrophenol per 10 gms. of phenol). Colourless liquid ; aromatic smell, insoluble in water ; B.P. 17°. (C. r., 132, 210.) 170 SYSTEMATIC ORGANIC CHEMISTRY Hexahydro toluene, hexahydrocresol, etc., may be obtained by methods exactly similar to the foregoing. Reaction LVIII. (a) Reduction of Phenols and Quinones by Distillation with Zinc Dust. (A., 140, 205.) — When certain aromatic oxygen com- pounds (phenols, naphthols, quinones, etc.), are heated with zinc dust, they are reduced to the corresponding hydrocarbons. Thus, phenol yields benzene, the naphthols, naphthalene ; while anthracene can be obtained from anthraquinone or its hydroxy derivatives, alizarin, or quinizarin. It was in this way that alizarin was first proved to be an anthracene derivative. (B., 1, 43.) CO OH /\/\/\OH /\/\/\ | + 4Zn =i 1 I + 4ZnO. co V/ Pkepakation 100. — Anthracene (s-Dibenz-benzene). 178. Pieces of porous pumice stone of a size that will conveniently pass into a combustion tube are added to a paste prepared from 100 gms. of good zinc dust and 30 c.cs. of alcohol, and are stirred round so that they become covered with the paste. They are removed from the paste with tongs, and heated in a porcelain dish with constant motion over a free flame until the alcohol is evaporated. A hard glass combustion tube, 70 cms. long, is drawn out at one end to a narrow tube, the narrowed end is closed by a loose plug of asbestos, and a layer of zinc dust, 5 cms. long, is placed next to the plug, then comes a mixture of 2 gms. of quinizarin (see p. 102), alizarin, or anthraquinone with 20 gms. (excess) of zinc dust, and finally a layer of pumice zinc dust, 30 cms. long. After a canal has been formed over the zinc dust by placing the tube in a horizontal position and tapping it, the latter is transferred to a combustion furnace, tilted forwards, as in a nitrogen estimation (see p. 451) and a rapid current of dry hydrogen (see p. 410) is passed through the tube without heating. The open end of the tube is closed by a one-holed cork, and the issuing gas led to a draught pipe. After the gas has been passed for some time a test-tube of the issuing gas is collected over water at intervals, and a light applied to the mouth of the test-tube at least 12 ft. from the apparatus. When the contents of the tube burn quietly, all the air has been displaced from the apparatus. The gas current is then diminished to about 150 c.cs. per minute, and the pumice zinc dust is heated with small flames. (On no account must the apparatus be heated until all the air has been dis- placed.) The heating is gradually increased from the front backwards, until finally the tube is heated as strongly as possible. The rear layer of 5 cms. of zinc dust is next similarly heated, and when this glows, THE LINKING OF HYDROGEN TO CARBON 171 the mixture of anthracene derivative and zinc dust is gradually heated, all being done as in the estimation of nitrogen. The anthracene formed condenses to crystals in the forward cool part of the tube. After the reaction is complete, a rapid current of hydrogen is passed while the tube is cooling ; when cold the part containing the anthracene is broken off, and the substance removed with a small spatula ; it is purified by sublima- tion (see p. 28). CO OH CH + 5H 2 = C,h/ I \c.H 4 + 4H 2 0. CO OH Yield. — Almost theoretical (1-5 gms.). Colourless crystals ; insoluble in water ; soluble in warm benzene and in glacial acetic acid ; M.P. 213° ; B.P. 351° ; M.P. of picrate, 138°. (A., 140, 205.) It is better to use alcohol in making zinc dust paste, for if there is much oxide present in the dust a great deal of heat may be evolved on adding water, and much oxidation of the metal occur. The following is one of the methods employed for the separation of pure anthracene from the coal tar fraction containing it. Carbazole and phenanthrene are the chief impurities present. Purification of Crude Anthracene. Crude anthracene (about 40%) is mixed with 1\ times its weight of benzene or solvent naphtha (90% at 160°) in a vessel fitted with a mechanical stirrer. Sodium nitrite to one-tenth of the weight of crude anthracene taken, is dissolved in 10 times its weight of water, and sufficient 10% sulphuric acid (7-2 gms. for each 1 gm. of 10% nitrite) to decompose this quantity of nitrite is added to the benzene — anthracene mixture and the temperature maintained at 25°. The nitrite solution is then run in at such a speed that no red fumes escape. When all the solution has been added the mixture is filtered at the pump. The nitrate consists of two layers, one of sodium sulphate solution and one of solvent naphtha, or benzene containing the impurities such as nitroso-carbazol. The purified anthracene on the filter is washed with benzene or solvent naphtha ; this latter on a large scale is used for the final treatment of a fresh lot of crude anthracene. The initial benzene or solvent naphtha, after separation from the aqueous solution, is recovered by distillation. The anthracene from this treatment will be about 80% pure. It may be purified to 95% by crystallising from heavy bases (pyridine, etc.), and is finally raised by sublimation and recrystallisation from benzene to 98%. (For the estimation of purity, see p. 494.) (C. T., 23, 8, 21 ; D.R.P., 122852.) Reaction LVIII. (6) Reduction of Aromatic Ketones to the corre- sponding Hydrocarbons by treatment with Hydriodic Acid or with Sodium in Alcoholic Solution. (B., 7, 1624 ; 31, 999.)— Two methods for the 172 SYSTEMATIC ORGANIC CHEMISTRY reduction of aromatic ketones to the corresponding hydrocarbons are exemplified below. Method I. using hydriodic acid is a standard method for the reduction, especially the complete reduction, of an organic com- pound ; the sodium-alcohol method given in II. is not so universally applicable — it is a milder reducing agent and more selective ; thus, it was used by Bamberger in his researches on the formula of naphthalene, to reduce one only of the two rings in that compound and its derivatives. The nickel oxide-hydrogen method can be applied here, as also to the reduction of mixed aliphatic-aromatic ketones ; aliphatic ketones are best directly reduced by Method I. Peepaeation 101. — Diphenylmethane (Benzyl-benzene.) C 6 H 5 .CH 2 C 6 H 5 . C 13 H 12 . 168. Method I. — 10 gms. (1 mol.) of benzophenone, 12 gms. (nearly 2mols.) of hydriodic acid (B.P. 127°) and 2 gms. (more than 1 atom) of red phos- phorus are heated together in a sealed tube for 6 hours at 160° (see p. 38). The reaction mixture is extracted with ether and the extract washed with water several times. It is then filtered, dried over calcium chloride for 24 hours, the ether removed on a water bath and the residue distilled. C 6 H 5 .CO.C 6 H 5 + 4HI = C 6 H 5 .CH 2 .C 6 H 5 + H 2 0 + 2I 2 . Yield.- Theoretical (9 gms.) (B., 7, 1624.) Method II. — 10 gms. (1 mol.) of benzophenone are refluxed with 100 gms. (excess) of alcohol, and 10 gms. (excess) of sodium wire are gradu- ally added through an addition tube (see p. 47) to the boiling liquid. When the solution of the sodium is complete the liquid in the flask is cooled, saturated with carbon dioxide, poured into cold water and the whole extracted with benzene. The extract is dried for 24 hours over calcium chloride, the benzene removed on a water bath, and the residue distilled under reduced pressure, the fraction 174° — 176° at 80 mms. being retained. C 6 H 5 .CO.C 6 H 5 -f- 2H 2 = C 6 H 5 .CH 2 .C 6 H 5 + H 2 0. Almost theoretical (8*5 gms.). Colourless oil ; orange like odour, solidifies to needle-shaped crystals ; M.P. 26° ; B.P. 760 , 263° ; B.P. 80 , 175°. (B., 31, 999.) Reaction LIX. Reduction o£ a Primary Aryl Hydrazine to the corre- sponding Hydrocarbon by the action of Copper Sulphate or Ferric Chloride. (B., 18, 90, 786). When a primary aryl hydrazine is boiled with neutral copper sulphate or ferric chloride, or treated with alkaline copper sulphate in the cold, the hydrazine radical is replaced by hydrogen, the corre- sponding aryl hydrocarbon being formed. C 6 H 5 NH.NH 2 + 2CuO = C 6 H 6 + N 2 + H 2 0 + Cu 2 0. This reaction can be employed to remove a primary amino group from an aromatic compound, especially when the ordinary method of direct reduction of the diazonium compound by sodium stannite or alcohol is THE LINKING OF HYDROGEN TO CAKBON 173 not applicable. Although in the application of this method the hydrazin , can be prepared as the hydrochloride, and reduced in the same solution yet it is better to isolate the free base and oxidise it separately, since in, the oxidation of the hydrochloride there is a tendency for the hydrazine radical to be replaced by chlorine. Reaction LX. Action of Water on Magnesium Alkyl or Aryl Halides (Grignard). (B., 39, 634.) — When a Grignard compound is treated with water or other substance containing a hydroxyl group hydrolysis occurs, and the corresponding hydrocarbon is obtained. C 6 H 5 .Mg.I + H 2 0 = C 6 H 6 + OH.Mg.I. C 6 H 5 MgI + C 2 H 5 OH = C 6 H 6 + C 2 H 5 O.MgI. This reaction is of theoretical rather than practical importance. Preparation 102. — Triphenyl Methane ( ( ( Di-phenyl)-methyl)-benzene) HC(C 6 H 5 ) 3 . C 19 H 16 . 244. 10 gms. (1 mol.) of triphenylmethyl chloride and 0-1 gms. of iodine are dissolved with gentle heating in 50 c.cs. of sodium-dried ether in a dry round-bottomed flask of 500 c.cs. capacity, fitted with a long reflux con- denser, 2 gms. (excess) of clean, dry magnesium filings or small pieces of the ribbon are added (see p. 68). A slow stream of well-dried hydrogen is passed through the liquid by means of a tube through the cork to the bottom of the flask ; the hydrogen coming from the top of the reflux condenser must be led to a good draught pipe (the flask heated on a water bath to vigorous boiling, and the water bath removed). After the removal of the water bath the flask is wrapped in a cloth to conserve the heat of reaction, which is then sufficient to keep the ether boiling for about 1 hour, by which time bright yellow crystals of the magnesium compound have separated. The whole is again heated to boiling on a water bath for 1 hour, and then all the water is run out of the condenser. The ether evaporates and the solid magnesium compound remains. To it is added after increasing the rate of passage of hydrogen with complete exclusion of air 60 c.cs. (excess) of distilled water, and then in small portions, 40 gms. of cone, sulphuric acid. The flask is well shaken and the contents boiled on a wire gauze for 15 minutes. The yellow crystalline cake of the magnesium compound at first swims on the surface, but gradually decomposes to a surface layer of homogeneous liquid. The reaction is complete when all the magnesium compound has disappeared and the whole is clear. Towards the end the flask is shaken vigorously at short intervals to prevent spurting of the accumu- lating oil. The flame is removed, the hydrogen stream shut off, and 150 c.cs. of pure benzene added to the liquid while still hot, the whole being vigorously shaken. The benzene solution, which is coloured red with iodine^ is separated and treated in turn with warm water, warm aqueous caustic soda, warm sodium thiosulphate solution, and again with warm water. The turbid liquid is shaken with calcium chloride, and warmed until it becomes clear. It is filtered hot, allowed to stand over fresh calcium chloride for 24 hours, again filtered hot, and evaporated on a water 174 SYSTEMATIC ORGANIC CHEMISTRY bath to a bulk of 10 c.cs. On cooling triphenylmethane crystals containing benzene of crystallisation separate. These crystals slowly lose benzene on standing and more quickly on heating on a water bath. The hydro- carbon is finally recrystaUised from hot alcohol. (C 6 H 5 ) 3 CC1 -> (C 6 H 5 ) 3 CMgCl -> (C 6 H 5 ) 3 CH. Yield— 90% theoretical (8 gms.). Colourless plates ; soluble in benzene and in hot alcohol ; M.P. 93° ; B.P. 300° ; separates from benzene in crystals containing 1 mol. of benzene of crystallisation ; M.P. 76°. (B., 39, 634.) Reaction LXI. Reduction of Diazonium Compounds to the correspond- ing Hydrocarbon. (A., 137,39; B., 22, 587 ; 35,162; 36,815,2065; 40, 858). When a diazonium compound is boiled with an alcohol, oxidation of the latter to the corresponding aldehyde and simultaneous replacement of the diazo group by hydrogen occurs. E.N 1 N + C 2 H 5 OH CI = EH + N 2 + HC1 + CH 3 CHO. This is the classical method of reducing diazonium compounds, but other reducing agents, notably sodium stannite, give better results ; the alcohol always tends to form with the diazonium compound more or less of the corresponding mixed ether, unless a large number of negative groups be present. Hypophosphorous acid and alkaline sodium hydro- sulphite also give good yields with certain types of compounds. The method is much used to remove the amino group from an aromatic nucleus, and has had some theoretically important applications. Preparation 103. — s-Tri-bromobenzene (1:3: 5-Tri-bromobenzene). Br /\ I I C 6 H 5 Br 3 . 315. Br^/'Br 50 gms. (1 mol.) of finely powdered s-tribromaniline (see p. 349) are treated with 300 c.cs. (excess) of absolute alcohol and 75 c.cs. of benzene added to insure complete solution. 20 c.cs. (excess) of cone, sulphuric acid are run in ; should a precipitate form, it is redissolved by the addition of more benzene. 20 gms. (excess) of pure finely powdered sodium nitrite are added to the hot liquid as rapidly as possible without the reaction becoming too violent, and the whole heated until effervescence ceases. After standing over-night the precipitate is filtered, washed at the pump with hot water until the washings give no precipitate with barium chloride, dried on a porous plate and recrystallised from absolute alcohol. NaN0 2 C 2 H 5 OH C 6 H 2 Br 3 NH 2 — > C 6 H 2 Br 3 .N 2 .S0 4 > C 6 H 3 Br 3 . H 2 S0 4 Yield. — Almost theoretical (47. gms.). Colourless prisms ; insoluble m water ; M.P., 119°. (B., 22, 587.) THE LINKING OF HYDROGEN TO CARBON 175 Preparation 104.— Diphenyl (Phenyl-benzene). C 6 H 5 .C 6 H 5 . C 12 H 10 . 154. 30 gms. (1 mol.) of benzidine are added to 60 c.cs. cone, hydrochloric acid and 400 c.cs. water. The whole is heated until the benzidine is dissolved. After cooling it is diazotised with 23 gms. (2 mols.) of sodium nitrite (see p. 366). To the ice-cold tetrazonium solution is added I 350 c.cs. of commercial hypophorous acid (D. 1*15). After standing for several days in an ice chest, until no more solid separates, the diphenyl is filtered off, treated with dilute caustic soda solution and steam distilled. It is then recrystallised from absolute alcohol. NH 2 C 6 H 4 .C 6 H 4 NH 2 -> C1N 2 C 6 H 4 .C 6 H 4 N 2 C1 -> C 6 H 5 .C 6 H 5 . Yield. — 60% theoretical (15 gms.). Colourless leaflets ; insoluble in cold alcohol ; M.P. 71° ; B.P. 254°. (B., 35, 162.) Hypophorous acid may be prepared by digesting 150 gms. finely powdered calcium hypophosphite with 45 c.cs. of cone, sulphuric acid, and 500 c.cs. water for 1 hour at 80°, and removing the calcium sulphate by filtration. Reaction LXII. Direct Reduction of Halogen Compounds. (J. C. S., (1902), 535). A very useful method for the preparation of hydrocarbons, more especially of aliphatic hydrocarbons consists in replacing the halogen atom of a halogen compound by an atom of hydrogen. RC1 + H 2 = EH + HC1. The reducing agents usually employed are phosphorus and hydriodic acid, or the zinc-copper or the aluminium-mercury couple. The method of using the first of these is given on p. 186. The couples have the advantage of readily yielding a pure gas, and are of wide application. Methane can be prepared from methyl iodide, or chloroform, etc., ethane from ethyl iodide, propane from propyl, and isopropyl iodides, and so on. The following will illustrate their use : — Preparation 105. — Methane (Methyl-hydride). H I H — C — H. CH 4 . 16. I H To one limb of a wide U -tube cooled in water and filled with the zinc- copper, or the aluminium-mercury couple is attached a small tap-funnel, and to the other a small reflux condenser. The zinc-copper couple is prepared by placing 30 gms. (excess) of zinc in an aqueous solution of copper sulphate until the surface of the metal is covered with a film of metallic copper. The couple is washed with water and then with absolute alcohol. The aluminium-mercury couple, which gives a better yield of 176 SYSTEMATIC ORGANIC CHEMISTRY gas, is prepared by immersing 20 gms. (1 atom) of small pieces of sheet aluminium in mercuric chloride solution until a film of mercury covers the surface of the aluminium, which is washed as above. 100 c.c. (excess) of methyl alcohol (acidified with 2 drops of dilute sulphuric acid if the zinc-copper couple be used) are poured on to the couple in the U-tube, and 50 gms. of methyl iodide are added gradually from the funnel so that the reaction does not become too violent nor the couple too hot. With the aluminium-mercury couple the reaction is especially vigorous, and good cooling is required. The gas is washed in worms containing (1) dis- tilled water ; (2) sodium methoxide dissolved in methyl alcohol — 2 worms ; (3) distilled water ; (4) fuming sulphuric acid — 2 worms ; (5) cone, sulphuric acid— 2 worms ; (6) distilled water ; (7) 50% caustic soda solution — 2 worms. Cone, sulphuric acid is used to condense the acid mist from the fuming sulphuric acid washings ; distilled water is always inserted between worms containing liquids, which will react violently if mixed. The gas is then passed through a U-tube heated in boiling water and containing palladium black to adsorb hydrogen, of which usually about 1% is present. Alternatively, palladium oxide may be used in the tube to oxidise the hydrogen. The gas is collected in a gas-holder over 50% aqueous glycerol, which does not dissolve methane, under a slight excess pressure, as described in Preparation 97, unless the dry gas be required, when the gas is collected over mercury or cone, sulphuric acid, being first dried by passage through two U -tubes contain- ing phosphorus pentoxide. Completely to free it from hydrogen three or four treatments with palladium or its oxide will be necessary. The gas obtained in this way is pure provided care be taken that all air has been swept out of the apparatus before collection is begun. With proper precautions, the ratio-contraction on explosion to absorption by baryta water after explosion should always be between 1-99 and 2-01, the theoretical value being 2-00. CH 3 I + Zn + CH3OH = ZnI(OCH 3 ) + CH 4 . 3CH 3 I + 2A1 + 3CH 3 OH = 3CH 4 + Al 2 I 3 (OCH 3 ) 3 . Colourless odourless gas ; solubility in water at N.T.P. = 5-25 ; B.P. 76 °, — 164° ; M.P. - 184° ; explosive limits : in oxygen, 5—60%, in air, 6—13%. (J. C. S., 81, 535.) Purification by Fractional Liquefaction or Evaporation. If liquid air be available, the hydrogen in the methane prepared above is best removed by fractional distillation. The following is an outline of the method (see Fig. 49). The gas from the gas-holder is passed through a series of U-tubes con- taining phosphorus pentoxide, then through a small bulb B. When all the air has been driven out of the apparatus, a vacuum vessel containing liquid air is brought below B and gradually raised so as slowly to increase the cooled surface of the bulb. The methane condenses rapidly in B, hydrogen passing away through C. When A is almost empty of gas, the THE LINKING OF HYDROGEN TO CARBON 177 remainder is run away by means of the three-way tap D. Meanwhile the liquid air container is raised or lowered around B, so that the liquid in B gently boils. When about one-fifth has boiled away C is closed, and a small amount of gas allowed to pass away through D. Connection is then made to the gas-holder, which is slowly filled under a pressure slightly above atmospheric. If preferred, the methane may be distilled into another holder through C, and the gas from several holders, such as A, purified and collected in one holder. Great care must be taken in manipu- lating the liquid air container, so that the liquid in B boils gently ; if the B Fig. 49. vacuum vessel be lowered too rapidly, vigorous boiling will occur, and a great pressure generated in the apparatus. The last traces of gas in B are not collected. This process can be repeated if a very pure gas is required. In each operation about one-third of the original gas is lost. To make quite certain that the gas which is being collected is pure, a platinum resistance thermometer may be enclosed in the liquefaction bulb, and the tempera- ture determined during the operation, as in the fractional distillation of any other liquid. This is more important in preparing the higher hydro- carbons pure. The methods of fractional liquefaction and distillation have very many similar and important applications in the chemistry of gases. s.o.c. CHAPTER X hydrogen to carbon Hydroxy Compounds Alcohols and Phenols The reactions discussed below are based on the reduction of the group — I I _ C = 0 to — C — OH. Such reactions comprise practically all those in which hydrogen is linked to carbon to produce of necessity a hydroxy compound. Reaction LXIII. Combined Oxidation and Reduction of Aromatic Aldehydes under the influence of Caustic Alkalis (Cannizzaro). (B., 14, 2394.) — When the lower aliphatic aldehydes are treated with caustic alkalis, resinification quickly occurs ; aromatic aldehydes, however, and some of the higher aliphatic aldehydes behave differently, two molecules smoothly interacting to give, by simultaneous oxidation and reduction, one molecule each of the corresponding acid and alcohol. KOH E.CHO + R.CHO > KCH 2 OH + RCOOH. This method is frequently used for the preparation of aromatic alcohols from the corresponding aromatic aldehydes which can usually be readily obtained. Preparation 106. — Benzyl Alcohol (Phenyl-methanol). C 6 H 5 CH 2 OH. C 7 H 8 0. 108. and Benzoic Acid (phenyl-methan acid) C 6 H 5 COOH. C 7 H 6 0 2 . 122. 30 gms. (2 mols.) of freshly distilled benzaldehyde are mechanically shaken in the cold with 45 gms. (excess) of a 60% solution of caustic potash until a permanent emulsion is formed. The mixture is allowed to stand for 24 hours, during which time much potassium benzoate separates. Owing to the presence of cone, alkali, a glass stopper must not be used to close the shaking bottle. Water is added until a clear solution is obtained, which is then extracted four times with ether. The extract which contains the benzyl alcohol formed is shaken with cone, sodium bisulphite solution (see p. 506) to remove traces of benzaldehyde, washed with dilute caustic soda and with water and filtered. The ether is removed 178 THE LINKING OF HYDROGEN TO CARBON 179 on a water bath, and the residue fractionated, the fraction 204° — 208° being redistilled to give pure benzyl alcohol. The alkaline solution from which benzyl alcohol has been extracted is carefully neutralised, and acidified with, at first, concentrated, and then dilute hydrochloric acid. The precipitated benzoic acid is recrystallised from hot water. 2C 6 H 5 CHO + KOH = C 6 H 5 CH 2 OH + C 6 H 5 COOK. Yield. — 90% theoretical of both compounds (benzyl alcohol, 13-5 gms. ; benzoic acid, 15-5 gms.). Benzyl Alcohol. — Colourless oil somewhat soluble in water ; faintly aromatic odour ; B.P. 206-5 ; D. 15 4 * 1-05. Benzoic Acid. — Colourless needles ; soluble in hot water, alcohol, ether ; melts and sublimes on heating ; can be distilled in steam ; M.P. 122° ; B.P. 250°. (B., 14, 2394.) Reaction LXIV. (a) Reduction of Aldehydes and Ketones to the corre- sponding Alcohols by the use of Alkaline Reducing Agents. (B., 31, 1003 ; J. pr., [2], 33, 184 ; [2], 76, 137.)— The alkaline reducing agent most usually employed is sodium amalgam and water, especially to obtain polyhydric alcohols from the corresponding sugars ; here it is easily applied owing to the solubility of the sugars in water. But even if the ketone or aldehyde be not soluble in water, the amalgam can be allowed directly to act on the moist substance, or the latter can be dissolved in ether or benzene, and the amalgam and water gradually added. Aluminium amalgam and water can also be employed in a similar way. Sodium and alcohol (see also Reaction CLXXIV.) are generally used in the aromatic series. In reducing ketones, especially aliphatic ketones, there is always more or less pinacone formation ; this is not so marked in the aromatic series, especially if acid reducing agents be not used (see p. 50). Here zinc dust and caustic soda or ammonia, and alcoholic sodium hydrosulphite give good results. The Sabatier- Sender ens reaction can also be employed (see p. 167). Pkepaeation 107. — Dulcitol (Hexahydroxyhexan H [-)• CH 2 OH.(CHOH) 4 CH 2 OH. C 6 H 14 0 6 . 182. 10 gms. (1 mol.) of galactose dissolved in 100 gms. of water are shaken in a stout 500-c.c. stoppered bottle with 30 gms. of 2J% sodium amalgam (see p. 505) until the first reaction has ceased. Every 10 minutes the liquid is neutralised with 10% sulphuric acid. Further amalgam is added in 20-gm. lots with shaking and neutralisation as before, until 1 c.c. of the solution will reduce not more than 0-2 c.c. of Fehling's solution. The temperature throughout must not exceed 20° C. ; the operation will take about 3 hours, and 400 gms. (excess) of 2-|% amalgam will be required. When reduction is complete, the solution is separated from the mercury, exactly neutralised with 10% sulphuric acid, heated on a water bath to 60°, and poured with stirring into 1 litre of alcohol, and the precipitated sodium sulphate filtered off at the pump. The filtrate is concentrated on a water bath to about 25 c.cs., and until crystals begin to separate, the N 2 180 SYSTEMATIC ORGANIC CHEMISTRY alcohol distilling being recovered. The residual liquid is cooled to 0° and filtered. The precipitated sodium sulphate is extracted with 80% alcohol to recover any dulcitol it may contain. H 2 CH 2 OH.(CHOH) 4 .CHO > CH 2 OH.(CHOH) 4 CH 2 OH. Yield. — 50% theoretical (5 gms.). Colourless crystals ; sweet taste ; very soluble in water ; M.P. 188°. (B., 20, 1091 ; 25, 2564.) Peepaeation 108. — Phenyl Methyl Carbinol (1-Phenyl-l-ethanol). CH(CH 3 )(C 6 H 5 )(OH). C 8 H 10 O. 122. 15 gms. (1 mol.) of acetophenone are dissolved in 150 gms. of absolute alcohol, and the whole warmed on a water bath. 15 gms. (excess) of sodium wire are rapidly added, and when reaction has ceased, carbon dioxide is passed in until it is no longer absorbed. 350 c.cs. of water are added and the mixture evaporated on a water bath until nothing further distils, the alcohol being recovered. The residue is extracted with ether and dried over potassium carbonate, the ether removed on a water bath, and the residue fractionated under reduced pressure, the fraction 97° — 103° at 15 mm. being retained. (Cf. Preparation 18). H 2 C 6 H 5 CO.CH 3 > C 6 H 5 .CHOH.CH 3 . Yield. — 45% theoretical (6-5 gms.). Colourless liquid ; slightly soluble in water; B.P. 760 , 198°; B.P. 40 , 118°; B.P. 20 , 111°; B.P. 15 , 100 c . (B., 31, 1003.) Peepaeation 109. — Benzhydrol (Diphenylmethanol). HC(C 6 H 5 ) 2 (OH). C 13 H 12 0. 184. 10 gms. (1 mol.) of benzophenone are dissolved in 200 c.cs. of alcohol, and 40 gms. of 50% aqueous caustic potash added. The mixture is treated with 100 gms. of good zinc dust, and the whole allowed to stand near a water bath for a week. After neutralisation with carbon dioxide, it is filtered at the pump, and the filtrate evaporated until crystals separate on cooling a sample. H 2 (C 6 H 5 ) 2 CO > (C 6 H 5 ) 2 CHOH. Yield— 10% theoretical (7 gms.). Colourless needles ; slightly soluble in water ; M.P. 68°. (J. pr., [2], 33, 184.) Reaction LXIV. (6) Reduction of Aldehydes and Ketones to the corresponding Alcohols by the use of Acid Reducing Agents. (B., 37, 1677.) — Acid reducing agents are not widely used owing to the danger of forming pinacones or of complete reduction to the corresponding hydro- carbon occurring ; the latter always takes place if hydriodic acid be used. But in the aromatic series, especially with diketones, the milder acid- reducing agents — zinc dust and sulphuric acid, zinc dust or iron and glacial acetic acid, and stannous chloride and hydrochloric acid give good results. THE LINKING OF HYDROGEN TO CARBON 181 Preparation 110.— Hydrobenzoin (1 : 2-Diphenyl-l : 2-ethandiol). C 6 H 5 .CHOH.CHOH.C 6 H 5 . C 14 H 14 0 2 . 214. 15 gms. (1 mol.) of benzoin dissolved in 200 c.cs. of alcohol are heated on a water bath with 20 gms. (excess) of stannous chloride in 50 c.cs. of 20% hydrochloric acid for about \ hour and until complete decolonsation has occurred. The cooled liquid is filtered at the pump, and the precipitate washed with water and recrystallised from glacial acetic acid or aqueous alcohol. C 6 H 5 .CO.CHOH.C 6 H 5 + SnCl 2 + 2HC1 = C 6 H 5 .CHOH.CHOH.C 6 H 5 + SnCl 4 . Yield.— Almost theoretical (15 gms.). Colourless leaflets ; insoluble in water ; M.P., 134°. (B., 37, 1677.) Reaction LXIV. (c) Reduction of Quinones. (A., 27, 268 ; 45, 354 ; 215, 127 ; B., 19, 1467 ; 20, 1854, 2283 ; 21, 1172 ; 40, 390, 924 ; J. pr., [2], 76, 141 ; Meyer and Jacobson, Lehrbuch (ii.), 421).— All benzqumones are very readily reduced to the corresponding quinols ; sulphurous acid being the reagent most usually employed. In the reduction the greenish coloured quinhydrone (see p. 218) is intermediately formed. O HO O OH 2 H 2) -> 2 I X/ II 0 Benzquinone. ■ O HO OH Quinol. Quinhydrone. Phenylhydrazine and hydroxylamine also reduce quinone to quinol ; they do not react with it as with other oxy-compounds. The anthraquinones may be reduced to the corresponding " anthra- quinols " (hydroxyanthranols) with alkaline sodium hydrosulphite ; this reaction has a wide application in the dye industry. These compounds are difficult to isolate pure, for they rapidly oxidise in air. The anthranols — y-monohydroxyanthracenes — however, are stable, and may be obtained by reducing anthraquinone with acid-reducing agents — tin and hydro- chloric acid, zinc and glacial acetic acid, copper or aluminium, and sulphuric acid, etc. For the complete reduction of anthraquinone^ see Reaction LVIII. (a). Preparation 111. — Quinol (1 : 4-Di-hydroxybenzene). C 6 H 4 (OH) 2 [l : 4]. C 6 H 6 0 2 . 110. 10 gms. (1 mol.) of finely powdered quinone are suspended in water, and the liquid saturated with sulphur dioxide until, after the intermediate formation of quinhydrone, complete solution and decolorisation have occurred, the operation being carried out in a fume cupboard. The liquid is repeatedly extracted with ether until nothing further is removed, the 182 SYSTEMATIC ORGANIC CHEMISTRY ether expelled on a water bath, and the residue recrystallised from dilute sulphurous acid with the addition of animal charcoal. If preferred, the crude suspension of quinone obtained from 25 gms. of aniline (see p. 229) may be employed, being saturated with sulphur dioxide until it smells very strongly of the gas. After standing for 2 hours, if it still smells of the gas the liquid is extracted with ether, as above. If the odour of the gas has vanished, the liquid must be resaturated, and so on, until the smell persists for the 2 hours. H 2 C 6 H 4 0 2 > C 6 H 4 (OH) 2 . Yield. — 80% theoretical (8 gms.). Colourless prisms ; soluble in ether, alcohol, and warm water ; sublimes at a gentle heat ; M.P. 169°. (A., 27, 268 ; 45, 354 ; 215, 127 ; B., 19, 1467 ; 20, 2283.) Peepaeation 112. — Anthranol (y-Mono-hydroxy-anthraquinone). CH C 6 H 4 OH.K.CH : NK X > OH.R.CHO This method of preparing phenolic aldehydes has the advantage over Reimer's (pp. 98, 117) of not giving a mixture of isomers. The yields also are improved. Preparation 113. — Salicyl-aldehyde (l-Hydroxy-2-benzaldehyde). C 6 H 4 .(OH).(CHO)[l : 2], C 7 H 6 0 2 . 122. 20 gms. (1 mol.) of salicylic acid dissolved in hot water are neutralised with N/1 caustic soda, using phenolphthalein as indicator, and the solution diluted to 1 litre and boiled. 30 gms. (excess) of j9-toluidine are added, and the whole cooled and mechanically stirred. 400 gms. of sodium chloride and 30 gms. (excess) of boric acid are added gradually, and still with stirring 400 gms. (excess) of 2J% sodium amalgam (see p. 505), bhe solution being maintained faintly acid by the addition of boric acid (about 200 gms.) from time to time. The reaction is complete when a sample, after filtration and acidification with hydrochloric acid, gives no precipitate of salicylic acid. The condensation product of the aldehyde and base is filtered at the pump, suspended in 10% sulphuric acid, and distilled in steam. The aldehyde distils and is extracted from the dis- tillate with ether. The extract is dried over calcium chloride, the ether removed on a water bath, and the residue fractionated between 195° and 183 184 SYSTEMATIC ORGANIC CHEMISTEY 197°. The aldehyde may also be purified by means of its bisulphite com- pound (see Preparation 154). C 6 H 4 (OH)(COOH) + H, + (CH 3 )(C 6 H 4 )NH 2 -> C 6 H 4 (OH)CH : NC 6 H 4 CH 3 + 2H 2 0 C 6 H 4 (OH)CHO + H 2 N.C 6 H 4 .CH 3 . Yield. — 60% theoretical (8 gms.). Colourless crystals or liquid ; pungent odour ; soluble in water ; miscible in all proportions with alcohol and ether ; volatile in steam ; M.P. 20° ; B.P. 196-5° ; D 13 4 5 , 1-173. (B, 41, 4147.) Reaction LXV. (b) Reduction of Lactones to the corresponding Hydroxy-aldehydes by the action of Sodium Amalgam in faintly Acid Solution. (A., 270, 72, 87 ; 272, 200.)— This is a reaction very similar to the previous one. It finds an extensive application in the sugar group for reducing the lactones of the poly-hydroxy acids to the corresponding aldoses. Combined with the cyanhydrin reaction (see p. 150) it forms a means of passing from one group of sugars to the next higher group — thus : CH 2 OH I CHOH I CHOH I CHOH (!ho CHOH HCN CH 2 OH CHOH I CHOH I CHOH CH(OH)CN H„0 CH 2 OH I CHOH /CH / I CHOH I CHOH H, CHOH I CHOH CHOH I CHOH CHO Preparation ■ +). 114.— a-Gluco-heptose (Hexahydroxy-heptanol + + CHO I HCOH HCOH ! HOCH HCOH C 7 H 14 0 7 . 210. HCOH L _ THE LINKING OF HYDROGEN TO CARBON 185 15 gms. (1 mol.) of the lactone of a~gluco-heptonic acid (see p. 123) are dissolved in 150 c.cs. of water in a thick- walled 500-c.c. vessel, and are cooled in a freezing-mixture to 0° C. 2 c.cs. of 10% sulphuric acid are added, and the whole mechanically agitated, being meanwhile kept immersed in the freezing mixture. 125 gms. (excess) of 2-|% sodium amalgam (see p. 505) are added, and at intervals further 2-c.c. lots of 10% sulphuric acid, so that the liquid always remains acid. The tempera- ture must not be allowed to rise above 5°. In about 10 minutes the amalgam will be used up, a further 125 gms. are added, and the procedure of treating with acid repeated. The whole operation will take about 40 minutes. The solution is separated from the mercury and any unchanged lactone, and converted to the sodium salt by adding sodium hydroxide until the liquid remains alkaline after standing for 30 minutes. The solution is then exactly neutralised, at first with 5% and ultimately with N/1 sulphuric acid, brought to the boil with animal charcoal and filtered ; 8 volumes of hot alcohol are added with constant stirring, the whole left at room temperature for 12 hours, and sodium sulphate and most of the organic sodium salts present which are precipitated are filtered off at the pump. The filtrate is slowly concentrated until crystal- lisation begins, is cooled and after some hours filtered at the pump. The precipitate is washed first with 55%, then with 85%, and finally with absolute alcohol. / co CHO / I H 2 ! O (CH 2 OH) 2 L> (CHOH) 5 \ | I \CH CH 2°H (CHOH) 2 CHOH. Yield— 35% theoretical (5 gms.). Colourless crystals ; soluble in water ; M.P. 190° (M.P. ozazone 195°). (A., 270, 72, 87 ; 272, 200.) Reaction LXVI. (a) Reduction of Unsaturated Acids by means of Sodium Amalgam in Alkaline Solution. (A., 121, 375 ; 137, 237.)— The preparation below illustrates an important application of sodium amalgam, this substance being especially useful for reducing groups or double bonds in compounds containing carboxyl, as the alkali present both keeps the substance in solution and protects the acid group. Preparation 115.— Hydrocinnamic Acid (3-Phenyl-propan Acid). C 6 H 5 .CH 2 .CH 2 .COOH. C 9 H 10 O 2 . 150. 20 gms. (1 mol.) of cinnamic acid dissolved in a little more than the equivalent amount of caustic soda (145 c.cs. of N-solution) are placed in a stout-walled vessel fitted with a mechanical stirrer and 350 gms. (excess) of 2J% sodium amalgam (see p. 505) are added gradually with vigorous agitation in the course of 1 hour. When no more hydrogen is evolved, the mercury is separated, washed with water, the washings being added 186 SYSTEMATIC ORGANIC CHEMISTRY to the rest. The liquid is acidified with an excess of 20% hydrochloric acid ; on cooling an oil separates, which, on rubbing with a glass rod, solidifies ; it is filtered off at the pump, dried, and recrystallised from petroleum ether, or from warm water, crystallisation at a low temperature being necessary owing to the relatively low melting point of the substance. C 6 H 5 .CH : CH.COOH + H 2 = C 6 H 5 .CH 2 .CH 2 .COOH. Yield. — 85% theoretical (17 gms.). Colourless prisms ; insoluble in cold, somewhat soluble in warm water ; soluble in alcohol ; volatile in steam. M.P. 47° ; B.P. 280°. (A., 121, 375 ; 137, 237.) Reaction LXVI. (b) Reduction of Hydroxy Acids by the action of Hydriodic Acid. (A., 114, 106.) — Hydriodic acid is especially useful in reducing groups or ethylene linkages in acids as, although a powerful reducing agent, it does not readily attack the carboxyl group. It may be used either in a solvent, e.g., glacial acetic acid, or more usually the reaction is carried out by heating to a high temperature in a sealed tube. Red phosphorus is as usual added so that it may react with the iodine freed in the reduction to reform hydriodic acid ; in this way if sufficient phosphorus be present a small amount of hydriodic acid can reduce a large quantity of substance. R 1 E 2 C(OH)COOH + 2HI = K^CHCOOH + H 2 0 + I 2 . P + 31 = PI 3 . PI 3 + 3H 2 0 = P(OH) 3 + 3HI. Phosphorous Acid. Preparation 116. — Succinic Acid (Butan diacid). COOH.CH 2 .CH 2 .COOH. C 4 H 6 0 4 . 118. 10 gms. (1 mol.) of mafic acid are dissolved in 40 gms. (excess) of 57% (constant boiling mixture) hydriodic acid (see p. 502) and the solu- tion, together with 3 gms. of red phosphorus, heated in a sealed tube (see p. 38) in a tube furnace at 130° for 6 hours. When cool, the tube is opened (caution ! see p. 41), the contents evaporated to dryness on a water bath, and the cold residue extracted with small quantities of chloroform until no more free iodine is removed. The succinic acid is then heated at 70° to remove all traces of chloroform, and recrystallised from hot water. COOH.CHOHCH 2 .COOH + 2HI = COOH.CH 2 .CH 2 .COOH + H 2 0 + I 2 , Yield. — 60% theoretical (5 gms.). Colourless prisms ; soluble in water, alcohol and ether ; insoluble in chloroform ; M.P. 182°. (A., 114, 106.) Preparation 117. — Diphenyl Acetic Acid (Diphenylethan acid). (C 6 H 5 ) 2 CH.COOH. C 14 H 12 0 2 . 212. 20 gms. (1 mol.) of benzilic acid (see p. 105), 10 gms. of 57% hydriodic acid (constant boiling acid), 10 gms. of red phosphorus (excess of P + HI) and 120 gms. of glacial acetic acid are refluxed in a round-bottomed flask, in a fume chamber for 2 hours. The solution is filtered at the pump, THE LINKING OF HYDROGEN TO CARBON 187 poured while still hot into an excess of water, the precipitate filtered of! at the pump, washed with water and recrystallised from alcohol. (C 6 H 5 ) 2 C(OH)COOH + 2HI = (C 6 H 5 ) 2 CHCOOH + H 2 0 + I 2 . Yield. — 80% theoretical (14 gms.). Colourless crystals ; insoluble in cold alcohol ; M.P. 46°. (A., 275, 84.) Reaction LXVII. (a) Ketonic Hydrolysis of Alkyl Derivatives of Aceto-acetic Ester. (A., 138, 211.) — This reaction illustrates one of many synthetical uses of aceto-acetic ester. When that ester or its mono- or di- alkyl derivatives is boiled with dilute aqueous or alcoholic alkalis or baryta water, or sulphuric acid, " ketonic hydrolysis " occurs, and acetone or its mono- or di-substituted derivatives are formed — CHgCOCRjR] H CO 0 H -> CH3CO.CH.EjKn + C0 2 + C 2 H 5 OH. Compounds such as aceto-succinic ester and its derivatives which contain the aceto-acetic ester grouping, also undergo this hydrolysis. H— OH CH 3 CO.CH.COOC 2 H 2 H — O.H CH 3 CO.CH 2 CH 2 .COCH 3 + 2C0 2 + 2C 2 H 6 OH. Peeparation 118. — Methyl-Ethyl Ketone (2-Butanon). CH 3 .CO.C 2 H 5 . C 4 H 8 0. 72. 20 gms. (1 mol.) of methyl-aceto-acetic ester are refluxed with 250 c.cs. (excess) of saturated baryta until the oily layer disappears. The solution is then distilled on a water bath to 90° CL The distillate is mechanically shaken for 3 hours with a saturated solution of sodium bisulphite, and the crystals which separate filtered, well dried and dis- tilled with an excess of dilute sulphuric acid or sodium carbonate solution to 90°. The distillate is dried over calcium chloride and redistilled, the fraction 79° — 82° being retained. CH 3 COCH(CH 3 )COOC 2 H 5 + H 2 0 = CH 3 .COCH 2 CH 3 + C0 2 + C 2 H 5 OH. Yield. — 70% theoretical (7 gms.). Colourless mobile liquid ; pleasant odour ; miscible with water ; B.P. 81°. (A., 138, 211.) In an exactly similar way acetone (B.P. 56°) can be prepared from aceto-acetic ester (see p. 143) ; methyl-propyl ketone (B.P. 102°) from monoethyl acetoacetic ester (see p. 135). The higher ketones may be purified by washing with saturated brine until alcohol is removed ; they are then, after drying over calcium chloride, fractionated. In all these hydrolyses dilute aqueous or alcoholic potash, or dilute sulphuric acid, may be used in place of baryta water. The yields in these preparations are all of the same order — 70%. 188 SYSTEMATIC ORGANIC CHEMISTRY Preparation 119. — Acetonyl Acetone (2 : 5-Hexandion). CH 3 COCH 2 .CH 2 .COCH 3 . C 6 H 10 O 2 . 114. 20 gms. (1 mol.) of di-aceto-succinic ester (see p. 145) are mechanically shaken for several days with 250 c.cs. (excess) of 5% aqueous caustic soda, and until no di-aceto-succinic ester separates on acidification of a sample with dilute hydrochloric acid. The solution is then saturated with potassium carbonate and extracted with ether, the extract is washed with brine to remove alcohol, dried over calcium chloride, and distilled, the fraction 192° — 198° being retained. CH 3 COCH.COOC 2 H 5 I + 2H 2 0 = CH 3 COCH.COOC 2 H 5 CH 3 COCH 2 .CH 2 COCH 3 + 2C0 2 + 2C 2 H 5 OH. Yield. — 70% theoretical (6 gms.). Colourless liquid ; agreeable odour ; miscible with water, alcohol and ether; M.P. —9°; B.P. 194°; D. 2 4 ° 0-973. (B., 18, 58 ; 33, 1217.) Reaction LXVH. (6) Acid Hydrolysis of Alkyl Derivatives of Aceto- acetic Ester. (B., 19, 227.) — When acetoacetic ester or its mono- or di-alkyl derivatives are refluxed with concentrated aqueous or alcoholic potash, acid hydrolysis occurs and 2 mols. of acetic acid, or 1 mol. of that acid, and 1 mol. of a mono- or di-substituted derivative are obtained. CH 3 CO— CRiKuCOOC.Hg -> CH 3 COOH + HCRiRnCOOH. HO II It is not possible to perform the acid hydrolysis without some ketonic hydrolysis occurring. This reaction and the preceding one are important in many syntheses of aliphatic ketones and acids. They might have equally well been included in the decomposition section (p. 403) ; in fact they are often referred to as the " ketonic " and " acid " decomposition of acetoacetic ester. The malonic ester synthesis of fatty acids may be compared with the present reaction. Preparation 120. — Methyl-ethyl Acetic Acid (2-Methyl-butan acid). HC(CH 3 )(C 2 H 5 )COOH. C 5 H 10 O 2 . 102. 20 gms. (1 mol.) of methyl ethyl aceto-acetic ester are refluxed for 4 hours with 40 gms. (excess) of caustic potash dissolved in 15 gms. of 50% alcohol. The mixture is poured into 250 c.cs. of water and acidified after extraction with ether to remove unchanged ester and methyl-^o-butyl ketone, a by-product formed as in the previous reaction. The acid which precipitates as an oil is extracted with ether, the extract dried over calcium chloride, and distilled, the fraction 172° — 178° being retained. CH 3 .CO.C(CH 3 )(C 2 H 5 )COOC 2 H 5 + 2H 2 0 = CH 3 .COOH + CH(CH 3 )(C 2 H 5 )COOH + C 2 H 5 OH. Yield. — 60% theoretical (11 gms.). Colourless liquid ; optically active ; B.P. 175°. (B., 19, 227.) THE LINKING OF HYDKOGEN TO CARBON 189 In an exactly similar way the esters shown in the following table yield the corresponding acids. Ester. Corresponding Acid. B.P. Acetoacetic ester ...... Acetic acid . 119° Methyl acetoacetic ester . . . Propionic acid . 141° Ethyl acetoacetic ester ..... Butyric acid . 162° Dimethyl acetoacetic ester .... Zsobutyric acid . 154° Diethyl acetoacetic ester . . . . isocaproic acid . 190° The higher acids need not be extracted from the acidified reaction product with ether, but may be separated directly as they are only very slightly soluble in water. CHAPTER XII hydrogen to carbon Halogen Compounds Only two reactions are of sufficient importance to be considered here. Reaction LXVIIL Simultaneous reduction and Halogenation of Poly- hydric Alcohols. (A., 138, 364.)— When polyhydric alcohols are heated with hydriodic acid, reduction of all the hydroxyl groups save one occurs, this latter is replaced by iodine to form a secondary iodide. In this way, e.g., dulcitol, or any of the hexose alcohols, yields normal secondary hexyl iodide ; this is of importance in determining the chain structure of the sugars. This reaction probably occurs — CH 2 OH CH 2 I HI (CHOH) 4 (CHI) 4 CH 2 OH 1 CH 2 I. CH 3 1 HI CHI 1 (CH 2 ) 3 I CH 3 . The primary iodide is never formed in such reactions. Preparation 121. — Isopropyl Iodide (2-Iodo-propan). CH 3 .CHICH 3 . C 3 H 7 I. 170. 70 gms. (excess) of iodine, 45 gms. (excess) of glycerol, and 30 gms. (excess) of water are placed in a 250-c.c. retort connected with a condenser and receiver and placed in a fume chamber. 10 gms. (5 atoms) of yellow phosphorus (caution !) are added gradually in small pieces, the phosphorus being cut under water, and transferred to the retort with crucible tongs. The violent reaction which usually occurs on adding the phosphorus must be allowed to subside before any more is added. Should no reaction take place on adding the first three pieces of phosphorus the retort is immersed in warm water until interaction commences. When the addition of the phosphorus is complete the retort is heated on a wire gauze until no further oily liquid distils. The distillate is replaced in the retort and redistilled, washed in turn with 10% caustic soda, with sodium thio- 190 THE LINKING OF HYDROGEN TO CARBON 191 sulphate, again with 10% caustic soda and with water ; it is dried over calcium chloride for 24 hours and fractionated between 88° — 90°. 5P + 151 = 5PI a . 5PI 3 + 15H 2 0 = 15HI + 5P(OH) 3 , CH 2 OH CH 2 I /N i t n n i l crTJ T \j 11 C 6 H 3 S0 3 N a (/3) > C 6 H 4 < >C 6 H 2 (OH) 2 [a,/3]. Alizarin. (See p. 384.) Preparation 123. — Triphenyl Carbinol (Triphenyl-methanol). (C 6 H 5 ) 3 C(OH). C 19 H 16 0. 260. 12 gms. (1 mol.) of triphenylmethane dissolved in 60 gms. of glacial acetic acid are treated gradually in the warm with 12 gms. (excess) of chromic acid. Gentle heating is continued until a sample poured into water gives a precipitate which does not melt below 100° (1 — 2 hours). The whole is then poured into water and the precipitate filtered, washed with water, dried on a water bath, and recrystallised from benzene. (C 6 H 5 ) 3 CH + O = (C 6 H 5 ) 3 C(OH). Yield. — 85% theoretical (11 gms,). Colourless crystals ; soluble in hot benzene and glacial acetic acid ; M.P. 158°. (B., 14, 1944.) s.o.c. 193 o 194 SYSTEMATIC ORGANIC CHEMISTRY Reaction LXXI. Replacement of Halogen by Hydroxyl. (B., 14, 2394 ; - 16, 2954 ; 25, 3290 ; J. pr., 11, 229 ; A. Ch., [3], 55, 400.)— When alkyl halides are refluxed with dilute caustic alkali or alkali carbonate, hydroxyla- tion smoothly occurs. If the halide be tertiary the replacement takes place with great ease, warming with water being sufficient ; a secondary halide reacts less readily, but more so than a primary. Aryl halides are replaced with great difficulty unless there be present negative sub- stituents in the ortho- or ^ara-positions when the halogen behaves as if it were attached to an alkyl. 2C 6 H 3 C1(N0 2 ) 2 [1 : 2 : 41 ■+ K 2 C0 3 + H 2 0 = 2C 6 H 3 (OH)(N0 2 ) 2 [l : 2 : 4] + C0 2 + 2KC1. Water can always be used to bring about the hydroxylation if the heating be carried out under pressure. It is to be noted that this reaction could also have been discussed under the hydrolysis of esters (p. 234). Peepaeation 124. — Benzyl Alcohol (Phenyl-methanol). C 6 H 5 .CH 2 OH. C 7 H 8 0. 108. 10 gms. (1 mol.) of benzyl chloride are refluxed with 10 gms. (excess) of potassium carbonate in 100 c.cs. of water until the smell of benzyl chloride has disappeared (6 hours). The liquid is extracted with ether, the extract dehydrated by standing 8 hours over anhydrous potassium carbonate, filtered into a small distilling flask, and the ether removed on a water bath. Distillation is continued with an air condenser over wire gauze, the fraction 200° — 210° being collected separately. 2C 6 H 5 CH 2 C1 + K 2 C0 3 + H 2 0 = 2C 6 H 5 CH 2 OH + 2KC1 + C0 2 . Yield. — 70% theoretical (7 gms.). Colourless liquid; aromatic odour; somewhat soluble in water ; miscible in all proportions with alcohol and ether ; B.P. 206-5° ; D. J 1-0628 ; D. 15 4 4 1-05. (B., 25, 3290.) In a similar manner, by refluxing ethyl chloride with excess of 10% caustic soda and subsequent distillation ethyl alcohol is obtained. The use of water in the hydroxylation of compounds containing a mobile halogen atom is illustrated in the following two preparations. Peepaeation 125. — m-Chloro-^-hydroxy-benzyl Alcohol ( ( (3-chlor-4- hydroxy-benzyl)-l)-methanol). CH 2 OH C 7 H 7 0 2 C1. 158-5. \/Cl OH 10 gms. (1 mol.) of 3-chlor-4-hydroxy-benzyl chloride are refluxed for 1 hour with 100 c.cs. of water. The cooled mixture is extracted with ether, the ether removed on a water bath and the oil which remains scratched with a glass rod until it crystallises. The crystals are pressed on a porous plate and recrystallised from benzene. THE LINKING OF OXYGEN TO CARBON 195 C 6 H 3 (CH 2 C1)(C1)(0H)[1 : 3 : 4] + H 2 0 = C 6 H 3 (CH 2 OH)(Cl)(OH)[l : 3 : 4] + HCL Colourless needles ; insoluble in water, soluble in hot benzene and in ether ; M.P. 123°. (B., 34, 2459.) It will be observed that the nuclear halogen atom in the above com- pound is not replaced in the reaction. Peepaeatton 126. — Glycollic Acid (2-Ethanol Acid). CH 2 (OH)COOH. C 2 H 4 0 3 . 76. 20 gms. (1 mol.) of potassium chloracetate or potassium bromacetate are dissolved in 80 c.cs. (excess) of water, and the solution exactly neutralised, with sodium carbonate solution, and refluxed for 16 hours — porcelain chips being added to prevent bumping. It is cooled and concentrated to half its bulk under reduced pressure. The potassium halide which has separated is filtered off, and the nitrate evaporated to dryness under reduced pressure. The residue is extracted in a reflux apparatus with 50 c.cs. of boiling acetone and the extract evaporated to dryness on a bath kept at 65°. CH 2 Cl.COOK + H 2 0 = CH 2 (OH)COOH + KC1. Yield. — 80% theoretical (13 gms.). Colourless deliquescent crystals ; soluble in water and in acetone ; M.P. 80° ; K = 0-0152. The presence £>f the carboxyl group renders halogen atoms attached to the a-carbon labile and easily replaceable. The above compound can also be prepared by boiling chloracetic acid with an aqueous suspension of chalk (B., 16, 2954). Peepakation 127. — Ethylene Glycol (1 : 2-Ethandiol). CH 2 OH. C 2 H e0 2 . 62. By-product : (1:2: 2-Tribromethan). CH 2 Br C 2 H 3 Br 3 . 267. CHBr 2 . Method I. — 9-4 gms. (1 mol.) of ethylene dibromide (see p. 332) are refluxed with 6-9 gms. (1 mol.) of pure potassium carbonate dissolved in 50 c.cs. of water. From the top of the reflux condenser a glass tube is led to a couple of wash bottles containing bromine. Some porcelain chips are added to the mixture to facilitate ebullition. When all the oily drops have disappeared (8 — 10 hours) the same quantities of ethylene dibromide and potassium carbonate are added to the solution, and the boiling con- tinued as before. The operation is prolonged until 564 gms. of ethylene dibromide have been decomposed. After the third addition of ethylene dibromide, crystals of potassium bromide separate out on standing over- night. These, and those which separate out after each succeeding opera- tion, are removed by filtration at the pump before the action is re- started. The crystals are then washed with absolute alcohol, the washings being subsequently used for the isolation of glycol (see p. 196). After o 2 196 SYSTEMATIC ORGANIC CHEMISTRY decomposition of the ethylene dibromide is complete, the solution of glycol is heated on a water bath at 50° under reduced pressure in the apparatus shown on p. 27, so as slowly to distil off the water. When the distillation has continued for some time, the liquid begins to bump violently, owing to the separation of potassium bromide. The solution is cooled, the crystals of potassium bromide removed as before, and the distillation con- tinued. When the solution becomes very viscid, and the temperature of the vapour passing over begins to rise, the distillation is stopped, and the residue is mixed with the alcohol used for washing the potassium bromide crystals, as explained above. After standing for some time, the crystals of potassium bromide which separate in quantity are removed by filtration at the pump, washed with absolute alcohol, and the combined alcoholic extracts concentrated by slow distillation as before from a flask fitted with a column. The residue is treated with absolute alcohol which separates more potassium bromide ; this treatment is repeated, using a mixture of alcohol and ether, until all the potassium bromide has been removed. The solvent is removed by evaporation as above, and the residual glycol twice fractionated, at first under reduced pressure (see B.P. table below), and finally at the ordinary pressure. CH 9 Br CH 2 .OH CELBr K 2 C0 3 + H 2 0 2KBr CH..OH Yield. — 50% theoretical (10 gms.). Colourless viscid liquid ; sweet taste ; blue in thick layers in transmitted light ; miscible with water in all proportions; D. 2 4 ° 1'134. Following is a table of boiling points at various pressures :— Pressure mms. 764-5 760-0 544-0 357-0 101-0 83-0 44-0 B.P. 0 197— 197 186-5 173 143-8 136-7 122-5 197-5 corrected. Isolation of By-product. — During the reaction, vinyl bromide (CH 2 : CHBr) is formed. It volatilises and is absorbed by the bromine in the wash bottles. The product is washed with dilute caustic soda until excess bromine is removed ; on fractionating, tribromethane is obtained (B.P. 187°). CH 2 Br I CH 2 Br CH 2 ji CHBr CH. CHBr HBr. Br, CHBr 2 . (J. C. S., 69, 176 ; J. pr., 11, 229 ; A., 192, 257 ; C, (1907), 1, 1314.) The above method is necessary where a good yield of glycol is required. THE LINKING OF OXYGEN TO CARBON 197 If yield be not a pressing consideration, the process may be shortened by refluxing all the materials together from the beginning, evaporating at 80° under reduced pressure until little more distils ; extracting the residue twice with absolute alcohol ; removing the alcohol under reduced pressure and fractionating the product. Both these methods suffer from the difficulty of separating glycol from a large excess of water without loss. There is, however, a second method available for replacing halogen by hydroxyl. It consists in preparing an ester of the desired alcohol by heating the halide with certain salts — silver, potassium, or sodium acetates — and saponifying the ester so formed. CH 2 Br CH 2 .OOCCH 3 I + 2CH 3 COOK = j + 2KBr CH 2 Br CH 2 .OOCCH 3 . For saponification, the ester is usually treated with hydrochloric acid dissolved in anhydrous methyl alcohol. CH 2 .OOC.CH 3 CH 2 OH j + 2HC1 = I + 2CH3COCJ. CH 2 .OOC.CH 3 CH 2 OH The acetyl chloride reacts with the methyl alcohol forming methyl acetate and a fresh quantity of hydrochloric acid. CH 3 COCl + CH 3 OH = CH 3 COOCH 3 + HC1. This method has a wide application, but it is especially useful for the preparation of glycol. Method II. — 200 gms. of pure potassium acetate are fused in a shallow dish, as described on p. 506, except that, unlike sodium acetate, the crystals contain no water of crystallisation, and only melt once. The solidified salt is finely powdered, and while still warm, placed in a desiccator. 60 gms. (1 mol.) of ethylene dibromide (see p. 332), 20 gms. (excess) of glacial acetic acid, and 60 gms. (excess) of freshly fused, finely powdered potassium acetate are refluxed in a 500-c.c. flask for 2 hours, and the reaction product distilled, using a condenser. The distillate is again treated with 60 gms. (1 mol.) of ethylene dibromide, and 80 gms. (excess) of freshly fused, finely powdered potassium acetate, refluxed for 3 hours as before, and again distilled, using a good fractionating' column (see p. 21), the fractions (1) 140°, (2) 140°— 175°, (3) above 175°, being collected separately. The last two fractions are redistilled, the fraction 180° — 190° being retained. The portion under 180° is again treated with 80 gms. of potassium acetate, refluxed and distilled as before. The total yield of glycol diacetate is about 90% theoretical (88 gms.). It boils at 180°. 40 gms. (excess) of pure anhydrous methyl alcohol (see p. 206) are cooled in water, and gaseous hydrogen chloride (see p. 502) led in until an increase in weight of 1 gm. has been- obtained. Should a greater increase be found, the required 2J% solution is obtained by adding the requisite quantity of pure anhydrous methyl alcohol. The 41 gms. of 198 SYSTEMATIC ORGANIC CHEMISTRY 2-5% alcoholic hydrogen chloride is refluxed with 50 gms. (1 mol.) of glycol diacetate on a water bath for 30 minutes, and the reaction mixture immediately distilled from the same bath. Methyl alcohol and methyl acetate are thus removed, the residue consisting of glycol and a small quantity of its acetate, two substances the boiling points of which lie close together. They are separated by extraction with an equal volume of dry ether, glycol remaining undissolved. It is removed and fractionated, the temperature being slowly raised to 100°C. The fraction 192° — 198° is redistilled. CH 2 Br CH,.O.COCH 3 CH 2 Br + 2CH 8 COOK = CH ;o.COCH 3 + 2KBr ' CH 2 OCOCH 3 CH 2 OH I + 2HC1 + 2CH3OH = I + 2CH3COOCH3 + 2HC1. CH 2 OCOCH 3 CH 2 OH Yield. — 85% theoretical (18 gms.) on the glycol diacetate taken ; 75% theoretical on the ethylene dibromide originally taken (24 per 10 of ethylene dibromide). (Cf. yield by Method I. See p. 196.) (Gattermann, " Practical Methods of Organic Chemistry," p. 196, Third American Edition.) The next preparation illustrates the activating effect of aromatic nitro groups on nuclear halogen atoms in the 0- and ^-positions. Prepaeation 128. — 2-4-Dinitrophenol (2-4-Dinitro-l-hydroxy-benzene). OH.C 6 H 3 (N0 2 ) 2 [l : 2 : 4]. C 6 H 4 0 5 N 2 . 184. 10 gms. (1 mol.) of chloro-di-nitro-benzene [1 : 2 : 4] are refluxed with 15 gms. (excess) of anhydrous sodium carbonate and 150 c.cs. of water until solution has occurred, cooled and acidified with dilute hydrochloric acid ; the precipitate is filtered, washed, and dried on a porous plate. 2C1.C 6 H 3 (N0 2 ) 2 [1 : 2 : 4] + Na 2 C0 3 + H 2 0 = 20H.C 6 H 3 (N0 2 ) 2 [1 : 2 : 4] + 2NaCl + C0 2 . Yield. — 90% theoretical (8 gms.). Colourless crystals ; insoluble in water ; M.P. 114°. (Z. Ch. (1870), 232.) Reaction LXXIL Replacement of the Diazo Group by Hydroxyl. (B., 22, 335 ; 23, 3705 ; 24, 1960 ; J. pr., 14, 451 ; A., 137, 39 ; D.R.P., 167211.) — -This is a reaction of great importance in the aromatic series, both in the laboratory and on a manufacturing scale. When diazonium salts, especially the sulphate, are boiled with water or acids, nitrogen is evolved, and the phenol corresponding to the diazonium compound is formed. It is not necessary to isolate the diazonium salt, the solution prepared in the usual way from the amine is boiled or slowly added to boiling dilute sulphuric acid, or an aqueous solution of sodium nitrite may be added to a boiling solution of the amine in dilute sulphuric acid. The use of the diazonium nitrate is to be avoided, as simultaneous nitration usually occurs. The reaction can be applied to substituted amines, amino-acids, amino-halogen compounds, etc., but the yields are often poor, especially with the amino-phenols ; they may be improved to some extent THE LINKING OF OXYGEN TO CARBON 199 by the use of copper sulphate solution. Although the method is of practical importance only in the aromatic series, since aliphatic diazo-com- pounds are not formed except at very low temperatures, yet aliphatic hydroxy compounds are readily obtained by the action of aqueous sodium nitrite solution on acid solutions of the primary amines. This reaction should be compared with the formation of ethers as a by-product in the reduction of diazo compounds with alcohol (Reaction, p. 369). C 6 H 5 .N 2 .S0 4 H + H 2 0 = C 6 H 5 OH + N 2 + H 2 S0 4 . Preparation 129. — Phenol (Hydroxybenzene). C 6 H 5 .OH. C 6 H 6 0. 94. 20 gms. (1 mol.) of freshly-distilled aniline are dissolved by gentle warming in 150 gms. of 30% sulphuric acid, and the cooled liquid treated with a 20% solution of sodium nitrite until a sample colours starch-iodide paper (see p. 501) ; some 16 gms. of NaN0 2 will be required. The whole is kept at 50° for an hour, steam distilled until no more phenol distils (this is shown by a sample of the distillate giving no precipitate with bromine water), the distillate is saturated with salt, extracted several times with ether until nothing more is removed, and the extract dried for 24 hours over fused sodium sulphate. The ether is removed on a water bath and the residue distilled, the fraction 175° — 185° being retained. H 2 S0 4 + NaNOo H 2 0 C 6 H 5 NH 2 > C 6 H 5 .N 2 .S0 4 H > C 6 H 5 OH. Yield. — 35% theoretical (7 gms.). Colourless needles ; characteristic odour ; somewhat soluble in water ; soluble in alcohol and ether ; M.P. 42° ; B.P. 182°. (B., 23, 3705 ; A., 137, 39 ; J. pr., 14, 451.) If the residue in the flask after the steam distillation be filtered hot, and cooled, crystals of j9-hydroxy-di-phenyl separate. It is formed by the coupling of a portion of the phenol first formed with undecomposed diazo compound. C 6 H 5 .N 2 .S0 4 H + H.C 6 H 4 OH = C 6 H 4 .C e H 3 OH + H 2 S0 4 + N 2 . (Cf. p. 369.) _ The yield is low owing to the heating with the mineral acid tending to cause resinification of the phenol. It has been suggested to avoid this to heat with a weak acid, e.g., boric acid, but no great improvement in the yield is obtained. In an exactly similar manner from 20 gms. of o- m- or ;p-toluidme, the o-, m-, or j?-cresols respectively are prepared (see also p. 369) ; for these it is better to use only 10% sulphuric acid, a quantity being taken equivalent to the 30% acid employed above. The yields are of the order of 50% (12-5 gms.). The melting and boiling points of the cresols are : M.P. BP. o-Cresol . . . . 31° . 191° m-Cresol. ... — . 202° ^-Cresol. ' . . . 36° . . 202° 200 SYSTEMATIC ORGANIC CHEMISTRY The method is often important in the preparation of hydroxy derivatives of compounds the groups in which render them difficult to prepare by more direct means. m-Hydroxybenzoic acid is such a compound. It is obtained by nitration of benzoic acid followed by reduction to m-amino benzoic acid and application of the present reaction (see below). Peepaeation 130. — m-Hydroxybenzoic Acid (l-Hydroxy-3-carboxy- benzene). C 6 H 4 (OH)(COOH)[l : 3]. C 7 H 6 0 3 . 138. 10 gms. (1 mol.) of m-amino benzoic acid hydrochloride are dissolved in 100 c.cs. of water (or 8 gms. of the free acid are dissolved in 200 c.cs. of 2% hydrochloric acid) and a 30% aqueous solution of 5 gms. (excess) of sodium nitrite slowly added. The whole is warmed until nitrogen ceases to be evolved, filtered at the pump and evaporated until, on cooling, crude m-hydroxybenzoic acid separates as a brown mass. It is purified by recrystallisation from water with addition of animal charcoal. HN0 2 C 6 H 4 (NH 2 )(COOH)[l : 3] - > C 6 H 4 (OH)(COOH)[l : 3]. Yield. — 60% theoretical (7 gms.). Colourless crystals ; soluble in hot water ; M.P. 200°. (A., 91, 189.) Di-amino compounds can also be made to yield di-hydroxy compounds in this way. Peepaeation 131. — ^-^-Dihydroxy-diphenyl (4 : 4 / -Dihydroxy-l : V- diphenyl). [4jOH.C6H4.C6H4.OHt4']. C 12 H 10 O 2 . 186. 50 gms. (1 mol.) of benzidine (see p. 356) are dissolved in 900 c.cs. (2 mols.) of 2% hydrochloric acid, and 5 litres (excess) of 5% sulphuric acid added. The solution is diazotised, as described on p. 366, with 20% aqueous sodium nitrite. About 40 gms. of sodium nitrite will be required. Steam is passed into the solution for 30 minutes, and until a sample gives no precipitate with an alkaline solution of phenol. The diphenyl derivative crystallises on cooling the solution, which is first filtered hot. HN0 2 + H 2 S0 4 [4]NH 2 .C 6 H 4 .C 6 H 4 .NH 2 [4'] > [4]OH.C 6 H 4 .C 6 H 4 OH.[4']. Yield. — 75% theoretical (37 gms.). Colourless needles ; soluble in hot water ; M.P. 272°. (B., 22, 335.) The next preparation illustrates the use of copper sulphate solution. Peepaeation 132. — Quinol (1 : 4-Dihydroxybenzene). C 6 H 4 (OH) 2 [l : 4]. C 6 H 6 0 2 . 110. 30 gms. (1 mol.) of j9-aminophenol are diazotised, as described on p. 365, and the diazo-solution slowly added to 400 gms. of a boiling 25% copper sulphate solution. When the evolution of nitrogen ceases the solution is cooled and extracted with ether until nothing further is removed. The ether is evaporated on a water bath, and the residue recrystallised from dilute sulphuric acid with the addition of a little animal charcoal. THE LINKING OF OXYGEN TO CARBON 201 HN0 2 C 6 H d (OH)(NH 2 )[l : 4] - > C 6 H 4 (OH) 2 [l : 4j. Yield. — 30% theoretical (9 gms.). Colourless prisms ; soluble in hot water, in ether, and in alcohol ; M.P. 169° ; sublimes at a moderate heat. (D.R.P., 167211.) o-, m- and j9-cresols (see p. 199) are obtained from the corresponding toluidines in an exactly similar way. Catechol (o-dihydroxybenzene, M.P. 104° ; B.P. 245°) is prepared in the same manner from o-aminophenol, a 10% solution of copper sulphate being employed. Below is illustrated the effect of boiling a diazonium nitrate with water (p. 369). Preparation 133. — m-Nitro-^-Hydroxy Toluene (l-Methyl-4-hydroxy- 3-nitrobenzene). C 6 H 3 (CH 3 )(OH)(N0 2 )[l : 4 : 3J. C 7 H 7 0 3 N. 153. 50 gms. (1 mol.) of finely powdered ^>-toluidine are dissolved in 500 gms. (excess) of warm 10% nitric acid (D = 1-06), and the solution diazotised at 0°, as described on p. 366, a 30% aqueous solution of 30 gms. of sodium nitrite being added until the solution colours starch iodide paper ; on no account must the temperature rise above 8°. After standing for 3 hours at 0°, 50 c.cs. of the solution are slowly heated in a litre round flask in an oil bath under a long reflux condenser until ebullition occurs and inter- action commences. When the reaction is complete the remainder of the diazo-solution is slowly added, then the boiling is continued for 10 minutes, and the solution steam distilled until no further oil comes over. The solid nitro-cresol is filtered from the distillate, well washed with water, and purified by precipitation from an alkaline solution of its sodium salt, using dilute hydrochloric acid. HN0 2 C 6 H 4 (CH 3 )(NH 2 )[1 : 4] > C 6 H 3 (CH 3 )(OH)(N0 2 )[l : 4 : 3]. HN0 3 Yield. — 60% theoretical (40 gms.). Yellowish crystals ; insoluble in water ; M.P. 36-5°. (B., 24, 1960.) Reaction L XXIII. Direct Replacement of the Aromatic Amino-group by Hydroxyl. (B., 7, 77, 809; D.K.P., 109102.)— The simple primary amino groups in the benzene series are not easily replaced directly by hydroxyl unless an activating group (e.g., N0 2 ) be present in the o- or ^-positions. a-Naphthols, however, are readily obtained by heating a-naphthylamine derivatives with fairly concentrated acid under pressure. C 10 H 7 NH 2 + H 2 0 = C 10 H 7 OH + NH 3 . (This reaction can be reversed, see p. 295.) It can be accomplished more readily by heating with sodium bisulphite solution, an unstable naphthol-sulphite being an intermediate product, ^-compounds also react. C 10 N 7 NH 2 + H 2 S0 3 = C 10 H 7 O.SO 2 H + NH 3 . C 10 H 7 O.SO 2 H 4- H 2 0 = C 10 H 7 OH + H 2 0 + S0 2 . This reaction is of technical importance, being applied to the prepara- tion of some hydroxy-sulphonic acids. 202 SYSTEMATIC ORGANIC CHEMISTRY With ^-nitroso-secondary and tertiary bases the alkyl amino group can readily be replaced by boiling with dilute alkali. This method, too, is illustrated below. Preparation 134. — cc-Naphthol (1-Hydroxy-naphthalene). OH | | | C 10 H 8 O. 144. 150 gms. (1 mol.) of a-naphthylamine (see p. 352) are heated, with 120 gms. (excess) of cone, sulphuric acid and 1 litre of water, to 200° for 8 hours at 14 atmospheres in an enamelled autoclave (see p. 42), fitted with a stirrer. On cooling, the autoclave is opened and a-naphthol filtered off, washed, and recrystallised from water, or distilled preferably under reduced pressure. NH 2 OH Yield. — 95% theoretical (140 gms.). Colourless crystals ; character- istic odour ; sparingly soluble in water ; M.P. 94° ; B.P. 280° ; is an important intermediate for dyestuffs. (D.R.P., 76545.) Prepaeation 135.— Nevile and Winther's Acid (l-Hydroxy-4-Naphtha- lene-sulphonic Acid). OH C 10 H 8 O 4 S. 224. SO.H-. 100 gms. (1 mol.) of naphthionic acid (100%) (or the equivalent of sodium naphthionate), dissolved in 200 c.cs. of water are refluxed for 24 hours with 600 gms. (excess) of sodium bisulphite solution (25% S0 2 ). 30% caustic soda solution is added until the solution is alkaline to phenolphthalein, and the whole boiled until no more ammonia is evolved. Hydrochloric acid is then added until the product is permanently acid. The Nevile and Winther's acid crystallises on cooling. It is separated from unchanged naphthionic acid by recrystallisation from warm water. It may be obtained as its sodium salt by neutralising the warm solution with caustic soda, and saturating with common salt. XI 1 2 OH SO3H S0 3 H. Yield. — 80% theoretical (80 gms.). Colourless crystals ; soluble in hot water ; decomposes on heating ; important intermediate for azo dyestuffs. (B., 24, 3157 ; 27, 3458 ; A., 273, 102 ; D.R.P., 109102.) THE LINKING OF OXYGEN TO CARBON 203 Preparation 136. — ^>-Nitroso-Phenol (l-Hydroxy-4-nitroso-benzene). C 6 H 4 (OH)(NO)[l : 4]. C 6 H 5 0 2 N. 123. 5 gms. (1 mol.) of ^-nitroso-di-methylaniline hydrochloride (see p. 278) are added gradually to 250 gms. (excess) of boiling 2J% caustic soda solution in a flask fitted with a reflux condenser, the free base which separates as an oil, being allowed each time to dissolve before the next addition. The boiling is continued after complete addition until the solution has become reddish-yellow. When cold, the liquid is acidified and extracted with ether, and the latter removed on a water bath. The residual nitroso-phenol is redissolved in a little boiling water, and after filtration and cooling it is again extracted with ether and recovered by evaporation of the ether. NO.C 6 H 4 .N(CH 3 ) 2 ri : 4] + H 2 0 = NO.C 6 H 4 OH + NH(CH 3 ) 2 . NOC 6 H 4 OH ^ZZ^ HON.C 6 H 4 : 0. Yield. — 90% theoretical (2-5 gms.). Colourless rhombic crystals ; soluble in water, and in ether ; M.P. 125°. (B., 7, 809.) This reaction is frequently applied to the preparation of dialkylamines. The dimethylamine evolved in the above reaction may be absorbed by leading through hydrochloric acid ; from the latter solution the hydro- chloride is obtained by evaporation. ^>-Nitroso-phenol, it is to be noted, is tautomeric, in some reactions behaving as quinone monoxime. Reaction LXXIV. Action of Mineral Acids on Phenylhydroxylamine. (B., 26, 1844, 2810 ; 27, 1927 ; 20, 3040.)— In the presence of mineral acids phenylhydroxylamine undergoes rearrangement to form p-amino- phenol. C 6 H 5 NH.OH -> OH.C 6 H 4 NH 2 . This isomerisation explains the course of the electrolytic reduction of aromatic nitro compounds (see p. 392) also the oxidation of aniline to quinone (see p. 229). Preparation 137. — £>-Amino-phenol ( l-Hydroxy-4- amino -benzene ) . C e H 4 (OH)(NH 2 )[l : 4]. -> C 6 H 7 ON. 109. 5 gms. (1 mol.) of phenylhydroxylamine (see p. 203) are slowly added to 100 c.cs. of 50% sulphuric acid, cooled in a freezing mixture, 500 c.cs. of water poured in, and the whole boiled until a sample, tested with chromic acid solution, gives a smell of quinone and no smell of nitro- benzene. The liquid is neutralised with sodium bicarbonate, saturated with common salt, and extracted with ether. The ether is removed by evaporation, and the residue washed with cold water and dissolved in hot water. The solution is filtered hot, and cooled, and the ^>-amino- phenol again extracted with ether. C 6 H 5 NHOH -> OH.C 6 H 4 .NH 2 . Yield. — Almost theoretical (5 gms.). Colourless crystals ; somewhat soluble in water ; M.P. 185°. (B., 26, 1844, 2810 ; 27, 1927 ; 29, 3040.) Reaction LXXV. — Fusion of Aromatic Sulphonic Acids with Caustic Alkalis. (Z. Ch. (1876), 3, 299 ; J. pr., [2], 17, 394 ; 20, 300.)— This method 204 SYSTEMATIC ORGANIC CHEMISTRY is of technical importance as it is employed to prepare various phenols and naphthols from the parent hydrocarbons via the corresponding sulphonic acids ; these phenols and naphthols are much used as intermediates in the dye industry. The method is also employed in the laboratory, but only as a preparative method ; it cannot easily be applied to determine structure, owing to rearrangement being liable to occur at the elevated temperatures used. Caustic potash is more convenient than soda, as simultaneous interaction with atmospheric oxygen is then less liable to occur, and also since it yields generally a more easily fusible mixture. A suitable apparatus for laboratory fusions is shown in Fig. 50. Preparation 138. — Phenol (Hydroxybenzene). C«H s OH. 94. 35 gms. (excess) of caustic potash are warmed with 5 c.cs. of water in an iron or nickel basin (for another suitable reaction vessel, see below). 20 gms. (1 mol.) of finely powdered potassium benzene sulphonate are added, and stirred in with a thermometer, protected by a glass or iron tube (Fig. 50). The temperature is brought to 250°, and kept at this point for 1 hour : it must not be allowed to exceed it. The cold melt is dissolved in the minimum quantity of water, and the solution carefully acidified under good cooling with cone, hydrochloric acid. It is repeatedly extracted with ether, until nothing further is removed, the extract is dried for 24 hours over anhydrous sodium sulphate, the ether removed on a water bath, and the residue fractionated at 175° — 185°. K 2 S0 3 - C 6 H 5 OH + KC1. H,0. C 6 H 5 OK + HC1 Yield. — 70% theoretical (65 gms.). Colourless needles ; characteristic odour ; somewhat soluble in water : soluble in alcohol and ether : M.P. 42° ; B.P. 182 s . (Z. Ch. (1867) 3, 299 ; J. pr., [2], 17, 394 : 20, 300.) Preparation 139. — /3-Naphthol (2-Hydroxy-naphthaiene). /\/\OH C 10 H 8 0. 144. 200 gms. (excess) of solid caustic soda free from chlorate, and 60 c.cs. water are placed in a fusion-pot (Fig. 50), which consists of a glue-pot of the ordinary type, the outer vessel containing a lead alloy. The thermometer is placed inside the iron tube containing a little mercury at the bottom, and this tube is used as stirrer. The pot is heated until the temperature is 270°. 300 gms. of dry powdered sodium /3-naphthalene sulphonate are then gradually added, the temperature being allowed to rise to 290' when half of the salt has been added, to 300 c when three-quarters have been added, and to 305° when all has been added, and finally to 318 c — but no higher for 15 minutes. The melt after cooling somewhat, is poured into 2 litres of Fig. 50. THE LINKING OF OXYGEN TO CARBON 205 water with continual stirring (caution!). The solution is then boiled and carefully neutralised with 50% sulphuric acid, an indicator being used. The solution is then filtered hot, and the ^-naphthol precipitated by adding 50% sulphuric acid to the filtrate until strongly acid. It is then filtered off, washed with water and dried, and may be recrystallised from hot water. C 10 H 7 SO 3 Na -> C 10 H 7 ONa -> C 10 H 7 OH. Yield. — 70% theoretical (130 gms.). Colourless crystals with charac- teristic odour ; M.P. 122° ; B.P. 286°. Important intermediate for dyestuffs. a-Naphthol (M.P. 94° ; B.P. 280°) is prepared from sodium a-naphtha- lene-sulphonate in an exactly similar manner. For the preparation of alizarin by the application of the same reaction, see p. 384. Reaction LXXVI. Addition of Hydroxyl to Ethylenic Bonds. (B., 21, 919 ; A., 268, 27.) — When compounds containing ethylenic linkages are treated with mild oxidising agents, e.g., bromine and caustic potash, dilute nitric acid and especially very dilute (2%) potassium permanganate solution, addition of hydroxyl at the double bond to form a 1 : 2-dihydroxy compound occurs. 0 2 RjCH : CHR 2 > RiCH.CH.R^ " H 2 0 OH OH If stronger oxidising agents be thus employed the carbon chain can be broken at that point. 0 2 RiCH.CH.R2-> RiCOOH + R 2 COOH. OH OH This reaction is used to determine the presence and position of double bonds in organic compounds ; it has been much applied to the elucidation of the structure of members of the terpene series. Preparation 140. — Phenyl-dihydroxy-propionic Acid (3-Phenyl-2 : 3- propan-diol Acid). C 6 H 5 .CHOH.CHOH.COOH. C 9 H 10 O 4 . 182. 20 gms. (1 mol.) of cinnamic acid (see p. 107) are dissolved in 3 litres of 5% aqueous caustic soda and 2 litres (excess) of 2% aqueous potassium permanganate solution are added with good cooling and mechanical stirring. The temperature must be kept at — 5° throughout. The liquid is filtered, nearly neutralised with 20% hydrochloric acid, and con- centrated until the dissolved salts begin to separate. Neutralisation is then completed with cone, hydrochloric acid, and the product repeatedly extracted with large quantities of ether until nothing further is removed. Owing to the solubility of phenyl-dihydroxy-propionic acid in water this will necessitate at least ten extractions. The ethereal solution is evaporated, and the residue redissolved in ether, the solution filtered, and evaporated to low bulk. The pure acid separates on cooling. 0 2 C 6 H 5 CH : CHCOOH -> C 6 H 5 CH(OH)CH(OH)COOH. 206 SYSTEMATIC ORGANIC CHEMISTRY Yield. — 70% theoretical (17 gms.). Colourless needles ; soluble in water ; somewhat soluble in ether ; M.P. 141°. (B., 21, 919 ; A., 268, 27.) As this section contains the most important methods of preparing alcohols, methods for the purification of commercial methyl and ethyl alcohols are given here. Purification of Methyl Alcohol. (Methanol). CH 3 OH. CH 4 0. 32. Methyl alcohol is manufactured by the dry distillation of wood. On this account the commercial article is usually contaminated with acetone , Fig. 51. its homologues and condensation products, and also with acetaldehyde, methyl acetate, dimethyl acetal, etc. It is purified by refluxing with 5% of solid caustic potash on a water bath and distilling. It is then THE LINKING OF OXYGEN TO CARBON 207 allowed to stand for 24 hours over 40% of freshly burnt quicklime, and redistilled from a water bath, the distillate being collected at 66° — 67°. This removes all but the very last traces of water. If absolutely pure methyl alcohol is required the product obtained above is boiled with about 1% of freshly prepared calcium turnings on a water bath, under a reflux condenser (see Fig. 51) fitted with a calcium chloride tube until the solid deposit, at first black, becomes almost white. It is then distilled into a receiver fitted with a calcium chloride tube, and the portion passing over at a constant temperature twice redistilled over 5% of calcium turnings, using a column. The solid formed should each time be white, and the alcohol should all distil at a constant temperature. As the anhydrous alcohol is very hygroscopic it must not be exposed to air. Colourless liquid ; spirituous odour ; miscible in all proportions with water ; B.P. 66-5° ; D. 2 ,° 0-79133. (B., 41, 4322.) Purification of Ethyl Alcohol. (Ethanol). C 2 H 5 OH. C 2 H 6 0. 46. To prepare absolute alcohol, 100 gms. of freshly burnt quicklime in the form of small lumps are placed in a 500-c.c. distilling flask, and 300 gms. of rectified spirits added. After 8 hours the alcohol is distilled off on a water bath until a thermometer in the neck of the flask indicates 80°. The alcohol so obtained still contains about 3% of water. For absolutely pure alcohol the above product is shaken with finely divided silver oxide. This oxidises any aldehyde present to acetic acid. Caustic soda is added to bind the acid, and the alcohol distilled, using a good column (see p. 21). The portion passing over at constant temperature is then treated with calcium turnings in the same way as methyl alcohol (see above). The anhydrous alcohol is very hygro- scopic, and must not be exposed to air. Colourless liquid ; spirituous odour ; miscible with water in all propor- tions ; binary mixture with water contains 75-57% alcohol, and boils at 78-1° at 760 nuns. ; B.P. 760 pure alcohol, 78-3° ; B.P. 21 13° ; D. * 0-790. It forms a ternary mixture with benzene and water, and this property can be utilised -to obtain absolute alcohol. (J. C. S., 81, 707; see Preparation 195 ; B., 38, 3612.) CHAPTER XIV oxygen to carbon Oxide Compounds Ethers This section deals with ethers and includes all the more usual methods of preparing them ; they are for the most part chemically inert substances, and are not of very great importance in the theory of organic chemistry. Reaction L XXVII, Action of Sulphuric Acid on an Alcohol or a Mixture of Alcohols. (J. Pharm., 1, 97 ; Phil. Mag. [3], 37, 350.)— This is the commercial method of obtaining the most important of the ethers — di- ethyl ether — from ethyl alcohol. The reaction occurs in two stages, the sulphuric acid acting as a catalytic rather than a dehydrating agent. In the first stage an alkyl hydrogen sulphate is formed — this yields ether on interaction with more alcohol. C 2 H 5 OH + HoS0 4 = C 2 H 5 .S0 4 H + H 2 0. C 2 H 5 .S0 4 H + C 2 H 5 OH = C 2 H 5 .O.C 2 H 5 + H 2 S0 4 . Thus, in theory, a limited quantity of sulphuric acid can convert an unlimited quantity of ethyl alcohol to diethyl ether, but in practice, owing to side reactions, this does not hold. Sulphuric acid may be replaced by phosphoric, arsenic, or benzene-sulphonic acids, while by using a mixture of alcohols " mixed ethers " may be obtained by the above reaction. The simple ethers are formed simultaneously, however ; so for mixed ethers it is better to use the methods given on pp. 209, 211, where only one product can result. As a catalyst in the above reaction, sand or aluminium sulphate may be employed. The method is applicable to naphthols, but not to phenols. Peeparation 141.— Di-Ethyl Ether (Ethan-oxy-ethan). (C 2 H 5 ) 2 0. C 4 H 10 O. 74. 100 gms. of 90% alcohol are placed in a ^-litre distilling flask, and under good cooling, 180 gms. (excess) of cone, sulphuric acid are slowly added. The flask, fitted with a thermometer dipping below the liquid, and a tap- funnel containing alcohol, is attached to the apparatus for the distillation of volatile liquids (see Fig. 8), and is heated on a sand bath to 140° — 145°, and the temperature kept between these limits. Alcohol is run in from the tap-funnel at the same rate as the liquid distils (two drops a second) until when about 150 gms. of alcohol have been added, heating is discontinued. The distillate is freed from sulphurous acid by shaking twice with 50 c.cs. of 10% caustic soda solution and from alcohol by 208 OXYGEN TO CARBON 209 shaking twice with the same quantity of saturated sodium chloride solution. The residual ether is dried by standing 8 hours over anhydrous calcium chloride. It is then distilled on a water bath, and collected at 35° C. The yield is improved by adding 10% of its weight of anhydrous ferric chloride, aluminium sulphate, stannous sulphate or sand, to the mixture of sulphuric acid and alcohol, the added substance acting as a surface catalyst. The ether obtained as above is pure enough for ordinary purposes but, when absolutely pure, dry ether is required ; the last traces of alcohol and water are removed by allowing the ether to stand in a flask over a mixture of 2 parts of metallic potassium and 1 part of metallic sodium in the form of thin slices or wire. The flask is fitted with a calcium chloride tube to allow hydrogen to escape and prevent the ingress of moisture. After 3 hours the ether is distilled over fresh metallic sodium, or better, phosphorus pentoxide. Owing to its volatility and inflammability ether should always be distilled from a water bath in the apparatus shown for the distillation of volatile liquids. C 2 H 5 OH -f H 2 S0 4 = C 2 H 5 O.S0 2 .OH + H 2 0. C 2 H 5 OS0 2 .OH + C 2 H 5 OH = (C 2 H 5 ) 2 .0 + H 2 SO,. Yield. — 80% theoretical (100 gms.). Colourless liquid ; characteristic odour ; miscible with alcohol in all proportions ; slightly soluble in water (1 in 10) ; B.P. 76,) 3449° ; D. 1 / 0-720. (J. Pharm., 1, 97 ; Phil. Mag, [3], 37, 350.) Purification of Commercial Ether. The chief impurities in commercial ether are alcohol and water. It con- tains traces of many, however, e.g., aldehyde, methyl alcohol, due to the fact that it is made from methylated spirit. To purify it for special purposes — Grignard's reaction, etc. — it is, as above, allowed to stand for 8 hours over calcium chloride, treated with sodium, or a mixture of sodium and potassium, and then distilled over sodium or phosphorus pentoxide. The presence of alcohol in ether may be proved by shaking the latter with a spirit soluble dye, e.g., aniline violet. If alcohol be present a blue solution is obtained, if absent none of the dyestuff passes into solution. Water is proved to be present by the cloud which is formed on mixing wet ether with carbon disulphide. Reaction L XXVIII. Action of Alkyl Halides on Alkali Alcoholates or Phenates. (P. K. S, 7, 135 ; J. C. S, 2, 198 ; A, 78, 226, 152, 164 ; B, 12, 116.) — This method is of importance as indicating the structure of ethers. It is applicable both in the aromatic and aliphatic series ; and can be used to obtain the ethers corresponding to the hypothetical di- and tri-hydric-alcohols, in which more than one hydroxyl group is attached to one carbon. CH 2 C1 2 + 2C 2 H 5 ONa = CH 2 (OC 2 H 5 ) 2 + 2NaCl. Preparation 142. — Phenetole (Ethoxy-benzene). C 6 H 5 .O.C 2 H 5 . C 8 H 10 O. 122. A 500-c.c. round flask containing 200 c.cs. (excess) of absolute ethyl s.o.c. p 210 SYSTEMATIC ORGANIC CHEMISTRY alcohol is attached to a reflux condenser, and 8 gms. (1 mol.) of sodium in thin slices or in small pieces of wire are added. When it has completely dissolved 31 gms. (1 mol.) of phenol and 75 gms. (excess) of dry ethyl iodide are added, and the whole refluxed on a water bath until the solution is no longer alkaline (4 hours). The alcohol and excess of ethyl iodide are distilled off on a water bath, the residue treated with water to dissolve sodium iodide, and extracted with ether. After drying over calcium chloride the ether is removed on a water bath and the phenetole distilled over the naked flame, the distillate being collected between 168°— 173°. C 6 H 5 OH + C 2 H 5 ONa = C 6 H 5 ONa + C 2 H 5 OH. C 6 H 5 ONa + C 2 H 5 I = C 6 H 5 .O.C 2 H 5 + Nal. Yield. — Almost theoretical (40 gms.). Colourless liquid ; pungent smell ; insoluble in water ; B.P. 172° ; D. ! 4 5 0«973. (A., 78, 226.) It should be noted that owing to the great affinity of the phenol for sodium, no sodium alcoholate remains to react with the ethyl iodide. Diethyl ether, however, may be prepared in a similar manner, using the same quantities of sodium, alcohol and ethyl iodide as above. The ether and excess of alcohol are distilled off and the ether separated from the alcohol by the addition of salt solution. Anisole (phenylmethyl ether B.P. 154°, see p. 211) can also be prepared in a similar way, using corre- sponding quantities of methyl alcohol and methyl iodide. The alkyl iodides give the best yields, but alkyl chlorides can also be employed. Preparation 143. — Ethyl Orthoformate (Triethoxymethan). CH(OC 2 H 5 ) 3 . C 7 H 16 0 3 . 148. 58-5 gms. (3 mols.) of metallic sodium, well pressed between filter paper, and cut into thin slices or pressed into wire (see p. 505) are placed in a dry flask of about 1\ litres capacity, and covered with a layer of anhydrous ether (see p. 209). The flask is connected to a condenser. A mixture of 117 gms. (3 mols.) of absolute alcohol and 100 gms. (1 mol.) of anhydrous chloroform is added drop by drop from a tap-funnel. At the beginning the reaction is violent, and the flask must be well cooled with ice ; sodium chloride separates and the liquid gradually changes to a brown colour. To complete the reaction the mass is warmed on a water bath until all the sodium present is converted into sodium chloride. The contents of the flask are poured into water, the ethereal solution of ethyl orthoformate which separates is removed, washed three times with water, dehydrated over calcium chloride, the ether removed on a water bath, and the residue distilled over a bare flame. That portion of the distillate which passes over above 100° is collected separately and redistilled, the fraction 143° — 150° being retained. CHC1 3 + 3C 2 H 5 ONa = CH(OC 2 H 5 ) 3 + 3NaCl. Yield. — 70% theoretical (85 gms.). Colourless liquid ; insoluble in water ; soluble in ether ; B.P. 145°— 147° ; D.' J 0-8964. (P. R. S., 7, . 135 ; J. C. S : . 2. 198 ; A., 152, 164 ; B., 12, 116.) OXYGEN TO CARBON 211 Reaction LXXIX. Action of Dimethyl Sulphate on Hydroxy Compounds. (A., 327, 114.) — This is the most important method of preparing methyl ethers — " methylation " — and has in fact almost superseded the older method, using diazomethane. The substance to be treated is dissolved or suspended in cold cone, caustic potash solution and a slight excess of dimethyl sulphate added. Great care must be taken in working with dimethyl sulphate, as it is excessively poisonous (see p. 64). RONa + (CH 3 ) 2 S0 4 = ROCH 3 + NaCH 3 S0 4 . This reagent has proved especially important in the study of the constitution of the sugars, and of cellulose. A series of methyl-celluloses have been obtained, and by the study of their hydrolysis, or decomposition in a vacuum, some light has been thrown on the structure of the cellulose molecule (J. S. C. I., 41, 362 E). In the laboratory dimethyl sulphate is much employed in the methylation of phenols and naphthols. Diethyl sulphate is not so suitable for such alkylations as its lower homologue. Prepakation 144. — Anisole (Methoxybenzene). C 6 H 5 .O.CH 3 . C 7 H 8 0. 108. Caution ! — Dimethyl sulphate is very poisonous and this preparation must be carried out in a good fume cupboard. 30gms. (1 mol.) of phenol dissolved in 160 gms. (excess) of 10% aqueous caustic soda solution in a |-litre round-bottomed flask are carefully treated with 50 c.cs. of commercial dimethyl sulphate, and the whole continually shaken. The flask is closed by a cork through which passes a thermometer and a glass tube, bent in a spiral to prevent liquid spurting. The beginning of the reaction is shown by the separation of an upper layer of oil, and by the evolution of heat. The temperature must be kept between 40° — 50°. When no more heat is evolved, excess of dimethyl sulphate is destroyed by boiling under a reflux condenser with frequent shaking. The liquid is cooled and caustic soda added until an alkaline reaction is obtained ; the whole is extracted with ether and the extract dried by shaking with anhydrous potassium carbonate and filtered. The ether is removed on a water bath and the residue distilled, the fraction 150°— 156° being retained. C 6 H 5 OH + NaOH = C 6 H 5 ONa + H 2 0. C 6 H 5 ONa + (CH 3 ) 2 S0 4 = C 6 H 5 .O.CH 3 + Na.CH 3 .S0 4 . (CH 3 ) 2 S0 4 + 2NaOH = 2CH 3 OH + Na 2 S0 4 . Yield. — 90% theoretical (32 gms.). Colourless oil ; pleasant odour ; insoluble in water ; soluble in ether ; B.P. 154° ; D. 1 * 0-991. (A., 41, 71 ; 48, 65 ; 78, 226 ; 327, 114.) Note. — The vapour of dimethyl sulphate is very poisonous, and great care should be taken not to inhale it. It should only be used in a fume cupboard through which a good draught is passing. It must never be allowed to touch the skin, and gloves and an overall must be worn when using it. These should be removed after use. Should any fall on the clothes they must be changed immediately. p 2 212 SYSTEMATIC OKGANIC CHEMISTRY The next preparation illustrates the preparation of the ethers of the polyhydric phenols. Prepaeation 145.— Pyrogallol-Trimethyl-Ether (1:2: 3-Trimethoxy- benzene). C 6 H 3 (OCH 3 ) 3 [l : 2 : 3]. C 9 H 12 0 3 . 168. Caution ! — Methyl sulphate is very poisonous. (See note to previous preparation.) 20 gms. (1 mol.) of pyrogallol are dissolved in 30 gms. (excess) of 35% aqueous caustic soda in a 1 -litre round-bottomed flask closed with a cork, through which pass a thermometer and an open tube bent in a spiral to prevent spurting. 50 c.cs. (excess) of commercial dimethyl sulphate are gradually added with continuous shaking, the cork being momentarily removed. The temperature is not allowed to rise above 45°. When heat is no longer evolved, the mixture is boiled under a reflux condenser, cooled, made alkaline with caustic soda if necessary, the dark-coloured precipitate filtered at the pump, and well washed with water. It is dissolved in ether, filtered, the ether removed on a water bath, and the residue recrystallised from dilute alcohol. (CH 3 ) 2 SO, C 6 H 3 (ONa) 3 [1:2:3] > C 6 H 3 (OCH 3 ) 3 [1:2.3]. Yield. — 70% theoretical (19 gms.). Colourless crystals ; insoluble in water ; soluble in alcohol and ether ; M.P. 47° ; B.P. 235°. (B., 21, 607, 2020 ; R., 126.) Peeparation 146. — /3-Naphthyl-Methyl Ether (2-Methoxy-naphthalene). -OCH 3 . C n H 10 O. 158. (See cautions to previous two preparations.) 10 gms. (1 mol.) of jS-naphthol are dissolved in 40 gms. (excess) of 10% caustic soda solution, and the cooled liquid mixed with 8 c.cs. of commercial dimethyl sulphate, as described in the two previous preparations. Gentle warming may be needed to start the reaction. The required ether sepa- rates as a solid which is filtered off after boiling and making alkaline if necessary, as before. The precipitate is washed with water and recrystal- lised from alcohol. (CH 3 ) 2 S0 4 C 10 H 7 OH[2]- — t C 10 H 7 .OCH 3 r2]. NaOH Yield. — Almost theoretical (11 gms.). Lustrous plates ; insoluble in water ; soluble in ether and in hot alcohol ; M.P. 71°. (B., 26, 2706.) The following preparations show the way in which cellulose, [C 6 H 7 0 2 (OH) 3 ] rt , can be methylated to give compounds having the empirical composition : [C 6 H 7 0 2 (OH) 2 (OCH 3 )] it , [C 6 H 7 0 2 (OH)(OCH 3 ) 2 ] ji and [C 6 H 7 0 2 (OCH 3 ) 3 ],, These compounds are known respectively as monomethyl cellulose, OXYGEN TO CARBON 213 dimethyl cellulose, and trimethyl cellulose. It lias not yet been proved, however, that they are definite chemical substances. Preparation 147. — The Methyl-celluloses. — (i.) Monomethylcellulose. (C e H 7 O a (OH) 2 (OCH 8 ) ),, (C 7 H 12 0 5 ) f , 176,. 50 gms. (1 mol.) of well-picked sliver cotton are shaken in a 2 -litre flask, closed, as described in Preparation 145, with 180 c.cs. (excess) of 23% caustic soda ; after standing for 1 hour the cotton is " pounded " in a glass mortar. It is returned to the flask, and 110 c.cs. (excess) of dimethyl sulphate gradually added (caution! see p. 64), the flask being shaken for \ hour between each addition. When no further evolu- tion of heat occurs, the flask is filled with water and the contents poured through a 100-mesh copper gauze. The methyl cotton is well washed with water and dried in an air oven. [C 6 H 7 0 2 (OH) 3 ] u -> [C 6 H 7 0 2 (OH) 2 (OCH 3 ) ] n Yield. — Almost theoretical (53 gms.). The methyl cotton is best characterised by its methoxyi content (see p. 476), which should be close to 17-65% OCH 3 . (ii.) Dimethylcellulose. [C 6 H 7 0 2 (OH)(OCH 3 ) 2 ], (C 8 H 14 0 5 ),. * 190,. 50 gms. (1 mol.) of monomethyl cellulose, prepared as above, are treated as before with 175 c.cs. (excess) of 20% caustic soda solution and 120 c.cs. of dimethyl sulphate added. The subsequent operations are as above. The dried product contains about 28% OCH 3 . 50 gms. of this latter product are treated with 400 gms. of water, and 100 c.cs. of 75% caustic soda solution added slowly and with shaking. 100 c.cs. of dimethyl sulphate are added under cooling. The subsequent operations are as in(i.) (C 6 H 7 0 2 (OH) 2 (OCH 3 ) ) n [C 6 H 7 0 2 (OH)(OCH s ) a ] B . Yield.— 90% theoretical (48 gms.). The product should contain close to 32-63% OCH 3 . (iii.) Trimethylcellulose. [C e H 7 0 2 (OCH 8 ) 3 ],, (0 9 H 16 0 5 V 204,, 50 gms. (1 mol.) of dimethyl cellulose are treated with 100 gms. of water, and 150 c.cs. of 75% aqueous caustic soda solution slowly poured in, with good shaking and cooling. 120 c.cs. of dimethyl sulphate are added, and the whole allowed to stand overnight and filtered. 100 c.cs. of 75% aqueous caustic soda are poured in, and 120 c.cs. more of dimethyl sulphate added, as before. The subsequent operations are as in (ii.). [C 6 H 7 0 2 (OH)(OCH 3 ) 2 ] (l [C 6 H 7 0 2 (OCH 3 ) 3 ] ( , Yield. — 80% theoretical (45 gms.). The product will contain about 42-5% methoxy ; the theoretical percentage for a trimethyl cellulose is 214 SYSTEMATIC ORGANIC CHEMISTRY 45-6%, but it is impossible to methylate cellulose completely. It will be noted how the strength of the caustic soda used varies with the percentage of methoxyl required in the product. Reaction LXXX. Action ol very Dilute Methyl Alcoholic Hydrogen Chloride on the Sugars. (B., 28, 1151.) — When the hexoses are heated for a long time at 100° with very dilute methyl alcoholic hydrogen chloride, methyl glucosides are produced. This synthesis is important, as it indi- cates methods for the synthesis of the higher sugars (cane sugar, etc.). which are themselves of the glucoside type. CHOH CHOH CHOH CHOH CHO Glucose. CH.OH + HC1 CH 2 OH I CHOH > CHOH I CHOH CHOH CH(OCH 3 ) 2 0. CHOH I CH CHOH . CHOH ^CHOCHa. Methyl-glucoside. Each sugar can yield two glucosides (a and /?) since the carbon to which the methoxy group becomes attached is in that way rendered asymmetric. It is assumed that each sugar first forms a dimethyl-acetal, which loses alcohol to yield the glucoside. In the following preparation it is the a-glucose which preponderates in the product. Preparation 148. — a-Methyl-Glucoside (1-Methoxy-pentol-hexan). C 6 H n 0 5 .OCH 3 . C 7 H 14 0 6 . 194. 10 gms. of methyl alcohol dehydrated and purified, as described on p. 206, are treated with dry gaseous hydrogen chloride until a little over 0-25 gm. has been absorbed, the flask being cooled in ice to prevent loss by evaporation. The liquid is then diluted with pure anhydrous methyl alcohol, so that it is exactly a 0-25% solution of hydrogen chloride in the alcohol. 25 gms. (1 mol.) of finely powdered anhydrous grape- sugar are then added to 100 gms. (excess) of the diluted solution, and the liquid refluxed for 1 hour until the sugar has all dissolved. The liquid now contains an intermediate product, thought to be glucose-dimethyl- acetal ; this is further heated in a sealed tube at 100° for 60 hours, and is thus converted to the glucoside (see p. 38). The sealed tube used should be a wide one and should be placed in a water bath, which is boiled behind a screen. The tube is then opened (see p. 41), and the solution evaporated to about one-third of its volume, and placed in a freezing mixture. After standing a time, or sooner if " inoculated " with a small crystal, the a-methyl-glucoside separates ; it is filtered off after 12 hours. By prolonged heating of the mother-liquor to 100° with fresh 0-25% methyl-alcoholic hydrogen chloride a further yield of glucoside may be prepared, The whole product is recrystallised from ethyl alcohol. OXYGEN TO CARBON 215 CH 2 OH CH3OH (CH0H) 4 > ! HC1 CHO Yield. — 40% theoretical (47 gms.). Colourless needles ; soluble in hot alcohol ; M.P. 105° ; [a] D + 157-6°. (B., 28, 1151 ; 34, 2899.) Reaction LXXXI. Action of Hydrogen Chloride on a Mixture of an Aldehyde and an Alcohol. (B., 30, 3053 ; 31, 545.)— The reaction is of the same type as the preceding. Under the influence of condensing agents calcium chloride, hydrogen chloride, etc., aldehydes combine with alcohols to yield the ethers of the hypothetical dihydroxy compounds from which the aldehydes are derived. Ketones only form these compounds with difficulty. ECHO + RiCHjjOH ~> RCH(OCH 2 R 1 ) 2 + H 2 0. Preparation 149. — Di-Ethyl-Acetal (1 : 1-Diethoxyethan). CH 3 CH : (OC 2 H 5 ) 2 . C 6 H 14 0 2 . 118. 15 gms. of anhydrous calcium chloride and a few drops of dilute hydro- chloric acid are added to a mixture of 44 gms. (1 mol.) of acetaldehyde and 100 gms. (excess) of alcohol. The whole is allowed to stand with occasional shaking for 1 hour, when the lower aqueous layer which has separated is siphoned off. The upper layer is placed over 15 gms. more of anhydrous calcium chloride, and after standing for 5 hours with constant shaking the separated aqueous layer is again siphoned off, and the upper layer added to a third 15 gms. of calcium chloride. This operation is once more repeated after 12 hours' standing, and the last lot allowed to act for 24 hours. It is filtered off and the filtrate fractionally distilled. The fraction 102°— 108° is collected separately. The fraction below 102° is again allowed to stand over calcium chloride for 24 hours, and again fractionated as before ; if preferred the fractionation may be performed under reduced pressure. CH3.CHO + 2C 2 H 5 OH = CH 3 CH(OC 2 H 5 ) 2 + H 2 0. Yield. — 60% theoretical (70 gms.). Colourless liquid ; aromatic odour ; soluble in 18 volumes of water at 25° C. ; miscible in all propor- 1 tions with alcohol ; B.P. 760 1 04° ; D. 2 4 ° 0-831. (J., (1880), 694 ; B., 30, 3053.) The same compound may be obtained by dissolving 10 gms. of acetalde- hyde in 50 gms. of a 1% absolute alcoholic solution of hydrogen chloride, and in 24 hours extracting the solution with ether after neutralisation with potassium carbonate. The extract is dried and purified by distilla- tion as before. Reaction LXXXII. Condensation of an Aldehyde with itself under the Action of Mineral Acids or of Calcium Chloride. (A., 27, 319 ; 162, 143 ; CH 2 OH CH 2 OH CHOH I I (CHOH) 4 > /CM I / I CH(OCH 3 ) 2 (CHOH) 2 \cHOCH 3 216 SYSTEMATIC ORGANIC CHEMISTEY 203, 26, 43.) — If acetaldehyde be treated with, calcium chloride or mineral acids, such as cone, sulphuric acid or gaseous hydrogen chloride, polymerisation occurs and paraldehyde is formed. A certain amount of a stereoisomer, metaldehyde, is also obtained ; its quantity increases with reduction in the temperature of polymerisation. 0 CH.CH 3 3CH 3 CHO CH 3 CH^ yo 0 CH.CH 3 Pkepakation 150. — Par-Aldehyde. /O.CHMe. ' CHMe< >0. C 6 H 12 0 3 . 132. ^O.CHMe/ 132 gms. (3 mols.) of freshly distilled absolute acetaldehyde are placed in a flask fitted with a thermometer, reflux condenser, and gas delivery tube, and the whole cooled to 5°. Dry hydrogen chloride is led in until an absorption of 6% (8 gms.) has taken place. The mixture is then allowed to stand for several hours at room temperature, and until the temperature has risen to the boiling point of acetaldehyde, 21°, when it is recooled to 5° and allowed to stand for 15 hours. Some metaldehyde has by then separated, and is filtered off. The liquid is shaken with a saturated solution of sodium carbonate to remove acid, and then washed with water. It is dried with anhydrous potassium carbonate and frac- tionated, the fraction 122° — 128° being retained. The distillation can be carried out under reduced pressure. 3CH 3 .CHO -> CH 3 CH(OCH(CH 3 ) ) 2 0. Yield. — 70% theoretical (90 gms.). Colourless liquid ; sparingly soluble in water ; M.P. 12-5° ; B.P. 184° ; metaldehyde forms bright feathery crystals which readily sublime. (A., 27, 319 ; 162, 143 ; 203, 26, 43.) Reaction LXXXIII. Action of Caustic Alkali on the a, ^-chlorhydrins. (A. Spl. (1861), 1, 221 ; J., 13, 456.)— When the chlorhydrins which contain chlorine and hydroxyl attached to adjacent carbons are heated with caustic alkali, elimination of hydrochloric acid occurs and an inner ether or oxide is obtained. E R I -I CHOH CH CHC1 I NaOH = |\ n + NaCl + H 2 0. \/° CH I These oxides are unstable, reacting with water to form glycols, with hydrochloric acid to regenerate the chlorhydrin, and so on. The simplest member of this group, ethylene oxide, is especially unstable, it behaves OXYGEN TO CARBON 217 almost as if it were unsaturated ; it will even absorb hydrochloric acid from metallic chlorides, and precipitate the base. Preparation 151. — Epichlorhydrin (l-Chlor-2 : 3-mon-oxy-propan). CH 2 C1.CH . CH 2 . C 3 H 5 0C1. 92-5. 100 gms. (excess) of caustic potash are dissolved in 200 c.cs. of water, and the cooled solution poured with stirring into 240 gms. of the crude dichlor- hydrin obtained in Preparation 316 or into 200 gms. (1 mol.) of pure dichlorhydrin ; cooling is continued throughout, the temperature being kept below 15°. The mixture is extracted with ether, the extract washed with a little water dried over calcium chloride, the ether removed on a water bath and the residue fractionated using a column (see p. 21), the fraction 114° — 120° being retained. If the crude dichlorhydrin is used, the portion boiling above this temperature is mainly aceto-dichlorhydrin, and may serve for the further preparation of epichlorhydrin by treat- ment with potash. If a pure specimen is required, it may be purified by distillation. CH 2 C1CH(0H).CH 2 C1 + KOH = CH 2 .CH.CH 2 C1 + KC1 + H 2 0. v O Yield. — 30% theoretical (45 gms.). Colourless mobile liquid ; ethereal smell; B.P. 117° ; D. J 1-203. (A. Spl., (1861), 1, 221 ; 138, 297 ; C. (1905), [1], 12 ; J. 13, 456.) Reaction LXXXIV. Addition of Phenols to Quinones. (A., 200, 251 ; 215, 134 ; B., 24, 1341.) — Quinones readily react with 1 mol. of ^>-di-hydric phenols and 2 mols. of other phenols to form the highly-coloured ether compounds, quinhydrones and |)henoquinones respectively. O OH Q _ !! /\ + OH y\ \/ II 0 OH 0 II /\ OH /\ \/ f 2 II 0 OH -O- Quinliydrone. OH X O / 0 OH X Phenoquinone. Quinhy drone can also be prepared from quinone or quinol by half reduction or half oxidation respectively (see Preparation 152). 218 SYSTEMATIC ORGANIC CHEMISTRY Preparation 152. — Quinhydrone. HO. C 12 H 10 O 4 . 218. HO Method I. — 10 gms. (1 mol.) of quinone and 10 gms. (1 mol.) of quinol are separately dissolved in the minimum quantity of water, and the solutions mixed and warmed. After cooling, the precipitate is filtered off and washed with water. 0 : C 6 H 4 : 0 + C 6 H 4 (OH) 2 [l : 4] = 1 : 4(OH) 2 C 6 H 4 / ^C 6 H 4 [1 : 4]. [4] ° Yield. — Almost theoretical (20 gms.). Method II. — 10 gms. (2 mols.) of quinol are dissolved in water and heated with an aqueous solution of 14-5 gms. (2 mols.) of ferric chloride. The quinhydrone rapidly separates. It is filtered off and washed with water. C 6 H 4 (0H o ) + 2FeCl 3 = C 6 H 4 0 2 + 2FeCL> + 2HGL C 6 H 4 0 2 + C 6 H 4 (OH) 2 = (0H) 2 C 6 H 4 .0 2 .C 6 H 4 . Yield, — Almost theoretical (10 gms.). Lustrous green prisms or leaflets ; quinone-like odour ; soluble in warm petroleum ether ; in- soluble in cold water ; M.P. 171°. (B., 24, 1341 ; 28, 1615.) Preparation 153. — Phenoquinone. C 6 H 5 O x /OC 6 H B >C 6 H 4 < C 18 H 16 0 4 . 296. HO/ X 0H. 20 gms. (1 mol.) of phenol and 12 gms. (1 mol.) of quinone are dissolved in petroleum ether or benzene and refluxed for 10 minutes. The solution is then concentrated on a water bath until crystals separate on cooling. They are filtered off and washed in water. 2C 6 H 5 OH + C 6 H 4 0, = (C 6 H 5 0) 2 (OH),C 6 H 4 . Yield. — Almost theoretical (32 gms.). Red acicular crystals ; insoluble in water ; somewhat soluble in warm petroleum ether ; M.P. 71° ; sub- limes on heating. (A., 204, 251 ; 215, 134.) The above preparation can also be performed in aqueous solution. Resorcinol quinone and pyrogallol quinone are similarly prepared ; they decompose at 90° and above 120° respectively. v CHAPTER XV oxygen to carbon Oxy Compounds Aldehydes, Ketones, and Quinones. Aldehydes, ketones and quinones are important ; most of the methods of preparing them come into this section. The reactions on which those methods are based are chiefly of two kinds — purely oxidising reactions, in which nascent oxygen directly acts {e.g., Preparation 439) and hydrolytic reactions, in which the oxygen is produced by the decom- position of a molecule of water (Preparation 154). Reaction LXXXV. Simultaneous oxidation and Hydrolysis o£ Mono- halogen Compounds. (A., 22, 1 ; 143, 186.) — When benzyl chloride or one of its derivatives is heated with an aqueous solution of a mild oxidising agent, such as copper nitrate, lead nitrate, etc., combined hydrolysis and oxidation occurs, and benzaldehyde or one of its derivatives is obtained. H 2 0 0 C 6 H 5 CH 2 C1 > C 6 H 5 CH 2 OH -> C 6 H 5 CHO. Peeparation 154. — Benzaldehyde (Phenyl-methanal). C 6 H 5 CHO. C 7 H 6 0. 106. 50 gms. (1 mol.) of benzylchloride (see p. 344), 50 gms. (excess) of copper nitrate and 300 c.cs. of water are refluxed together in a current of carbon dioxide for about 8 hours, and until a sample of the oil present contains very little chlorine (see p. 502). The mixture is extracted with ether, the ether removed on a water bath, and the residual oil mechanically shaken for 1 hour with a saturated solution of sodium bi- sulphite. After standing for 2 hours, the crystals which have separated are filtered at the pump and washed first with a little alcohol and then with ether. They are warmed with excess of 10% sulphuric acid ; the aldehyde which separates is extracted with ether, the extract dried over anhydrous sodium sulphate, the ether removed on a water bath and the residue distilled in a current of carbon dioxide. The fraction 176° — 181° is retained. 2C 6 H 5 CH 2 C1 + Cu(N0 3 ) 2 = 2C 6 H 5 CHO + CuCl 2 + 2HN0 2 . Yield. — 40% theoretical (17 gms.). Colourless oil ; characteristic odour ; M.P. 13-5°. B.P. 179° ; D. L | 1-0504. (A., 22, 1 ; 143, 186.) Reaction LXXXVI. Hydrolysis of certain Di-halogen Compounds. (A. SpL, 2, 253 ; A., 139, 319 ; D.R.P, 82927 ; 85493.)— When di-halogen 219 220 SYSTEMATIC ORGANIC CHEMISTRY compounds containing two halogen atoms attached to the one carbon atom are boiled with water in presence of an alkali or certain metals, hydrolysis occurs, and an aldehyde or ketone is obtained. 2H 2 0 E.CCl^! > E.C(OH) 2 E 1 > ECOKj. The process is used on a commercial scale to prepare benzaldehyde by heating benzal chloride with an aqueous suspension of chalk or milk of lime under pressure. Water is sufficient to bring about hydrolysis, the alkali is added to remove the hydrogen chloride formed, and so prevent the back reaction coming into play. In place of an alkali, a trace of iron powder can be used ; the reaction here takes a slightly different course, only 1 mol. of water being required for 1 mol. of the dichloride. Pkepaeation 155. — Benzaldehyde (Phenyl-methanal). C 6 H 5 CHO. C 7 H 6 0. 106. Method I. — 20 gms. (1 mol.) of benzal chloride (see p. 343) are refluxed for 4 hours in an atmosphere of carbon dioxide with 200 c.cs. of water and 40 gms. of precipitated chalk in a round flask heated on an oil bath which is kept at 130°. The whole is then steam-distilled in an atmosphere of carbon dioxide (see p. 23). The distillate is extracted with ether, the ether removed on a water bath and the residual benzalde- hyde purified by means of its bisulphite compound as described in Pre- paration 154. H 2 0 C 6 H 5 CHC1 2 > C 6 H 5 CH(OH) 2 > C 6 H 5 CHO. Yield.— 70% theoretical (9 gms.). (A., Spl. 2, 253 ; 139, 319.) Method II. — 150 gms. (1 mol.) of benzal chloride (see p. 343) are heated in a round-bottomed flask to 30° with agitation ; 0-5 gms. of iron powder, and 25 gms. (excess) of water are then added, and the mixture cautiously heated until hydrogen chloride is evolved (about 100°). Heat- ing may be discontinued until the action subsides, when more heat is applied. About 20 gms. sodium carbonate are added to give an alkaline reaction, and the benzaldehyde distilled in steam in an atmosphere of carbon dioxide and purified as described in Preparation 154. C 6 H 5 CHC1 2 + H 2 0 -> C 6 H 5 CHO + 2HC1. Yield. — 80% theoretical (75 gms.). Colourless oil ; characteristic odour ; insoluble in water ; soluble in ether ; M.P. — 13-5° ; B.P. 179° ; D. J 1-0504. (D.R.P., 82927 ; 85493.) In all these preparations of benzaldehyde the chief loss is due to oxida- tion of the aldehyde to benzoic acid. The acid may be removed from the reaction mixture from which the benzaldehyde has been steam distilled by filtration while still hot, and acidification with much concentrated hydro- chloric acid. Benzoic acid separates on cooling. Reaction LXXXVII. Hydrolysis of certain Anils. (B., 35, 1228; D.R.P., 121745.) — When derivatives of toluene which contain negative groups in the o- and ^-positions are treated with ^-nitroso-di-methyl- OXYGEN TO CARBON 221 aniline, owing to the activation of the methyl group by the presence of the two negative groups, condensation to an anil occurs. C 6 H 3 (N0 2 ) 2 (CH 3 )[2 : 4 : 1] + C 6 H 4 (NO).N(CH 3 ) 2 )[l : 4] = C 6 H 3 (N0 2 ) 2 CH : N.C 6 H 4 N(CH 3 ) 2 + H 2 0. These anils are readily hydrolysed by acids to yield derivatives of benzaldehyde. H 2 0 C 6 H 3 (N0 2 ) 2 CH : N.C 6 H 4 N(CH 3 ) 2 > C 6 H 3 (N0 2 ) 2 CHO + H 2 N.C 6 H 4 N(CH 3 ) 2 . Peeparation 156. — 2 : 4-Di-nitrobenzaldehyde (2 : 4-Di-nitro-l-(oxy- methyl)-benzene). . C 6 H 3 (N0 2 ) 2 (CHO)[2 : 4 : 1]. C 7 H 4 0 5 N 2 . 196. 50 gms. (1 mol.) of 2 : 4-dinitrotoluene, 50 gms. (excess) of £>-nitroso- dimethylaniline and 90 gms. of crystallised sodium carbonate are refluxed on a water bath for 6 hours with 300 c.cs. of alcohol. The anil which separates is filtered off, washed with boiling water, and recrystallised from acetone. The whole is then mechanically shaken for 4 hours with 350 gms. (excess) of nitric acid (D. 1-17) and 300 c.cs. of benzene, filtered, the benzene layer separated and the solvent removed on a water bath. The residue is recrystallised from alcohol, with the addition of animal charcoal, being precipitated from the alcoholic solution by dilution with water. The crystals which separate contain 1 mol. of alcohol of crystallisation ; this they lose at 90°. The aqueous layer above is re-shaken with benzene and nitric acid, and worked up for further aldehyde as above. C 6 H 3 (N0 2 ) 2 (CH 3 )[2 : 4 : 1] + NOC 6 H 4 N(CH 3 ) 2 [l : 4J H 2 0 -> C 6 H 3 (N0 2 ) 2 CH : NC 6 H 4 N(CH 3 ) 2 > C 6 H 3 (N0 2 ) 2 CHO[2 : 4 : 1] + H 2 NC 6 H 4 N(CH 3 ) 2 . Yield— 80% theoretical (42 gms.). Yellowish crystals ; insoluble in water ; soluble in alcohol and benzene ; M.P. 72° ; B.P. 10 190° ; B.P. 20 2 1 0°. (B., 35, 1228 ; D.R.P., 121745.) Reaction LXXXVIII. Action of Nitrous Acid on the Monoximes of a-Di-ketones. (A., 274, 71.) — When compounds containing the group — CH 2 — CO — • are treated with nitrous acid in presence of sodium, an " iso- nitroso compound " identical with the monoxime of the corresponding a-di-ketone is obtained (see p. 105). From the monoxime by the further action of nitrous acid in the presence of glacial acetic acid, the di-ketone itself is formed. /CH 2 HN09 /C:NOH HN q 2 /CO K R E.CO.NH 2 . Preparation 158. — Oxamide (Di-amide of ethan-diacid). CONH 2 . C 2 H 4 0 2 N 2 . 88. CONH 2 . (To be carried out in a good fume cupboard.) 25 gms. (1 mol.) of crystallised copper sulphate are dissolved in 75 c.cs. of water in a distilling flask heated on a water bath, and a warm solution of 13 gms. (2 mols.) of 98% potassium cyanide in 25 c.cs. of water is added (caution I cyanogen is extremely 'poisonous). The evolved cyanogen is led into 20 c.cs. of cold cone, hydrochloric acid. When all the cyanide has been added, the second equivalent of cyanogen is expelled by adding, in the same way, a solution of 16 gms. (1 mol.) of ferric chloride in 20c.es. of water. Oxamide now separates out, provided the hydrochloric acid is kept quite cool. It is washed with water. CN CO.NH 2 . • + 2H 2 0 = | CN CO.NH 2 . Yield. — 50% theoretical (4-5 gms.). White crystalline solid ; partly OXYGEN TO CARBON 223 sublimes on heating, but for the most part decomposes ; sparingly soluble in water and in alcohols. (B., 18, 355.) Preparation 159. — Benzamide (Amide of phenyl-methan acid). C 6 H 5 .CO.NH 2 . C 7 H 7 ON. 121. 20 gms. (1 mol.) of benzonitrile are added to 300 c.cs. (excess) of 3% (10 volumes) aqueous hydrogen peroxide containing 5 c.cs. of 2N caustic soda . The mixture is warmed on a water bath to 40°, and then shaken in an un- corked bottle until the oil has completely disappeared. The precipitate which forms is filtered off at the pump, and recrystallised from alcohol or hot water. 2C 6 H 5 CN + 2H 2 0 2 = 2C 6 H 5 CO.NH 2 + 0 2 . Yield. — Theoretical (21 gms.). White crystalline powder ; soluble in hot water ; M.P. 128°. (B., 18, 355.) Reaction XC. Hydrolysis of the Di-saccharoses. (J. pr., [2] 2, 1, 245 ; B., 13, 1761 ; 28, 1429.) — When the di-saccharoses, and in fact all the glucosides, are heated with mineral acids, they are hydrolysed into their component monosaccharoses or into their component monosaccharoses and alcohols. In this way cane sugar yields glucose and fructose, lactose yields glucose and galactose, maltose yields glucose, methyl glucoside yields glucose and methyl alcohol. These hydrolyses can also be brought about by means of various enzymes, e.g., invertase will hydrolyse cane sugar, maltase, maltose, and so on. More complicated compounds can be brought within the scope of the reaction ; thus starch can be hydrolysed to glucose in this way. CH 9 OH CH 9 0H CHOH ,CH CH /\ / ' O (CHOH), H 9 0 O (CHOH), V ! X CH O CH 2 OH CHOH I CHOH CHOH CHOH CHO G-lucose. CHOH CHOH I CHOH i CO I CH 2 OH. Fructose. Cane-sugar. Preparation 160. — Glucose (Pentolhexanal, -\ h +)• CHO H.COH HOC.H C 6 H 12 0 6 . 180. H.COH H.COH CH 2 OH. 70 gms. (excess) of fuming hydrochloric acid (38%) are mixed with 224 SYSTEMATIC ORGANIC CHEMISTRY 1,500 c.cs. of 95% alcohol, and the whole warmed on a water bath ; 500 gms. (1 mol.) of finely powdered cane sugar are gradually added with mechanical stirring, the temperature being kept at 50° throughout. When all the sugar has dissolved, the liquid is filtered, cooled, seeded with 0-5 gm. of glucose crystals, and allowed to stand for a week at ordinary temperatures. The crystals which separate are filtered off at the pump, washed with absolute alcohol, and recrystallised by dissolving in a very little hot water to form a syrup, and adding hot methyl or ethyl alcohol until the solution becomes turbid. On cooling, the sugar which separates is filtered off at the pump, and washed with absolute alcohol. C12H22O11 + H 2 0 = C 6 H 12 0 6 + C 6 H 12 0 6 . Cane-sugar. Glucose. Fructose. Colourless crystals ; verv soluble in water ; insoluble in alcohol ; M.P. 146°. (J. pr., [2], 21, 245.) Reaction XCI (a). Oxidation oi Aromatic Hydrocarbons to Aldehydes by the action of Chromyl Chloride in Carbon Disulphide Solution. (Etard). (B., 17, 1426 ; 21, R., 714.) — In this reaction the hydrocarbon and chromyl chloride are both dissolved in carbon disulphide, and the solutions care- , fully mixed. An explosive intermediate compound is precipitated, and this is separated and decomposed with water to give the aldehyde. The yields are very good, but the method is not often used owing to the inconvenience of working with carbon disulphide and the dangerous nature of the intermediate compounds. RCHg + 2Cr0 2 Cl 2 = KCH.(OCr.Cl 2 OH) 2 . E.CH.(OCrCl 2 OH) 2 + 3H 2 0 = ECHO + 2CrO(OH) 2 + 4HC1. Peepaeation 161. — Benzaldehyde (Phenyl-methanal). C 6 H 5 .CHO. C 7 H 6 0. 106. (Great caution must be observed in performing this experiment. No light must be brought near the apparatus.) 10 gms. (excess) of toluene and 30 gms. (2 mols.) of chromyl chloride (see p. 509) are each dissolved in anhydrous carbon disulphide, the former in 50 gms., and the latter in 120 gms. ; the former solution is placed in a litre flask fitted with a thermometer and long reflux condenser, and the T latter is added in 10 c.cs. quantities, the reaction each time being allowed to moderate before further addition. Should no reaction occur on the first addition, the mixture is allowed to stand for 15 minutes before further addition. The reaction is very vigorous, and the flask must be cooled by ■ immersing in a bath of ice- water, so that the temperature of the mixture never rises above 45°. When addition is complete, the mixture is allowed to stand for 3 hours, the explosive intermediate compound which appears as a precipitate, is filtered off at the pump, well washed with anhydrous carbon disulphide, dried by blowing air through it, and decomposed by adding in small quantities to 1 litre of cold water. The chromic acid formed is reduced with gaseous sulphur dioxide, and the liquid steam- distilled in a current of carbon dioxide to remove benzaldehyde, which is OXYGEN TO CARBON 225 extracted from the distillate with ether. The extract is dried over calcium chloride, the ether removed on a water bath, and the residue distilled in a current of carbon dioxide, the fraction 177° — 182° being retained. (For the purification of the aldehyde by means of its bisulphite compound, see p. 219). Cr0 2 Cl 2 HoO C 6 H 5 CH 3 •->C 6 H 5 CH(OCrCl 2 (OH) ) 2 - -> C 6 H 5 .CHO. Yield. — Almost theoretical (116 gms.). Colourless oil ; pleasant odour ; insoluble in water ; B.P. 179° ; D. A | 1-0504. (B., 17, 1426 ; 21 R., 714.) Reaction XCI. (b) Oxidation of Aromatic Hydrocarbons to Aldehydes by the action of Chromic Acid in Acetic Anhydride Solution. (A., 311, 353 ; D.R.P., 121788.) — In the ordinary way, chromic acid oxidises hydro- carbons to aldehydes and then to acids. But if acetic anhydride and cone, sulphuric acid be present, the di-acetyl derivative of the aldehyde is formed and this does not undergo further oxidation. The aldehyde is obtained from the di-ester by hydrolysis. (Cf. the preparation of salicylaldehyde, P- 99.) 0 2 (CH 3 CO) 2 0 HC1 RCH 3 -> ECHO > R.CH.(OCOCH 3 ) 2 > R.CIIO. Preparation 162. — Zso-Phthalaldehyde. C 6 H 4 (CHO) 2 [l : 3]. C 8 H 6 0 2 . 134. 60 gms. (excess) of chromic acid is slowly added, with good agitation and cooling in a freezing mixture, to 15 gms. (1 mol.) of m-xylene mixed with 250 gms. glacial acetic acid, 500 gms. (excess) acetic anhydride, and 10 c.cs. cone, sulphuric acid. When all has been added, the mixture is kept at 0° until a sample gives a bulky white precipitate when shaken with cold water till the anhydride is decomposed., It is then poured on to powdered ice and stirred, until the oil formed solidifies. The ^so-phthal- aldehyde tetracetate is filtered off and recrystallised from methyl alcohol (M.P. 101°). The crystallised product is now heated under a reflux for 15 minutes with 150 c.cs. of 5% hydrochloric acid. On cooling, the aldehyde separates, is filtered and recrystallised from hot water. C 6 H 4 (CH 3 ) 2 > C 6 H 4 [CH(OCOCH 3 ) 2 ] 2 > C 6 H 4 (CHO) 2 . Yield. — -80% theoretical (15 gms.). Colourless needles ; soluble in hot water; M.P. 89°. (A., 311, 353 ; D.R.P., 121788.) Reaction XCI. (c) Oxidation of Aromatic Hydrocarbons to Aldehydes by the action of Cerium Dioxide in presence of Concentrated Sulphuric Acid. (D.R.P., 158609.) — Cerium dioxide has the property of oxidising aromatic hydrocarbons to aldehydes and no further. The addition of a reagent to combine with the aldehyde group as formed is unnecessary. CeO, RCH 3 > R.CHO. Preparation 163. — Benzaldehyde (Phenyl-methanal). C 6 H 5 CHO. C 7 H 6 0. 106. 30 gms. (1 mol.) of toluene are heated to 60° with 1,500 gms. (excess) of s.o.c. Q 226 SYSTEMATIC ORGANIC CHEMISTRY sulphuric acid (D. 1-5) in a 2-litre round-bottomed flask fitted with a reflux condenser and mechanical stirrer (see fig. 37). 250 gms. (excess) of cerium dioxide are gradually added, and the temperature allowed to * rise to 90°. When no more dioxide remains, the whole is steam-distilled until no more benzaldehyde passes over. Benzaldehyde is then recovered from the distillate as in Preparation 161. C 6 H 5 CH 3 + 0 2 = C 6 H 5 CHO + H 2 0. Yield. — 70% theoretical (25 gms.). Colourless oil ; pleasant odour ; insoluble in water ; B.P. 179° ; D. ? 1-0504. (D.R.P., 158609.) Reaction XCII. Action o£ Oxidising Agents on Methylene Groups in Aromatic Compounds. (B, 6, 1347 ; A. Spl. (1869), 7, 284 ; A., 279, ' 258.) — When compounds containing methylene groups attached to two aromatic residues are heated with oxidising agents — chromic acid is 4 usually employed — the two hydrogens of each methylene group are replaced by oxygen to yield oxy-compounds, which have some or all of ihe properties of ketones and of quinones. C 6 H 6 CH 2 .C e H 5 —■ ^ C 6 H 5 .CO.C 6 H 5 . C 6 H 4 < >C 6 H 4 — > C 6 H 4 < >C 6 H 4 . Preparation 164. — Anthraquinone (s-di-phenylene-di-oxy-ethan). / co \ \m C 6 H4\ /C 6 H 4 , C 14 H 8 0 2 . 208. A Anthracene is sublimed with superheated steam (see p. 23) at 200°. y This reduces it to a fine state of division. 100 gms. (1 mol.) of moist sublimed anthracene are stirred up with 2 litres of water in a lead-lined pot, fitted with a glass agitator, and 200 gms. (excess) of sodium dichromate are dissolved in it at the same time., The mixture is heated to 80°, and 600 gms. (excess) of 50% sulphuric acid are added from a dropping-funnel during 10 hours. The presence of chromic acid must always be clearly shown (test with hydrogen peroxide)? ' The mixture is then boiled for 2 hours, evaporated water being replaced at intervals. The product is filtered off, thoroughly washed and dried. It is heated in 2 J times its weight of cone, sulphuric acid at 120° as long as S0 2 is evolved. After 3 hours it is poured into 3 times its weight of water, and the anthraquinone, which is precipitated, filtered off at the pump. It may T .| be further purified by sublimation at 250°. /CHv 0 2 / C0 \ CfiH 4 <^ /C 6 H 4 — > C 6 H 4 ^ \C 6 H 4 . Yield.- 90% theoretical (105 gms.). Yellow needles ; insoluble irl? water ; soluble in glacial acetic acid ; sublimes on heating at 250° OXYGEN TO CARBON 227 M.P. 277° ; B.P. 382° ; is an important intermediate in the preparation of vat dyestuffs. (B., 6, 1347 ; A. SpL, 1869, 7, 284.) Anthraquinone does not possess the properties of a true quinone. Reaction XCIII. Oxidation of Aromatic Hydrocarbons to Quinones. (J. C. S., 37, 634 ; A., 167, 139, 357.)— Although benzene does not react in this way polynuclear aromatic hydrocarbons can be oxidised directly to give quinones analogous to both o- and j9-quinones. The oxidising agent used is chromic acid in glacial acetic acid. The amino compounds, however, give better yields (see Reaction XCIV). 0 Preparation 165.— ct-Naphthaquinone (s-Benz-benzoquinone). O C 10 H 6 O 2 . 158. 10 gms. (1 mol.) of naphthalene dissolved in 100 c.cs. glacial acetic acid are gradually added with good agitation to 10 gms. (excess) of chromic acid dissolved in 70 c.cs. of 80% acetic acid, the whole being kept at 0°. After standing for 4 days at the ordinary tern perature with occasional shaking, the liquid is poured into a litre of water. Th e precipitated naphthaquinone is then filtered, washed with water and recrystallised from alcohol . C 10 H 8 + 30 -» C 10 H 6 O 2 + H 2 0. Yield. — 40% theoretical (5 gms.) (cf. yield in Preparation 169). Yellow plates with sharp odour ; insoluble in water ; soluble in hot alcohol ; volatile in steam ; M.P. 125°. (J. C. S., 37, 634 ; A., 167, 357.) (Cf. ^9-benzoquinone, p. 229.) Preparation 166. — Phenanthraquinone (s-(Di-benz)-benz-or^o- quinone). O 0 II II CH.-O,. 208. 30 gms. (1 mol.) of phenanthrene are dissolved in 150 gms. of warm glacial acetic acid, 80 gms. (excess) of chromic acid dissolved in about 250 gms. of glacial acetic acid are gradually added. This latter Q 2 228 SYSTEMATIC ORGANIC CHEMISTRY solution is prepared by dissolving the chromic acid in the minimum quantity of water, and pouring into glacial acetic acid. The addition is regulated so that the heat of reaction keeps the mixture just on the boil throughout. When addition is complete most of the acetic acid is dis- tilled off, and the residue treated with much water. The precipitate is filtered at the pump, washed with a little hot water, shaken with a warm dilute sodium bisulphite solution and filtered ; the filtrate is warmed on a water bath, and the quinone precipitated by addition of sulphuric acid. This precipitate is recrystallised from an excess of boiling alcohol. C 14 H 10 + 30 = C 14 H 8 0 2 + H 2 0. Yield. — Almost theoretical (35 gms.). Orange needles ; odourless ; not volatile in steam ; insoluble in water and in cold alcohol ; soluble in glacial acetic acid ; M.P. 198°. (A., 167, 139.) (Cf. o-benzoquinone, p. 229.) Reaction XCIV. Oxidation of Primary Aromatic Amines and their para- substituted Derivatives to Quinones. (A., 27, 268; 194, 202; 211, 49; 215, 125 ; B., 19, 1467 ; 20, 2283 ; 25, 982 ; 36, 4390.)— Many primary aromatic amines, when oxidised with chromic acid, readily yield p-quinones, aniline, for example, giving ^-benzoquinone. 0 NH 2 || The mechanism of this reaction is not simple, but is probably as follows : — - C 6 H 5 NH 2 -> C 6 H 5 N = 0 -> C 6 H 5 NHOH Aniline. Phenyl -am- Phenyl -hy- monium oxide. droxylamine. NH 2 .C 6 H 4 .OH -> 0 : C 6 H 4 : 0. p-Aminophenol Benzoquinone. (see Prep. 137.) In support of this view the j>-amino phenols themselves readily yield * quinones. Also most ^-substituted primary amines, e.g., ^-diamines, j9-alkylamines, such as ^-toluidine, sulphanilic acid and its derivatives, 1 behave similarly. In fact, the reaction can be used as a test for ^-substituted primary amines. ^-Benzoquinone is usually made from aniline ; for the other ^-quinones the j9-amino-phenols, which are easily obtained by reduction of the ^9-nitroso-phenols and of azo colours, are employed. These reactions also apply, but not so widely, in the naphthalene series. OXYGEN TO CARBON 229 Preparation 167.— p-Benzoquinone (1 : 4-Di-oxy-2 : 5-hexadien). 0 CJLCL, 108. 0 To 50 gms. (1 mol.) of aniline dissolved in 1,300 gms. (excess) of 25% sulphuric acid a cold 20% solution of 50 gms. of sodium dichromate is slowly added in 3 hours, with good cooling and mechanical stirring. The temperature must throughout be kept below 4°. When all the dichromate has been dropped in the whole is allowed to stand for 24 hours, and 100 gms. of sodium dichromate added in the same manner as before. After 6 hours the liquid is extracted 6 times with its own volume of ether, the latter being recovered each time by distillation and used again. The shaking must not be too vigorous as the mixture tends to emulsify very readily. The crude product from the ether extraction is sublimed in steam (see p. 23). If sodium dichromate be not available the potassium salt may be employed. The same quantities are taken as with the sodium salt, but the potassium salt is added in the form of powder, and not in aqueous solution. It is usual to treat half of the solution, after oxidation is complete, with sulphur dioxide to obtain quinol (see p. 181). As quinone is more difficult to extract with ether from water than quinol, the whole resulting solution may be worked up for quinol, and the latter, when purified, oxidised with sodium dichromate solution to quinone. 0 2 C 6 H 5 NH 2 >0:C 6 H 4 : O, Yield. — 70% theoretical (40 gms.). Yellow, acicular crystals ; pene- trating odour ; slightly soluble in water ; soluble in alcohol and ether ; sublimes on heating ; M.P. 116°. (A., 27, 268 ; 45, 354 ; 215, 125 ; B., 19, 1467 ; 20, 2283.) In an exactly similar way o-tolu-^>-quinone (M.P. 67°) may be prepared from o-toluidine. The next preparation illustrates the use of ^-diamines. Preparation 168.— Chloranil (1 : 4-Di-oxy-2 : 3:5: 6-tetrachloro-2 : 5- cyclo-hexadien). 0 I! ci/\ci II 0 20 gms. (1 mol.) of 2 : 6-dichloro-4-nitraniHne are reduced to 2:6. C 6 0 2 C1 4 . 246. 230 SYSTEMATIC OKGANIC CHEMISTRY dichloro-1 : 4-diaminobenzene by refluxing with 800 c.cs. (excess) of cone, hydrochloric acid and 30 gms. (excess) of tin. While still hot, 20 gms. (excess) of potassium chlorate are gradually added, the liquid being maintained at the boil for 15 minutes after all the chlorate has been added. The liquid is diluted with much water and filtered ; the precipitate is well washed with water, dried, and recrystallised from boiling toluene. 0 2 + ci 2 C 6 H 2 C1 2 (NH 2 ) 2 [2 : 6 : 1 : 4] > C 6 C1 4 0 2 . Yield. — 90% theoretical (22 gms.). Yellow leaflets ; characteristic odour ; insoluble in water ; sublimes on heating. (B., 36, 4390.) The potassium chlorate here both oxidises and chlorinates. If chromic acid, or even weaker oxidising agents, be employed the dichloro-quinone is obtained. The oxidation of aminophenols is illustrated in the follow- ing, in which nitrous acid serves as oxidising agent. Preparation 169. — a-Naphthoquinone (Benz-^-benzoquinone). 158. II O To 20 gms. (1 mol.) of finely powdered j9-amino naphthol, or an equiva- lent amount of one of its salts suspended in 100 c.cs. (excess) of hydro- chloric acid (D. 1-05), 20 gms. (excess) of sodium nitrite are slowly added. The precipitate formed is well washed with water, filtered, and dried on a porous plate. The filtrate is extracted with ether, the extract dried over calcium chloride, filtered, and the ether removed on a water bath at 60°. The residue and the dried precipitate are recrystallised from petroleum ether. 0 2 C 10 H 6 (OH)(NH 2 )[1 : 4] -> C 10 H 6 O 2 [l : 4]. Yield. — 80% theoretical (16 gms.). Yellowish plates ; characteristic odour ; soluble in hot alcohol ; volatile in steam ; sublimes at 100° ; M.P. 125°. (A., 183, 242.) Preparation 170. — /^-Naphthoquinone (Benz-o-benzoquinone). 0 158. 50 gms. (1 mol.) of finely powdered l-amino-2-naphthol (see p. 359) are suspended in 250 c.cs. of 30% sulphuric acid, and 30 gms. (excess) of 10% aqueous potassium or sodium dichromate solution slowly added with OXYGEN TO CARBON 231 mechanical stirring, the temperature being maintained at 0°. The precipitate is filtered off, well washed with water, dried on a porous plate, and recrystallised from petroleum ether. C 10 H 6 (OH)(NH 2 )[1 : 2] -> C 10 H 6 O 2 [l : 2]. Yield. — 75% theoretical (35 gms.). Red acicular crystals ; odourless ; non-volatile in steam ; M.P. 115°. (A., 189, 153 ; 194, 202 ; 211, 49 ; B., 25, 982.) The preparations of a- and ^-napthoquinone should be compared with those of phenanthraquinone, and the corresponding benzoquinones (see p. 227). CHAPTER XVI oxygen to carbon Hydroxy-Oxy Compounds Acids. Various hydrolytic and oxidation reactions give rise to acids — the hydroxy-oxy compounds which have the hydroxy and oxy groups attached to the one carbon. In none of the reactions is the product of necessity a hydroxy-oxy compound with these groups attached to different carbons. Reaction XCV. Hydrolysis of Nitriles (B., 19, 1950 ; 20, 241, 592 ; A,, 258, 10.) — On heating with aqueous solutions of mineral acids or alkalis, the nitriles are converted respectively into the corresponding acids or into the alkali salts of the latter. Aqueous solutions of sodium car- bonate can also be employed if the heating be performed under pressure. The reaction occurs in two stages. H 2 0 HOH EC i N > E.CO. NH 2 > E.COOH. It is difficult to stop the hydrolysis at the intermediate amide stage (see p. 222). It is not always necessary to isolate the nitriles on their formation in order to hydrolyse them to acids (see p. 153). Still without isolation, the acid formed can be simultaneously esterified by using for hydrolysis aqueous alcoholic solutions of sulphuric acid (see p. 249 ; cf. also p. 250). In all these hydrolyses water is always the hydrolysing agent ; the acid or alkali acts as a catalyst. Preparation 171. — Benzoic Acid (Phenyl-methan acid.) C 6 H 5 .COOH. C 7 H 6 0 2 . 122. 20 gms. (1 mol.) of phenyl cyanide (see p. 149) are refluxed with 300 c.cs. (excess) of 25% aqueous caustic potash until ammonia ceases to be evolved. The solution is diluted with half its volume of water, and cautiously acidified with concentrated hydrochloric acid under good cooling. The precipitate is filtered off at the pump, washed with cold water, and recrystallised from boiling water. C 6 H 5 CN + KOH + H 2 0 = C 6 H 5 COOK + NH 3 . Yield. — 90% theoretical (21 gms.). Colourless needles ; soluble in hot water, alcohol and ether ; volatile in steam ; sublimes on heating ; M.P. i 121°. 232 OXYGEN TO CARBON 233 Preparation 172.— ^J-Toluic Acid (l-Methyl-4-carboxyl-benzene). C 6 H 4 (CH 3 )(COOH)[I : 4]. C 8 H 8 0 2 . 136. 20 gms. (1 mol.) of ^-tolu-nitrile (see p. 149) are refluxed with 160 gms. (excess) of 85% sulphuric acid, until crystals appear in the condenser tube. The well-cooled mixture is diluted with two volumes of water, and the precipitate filtered off at the pump, well washed with cold water, and recrystallised from hot water or dilute aqueous alcohol with the addition of a little animal charcoal. H 2 0 C 6 H 4 (CH 3 )(CN)[1 : 4J > C 6 H 4 (CH 3 )(COOH)[l : 4]. Yield. — 85% theoretical (14 gms.). Colourless crystals ; soluble in hot water and in alcohol ; M.P. 178°. (A., 258, 10.) Preparation 173. — Phenyl Acetic Acid (Phenyl-ethan acid). C 6 H 5 CH 2 COOH. C 8 H 8 0 2 . 136. 50 gms. (1 mol.) of benzyl cyanide and 150 gms. (excess) of 80% sul- phuric acid are placed in a ^-litre round-bottomed flask connected by a glass tube bent twice at right angles with a second ^-litre round-bottomed flask fitted with a two-holed cork. The end of the tube is flush with the cork in one hole. Through the second hole passes a vertical glass tube, 50 cms. long, dipping just below the surface of 250 c.cs. of water in the flask. In the middle of this tube a large bulb is blown. The whole apparatus is fitted up in a fume cupboard. The mixture is gently heated by a naked flame, until small bubbles are seen to rise from the surface of the lower layer of acid. In a few minutes a vigorous reaction begins, the liquid in the flask boils, and a small quantity of benzyl cyanide distils over into the second flask, some of the water in which is forced up into the bulb. When the reaction is over, the flask is again heated for 3 minutes and allowed to cool, its contents solidifying in so doing. The solid residue is washed with cold water, dissolved in hot water, the solution neutralised with sodium carbonate, filtered hot, the nitrate acidified with dilute sulphuric acid, and allowed to stand. The crystals which separate are filtered off, washed with cold water, and recrystallised from hot water. 2C 6 H 5 CH 2 .CN + 4H 2 0 + H 2 S0 4 = 2C 6 H 5 CH 2 COOH + (NH 4 ) 2 S0 4 . Yield. — 80% theoretical (46 gms.). Colourless thin laminated crystals ; soluble in hot water ; M.P. 76-5 ; B.P. 262° ; K = 0-0056. (B., 19, , 1950 ; 20, 592.) Preparation 174. — a-Naphthoic Acid (l-Carboxyl-naphthalene)o COOH C 13L H 8 0 2 . 172. r 15 gms. (1 mol.) of a-naphthonitrile, 10 gms. (excess) of caustic soda, and 75 c.cs. of 95% alcohol are heated in a sealed tube (see p. 38) 234 SYSTEMATIC OKGANIC CHEMISTRY at 170° for 5 hours. On opening, the contents of the tube are diluted with 5 volumes of water, and carefully acidified with cone, hydrochloric acid. The precipitate is filtered at the pump, washed with water, and recrystallised from alcohol. C 10 H 7 CN + NaOH + H 2 0 = C 10 H 7 COONa + NH 3 . Yield. — 90% theoretical (15 gms.). Colourless crystals ; insoluble in water ; soluble in alcohol ; M.P. 160°. (B., 20, 241.) Reaction XCVI. Hydrolysis of Esters to Acids. (A., 186, 161 ; 204, 127 ; 215, 26.)— When esters are heated with water, hydrolysis occurs, but does not go to completion, the reaction being reversible. K.CO.ORi + H 2 0 ^ ECOOH + HOR^ If, however, aqueous or alcoholic caustic alkali be used, by combining with the acid as formed, it shifts the equilibrium point of the reaction, and almost complete hydrolysis occurs. This reaction could also have been dealt with under Chapter XIII, since alcohols are simultaneously formed ; however, the hydrolysis is more usually undertaken to obtain the acid. Other special cases of hydrolysis have been dealt with elsewhere (see Reaction LVIL). The general method of procedure will be clear from the following. Pkepaeation 175. — Acetic Acid (Ethan-acid). CH3.COOH. C 2 H 4 0 2 . 60. 20 gms. (1 mol.) of ethyl acetate (see p. 249) are refluxed with 80 gms. (excess) of 25% aqueous caustic potash for 1 hour, until the layer of ester has disappeared, and the mixture no longer smells of it. The whole is then distilled to 100° ; ethyl alcohol can be separated from the distillate by addition of anhydrous potassium carbonate. The residue in the flask is neutralised with dilute sulphuric acid and evaporated to dryness on a water bath. The solid residue is powdered and redistilled with 50 gms. of cone, sulphuric acid to 130°, and the distillate fractionated between 115° and 120°. CH 3 COOC 2 H 5 + KOH = CH 3 COOK + C 2 H 5 OH. 2CH3COOK + H 2 S0 4 = 2CH3COOH + K 2 S0 4 . Yield. — 90% theoretical (12 gms.). Colourless liquid or crystals ; characteristic odour; miscible with water; M.P. 16-7°; B.P. 119°; D. * 1-055. (Phil. Trans,, 156, 37 ; BL, 33, 350.) Pkepaeation 176. — Ethyl-malonic Acid (Ethyl-propan diacid). C 2 H 5 .CH(COOH) 2 . C 5 H 8 0 4 . 132. 20 gms. (1 mol.) of di-ethyl-malonate (see p. 251) are gradually added to 50 gms. (excess) of 50% aqueous caustic potash in a flask fitted with a reflux condenser, and cooled in water. The mixture so obtained is heated on a water bath with shaking until, after a vigorous reaction, complete liquefaction has occurred (1 hour). The liquid is cooled, diluted with an equal volume of water, acidified with cone, hydrochloric acid, and extracted with ether. The extract is dried over anhydrous sodium sulphate, OXYGEN TO CARBON 235 filtered, the ether removed on a water bath, and the residue recrystallised from benzene. The ethyl-malonic acid can also be worked up by precipitating its cal- cium salt from the neutralised solution by addition of a concentrated solution of calcium chloride, and treating the solid salt with cone, hydro- chloric acid, extracting the liberated acid with ether, and proceeding as above. C 2 H 5 CH(COOC 2 H 5 ) 2 + 2KOH = C 2 H 5 CH(COOK) 2 + 2C 2 H 5 OH. Yield. — 85% theoretical (12 gms.). Colourless prisms ; soluble in water, alcohol and ether ; M.P. 112°. (A., 204, 134.) Like all the malonic acids, this acid loses carbon dioxide on heating, yielding butyric acid, B.P. 163°. The reaction is carried out by heating 10 gms. of the acid in a reflux apparatus to 180° until carbon dioxide is no longer evolved (J hour). The residue is fractionated for butyric acid between 160° and 165°. Pkepakation 177. — Benzylmalonic Acid (Benzyl-propan diacid). C 6 H 5 .CH 2 .CH(COOH) 2 . C 10 H 10 O 4 . 194. 30 gms. (1 mol.) of benzylmalonic ester (cf. p. 136) are vigorously shaken in a 250-c.c. round-bottomed flask with 35 gms. (excess) of 33% aqueous caustic potash, the mixture warmed until solution occurs, and then heated for 1 hour on a water bath, no condenser being used. Oily by-products are extracted with ether, the liquid is made faintly acid with dilute hydrochloric acid, and the benzylmalonic acid liberated is extracted with ether, several treatments being necessary. The extract is dried over anhydrous sodium sulphate and filtered, the ether removed on a water bath, and the residue recrystallised from benzene. C 6 H 5 CH 2 CH(COOC 2 H 5 ) 2 + 2KOH = C 6 H 5 CH 2 CH(COOK) 2 + 2C 2 H 5 OH. Yield. — 85% theoretical (20 gms.). Colourless crystals ; insoluble in water ; M.P. 117° (Coir.). (A., 204, 174.) This acid on heating to 180° loses carbon dioxide and yields hydro- cinnamic acid (M.P. 47°) in almost theoretical yield. The following hydrolysis is important in the synthesis of collidine (see p. 404). Preparation 178.- — Potassium Collidine Dicarboxylate (Di-potassium- 2:4: 6-trimethyl-pyridine-3 : 5-dicarboxylate). C.CH 3 KO.OCc/^Sc-CO.OK. I C 14 H 9 0 4 NK 2 . 285. N 10 gms. (1 mol.) of diethyl-collidine dicarboxylate are refluxed on a water bath for 4 hours with about 10 times the volume (excess) of alcoholic potash (2-5 N approx.). The alcoholic solution is decanted from the separated potassium salt, a further yield of which is obtained by 236 SYSTEMATIC ORGANIC CHEMISTRY adding ether to the alcoholic solution. The total product is washed with alcohol then with ether and dried. C 5 N(CH 3 ) 3 (COOC 2 H 5 ) 2 - 2KOH = C 5 N(CH 3 ) 3 (COOK) 2 - 2C 2 H 5 OH. Yield. — Almost theoretical (11 gms.). White crystalline mass ; in- soluble in ether. (A.. 215. 26.) Reaction XCVII. Hydrolysis of Amides, Acyl Chlorides, and Acid Anhydrides. (A.. 188 3 73 : B.. 26. R.. 773 : 2S. R.. 917. 32. 1118.) — All these compounds on hydrolysis yield acids. The anhydrides are hydro- lysed by treatment with water or dilute alkali, the acid chlorides, are usually very rapidly hydrolysed by water, but in the aromatic series 10% caustic alkali is sometimes necessary. The amides are boiled with caustic alkali solution (10° 0 ), or with cone, hydrochloric or sulphuric acid. They are. especially the substituted aromatic amides, very resistant to the •Action of acids, so that the former method is the better. Another method is to dissolve the amide in cone, sulphuric acid, and add sodium nitrite in the cold, afterwards gently warming. Sometimes dilute sulphuric acid and addition of the nitrite in the warm gives better results. e 6 H 5 COXH 2 -f O : NOH = C 6 H 5 COOH + N 2 - H 2 0. Preparation 179. — Citraconic Acid ((7^-3-carboxyl-2-buten acid). CH 3 C.COOH C 5 H 6 0 4 . 130. II CH.COOH. 3-2 gms. (1 mol.) of water are added to 20 gms. (1 mol.) of citraconic anhydride, and the mixture well stirred. The whole solidifies, on standing, to a mass of crystals which are dried on a porous plate. CH 3 CH 3 ceo ceo. oh ; + H 2 0 CH.CO CH. CO. OH. Yield. — Theoretical (23 gms.). Colourless crystals : soluble in ether and chloroform : very soluble in water : M.P. 85° : K = 0-310. (A., 188. 73.) Reaction XCVIII. Simultaneous Oxidation and Hydrolysis of Benzyl and Benzal Chlorides and their Derivatives. (BL. 7. 100 ; B.. 10. 1275). — If benzyl or benzal chlorides, or their derivatives, be rerluxed with an aqueous solution containing sodium carbonate and potassium perman- ganate,, simultaneous hydrolysis and oxidation occurs, and benzoic acid or one of its derivatives is produced. NaoCo, 0 2 C fl H 5 .CH,.Cl C 6 H 5 CH,OH — ■> C 6 H 5 COOH. Na 2 C0 3 o„ C 6 H 5 .CH.C1 2 ► C 6 H 5 .CHO V C 6 H 5 COOH. OXYGEN TO CARBON 237 Preparation 180. — Benzoic Acid (Phenyl-methari acid). C 6 H 5 COOH. C 7 H 6 0 2 . 122. To a mixture of 10 gms. (6 mols.) of benzyl chloride, 8 gms. (excess) of anhydrous sodium carbonate, and 150 c.cs. of water boiling under a reflux condenser, 17 gms. (8 mols.) of potassium permanganate in 250 c.cs. of water are added gradually, and the boiling continued until the colour of the permanganate has been discharged. Sulphur dioxide is then bubbled through the warm liquid until the precipitated manganese dioxide has completely dissolved. On cooling, benzoic acid separates ; it is filtered at the pump, washed with a little cold water, and recrystallised from hot water. 6C 6 H 5 CH 2 C1 + 3Na 2 C0 3 + 3H 2 0 = 6C 6 H 5 CH 2 OH + 6NaCl + 3C0 2 . 6C 6 H 5 CH 2 OH + 8KMn0 4 = 6C 6 H 5 COOK + 8Mn0 2 + 2KOH + 8H 2 0. Yield. — Theoretical (9 gms.). Colourless needles ; soluble in hot water, alcohol and ether ; volatile in steam ; on heating melts and sublimes ; M.P. 121°. (Bl., 7, 100 ; B., 10, 1275.) Reaction XCIX. Oxidation of certain Carbon Compounds to less com- plex Compounds. (J. pr., 75, 146.) — Complex carbon compounds under vigorous oxidisation break up yielding simpler compounds usually highly oxygenated. These reactions are difficult to represent by means of equations, though a study of the structure of the original compound will indicate how the products come to be formed. The structure of a com- pound can often be deduced from its oxidation products. Oxalic acid is a frequent product of vigorous oxidation, especially of members of the sugar group. Its formation can be promoted by the use of catalysts. Preparation 181. — Oxalic Acid (Ethan diacid). COOH ( + 2H 2 0). C 2 H 2 0 4 ( + H 4 0 2 ). 90( + 36). COGH 140 c.cs. (excess) of cone, nitric acid and 0-1 gm. of vanadium pent- oxide are gently warmed in a 1 -litre round-bottomed flask on a water bath. The flask is then removed to a fume cupboard, and 20 gms. (1 mol.) of cane sugar are added all at once. As soon as brown fumes are evolved in large quantities, the flask is placed in cold water, and allowed to stand 24 hours, when the crystals which have separated are filtered off. A further small quantity may be obtained by allowing the mother liquors to stand. The crystals are drained on a small porcelain funnel without filter paper, and recrystallised from a very small quantity of water. C 12 H 22 O n + 90 2 = 6(COOH) 2 + 5H 2 0. Yield. — 25% theoretical (20 gms.). Colourless needles ; soluble in water and alcohol ; sparingly soluble in ether ; water of crystallisation given off at 100°— 105° ; M.P. 101-5° ; K = 10. (J. pr., 75, 146.) Reaction C. Oxidation of the Side chain in Aromatic Compounds. (A., 122, 184 ; 133, 41 ; 137, 308 ; 141, 144 ; 147, 292 ; B., 7, 1057 ; 19, 705 ; 238 SYSTEMATIC ORGANIC CHEMISTRY Z. Ch., 4, 119) (Fittig). — When aromatic compounds containing aliphatic side chains attached to the nucleus are treated with certain oxidising agents (potassium permanganate, dilute nitric acid, and chromic acid), the side chain is oxidised until only a carboxylic group attached to the nucleus remains ; the end methyl group, if there be several carbon atoms present, being first oxidised to carboxyl and split off, and so on down to the first. If several side chains be present the results vary with the reagent and the orientation of the side chains. Thus, if there be two, dilute nitric acid and potassium permanganate, oxidise only one side chain, while chromic acid oxidises both, unless they be in the or^o-position to one another, when the compound is either not attacked or destroyed. Some- what the same applies to nuclear substituted benzenes with one side chain ; the or^o-compound is often unattacked or destroyed, whereas the para- and meta-compounds yield the corresponding acids. Nitro groups in the ortho-position hinder oxidation ; with halogen groups the meta-compound is least, and the para most readily attacked. The methods for the employment of the various reagents mentioned will be clear from the following preparations. Particular attention should be paid to the method of oxidation of the side chains in phenols and amines. Before such oxidation can be carried out these substituting groups have to be protected, the phenol by forming its sulphuric or phosphoric acid ester, the amine by benzoylation or acetylation. For the protected amides, potassium permanganate in presence of magnesium sulphate is used : alkaline permanganate is the best oxidising agent for phenol esters. Peepakation 182. — Mesitylenic Acid (s-Dimethyl-benzoic acid). C e H 8 .(CH 8 ) a (COOH)[1.3.5]. C 9 H 10 O 2 . 150. Uvitic Acid (l-Methyl-3-5-dicarboxyl-benzene). C 6 H 3 (CH 3 )(COOH) 2 (l : 3 : 5). C 9 H 8 0 4 . 180. 20 gms. (1 mol.) of mesitylene are refluxed with 80 gms. (excess) of 30% nitric acid in a 250-c.c. round-bottomed flask, on a sand bath in a fume cupboard for 18 hours. The white residue is filtered off on cooling, washed with cold water, dissolved in sodium carbonate solution, unattacked mesitylene and nitromesitylene separated, and the mixed acids reprecipitated by acidification with dilute hydrochloric acid. The white precipitate is filtered off, washed with cold water, and heated on a water bath with tin and excess of strong hydrochloric acid for 2 hours with constant shaking in a capacious flask (caution ! hydrogen evolved). Nitro- mesitylenic acid, a by-product in the reaction, is thus reduced and brought into solution. On cooling, the undissolved portion is filtered off, washed with cold water, dissolved in dilute caustic soda, and reprecipitated from the hot filtered solution with dilute hydrochloric acid. The precipitate is a mixture of mesitylenic and uvitic acids. It is filtered off, washed with cold water and distilled in steam, till after several hours no further trace of mesitylene acid appears in the condenser, and the distillate ceases to have an acid reaction. The greater portion of the mesitylenic acid, v free from uvitic acid, is suspended in the distillate. It is filtered off OXYGEN TO CARBON 239 and the nitrate neutralised with caustic soda solution, evaporated to small bulk, acidified with dilute hydrochloric acid, and the usually some- what yellow-coloured acid thus obtained united to the first portion. The whole is redissolved in caustic soda solution, filtered boiling hot, precipitated by addition of dilute hydrochloric acid, washed wrEtroold water, and recrystallised from alcohol. It is then pure mesitylenic acid. Uvitic acid containing slight traces of mesitylenic acid separates from the residual liquid in the distilling flask on cooling. It is recrystallised from hot alcohol, after precipitation by acid from alkaline solution. C 6 H 3 (CH 3 ) 3 + 30 = C 6 H 3 (CH 3 ) 2 COOH + H 2 0. C 6 H 3 (CH 3 ) 2 .COOH + 30 = C 6 H 3 (CH 3 )(COOH) 2 + H 2 0. Yield. — Mesitylenic acid 50% theoretical (12 gms.). Uvitic acid 40% theoretical (12 gms.). Mesitylenic acid forms colourless monoclinic crystals ; difficultly soluble in hot water ; easily soluble in cold alcohol ; M.P. 166°. Uvitic acid forms colourless fine needles ; insoluble in cold and hot water ; readily soluble in alcohol and ether ; M.P. 287° — 288°. (A., 122, 184 ; 141, 144 ; 147, 292 ; Z. Ch., 4, 119.) The above illustrates the action of nitric acid in only oxidising one or two, and not all of the alkyl groups present, unless the heating be very r>rolonged. In the next preparation Method I. shows how chromic acid or alkali bichromate and sulphuric acid completely oxidises all the side chains present ; Method II. indicates how to oxidise completely the partially oxidised compound, potassium permanganate being sufficient. Preparation 183. — Terephthalic Acid (1 : 4-Benzene-dicarboxylic acid). C 6 H 4 (C00H) 2 [1 : 4]. C 8 H 6 0 4 . 166. Method I. (from ^-xylene). — 20 gms. (1 mol.) of ^-xylene are refluxed for 24 hours with 80 gms. (excess) of sodium or potassium bichromate and 250 gms. of 50% sulphuric acid. The unoxidised hydrocarbon is removed by distillation in steam, and the cooled solution filtered. The precipitate is purified by reprecipitation with acid from its dilute solution in sodium carbonate or caustic alkali. C 6 H 4 (CH 3 ) 2 [1 : 4] -> C 6 H 4 (C00H) 2 [1 : 4]. Yield.— 90% theoretical (28 gms.). (A., 133, 41.) Method II. (from j9-toluic acid). — 10 gms. (1 mol.) of jo-toluic acid (see p. 233) dissolved in 600 c.cs. (excess) of 1% caustic soda solution are refluxed on a water bath, and 5% aqueous potassium permanganate solution added until the red colour of the permanganate solution persists on boiling ; for this about 500 c.cs. of potassium permanganate solution will be required. Excess of permanganate is destroyed either by adding alcohol until the liquid is colourless, the alcohol being oxidised to acetalde- hyde or acetic acid, or sulphur dioxide is bubbled through the warm solution until all the manganese dioxide precipitated during the reaction dissolves. In the former method terephthalic acid is then precipitated after 'filtering off the manganese dioxide by addition of cone, hydrochloric 240 SYSTEMATIC OKGANIC CHEMISTRY acid at the boiling point, in the latter terephthalic acid is precipitated by the sulphur dioxide during the removal of excess of permanganate. In both, the acid is filtered from the cooled reaction mixture, well washed with cold water, and dried on a water bath. It is purified by reprecipita- tion with acid from an alkaline solution. CH 3 .C 6 H 4 .COONa + NaOH + 2KMn0 4 = C 6 H 4 (COONa), + 2KOH + Mn0 2 + 2H 2 0. Yield. — 90% theoretical (12 gms.). Colourless crystals ; insoluble in water and in alcohol ; sublimes without melting at 300°. (A., 137. 308.) The next preparation proves how, even when two side chains form part of a ring, the oxidation follows the same course, and an or$o-dicarboxyli< acid is obtained. The oxidising agent used will be noted ; it is more or less unique to this reaction. Preparation 184.— Phthalic Acid (1 : 2-Dicarboxy-benzene). C 6 H 4 (COOH) 2 [l : 2]. C 8 H 6 0 4 . 166. (This preparation must be carried out in a good fume cupboard.) 20 gms. (1 mol.) of naphthalene, 15 gms. of mercuric sulphate, and 350 gms. (excess) of cone, sulphuric acid are heated in a retort with its neck sealed to an air condenser acting as a reflux until all the naphthalene is dissolved. The retort is then lowered so that the air condenser slopes downwards and delivers into a receiver, cooled in water and containing 200 c.cs. of cold water. The contents of the retort are heated cautiously at first, and then vigorously at 300° until the residue in the retort is nearly dry. Unchanged naphthalene, phthalic acid and anhydride, carbon dioxide, sulphur dioxide, and water all distil. The distillate is filtered, the precipitate well washed with cold water, dissolved in caustic soda, filtered from unchanged naphthalene, reprecipitated by acidification with hydrochloric acid, and crystallised from water, or aqueous alcohol. C 10 H 8 + 9H 2 S0 4 = C 6 H 4 (COOH) 2 + 2C0 2 + 9S0 2 + 10H 2 O. Yield. — 60% theoretical (16 gms.). Colourless plates slightly soluble in cold water ; soluble in alcohol and hot water ; sublimes on heating to give phthalic anhydride (long needles ; M.P. 128°). (D.R.P., 91202.) Mercuric sulphate is used as a catalyst in the above oxidation, which is carried out on a large scale in the industrial preparation of indigo. Sulphuric acid may be looked upon as a carrier of the oxygen of the air, since in practice the sulphur dioxide evolved is reconverted to sulphuric acid by the contact process. The following two preparations illustrate the oxidation of side chains in phenols and purines respectively. Preparation 185. — ^-Hydroxy Benzoic Acid (l-Hydroxyl-4-carboxyl benzene). C 6 H 4 (OH)(COOH)[l : 4]. C v H 6 0 3 . 138. 10 gms. (1 mol.) of p-cresol are dissolved in the minimum quantity of water, and the solution heated at 70° for 10 hours with 15 gms. (excess) of potassium pyrosulphate. The crude potassium j?-cresyl sulphate formed is heated on a water bath with 25 gms. (excess) of potassium OXYGEN TO CARBON 241 hydroxide dissolved in 20 c.cs. of water, and 30 gms. (excess) of potassium permanganate in 750 c.cs. water gradually added. The whole is heated for 6 hours. Sulphur dioxide is then passed through the mixture to remove excess of permanganate, and the whole filtered hot. The filtrate is then boiled and acidified with hydrochloric acid, and heated to hydrolyse the sulphuric ester. On cooling, the acid crystallises out, the remainder being obtained by extracting with ether. It is recrystallised from ether. C 6 H 4 OH.CH 3 + 2KMn0 4 ->C 6 H 4 OHCOOH + 2Mn0 2 + 2KOH. Yield. — 90% theoretical (12 gms.). Colourless crystals ; soluble in hot water and in ether ; M.P. 210°. (B., 19, 705.) Preparation 186. — Anthranilic Acid (l-Amino-2-carboxyl-benzene). C 6 H 4 (NH 2 )(COOH)[l : 2]. C 7 H 7 0 2 N. 137. 20 gms. (1 mol.) of acet-o-toluidide (cf. Preparation 271) and 50 gms. (excess) of magnesium sulphate crystals are dissolved in 2 \ litres of water, the mixture heated to 80°, and 60 gms. (excess) of solid, finely powdered, potassium permanganate are added with mechanical stirring ; this is continued for 2 hours, during which the temperature is maintained at 85°. Excess of permanganate is removed by the addition of alcohol, the hot solution filtered, and the filtrate acidified with dilute sulphuric acid. The acetanthranilic acid precipitated is purified by reprecipitation from alkaline solution (M.P. 185°), It is hydrolysed to anthranilic acid by boiling with excess of dilute hydrochloric acid ; dilute alkali can also be employed. The acid is recrystallised from hot water. C 6 H 4 (NH.CO.CH 3 )(CH 3 )[l : 2] + 2KMn0 4 = C 6 H 4 (NHCOCH 3 )(COOH)[l : 2] + 2Mn0 2 + 2KOH. 2KOH + MgS0 4 = Mg(OH) 2 + K 2 S0 4 . H 2 0 C 6 H 4 (NHCOCH 3 )(COOH)[l : 2] > C 6 H 4 (NH 2 )(COOH)[l : 2]. Yield. — 80% theoretical (15 gms.). Colourless crystals ; soluble in - water and in alcohol ; sublimes on heating ; M.P. 145°. (D.R.P., 94629.) Reaction CI. (a) Oxidation of Primary Alcohols to the corresponding Carboxylic Acids. (A., 106, 79, 95; 120, 226 ; B., 9, 1902 ; C. (1907), 1, 1179.) — The primary alcohols are readily oxidised through the corre- sponding aldehyde to carboxylic acids containing the same number of carbon atoms. I K.CH 2 OH -> R.CHO -> R.COOH. Chromic acid or alkali dichft>mate and sulphuric acid is employed for the simpler alcohols ; polyhydric alcohols are usually oxidised with moderately dilute nitric acid ; if the acid be too concentrated the molecule may be attached as a whole (cf. Preparation 181). Preparation 187. — Acetic Acid (Ethan-acid). CH 3 COOH. C 2 H 4 0 2 . 60. To 80 gms. (excess) of finely powdered potassium or sodium dichromate, S.O.C. li 242 SYSTEMATIC ORGANIC CHEMISTRY and 100 gms. of 50% sulphuric acid placed in a reflux apparatus (see p. 206), 70 gms. (1 mol.) of 25% alcohol are slowly added. The mixture is heated for 30 minutes and distilled until only very little acid passes over. The distillate is neutralised with caustic potash, and evaporated to dryness on a water bath. The residue is powdered and distilled with cone, sulphuric acid to 139°, and the distillate fractionated between 115 c and 120°. 3C 2 H 5 OH + 2K 2 Cr 2 0 7 + 8H 2 S0 4 = 3CH 3 COOH + 2K 2 S0 4 + 2Cr 2 (S0 4 ) 3 + 11H 2 0. Yield. — 80% theoretical (18 gms.). Colourless liquid or crystals ; pungent odour ; miscible with water ; M.P. 16-7° ; B.P. 119° ; D. y 1-055. (C. (1907), I., 1179.) Preparation 188. — Glyceric Acid (2 : 3-Di-ol-propan-acid). OH.CH 2 .CH(OH).COOH. C 3 H 6 0 4 . 106. 50 gms. (1 mol.) of glycerol diluted with an equal volume of water are treated in a tall narrow glass cylinder with 50 gms. (excess) of 90% nitric acid, the latter being carefully run in below the surface of the glycerol from a funnel, the neck of which is drawn out into a fine tube, so that two layers are formed. The whole is allowed to stand at the ordinary temperature, till after some little time the liquid becomes homogeneous. The contents of several (six) such cylinders are slowly evaporated on a water bath to a syrup, 2 litres of water are added, and the solution (a) neutralised with lead carbonate and a small quantity of lead oxide. Towards the end of the operation the liquid is boiled and filtered hot. Crude lead gly cerate separates on concentrating and cooling the filtrate. The salt is detached by warming from the sides of the vessel, to which it adheres firmly. A second crop of crystals slowly separates on concen- trating the mother liquors. The finely powdered salt made into a paste with water is treated with hydrogen sulphide in 2-5 gm. lots, and the solution, filtered from lead sulphide, evaporated on a water bath, when the acid, remains as a thick syrup. The aqueous solution (a) may also be worked up for glyceric acid by boiling it with excess of calcium carbonate and filtering hot. The calcium gly cerate, which separates on cooling and concentrating, is recrystalfised from hot water, suspended in water, and decomposed by treatment with the theoretical quantity of oxalic acid determined by estimating the calcium by ignition in a sample of the salt. The clear solution filtered from calcium oxalate is evaporated as above. (OH)CH 2 .CH(OH)CH 2 (OH) + 0 2 = (OH)CH 2 CH(OH)COOH + H 2 0. Yield. — 80% theoretical (275 gms. from 300 gms. of glycerol). Strongly acid syrup, faintly yellow colour ; has never been crystallised ; soluble in water, alcohol and acetone ; insoluble in ether ; decomposes on boiling. (A., 106, 79, 95 ; 120, 226 ; B., 9, 1902.) Reaction CI. (b) Oxidation of Aldehydes to Carboxylic Acids. (B., 17, 1298 ; 24, 521 ; A., 227, 224.)— The aldehydes are very readily oxidised OXYGEN TO CARBON 243 to the corresponding acids ; in the oxidation of primary alcohols to acids, it is the first stage which is the more difficult to achieve. A great variety of oxidising agents may be employed — nitric acid is used for the less complex aldehydes ; in the sugar group, where the reaction is of importance (see below), bromine gives very good results. E.CHO + 0 = R.COOH. Preparation 189. — Gluconic Acid (Pentol-hexan acid -| 1 — \-). COOH H.C.OH H hJ'.oh c « h "°" 196 ' H.C.OH CH 2 OH. 50 gms. (1 mol) of glucose dissolved in 400 c.cs. of water are treated in a stoppered bottle with 100 gms. (excess) of bromine. The mixture is allowed to stand, with frequent shaking, for 3 days at ordinary tempera- tures, and then boiled in a porcelain dish in a fume cupboard with constant stirring, until all the bromine has disappeared. The solution is cooled, diluted with water to 500 c.cs., and neutralised with lead carbonate sus- pended in water. The precipitate is filtered at the pump, suspended in water and saturated with hydrogen sulphide, filtered and neutralised by boiling for J hour with precipitated chalk. The filtrate is evaporated to about 100 c.cs. and seeded in the cold with a crystal of calcium gluconate. After 24 hours the whole is filtered at the pump and the precipitate washed with cold water, redissolved in a small quantity of hot water, and boiled with addition of animal charcoal. The latter is filtered off and the solution treated with the exact quantity of oxalic acid in aqueous solution necessary to precipitate the calcium present, a portion of the precipitate obtained above being ignited and the calcium in it estimated for the purpose. The precipitated calcium oxalate is filtered off and washed, and the washings and filtrate evaporated to a syrup on a warm water bath under reduced pressure. C 5 H n 0 5 CHO + H 2 0 + Br 2 = C 5 H n 0 5 COOH + 2HBr. Yield. — 50% theoretical (30 gms.). Acid syrup ; has never been crystallised ; soluble in water ; on standing or heating changes in part to a crystalline lactone ; M.P. 130°— 135°. (B. 17, 1298.) This preparation is important in the sugar group, as it is possible to pass from one stereoisomeric acid to another by heating with pyridine — this enables the corresponding sugars to be transformed one into another by oxidation to the acid, transformation of the acid to its stereoisomer, and reduction of the lactone of the latter acid (see p. 184). Preparation 190. — Saccharic Acid (Tetrol-hexan-diacid -\ h +). COOH.(CHOH) 4 .COOH. C 6 H 10 O 8 . 210. 50 gms. (1 mol) of anhydrous glucose are heated in a dish on a water R 2 244 SYSTEMATIC ORGANIC CHEMISTRY bath with 350 gms. (excess) of 25% nitric acid and, while stirred mechani- cally, are evaporated to a syrup, which is dissolved in a little water, and again evaporated. Should the mass begin to show the slightest sign of charring, heating is immediately discontinued. The whole is dissolved in 200 c.cs. of water, and neutralised with a saturated solution of potassium carbonate. 25 c.cs. of 50% acetic acid are added and the liquid evaporated to about 75 c.cs. On frequent rubbing and long standing in the cold, acid potassium saccharate crystallises out, and is filtered at the pump after a further 12 hours standing, washed with a very little cold water, and recrystallised from hot water with addition of animal charcoal ; if not quite colourless, the operation is repeated. The salt is treated with excess of 10% hydrochloric acid and evaporated on a warm water bath under reduced pressure to a deliquescent mass, which is treated with absolute alcohol, filtered, and the nitrate evaporated under reduced pressure till all the alcohol is removed. CH„OH COOH )H) 4 > (CHOH) 4 'CI I CHO COOH. Yield. — 20% theoretical (12 gms.). Colourless deliquescent mass ; soluble in water ; very soluble in alcohol ; changes on standing to a crystalline lactone (M.P. 131°). (B., 24, 521.) This preparation illustrates the oxidation to a carboxylic acid, both of a primary alcohol and an aldehyde. The reaction also is of im- portance in the sugar group, for it is possible to reduce the carboxyl group in saccharic acid which comes from the aldehyde group, to a primary alcohol group while the carboxyl corresponding to the primary alcohol group is reduced to an aldehyde. In this way a new sugar stereoisomeric with the first may be obtained. Following is one of the applications of the method — (+- + +) > (+- + +) — M+ - + +) or ( + •+ - +) Glucose Gluconic acid Saccharic acid > (+ + -+) (+ + -+) Gulonic acid > Gulose. The next preparation illustrates the hydrolysis of a di-saccharose, and the simultaneous oxidation of the mono-saccharoses so formed. Preparation 191. — Mucic Acid (Tetrol-hexan-diacid -\ \-). COOH H.C.OH OH.C.H OH.C.H b 6 n 10 U 8 I ZAU - H.C.OH COOH OXYGEN TO CARBON 245 100 gms. (1 mol.) of lactose are heated on a water bath with 1,500 gms. (excess) of 25% nitric acid, the whole being continuously stirred, until the volume is reduced to 250 c.cs. The cooled acid mass is diluted with 750 c.cs. of water, filtered at the pump, well washed with cold water, and dissolved in just sufficient N/1 caustic soda solution (excess tends to repreeipitate the sodium salt). The latter solution is warmed with animal charcoal and filtered, and the acid reprecipitated by addition of the equivalent in 5N hydrochloric acid of the N/1 caustic soda used for solution. During this addition the temperature must not rise above 15°, otherwise the lactone of the acid may be formed. The whole is kept for 12 hours in a freezing mixture, and the precipitate filtered at the pump, well washed with cold water and dried on a water bath. C12H22OH + H 2 0 = C 6 H 12 0 6 + C 6 H 12 0 6 . Lactose. Glucose. Galactose. _0 2 C 6 H 12 0 6 > C 6 H 10 O 8 . Glucose. Saccharic acid. _0 2 C 6 H 12 0 6 > C 6 H 10 O 8 . Galactose. Mucij acid. Saccharic acid being soluble in water remains in solution. Yield. — 55% theoretical (32 gms.). White crystalline powder ; almost insoluble in cold water and in alcohol ; M.P. 210° (with decomposition). (A, 227, 224.) CHAPTER XVII oxygen to carbon Oxide-Oxy Compounds Esters and Acid Anhydrides This section deals first with the preparation of alkyl-acyl oxide com- pounds — esters — by the interaction of an acid or an acid derivative and an alcohol. The various methods used all have their origin in the fact that the formation of an ester and water from a mixture of an acid and an alcohol is a reversible reaction, and special measures have to be adopted to displace the equilibrium towards the complete formation of ester. The second portion of the section discusses the preparation of di-acyl oxide compounds — acid anhydrides. Reaction CII. Direct Action of an Acid on an Alcohol. (A. Ch., 58, 44.) — Few normal esters are prepared in this way — dimethyl oxalate being an exception ; in this case the water formed is probably prevented from inducing the back reaction by the presence of anhydrous oxalic acid — even so, the yield is only 40%. With acid esters, however, good yields can be obtained, since only incomplete esteriflcation is required. /COOH /COOEi E.< + KiOH = E< + H 2 0. \COOH \COOH Preparation 192. — Di-Methyl Oxalate (Di-methyl ester of ethan-diacid). COO.CHg I C 4 H 6 0 4 . 118. COO.CH3 In order to prevent hydrolysis of the ester as it is formed, it is necessary in this preparation to use anhydrous oxalic acid and to purify and dry the methyl alcohol as described on p. 206. 63 gms. (1 mol.) of oxalic acid crystals are powdered and heated on a boiling water bath till no more water is given off (1 — 2 hours), and are then heated in an air oven at 110° — 120° until the required loss in weight (18 gms.) has taken place. During the heating, the acid should be pow- dered occasionally. The anhydrous acid is refluxed on a water bath with 50 gms. (excess) of pure anhydrous methyl alcohol for 2 J hours, excess alcohol removed on a water bath, and the residue distilled to 120° ; the water is run out of the condenser, and the fraction 160° — 165° collected. The solid portion is filtered off, dried on a porous plate, and recrystallised from methyl or ethyl alcohol. 246 OXYGEN TO CARBON 247 COOH | + 2CH 3 .OH = j < + 2H 2 0. COOH COOCH3 Yield. — 40% theoretical (25 gms.). Colourless crystalline plates ; somewhat soluble in alcohol ; M.P. 54° ; B.P. 163°. (A. Ch., 58, 44.) In the next preparation the forward reaction is assisted by removal of the ester as fast as it is produced (cf. Reaction CIIL). This is only possible when a strong acid is present to act as a catalyst— the hydrogen ions cause fresh ester rapidly to be formed (see also under Reaction CVIL). It is necessary that the ester should be volatile, or in some other manner readily removable from the sphere of the reaction. Preparation 193.— Ethyl Nitrate (Ethyl-ester of nitric acid). CH 3 .CH 2 .O.N0 2 . C 2 H 5 0 3 N. 91. To 20 gms. (1 mol.) of cold " boiled-out " 67% nitric acid, 2 gms. of urea in 15 gms. (excess) of absolute alcohol are added, and half of the mixture distilled off on a water bath in a tubulated retort attached to condenser and receiver. 40 gms. of similar nitric acid mixed with 30 gms. of absolute alcohol, and containing 0-5 gm. of urea, are now allowed to drop in through the tubulus from a tap-funnel at the same- rate as the liquid distils. Water is added to the distillate, the ester which separates is washed several times with cold water, dried over calcium chloride, and distilled from a water bath, the fraction 84° — 88° being retained. Care must be taken in this experiment, as the ester is liable to explode when quickly heated. All operations should be carried out behind a metal screen. C 2 H 5 OH + HNO3 = C 2 H 5 N0 3 + H 2 0. Yield. — 75% theoretical (22 gms.). Colourless liquid ; characteristic odour ; liable to explode when quickly heated ; B.P. 86° ; D. x 4 5 1-112. Urea is used above to decompose any nitrous acid formed, as the presence of the latter tends to cause explosion. CO(NH 2 ) 2 + 2HN0 2 = C0 2 4- 2N 2 + 3H 2 0. (C. (1903), II., 338 ; B., 14, 421.) The following illustrates the preparation of acid esters. Preparation 194. — Ethyl Hydrogen Tartrate (Monoethyl ester of di- hydroxy-butan diacid). CH(OH).COOH I CH(OH).COOC 2 H 5 C 6 H 10 O 6 . 178. 20 gms. (1 mol.) of finely powdered tartaric acid and 30 gms. (excess) of absolute alcohol are heated for 6 hours at 70° on a water bath in a reflux apparatus. An equal volume of water and then an excess of powdered barium carbonate are added, and the liquid filtered from barium tartrate and excess of barium carbonate. The filtrate is evaporated to crystal- lisation on a water bath, cooled, and the crystals of barium ethyl-tartrate which separate filtered off at the pump and dried on a porous plate. 248 SYSTEMATIC ORGANIC CHEMISTRY They are weighed and treated with the theoretical amount of 2N sulphuric acid to precipitate the barium present, barium sulphate is filtered off, and the nitrate evaporated to crystallisation point. The crystals which separate are recrystallised from a little water. CH(OH)COOH CH(OH)COOC 2 H 5 I + C 2 H 5 .OH = | • +HoO, CH(OH)COOH CH(OH)COOH Yield. — 70% theoretical (17 gms.). Colourless crystals ; somewhat soluble in water ; M.P. 90°. (A., 22, 248.) By a repetition of the above process, using the alkyl hydrogen tartrate, di-ethyl tartrate can be obtained but the yield is poor. When cone, sulphuric acid acts on the alcohols, the acid esters only are formed, though sulphuric acid, by its great affinity for water, promotes almost complete esterification in other instances (see Reaction CVII.) ; for the preparation of normal sulphuric esters, see Preparation 207. Reaction CIII. — Continual removal of Water in a suitable Apparatus. (P. R. S., 25, 831 ; J. C. S., 87, 1657.)— In this method, which requires little elaboration, it is necessary that the acid and ester have high boiling- points compared with that of water. The latter is continually volatilised with the alcohol and circulated over a dehydrating agent which absorbs it — the alcohol being returned to the reaction vessel. Prepaeation 195. — Di-ethyl Tartrate (Di-ethyl ester of di-hydroxy- butan-diacid). CH(OH)COOC 2 H 5 I C 8 H 14 0 6 . 206. CH(OH)COOC 2 H 5 . Method I. — The apparatus described in Preparation 1 is fitted up, a 500-c.c. flask being used, and 30 gms. (1 mol.) of finely powdered tartaric acid, 150 gms. (excess) of absolute alcohol, and 50 gms. of crystallised benzene are placed in the flask. The object of the benzene is to help to volatilise the water produced by forming with it and the alcohol the low boiling ternary system — alcohol-benzene-water. The iron tube is packed with small lumps of good quicklime, and is heated to a temperature of 90°. The mixture in the flask is boiled, a few pieces of porous porcelain being added to promote steady ebullition. Esterification proceeds almost to completion, owing to the removal by the quicklime of the water formed. After 6 hours, the liquid in the flask, which will have become quite viscid owing to the formation of the ester, is distilled on a water bath until all the benzene and excess of alcohol have been removed ; the residue is fractionated from a metal bath under reduced pressure. Yield.— 90% theoretical (37 gms.). (P. R. S., 25, 831 ; J. C. S., 87, 1657.) Method II. — The apparatus (Fig. 46) is fitted up, being held in position by a clamp holding the condenser C. In the flask A are placed 150 gms. of tartaric acid (or other acid to be esterified), which need not be specially dried or powdered, and which is just covered with alcohol. B contains 140 gms. (3 mols.) of the latter, and 100 gms. of fresh potassium carbonate OXYGEN TO CARBON 249 or other suitable solid desiccating agent. The apparatus communicates with the open air only by means of the tube E. A is immersed to the neck in an oil bath which is slowly heated to 130°, and as soon as most of the alcohol in it has distilled into B, the latter is heated on a boiling water bath. The alcohol in B passes up the fractionating column D, which assists the action of the dehydrating agent, and into A whence what does not combine with the acid, and the water formed in the esterification, distil into B. After 10 hours, the excess of alcohol is distilled off from A, and the residue fractionated from a metal bath under reduced pressure. Yield.— 80% theoretical (165 gms.). (J. C. S., 79, 517.) (CH(OH)COOH) 2 + 2C 2 H 5 OH = (CH(OH)COOC 2 H 5 ) 2 + 2H 2 0. Colourless viscid liquid ; insoluble in water ; miscible with alcohol ; B.P. 11 155° ; B.P. 28 164° ; D. 2 1-072. Di-methyl tartrate (B.P. 760 280° ; D. 1-34) is prepared in an exactly similar manner. Reaction CIV. Use of Concentrated Sulphuric Acid or of Hydrogen Chloride to promote Esterification. (B., 13, 1176 ; 28, 1150, 3252 ; Phil. Trans., 156, 37 ; BL, 33, 350 ; J., (1874), 352 ; A., 204, 126.)— Cone, sulphuric acid being a dehydrating agent is frequently used to promote esterification ; it also acts as a catalyst increasing the speed of the reaction, though in so doing it does not change the equinbrium point. Saturation of the alcohol used with hydrochloric acid has also been employed with the same end in view, but it has been found that 4% hydrogen chloride in the alcohol gives even better results. Hence it is probable that this acid acts catalytically and not as a dehydrating agent. Peepaeation 196.— Ethyl Acetate (Ethyl ester of ethan acid). CH 3 .COOC 2 H 5 . C 4 H 8 0 2 . 88. 200 c.cs. of a mixture of equal volumes of glacial acetic acid (1 mol.), and absolute alcohol (1 mol.), are added drop by drop at the same speed as the liquid distils, to a mixture of 50 c.cs. of cone, sulphuric acid, and 50 c.cs. (excess) of absolute alcohol in a distilling flask attached to a condenser and receiver and heated in a metal bath kept at 140°. The distillate is shaken in an open tap-funnel with aqueous sodium carbonate solution until the upper layer is no longer acid to moistened blue litmus paper. This layer is shaken with 50 c.cs. of a 50% aqueous solution of calcium chloride to remove alcohol, and then allowed to stand 24 hours in contact with calcium chloride. It is filtered through a dry filter paper and fractionated on a water bath, the fraction 73° — £0° being redistilled. CH3COOH + C 2 H 5 OH = CH 3 COOC 2 H 5 + H 2 0. Yield. — 85% theoretical (130 gms.). Colourless liquid ; characteristic odour ; somewhat soluble in water ; miscible with alcohol, ether and acetic acid ; B.P. 78° ; D. * 0-9068 : D. 2 4 ° 0-900. (Phil. Trans., 156, 37 ; BL, 33, 350). Methyl acetate (B.P. 57°, D, f 0-904) is prepared in a similar manner from methyl alcohol. 250 SYSTEMATIC ORGANIC CHEMISTRY Preparation 197. — Di-ethyl Tartrate (Di-ethyl ester of butan-diol diacid). (CH(OH)COOC 2 H 5 ) 2 . C 8 H 14 0 6 , 206. 50 gms. (1 moL) of finely powdered tartaric acid are refluxed on a water bath with 150 c.cs. (excess) of absolute alcohol until dissolved, and the solution saturated with hydrogen chloride at 0° C. After 12 hours it is heated under reduced pressure on a water bath to remove hydrogen chloride, excess of alcohol and water, and the residue, which consists chiefly of ethyl hydrogen tartrate, treated with a further 150 c.cs. (excess) of absolute alcohol, the mixture again saturated with hydrogen chloride at 0° C, and allowed to stand for 12 hours. It is then fractionated under reduced pressure, and the fraction, B.P. 11 152°— 158° or B.P. 18 - 20 159°— 168°, refractionated under reduced pressure. Yield. — 80% theoretical (55 gms.). Colourless viscid liquid ; insoluble in water ; miscible with alcohol ; B.P. 11 155° ; B.P. 23 164° ; D. J 1-072. (B., 13, 1176.) The above exemplifies the old method of saturation of the mixture with hydrogen chloride ; the Fischer-Speir modification, illustrated in the following preparation, can be employed ; the time for the preparation is shortened, and only half the above quantity of alcohol is required. Preparation 198. — Ethyl Benzoate (Ethyl ester of benzoic acid). C 6 H 5 .COOC 2 H 5 . C 9 H 10 O 2 . 150. 150 gms. (excess) of absolute alcohol are cooled in ice, and dry hydrogen chloride bubbled through it until an increase in weight of 6 gms. has been obtained. 50 gms. (1 mol.) of benzoic acid are added, and the whole refluxed for 2 hours until on pouring a sample into water no benzoic acid separates. The excess of alcohol is removed on a water bath, the residue diluted with 2 volumes of water, and the whole shaken in an open vessel with solid sodium carbonate until any acid present is removed. The ester is then extracted with ether, the extract dried for 24 hours over pure potassium carbonate and fractionated, the fraction 204° — 213° being redistilled. The carbonate should be made by heating the bicarbonate, in order to ensure its being pure and anhydrous. C 6 H 5 .COOH + C 2 H 5 OH = C 6 H 5 COOC 2 H 5 + H 2 0. Yield. — 80% theoretical (49 gms.). Colourless oil ; sweetish odour ; insoluble in water; miscible with alcohol and ether; B.P. 700 211°; D. l ! 1-05 ; D. 20 1-047. (B., 28, 1150.) The above preparation can also be performed using 10 gms. of sulphuric acid, 100 gms. of absolute alcohol, and 50 gms. of benzoic acid. Although less alcohol is used, the yield is 90% theoretical, being probably increased by the dehydrating action of the sulphuric acid. Methyl benzoate (B.P. 199°) can be prepared in a similar manner. The following exemplifies the preparation of an ester by the above methods, using a salt of an acid from which the mineral acid present liberates the free acid. This modification is especially useful when the acid it is required to esterify is difficult to isolate in a free state. OXYGEN TO CARBON 251 Preparation 199. — Di-ethyl Malonate (Di-ethyl ester of propan diacid). CH 2 (COOC 2 H 5 ) 2 . C 7 H 12 0 4 . 160. For this esterification 250 c.cs. (excess) of absolute alcohol are employed to 100 gms. of hydrated calcium malonate, which has been dried as com- pletely as possible on a water bath, or to 95 gms. of the anhydrous salt of the acid. It is better to use the latter. 20 gms. of the dried salt are placed in a litre flask, all the absolute alcohol is poured on to it, and a stream of well-dried hydrogen chloride is passed in, so that the liquid becomes warm. The remainder of the calcium salt is added in 15-gm. lots as fast as the previous portion disappears. By this means caking of the calcium salt is prevented. The complete solution should take about 30 minutes, by which time the alcoholic liquid will be saturated with hydrogen chloride. After standing for 24 hours, the solution is evaporated to a small volume under reduced pressure, and the residual ester dissolved in ether. The ethereal solution is dried over calcium chloride, the ether removed on a water bath, and the residue fractionated, the fraction 195° — 198° being retained. CH 2 (COO) 2 Ca + 2HC1 + 2C 2 H 5 OH = CH 2 (COOC 2 H 5 ) 2 + CaCl 2 + 2H 2 0. Yield. — 75% theoretical (65 gms.). Colourless liquid ; B.P. (uncorr.) 195° ; B.P. (corr.) 197°— 198° ; D. « 1-068. (A., 204, 126.) Preparation 200. — Amyl Nitrite (Amyl ester of nitrous acid). 0:N.O.C 5 H u . C 5 H n 0 2 N. 117. 30 gms. (2 mols.) of amyl alcohol and 20 gms. (excess) of sodium nitrite are treated in a 500-c.c. round-bottomed flask cooled in ice, with 18 gms. (excess) of cone, sulphuric acid added drop by drop with constant shaking. The addition must be carried out in a fume cupboard, and care must be taken not to inhale the vapour of the amyl nitrite. When all the acid is added, the top layer of ester is separated and the residue shaken with water ; the further quantity of ester which separates is added to that first obtained, and the whole washed with water, separated, dried for 24 hours over calcium chloride and distilled, the fraction 94° — 101° being redistilled. 2C 5 H n OH + 2NaN0 2 + H 2 S0 4 = 2C 6 H u ONO + Na 2 S0 4 + 2H 2 0. Yield. — 75% theoretical (30 gms.). Greenish-yellow liquid ; charac- teristic odour ; insoluble in water ; miscible with ether and alcohol ; B.P. 760 96° ; D. J 0-902. (J., (1874), 352.) Reaction CV. Action of Acid Anhydrides on Alcohols and Phenols. (B., 12, 2059 ; 21, 1172.)— This method is not greatly used, owing to the acid anhydrides not being so readily obtainable as the acids themselves or the acid chlorides (see Reaction CIX.). It is chiefly employed in the preparation of the acetates of alcohols with the purpose of determining the percentage of hydroxyl present. 2K 1 OH + (R u CO) 2 0 = 2E- 11 COOE 1 + H 2 0. 252 SYSTEMATIC OKGANIC CHEMISTRY The esterification is brought about by heating the alcohol and anhydride together, usually with the addition of a dehydrating agent — e.g., fused zinc chloride, anhydrous sodium acetate, etc. The presence of alkali often facilitates the interaction. Preparation 201. — Mannitol Hexacetate. (CH 2 O.COCH3)(CHO.COCH 3 ) 4 (CH 2 O.COCH 3 ). C 18 H 26 0 12 . 434. 10 gms. of mannitol, 10 gms. of fused sodium acetate, and 40 gms. acetic anhydride, are placed in a small flask provided with a reflux con- denser and heated, at some distance above a wire gauze, to gentle boiling for an hour. The product is poured into water, well stirred and broken up with a glass rod. After some time it is filtered off, washed with water, and recrystallised from alcohol. CH 2 OH(CHOH) 4 CH 2 OH + 3(CH 3 CO) 2 0 -> C 18 H 26 0 12 + 3H 2 0. Yield. — Almost theoretical (24 gms.). Colourless crystals ; insoluble in water ; soluble in hot alcohol ; M.P. 119°. (B., 12, 2059.) The above preparation represents a general method for the preparation of acetyl derivatives of hydroxy compounds. Fused zinc chloride may be used in place of fused sodium acetate, but charring of the product is more likely to occur. The next preparation illustrates the action of the anhydride of a dibasic acid. Preparation 202. — Methyl Hydrogen Succinate (Mono-methyl-ester of butan diacid). CH 2 COOCH 3 | C 5 H 8 0 4 . 132. CH 2 COOH. 10 gms. (1 mol.) of succinic anhydride (see p. 259) are refluxed with 10 gms. (excess) of pure methyl alcohol (see p. 206) for 1 hour, excess of alcohol is removed under reduced pressure at ordinary temperature, and the residue recrystallised from hot carbon disulphide (Caution !) CH 2 CO x CH 2 CO.OCH 3 | >0 + CH 3 OH = | CH 2 C(K CH 2 CO.OH. Yield. — Almost theoretical (13 gms.). Glistening plates ; ' insoluble in water ; M.P. 57° ; B.P. 20 151°. (C, (1904), [1], 1484.) Phenols and naphthols also can be readily acetylated, using acetic anhydride. The general method is shown in the next preparation. Preparation 203. — ^-Naphthyl Acetate (Acetyl derivative of 2-hydroxy- naphthalene). /\/\O.CO.CH 3 . I I I C 12 H 10 O 2 . 186. 10 gms. (1 mol.) of /S-naphthol are refluxed for 15 minutes with 20 gms. (excess) of acetic anhydride, and the whole poured into cold water. OXYGEN TO CARBON 253 The precipitate is filtered at the pump, washed with cold water, and recrystallised from aqueous alcohol. 2C 10 H 7 OH + (CH 3 CO) 2 0 = 2C 10 H 7 O.COCH 3 + H 2 0. Yield. — Theoretical (135 gms.). Colourless crystals ; insoluble in water ; M.P. 70°. (A., 209, 150.) An example is here given of the reduction of an anthraquinone to its unstable dihydroxy-anthracene derivative, and the simultaneous acetylation of the latter to form the stable di-acetyl compound. Preparation 204. — Di-acetoxy-Anthracene (Di-acetyl derivative of 9 : 10-di-hydroxy-anthracene). C.O.CO.CHg C 6 H 4 /|\c 6 H 4 C 18 H 14 0 4 . 294. C.O.CO.CH3. 10 gms. (1 mol.) of anthraquinone are refluxed for 30 minutes with 150 gms. (excess) of acetic anhydride, 10 gms. of fused sodium acetate (see p. 506), and 40 gms. (excess) of zinc dust, and the cooled mixture filtered at the pump. The residue is recrystallised three times from glacial acetic acid. C 6 H 4 (CO.) 2 C 6 H 4 + (CH 3 CO) 2 0 + H 2 = (C 6 H 4 )(CO.COCH 3 ) 2 C 6 H 4 + H 2 0. Yield. — Almost theoretical (14 gms.). Colourless needles ; insoluble in water ; M.P. 260°. (B., 21, 1172.) Reaction CVI. Action of Acyl Chlorides on Alcohols. (B., 17, 2545 ; 19, 3218 ; 21, 2744 ; 23, 2962 ; A., 245, 140 ; 301, 102 ; 327, 105 ; J. pr., [2], 20, 263.) — Acid chlorides, especially of the aliphatic series, react with alcohols and phenols to give esters. K^OH + K^CO.Cl = Kn.CO.OKj + HC1. With aromatic acyl chlorides the reaction is not so rapid, but it can be greatly facilitated by the presence of caustic soda or caustic potash in dilute aqueous solution (Schotten-Baumann). RiOH. + RuCOCl + NaOH = Rn.CO.ORj + NaCl + H 2 0. Other alkalis can be employed — carbonates of the alkali and alkaline earth metals — pyridine, too, gives very good results, though with poly- hydric alcohols the number of groups esterified may differ with organic and inorganic bases. Acetyl and such- like aliphatic derivatives of hydroxy compounds cannot be prepared in this way, owing to the great instability of the acyl chlorides in presence of alkali ; however, the esteriflcation here takes place sufficiently rapidly without its use. The Schotten-Baumann reaction can also be applied to primary and secondary aromatic amines (see p. 296) ; it is much used in the identi- fication of compounds to which it can be applied, by the preparation of their benzoyl, phenyl acetyl, or benzene sulphonyl derivatives. 254 SYSTEMATIC ORGANIC CHEMISTRY Preparation 205.— Ethyl Acetate (Ethyl ester of ethan acid). CH 3 .COO.C 2 H 5 . C 4 H 8 0 2 . 88. To 10 gms. (excess) of absolute alcohol, 15 gms. (1 mol.) of acetyl chloride see p. 324) are added drop by drop with good cooling and shaking, the temperature not being allowed to rise above 20°. The whole is carefully diluted with an equal volume of saturated brine, and the ethyl acetate which floats on the surface separated, well washed with a 50% solution of calcium chloride to remove alcohol, dried for 24 hours over calcium chloride, and fractionated, the fraction 74° — 81° being redistilled. CH3COCI + C 2 H 5 OH = CH 3 .COOC 2 H 5 + HC1. Yield. — Almost theoretical (16 gms.) (see p. 249). Preparation 206. — Methyl Benzoate (Methyl ester of benzene-mono- carboxylic acid). C 6 H 5 .COOCH 3 . C 8 H 8 0 2 . 136. 10 gms. (1 mol.) of benzoyl chloride are refluxed for 15 minutes with 15 gms. (excess) of methyl alcohol, and the product twice fractionated between 190° and 203°. C 6 H 5 C0C1 + CH3OH = C 6 H 5 COOCH 3 + HC1. Yield. — Almost theoretical (9 gms.). Colourless sweet-smelling oil ; insoluble in water ; B.P. 700 199° ; D. w 1-086. Ethyl benzoate (see p. 250) can be prepared in an exactly similar manner. The following preparation shows the use of a sulphonic acid chloride. Preparation 207. — Di-methyl Sulphate (Di-methyl ester of sulphuric acid). (CH 3 ) 2 S0 4 . C 2 H 6 0 4 S. 126. (Di-methyl sulphate is very poisonous, and great care must be taken not to inhale any of its vapour. This preparation must be carried out in a good fume cupboard.) 100 gms. (excess) of chlorosulphonic acid (see p. 507) are placed in a 250-c.c. distilling flask fitted with a rubber stopper, carrying a thermometer the bulb of which is immersed in the acid, and cooled to —10° ; 30 gms. (excess) of pure anhydrous methyl alcohol are slowly dropped in during 2 hours by means of a dropping funnel, the stem of which is drawn out to a fine point, and then bent upwards so that the opening is just below the surface of the acid in the flask. Care must be taken that initially the stem of the funnel is full of alcohol. The side tube of the flask is con- nected with three wash-bottles, the first containing cone, sulphuric acid, and the third cold water to absorb the hydrogen chloride evolved ; the second is empty, and reversed to prevent the water sucking back into the sulphuric acid. During the addition, the flask is frequently shaken, and throughout the temperature must not be allowed to rise above — 10°. When all the alcohol has been added, the mixture is cautiously distilled at 20mms. from an oil bath at 140°. The ester which comes over is washed OXYGEN TO CARBON 255 with a little ice-water, dried over anhydrous sodium sulphate for 24 hours, and re-distilled at 20 mms. as before. Cl.S0 2 .OH + 2CH 3 .OH = S0 2 (OCH 3 ) 2 + HC1 + H 2 0. Yield. — 90% theoretical (50 gms.). Colourless odourless liquid ; emits a very poisonous vapour ; B.P. 7i; " 188°. (A., 327, 105.) An acid chloride as prepared from the acid can often be used directly, without any special purification. Preparation 208.— Dimethyl Terephthalate (Di-methyl ester of 1 : 4- benzene-dicarboxylic acid). COOCH3. /\ C 10 H 10 O 4 . 194. coocHg. 10 gms. (1 mol.) of terephthalic acid (see p. 239) are warmed with 13 gms. (2 mols.) of phosphorus pentachloride until liquefaction occurs, 20 gms. (excess) of methyl alcohol are added, and the whole refluxed for 2 hours. On cooling, the precipitate is filtered off and recrystallised from methyl alcohol. PC1 5 CH3OH C 6 H 4 (COOH) 2 C 6 H 4 (C0C1) 2 > C 6 H 4 (COOCH 3 ) 2 . Yield. — 80% theoretical (9 gms.). Colourless crystals ; insoluble in water ; M.P. 140°. (A., 245, 140 ; J. pr., [21, 20, 263 ; D.K.P., 38973 ; 70483; 71446.) Sodium terephthalate can be used alone in place of the free acid. The following preparations exemplify the Schotten-Baumann reaction. Preparation 209. — Methyl Benzoate (Methyl ester o£ benzene mono- carboxylic acid). C 6 H 5 COOCH 3 . C 8 H 8 0 2 . 136. 20 gms. (excess) of methyl alcohol are added to 15 gms. (1 mol.) of benzoyl chloride and then 10% caustic soda solution, until the whole is alkaline. The mixture is well shaken, warmed gently, until the smell of benzoyl chloride has completely disappeared, and poured into water. The layer of ester is dissolved in ether, the solution dried over calcium chloride, and distilled, the fraction 195° — 205° being redistilled. C 6 H 5 .C0C1 + CH 3 OH + NaOH = C 6 H 5 COOCH 3 + NaCl + H 2 0. Yield.— 90% theoretical (12 gms.) (see p. 254). (B., 17, 2545 ; 19, 3218 ; 21, 2744 ; 23, 2962.) Ethyl benzoate, glyceryl tri -benzoate, etc., are prepared in an exactly similar manner. The reaction can also be applied to phenols and naphthols. Preparation 210. — Phenyl Benzoate (Phenyl ester of benzene -m duo- carboxylic acid). C 6 H 5 COOC 6 H 5 . C 13 H 10 O 2 . 198. 10 gms. (excess) of phenol are dissolved in 100 c.cs. of water and 10 gms. 256 SYSTEMATIC ORGANIC CHEMISTRY (1 mol.) of benzoyl chloride added, and then 10% aqueous caustic soda solution until the whole is alkaline. The mixture is warmed and shaken until the smell of benzoyl chloride has disappeared ; the ester which separates is filtered off at the pump, washed with cold water, dried on a porous plate, and recrystallised from alcohol. C 6 H 5 .C0.C1 + C 6 H 5 OH + NaOH = C 6 H 5 COOC 6 H 5 + NaCl + H 2 0. Yield. — Almost theoretical (21 gms.). Colourless crystals ; insoluble in water ; M.P. 68°. (B., 17, 2545 ; 19, 3218 ; 21, 2744 ; 23, 2962.) a- and /3-naphthyl benzoates (M.P. ; 56° and 107° respectively) are similarly prepared. Pyridine is the base used in the next preparation. Preparation 211. — Mannitol Di-benzoate (Dibenzoic ester of hexcl- hexan). C 6 H 8 (OH) 4 (O.OC.C 6 H 5 ) 2 . C 20 H 22 O 8 . 390. To 10 gms. (1 mol.) of manitol dissolved in 500 c.cs. of pyridine, 50 gms. (excess) of benzoyl chloride are slowly added in the warm, the whole allowed to stand overnight and poured into 1 litre of cold 10% sulphuric acid. The ester is filtered off at the pump, washed with cold water and recrystallised from alcohol. CH 2 OH C H N CH 2 O.OC.C 6 H 5 (CHOH) 4 + 2C 6 H 5 C0C1— 5 . 5 > (CHOH) 4 + 2HC1. CH 2 OH CH 2 O.OC.C 6 H 5 Yield. — 80% theoretical (17 gms.). Colourless needles ; insoluble in water ; M.P. 178°. (A., 301, 102.) Ethyl acetate can be prepared in a like manner. Reaction CVII. Action of an Alkyl Iodide on the Silver Salt of an Acid. (J. C. S., 67, 600.) — This method is used when an ester is not easily ob- tained by the usual methods owing to steric hindrance or some such cause. The silver salt and alkyl iodide are heated or shaken together with or without an inert solvent, benzene, etc. The precipitated silver halide is filtered off, and the ester separated from the nitrate by distillation or some similar method. R X I + KCOOAg = E.COO.Rj + Agl. Preparation 212. — Methyl Trinitrobenzoate (Methyl ester of s-tri-nitrc- benzoic acid) COOCH 3 o 2 n/Nno 2 I C 8 H 5 0 8 N 3 . 271. X N0 2 10 gms. (1 mol.) of s-trinitrobenzoic acid are treated with 14 gme. (1 mol. NH 4 OH) of 10% (D. 0-959) ammonium hydroxide solution, slight excess of aqueous silver nitrate solution added, and the pre- cipitate filtered at the pump, washed with cold water and dried as described on p. 473. The dried silver salt and 20 gms. (excess) of methyl OXYGEN TO CARBON 257 iodide are refluxed on a water bath for 1 hour, excess of methyl iodide is distilled off, and the residue extracted with boiling alcohol and filtered The filtrate is concentrated to small bulk, cooled, and the precipitate recrystallised from alcohol. C 6 H 2 (N0 2 ) 3 (COOAg)[2 : 4 : 6 : 1] + CH 3 I = C 6 H 2 (N0 2 ) 3 (COOCH 3 )[2 : 4 : 6 : 1] + Agl. Yield. — 80% theoretical (8 gms.). Colourless crystals ; insoluble in water ; M.P. 157°. (J. C. S., 67, 600.) Reaction CVIII. Polymerisation of an Aldehyde to an Ester. (B., 20, 647.) — In the presence of sodium benzylate 2 mols. of benzaldehyde polymerise to yield benzyl benzoate. The reaction is peculiar to aromatic aldehydes. 0 : CHC 6 H 5 /OCH 2 C 6 H 5 C 6 H 5 .CH 2 .ONa + -> C 6 H 5 .C— 0 . Na 0 : CHC 6 H 5 \:OCn 2 C 6 H 5 C 6 H 5 CH 2 .O.COC 6 H 5 + NaOCH 2 C 6 H 5 . The reaction should be compared with the simultaneous oxidation and reduction of aromatic aldehydes under the influence of concentrated caustic alkali (Reaction LXIIL). Prepaeation 213. — Benzyl Benzoate (Phenyl-methanol ester of phenyl- methan acid). C 6 H 5 CO.O.CH 2 C 6 H 5 . C 14 H 12 0 2 . 212. A solution of 0-75 gm. of sodium in a sufficient quantity of benzyl alcohol (previously dried over potassium hydroxide and redistilled) is heated on a water bath using a calcium chloride tube on the flask, and added to 75 gms. (2 mols.) of benzaldehyde (previously dried over calcium chloride and distilled in a current of carbon dioxide). The whole is heated on a water bath for 20 hours, and acidified with 5 c.cs. of glacial acetic acid. Water is added, and the oil which separates dried over calcium chloride and distilled in a high-temperature distilling flask (see p. 18). Some unchanged benzaldehyde comes over ; the fraction 320°— 326° is retained. C 6 H 5 CH 2 ONa 2C 6 H 5 .CHO >C 6 H 5 .CH 2 .O.CO.C 6 H 5 . Yield. — 80% theoretical (60 gms.). Colourless crystals ; insoluble in water ; M.P. 20° ; B.P. 323°. (B., 20, 649.) Reaction CIX. Action of Heat on certain Dibasic Acids. (B., 10, 326.) — When acids such as phthalic acid or succinic acid, which contain two carboxyl groups attached to adjacent carbons, are heated, they readily lose water and pass into the acid anhydride. CH 2 COOH CH 2 CO CH 2 COOH CH 2 CO Dibasic acids with the carboxyl groups not attached to adjacent carbons only form anhydrides with difficulty or not at all. S.O.C, a 258 SYSTEMATIC OKGANIC CHEMISTRY Preparation 214. — Phthalic Anhydride (Anhydride of 1 : 2 -benzene- dicarboxylic acid). >0 C 8 H 4 0 3 . 148. ,CO. 20 gms. (1 mol.) of phthalic acid are sublimed over a naked flame in the apparatus described on p. 28. Long needles collect on the filter paper and funnel. C 6 H 4 (COOH) 2 [l : 2] C 6 H 4 (CO) 2 0[l : 2], Yield. — Almost theoretical (18 gms.). Colourless needles ; yield phthalic acid on treatment with water ; M.P. 128° ; B.P. 284°. (B., 10, 326.) * Succinic anhydride (see Preparation 217) can be similarly prepared. The following reactions, unlike the above, deal mostly with the prepara- tion of anhydrides in which the carboxyl groups belong to different molecules : — Reaction CX. Action of an Acyl Chloride on the Sodium Salt of an Acid. (A. Ch., [3], 37, 311.) — This is a standard method of preparing acid anhydrides. By using the sodium salt of an acid different from the acid the chloride of which is being taken, mixed anhydrides may be obtained. KiCOONa + Cl.CO.Ri! - RiCO.O.COEn + NaCl. Simple anhydrides can also be prepared by the action of the alkali salt of an acid on half the quantity of phosphorus oxy chloride necessary for its conversion to the acid chloride which is intermediately formed. 2CH 3 COONa + P0C1 3 = 2CH 3 C0C1 + NaP0 3 + NaCl. 2CH 3 COONa + 2CH 3 C0.C1 - 2(CH 3 CO) 2 0 + 2NaCl. This latter method is used industrially. Preparation 215. — Acetic Anhydride (Di-ethanoyl oxide). (CH 3 CO) 2 0. C 4 H 6 0 3 . 102. 10 gms. (excess) of crystallised sodium acetate are heated on a metal tray or in a porcelain basin until the crystals melt in their own water of crystallisation (3 mols.), solidify, and finally remelt. (Caution!) When the whole mass has fused (315°), it is allowed to cool and is powdered ; overheating must be avoided. It is immediately introduced into a 250-c.c. retort connected by a water condenser to a receiver consisting of a distilling flask, the side tube of which is fitted with a calcium chloride tube con- nected with a draught pipe. The whole apparatus is fitted up in a fume cupboard. 40 gms. (1 mol.) of acetyl chloride are slowly added by means of a dropping funnel fixed in the tubulus of the retort, which is meantime cooled in water and shaken at intervals. When addition is complete, the dropping funnel is removed, the mixture stirred with a glass rod, and the tubulus closed with a glass stopper. The retort is now heated with a OXYGEN TO CARBON 259 luminous flame, which is constantly moved about, until nothing further distils. Some fused sodium acetate is added to the distillate and the latter redistilled from the receiving flask into another distilling flask fitted with a calcium chloride tube as before. Each time before beginning dis- tillation the air in the apparatus should be displaced by dry air blown into it via the calcium chloride tube by means of a rubber bulb attachment. This will help in the production of a colourless liquid. In the second distillation the fraction distilling at 130° — 140° is collected separately. Yield. — 80% theoretical (45 gms.). Colourless liquid ; suffocating smell ; B.P. 138° ; D. 1 * 1-08. (A. Ch., [3], 37, 311.) Note. — If an absolutely pure product is desired, distillation over fused sodium acetate must be repeated until a drop of the distillate shaken with a little warm water (Caution !) gives no precipitate on addition of dilute nitric acid and silver nitrate. This test shows the complete absence of acetyl chloride. Propionic anhydride, benzoic anhydride (see p. 260), etc., are obtained in a similar manner. Reaction CXI. Action of Dehydrating Agents on a Free Acid. (B., 34, 186, 2074 ; A., 226, 8.) — This is a usual method of preparing the anhy- drides of acids, the chlorides of which are not readily available. Acetic anhydride is very frequently used — acetyl chloride can also be employed. 2K.COOH + (CH 3 CO) 2 0 = (RCO) 2 0 + 2CH 3 COOH. Preparation 216. — Cinnamic Anhydride (Anhydride of 3-phenyl-2- propen acid). (C 6 H 5 CH : CHCO) 2 0. C 18 H 14 0 3 . 278. 50 gms. (2 mols.) of dry finely powdered cinnamic acid and 250 gms. (excess) of acetic anhydride are refluxed together for 8 hours, and dis- tilled to 146°. The cold residue is extracted with ether, the extract filtered, and ether removed on a water bath. The residue is recrystallised from alcohol. Yield. — Almost theoretical (46 gms.). Colourless needles ; soluble in ether and in hot alcohol ; M.P. 136°. (B., 34, 186, 2074.) Preparation 217.— Succinic Anhydride (Anhydride of butan diacid). CHgCOCl + NaO.CO.CH3 = (CH 3 CO) 2 0 + NaCl. 2C 6 H 5 CH : CHCOOH 2 _> (C 6 H 5 CH : CHCO) 2 0. CH 2 .CO ! > CH 2 CO. O. C 4 H 4 0 3 . 100. 10 gms. (1 mol.) of finely-powdered succinic acid are refluxed for 3 hours with 20 gms, (excess) of acetyl chloride and allowed to stand in a s 2 260 SYSTEMATIC ORGANIC CHEMISTRY soda-lime desiccator until acetyl chloride and acetic acid are completely removed. The residue is recrystallised from absolute alcohol. CH 2 COOH CH 2 CO | - H *° | >0. CH.COOH CH 2 CO Yield. — Almost theoretical (12 gms.). Long needles ; M.P. 119-6° ; B.P. 10 131° ; B.P. 7,i » 261°. (A., 226, 8.) Reaction CXII. Action of certain Bases on Acyl Chlorides. (B., 34, 2070 ; J. pr., [2], 50, 479.) — When pyridine or quinoline act on an acid chloride, and the addition product which is formed treated with water, the acid anhydride is obtained (cf. Reaction CIX.). C H N 2R.CO.C1 ^ (RCO) 2 0 + 2HC1. H 2 0 Preparation 218. — Benzoic Anhydride (Anhydride of benzene-mono- carboxylic acid). (C 6 H 5 CO) 2 0. C 14 H 10 O 3 . 226. 25 gms. (2 mols.) of benzoyl chloride are slowly added to 20 c.cs. of pyridine and 8 gms. of anhydrous sodium carbonate ; after J hour the whole is poured into water, the precipitate filtered and washed with cold water, and dried first on a porous plate, and then in a desiccator. It is recrystallised from petroleum ether, which is removed under reduced pressure. Colourless needles ; insoluble in water ; M.P. 42°. (J. pr., [2], 50, 479.) CHAPTER XVIII THE LINKING OF NITROGEN TO CARBON Nitro Compounds Reaction CXIII. Action of Dilute Nitric Acid on some Organic Com- pounds. — Dilute nitric acid, which very often acts as an oxidising agent, can be used for introducing the nitro group, N0 2 , under certain con- ditions. For example, phenol can be converted into nitro-phenol by 3% nitric acid, while 4% acid converts methyl- and ethyl-acetanilide into the corresponding dinitro derivatives. The nitro group can also be sub- stituted in the side chain by heating, say, toluene with dilute nitric acid under pressure. The reaction, however, is not generally employed, as it is necessary to boil for some hours. Sodium and potassium nitrates in dilute sulphuric acid and solutions of nitric acid in glacial acetic acid, ether, acetone, and acetic anhydride are also used. Preparation 219 . — Dinitromethylaniline. NO,/ \nH.CH 3 . C v H 7 0 4 N 3 . 197- K0 2 10 gms. methyl acetanilide* are dissolved in 1 litre of dilute nitric acid (D. 1-029), and the solution heated to boiling under a reflux condenser. The liquid instantaneously assumes a brown colour, and after half an hour's heating, becomes turbid and a yellow substance begins to separate out. Two hours' heating is, however, necessary to complete the reaction. On cooling, the substance separates out in yellow crystals, which are recrystallised from aqueous alcohol. C 6 H 5 N.CH 3 COCH 3 + 2HN0 3 + H 2 0 -> G 6 H 3 (N0 2 ) 2 NH.CH 3 + CH 3 COOH + 2H 2 0. M.P. 175°. (B., 18, 1995.) Reaction CXIV. Action of Concentrated Nitric Acid on Aromatic Com- pounds. (B., 20, 333.) — Concentrated nitric acid up to 100% is required for nitrating many compounds which are not oxidised by this treatment. For this reason it is not used in the aliphatic series, nor with compounds containing an easily oxidisable side chain. The reaction is represented by the equation KH + HON0 2 -> E.N0 2 + H 2 0. In this reaction the question of temperature is one of importance. In * Methyl acetanilide is prepared by heatinsj mono-methylaniline with acetyl chloride, It can be purified by recrystallisation or sublimation. M.P. 101°— 102°. (B. 10, 323.) 261 262 SYSTEMATIC ORGANIC CHEMISTRY general it should be kept as low as possible to avoid oxidation. When the temperature is raised the tendency to form dinitro, trinitro, and poly- nitro derivatives is much increased. Pkeparation 220.— 4-Nitro-3-hydroxy Benzoic Acid. _COOH HO<^ ^>N0 2 . C 7 H 5 0 5 N. 183. 50 gms. m-hydroxy benzoic acid are dissolved in 175 c.cs. of hot nitro- benzene. The solution is cooled to 35° — 40°, and 17 c.cs. fuming nitric acid dissolved in an equal amount of nitrobenzene are slowly added with stirring during 4 hours. The product is filtered, washed with carbon tetrachloride, and crystallised from dilute alcohol. Yield.— 15% theoretical (10 gms.). M.P. 227°— 228°. (J. C. S., 119, 1428.) Reaction CXV. — Action of a Mixture of Concentrated Nitric Acid and Concentrated Sulphuric Acid (mixed acid) on Aromatic Compounds.— This reaction is the most important for nitration and is represented, as before, by the equation — R.H + HON0 2 ^ R.N0 2 + H 2 0. (a) The theoretical quantity of nitric acid is added to a large excess of cone, sulphuric acid, and the mixed acid added to the compound to be nitrated. Or the compound may be dissolved in excess of cone, sulphuric acid, and the theoretical quantity of strong nitric acid then added. The excess of sulphuric acid is added to absorb the water formed in the reaction, and which would reduce the concentration of nitric acid ultimately to a point where no nitration would take place. The quantity of sulphuric acid added must be such that its final concentration after nitration, i.e., when it contains the water formed in the reaction plus the water originally present in the nitric acid, must be above a certain minimum, depending on the compound to be nitrated. When this minimum concentration of sulphuric acid is reached nitration again stops. (b) In nitrating bases, the basic group must be protected from oxidation. This may be done in several ways : — 1. By carrying out the nitration in presence of a large excess of cone. H 2 S0 4 . The amine sulphate is first formed, and then nitration takes place. 2. By introducing acyl groups previous to nitration, E.NH 2 -> R.NH.COR! -> R^COR^, where R x == alkyl or aryl group. After nitration, the acid group is split off by hydrolysis. H 2 0 NOaR.NH.CORi >N0 2 R.NH 2 + R^OOH. 3. By combining with benzaldehyde to form a benzylidene derivative, R.NH 2 + OCH.C 6 H 5 -> R.N = CH.C 6 H 5 , THE LINKING OF NITROGEN TO CARBON 263 which can be readily nitrated, and the benzylidene group removed subse- quently by hydrolysis. By these methods usually only one isomer is formed in nitration, e.g., NH 2 HNO. NH 2 NH 2 NH 2 /\t\to ||+ H \/ \>°* u N0 2 50% 10% 40% NH.COCHg /\ NH, /V NaOH | | +' a little ortho \/ N0 2 \/ N0 2 HNO, (v x r> HN03 i / YY H ' + > NO, H 2 /\/\nh.coch, HNO N0 2 /\/\nh.coch. NaOH NO. H, (c) Sometimes it is necessary to protect the OH group, and the same acyl groups are introduced. Rules of Nitration. — The position taken by the N0 2 group on entering the nucleus depends on the group or groups already present in the nucleus. When the substance contains an OH, NH 2 , CI or CH 3 group, nitration gives a mixture of ortho- and para-nitro compounds. When a S0 3 H, COOH, CN, CHO, or N0 2 group is present, nitration gives chiefly the meta compound. By nitrating toluene by the usual method, i.e., using mixed acid, the following proportions are obtained : — 63% ortho-, 35% para-, 2% meta-nitro toluene. Influence of Temperature. — The proportion of different isomers formed in nitration is influenced by temperature. The table shows the alteration in proportion when nitration is carried out at different temperatures on toluene. Temp. - 30° 0° 30° Ortho. 55- 6% 56% 56- 9% Meta. 2- 7% 3- 1% 3-2% Para. 41-7% 40-9% 39-9% Analysis of a Mixed Acid. — 1. Total Acidity (calculated as H 2 S0 4 ). — About 5 c.cs. of mixed acid are put into a tared weighing bottle and its 264 SYSTEMATIC ORGANIC CHEMISTRY weight found. This is then washed into a beaker and titrated with N/caustic soda solution, using methyl orange as indicator. °/ H SO — 4,9 x c c s - of NaOH /° 2 * — weight taken 2. Real H 2 S0 4 . — About 5 c.cs. are weighed out into a tared dish, and heated on a water bath till all the HN0 3 and HC1 (if any) is driven off. This is then washed into a flask and titrated, as in 1. Total acidity as H 2 S0 4 - (hN0 3 x ||) = real H 2 S0 4 . It is better, however, to estimate HN0 3 as in 3. 3. HNO3 by Nitrometer. — About 5 gms. of mixed acid are weighed out and placed in the funnel of a nitrometer, and washed in with a little pure cone. H 2 S0 4 . The nitrometer is then shaken until all the NO is evolved. It is then allowed to stand till room temperature is reached, when the temperature and barometric pressure are noted. The volume of NO at N.T.P. is then calculated. 63 This volume X ^2^00 = we ^^ °^ HN0 2 = x. % HNO3 = . , x .. . — X 100. /u * weight taken This figure includes HN0 2 , as it also gives NO in the nitrometer. It can be estimated as in 4. 4. HN0 2 (Small Amounts). — 5 c.cs. N/10 permanganate solution are diluted with distilled water to 100 c.cs. The mixed acid is then run in from a burette until the KMnO^ is decolorised. The weight of mixed acid is then calculated from its specific gravity. HNO3 by nitrometer - (hN0 2 x ~) = real HN0 3 1 mol. KMn0 4 = 5 mols. HN0 2 . The Isolation of Nitro Compounds. — There is usually little difficulty experienced in isolating liquid nitro compounds, owing to the differences in specific gravity of these compounds and that of the mixed acid. Emul- sions are sometimes formed, but on standing these usually separate so far as to give a partial separation. By cautiously diluting the mixture until the specific gravity of the nitro compound is greater than that of the acid, separation may be effected, and is usually hastened by gently heating. Solid nitro compounds can be separated by crystallisation, and in some cases by diluting the mixed acid, or simply pouring into water. If both these methods prove unsuccessful, extraction with ether, after dilution, may be attempted. THE LINKING OF NITROGEN TO CARBON 265 Preparation 221. — Nitrobenzene. C 6 H 5 .N0 2 . 123. 100 gms. of benzene are placed in a vessel, which is provided with a good efficient mechanical agitator. A mixed acid is made by taking 140 gms. nitric acid (D. 141) and 180 gms. cone, sulphuric acid, and mixing well together. Considerable heat is generated in mixing these acids, and before proceeding further the mixture should be cooled. The benzene should now be agitated briskly, and the mixed acid run in slowly. The temperature rises quickly to about 45° C, when the flow of acid is reduced, and, if necessary, cooling water applied to the outside of the nitrating vessel. The acid should now be added at such a speed that, when it is all in, the temperature has risen to 60° C. The temperature is kept at 60° — 70° C. until nitration is complete. This may be tested by taking a small sample of the oil and pouring into water. Nitrobenzene sinks at once to the bottom (D. 1 ! 1-2116), while any unchanged benzene floats on the surface of the water (D. ^ 0-839). It may also be tested by taking the specific gravity of the oil by means of a hydrometer. When nitration is complete, agitation is stopped, and the nitrobenzene and the waste acid run into a separator, where it is allowed to settle. The waste acid is run off from the bottom ; water and a little carbonate solution is added, and the nitrobenzene washed. After settling, the nitrobenzene is run off from the bottom, and freed from water by anhydrous calcium chloride until it is clear. The water and any unchanged benzene may also be removed by distillation under vacuum. The nitrobenzene is then distilled, distillation being stopped when the contents of the flask turn dark in colour, the fraction 208° — 212° being collected. C 6 H 6 + HN0 3 ->C 6 H 5 N0 2 + H 2 0. Yield. — 85% theoretical (134 gms.). Pale yellow liquid with characteristic smell; M.P. 5-7°; B.P. 210°; D. !? 1-2116; important intermediate for dyestuffs. (A., 12, 305 ; J. pr., 19, 375.) Preparation 222 . — m-Dinitrobenzene, C 6 H 4 (N0 2 ) 2 . 168. To a mixture of 30 gms. cone, sulphuric acid and 18 gms. of fuming nitric acid, contained in a flask of about 700 c.cs. capacity, 12 gms. of nitrobenzene are gradually added with shaking. The flask is heated on a water bath in a fume cupboard until a test sample solidifies on pouring into cold water ; about 30 minutes' heating is generally required. The contents of the flask are then poured in a thin stream into a large volume of vigorously agitated ice-cold water. The crude dinitrobenzene, which contains about 3% ^-dinitro- and 1% o-dinitrobenzene is filtered off, washed well with water, and recrystallised from alcohol. C 6 H 5 N0 2 + HN0 3 -^C 6 H 4 (N0 2 ) 2 + H 2 0. Yield. — 75—87% theoretical (12 — 14 gms.). Pale yellow needles ; M.P. 90°. (A., 57, 214.) 266 SYSTEMATIC ORGANIC CHEMISTRY Preparation 223.— o- and ^-Nitrc -Toluene (l-Methyl-2-nitro-benzene (l-methyl-4-nitro-benzene)). NQ 2 CH 3 <^ ^> and CH 3 <^ /N0 2 C 7 H 7 0 2 N. 137. 100 gms. toluene are placed in a nitrating vessel. A mixed acid, con- sisting of 150 gms. cone, sulphuric acid and 100 gms. nitric acid (D. 144) is cooled and run into the toluene, which is vigorously agitated. The temperature rises up to 20° — 30°, and is maintained at that, cooling water being passed into the water bath, if necessary. After all the acid has been added the temperature is allowed to rise to 50°. This temperature is maintained until the specific gravity of the oil (taken by hydrometer) is 1-15. The oil is then separated from the waste acid in the usual way, washed with water and sodium carbonate solution, and then dried on the water bath. Any unnitrated toluene can be removed by distillation. The o-com- pound may be separated from the ^-compound by fractional distillation, using a column. 40% of the mixture is distilled off, consisting chiefly of o-compound. The ^-compound is obtained from the residue bv cooling atO°C. If the mixture is cooled to about — 20° (see p. 10) the ^-compound crystallises out. The mixture consists of about 65 — 70% o, and about 30% p, with a small percentage of the meta-compound. Yield. — Total — almost theoretical (148 gms.). (Z. e., 16, 161 ; Phil. Mag., 1876, IV., 1, 17.) 0. m. p. a p M.P. - 10° - 4° 16° 514° B.P. 2° 230°— 231° 238° D. 1468 1468 1423 Preparation 224 . — Dinitro-chlor-benzene. N0 2 NO,/ ^>C1. C e H 3 0 4 N 2 Cl. 202-5. 350 gms. of a mixed acid containing 50% nitric acid are placed in a cast- iron pot with good agitation. 113 gms. of chlor-benzene are then run in, the temperature being kept under 5° by external cooling. After all the mixed acid has been added the stirring is maintained for another hour at 5° — 10° C. The temperature is then slowly raised to 50° and kept at this for 1 hour. 350 gms. cone, sulphuric acid are then dropped in very cautiously with good stirring, and the mixture finally heated up to 115° for half an hour. After cooling, the product is poured into cold water, THE LINKING OF NITROGEN TO CARBON 267 when it immediately solidifies. The mother liquor is poured off and the dinitro-chlor-benzene washed free of acid by heating up in water beyond its melting point (51° C.) and stirring. The water is then poured off. Yield. — Almost theoretical (630 gms.). Yellow crystals ; M.P. 51°. Note. — Care should be exercised that dinitro-chlor-benzene is not allowed to touch the skin, as it is liable to produce eczema and sores. (B., 27, 2457 ; U.S.P., 1220078.) Preparation 225. — a-Nitro-Naphthalene (1-Nitro naphthalene). NO, C 10 H 7 O 2 N. 173. 80 gms. nitric acid (D. 14) are mixed with 100 gms. cone. H 2 S0 4 and 300 gms. waste acid from a previous nitration. The temperature is raised to 40°, and 100 gms. naphthalene, which has been previously melted, is run in gradually, the agitation being maintained. The temperature is not allowed to rise beyond 50° C. until all the naphthalene has been added, when it is raised to 60° C. The nitro-naphthalene forms a cake on the top of the nitrating vessel as soon as agitation is stopped and cooling is applied. The nitration should be tested every hour after the temperature has reached 60° C. by removing part of the cake, which forms on cooling, melting and washing quickly with dilute sodium carbonate solution, removing the alkali and drying with filter paper, and taking the setting point, as described on p. 17. The temperature is maintained at 60° until a setting point of 56° — 58° is obtained. When nitration is com- plete agitation is stopped, the nitrating vessel is cooled, and the cake which forms is removed from the waste acid. The cake is then melted under water, and some sodium carbonate solution added to remove any adhering acid. The cake is then allowed to solidify, the wash water is run off, and the nitro-naphthalene dried by heating on a water bath. It may be recrystallised from alcohol. If any unchanged naphthalene is present, it may be removed by steam distillation. + HO.N0 2 -> | ( | Yield.— 90— 95% theoretical (121—128 gms.). Yellow needles ; M.P. 58-5° ; B.P. 304°. (D.R.P., 100417.) Preparation 226. — Picric Acid. N Q 2 OH<^ ^>N0 2 C 6 H 3 0 7 . 187. 93 gms. phenol are placed in the sulphonating pot and heated to 100°, when 300 gms. 100% sulphuric acid is added, the temperature being kept 268 SYSTEMATIC ORGANIC CHEMISTRY under 110°, and maintained at this temperature for an hour until sulphona- tion is complete (test). It is then cooled down to 0°, agitation being maintained. 220 gms. nitric acid (D. 1-5) and 220 gms. 100% sulphuric acid are mixed together and cooled. This is added drop by drop to the sulphonic acid in the pot. It is then allowed to stand overnight at ordinary tempera- ture, and is then very gradually heated up to 30°, and then up to 45°, but no higher. About 50 c.cs. of the nitrating mixture is then removed from the pot and heated with, stirring in a large porcelain basin on a sand bath to 110° — 125°. The rest of the mixture is then removed, and is poured gradually into the preheated portion. When all has been added the temperature is kept at 110°— 120° for half an hour. 700 c.cs. of water are then added at such a speed that the temperature is kept at 120°. The picric acid separates out on cooling, and is filtered through cotton and washed with water. Yield. — 90% theoretical (165 gms.). Yellow powder ; explosive ; solubility in water at 20°, 1 in 90 ; M.P. 122-5°. (A., 43. 219 ; B., 2, 52.) Preparation 227. — (1) ^-Nitro-acetanilide. N0 2 C 6 H 4 NH.CO.CH 3 . 180. (2) p-Nitraniline. N0 2 C 6 H 4 NH 2 . 138. 1. 20 gms. of finely ground acetanilide are added to 80 gms. cone, sulphuric acid, which, is continuously stirred. The solid slowly dissolves, and the temperature, which gradually rises, must not exceed 30°. When all is dissolved the solution is cooled in a freezing mixture to 0°, and a mixed acid, previously cooled, containing 15-5 gms. nitric acid (D. 1-38), and 15 gms. cone, sulphuric acid gradually added during the course of 5 minutes, the temperature not exceeding 3°. When all is added, the solution is allowed to stand for 2 hours or longer, until a sample on pouring into water and boiling with caustic soda gives no odour of aniline. The reaction mixture is poured on to a mixture of 50 gms. of water and 50 gms. of ice, when the nitro-acetanilide is precipitated. The precipitate is filtered off and washed with water ; it is then stirred with 100 c.cs. of water, sufficient sodium carbonate to render the liquid alkaline to litmus being added, and the whole boiled. By this treatment any o-nitro-acetanilide present is hydrolised, but the ^-compound remains unchanged, and is filtered off at about 50° and washed with water. Yield. — 90% theoretical (23 gms.). May be recrystallised from alcohol (M.P. 207°), but is generally used in the crude form for further prepara- tions. 2. j>-Nitraniline. — The product of the last preparation is stirred with an equal quantity of water, 20 gms. of 35% caustic soda added, and the whole boiled for 2 — 3 hours. At the end of this time the solution should still show a faint alkaline reaction, and the hydrolysis is complete when a sample dissolves to a clear solution in hydrochloric acid. The liquet" THE LINKING OF NITROGEN TO CARBON 269 is cooled, the ^-nitraniline filtered off and washed with a little cold water. It is practically pure, but may be recrystallised from water. C 6 H 5 NH.COCH 3 + HN0 3 -> N0 2 .C 6 H 4 .NHCOCH 3 + H 2 0. N0 2 .C 6 H 4 NH.CO.CH 3 + H 2 0 -> N0 2 .C 6 H 4 .NH 2 + CH 3 COOH. Yield.— 80% theoretical (21 gms.). Yellow needles; M.P. 147°. (C. Z., 1912, 36, 1055.) p-Nitraniline (Second Method). — 18 gms. of benzylidine aniline are added to 70 gms. of cone, sulphuric acid, the temperature being kept below 50°. The product is cooled to about 5° — 10° and maintained at this temperature while a mixture of 11 gms. of nitric acid (D. 1-38) and 11 gms. of cone, sulphuric acid is run in. After standing for 20 minutes the nitration mixture is added to an equal volume of water, and the benzaldehyde removed in a current of steam. The residual liquor is cooled, diluted with water, and neutralised with caustic soda ; this causes complete separation in a very pure form, of the ^-nitraniline, which is filtered off, washed with water and dried. C 6 H 5 N = CH.C 6 H 5 + HN0 3 -> N0 2 C 6 H 4 N = CH.C 6 H 5 + H 2 0. N0 2 C 6 H 4 N = CH.C 6 H 5 + H 2 0 ~> N0 2 C 6 H 4 NH 2 + C 6 H 5 CHO. Yield. — 90% theoretical (12 gms.). (D.R.P.,72173.) Preparation 228. — m-Nitrotoluidine 0 NH 2 / ^>CH 3 . C 7 H 8 0 2 N 2 . 152. ~^0 2 10 gms. ^-toluidine are dissolved in 200 gms. cone, sulphuric acid. The solution is cooled by a freezing mixture to below 0°. A mixture containing 7-5 gms. nitric acid (D. 148) and 30 gms. cone, sulphuric acid is allowed to flow into the well-stirred solution, the temperature being maintained at 0°. When all the mixed acid has been added the mixture is allowed to stand for a short time and is then poured into 500 c.cs. of ice-cold water, the temperature being kept below 25° by the addition of more ice if necessary. The solution is now filtered from impurity and diluted to 3 times its bulk and neutralised with solid sodium carbonate, the temperature being kept as low as possible. The precipitate is then filtered off, pressed dry and finally recrystallised from alcohol. CH 8 /~ _ \NH 2 CH 3 /~ )NH 2 NOT Yield. — 65 — 70% theoretical (10 gms.). Yellow monclinic needles ; M.P. 77-5°. (B., 17, 263.) Reaction CXVI. — Action of Nascent Nitric Acid on Aromatic Compounds in presence of Concentrated Sulphuric Acid. — This reaction gives nitro compounds which, in many cases, are only obtained with difficulty by the action of mixed acid, Sodium or potassium nitrate is usually added to the 270 SYSTEMATIC ORGANIC CHEMISTRY solution of the compound in cone, sulphuric acid. It is usually necessary to keep the temperature below ordinary room temperature. Peepaeation 229. — o- and ^>-Nitrophenol (1-Hydroxy 2- and 4-nitro- benzene). NO^ IK)/ \ and HO/ \n0 9 . CJI.CkN. 139. 20 c.cs. of water are added to 94 gms. of phenol, and this mixture is allowed to drop into a solution of 150 gms. sodium nitrate in 400 c.cs. water and 250 gms. cone, sulphuric acid. The agitation must be good and during the addition the temperature must be kept under 20°. The stirring is maintained for 2 hours after all has been added. A resinous mixture of nitro bodies is formed from which the supernatant liquor is poured off. The residue is then melted in 500 c.cs. of water and chalk is added with stirring until the mixture is neutral to litmus. This frees the nitro bodies from acid. The wash liquor is poured off and the nitro bodies are distilled in steam, using a wide air condenser. The ortho compound passes over. The residue in the flask is allowed to cool and is then filtered from the mother liquor. The residue which contains the para compound is then boiled up with a litre of 2% hydrochloric acid and filtered through a hot filter (see p. 10). The para compound crystallises from the hot solution in needles. N0 2 - : <^ ^OH -> <^ ^>OH and N0 2 <^ ^OH. Yield. — Ortho, 40 gms. ; para, 40 gms. ; total nitrophenol, 60% theoretical ; ortho M.P. 44-3° : B.P., 214° ; para, M.P. 114°, decomposes on boiling. (A., 103, 347 ; 110, 150.) Peepaeation 230. — m-Nitrobenzaldehyde. NQ 2 <^ ^>CHO. C 7 H 5 0 3 N. 151. 100 gms. benzaldehyde is added to a cooled solution of 85 gms. of sodium nitrate in 200 gms. of cone, sulphuric acid. The temperature is not allowed to rise above 30° — 35°. The smell of benzaldehyde disappears after the nitration is complete. The separation of the o- and ^-compounds which are formed is similar to that used in the case of the toluidines. The nitration product is poured into ice and water, the m-compound solidifies and is filtered from the oily o-compound. NQ 2 <^ ^>CHO + HN0 3 -> <^ ^>CHO Yield. — 100 gms. meta compound, 25 gms. ortho compound; 90% theoretical ; M.P. 0- 46 °, m- 58 °, p- 107 °. (B., 14, 2802.) THE LINKING OF NITROGEN TO CARBON 271 Preparation 231. — 1.5 and 1.8 Dinitro-anthraquinone. CO NO, N0 2 CO N0 2 and | | | C 1d H«0«N,. 298. NO,, CO CO 10 gms. anthraquinone are dissolved in 200 gms. cone, sulphuric acid; 10 gms. sodium nitrate (dry) are added with agitation. The mixture is kept at 60° — $0° C. for 12 hours. It is then poured into water and the 1.5 and 1.8 compounds, along with any unchanged anthraquinone, separated and washed. The L5 is separated from the L8 by using alcohol as a solvent, the 1.8 going into solution. Yield.— Almost theoretical; M.P. 1.5- above 330°; 1.8- above 312°. (B., 16, 363.) Preparation 2 32 . — 2.2 '-Dinitro-benzidine. NH 2 / \-/ )NH 2 . C 12 H 10 O 4 N 4 . 274. ~^0 2 N0 2 ' To 56 gms. of pure benzidine sulphate 600 gms. of pure cone, sulphuric acid are added and the mixture well stirred. Solution is completed by heating up to 60° if necessary. The solution is cooled down to about 10°, but not lower, and 40 gms. potassium nitrate slowly added. After several hours' stirring the solution is poured into about 2 litres of cold water and the dinitro-benzidine sulphate, which is precipitated, filtered off and washed with a little water. The sulphate is then made into a cream with hot water and caustic soda solution added until an alkaline reaction is given to phenolphthalein. The free base is then filtered off, washed with water, and recrystallised from water or from alcohol. NH2< C I/~\ZI) NH2 NH2 \H/~\ZI> HN2 N0 2 N0 2 Yellow leaflets, M.P. 214°. (B., 23, 795.) Reaction CXVII. Action of Nitrous Fumes on Certain Organic Com- pounds.— The nitro group, N0 2 , can be introduced in some cases by the action of nitrous fumes, the nitrous fumes being passed through the solu- tion in glacial acetic acid. Sodium nitrite in acid solution may also be used, and this reaction gives good yields with amines and phenols, the amines passing through the diazo stage into phenols, e.g., OH OH /\NO, (90 % yield). COOH COOH 272 SYSTEMATIC ORGANIC CHEMISTRY The nitrous acid in the reaction is oxidised to nitric acid, and this produces nitration. 3HN0 2 -> HN0 3 + 2NO + H 2 0. NH 2 N = NHS0 4 OH OH /X /\ /\NO, j — * > and When the ^-position is occupied, the yield is almost theoretical, e.g., CH 3 CH 3 NH 2 OH Preparation 233. — m-Nitro-Salicylic Acid. OH / ^COOH C 7 H 5 0 5 N. 183. NOT / 100 gms. salicylic acid and 130 gms. sodium nitrite are mixed with 150 c.cs. water and 1,200 c.cs. sulphuric acid (D. 1-52) are slowly added, the tempera- ture being kept below 15°. After 4 hours the mixture is warmed to 50° and then set aside till the evolution of nitrous fumes ceases. The mass is then warmed on the water bath. On cooling, crystals of m-nitro salicylic acid separate out, and are filtered off, washed and recrystallised twice from water. - OH OH <^ ^>COOH -> <^ ^>COOH. Yield.— 64% theoretical (85 gms.). Needles ; M.P. 228°. (J. pr., [11], 42, 550.) Preparation 234. — o and ^-nitrophenol. N0 2 ( ^>OH and OH/ ^NO,. C fi H,0,N. 139. 10 gms. aniline are dissolved in 100 c.cs. of 25% sulphuric acid and the solution cooled to 15°. 300 gms. sodium nitrite are dissolved in 100 c.cs. water and this solution added in two portions. When the first third is added cooling is applied, and the remainder of the nitrite is added without cooling. The mixture is then poured into a large evaporating basin on a water bath and boiling 50% sulphuric acid is cautiously added. When the action is over, the whole is steam distilled when the o-nitro-phenol passes THE LINKING OF NITROGEN TO CARBON 273 over. The ^-compound is then extracted from the residue as in Preparation 229. ^>NH 2 -> ^>N 2 .HS0 4 N0 2 <^ ^>OH and <^ ^OH ~N0 2 Yield. — o-compound (4-7 gms.), ^-compound (3-3 gms.), total 53% theoretical (see p. 270). (J. pr., 148, 298.) Reaction CXVIII. Action of Nitrous Acid on Aromatic Amines in presence of Cuprous Salts (Sandmeyer). K.NH 2 — > R.N0 2 . For other examples and a discussion of the Sandmeyer reaction, see pp. 149, 338. Peeparation 235. — Nitrobenzene (Sandmeyer). C 6 H 5 N0 2 . 123. 9 gms. aniline are mixed with 50 c.cs. water and 20 gms. cone, nitric acid (D. 1-4). The solution is cooled to below 5° and 15 gms. sodium nitrite in 50 c.cs. water added. The mixture is then poured into a flask containing the cuprous salt, prepared by dissolving 50 gms. cupric sulphate and 15 gms. grape sugar in 100 c.cs. water, and adding 20 gms. caustic soda in 60 c.cs. water to the boiling solution ; the mixture is shaken till all the copper is reduced, and is then rapidly cooled, and finally neutralised by a slight excess of acetic acid. The combined mixtures are allowed to stand for 1 hour, or until the evolution of nitrogen ceases. The nitrobenzene is then separated by steam distillation. <( ^>NH 2 -> <( ^>N 2 NQ 3 -> <( ^>N0 2 . Yield.— 50% theoretical (5 gms.). Yellow liquid ; M.P. 5-7° ; B.P. 210°. (B., 20, 1494.) Reaction CXIX. Action of Silver Nitrite on Alkyl Halides. E.I + AgX0 2 -> R.N0 2 + Agl. This is the only method of preparing aliphatic nitro compounds. Pkepaeation 236. — Nitro-methane (Nitro-methan). CH 3 N0 2 . CH 3 0 2 N. 61. 44 gms. (slight excess) of dry silver nitrite (see p. 505) are mixed with an equal bulk of dry sand and placed in a reflux apparatus ; 41 gms. (1 mol.) of methyl iodide are gradually added, and the whole heated on a water bath for 2 hours. The mixture is then distilled from a water bath, the fraction 95° — 101° being separately collected. It is redistilled over silver nitrite to remove the last traces of iodide. CH 3 I + AgN0 2 -> Agl + CH 3 N0 2 . Yield. — 70% theoretical (12 gms.). Heavv, inert, insoluble, colourless liquid ; B.P. 101° ; D. l f 1-0236, D. \ M580' (A., 171, 18.) S.O.C. T 274 SYSTEMATIC ORGANIC CHEMISTRY Preparation 237. — Nitro-ethane (Nitro-ethan). C 2 H 5 .N0 2 . C 2 H 5 0 2 N. 75. By-product.— Ethyl Nitrite (Ethyl ester of nitrous acid). C 2 H 5 .0.X0. C 2 H 5 0 2 X. 75. 42 gms. (a slight excess) of dry silver nitrite (see p. 505) are placed in a round-bottomed flask fitted with a reflux condenser. If a yield of ethyl nitrite is required ice-water must be used in the condenser, which should be a long one. 34 gms. (1 mol.) of ethyl iodide are added, gradually, through the condenser tube, so that the liquid boils vigorously, but not too violently. The flask must not be disturbed during the process for it is important that the silver nitrite should be gradually penetrated by the iodide. The flask is then warmed for 2 hours on a water bath, well cooled, fitted to a distillation apparatus, and the contents fractionally distilled. Ethyl nitrite distils over at 68°, and is collected in the same way as ether (see p. 208) in a flask cooled in a good freezing mixture. The temperature then rises and the second fraction, nitroethane, is collected at 110°— 114° and redistilled. C 2 H 5 I + Ag^0 2 C2 h 5 o NO + AgL Yield. — Nitro-ethane : 50% theoretical (8 — 9 gms.). Colourless liquid : insoluble in water ; B.P. 113°— 114° ; D. ? 1-058. Yield. — Ethyl-nitrite: 50% theoretical (8 — 9 gms.). Volatile liquid ; oppressive odour ; resembling that of apples when dilute ; B.P, 17° ; D. 15 4 5 0-947. (A., 171, 18.) Reaction CXX. Action of Concentrated Nitric Acid on Certain Sulphonic Acids. R,S0 3 H + HN0 3 ^ R.N0 2 . This reaction goes easily in the anthraquinone series, but only in the naphthalene series when the S0 3 H is in a special position — the a position. OH OH I + HXO3 -> SO3H N0 2 In the process of nitration with mixed acid, in many cases a sulphonic acid is formed in the first instance, the sulphonic group being ultimately replaced by the N0 2 group. Reaction CXXI. — Action of Tetranitromethane on Bases. (B., 1920, 53, 1529.) — The tetranitromethane is decomposed by weak bases in alcohol or acetone solution into nitroform and nitric acid C(N0 2 ) 4 + H 2 0 -> HC(X0 2 ) 3 + HNO3, the base becoming nitrated during the process. CHAPTER XIX THE LINKING OF NITROGEN TO CARBON (continued) Reaction CXXII. Action of Phenols and Primary Aromatic Amines on Diazonium Compounds. — Diazonium compounds combine with phenols and aromatic bases to form azo dyestuffs. H E — N — CI + H.E 1 .NH 2 -> R.N.C1 IIL (° H ) II N N.R 1 .NH 2 (OH) Intermediate compound. HC1 is split off and an azo colour is formed. R — N = N.R 1 .NH 2 (OH). The process is known as " coupling." R is seldom aliphatic. In the azo compound N is trivalent, while in the diazonium compound N is pentavalent. The diagram shows the name given to the different groups in the azo compound. (OH) (OH) NH 2 NH 2 I N = N — auxo chrome group. chromogen group, chromophore group. Laws of Formation of Azo Colours Bases are " coupled " in slightly acid solution, while phenols are " coupled " in shghtly alkaline solution. Coupling usually takes place in the ^-position to the NH 2 or OH group, and, if this is occupied, in the o-position, but never in the m-position. If the NH 2 or OH groups are substituted by an acetyl group no coupling takes place, e.g. NH.COCH, O.COCH. or do not couple. If the NH 2 is substituted by an alkyl or aryl group coupling takes place, e.g. NH.CH 3 NH.C 6 H 5 and do couple. If the H in OH is replaced by any group, no coupling takes place. 275 t 2 276 SYSTEMATIC OKGANIC CHEMISTRY When both, an OH and NH 2 are present in the azo component (the com- pound which is diazotised is termed the diazo component), and coupling does take place, e.g., H acid, then the coupling can be carried out in acid or in alkaline solution, taking place in the ortho position to the NH 2 in acid solution, and ortho to the OH in alkaline solution. When one azo component is used then the colour is termed a mono-azo colour. When two azo components are used, e.g., with benzidine, then dis-azo colours are formed, e.g. benzidine benzidine salicylic acid. salicylic acid, resorcinol. 1 a-naphthylamineJ — > N.W. acid (Trisazo colour). The sign -> being used to indicate " coupled to." For examples, see section on Dyes, etc. Reaction CXXIIL— Action of Nitrous Acid on Phenols, and Tertiary Aromatic Amines. (A. 277, 85.) ^>OH >N(CH 3 ) 2 HN0 2 HNOo NO: NO< "V(CH 3 ) 2 . The nitrous acid is usually generated by the action of sodium nitrite on the acid solution. The nitroso phenols are identical with the quinone oximes, formed by acting on quinone with hydroxylamine. no/ >OH = NOH The NO group in the benzene series is introduced in the para position in both cases. In the naphthalene series the ^-compound gives the 1-nitroso compound, while the a-compound gives a mixture of the 2- and 4-nitroso compounds. NO OH OH OH + OH THE LINKING OF NITROGEN TO CARBON 277 Dihydroxy phenols give di-nitroso compounds. 0 OH OH || /^NO /^^NOH ' or OH I JOH I J=0 NO NOH Kesorcinol Resorcin green Nitrous acid has no action with tertiary aliphatic amines and, with alcohols, yields nitrites. Preparation 238. — £>-Nitroso-Phenol. 0H<^ ^>N0. C 6 H 5 0 2 N. 123. 100 gms. of phenol are dissolved in a solution of 50 gms. of caustic soda, 100 gms. sodium nitrite and 2 litres water. The temperature is reduced to 7°. 200 c.cs. cone, sulphuric acid ar3 added to 600 c.cs. water, and when cooled is gradually run into the solution. The nitroso-phenol gradually separates out, and after stirring for 2 hours, is filtered of! and washed with ice water. <^ ^>OH + HO. NO -> HO<^ y^O. Yield. — 95% theoretical (124 gms.). Colourless crystals ; soluble in hot water, alcohol, and ether ; M.P. 126° C. with violent decomposition. (A., 277, 85.) Preparation 239. — Nitroso-/?-Naphthol (l-nitroso-2-hydroxy naphtha- lene). NO \0H. C 10 H 7 O 2 N. 173. 10 gms. /?-naphthol are dissolved in 2-8 gms. caustic soda in 100 c.cs., water, and made up to 200 c.cs. with water. 5 gms. sodium nitrite dis • solved in a little water are carefully added. The mixture is cooled by the addition of 100 gms. ice, and 140 c.cs. 10% sulphuric acid are slowly run in with constant stirring, the temperature being kept below 5°. The nitroso compound separates as a pale yellow precipitate. It is allowed to stand for 2 hours, filtered, and washed with water until the washings are only slightly acid. It is then dried and crystallised from petroleum ether. NO Yield.— Almost theoretical (12 gms.). Red needles ; M.P. 110° C. sparingly soluble in water. (B., 27, 3075.) 278 SYSTEMATIC ORGANIC CHEMISTRY Preparaton 240. — j9-Nitroso-Dimethylaniline. NO^ X N(CH 3 ) 2 . C 8 H 10 ON 2 . 150. 10 gms. dimethylaniline are dissolved in 26 gms. cone, hydrochloric acid in 50 c.cs. water, and cooled in a freezing mixture. 6 gms. sodium nitrite in 10 c.cs. water are then slowly added with constant stirring. The separation of the hydrochloride of nitroso di-methylaniline soon begins. After standing for ^ hour it is filtered and washed with about 20 c.cs. alcohol, to which 1 or 2 c.cs. hydrochloric acid has been added. The hydrochloride is then made into a paste with water and caustic soda solution added in the cold till alkaline. The yellow colour of the salt changes to the green of the free base. The base is now filtered and the residue well pressed. It may be crystallised from benzene. (CH 3 ) 2 N<^ ^> + HONO -> (CH 3 ) 2 N<^ ^>NO + H 2 0. Yield. — Almost theoretical (12 gms.). Green crystals ; M.P. 85° ; somewhat volatile in steam ; used in preparation of oxazine dyestuffs. (B., 7, 810 ; 8, 616 ; 12, 523.) Reaction CXXXV. Action of Nitrous Acid on Secondary Amines, and subsequent Rearrangement of the Products. E 2 .NH ;- HO.NO -> E 2 N.NO. The nitrosamines are neutral oily liquids of little importance in them- selves. This reaction, however, serves to separate secondary bases from mixtures of primary, secondary and tertiary. The aromatic nitrosamines undergo an interesting rearrangement when heated with alcoholic hydro- chloric acid (B., 20, 1247), the nitroso group migrating to a position in the nucleus, forming ^-nitroso compounds. .NO C 6 H 5 N< -> NOC 6 H 4 NH.CH 3 . X CH 3 Preparation 241 . — ^-Nitroso-Methylaniline. NO<^ ^>NH.CH 3 . C 7 H 8 ON 2 . 136. Methylaniline (1 mol.) is dissolved in hydrochloric acid until strongly acid, and then treated with a 20% solution of sodium nitrite (1 mol.). Methyl-phenyl nitrosamine separates as a yellow oil, which solidifies on cooling (M.P. 12° — 15°). 2 gms. methyl-phenyl nitrosamine are dissolved in 4 gms. ether. 8 gms. absolute alcohol which have been saturated with hydrochloric acid gas are then added and after a time needles separate out, which are filtered and washed with a mixture of alcohol and ether. <^ ^>NHCH 3 -> <^ ^>N.NO.CH 3 -> NO<^ ^>NH.CH 3 . Yield.— Almost theoretical ; M.P. 118°. (B., 19, 2991.) THE LINKING OF NITROGEN TO CARBON 279 Reaction CXXV. Action of Alkyl Halides on Phthalimide (Potassium Salt). — When an alcoholic solution of phthalimide is treated with the theoretical quantity of caustic potash dissolved in alcohol, a crystalline compound — potassium phthalimide — separates out (see p. 420). CO .CO C 6 H 4 < )NH -> C 6 H 4 < >N.K. X!(K X!n.k + r.i -> c 6 h 4 < >n.r + ki. xkk xkk The reaction is used chiefly with alkyl halides, although when certain acidic groups are present in the nucleus in the o- and ^-position to the halogen, the reaction gives satisfactory results with aryl halides. When the phthalimide derivative is hydrolysed, primary amines are formed, so that the reaction is useful for preparing certain aliphatic amines. y CO v XJOOH C 6 H 4 < >N.R + 2H 2 0 -> C 6 H 4 < + R.NH 2 . X)0/ \COOH A similar reaction can also be used for the preparation of amino acids, e.g., / co \ / C0 \ C 6 H 4 < >NK + C1CH 2 C00C 2 H 5 -> C 6 H 4 < >N.CH 2 COOC 2 H 5 xkk \co/ H 2 0 /COOH H 2 0 /COOH > C 6 H 4 < > C 6 H 4 < + NH 2 CH 2 COOH. (KOH) \CONH.CH 2 COOH (HC1) ^COOH Reaction CXXVI. — Action of Hydroxylamine on Aldehydes and Ketones. — The majority of aldehydes and ketones react with hydroxylamine, forming oximes. RR x CO + NH 2 OH -> RR X C = NOH + H 2 0. Hydroxylamine hydrochloride (NH 2 OH.HCl) is generally used ; in most cases the free base is liberated by the subsequent addition of the theoretical quantity of a basic substance (caustic potash, sodium car- bonate, etc.). W r ith aldehydes it is advisable to reduce the quantity of alkali to a minimum, and to warm but gently, if at all. Ketones react much less readily and usually require vigorous heating for 2 — 3 hours. The reaction is mostly carried out in aqueous-alcoholic solution. The purification of some oximes is best effected by distillation under reduced pressure. 280 SYSTEMATIC ORGANIC CHEMISTRY Preparation 242. — Acetophenone Oxime. C H 5 ^C : NOH. C 8 H 9 ON. 135. CR/ To 5 gms. (1 mol.) of hydroxy lamine hydrochloride, dissolved in 10 c.cs. of water and contained in a flask, 3 gms. (less than 1 mol.) of potassium hydroxide dissolved in 5 c.cs. of water are added. 8 gms. (slightly less than 1 mol.) of acetophenone are then added, and the mixture heated in a reflux apparatus on a boiling water bath. Alcohol, in small quantities at a time, is added down the reflux condenser until the boiling solution just becomes clear. After an hour heating is stopped, the solution cooled, and a drop tested with litmus paper. It should be acid owing to the absorption of the hydroxylamine by the ketone. Caustic potash solution is carefully added until the solution is no longer acid. The condenser is again attached, and boiling continued for about 30 minutes, at the end of which time the solution is tested, and if acid, is neutralised with caustic potash. After about 10 minutes further boiling the solution is once more tested with litmus, and a few drops of it mixed with ice water. If the test sample solidifies quickly, the reaction is complete, and the contents of the flask are poured into 100 c.cs. of water containing a few lumps of ice. (If the test sample does not solidify, further heating is necessary.) The water should be vigorously stirred during the addition to cause the separation of the oxime in small lumps and flakes. The product is filtered off, washed with water, pressed on a porous plate to dry, and recrystallised from petroleum ether. CH 3X CH 3X >>CO + H 2 NOH -> = NOH. C6H5 C 6 H 5 ^ 0 Yield.— 89% theoretical (8 gms.). Colourless needles: M.P. m° ; B.P. 763 246° (with decomposition) ; B.P. 20 156°— 157° (without decom- position). (B., 15, 2781.) Preparation 243. — Camphoroxime (Oxime of (/-camphor). CH, r ;X (!>!!! C 10 H 17 ON. 167. 10 gms. (excess) of hydroxylamine hydrochloride, dissolved in the minimum amount of water, are added to 10 gms. (1 mol.) of camphor dissolved in 150 gms. of 90% alcohol, and the mixture treated with 15 gms. of solid caustic soda. The whole is heated on a water bath, alcohol being added if necessary to keep the camphor in solution, till after about an hour's heating no camphor is precipitated on diluting a test portion of the liquid with an excess of water. The whole liquid is then diluted with a large excess of water, filtered if necessary from a very small THE LINKING OF NITROGEN TO CARBON 281 precipitate that may come down, and slightly acidified with acetic acid. The precipitated camphoroxime is recrystallised from dilute alcohol. C 9 H 16 CO + H 2 NOH = C 9 H 16 CNOH + H 2 0. Yield.— 75% theoretical (8 gms.). Colourless crystals; M.P. 115°. (B., 22, 605.) Preparation 244. — Benz-anti-aldoxime (a-Benzaldoxime). C 6 H 5 C.H || C 7 H 7 ON. 121. HON 14 gms. of caustic soda dissolved in 40 c.cs. of water and 21 gms. of benzaldehyde are mixed in a flask. 14 gms. of hydroxy lamine hydro- chloride are added in small portions at a time, the mixture being con- tinually shaken. The benzaldehyde gradually disappears, and some heat is developed. On cooling, the hydrochloride of benzaldoxime separates. Sufficient water is added to redissolve, and carbon dioxide is passed in until saturated. The oxime then separates, and is extracted with ether ; the ethereal solution is dried over anhydrous sodium sulphate. The ether is removed (see p. 32), and the residue distilled under greatly diminished pressure. C 6 H 5 .CHO + NH 2 OH -> C 6 H 5 CH : NOH + H 2 0. Yield.— 50% theoretical (12 gms.). M.P. 34°; B.P. 11 123°; B.P. 10 118°. Reaction CXXVII. Action of Acids, Acid Chlorides, Anhydrides and Phosphorus Pentachloride on Oximes (Beckmann Transformation). (B., 20, 1507.) — Aldoximes (oximes obtained from aldehydes) exist in two stereoisomeric forms depending on the relative position of the OH group. R.C.H R.C.H .11 ■ II N.OH OH.N %/i-aldoxime. A nti- a Id oxime. Syh -aldoximes give nitriles with dehydrating agents, such as acety chloride, H R.C=N R.C II N OH while II HON CH 3 CO.ON. When H is replaced by R, then no isomerism occurs. R.C.R II NOH. 282 SYSTEMATIC ORGANIC CHEMISTRY If H is replaced by R 1? as in the case of mixed ketones, isomerism again occurs. II II NOH OH.N. The one isomer can usually be transformed into the other by heat, exposure to light, or treatment with hydrochloric acid. When these isomers are treated with the reagents mentioned (p. 281) a rearrangement takes place in the molecule, especially with aromatic aldoximes and mixed ketoximes, due to the migration of the OH group. RCR X R.C.OH (1) II -> II N.OH . R P N. RCRi OH.C.Ri (2) || -> II OH.N N.R. These intermediate compounds are then immediately transformed into tautomeric forms, giving acid amides. (1) R.CO.NHRi and (2) R^ONH.R. II N.OH oxime of phenyl p-tolj\ ketone. benzo-p-toluidide. C 6 H 5 C.C 6 H 4 CH 3 || -> C 6 H 5 NH.CO.C 6 H 4 CH 3 . OH.N anilide of ^-toluic acid. The configuration of the oxime can be determined bv an examination of the transformation product. (Contrast B., 20, 1507 with B., 54, 3206). Prepakation 245. — Transformation of Acetophenone-oxime (Beckmann). 5 gms. acetophenone-oxime are dissolved in 60 c.cs. of ether, which has been dried over metallic sodium and redistilled, and to this solution is gradually added 7 — 8 gms. of powdered phosphorus pentachloride. The ether is then removed by distillation. To the residue after cooling is added slowly 25 c.cs. of water. The acetanilide is then filtered off and recrystal- lised from water, when its melting point is taken. M.P. Acetophenoneoxime .. . . . 59° Acetanilide 112° CH 3 C.C 6 H 5 CH 3 CO N.OH NH.C 6 H 5 . (B., 19, 989 ; 20, 1507.) Reaction C XXVIII. Action of Phenylhydrazine, etc., on Aldehydes and Ketones. — Phenylhydrazones of aldehydes and ketones are generally formed by warming these substances in aqueous-alcoholic solution with THE LINKING OF NITROGEN TO CARBON 283 phenylhydrazine, phenylhydrazine acetate or phenylhydrazine hydro- chloride in presence of excess sodium acetate. Derivatives of phenyl- hydrazine (e.g., £>-nitro-phenylhydrazine) also react in a similar manner. a-hydroxy aldehydes and a-hydroxy ketones can react with 3 mols. of phenylhydrazine in the following manner : — — CHOH.CHO + H 2 N.NH.C 6 H 5 ^ — CHOH.CH = N.NH.C 6 H 5 + H 2 0. — CH.OH.CH = N.NH.C 6 H 5 + NH 2 .NH.C 6 H 5 —> — CO.CH = N.NH.C 6 H 5 + NH 3 + C 6 H 5 NH 2 . — C.CH = N.NH.C 6 H 5 — CO.CH = N.NH.C 6 H 5 + NH 2 .NH.C 6 H 5 -> || + H 2 0. N.NH.C 6 H 5 Many of the simpler sugars react after this manner, forming osazones, which have a characteristic appearance under the microscope, and are of special value for identification purposes. Preparation 246. — Glucosazone. C 4 H 5 (OH) 4 .CNNH.C 6 H 5 .CH.N.NHC 6 H 5 , C 18 H 22 N 4 0 4 . 358. 2 gms. of glucose are dissolved in 10 c.cs. water and a solution of 4 gms. phenylhydrazine in 4 gms. glacial acetic acid and 10 c.cs. water is added. The mixture is heated on the water bath for 90 minutes, when the yellow osazone separates out. It is filtered, washed with water, and recrystallised from alcohol. Yield.— 2 gms. Golden yellow needles ; M.P. 204°. (B., 17, 579 ; 20, 821.) Preparation 247. — Acetone Phenylhydrazone (2-Propan-phenyl- hydrazone). (CH 3 ) 2 C = N.NHC 6 H 5 . C 9 H 12 N 2 . 148. 1 volume of glacial acetic acid is added to phenylhydrazine (1 mol.). The solution is diluted with 2 volumes of water, and acetone (1 mol.) is added. The acetone phenylhydrazone which separates is extracted with ether. The latter is separated, dried over anhydrous potassium carbonate, and distilled under reduced pressure, the fraction 165° at 91 mms. being retained. The oil still contains traces of ammonia, but this may be removed by allowing to stand in a vacuum desiccator over sulphuric acid for a short time. (CH 3 ) 2 CO + H 2 N.NH.C 6 H 5 -> (CH 3 ) 2 C = N.NH.C 6 H 5 + H 2 0. Yield. — Theoretical. Colourless, somewhat unstable oil; B.P. 91 165°. (B., 16, 662.) Preparation 248. — Phenylhydrazone of Pyruvic Acid (Phenylhydrazone of 2-oxy-propan acid). CH 3 C:N.NHC 6 H 5 . I C 9 H 10 O 2 N 2 . 178. COOH. 5 gms. (2 mols.) of phenylhydrazine are dissolved in 5 gms. (excess) of glacial acetic acid and 5 c.cs. of water added. 2 gms. (1 mol.) of pyruvic 284 SYSTEMATIC ORGANIC CHEMISTRY acid are added, and the mixture shaken. The precipitate, after filtration, is washed with dilute acetic acid. It may be recrystallised from alcohol. CH3.CO.COOH + H 2 N.NH.C 6 H 5 = CH 3 .C: (N.NHC 6 H 5 )COOH + H 2 0. Yield. — Theoretical (4 gms.). Yellow needles ; M.P. 192° (the substance must be heated quicklv, as it decomposes somewhat below its melting point). (J. pr. [2], 52, 39 ; B., 16, 2241.) The following modification of the reaction is of interest : — Preparation 249. — l-Phenyl-3-methyl-pyrazolone. N N.C 6 H 5 I ^>CO C 10 H 10 ON 2 . 174. CH 3 C CHo 13-5 gms. of ethyl acetoacetate are added to 10 gms. of phenylhydrazine and vigorously shaken. The oil thus obtained is removed and heated on the water bath for about 2 hours until a test portion solidifies when treated with ether. A little ether is poured into the warm liquid, the white crystals which separate being washed with ether and dried at 100°. The product is recrystallised from hot water or alcohol. N — NHC 6 H 5 CH 3 .CO.CH 2 .CO.OC 2 H 5 + H 2 N.NH.C 6 H 5 = || + H 2 0. CH 3 C.CH 2 .C0 2 C 2 H 5 N NHC 6 H 5 N N(C 6 H 5 ) = CO + C 2 H 5 OH. I CH 3 .C.CH 2 .CO.OC 2 H 5 CH 3 .C CH 2 Yield. — Theoretical (16 gms.). White crystals ; almost insoluble in cold water, ether, and ligroin ; fairlv soluble in hot water ; easily soluble in alcohol ; M.P. 127°. (B., 16, 2597.) Reaction CXXIX. Action of Semicarbazide on Aldehydes and Ketones. Most aldehydes and ketones condense readily with semicarbazide, yielding semicarbazones. E.CHO + NH 2 .NH.CO.NH 2 -> ECH : N.NH.CO.NH 2 + H 2 0. The operation is usually carried out as follows : — Semicarbazide hydrochloride (1 mol.) is dissolved in the minimum quantity of cold water ; sodium or potassium acetate (1 mol.) is dissolved in 96% alcohol, and to a mixture of these two solutions the aldehyde or ketone (1 mol.) is added. The semicarbazone separates at once, or on standing. Phenylsemicarbazide reacts similarly. Preparation 250. — Benzaldehyde Semicarbazone. C 6 H 5 CH = N.NH.CO.NH 2 . C 8 H 9 ON 3 . 163. 13 gms. of hydrazine sulphate are dissolved in 100 c.cs. of water and neutralised by the gradual addition of 5-5 gms. anhydrous sodium car- THE LINKING OF NITROGEN TO CARBON 285 bonate. After cooling, 8-5 gms. potassium cyanate are added, and left to stand overnight. The solution is then acidified with acetic acid and filtered. The filtrate is treated with 10 gms. benzaldehyde and placed in a mechanical shaker for 30 minutes. It is then allowed to stand overnight. Benzaldehyde semicarbazone separates out in almost theoretical yield, and is filtered off and recrystallised from aqueous alcohol. 2N 2 H 4 H 2 S0 4 + Na 2 C0 3 -> 2N 2 H 4 HS0 4 + Na 2 S0 4 + H 2 C0 3 . (NH 2 .NH 2 )HS0 4 + KCNO — > NH 2 NHCONH 2 + KHS0 4 . NH 2 .NH.CO.NH 2 + C 6 H 5 CHO -> C 6 H 5 CH : N.NH.CO.NH 2 + H 2 0. M.P. about 214° with decomposition. Benzaldehyde semicarbazone may also be obtained in theoretical yield by agitating benzaldehyde (1 mol.) with an aqueous solution of semi- carbazide hydrochloride (1 mol.). (A., 270, 34 ; B., 27, 32.) Peeparation 251. — Acetone Semicarbazone. (CH 3 ) 2 C = N.NH.CONH 2 . C 4 H 9 ON 3 . 115. 25 gms. of semicarbazide hydrochloride are dissolved in a small quantity of water ; to this a solution of 21 -8 gms. of potassium acetate in a small quantity of alcohol is added. The mixed solutions are well shaken and cooled in ice in order to precipitate as much of the potassium chloride as possible, and then filtered. To the nitrate 12-9 gms. of acetone are added and the solution allowed to stand overnight. The precipitated acetone semicarbazone is filtered off. If more acetone is added to the filtrate further precipitation occurs. It is then recrystallised from hot alcohol. CH CH 3X \C = 0 + H 2 N.NH.CONH 2 -> 3N >C = N.NH.CONH 2 + H 2 0. CH/ OH/ Yield. — 95% theoretical (24 gms.). M.P. 188°— 189° with decom- position. (A., 283, 19.) Reaction CXXX. Formation o£ Amino Guanidine Derivatives. — Amino guanidine combines with aldehydes and ketones in presence of a mineral acid. KRjCO + NH 2 .NH V >C : NH -> RR 1 C = N.NH X NH/ >C : NH + H,0, NH/ Many of the resulting compounds form crystalline picrates, and are isolated as such. The compounds with aromatic aldehydes are isolated as difficultly soluble nitrates. Reaction CXXXI. Formation of Semioxamazones. — Semioxamazide, NH 2 .CO.CO.NH.NIT 2 possesses similar properties to semicarbazide, and reacts well with aldehydes, but with ketones the reaction does not seem to be generally applicable. R.CHO + H 2 N.NH.CO.CO.NH 2 -> R.CH : N.NH.CO.CO.NH 2 + H 2 0. The aldehydes or ketones and the semioxamazide are weighed in mole- 286 SYSTEMATIC ORGANIC CHEMISTRY cular proportions, and when the former are insoluble in water it is best to dissolve them in a small quantity of alcohol. The semioxamazide, dissolved in the minimum quantity of water, is then added and the mixture thoroughly shaken for some time, when a precipitate of the semi- oxamazone separates. The semioxamazones are usually white powders of definite melting point, sparingly soluble in the usual organic solvents and insoluble in water. (See also J. C. S., 123, 394.) Reaction CXXXII. Action of Aliphatic Halogen Compounds on Aliphatic or Aromatic Primary Amines. — Secondary, tertiary and quaternary compounds may be formed. EiCl EiCl EjCl E.NH 2 > E.NHE X > ENfE^ > EN(E 1 ) 3 C1. In this way secondary and tertiary amines may be obtained from primary. Quaternary compounds are obtained by prolonged action of an excess of halogen compound on primary amines, or more usually by the action of halogen compound on a tertiary amine. Preparation 252. — Dimethyl-benzyl-phenyl-ammonium chloride (Meth- chloride of methyl-benzyl-phenyl amine). N(CH 8 ) 2 (CH 2 .C e H 6 )(C 6 H 6 ).Cl. C 15 H 18 NC1. 247-5. A mixture of 5 gms. (1 mol.) of dimethyl aniline and 5-3 gms. (1 mol. of benzyl chloride is placed in a basin, which is left in a desiccator at ordinary temperature for 2 — 3 months. At the end of this time the mass is practically solid ; it is pressed out on porous plate, washed with ether and recrystallised from water or alcohol. C 6 H 5 N(CH 3 ) 2 + C 6 H 5 CH 2 C1 -> N(CH 8 ) a (CH a C 6 H 5 )(C 6 H 5 )Cl. ' Yield. — Theoretical (10 gms.). Colourless plates, containing l.H o 0 of crystallisation ; M.P. 110°. (B., 10, 2079.) Preparation 253. — Trimethyl- ft -naphthyl-ammonium iodide (Meth- iodide of dimethyl-/3-naphthylamine). C 10 H 7 N(CH 8 ) 2 I. C 13 H 16 NI. 313. 5 gms. (1 mol.) of f$ naphthylamine, 20 gms. (excess) of methyl iodide, and 20 c.cs. of water are placed in a flask and boiled under reflux until the amine completely dissolves (about 3 hours). The quaternary com- pound formed separates out on cooling. It is filtered off, washed sparingly with water, and dried on porous plate. C 10 H 7 NH 2 + 3CH 3 I -> C 10 H 7 N(CH 3 ) 3 I + 2HI. Yield. — Theoretical (12 gms.). Colourless needles ; decompose when heated or exposed to air. (B., 11, 638 ; 13, 2054.) Preparation 254.— Pyridine Methiodide. C 5 H 5 NCH 3 .I. C 6 H 8 NL 221. 1 c.c. of pyridine and 1 c.c. of methyl iodide are mixed with a glass rod in a small test tube. A vigorous reaction sets in and product becomes THE LINKING OF NITROGEN TO CARBON 287 very hot. After a few minutes, 5 c.es. absolute alcohol are added, and gently warmed to dissolve. On cooling, the product crystallises out in flat needles, which are filtered off and washed with a little alcohol. h CH 3 I -5 N N CH 3 X I M.P. 117°. (B., 18, 3438.) Following are developments and modifications of the present reaction : — Preparation 255.— Methyl Aniline (Phenyl-methylamine). C 6 H 5 NH.(CH 3 ). C 7 H 9 N. 107. 20 gms, (1 mol.) of acetanilide (see p. 296), 5 gms. (excess) of sodium wire, and 100 gms. of pure xylene (dried over sodium) are refluxed for 2 — 3 hours in an oil bath at 130°. After cooling, 15 gms. (rather more than theoretical) of methyl iodide are added, and the mixture digested for a short time until no more methyl iodide condenses in the condenser tube. The xylene is then distilled off. The methyl acetanilide is boiled with concentrated alcoholic potash solution for about 24 hours in a reflux apparatus. The alcohol is distilled off, and the residue neutralised by addition of hydrochloric acid. The residual xylene is then distilled ofi in steam, the solution made alkaline, and the methylaniline steam-distilled. It is taken up with ether, dried over fused sodium sulphate or potassium hydroxide and fractionated. C 6 H 5 NH.COCH 3 + CH3I -> C 6 H 5 N.(CH 3 )CO.CH 3 -> C 6 H 5 NH.CH 3 . Yield.— Theoretical (15 gms.). Yellowish oil ; B.P. 192° ; D. 1 , 5 0-976. (B., 10, 328 = ) In certain cases addition of sodium carbonate is effective. Preparation 256. — Dimethyl-o-toluidine. /N(CH 3 ) 2 C 6 H< C 9 H 13 N. 135. * X CH 3 . 15 gms. o-toluidine, 42 gms. methyl iodide and 16 gms. sodium carbonate dissolved in 250 c.cs. water are heated in a reflux apparatus on a water bath for about 2 hours until methyl iodide no longer condenses in the condenser tube. The liquid is then made strongly alkaline with caustic soda solution ; the amine is extracted with ether, the extract dried over solid potash and distilled. The amine comes over at 175° — 185°. /NH 2 y N(CH 3 ) 2 C 6 H 4 < + 2CH 3 I + Na 2 C0 3 -> C 6 H 4 < + 2NaI + H 2 0 + C0 2 . X CH 3 \CH 3 Yield.— 80% theoretical (15 gms.). Pale yellow liquid ; B.P. 183°. B., 24, 563.) 288 SYSTEMATIC ORGANIC CHEMISTRY The following preparation is of interest in connection with. Fischer's researches on the proteins : — ■ Preparation 257. — Leucyl-glycine ( { 5-Methyl-l-oxy-2-amino-l- pentanyl} amino ethan acid). (CH 3 ) 2 : CH.CH 2 .CH(NH 2 ).CO. C 8 H 16 0 3 N 2 . 188. HOOC.CH 2 .NH. 10 gms. (1 mol.) of glycocoll are dissolved in 133 c.cs. (1 mol.) of normal caustic soda, and while cooled with ice and vigorously shaken, the solution is treated alternately with 170 c.cs. (excess) of cold N. caustic soda, and 37 gms. (1 mol.) of a-bromisocapronyl-bromide (C. 1910, I. 1345) in four portions, each new addition being made only when the smell of the acid bromide has disappeared. The whole operation lasts about 20 minutes. The liquid is filtered from the small amount of oil it contains, and then treated with 35 c.cs. (excess) of 5N. hydrochloric acid. The oil which is precipitated is extracted with ether, and the condensation product pre- cipitated from the ethereal solution after the latter has been concen- trated, by the addition of a large quantity of petroleum ether. The pro- duct a-bromisocapronyl-glycine soon crystallises. It is filtered at the pump, washed with petroleum ether, and recrystallised from hot water, or from chloroform. (CH 3 ) 2 : CHCH 2 CHBrCOBr + NH 2 CH 2 COOH = (CH 3 ) 2 : CHCH 2 CHBr.CO.NH.CH 2 COOH + HBr. Yield.— 75% theoretical (26 gms.). Colourless crystals ; M.P. 133°. The chief fraction of the raw product can also be obtained in crystalline form at once if the alkaline solution is first made slightly acid, treated with a few crystals previously prepared, and then continually stirred while the rest of the hydrochloric acid is slowly poured into it. The a-bromisocapronyl-glycine is converted into leucyl-glycine by dissolving it in 5 times its weight (excess) of 25% ammonia (D. 0*910), and allowing the solution to stand for 4 days at room temperature. The crystalline paste of ammonium bromide and dipeptide, which is produced when the solution is concentrated on a water bath, is treated with absolute alcohol and again evaporated. The residue is boiled with alcohol, and when cold the leucyl-glycine, which is insoluble in alcohol, is filtered off at the pump and washed with alcohol until a sample of it dissolved in water gives no further precipitate with silver nitrate. The dipeptide is purified by dissolving it in 15 times its weight of hot water. On cooling, about half the product separates out in crystalline form. By concen- trating the mother liquor and precipitating with alcohol, the rest may be obtained. The product should be free from bromine. (CH 3 ) 2 : CH.CH 2 CHBr.CO.NH.CH 2 .COOH + 2NH 3 = (CH 3 ) 2 : CH.CH 2 CH(NH 2 ).CO.NH.CH 2 .COOH + NH 4 Br. Yield. — 80% theoretical (6 gms. for each 10 gms. of the a-bromiso- capronyl-glycine taken). Colourless crystals ; soluble in water ; insoluble in alcohol ; M.P. (decomposition) 243°. (B., 42, 3398 ; C, 1909, II., 1546.) THE LINKING OF NITROGEN TO CARBON 289 Reaction C XXXIII. Action of Aromatic Halogen Compounds on Ammonia or Amino Compounds. — While aliphatic halides readily react with ammonia and amines according to Reaction CXXXII, the halogen of aromatic halides is but slightly reactive, unless a number of negative groups (e.g., nitro) are also present in the molecule. It is found, however, that the addition of copper powder or cuprous halide greatly accelerates the elimination of halogen hydride when aromatic halides and amino compounds interact. Pkepakation 258. — Diphenylamine (Phenyl-aniline). C 6 H 5 NHC 6 H 5 . C 12 H n N. 169. 10 gms. (1 mol.) of acetanilide, 5 gms. of dry potassium carbonate, 20 gms. (excess) of brom-benzene, and a little cuprous iodide in nitro- benzene solution, are remixed for 15 hours. The dark-brown liquid is then steam-distilled until no more nitrobenzene passes over. The residue in the distillation flask, consisting of the acetyl derivative of diphenylamine, is a thick brown oil. It is dissolved in ether, filtered, dried over calcium chloride, and the ether removed on a water bath. The residue is crystallised from alcohol, from which it separates as white plates, melting at 102°. The crystals are dissolved in 30 c.cs. of alcohol, and hydrolysed by boiling with 30 c.cs. of cone, hydrochloric acid for 2 — 3 hours. The product is distilled in steam, a yellow oil passing over, which solidifies in the con- denser. C 6 H 5 NHCOCH 3 +C 6 H 5 Br-^ (C 6 H 5 ) 2 N.COCH 3 ^(C 6 H 5 ) 2 NH + CH 3 COOH. Yield.- — 60% theoretical (7-5 gms.). Yellow plates ; soluble in hot alcohol ; M.P. 53° ; B.P. 310°. (B., 40, 4543.) Pkepakation 259. — Phenylglycine-o-carboxylic Acid. /NH.CH 2 .COOH C 6 H 4 < C 9 H 9 0 4 N. 195. \COOH. 20 gms. potassium-o-chlorbenzoate (prepared from the free acid and caustic potash), 5-5 gms. solid caustic potash, 7 gms. potassium carbonate, 7-5 gms. glycocoll, 15 c.cs. water, and a small quantity of copper powder are placed in a flask provided with a reflux condenser. The mixture is heated to boiling in an oil bath for an hour, the contents finally becoming yellow in colour. The product is cooled somewhat, and boiling water added to redissolve the crystals which have separated. The solution is filtered and the filtrate, while hot, treated with excess of hydrochloric acid ; phenylglycine o-carboxylic acid separates, and after some time is filtered off and recrystallised from water. .CI /NH.CH 2 .COOH C 6 H 4 < + H 2 N.CH 2 COOH -> C 6 H 4 < \COOK \COOH Yield. — Practically theoretical (19 gms.). M.P. 200° (with decomposi- tion). (D.R.P., 142507.) 290 SYSTEMATIC ORGANIC CHEMISTRY Reaction CXXXIV. Action of Silver Cyanide on Alkyl Halides. EX + AgNC -> RNC + AgX. Isocyanides (isonitriles or carbylamines) are formed in this reaction, which is illustrated in the following : — Preparation 260. — Ethyl Isocyanide (Ethyl-carbylamine). C 2 H 5 .NC. C 3 H 5 N. 55. 20 gms. (1 mol.) of ethyl iodide are gently renuxed in a fume cupboard under a long condenser with 30 gms. (excess) of dry silver cyanide until the liquid ceases to drip back, and the mass is pasty (about 1 hour). A soluble crystalline compound ethyl argento -cyanide, C 2 H 5 Ag(NC) 2 , is now contained in the flask. Ethyl isocyanide is formed from it either by heating it to 180°, or better, by heating to 100° with concen- trated potassium cyanide solution. A solution of 10 gms. (1 mol.) powdered 98% potassium cyanide in 25 c.cs. of water is added, and the contents of the flask distilled from a water bath in a fume cupboard, the distillate being collected in a flask with an outlet to a good draught pipe. It is redistilled with the same precautions, the fraction 75° — 78° being separately collected. C 2 H 5 I + 2 AgNC - C 2 H 5 Ag(NC) 2 + AgL C 2 H 5 Ag(NC) 2 + KNC = KAg(NC) 2 + C 2 H 5 NC. Volatile liquid ; very offensive odour ; B.P. 78°. (J. pr. [2], 30, 319.) Reaction CXXXV. Action of Chloroform and Alcoholic Potash on Aliphatic and Aromatic Primary Amines. E.NH 2 + CHC1 3 + 3KOH -> R.NC + 3KC1 + 3H 2 0. Isonitriles are formed. The reaction is convenient for the detection of primary amines ; the isonitriles have a characteristic, but poisonous, odour ; the operation should, therefore, be conducted in a good draught cupboard. Reaction CXXXVI. — Action of the Hydrochloride of a Primary Aromatic Base on the Base. R.NH 2 + HC1.NH 2 R -> R.NH.E + NH 4 C1. The reaction takes place at a high temperature and usually under high pressure in an autoclave, secondary amines being formed. Preparation 261. — Diphenylamine. <( )-NH-( ^> C 12 H n N. 169. 93 gms. aniline and 93 gms. aniline hydrochloride are heated for 20 hours to 230° in an enamelled autoclave, the pressure reaching about 6 atms. No iron should be in contact with the reaction products, else the yield is reduced. After 2 hours, the water present is cautiously blown off through the valve, this process being repeated three times during an hour. The presence of water has a very marked influence on THE LINKING OF NITROGEN TO CARBON 291 the reaction. Some aniline and ammonia also escapes. The reaction is complete after about 20 hours. The contents of the autoclave are then placed in a porcelain basin with a litre of water, and heated to 80°. 70 c.cs. strong hydrochloric acid are added until the reaction is just acid to Congo Red. It is then allowed to cool. After several hours the crude diphenyl- amine separates as a solid cake, which can easily be removed from the mother liquor. It is then melted under a little water, and any unchanged aniline extracted with a little hydrochloric acid, and washed with dilute sodium carbonate. The diphenylamine is then purified by distilla- tion with superheated steam (see p. 23), the temperature of the oil bath being 250°, and that of the superheated steam 300°. The diphenyl- amine is obtained as an almost colourless liquid, which solidifies to a pale-yellow cake. Aniline can be recovered from the acid mother liquors. )NH 2 + HC1.NH 2 ^ / \ )-NH-( ^> + NH 4 C1. Yield. — 60% theoretical (100 gms.). Colourless crystals ; peculiar smell ; M.P. 53° ; B.P. 310° ; important intermediate for dyestuffs. (B., 40, 4541.) Reaction C XXXVII. Action of Bromine (or Chlorine) and Alkali on Certain Amides and Imides (Hofmann's Reaction). — This method is applicable for the preparation of both aliphatic and aromatic amines. E.CO.NH 2 + Br 2 — > R.CO.NHBr + HBr. R.CO.NHBr -> R.N : CO + HBr. RNCO + H 2 0 -> R.NH 2 + C0 2 . The reaction proceeds in stages, a bromamide being first formed ; this loses a molecule of hydrogen bromide on further action with caustic soda, yielding probably an isocyanate, which, being unstable in presence of excess of alkali, is hydrolysed to an amine and carbon dioxide. Sodium hypochlorite (or hypobromite) and sodium hydroxide are the reagents used. The reaction finds industrial application in the prepara- tion of anthranilic acid for the synthesis of indigo. On a technical scale sodium hypochlorite is always employed, but on a small scale sodium (or potassium) hypobromite is frequently used owing to the ease with which a solution of known strength can be made up from weighed quantities of bromine and alkali. Preparation 262. — Anthranilic Acid (Ortho-amino-benzoic acid). NH 2 C 6 H 4 < C 7 H 7 0 2 N. 137. \COOH 40 gms. of finely powdered phthalimide and 80 gms. of caustic soda are dissolved together in 280 c.cs. of water, the solution being cooled during the operation. The solution is agitated, and 400 gms. of a 5% solution of sodium hypochlorite run in. When all is added, the solution is warmed for a few minutes at 80° to complete the reaction ; it is then cooled and neu- tralised exactly with hydrochloric or sulphuric acid. An excess of strong u 2 292 SYSTEMATIC ORGANIC CHEMISTRY acetic acid is added to precipitate the anthranilic acid, which is filtered off and washed with water. Any anthranilic acid remaining in the filtrate is precipitated as copper anthranilate by the addition of a saturated solution of copper acetate. After standing for some time the precipitate is filtered off and suspended in a small quantity of warm water, while a current of sulphuretted hydrogen is passed into the suspension. The copper sulphide formed is filtered off, and anthranilic acid recovered from the filtrate by concentration on a water bath. It may be recrystallised from hot water. /C0 X y NH 2 C ° H H ^ C ' H R.CO.NH 2 + H 2 0. While those of dibasic acids yield imides. CH 2 .COOH CH 2 .CCK | -> | >NH + 2H 2 0. . ' CH 2 .CO.ONH 4 CH 2 .C(K Peepaeation 263. — Acetamide. CH 3 CO.NH 2 . C 2 H 5 ON. 59. 20 gms. ammonium acetate (as dry as possible), and 25 gms. glacial acetic acid are placed in a small round-bottomed flask provided with a reflux condenser, and heated to gentle boiling over a wire gauze for 3 hours. The flask is then connected by means of a cork and delivery tube with a sloping water condenser and distillation commenced. The distillate up to 160° is discarded. Above 160° the water is run out of the condenser and the distillate collected in a small distilling flask. This portion is redistilled and the fraction 210° — 225° separately collected ; it solidifies on cooling to a mass of white crystals. These may be recrystal- lised from ether as long needles. CH 3 .COONH 4 -> CH 3 .CONH 2 + H 2 0. Yield.— 80% theoretical (12 gms.). M.P. 82° ; B.P. 222°. (B., 15, 980.) For modification of above, see Am. Soc. 44, 2286. Peepaeation 264. — Succinimide (Imide o£ butan-di acid). CH 2 .CO x I )NH. C 4 H 5 0 2 N. 99. CH 2 .CCK 20 gms. of succinic acid are dissolved in a small quantity of water in a basin, and the solution neutralised with ammonia. The solution is boiled to expel excess of ammonia, after which a further 20 gms. of succinic THE LINKING OF NITROGEN TO CARBON 293 acid dissolved in water is added. The solution is evaporated to complete dryness on a water bath ; the dry residue is transferred to a retort and heated quickly with a large luminous flame. The sublimate of succinimide is recrystallised from pure acetone. CH 2 COOH CH 2 .C(X | -> j )NH + 2H 2 0. CH 2 .COONH 4 CH 2 .C(K Yield. — 70% theoretical (11 gms.). Colourless rhombic plates ; M.P. 126° ; B.P. 288°. (A., 49, 198.) Preparation 265. — Formamide (Amide of formic acid). H.CONH 2 . CH 3 ON. 45. 150 c.C3. of pure formic acid are placed in round-bottomed flask attached to a condenser, and having also a delivery tube dipping nearly to the bottom of the acid in the flask. Dry ammonia gas is led into the acid through the delivery tube, passing first through a tower of solid caustic soda, and then soda -lime. Much heat is evolved during the reaction, and the flask must be cooled. -After about 15 minutes the acid is neutralised, and crystals of ammonium formate are deposited. The flask is then heated on a paraffin bath, and at 150° the salt begins to decompose and water passes over. The temperature is gradually raised to 180°, at which temperature no more water distils over. The resulting brown liquid is distilled under greatly reduced pressure, the fraction 85° — 95° at 0-5 mm. being collected. After standing over anhydrous sodium sulphate for some days, it is again distilled under reduced pressure. H.COONH 4 — H 2 0 -> H.CONH 2 . Yield. — 66% theoretical (98 gms.). Viscous colourless liquid ; M.P. 2-25° ; D. 14 1-337. (Am. Soc, 40, 794.) Reaction CXXXIX. Action of Ammonia on Esters, Acid Chlorides or Anhydrides. (1) E.COOK! + NH 3 -> R.CO.NH 2 + R 1 OH. (2) R.COC1 + NH 3 -> R.CO.NH 2 + HC1. RCO, RCO- (3) >0 + 2NH 3 -> 2R.CO.NH 2 + H 2 0. (1) Is restricted mostly to esters of aliphatic acids. (2) Is employed for the preparation of aromatic amides. If the anhydride of a dibasic acid. e.g., phthalic, is employed, an imide results. Preparation 266. — Acetamide. 15 gms. ethyl acetate are treated in a small conical flask with an equal weight of cone, ammonia solution. The flask is corked and left in a warm place (say, near a steam bath) until the two layers originally present give place to one uniform solution. This solution is then distilled, water, alcohol and ammonia passing over up to 100° ; the fraction 210° — 225° 294 SYSTEMATIC ORGANIC CHEMISTRY is separately collected, and if it does Dot solidify on cooling it is redistilled. The final product is recrystallised from ether. CH 3 .CO.OC 2 H 5 + NH 3 -> CH 3 .CONH 2 + C 2 H 5 .OH. Yield— 80% theoretical (8-5 gms.). M.P. 82°. (B., 15, 981 ; Am. Soc, 33, 974.) Oxamide is obtained as a white amorphous precipitate when equal weights of dimethyl (or diethyl) oxalate and cone, ammonia are mixed. The precipitate is filtered off and recrystallised from alcohol. CH3O.OC.CO.CH3 + 2NH 3 -> NH 2 OC.CONH 2 + 2H 2 0. Peepaeation 267. — Benzamide. C 6 H 5 .CONH 2 . C 7 H 7 ON. 121. 10 gms. finely powdered dry ammonium bicarbonate are placed in a mortar in a fume cupboard. 5 gms. benzoyl chloride are added and the whole well mixed with a pestle during 10 minutes. If the odour of benzoyl chloride persists at the end of this time, a few drops of cone, ammonia are added. The product is diluted with water, the benzamide filtered off and recrystallised from boiling water. C 6 H 5 C0C1 + 2NH 4 HC0 3 -> C 6 H 5 CONH 2 + NH 4 C1 + 2C0 2 + 2H 2 0. Yield— 93% theoretical (4 gms.). Glistening plates; M.P. 130°* (A, 3, 268 ; B, 10, 1785.) Benzamide may also be prepared by adding 5 gms. benzoyl chloride drop by drop to 20 c.cs. cone, ammonia solution. Peepaeation 268. — Phthalimide. C 6 H 4 <^°\NH. C 8 H 5 0 2 N. 147. 20 gms. phthalic anhydride are placed in a 100-c.c, conical flask fitted with a cork carrying inlet and exit delivery tubes. The flask is heated in a paraffin-wax bath until the anhydride melts, when a current of dry ammonia is led in through the inlet tube, which reaches to within 1 cm. of the substance. The temperature of the bath is gradually raised during an hour to 230°. The contents of the flask are then cooled and recrystal- lised from ether. C 6 H 4 / cQ ^0 + NH 3 -> C 6 H 4 / c(y >NH + H 2 0. Yield.— 70% theoretical (14 gms.). White needles ; M.P. 232° (A 247, 294 ; B., 10, 579.) Reaction CXL. Action of Ammonia on Phenols and Sulphonic Acids. (1) K.OH+NH 3 -^E.NH 2 + H 2 0. (2) K.S0 3 H + NH 8 -> E.NH 2 + H 2 S0 3 . (1) Takes place readily with polyhydric phenols and naphthols, also if THE LINKING- OF NITROGEN TO CARBON 295 negative groups are present in the molecule, e.g., nitrophenols (B., 19, 2161). The reaction is usually carried out under pressure, and the yield is improved by the presence of sodium or ammonium sulphite (BuchererV method), the sulphurous esters of phenols reacting more readily than phenols. The ammonia is used in the form of its concentrated solution, or as its addition compound with zinc chloride. The reaction (2) is carried out similarly to (1). The reaction is easy in the anthraquinone series, but not in the naphthalene series, where sodamide is sometimes used. R.S0 3 H + NaNH 2 -> R.NH 2 + NaHS0 3 . An interesting case of group migration may be mentioned here ( y 0H 1 Y i 0H + NaNH 2 _> S chaffer's acid. NH 2 If excess NaNH 2 is used, the OH group is also replaced by NH 2 . Preparation 269. — /?-Naphthylamine (2-Amido-naphthalene). C 10 H 9 N. 143. Method I. — 144 gms. /?-naphthol and 600 gms. ammonium sulphite are heated in an autoclave with stirrer and oil bath. 125 gms. 20% ammonia are also added, and the mixture is heated for 8 hours at an internal tem- perature of 150°, and a pressure of 6 atms. (Note. — No brass gauges should be used.) The contents are allowed to cool and the cake of ^-naphthylamine is broken up and thoroughly washed with water on a filter. After washing it is dissolved in 1-| litres of water and 110 gms. hydrochloric acid (which should be free from sulphuric acid) and filtered. To the filtrate is added about 400 gms. saturated sodium sulphate solution until precipitation of the naphthylamine sulphate is complete (test). It is then filtered and washed with water. The free base is obtained by making a thin paste of the sulphate and heating to 80° with stirring, when caustic soda solution is added until the liquid gives an alkaline reaction to phenolphthalein. It is then filtered, washed, and dried at 80°. + NH3 -> \/\y \/\/ Yield.— 85— 95% theoretical (120—135 gms.). White plates ; M.P. 112° ; B.P. 294° ; the sulphate is less soluble than that of a naphthyl- amine ; important intermediate for dyestuffs. (E.P., 1387, 1900 ; F.P., 297464, 394820.) Method II. — 50 gms. ^-naphthol and 200 gms. powdered zinc ammonia chloride are mixed and heated on an oil bath in a vessel provided with a reflux condenser for 2 hours at 200°. The product, after cooling, is treated with 25% caustic soda solution until the 296 SYSTEMATIC ORGANIC CHEMISTRY zinc oxide redissolves, and the solution boiled for a few minutes. On cooling, ^naphthylamine separates. It may be removed and purified, as described in Method I. It may also be separated by extraction with ether, or by distillation in a current of superheated steam. (B., 13, 1300.) Peepaeation 270. — 2-Amino-anthraquinone. /\/ C0 \/\ NH , C 14 H 9 0 2 N. 223. \A C0 /\/ 20 gms. sodium anthraquinone sulphonate (silver salt) and 200 c.cs. of cone, aqueous ammonia (D. 0-88) are heated in an autoclave of 500 c.cs. capacity to 180°, and maintained at this temperature for 6 hours. The autoclave is left to cool overnight, then opened, and the amino anthra- quinone filtered off and dried. Red crystals ; M.P. 302°. (B., 12, 1567.) Reaction CXLI. Action of Acids, Acid Anhydrides and Chlorides on Primary and Secondary Amines. — These derivatives are usually prepared by treating the amine with the organic acid, or with the acyl chloride or anhydride. When the acid is used a salt is first formed from which a molecule of water is eliminated on further heating. ECOOH + EiNHa -> E-COONHgEj -> E-CONHEj + H 2 0. ECOC1 + RiNH 2 — > E.CONHEj + HC1. (ECO) 2 0 + 2E X NH 2 -> 2ECONHE, + H 2 0. When benzoyl chloride is used it is necessary to have present, or to add subsequently, an excess of caustic soda or some other basic substance (Schotten-Baumann Reaction). When an acid anhydride is used the reaction is usually carried out by the application of heat, and may be hastened by the addition of dehy- drating agents, e.g., fused sodium acetate or fused zinc chloride. Peeeaeatton 271. — Acetanilide (Phenyl-amide of ethan acid). A mixture of 25 gms. (1 mol.) of redistilled aniline and 30 gms. (excess) of glacial acetic acid is boiled under an air condenser, preferably in a flask with a condenser ground into the neck, until no aniline separates on treating a sample with a cold caustic soda solution (8 hours). The hot liquid is at once poured into 500 c.cs. of cold water, filtered, and washed with cold water. The crude acetanilide is boiled with a litre of water, a little alcohol being added until it all goes into solution. It is filtered through a hot water filter (see p. 10), and the solution allowed to crystallise. If the product is dark coloured, it is redissolved as before, boiled with 5 gms. of animal charcoal for J hour, filtered, and allowed to crystallise. C 6 H 5 NH 2 + CHgCOOH = CH 3 CONHC 6 H 5 + H 2 0. Yield. — 85% theoretical (30 gms.). Rhombic plates ; sparingly soluble in hot water ; M.P. 112° ; B.P. 295°. (J. C. S., 2, 106.) If 10 gms. of fused sodium acetate (see p. 506) be added to the reaction mixture, the time of heating can be shortened to 6 hours. An THE LINKING OF NITROGEN TO CARBON 297 older method of working up the reaction product was to distil fractionally the mixture of acetanilide and excess acetic acid, the former coming over at 280°, and being then recrystallised (A. Ch. [3], 37, 328). Preparation 272. — Benzanilide (Phenylamide of benzene-carboxylic acid). C 6 H 5 NH.CO.C 6 H 5 . C 13 H n ON. 197. Method I. — 12 gms. of aniline are placed in a dish in a fume cupboard, and 10 gms. of benzoyl chloride are gradually added. Much heat is developed. When cold the product is extracted first with dilute hydro- chloric acid to remove aniline, then with dilute caustic soda to remove benzoic acid, and finally with water. After pressing it is crystallised from alcohol. C 6 H 5 .C0.C1 + 2C 6 H 5 NH 2 -> C 6 H 5 .CO.NH.C 6 H 5 + C 6 H 5 NH 2 .HC1. Yield.— Almost theoretical (20 gms.). (A., 60, 311.) In the above process only one-half of the amine is transformed into its benzoyl derivative. By working in presence of dilute caustic soda or other alkali (Schotten-Baumann reaction, see benzoyl-£>-toluidide), the amine is completely converted into its benzoyl derivative. Method II. — A mixture of 15 gms. (1 mol.) of aniline, and 20 gms. (1 mol.) of benzoic acid is heated in a retort at 180°, and the temperature raised gradually to 225° ; a further 10 gms. of aniline are added, and the heating continued. The hot mass is then poured into an evaporating dish and allowed to solidify. It is powdered, washed with dilute hydro- chloric acid to remove unchanged base, then with water to remove the benzoate, then with dilute caustic soda to remove free acid, and finally with water. It is dried and crystallised from alcohol. C 6 H 5 NH 2 + C 6 H 5 COOH — > C 6 H 5 NH 2 .C 6 H 5 COOH -> C 6 H 5 NHCOC 6 H 5 + H 2 0. Yield. — 80% theoretical (26 gms.). Colourless plates ; insoluble in water; M.P. 162°. (Bl. [Ill] 11, 893.) Preparation 273. — Benzoyl-j>toluidide (^-Tolyl-amide oi benzene carboxylic acid). C 6 H 5 CONH.C 6 H 4 CH 3 [4.1]. C 14 H 13 ON. 211. 2 gms. (1 mol.) of finely divided ^-toluidine are mixed with 10 c.cs. of a 10% aqueous solution of sodium hydroxide, and 2 c.cs. benzoyl chloride (excess) are added gradually to the warm mixture in a corked flask, which is mechanically shaken. Thorough shaking is essential. If any excess of benzoyl chloride remains, it is destroyed by warming with a further quantity of sodium hydroxide solution. The mixture is then poured into water, and the precipitate filtered, dried, and recrystallised from alcohol. CH 3 C 6 H 4 NH 2 + C 6 H 5 C0C1 + NaOH= C 6 H 5 CONHC 6 H 4 CH 3 + NaCl + H 2 0. Yield. — Almost theoretical (4 gms.). Colourless crystals ; insoluble in water ; M.P. 158°. (B., 19, 3219.) 298 SYSTEMATIC OKGANIC CHEMISTRY Preparation 274. — Diacet-o-toluidide (Di-ethanoyl derivative of o- toluidine). CH 3 .C 6 H 4 N(CO.CH 3 ) 2 [1.2]. C n H 13 0 2 N. 191. 10 gms. of o-toluidine, 38 gms. of acetic anhydride and 5 gms. fused sodium acetate are heated to boiling for 1 hour in a flask provided with an air condenser and calcium chloride tube. After this time the product is distilled from a distilling flask at a pressure of 20 mms. Acetic acid and acetic anhydride pass over first ; the diacetyl derivative distils at 152° — 153°, and sodium acetate and some mono-acetyl derivative remain in the flask. CH 3 .C 6 H 4 NH 2 + (CH 3 CO) 2 0 -> CH 3 .C 6 H 4 N(COCH 3 ) 2 + H 2 0. Yield. — 80% theoretical (14 gms.). Colourless crystals ; somewhat unstable ; M.P. 18°. (B., 26, 2855.) Reaction CXLII. Action of Primary Aromatic Amines on Alcohols — The reaction is generally carried out by heating under pressure, and in presence of a mineral acid. Secondary and tertiary amines are formed. ENH 2 + RiOH -> RNHRi + H 2 0. R.NHR! + RiOH -> RN(R 1 ) 2 + H 2 0. Preparation 275. — Dimethylaniline. C 6 H 5 N(CH 3 ) 2 . C 9 H U N. 133. 93 gms. pure aniline, 105 gms. pure methyl alcohol and 9-4 gms. cone, sulphuric acid are heated in an enamelled autoclave to 200°. The pressure rises to about 30 atms., and the contents are left for 6 hours at 215°. They are allowed to cool, and then 25 gms. 30% caustic soda solution added. The product is now heated to 170° in the autoclave for a further 5 hours. This second heating is necessary to decompose the sulpho- ammonium bases formed, and which are decomposed into sulphuric acid, alcohol, and tertiary amine. The contents of the autoclave, after cooling, are distilled in steam. The dimethylaniline is salted out of the distillate with common salt. It is then separated and distilled. C 6 H 5 N H 2 + HO HO CH 3 CH? C e H 5 N.(CH s ) s Yield. — 95% theoretical (126 gms.). Colourless liquid when pure ; turns brown on standing ; B.P. 192° ; D. 0-96 ; important intermediate for dyestuffs. Purity Test (anhydride test). — Some monomethylaniline is always present, and if 4 c.cs. of the dimethylaniline is shaken up with 2 c.cs. acetic anhydride, this should not give an increase in the temperature of more than 1° (C. Z., 34, 641). Preparation 276. — Diethylaniline. C 6 H 5 N(C 2 H 5 ) 2 . C 10 H 15 K 149. 130 gms. dried aniline hydrochloride and 140 gms. 95% alcohol are heated in an enamelled autoclave at 180° for 8 hours. After cooling, THE LINKING OF NITROGEN TO CARBON 299 the contents of the autoclave are placed in a round-bottomed flask and the alcohol and ethyl ether distilled off. The residual mixture of mono- and diethylaniline is treated with 110 gms. 30% caustic soda solution. The product is stirred up at ordinary temperature with 40 gms. of jy-toluene sulphonic chloride, which forms a non- volatile derivative with the mono-ethyl aniline. The diethylaniline is then distilled from the mixture in steam, and separated as in Preparation 275. The mono-ethylaniline can be obtained by hydrolysing the toluene sulphonic derivative with cone, sulphuric acid. HOC 2 H* ~* C e H 5 N ( C 2H 5 ) 2 . CH 3 / _ _ ^S0 2 C1 + C 2 H 5 NH.C 6 H 5 -> CH,/ _ _^>S0 2 .N<^ £s_0 CH s S0 3 H + C 2 H 5 NH.C 6 H Yield. — 80% theoretical (120 gms.). Colourless liquid when pure ; B.P. 216-5° ; ' D. 0-939 ; important intermediate for dyestuffs. (A.. 74, 128 ; D.R.P., 250236.) Reaction CXLIII. Condensation of Aromatic Aldehydes with Primary Aromatic Amines. — This reaction generally takes place readily on heating. R.CHO + NHA -> RCH = NR 1 + H a O. Substituted aldehydes and substituted amines also react ; for example, the sodium salt of a-naphthylamine 4-sulphonic acid when dissolved in water and shaken with an alcoholic solution of benzaldehyde yields sodium benzylidine naphthionate. With aliphatic aldehydes the reaction takes the following course : — CH3.CHO + 2NH 2 .C 6 H 5 -> CH 3 CH(NH.C 6 H 5 ) 2 + H 2 0. Formaldehyde reacts like the aromatic aldehydes, yielding dihydro- formaldehyde (or methylene) compounds. C 6 H 5 NH 2 + OCH 2 -> C 6 H 5 N = CH 2 + H 2 0. Preparation 277. — Benzylidene Aniline. C 6 H 5 N = CH.C 6 H 5 . C 13 H n N. 181. 9-3 gms. of aniline (1 mol.) and 10-6 gms. of benzaldehyde (1 mol.) are placed in porcelain dish on a water bath and heated for an hour. The product, while still warm, is poured into a separating funnel previously warmed in a steam bath, and the lower layer of benzylidene aniline separated from the upper layer of water. The product can be used directly for the preparation of ^-rdtraniline. It is insoluble in water, but can be recrystallised from alcohol. C 6 H 5 NH 2 + OCH.C 6 H 5 C 6 H 5 N = CH.C 6 H 5 + H 2 0. Yield,— Theoretical (18 gms.). M.P. 42°. (J., 1850, 488.) 300 SYSTEMATIC ORGANIC CHEMISTRY Reaction CXLXV. Action of Ammonia on Aldehydes. — The simplest case is the formation of an aldehyde ammonia by the action of dry ammonia gas on the aldehyde in dry ethereal solution. Acetaldehyde and several of the aliphatic aldehydes react after this fashion. R.CHO + NH 3 -> K.CHOH.NH 2 . Formaldehyde and most of the aromatic aldehydes do not react in this way with ammonia, but form complex condensation products. Peepakation 278— Acetaldehyde Ammonia. CH 3 CHOHNH 2 . C 2 H 7 ON. 61. Owing to the easy volatility of acetaldehyde (B.P. 21°) it is rather difficult to collect. It can, however, be readily absorbed in a dry ether contained in a vessel immersed in ice water. If the ethereal solution is now saturated with dry ammonia gas, colourless crystals of aldehyde ammonia separate, which are filtered off, and dried either by exposure on filter paper or in a vacuum desiccator. As aldehyde ammonia is some- what soluble in ether a second crop may be obtained by concentrating the mother liquor. If the ethereal solution of aldehyde is moist it should be dried in contact with anhydrous sodium sulphate, and decanted before the ammonia is passed in. CH 3 CHO + NH 3 -> CH 3 CHOH.NH 2 . M.P. 70°— 80° ; B.P. 100° ; on warming with dilute acids yields acetaldehyde and ammonium salts. (A., 14, 133.) Preparation 279. — Hexamethylene Tetramine (Hexamine). (CH 2 ) 6 N 4 . 140. 50 c.cs. of " formalin " containing 40% formaldehyde and 30 c.cs. of cone, ammonium hydroxide solution (D. 0-88) are mixed in a round- bottomed flask. The flask is connected to a suction pump and the contents evaporated on a water bath under diminished pressure to a thick paste. A second equal quantity of ammonium hydroxide is then added and evaporated, as before. The residue is treated with sufficient boiling absolute alcohol to dissolve, filtered hot, and the filtrate set aside to cool. Colourless crystals separate, which are filtered off and washed with a little absolute alcohol. 6CH 2 0 + 4NH 4 OH -> (CH 2 ) 6 N 4 + 10H 2 O. Sublimes about 260° ; very soluble in water. (B./ 19, 1842.) Preparation 280. — Hydrobenzamide. (C 6 H 5 CH) 3 N 2 . C 21 H 18 N 2 . 298. 5 c.cs. of benzaldehyde and 25 c.cs. cone, ammonium hydroxide solution are placed in stoppered flask and allowed to stand for 2 days. Crystals of hydrobenzamide separate, which are filtered off, washed with water, and recrystallised from alcohol. THE LINKING OF NITROGEN TO CARBON 301 3C 6 H 6 CHO + 2NH 3 = C 6 H 5 CH< + 3H 2 0. X N : CH.C B H 5 M.P. 1 10° ; insoluble in water, easily soluble in alcohol. (A., 21, 130.) Reaction CXLV. — Action of Nitrous Acid on Certain Ketones. — Forma- tion of iso-nitroso compounds. Iso-nitroso compounds are formed by the action of nitrous acid on ketones which contain the — CH 2 .CO — group. — CH 2 .CO— + HONO -> — C.CO— II + H 2 0. NOH Preparation 281 . — Iso-nitroso-camphor. ,C : NOH C 8 H 14 < | C 10 H 15 O 2 N. 181. \co. 102 gms. of camphor are dissolved in 550 c.cs. of pure dry ether in a litre flask, and 15-2 gms. sodium wire added. The flask is well cooled in a mixture of ice and salt, and 78 gms. of isoamylnitrite added in small portions, the flask being thoroughly shaken after each addition. After standing for an hour, during which time a part of the sodium iso-nitroso camphor separates, the contents of the flask are slowly poured into ice water. An ethereal layer, containing borneol and unchanged camphor, separates, while the reddish-yellow aqueous layer contains the sodium iso-nitroso camphor. The aqueous layer is separated, extracted twice with ether, and any dissolved ether removed from it by blowing a current of air through it. It is then neutralised with dilute acetic acid when the iso-nitroso camphor is precipitated. The precipitate is filtered off, washed with water, and after being dried in a steam bath, is recrystallised from a mixture of petroleum ether and benzene. /CH 2 /C : NOH C 8 H 14 < | + C 5 H n ONO -> C 8 H 14 < | + C 5 H n OH. x CO x CO M.P. 152° — 154° ; long prisms ; easily soluble in ether, alcohol, alkali and benzene ; difficultly soluble in petroleum ether. (A., 274, 73.) CHAPTER XX THE LINKING OF SULPHUR TO CARBON Sulphonic Acids. Reaction CXLVL— Action of Concentrated Sulphuric Acid on Hydro- carbons or Substituted Hydrocarbons. — When cone, sulphuric acid acts on an aromatic hydrocarbon or substituted hydrocarbon, one or more of the H atoms in the nucleus are replaced by the sulphonic group (S0 2 ,OH). E.H + H 2 S0 4 — > R.S0 2 OH + H 2 0. It is necessary to have an excess of sulphuric acid present to avoid dilution of the acid, which would occur from the formation of water in the reaction. Some sulphonic acids, e.g., benzene and toluene sulphonic acids, may be formed at ordinary temperatures, while others require a considerably higher temperature. In some cases 100% H 2 S0 4 (monohydrate- — S0 3 .H 2 0) is necessary. The influence of temperature, concentration of acid, time of reaction, and the presence of other substituted groups is very marked, and different isomers are formed under different conditions. The reaction may be assisted mechanically by mixing with kiesulgdhr, or other finely-divided material, and catalytically by the addition of iodine in the case of benzene, and of boric acid, mercury and mercury salts in the case of anthraquinone. The sulphonic group is strongly acidic, and will decompose carbonates with the formation of stable salts, a property which is used in their separation. The presence of a basic group in the nucleus is not sufficient to neutralise its acidity, thus sulphanilic acid is distinctly acid. Isolation of Sulphonic Acids. — Sulphonic acids are usually isolated in the form of their salts in order to get rid of the excess of sulphuric acid used in the reaction. The calcium or barium salts are formed where these are soluble by adding lime or barium carbonate, and the excess sulphuric acid precipitated as CaS0 4 or BaS0 4 , and removed by filtration. The filtrate containing the salt in solution may then be concentrated till the salt crystallises out or it may be evaporated to dryness. The sodium salt may be obtained from the sulphonation mixture by diluting and adding a saturated solution of common salt, and allowing to crystallise. Isomers may be separated by the fractional crystallisation of their salts ; it is often best, however, to form the sulphonyl chlorides by treatment with PC1 5 , and then the amides by the action of ammonia ("See Preparation 289) ; after fractional crystallisation of the amides the acids are set free by heating under pressure with hydrochloric acid. The sulphonyl chlorides, 302 THE LINKING OF SULPHUR TO CARBON 303 and the sulphonamides which generally crystallise well and have definite melting points, are used for the identification of sulphonic acids. Tests for Complete Sulphonation. — The sulphonation is tested by the solubility of the product in water or dilute alkali. Complete solubility is seldom obtained owing to the formation of a sulphone by condensation. R.SO3H + H.K -> R.S0 2 .E + H 2 0. The sulphones are insoluble in water, but may be distinguished, say, from unchanged naphthalene by extracting and taking the melting point. The following factors influence the formation of sulphones : concentration of acid (H 2 S0 4 or S0 3 ), temperature of sulphonation, duration of sulphona- tion. Conditions have to be chosen so that the quantity of sulphone is reduced to a minimum. Apparatus Used in Sulphonation. — The most convenient type of appara- tus for this process is a cast-iron pot with a good mechanical agitator, a thermometer pocket, and an opening for reflux condenser (see Fig. 36). It is of the utmost importance that the agitation should be as efficient as possible. Fig. 37 shows a convenient apparatus in glass, when the cast- iron pot is not procurable. Preparation 282. — Benzene Sulphonic Acid. C 6 H 5 .S0 3 H. C 6 H 6 0 3 S. 160. Method I. — 300 gms. of cone, sulphuric acid (96%) and 60 gms. of benzene are placed in the sulphonating vessel and the temperature raised to the boiling point of benzene, 80° C, the agitation being maintained from the commencement of the heating. The benzene vapour is condensed and returned by the reflux. The heating is continued for 8 — 10 hours, when the sulphonation should be complete (test). Milk of lime is made up in a basin by adding 1 part of lime to 5 parts of hot water, and stirring. The sulphonation is cooled down and poured into 300 c.cs. of water. Isolation of Calcium Salt. — The milk of lime is now carefully added with stirring until the solution is just neutral (test with phenolphthalein paper). It is then boiled, and after cooling to 60° C. the CaS0 4 is filtered off on a Buchner funnel, and washed with a little hot water. Isolation of Free Acid. — To the filtrate which contains the Ca salt in solution, dilute sulphuric acid is added until all the Ca is precipitated (test), and this is filtered off and washed with a little hot water. The filtrate is then evaporated until the free acid crystallises out. Isolation of Sodium Salt. — If the acid is required for fusion with caustic soda, the sodium salt is formed. To the filtrate containing the Ca salt in solution, sodium carbonate is added until no more CaC0 3 is precipitated (test). The CaC0 3 is filtered off and washed, and the filtrate evaporated, leaving the Na salt. C 6 H 6 + H 2 S0 4 -> C 6 H 5 .S0 3 H + H 2 0. Yield. — 75 — 80% theoretical. Na and Ca salts white powders, soluble in water ; used in preparation of phenol, see p. 204. 304 SYSTEMATIC ORGANIC CHEMISTRY Method II. — 15 gms. pure benzene, 90 gms. of sulphuric acid (D. 1-842) and sufficient washed and ignited kieselgiihr to form a thin paste are shaken together and allowed to stand for 24 hours. The acid is isolated as before. Yield. — Theoretical (30 gms.). (D.R.P., 71556.) Preparation 283.— Naphthalene /5-Sulphonic Acid (Na salt). C 10 H 8 SO 3 . 208. 120 gms. of cone, sulphuric acid are heated to 160° and 100 gms. of melted naphthalene is poured in from a basin, good agitation being maintained. When all the naphthalene is added, the temperature is raised to 170° for 3 hours, and then to 180° for 1 hour, until sulphonation is complete (test). Excess sulphuric acid is removed as CaS0 4 , as in benzene sulphonic acid. The filtrate containing the calcium salt of the /?-acid, as well as some calcium salt of the a-acid is concentrated until a sample, on cooling, sets to a thick mass. It is allowed to crystallise overnight and filtered, the other impurities remaining in the nitrate. The calcium salt is then dissolved in hot water, and the sodium salt isolated as before. above 100° ^N^NsOgH + H 2 S0 4 > ,3-acid. Yield. — 75% theoretical (130 gms.). White powder ; soluble in water ; used in preparation of /5-naphthol. (Rec, 1917, 20, 197.) Preparation 284. — rZ-Camphor-sulphonic Acid (Reychler's Acid). C 10 H 15 O.SO 3 H. C 10 H 16 O 4 S. 232. 45 gms. (1 mol.) of camphor are finely powdered and added to a well- stirred mixture containing 30 gms. (1 mol.) of cone, sulphuric acid, and 60 gms. of acetic anhydride. The camphor dissolves readily, and the solution is allowed to stand for 2 — 3 days until no more (^-camphor sulphonic acid crystallises out. The crystals are then filtered through asbestos or glass wool, washed with acetic acid until colourless, and recrystallised from acetic acid or ethyl acetate. C 10 H 16 O + H 2 S0 4 -> C 10 H 15 O.SO 2 OH + H 2 0. Yield. — 50% theoretical (27 gms.). Large prisms ; decompose at 193° ; [a] D = + 21°. (Bl. [hi.], 19, 120 ; J. C. S., 81, 1442.) Preparation 285.— o- and ^-Toluene Sulphonic Acids. /CH 3 C 6 H 4 < C 7 H 8 0 3 S. 172. 130 gms. pure toluene are heated with 450 gms. cone, sulphuric acid in a cast-iron pot fitted with a suitable agitator (see Fig. 36). The THE LINKING OF SULPHUR TO CARBON 305 , temperature is allowed to rise to 100°, a crystal of iodine being added. The sulphonation is complete in about 6 hours, when the reaction mixture is transferred to a large basin, diluted with water, and milk of lime added gradually to neutralise the excess acid. The calcium sulphate and any ferric hydroxide present are removed by filtration and washed with hot f water. Sodium carbonate is added to the filtrate until just alkaline to phenolphthalein, and the calcium carbonate filtered off. The filtrate is then evaporated almost to dryness, when the sodium salts of o- and p-sulphonic acids separate out. Yield. — 95% theoretical (340 gms.) (total o and C 6 H 4 CH 3 S0 2 C1 + POCl 3 + NaCl. jo-Sulphonyl chloride.— Plates ; M.P. 69° ; B.P. 15 145°. o-Sulphonyl chloride,— Oil. (B., 44, 2504.) Reaction CXLVIX. Action of Fuming Sulphuric Acid (oleum) on Hydro- carbons or Substituted Hydrocarbons. — It is sometimes difficult to intro- | duce a sulphonic group by means of cone, sulphuric acid, and it is then .necessary to use fuming acid (i.e., acid containing up to 70% free S0 3 ). The same factors as before have an important influence on the reaction. Usually a high temperature is necessary where more than one S0 3 H has to be introduced. In some cases oleum is used in preference to sulphuric acid, in order to reduce the time and the temperature of sulphonation. Estimation of S0 3 in Oleum. — The oleum is melted, if necessary, by placing the bottle in hot water (caution !), and a quantity is dropped into the bottom of a clean, dry, tared test tube to a depth of about 1| inches (8 — 10 gms.). The whole is weighed, and the weight of oleum obtained by difference. The test tube is now heated and drawn out near its open end and sealed. This is then carefully placed in a graduated litre flask containing about 500 c.cs. of water. The flask is securely stoppered, and the test tube broken by shaking. Shaking is continued till all the white fumes disappear. The flask is then allowed to cool, and its contents |made up to 1 litre. 250 c.cs. are then removed and titrated with normal caustic soda solution, using Methyl Orange as an indicator. If W = weight of oleum n = c.cs. of N NaOH to neutralise W, 0/ QA 4-9n - 100W then%S0 3 = . 225W . S.O.C. X 306 SYSTEMATIC OKGANIC CHEMISTEY The percentage of S0 3 can also be obtained by estimating the total H 2 S0 4 by titration given by the oleum, reckoned as H 2 S0 4 . The % excess of H 2 S0 4 over 100, when multiplied by 444, gives the percentage of S0 3 , e.g., if total H 2 S0 4 = 105% of the oleum, then % S0 3 = 5 X 4-44 = 22-2. The results obtained are a little high, as oleum contains a small per- centage of S0 2 . This may be estimated by titrating 250 c.cs. with N/10 iodine solution, using starch as indicator. By subtracting this result from the total obtained by titration with NaOH, the true percentage of S0 3 can be calculated. Preparation of Oleum of a given Strength. 1. From two oleums of different strength. oleum = a% S0 3 oleum = c% S0 3 oleum = b% S0 3 required, then x 100 {a - h) o— c where x = quantity of c to be added to 100 gms. of a to give b. 2. From oleum and cone, sulphuric acid. oleum = a% S0 3 cone, sulphuric acid = c% H 2 SOi oleum = b% required, then x - 100 6 ) then x - fiT — 444^+5 where x = quantity of cone. H 2 S0 4 to be added to 100 gms. of a to give b, Pkepakation 286. — Nitrobenzene m-sulphonic Acid. SO~oH. N0 2 <^ y C 6 H 5 0 5 NS. 203. 375 gms. oleum (25% S0 3 ) are placed in a cast-iron sulphonation pot and heated to 70°. 123 gms. nitrobenzene are run in carefully. Heat is evolved and the temperature rises up to 100° — 110°, and must not be allowed to rise higher. The inflow of nitro-benzene must be slackened, or external cooling applied, if necessary. When all the nitrobenzene has been added, the mixture is heated to 110° — 115°, until sulphonation is complete (test). The odour of nitrobenzene should be absent. If the sulphonation is not complete after half an hour, more oleum is added. The mixture is allowed to cool, and is then poured on to about 500 gms. ice, with good stirring. The sulphonic acid passes into solution, except some sulphone formed. This may be removed by filtration. 200 gms. common salt are slowly added to the solution, with continuous stirring, when the sodium salt crystallises out, and after standing for about 10 hours, is filtered off. THE LINKING OF SULPHUR TO CARBON 307 Yield,— 90— 95% theoretical (200—214 gms.). Plates; chloride melts at 60-5° ; used for preparation of metanilic acid (see p. 353). (A., 120, 164.) This process is used in the sulphonation of j9-nitro-chlor-benzene, ^-nitro-toluene, o-nitro-chlor-benzene, chlor-benzenes, etc. Preparation 287. — Anthraquinone -Sodium Sulphonate (Silver Salt). CO X 30 3 Na. C 14 H 7 0 5 SNa, 310. CO 100 gms. dry, finely divided anthraquinone are added cautiously to 150 gms. oleum containing 25% S0 3 , with continuous stirring, the tempera- ture being kept under 30°. The temperature is then raised to 120° during 4 hours, and then to 140° during a further 2 hours, using an oil bath. The vessel must be kept closed to prevent loss of S0 3 . After cooling, the mixture is poured into 3 litres of water (caution !) and the unchanged anthraquinone filtered off (25 — 40 gms.). Chalk is added to the filtrate until completely neutralised, and the calcium sulphate filtered off. The calcium salt in solution is then precipitated as carbonate by adding dilute sodium carbonate (test). It is then filtered and the filtrate evapo- rated down to about 400 c.cs., and allowed to cool. The sodium salt separates out after standing for about 2 days. It is then filtered and washed with a little water. Yield. — 40 — 60% theoretical (60 — 90 gms.). Silvery glistening plates ; soluble in water ; crystallises with 1H 2 0 ; used for making alizarin (see p. 384). (A., 160, 131.) Preparation 288. — 1.8-Amino Naphthol 3.6-Disulphonic Acid (H. acid)— Sodium Salt. OH NH, C 10 H 9 O 7 NS 2 . 319. Sulphonation. — 1024 gms. of 24% fuming sulphuric acid (fuming acid of higher strength than this may be diluted with 100% sulphuric acid), or the equivalent of fuming acid of strength, 22 — 24%, is weighed and introduced into a sulphonation pot. The acid is stirred and heat applied until the temperature reaches 100° ; 128 gms. of naphthalene are added quickly in portions at a time, and this causes a considerable rise in temperature. When the naphthalene is all in, the temperature is raised to 165°, at which it is maintained for 8 hours, with slow stirring. During this process naphthalene 3.6.8-trisulphonic acid is the chief product formed. After the above time the pot is allowed to cool to room temperature. titration, — At room temperature the sulphonation mixture should be capable of being stirred, but if not, cone, sulphuric acid must be added until the contents can be stirred. The pot is then placed in a bath, which 308 SYSTEMATIC ORGANIC CHEMISTRY can be filled with cold water, the agitator is set in motion, and cone, nitric acid slowly run from a dropping-funnel to effect nitration. The tempera- ture should be maintained about 20° during nitration. The theoretical quantity of nitric acid, calculated from the naphthalene used, is necessary, and acid of about 60% is preferable, the strength being ascertained by use of a hydrometer. After the nitric acid has been added, the mixture is allowed to stand at 25° for an hour, and then the temperature is raised to 50° in the course of the next hour. After this time it is poured into 1,500 c.cs. water ; volumes of nitrous fumes are given off, and the temperature rises con- siderably. During this process l.nitro-3.6.8-naphthalene-trisulphonic acid is the chief product formed. Reduction. — 256 gms. of iron borings are weighed and about 10 gms. of these added to the solution of nitro-sulphonic acid at about 50° ; this causes the evolution of nitrous fumes. The remaining iron is added in portions at such a rate that the reduction proceeds briskly ; the agitation should be vigorous enough to keep the iron swirling round. After all the iron has been added, agitation is continued for an hour ; the tempera- ture is then raised to 50°, 150 gms. of common salt added, and the agitation continued for an hour while the mixture cools. The acid sodium salt of naphthylamine-trisulphonic acid is by this means precipitated ; along with any unattached iron this is filtered off and washed with 10% brine. The contents of the funnel are placed in a vessel and boiled up with water until all the naphthylamine-sulphonic acid dissolves ; while still almost boiling the solution is again filtered to separate the iron residue. The filtrate, while still warm, is treated with 15 gms. common salt for each 100 c.cs. volume and agitated while the salt dissolves ; before this is complete, separation of the sulphonic acid begins. The mixture is after- wards cooled to 15°, and the purified aminosulphonic acid (Na salt) filtered off. The precipitate is washed on the funnel with 100 c.cs. of 10% brine, pressed in a screw press and dried at 100°. When dry it is ground up, and a sample estimated with standard nitrite (see p. 490) ; it is generally of 75— 80% purity. Caustic Fusion. — This operation is performed in a small autoclave, for manipulation of which see p. 42. 85 gms. caustic soda and 134 c.cs. water are placed in the vessel and heat applied until solution takes place ; 128 gms. of naphthylamine-trisulphonic acid (70%- — 80%) are then added, and the lid of the autoclave bolted on. The mixture is gradually heated up to 180° and maintained at this point for 5 hours, the pressure being about 100 lbs. After cooling, the autoclave is opened, allowing any residual pressure to escape gradually — a certain amount of ammonia is always present. The reaction product is introduced into a large beaker or stoneware jar, diluted with 750 c.cs. water, and acidified with cone, hydrochloric, or 50% sulphuric acid ; volumes of sulphur dioxide from the decomposition of the sodium sulphite are given off. When testing for acidity, a small sample should be withdrawn and boiled to expel sulphur dioxide, prior to testing with Congo paper. The aminonaphthol-disul- phonic acid, which is formed in this reaction, being only very sparingly THE LINKING OF SULPHUR TO CARBON 309 soluble in solutions of sodium chloride or sulphate, is practically all precipitated as the mono-sodium salt on acidification. After acidification the mixture is cooled to room temperature and allowed to stand for 1 hour. The precipitate is then filtered off, washed with 100 c.cs. of 10% brine, pressed, and dried at 100°. SOJI NIL NO, SO,H S0 3 H OH NH SO,H SO,Hl SO»H SO,H lSO,H. Sodium (B., 27, Yield. — 50 gms. of 80—85% purity (see estimation, p. 490). salt soluble in water and crystallises with 1 JH 2 0 ; fine needles. 2148 ; D.R.P., 69722.) Reaction CXLVIII. Action of Cfoloro-sulplionic Acid (C1.S0 3 H) on Hydrocarbons or Substituted Hydrocarbons. — Ohloro-sulphonic acid (see p. 507) is used for sulphonating in special cases. In this sulphonation HC1 is evolved. E.H + Cl.SO„H HC1. The chief advantage in the use of this acid is its selective property, whereby certain sulphonic acids are formed, which could not be formed by direct sulphonation with sulphuric acid or oleum, or which might be formed only in presence of other isomers, the separation of which might be difficult. For example, naphthalene sulphonated with oleum at the ordinary temperature gives a mixture of 1-5- and 1-6-disulphonic acids, while chloro-sulphonic acid yields only the 1-5-acid. Similarly, with toluene, chiefly the ortho acid is formed. With excess of chloro-sulphonic acid a sulphonyl chloride is formed, except in the case of phenols or naphthols, which give the free sulphonic acid. E.H ~> K.S0 2 OH -> R.S0 2 C1. When chlorosulphonic acid reacts with amides, acid chlorides are formed, while amines yield sulphaminic acids. SO3HCI + 3C 6 H 5 NH 2 -> C 6 H 5 NH.S0 3 H.C 6 H 5 NH 2 + C 6 H 5 NH 2 .HCL When the sulphonic acid produced by the interaction of chloro-sulphonic acid has to be nitrated afterwards, it must be isolated previous to nitration, otherwise the chlorine liberated may form chlor-derivatives. Preparation 289. — Saccharin (^-Benzoyl sulphonimide). 183. 1. Toluene o -sulphonyl chloride. — 100 gms. pure toluene are slowly run 310 SYSTEMATIC ORGANIC CHEMISTEY into 500 gms. of chloro-sulphonic acid cooled to 0° in a pot fitted with good mechanical agitation, the temperature during the addition being kept below 5°. When all the toluene has been added stirring is continued for about 12 hours at the same temperature. The mass is then poured on to ice, when an oily layer separates. The liquid ortho-sulphonyl chloride, which usually contains some of the solid para-compound, is then separated and, after further treatment with ice and salt, is filtered and the ortho compound separated from the salt solution in a funnel. The pot in which the sulphonation is carried out should have an exit tube for the escape of HC1, which may be absorbed in fuming sulphuric acid with the formation of more chlorosulphonic acid. ,CH 3 C 6 H 6 CH 3 — > C 6 H 4 <( \S0 2 C1. Yield.— Ortho 85% theoretical (110 gms.). (E.P., 25273, 1894.) 2. Toluene o-sulphonamide. — The o-sulphonyl chloride is gradually added to an equal quantity of 20% ammonia solution, which is cooled in a freezing mixture. When all has been added, the reaction is completed by removing the freezing mixture and gently heating. The sulphon- amide is then filtered off and dissolved in N. caustic soda solution, filtered, and reprecipitated by adding sufficient hydrochloric or sulphuric acid to precipitate 75% of the amide in solution. The precipitate is redissolved by heating, and almost pure o-sulphonamide crystallises out on cooling (M.P. 133°— 134°). /CHo /CHo C 6 H4\ ~~ > C 6 H 4 / X S0 2 C1 \S0 2 NH 2 . (E.P., 22726, 1894 ; 3930, 1895 ; 848, 1903 ; D.R.P., 133919.) 3. Saccharin. — One equivalent of the o-sulphonamide (171 gms.) is dissolved in one equivalent of caustic soda (40 gms.) and 2,565 gms. of water. This is heated to 40° — 50°, and 256 gms. of solid potassium permanganate are slowly added with stirring. When all the permanganate has been added and the colour has almost disappeared, a little NaHS is added to decolorise, and the precipitated manganese compound filtered off and washed with water until acid added to the filtrate gives no precipi- tate of saccharin. The combined nitrate and washings is then cooled down to ordinary temperature and neutralised with hydrochloric acid, using methyl orange as indicator. This treatment precipitates unchanged o sulphonamide, which is filtered off. Hydrochloric acid is then added to the filtrate, and the precipitated saccharin filtered off, washed with water, and dried at 40°. /CH 3 .CO x C 6 H/ -> C 6 H 4 < \nH. \S0 2 NH 2 \SO/ White crystalline powder ; M,P. 220° ; soluble in hot water and in THE LINKING OF SULPHUR TO CARBON 311 alcohol, and in alkalis or alkali carbonates with formation of salts. (E.P., 3563, 1903.) Reaction CXLIX. Intramolecular Rearrangement of Aromatic Amine Sulphates. — When sulphuric acid is added to an amine a sulphate is usually formed. If the sulphate is heated either alone (baking process) or with excess of cone, sulphuric acid, a rearrangement takes place, the sulphonic group entering the ^-position to the basic group. ")nh 2 — > /" ~\nh 2 .h 2 so 4 -> so 3 h/ \nh 2 -f H 2 0. Sulphonic acids can be made by the baking process, which are difficult to make in the ordinary way, e.g., By ordinary process NH 2 <^ ^> — ^>NH 2 (a) £OzK S0 3 H By baking process -> NH 2 ^ ^>-^ ^>NH 2 (b) S0 3 H SO^H (a) yields cotton dyestuffs, while (b) yields wool dyestuffs. Another advantage of the baking process is that much less sulphuric acid is required. Preparation 290. — Sulphanilic Acid (l.Amino-4.benzene-sulphonic acid). NH 2 <^ ^S0 3 H. C 6 H 7 0 3 NS. 173. Method I. — 20 gms. of aniline are gradually added to 65 gms. of cone, sulphuric acid placed in a round-bottomed flask. Much heat is developed, and the contents of the flask should be cooled when the aniline is being added. The flask which contains aniline sulphate and excess cone, sulphuric acid is now heated on an oil or paraffin bath to 185° for about 5 hours. When a test portion, treated with dilute caustic soda solution, liberates no free aniline, the sulphonation is complete. The contents of the flask, after cooling, are poured into cold water, when the sulphanilic acid separates, usually as discoloured crystals. These are filtered off and recrystalhsed from water, adding a little animal charcoal, if necessary. A further crop can be obtained from the mother liquor. /~ - )NH 2 -> S0 3 H<^ ~\NH 2 . Yield. — 55% theoretical (20 gms.). Method II. (baking process). — 93 gms. of aniline are placed in a basin and 105 gms. of cone, sulphuric acid gradually added in a stream, with good agitation. The hot paste is then spread on a lead tray and placed in an air oven at 190° — 200° for 8 hours. The cake is now ground up and boiled for some time with water to which some caustic soda has been added till alkaline, to remove the unchanged aniline present (about 3%). It is then filtered through a cotton filter, and the acid is 312 SYSTEMATIC OKGANIC CHEMISTRY obtained by adding sulphuric acid to the filtrate until acid to Congo paper. If the acid is discoloured it may be boiled up with animal charcoal, filtered, and allowed to crystallise. /~ ~^>NH 2 + H 2 S0 4 -> /" \NH 2 .H 2 S0 4 -> NH 2 ^' ^>$0 3 H + H 2 0. Yield. — 90% theoretical (155 gms.). Rhombic crystals ; does not melt ; forms two hydrates : -2H 2 0 when crystallised below 20° ; -1H 2 0 when crystallised between 20° — 44° ; important intermediate for dye- stuffs. (A., 100, 163 ; Z. a. (1896), 9, 685.) Preparation 291, — Naphthionic Acid (1-Naphthylamine 4-sulphonic acid). / >S0 3 H C 10 H 9 O 3 NS. 223. The process is similar to that used for sulphanilic acid. 70 gms. of a-naphthylamine and 50 gms. of cone, sulphuric acid are used. Before the paste is spread on the tray it is mixed with about 3 gms. of oxalic acid. It is then placed in the oven and heated, as before. When the mass has been cooled and powdered, it is boiled up with water and neutralised with milk of lime (test) and filtered. The acid is obtained by acidifying the filtrate with hydrochloric acid. Yield.— 80— 85% theoretical (88—94 gms.). Crystallises with 1H 2 0 ; used largely in preparation of azo dyestuffs. (B., 13, 1948 ; 19, 578 ; Z. a. (1896), 9, 685.) Reaction CL. Action of Sulphites and Bisulphites on Substituted Hydro- carbons. — (a) Metallic sulphites and bisulphites are used in certain cases for introducing the S0 3 H group, and especially to replace halogens where the halogen is in the nucleus, and ortho to a N0 2 , S0 3 H or CHO group. _N0 2 _N0 2 N0 2 <^ + Na 2 S0 3 -> N0 2 <^ ^>S0 3 Na + NaCl. (6) In some cases reduction takes place simultaneously with sulphona- tion, e.g., m-dinitrobenzene gives m-nitranihne sulphonic acid, and nitro- benzene diazonium chloride gives ^-nitrophenylhydrazine sulphonic acid. (c) The same reagents are used for the formation of alkyl sulphonic acids by interaction with alkyl halides. C 2 H 5 I + Na 2 S0 3 -> C 2 H 5 S0 3 Na + Nal. Halogens in the side chain of aromatic compounds also undergo this reaction. (d) With certain olefinic compounds, additive compounds are formed. E.CH = CH.COOH + K 2 S0 3 -> K.CH 2 CH(COOH)S0 3 K. THE LINKING OF SULPHUR TO CARBON 313 Preparation 292. — Phenylhydrazine ^ Sulphonic Acid. NH.NH, C 6 H 8 0 3 N 2 S. 188. 0,H. 51 gms. sulphanilic acid (100%) are dissolved in 200 c.cs. water and 16 gms. caustic soda. Any aniline which may be present is boiled off. The solution is filtered and cooled, and 35 gms. cone, sulphuric acid are added. The whole is then cooled to 12° (external cooling), and treated with a solution of 21 gms. sodium nitrite in 50 c.cs. water during ^ hour with continuous stirring until a distinct and permanent reaction is given with starch iodide paper. The diazo sulphanilic acid separates out as fine crystals, which are filtered off, but not dried. The moist diazo acid is then added to a mixture of 130 gms. bisulphite solution (containing 25% S0 2 ) and enough 35% caustic soda solution to give a distinct alkaline reaction with phenolphthalein to the sulphite solution (25 — 45 gms. may be necessary). The temperature of the mixture is kept below 50° by placing the vessel in ice-water and stirring. The diazo sulphanilic acid is at once converted into the sulpho-phenyl azo sulphonic acid, which is allowed to stand for an hour. The yellow solution is then heated to boiling, and then about 250 gms. cone, hydro- chloric acid are added until reaction is strongly acid. This reaction should be performed in a fume cupboard. The reduction takes place by means of the S0 2 produced. If the solution does not become decolorised a little zinc dust may be added. The phenylhydrazine sulphonic acid crys- tallises out on standing. It is filtered and washed with a little water. N = N- N = N.SO,H NH.NH.SO,H NH.NH S0 3 H S0 3 — Yield. — 90% theoretical (47 gms.). Acid ; crystallises with |H 2 0 ; soluble in hot water ; alkali salts readily soluble ; important intermediate for dyes. (B., 18, 3172 ; A., 190, 69.) Preparation 293.— m-Phenylene Diamine Sulphonic Acid (1.2.4). NH 2 S0 3 H<^ ^>NH 2 . C 6 H 8 0 3 N 2 S. 188. 101 gms. dinitro chlor-benzene are dissolved in 250 c.cs. of methylated spirits. To this is added 40 gms. S0 2 , in the form of a cone, solution of sodium sulphite — about 160 gms. NaHS0 3 , containing 25% S0 2 mixed with 50 gms. 40% NaOH until alkaline to phenolphthalein. The sulphite may separate out, even when mixture is hot, but this is of no consequence. The mixture is heated on the water bath to boiling for 5 hours with good 314 SYSTEMATIC ORGANIC CHEMISTRY stirring. The product is then cooled, and the sodium salt of the dinitro- benzene sulpho acid separates in glistening, yellow leaflets. The sodium salt is then reduced, as in the preparation of m-phenylene diamine (see p 352.). The solution of the diamine sulphonic acid is evaporated down to about 200 c.cs. and 50 gms. common salt added. It is then just acidified with HC1 (Congo paper should be turned only faint violet), and the free acid crystallises out. It is filtered and washed with very little water. NQ 2 NQ 2 NH 2 Cl<^ ^>N0 2 -> S0 3 H<^ ^>N0 2 -> S0 3 H<^ ^>NH 2 . Yield. — 65% theoretical (61 gms.). Dimorphous ; a-form, monoclinic plates ; /?-form, triclinic prisms ; calcium and barium salts easily soluble in water. (A., 205, 104.) Preparation 294. — Dinitro-Stilbene-Disulphonic Acid (Na salt). _S0 3 H SQ 3 H N0 2 <^^^)CH = CH<( ^>N0 2 . C 14 H 10 O 10 N 2 S 2 . 430. 100 gms. ^-nitrotoluene are sulphonated, as described for nitrobenzene (p. 3C6), and the sodium salt separated. It is dissolved in 500 c.cs. water at 60° with the addition of sodium carbonate (about 50 gms.). The solution is filtered from iron oxide and made up to 2 litres at 50°. 160 gms. of 35% caustic soda solution are added during \ hour. No sodium salt should separate out. A mixture of 1,700 gms. sodium hypochlorite solution, containing about 5% NaOCl and 300 gms. of 35% caustic soda solution is allowed to drop in during 10 hours. The temperature must not exceed 56°, otherwise yellow dyestuffs are formed. The mixture is allowed to stand at 55° for 24 hours. Free chlorine should be present during the whole period (test with starch potassium iodide paper). It is then cooled to ordinary temperature and 400 gms. salt added. After standing for a day the yellow crystalline sodium salt of the acid is precipitated, and is filtered off and washed with brine. SO3H _ S0 3 H SQ 3 H CH 3 <^ \n<3 2 — > CH 3 <^ ^>N0 2 -> N0 2 / ^CH = CH<^ ^>N0 Yield. — About 40% theoretical (60 gms.). Used for preparation of diamido-stilbene-disulphonic acid and stilbene dyestuffs. (B., 30, 3100.) Preparation 295. — 1-2*4 Amino-naphthol Sulphonic Acid. NH 2 C 10 H 9 O 4 NS. 239. 100 gms. of ^-naphthol are converted into the corresponding nitroso- naphthol (see preparation, p. 277). The moist nitroso-naphthol is stirred up with a little water and cooled to 5° C. with ice. To the paste 260 gms. THE LINKING OF SULPHUR TO CARBON 315 sodium bisulphite solution, containing 25% S0 2 , is quickly added. The nitroso-naphthol goes into solution after a few minutes ; a small quantity of dilute caustic soda can be cautiously added, if necessary. The solution is filtered to remove resinous matter. The filtered solution is treated at 25° with 100 gms. cone, sulphuric acid, which has been diluted with 200 gms. of water. The solution should then give a strongly acid reaction. It is allowed to stand for 1 hour, and is then warmed to 50° and left over- night — it solidifies to a solid cake. It is filtered off and washed well with water. OH N.S0 3 Na OH /\/\0H Dioxine." SO,H. Yield. — 90% theoretical (149 gms.). Almost insoluble in cold water, sparingly soluble in hot ; sodium salt sparingly soluble in hot water. (B., 27, 23.) Preparation 296. — Phenyl-Sulpho-Propionic Acid (K salt) (2-Sulphonic acid-3-phenyl-propan acid). C 6 H 5 .CH 2 CH.(COOH)(S0 3 K). C 9 H 9 0 5 SK. 268. 15 gms. (1 mol.) of cinnamic acid and 13 gms. (1 mol.) of normal potassium sulphite are refluxed with 280 c.cs. of water for 12 hours, then allowed to cool, and acidified with acetic acid. A crystalline precipitate of phenyl sulpho propionic acid separates, which is filtered off and recrystal- lised from water. A further yield may be obtained by evaporating the filtrate to dryness, extracting the potassium acetate with hot alcohol, and crystallising the residue of phenyl- sulpho- propionic acid from water. C 6 H 5 CH : CH.COOH + K 2 S0 3 + CH 3 .COOH -> C 6 H 5 CH 2 .CH(COOH)(S0 3 K) + CH 3 COOK. Needles ; melts and decomposes on heating ; soluble in hot water (A., 154, 63.) Preparation 297. — Ethyl Sulphonic Acid (Ba salt). CH 3 .CH 2 .S0 3 H. C 2 H 6 0 3 S. 110. 20 gms. (2 mols.) of ethyl iodide are boiled under reflux with a solution of 20 gms. (excess) of crystallised ammonium sulphite in 40 c.cs. of water until all goes into solution (6 hours). 100 c.cs. of water are added, and the solution boiled with 30 gms. (excess) of lead oxide until all ammonia is expelled. The lead salt of ethylsulphonic acid and lead iodide are formed ; the latter is removed by nitration after the solution cools. Sulphuretted hydrogen is passed into the filtrate until no more lead sulphide — from the decomposition of the lead salt of ethylsulphonic acid — is formed. Lead sulphide is filtered off, and the filtrate neutralised by the addition of excess (20 gms.) of barium carbonate. After filtration, the filtrate containing barium ethyl sulphonate is evaporated. 316 2C 2 H 5 I SYSTEMATIC ORGANIC CHEMISTRY 2NH 4 OH + 2NHJ. ->(C a H 5 S0 2 0) 3 Ba. 2(NH 4 ) 2 S0 3 + 2H 2 0 -> 2C 2 H 5 S0 2 OH PbO H 2 S 2C 9 H 5 S0 2 OH > (C 2 H 5 SOoO) 2 Pb > 2C 2 H 5 S0 2 OH Yield.— 90% theoretical (22 gms.). (A., 168, 146.) The free acid is stable and forms a deliquescent crystalline mass (B., 15, 445). Reaction CLL Action of Poly-sulphates on Certain Hydrocarbons. — The S0 3 H group may be introduced in certain cases. C 6 H 6 + KH 3 (S0 4 ) 3 Na 2 S 2 0 7 may also be used. C«H,SO,H + KHSO, SO,H H ft O. .H. + Na 2 S 2 0, In the anthraquinone series NaHS0 4 may be used. Prepaeation 298— Benzene Sulphonic Acid. 20 gms. of benzene and 50 gms. potassium polysulphate are heated under a reflux until all the benzene has dissolved. The cold product is dissolved in water and neutralised with milk of lime and isolated as before. C 6 H 6 + KH 3 (S0 4 ) 2 -> C 6 H 5 S0 3 H + KHS0 4 + H 2 0. (D.R.P., 113784.) Reactions of the Sulphonic Group. E.OH E.COOH t E.H E.CN E.SOJE E.S0 9 C1 E.C1 K.NO, HC1 (a) (&) (a) (*) E.OH. -> E.H. E.SO3H + NaOH E.S0 3 H + H 2 0 pressure E.S0 3 H + H + + OH' -> E.H NaHS0 3 R.BO,Il 4- XII, — > R.NH,. pressure E.S0 3 H + NaNH 2 E.S0 3 H + HNO3 E.S0 3 H + CI (a) (b) E.S0 3 H + PCI, E.SO JI + PCI, E.S0 3 Na E.SO,Na NaCN NaCOOH E.N0 2 . E.C1 (goes readily if S0 3 H in a -position). E.CL E.S0 2 C1. E.CN. E t C00H, :! CHAPTER XXI THE LINKING OF SULPHUR TO CARBON (continued) Reaction CLII. Action of Sulphur and Sodium Sulphide on Aromatic Bases. — Aromatic amines usually react with sulphur when heated some- times in presence of sodium sulphide to give compounds of complex * structure, two nuclei joining together through the $-atom. Several compounds are usually formed in the reaction, e.g., ^-toluidine gives 'four different products when fused with sulphur. The final products are dyestuffs, some of unknown constitution, and are known as sulphur or sulphide dyestuffs. The formulae show the compounds obtained from j9-toluidine. CHq CHo CHo CHo -S- Thio-^-tohiidine. N= =C — \_ _/NH 2 . Dehydro-thio-j9-tolujdine. Bis-dehydro-thio-p-toluidine or Primuline base. The dyestuffs produced are of various shades ; generally speaking, diphenylamines give blue and black dyes, toluidines yellow and brown, and diamines red dyes. For dyestuff preparations, see section on Dyes. Preparation 299. — Thiodiphenylamine (o-Diphenylene-sulpho-imide) . I ... /NHv C 6 H 4 < >C 6 H 4 . C 12 H 9 NS. 199. 22 gms. of diphenylamine, 8-2 gms. of sulphur, and 3-2 gms. of anhydrous aluminium chloride are melted together. The reaction sets in at 140° — 150° with rapid evolution of sulphuretted hydrogen ; by lowering the temperature a few degrees the reaction can be slackened. When it has 317 318 SYSTEMATIC ORGANIC CHEMISTRY moderated, the temperature is raised to 160° for a time. The melt, when cool, is ground up and extracted, first with water and then with dilute alcohol. The residue consists of almost pure thiodiphenylamine. It can be recrystallised from alcohol. C 6 H 5 — NH-C 6 H 5 + 2S -> C 6 H 4 / \C 6 H 4 + H 2 S. Yield.— 93% theoretical (23-5 gms.). Yellowish leaflets ; M.P. 180°. (D.R.P., 237771.) Preparation 300.— Dehydro-thiotoluidine. CH 3 <^ = C— ( _ ")NH 2 . C 14 H 12 N 2 S. 240. 107 gms. jo-toluidine are heated with 70 gms. powdered sulphur (not flowers of sulphur) and 1 gm. sodium carbonate (to remove acidic sub- stances in the sulphur) to 180° in a sulphonating pot fitted with a good agitator and reflux condenser. The H 2 S which is evolved is absorbed by a tower filled with lumps of moist caustic soda. The temperature is raised to 220° after about 8 hours, by which time the evolution of H 2 S slackens, and kept at 220° for 5 hours. The evolution of H 2 S now practically ceases, and the melt is then poured on to a tray to solidify. The yellow crust is then finely ground and extracted with 95% alcohol. This dissolves the toluidine, thiotoluidine, and the dehydro-thiotoluidine, leaving the insoluble primuline base. The extract is evaporated to dryness and heated to 250°, which removes the toluidine and part of the thiotoluidine. The mixture is then sulphonated with 25% oleum and poured on to ice, filtered, and well washed with water until the washings give only a faint acid reaction. The toluidine and thiotoluidine sulphonic acids pass into solution. The residue is dissolved in 50 gms. of 20% ammonia solution and 800 c.cs. water, and heated to 80°, other 400 c.cs. of water being then added. The solution is filtered hot, if necessary, and the ammonium salt of dehydro-thiotoluidine sulphonic acid separates out in the course of 2 days. Primuline can be obtained from the mother liquor by saturating with 15% common salt at the boiling point. Yield. — Ammonium salt, 25 gms. ; primuline, 80 gms. Base — needles (from alcohol) ; M.P. 190°— 191° ; B.P. 434° ; primuline (see p. 382). (B., 22, 333 ; 22, 424 ; 25, 1084.) Reaction CLXII. Action of Sulphur Dioxide on Aromatic Hydrocarbons in presence of Aluminium Chloride or Mercuric Chloride. (A. Ch. [6], 14, 443.) A1C1 3 C 6 H 6 +S0 2 >C 6 H 5 S0 2 H. The sulphinic acids are unstable liquids passing readily into sulphonic acids on oxidation with alkaline permanganate. THE LINKING OF SULPHUR TO CARBON 319 Sulphinates may also be formed by : — 1. Action of S0 2 on zinc alkyls. (C 2 H 5 ) 2 Zn + 2S0 2 -> (C 2 H 5 S0 2 ) 2 Zn. 2. Action of zinc on sulphonyl chlorides. 2C 2 H 5 S0 2 C1 + 2Zn -> (C 2 H 5 S0 2 ) 2 Zn + ZnCl 2 . Reaction CLIV. Action o£ Sulphur Dioxide on a Diazonium Compound in presence of Finely Divided Copper. (Gattermann B., 32, 1136.) Cu R.N 2 C1 + S0 2 + H 2 0 -> R.S0 2 H + N 2 + HC1. This method gives good yields, and is specially useful where isomers are formed by ordinary or direct sulphonation. For example, the o-toluene sulphonic acid is prepared from o-toluidine, and so on. Preparation 301. — Benzene Sulphinic Acid. C 6 H 5 S0 2 H. C 6 H 6 0 2 S. 142. About 6 gms. of aniline are dissolved in dilute sulphuric acid and the solution diazotised in the usual manner. Sulphur dioxide is passed into the diazo solution until it is almost saturated, the temperature being kept below 0° ; without stopping the stream of the gas copper powder is added slowly until nitrogen ceases to be evolved. The whole is filtered and the copper washed well with cold dilute ammonia. The united filtrates, which must still contain an excess of free sulphuric acid, are treated with a cone, solution of ferric chloride until precipitation is complete. Ferric benzene sulphinate separates and is converted into the free acid by shaking with a slight excess of dilute aqueous ammonia. The free acid separates out on adding cold cone, hydrochloric acid to the filtrate. \NH 2 -> (~ _S >N 2 HS0 4 > C ^S0 2 H. Strong acid ; soluble in hot water and in alcohol ; prisms ; M.P. 83 c 84° ; decomposes above 100°. (J. C. S., 95, 342 ; B., 24, 716.) Preparation 302. — Naphthalene 1-4-Sulpho-Sulphinic Acid. SO a H C 10 H 8 O 5 S 2 . 272. 50 gms. sodium naphthionate (see p. 312) are diazotised in the usual way (see p. 365). The diazonium compound separates out. Sulphur dioxide is then passed in until the solution is saturated, the temperature being kept below 0°. Copper powder (see p. 504) is then added very gradually until the evolution of nitrogen ceases, a slow stream of S0 2 being passed through during the addition. The whole is then filtered, and common salt is added to saturate the filtrate, when the sodium salt of 14-sulpho-sulphinic acid separates, and after filtration is recrystallised 320 SYSTEMATIC OKGANIC CHEMISTRY from water. The free acid may be isolated by passing hydrochloric acid gas into the solution in water of the sodium salt. NH 2 N = NCI S0 2 H. S0 3 H S0 3 H SO3H Yield.— Almost theoretical (62 gms.). (J. C. S., 95, 342.) Reaction CLV. Action of Potassium Xanthate on Diazonium Compounds with Subsequent Hydrolysis and Oxidation. (E.P., 11865, 1892). / S ■ / S C 6 H 5 N 2 C1 + KSC -> C 6 H 5 SC \0C 2 H 5 \0C 2 H 5 H 2 0 0 * C 6 H 5 SH ^* CgH 5 S0 3 II. Reaction CLVI. — Action of Hydrogen Sulphide on Diazonium Com- pounds. (B., 29, 272.) In neutral solution at 0° diazo sulphides are formed, e.g., N0 2 C 6 H 4 N 2 C1 -> (N0 2 C 6 H 4 N 2 ) 2 S. p-nitro -diazobenzene. In hydrochloric acid solution the disulphide is ultimately formed — (N0 2 C 6 H 4 N 2 ) 2 S 2 . On heating a diazo solution, nitrogen is evolved, and a mercaptan is formed — K.N 2 C1 + H 2 S -> E.SH. Preparation 303. — Thiosalicylic Acid. (l-Sulphydro-2-carboxyl benzene.) ;h C v H 6 0 2 S. 154. COOH. 10 gms. anthranilic acid (see p. 241) are dissolved in 150 c.cs. water and 5 gms. hydrochloric acid. 20 gms. of ice are added and the whole diazotised in the usual way. H 2 S is passed through the diazo solution until the yellow precipitate becomes red. /N 2 SH C 6 H 4 is formed, and after filtration the moist precipitate is \COOH dissolved in sodium carbonate solution, and heat is applied until a test portion gives a white precipitate with hydrochloric acid. The solution is acidified with hydrochloric acid and the thiosalicylic acid filtered off and washed with cold water. Insoluble in water ; M.P. 163°— 164° ; salts amorphous. (D.K.P., 69073 ; B., 22, 2206 ; 31, 1666.) THE LINKING OF SULPHUR TO CARBON 321 Reaction CLVII. Action of Hydrosulphides on Alkyl Halides or Sulphates, or on Certain Aromatic Halogen Derivatives. K.C1 + KSH -> K.SH + KCL K.HS0 4 + KSH -> K.SH + KHS0 4 . /CI /SH R + KSH -> R \C00H . \C00H. The mercaptans are colourless liquids, mostly insoluble in water, possessing a characteristic disagreeable odour. Other methods by which mercaptans can be formed are : — 1. Action of KCNS on diazo salts and subsequent hydrolysis (B., 23, 738). R.N 2 C1 R.CNS — > R.SH. 2. Action of KSH on diazo salts (B., 20, 349). R.N 2 C1 -> R.SH. 3. See Reaction CLVI. Preparation 304. — Thiosalicylic Acid. (See Preparation 303.) 50 gms. o-chlor-benzoic acid are dissolved in 38-5 gms. caustic soda solu- tion containing 13-5 gms. caustic soda. 100 gms. of sodium hydrosulphide and 0-5 gm. copper sulphate are then added, and the whole heated with stirring to about 200°. The mass becomes dark red and melts, when the temperature is raised to 250°. It then gradually solidifies. The melt is dissolved in a litre of water and boiled up with animal charcoal, if necessary, and the thiosalicylic acid precipitated from the filtrate by adding hydrochloric acid. ' Yield.— Almost theoretical (48 gms.). (D.R.P., 189200, 205450.) Preparation 305. — Ethyl Mercaptan. C 2 H 5 SH. C 2 H 6 S. 62. 50 c.cs. cone, sulphuric acid and 50 c.cs. 20% oleum' are added to 100 c.cs. 99% alcohol, the temperature being kept below 70°. The mixture is allowed to stand overnight in a freezing mixture, and then poured on to a mixture of ice and 8% sodium carbonate solution, with stirring. The neutral solution is concentrated until a crust of salt forms on the surface. Sodium sulphate separates out on cooling and is filtered off. A 40% solution of caustic potash in water is saturated with H 2 S, the volume of the solution being \\ times the volume of the filtrate. This solution of potassium sulphide is then added to the filtrate and the whole gently distilled, when the ethyl mercaptan passes over. It is shaken up with cone, caustic soda solution to separate ethyl sulphide. The ethyl mercaptan, after removing the oil, is precipitated by adding acid to the alkaline solution. C 2 H 5 OH -> C 2 H 5 .HS0 4 -> C 2 H 5 .SH. Colourless liquid ; almost insoluble in water ; offensive odour ; B.P. 36°. (A., 34, 25.X S.O.C. , Y 322 SYSTEMATIC ORGANIC CHEMISTRY Reaction CLVIII. Action of Phosphorus Pentasulphide on Acids or Alcohols. 5C 2 H 5 OH + P 2 S 5 -> C 2 H 5 SH + P 2 0 5 . 5CH 3 COOH + P 2 S 5 -> CH3COSH + P 2 0 5 . The oxygen is replaced by sulphur with the formation of mercaptans and thio-acids. Prepaeation 306. — Thioacetic Acid. CH3COSH. C 2 H 4 OS. 76. 150 gms. of phosphorus pentasulphide are ground up and mixed with an equal weight of glacial acetic acid and 50 gms. of glass beads. The whole is placed in a distilling flask of at least 1 litre capacity, fitted with a condenser and thermometer, and continuously warmed with a naked flame. Heating is stopped as soon as the reaction begins, which is allowed to proceed spontaneously, heat being applied when it moderates. Much frothing may take place. The reaction is stopped when the thermometer reaches 103° C. and the product fractionated. Yield. — 25% theoretical (47-5 gms.). Evil-smelling liquid, decomposed by water ; B.P. 93°. (B., 28, 1205.) Reaction CLIX. Action of Sulphonyl Chlorides on Hydrocarbons in presence of Aluminium Chloride. (B., 26, 2940.) AICI3 R.S0 2 C1 + C 6 H 6 > E.S0 2 .C 6 H 5 + HC1. The compounds formed are termed sulphones ; they are also formed by the action of cone, and fuming sulphuric acid on hydrocarbons (see p. 305), and by heating aromatic sulphonic acids with an aromatic hydrocarbon in presence of a dehydrating agent, such as P 2 0 5 . P 2 0 5 E.S0 2 OH + C 6 H 6 > K.S0 2 .C 6 H 5 . The interaction of halogen compounds and the salts of sulphinic acids yields the same products. R.S0 2 Na + BrC 6 H 5 — > R.S0 2 C 6 H 5 + NaBr. The sulphones are inert compounds, and are of little importance. Reaction CLX. Action of Phosphorus Pentasulphide on Ethers. (B., 27, 1239.) Thio-ethers are obtained according to the equation : 5(C 2 H 5 ) 2 0 + P 2 S 5 -> 5(C 2 H 5 ) 2 S + P 2 0 5 . The thio-ethers are neutral volatile compounds of little importance. Reaction CLXI. Action of Sodium or Potassium Sulphide on Alkyl Halides or Alkyl Sulphates. (B. 27, 1239.) Thio-ethers are obtained. 2C 2 H 5 I + K 2 S (C 2 H 5 ) 2 S + 2KI. 2C 2 H 5 .S0 4 K + K 2 S -> (C 2 H 5 ) 2 S + 2K 2 S0 4 . CHAPTER XXII THE LINKING OF HALOGEN TO CARBON Reaction CLXII. Replacement of Oxygen and Hydroxyl by Halogens.— The oxygen of ketone and aldehyde groups is readily replaced by halogen under the influence of phosphorus trichloride or pentachloride ; the reaction may be carried out with or without a solvent ; solvents commonly employed are chloroform, benzene, petroleum ether, acetyl chloride and phosphorus oxy chloride. Alcoholic hydroxyl may be replaced by halogen : — (a) With halogen acids. The action is slow with hydrochloric acid, heating under pressure or the use of a dehydrating agent being usually necessary. Hydrobromic acid reacts more easily and hydriodic still more easily. Instead of the acids, bromine and iodine may be allowed to act on the alcohols in presence of phosphorus. (b) With phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or tribromide, or sulphur monochloride. The pentachloride, trichloride and tribromide of phosphorus are also used for replacing hydroxyl by halogen in phenols, carboxylic acids and sulphonic acids. The use of phosphorus trichloride is to be preferred in the preparation of many acid chlorides, since three molecules of acid chloride are then formed per molecule of phosphorus halide, as against one molecule of acid chloride when the pentachloride is used : 3R.COOH + PC1 3 -> 3R.CO.C1 + H 3 P0 3 . R.COOH + PC1 5 -> R.CO.C1 + POCI3 + HC1. and further, no volatile compound of phosphorus is formed. Phosphorus tribromide, and not the pentabromide, is generally used for the preparation of acid bromides. Thionyl chloride does not react with aldehydic and ketonic groups, but reacts readily with carboxyl groups, and sometimes with alcoholic hydroxyl groups. 2R.COOH + SOClo -> 2KCOC1 + S0 2 + H 2 0. Excess of the reagent (SOCl 2 ), without solvent, is generally employed, and the excess removed by distillation or by treatment with formic acid. Other compounds used for replacing hydroxyl by halogen are carbonyl chloride, benzenesulphonyl chloride and sulphuryl chloride. Preparation 307. — Benzophenone Chloride (Diphenyl-dichlor-methane). (C 6 H 5 ) 2 CC1 2 . C 13 H 10 C1 2 . 237. 24 gms. (1 mol.) of benzophenone are renuxed with 40 gms. (excess) of phosphorus pentachloride on an oil bath at 220° — 240° for 4 hours. The 323 y 2 324 SYSTEMATIC ORGANIC CHEMISTRY mixture is fractionally distilled under reduced pressure, the fraction boiling at 193° at 30 mms. being retained. It is redistilled under reduced pressure. (C 6 H 5 ) 2 CO + 2PC1 5 = (C 6 H 5 ) 2 CC1 2 + POCl 3 . Colourless oil ; B.P. 3a 193° ; B.P. 760 3 05°, with decomposition ; D. 18 4 5 1-235. (B., 3, 752 ; 29, 2944.) Preparation 308. — Hippuryl Chloride. C 6 H 5 .CONH.CH 2 .COCl. C 9 H 8 0 2 NC1. 197-5. In this preparation moisture must be excluded as far as possible. 5 gms. (1 mol.) of hippuric acid are finely ground and passed through a fine sieve. The powder is added to a solution of 6-5 gms. (excess) phos- phorus pentachloride in 50 gms. of acetyl chloride contained in a strong glass bottle. The bottle is fitted with a good stopper and agitated in a shaking machine for 2 hours. The crystals formed are filtered off, washed with petroleum ether, and dried in a vacuum desiccator containing sulphuric acid. The product may be recrystallised from warm acetyl chloride (i.e., heated on a water bath) ; a higher temperature, or very prolonged heating, brings about some decomposition. C 6 H 5 .CO.NH.CH 2 .COOH + PC1 5 -> C 6 H 5 CO.NH.CH 2 .COCl + P0C1 3 + HC1. Yield. — 80% theoretical (4-5 gms.). Colourless needles ; becomes yellow at 125°, then dark red, and melts at a higher temperature ; with alcohol or water yields hippuric acid. (B., 38, 605.) Preparation 309. — Benzoyl Chloride (Acyl chloride of benzoic acid). C 6 H 5 C0C1. C 7 H 5 0C1. 140-5. 50 gms. (1 mol.) of phosphorus pentachloride are weighed by difference in a fume cupboard into a 250-c.c. distilling flask. 28 gms. (1 mol.) of benzoic acid are added. Dense clouds of hydrogen chloride are evolved during the reaction, and when this is over, the contents of the distilling flask are fractionally distilled, the phosphorus oxychloride which passes over about 107° being rejected, and the fraction 190° — 200° collected separately. C 6 H 5 COOH + PC1 5 - C 6 H 5 C0C1 + POCl 3 + HC1. Yield. — 75% theoretical (25 gms.). Colourless liquid ; pungent smell ; fumes in moist air ; B.P. 198-5° ; D. ] | 1-214. (A., 3, 262 ; 60, 255.) Preparation 310. — Acetyl Chloride (Ethanoyl Chloride). CH3COCI. C 2 H 3 0C1. 78-5. 50 gms. (excess) of glacial acetic acid are placed in a 250-c.c. distilling flask connected by a water condenser with another distilling flask the side of which is fitted with a calcium chloride tube. 40 gms. of phosphorus THE LINKING OF HALOGEN TO CARBON 325 trichloride (2 mols.) are slowly added through a dropping-funnel, the distilling flask being cooled in a cold water bath. The latter is then heated at 45° (caution !) until the evolution of hydrogen chloride diminishes when the water bath is heated to boiling till nothing further distils. The acetyl chloride contains some phosphorus trichloride, so it is redistilled from the collecting flask over fused sodium acetate, the fraction 53° — 56° being separately collected in the same way as before. 3CH 3 COOH + PC1 3 = 3CH 8 C0C1 + H3PO3. Yield. — 55% theoretical calculated on acetic acid taken (45 gms.). Colourless, pungent smelling liquid ; fumes in moist air ; B.P. 55° ; D. 2 ;» 1-105. (A. Ch., [3], 37, 285 ; C. r., 40, 944 ; 42, 224.) The presence of phosphorus trichloride in the first distillate may be proved by adding a few drops of water to a drop of the distillate (caution !), oxidising the phosphorous acid formed to phosphoric acid by boiling with nitric acid, and the testing with ammonium molybdate. The acetyl- phosphorous acid remaining in the residue from the second distillation can be proved to be present by evaporating with water on a water bath till the smell of acetic acid disappears, and then testing for phosphoric acid after treatment with nitric acid. Preparation 311. — o-Nitrobenzyl Chloride (l-Chlorometliyl-2-nitrc- benzene). C 6 H 4 (CH 2 C1)N0 2 [1.2]. C 7 H 6 0 2 NC1. 171-5. 10 gms. of o-nitrobenzyl alcohol (2 mols.) dissolved in 100 gms. dry chloroform are placed in a flask in a fume cupboard. The flask is well cooled and 6 gms. (approx. 1 mol.) of powdered phosphorus pentachloride added. When the reaction is over cold water is added, and the mixture shaken. The chloroform layer is then separated, the chloroform removed by distillation and the residue, after solidification, crystallised from chloroform. N0 2 C 6 H 4 .CH 2 OH + PC1 5 -> N0 2 C 6 H 4 .CH 2 C1 + HC1 + POCl 3 . Pale yellow needles ; M.P. 49°. (B., 18, 2402.) Preparation 312. — 2.6-Dichloruric Acid (2.6-Dichlor-S-oxy-punne). N = C.C1 I C1C C-NH \3.OH. C 5 H 2 ON 4 CL. 205. N — C N 20 gms. (3 mols.) of dry potassium urate and 24 gms. (excess) of phos- phorus oxy chloride are heated in a sealed tube for 6 hours at 160° — 170°. When cold, the tube is carefully opened and the product poured into water. The precipitate formed is filtered off, dried and powdered. It is then 326 SYSTEMATIC ORGANIC CHEMISTRY added slowly to 5 parts of cone, nitric acid and boiled for 20 minutes. Only a small portion of the dichloruric acid goes into solution, and this is reprecipitated by diluting with water. The crude acid is collected, well washed with water, and while suspended in 24 parts of boiling alcohol, is treated with ammonia solution until all save a slight impurity is dis- solved. Animal charcoal is added and the whole boiled and filtered. The ammonium salt of the acid separates out in pale yellow leaflets on cooling, and further crops may be obtained by concentrating the mother liquors. The salt is redissolved in water, and the free acid obtained by precipitation with mineral acid. 3C 5 H 4 0 3 N 4 + 2P0C1 3 -> 3C 5 H 2 0N 4 C1 2 + 2H 3 P0 4 . Yield. — 35% theoretical (7 gms.). Colourless crystalline powder which does not melt. (B., 30, 2208.) Preparation 313— Diphenyl Chlor acetic Acid. (C 6 H 5 ) 2 C(Cl).COOH. C 14 H n 0 2 Cl. 246-5. 15 gms. (1 mol.) benzilic acid and 15 gms. (excess) phosphorus oxy- chloride are gently warmed together until a slight red colour appears. The melt is then cooled and shaken with a litre of cold water until (1 — 2 hours) the product becomes quite solid. It is then filtered off, washed with water and dried. It is purified by recrystallisation from a mixture of benzene and petroleum ether. 3(C 6 H 5 ) 2 C(OH).COOH + POCl 3 -> 3(C 6 H 5 ) 2 C(Cl)COOH + H 3 P0 4 . Yield.— 65% theoretical (14 gms.). Rhombic plates; M.P. 118°— 119°, with decomposition. (B., 36, 145.) Preparation 314. — /?-Iodo Propionic Acid (3-Iod-pentan acid). CHJ.CH 2 .COOH. C 3 H 5 0 2 I. 200. 100 gms. (a little more than 1 mol.) of phosphorus di-iodide (see p. 507) are added in small quantities to 52 c.cs. (2 mols.) of glyceric acid (D. 1-26) in a large round flask, and the mixture gently heated till a violent reaction sets in. Should it become too violent the flask is cooled in water. The product, a dark brown syrupy liquid, is again heated, when a second less violent reaction occurs, and a light yellow liquid, which, on cooling, solidifies to a crystalline mass, is formed. From this iodo propionic acid is extracted with hot carbon bisulphide (caution!) or petroleum ether (caution!). The solvent is distilled off and the discoloured residue recrystallised from carbon bisulphide or petroleum ether. CH 2 (OH).CH(OH.).COOH + 3HI - CH 2 I.CH 2 .COOH + 2H 2 0 + I 2 . Colourless pearly laminae ; slightlv soluble in cold, readily in hot water and in alcohol ; M.P. 83-5°. (A., 131, 323 ; 166, 1 ; B., 9, 1902.) THE LINKING OF HALOGEN TO CARBON 327 Preparation 315.— Menthyl Chloride (l-Methyl-4-(l-methyl-ethyl)-3- chlor-R-hexen). CH(CH 3 ) 2 C 10 H 19 C1. 174-5. CH CHCl^CH, ^H 2X ^^CH 2 CH CH 3 50 gms. (1 mol.) phosphorus pentachloride are covered with dry petroleum ether in a flask and the whole w^ell cooled in ice. 50 gms. (excess) of menthol are added in small portions to the cooled mixture, no fresh menthol being added until the evolution of hydrochloric acid has ceased. The petroleum ether is then distilled off, and the residue distilled with the aid of a fractionating column ; crude menthyl chloride passes over at 205° — 215°, and it may be purified by redistilling several times. In the crude state it may be used for Preparation 443. C 10 H 19 OH + PC1 5 -> C 10 H 19 C1 + POCl 3 + HC1. Yield. — 55% theoretical (30 gms.). B.P. 209-5°— 210-5°. (B., 29, 317 ; 25, 686 ; J. C. S., 41, 54.) Preparation 316. — a-a-Propenyl-dichlorhydrin (1.3-Dichlor-2-pro- panol). CH 2 C1.CH(0H).CH 2 C1. C 3 H 6 0C1 2 . 129. Method I. — 100 gms. (1 mol.) of glycerol are dehydrated by gradually warming on a sand bath to 175°. When cold it is mixed with 80 c.cs. of glacial acetic acid, and a stream of dry hydrochloric acid is conducted through the cold liquid for about 2 hours until no more is absorbed. The mixture is heated on a water bath, and after standing at room temperature for 24 hours, the stream of hydrochloric acid is again passed through for 6 hours. The product is then distilled ; hydrogen chloride and dilute acetic acid pass over first, and as the temperature rises propenyl dichlorhydrin and aceto-dichlorhydrin distil. The fraction 160° — 220° is redistilled with the aid of a column until a fraction of boiling point 175°— 177° is obtained. CH 2 (OH).CH(OH).CH 2 (OH) + 2HC1 -> CH 2 C1.CH(0H).CH 2 C1 -f 2H 2 0. Yield.— 70% theoretical (100 gms.). Method II. — 125 gms. (less than 2 mols.) of sulphur monochloride (p. 507) are slowly added in small quantities at a time from a tap funnel to 50 gms. of anhydrous glycerol (dehydrated, as in Method I.) contained in a retort fitted with a reflux condenser. The experiment should be conducted in a fume chamber. The retort is occasionally shaken, and the reaction is completed by heating in a boiling brine bath until the evolution of hydrogen chloride from the condenser has almost ceased. The condenser is then removed and the mass again heated until all sulphur dioxide and 328 SYSTEMATIC ORGANIC CHEMISTRY hydrogen chloride are expelled. When cold, the semi-solid mass is twice extracted with twice its volume of ether. The ethereal extract is filtered free from sulphur, and the ether removed by distillation on a water bath. The residue is repeatedly fractionated until a fraction of boiling point 175°— 178° is obtained. CH 2 (OH)CH(OH)CH 2 (OH) + 2S 2 C1 2 -> CH 2 C1.CH(0H)CH 2 C1 + 2HC1 + SO a + 3S. Colourless ethereal liquid ; easily soluble in ether ; B.P. 176° ; D. J 1-383. (J., 13, 456 ; A. Spl., 1, 221 ; A.,*122, 73 ; 168, 42.) Preparation 317. — Isopropyl Iodide (2-Iod-propan). CH3.CHI.CH3. C 3 H 7 I. 170. 5-5 gms. (1 atom) of yellow phosphorus are added in small pieces to 20 gms. (excess) of glycerol, 20 c.cs. of water, and 30 gms. (excess) of iodine, in a retort attached to a condenser. At the beginning a flash of light attends the introduction of each piece of phosphorus. The retort is shaken vigorously till when about one-third of the phosphorus has been added the iodine has all dissolved. The remainder of the phosphorus is then added more quickly. The contents of the retort are distilled till no more oily drops collect, and the distillate replaced in the retort and redistilled. The second distillate is washed with water, dilute sodium hydroxide solution, and again with water. After drying over calcium chloride it is redistilled. CH 2 OH CH 2 I CH 3 3HI ! 2HI CHOH > CHI — > CHI 1 , 1 I CH,OH CH 2 I CH 3 Yield. — 70% theoretical (15 gms.). Colourless liquid ; insoluble in water; B.P. 89-5° ; D. J 1-744. (A., 138, 364.) Preparation 318. — Ethyl Bromide (Monobrom-ethan). CH 3 .CH 2 .Br. C 2 H 5 Br. 109. Method I. — A General Method for the Preparation of Alkyl Bromides. — - The details of this preparation are very similar to those given in the general method for the preparation of alkyl iodides (see p. 330). 10 gms. (excess) of red phosphorus and 50 gms. (excess) of ethyl alcohol are placed in a distilling flask, attached to a condenser and receiver. The receiver consists of a Buchner flask, attached by means of a cork to the end of the condenser, its side tube being connected with a soda-lime tower to trap any fumes of hydrobromic acid. A tap-funnel containing 65 gms. (5 mols.) of bromine is fixed through a cork in the neck of the distilling flask. The flask is cooled in water, the bromine slowly added, the whole left for several hours, and the contents of the flask then distilled from the water THE LINKING OF HALOGEN TO CARBON 329 bath at 50°, the receiver being cooled in ice. The distillate is purified as in the preparation of ethyl iodide, given on p. 331. 5ROH + P + 5Br = 5R.Br + H 3 P0 4 + H 2 0. Yield. — Almost theoretical (80 gms.). Colourless, highly-refractive liquid ; characteristic odour ; soluble in all the usual organic solvents ; insoluble in water ; B.P. 7; " 38-8° ; D. »£ 147 ; D. ° 1485. (J., 1857, 441.) Note. — The other alkyl bromides may be prepared in a similar manner, with the aid of the table of boiling points given below. For those bromides which boil over 100°, the same precautions must be taken as detailed in the General Method for the Preparation of Iodides (p. 330). Substance. Boiling Point. ^-Propyl bromide . . 71° w-Butyl bromide . . ' 100° iso-Butyl bromide . . 92° is-o-Amyl bromide . . 120° (B., 14, 608 ; A., 158, 161 ; 93, 114 ; 159, 73.) Method II. — 100 gms. (excess) of cone, sulphuric acid and 60 gms. (excess) of absolute alcohol are mixed in a litre distilling flask, cooled under the tap, and 100 gms. (1 mol.) of coarsely powdered potassium bromide added. The flask is closed by a cork, and attached to a condenser leading, by means of an adapter, into a 250-c.c. conical flask, which serves as a receiver. Enough water is poured into the latter to close the end of the adapter. The distilling flask is then heated on a sand bath until no more oil distils, the receiver being meanwhile cooled in ice. Should the reaction mixture threaten to froth over the flask must be raised from the sand bath for a moment. The ethyl bromide is separated in a funnel, washed with an equal bulk of dilute sodium carbonate solution, and with water, dehydrated over calcium chloride, and distilled on a water bath, the fraction 35° — 43° being retained. Ethyl bromide prepared by this method usually contains traces of ether. A new and better method, which gives the pure substance, is given below. C 2 H 5 OH + H 2 S0 4 = C 2 H 5 .H.S0 4 + H 2 0. C 2 H 5 .H.S0 4 + KBr = C 2 H 5 Br + KHS0 4 . Yield.— 83% theoretical (75 gms.). Method III. — A mixture of 20 gms. (1 mol.) of ethyl alcohol and 300 gms. (4 mols.) of hydrobromic acid of constant boiling point, 126°, and D. 149 (for preparation see p. 502) are gradually heated in a distillation flask or retort connected with a condenser. The heating is continued until no more oily drops pass over. The distillate is then washed, dried, and dis- tilled, as above. Only a small portion of the acid distils over, and if the residue left in the flask is slowly distilled the excess of hydrobromic 330 SYSTEMATIC ORGANIC CHEMISTRY acid can be obtained in the form of the solution of constant boiling point, and again used. C 2 H 5 OH + HBr = C 2 H 5 Br + H 2 0. Yield— 86% theoretical (41 gms.). (Am. Soc, 38, 640; Bl. [iv.j, 9, 134.) Preparation 319. — Ethyl Chloride (Mono-chlor-ethan). CH 3 .CH 2 C1. C 2 H 5 C1. 64-5. Dry hydrogen chloride is passed through a trap into 200 gms. of absolute alcohol containing 100 gms. of fused coarsely powdered zinc chloride, in a 500-c.c. round-bottomed flask heated on a water bath and fitted with an upright condenser, from the top of which the vapour is led into a conical flask containing water. The inlet tube is cut off just above the surface of the water. Thence the vapour passes through a tower filled with soda- lime, and finally into a U -tube surrounded by ice, and fitted with an open tube at its lowest point. The condensed ethyl chloride drops from the bottom of the U-tube, and is collected in a small conical flask standing in ice. The upright condenser returns all alcohol to the flask. The excess of hydrogen chloride which passes on is absorbed by the water in the conical flask, and what remains is removed in the soda-lime tower. A fairly rapid stream of gas must be maintained on starting or the alcohol will be sucked back into the trap. The passage of the gas is continued until a sufficient quantity of ethyl chloride has been obtained. It must be stored in a well-stoppered bottle, wrapped in a cloth, and placed in an ice chest, but owing to the risk of its breaking the bottle a quantity should only be kept when there is necessity for so doing. C 2 H 5 OH + HC1 = C 2 H 5 C1 + H 2 0. Yield. — Almost theoretical (280 gms.). Colourless liquid ; charac- teristic odour ; soluble in all the usual organic solvents ; insoluble in water ; B.P. 12-5° ; D. J 0-9214. (A., 150, 216 ; 174, 372 ; Z. Ch., 1871, 147.) Preparation 320. Methyl Iodide and Ethyl Iodide. Methyl iodide CH 3 I. 142. Ethyl-iodide. CH 3 .CH 2 I. C 2 H 5 I. 156. A General Method for the Preparation of Alkyl Iodides. — 36 gms. (excess) of methyl alcohol (52 gms. of ethyl alcohol) are placed in a 500-c.c. flask with an upright condenser, along with 10 gms. (excess) of red phosphorus. 100 gms. (5 mols.) of powdered iodine are slowly added during 1 hour with frequent shaking, the condenser being detached from the flask momen- tarily during the addition. The latter is cooled in cold water if necessary. The whole is then allowed to stand overnight, or should that time be not available, it is left for 3 hours with occasional shaking, and then gently boiled on a water bath under a reflux condenser for 1 hour. The former method, however, gives the better yield. The contents of the flask are then distilled oft on a water bath into a receiver containing water and THE LINKING OF HALOGEN TO CARBON 331 cooled in ice ; the method and apparatus described in Preparation 319 may be used . The distillation is continued till the greater part of the liquid has distilled over, and no oily drops are to be seen in the condenser. The residue consisting of a concentrated solution of phosphorous and phosphoric acids in addition to excess of red phosphorus is discarded. The distillate is shaken up with water to remove alcohol, and then with dilute caustic soda to remove free iodine. Enough alkali must be used to render the lower layer of alkyl halide colourless.* The latter is then separated off, dried over granular calcium chloride (6 gins.) and distilled. The prepara- tion should be kept in the dark in a well-stoppered bottle. If exposed to light, iodine slowly separates, but may be prevented from so doing by adding a small quantity of colloidal silver to the liquid. 5ROH + P + 51 = 5RI + H 3 P0 4 + H 2 0. Yield.— Almost theoretical (methyl iodide, 90 gms. ; ethyl iodide, 100 gms.). Colourless, highly refractive liquids ; characteristic odour ; B.P. 760 methyl iodide, 42-8° ; B.P. 760 ethyl iodide, 72-2°; D.J methyl iodide 2-27 ; D.'j ethyl iodide 1-975. (A. Ch., [1] 91, 89 ; [2] 25, 323 ; 42, 119 ; A., 126, 250 ; J. C. S., 117, 1592.) Note, — The following table of boiling points will enable the iodides in it to be prepared from the corresponding alcohols. In distilling off the iodide from the reaction mixture an oil bath is used if the iodide boils at over 100°. Care should be taken not to raise the temperature too high, as there is a danger that the red phosphorus may take fire if air leaks in. To avoid this the distillation, if not done on a water bath, is best carried out in a current of carbon dioxide. Compound. Boiling Point. ^-Propyl iodide n-Butyl iodide iso-Butyl iodide 150- Amy 1 iodide 102° 130° 120° 148° Reaction CLXIII. Addition of Halogen or Halogen Hydride to Unsatu- rated Compounds. — Unsaturated compounds readily combine with chlorine, bromine, hydriodic or hydrobromic acid. The addition of iodine or of hydrochloric acid is generally a matter of difficulty. The unsaturated terpenes, however, unite readily with hydrochloric acid. In the addition of halogen hydrides to unsaturated hydrocarbons, the halogen attaches itself to the carbon atom having the lesser amount of hydrogen ; with * Should difficulty be experienced in freeing the liquid of iodine, addition of a little sodium thiosulphate solution is extremely effective. 332 SYSTEMATIC ORGANIC CHEMISTRY hydrocarbons, containing the group — C == C — , two atoms of halogen are fixed to the carbon atom having the lesser amount of hydrogen. In the addition of halogen hydrides to unsaturated acids and aldehydes, the halogen generally enters the ^-position. CH 2 : CH.COOH + HC1 ~> CH 2 Cl.CH 2 .COOH. In many of these reactions a solvent is employed, either for the purpose of dissolving a substance or for moderating the action of the reagent. Where the reagent is used in the gaseous form its action may be moderated by previous admixture with an inert gas, e.g., carbon dioxide or air. Preparation 321. — Ethylene Dibromide (1.2-Dibrom-ethan). CH 2 Br.CH 2 Br. C 2 H 4 Br 2 . 188. Ethylene is prepared by gently heating a mixture of 25 gms. ethyl alcohol, 150 gms. cone, sulphuric acid, and a little sand, in a 2-litre round flask on a sand bath till a steady stream of gas is evolved. A mixture of 1 part of alcohol and 2 parts by weight of cone, sulphuric acid is then slowly added through a tap-funnel, the lower opening of which has been drawn out somewhat, at such a rate that the gas is constantly evolved without frothing. The gas is purified by passing it through two wash- bottles in series containing dilute caustic soda solution, to which a little phenolphthalein has been added. The wash-bottles are fitted with safety tubes, and their contents must be renewed occasionally, the phenol- phthalein serving to show when they are becoming exhausted. The gas is then bubbled slowly through two wash-bottles with ground glass stoppers, each containing 15 gms. of bromine (1 mol.) and 50 c.cs. of water, and immersed in water, the temperature of which is kept below 25°. Should the contents of the ethylene generating flask char too badly (some charring is inevitable) a fresh supply of gas must be made. When decolorisation of the bromine is complete (several hours) the crude ethylene bromide is washed with dilute caustic soda solution and with water, dried over calcium chloride and distilled*, • the fraction 130° — 132° being collected separately. CH 3 CH 2 OH - H 2 0 = CH 2 : CH 2 . CH 2 : CH 2 + Br 2 = CH 2 Br.CH,Br. Yield. — 85% theoretical (30 gms.). Colourless oil ; insoluble in water ; B.P. 760 131-5 ; D. ] ! 2-19. (A., 168, 64.) Preparation 322. — Cinnamic Acid Dibromide (3-Phenyl-2-3-dibrom- propan acid). C 6 H 5 .CHBr.CHBr.COOH. C 9 H 8 0 2 Br 2 . 308. Method I. — 40 gms. (1 mol.) of finely divided cinnamic acid are spread out on a large clock-glass and placed in a desiccator over concentrated sulphuric acid. A dish containing 45 gms. (slightly more than 1 mol.) of dry bromine is supported on a glass tripod above the cinnamic acid, the desiccator is closed, and allowed to stand until all the bromine has evapo- rated from the dish, and has been absorbed from the acid (about 3 days). THE LINKING OF HALOGEN TO CARBON 333 The clock-glass is removed, the product exposed to the air for several hours, weighed in order to make sure that the theoretical amount of bromine has been absorbed, and recrystallised from dilute alcohol. C 6 H 5 .CH : CH.COOH + Br 2 = C 6 H 5 CHBr.CHBr.COOH. Yield.— Theoretical (80 gms.). Colourless leaflets ; M.P. 195° (decom- position) (J. C. S., 83, 669.) Method II. — 12-5 gms. (1 mol.) of cinnamic acid are dissolved in 65 c.cs. of anhydrous ether, and the solution cooled to 0° in a freezing mixture. 4-3 c.cs. (1 mol.) of bromine are then slowly added from a burette while all but diffused daylight is excluded, as the reaction is very violent in direct sunlight. The ether is removed on a water bath, and the residue recrystallised from dilute alcohol. Yield.— Theoretical (25 gms.). Colourless leaflets. (A., 195, 140.) Preparation 323. — Dichlor-cinnamic Acid ( 4-Pheny 1-2.3 -dichlor- propan acid). C 6 H 5 .CHC1.CHC1.C00H. C 9 H 8 0 2 CL>, 219. Direct sunlight or some other source of ultra-violet rays is essential for this preparation. 10 gms. of finely ground cinnamic acid are suspended in 80 gms. of freshly distilled carbon disulphide in a quartz flask. A stream of dry chlorine gas (p. 502) is passed in until the liquid assumes a greenish-yellow colour. The mixture is alternately shaken until this colour disappears, and resaturated with chlorine gas until an increase in weight of 5 gms. has taken place. The precipitate is filtered off and recrystallised from aqueous alcohol. C 6 H 5 CH : CH.COOH + Cl 2 -> C 6 H 5 CHC1.CHC1.C00H. Yield.— 90% theoretical (14 gms.). Colourless leaflets ; M.P. 162°— 164° (slight decomposition). (B., 14, 1867.) Preparation 324.— ft -Phenyl-/?- Bromo Propionic Acid (3-Phenyl-3- brom-propan acid). C 6 H 5 CHBiCH 2 COOH. C 9 H 9 0 2 Br. 229. 10 gms. (1 mol.) of finely powdered cinnamic acid are heated in a sealed tube (see p. 38) for 2 hours at 100° with 10 gms. of glacial acetic acid which has been saturated with hydrogen bromide at ordinary temperature. (1 gm. of glacial acetic acid dissolves about 0-6 gm. of hydrogen bromide, so there is an excess of the latter present.) The precipitate is recrystallised from dry carbon bisulphide (the acid is readily decomposed by water) in which cinnamic acid is readily soluble, even in the cold. C 6 H 5 CH : CHCOOH + HBr = C 6 H 5 CHBr— CH 2 COOH. Colourless crystals ; soluble in hot, slightlv soluble in cold carbon bisulphide ; M.P. 137°. (B., 11, 1221.) 334 SYSTEMATIC ORGANIC CHEMISTRY Preparation 325— Dipentene Hydrochloride (l-[l-En-l-methyl-ethyl]. 4-methyl-4-chlor-cyclo-hexan) . CH 3 CC1 CH/^CH, CH 2 i JcH 2 c io h itC1. 172-5. CH i CH., : C.CH,. This reaction must be carried out in a fume cupboard. r 20 gms.(l mol.) of dipentene, which has been thoroughly dried over metallic sodium, are dissolved in an equal volume of dry carbon disulphide, the solution placed in a dry distilling flask — the side tube of which is con- nected with a calcium chloride tube — and a current of dry hydrogen chloride (see p. 502) led into the solution through the neck of the flask, which is meanwhile surrounded with ice. After 8 hours the operation is interrupted, the carbon disulphide removed on a water bath, and the residue fractionated under reduced pressure, the fraction 97° — 98° at 11 — 12 mms. being retained. CH 3 I ,CH 3 C I /\ C-€l CH, CH CH/NCH- I + HC1 = CH 2 CH 2 CH | J CH CH |CH CH 3 C CH 2 Colourless liquid ; B.P. 11 97-98°. Note.— Every trace of moisture must be excluded m this preparation (A., 270, 188.) Preparation 326.— Ethylene Bichloride (1.2-Dichlor-ethan). CH 2 C1 | C 2 H 4 C1,. 99. CH 2 C1. Ethylene is prepared by dropping ethyl alcohol slowly into phosphoric acid heated to about 210°. The gas is passed first into an empty wash- bottle surrounded by a freezing mixture, and then through a second containing cone, sulphuric acid. The gas is next passed into antimony trichloride at 40°— 50°, through which dry chlorine is also passed. The ethylene dichloride formed is distilled from the antimony trichloride. Sweet smelling liquid ; B.P. 85°. (P. A., 13, 297.) THE LINKING OF HALOGEN TO CARBON 335 Reaction CLXIV.— Replacement of Hydrogen by Nascent Halogen.— When nascent bromine is required, sodium bromide and bromate are added to the substance, and the amount of sulphuric acid required by the following equation is added : — 5NaBr + NaBr0 3 + 6H 2 S0 4 -> 6NaHS0 4 + 3H 2 0 + 6Br. An excess of bromate and sulphuric acid are often employed to react with the hydrobromic acid formed during the bromination of the sub- stance. K.H + 2Br — > R.Br + HBr. HB1O3 + 5HBr — > 6Br + 3H 2 0. Nascent chlorine or iodine can be generated from their corresponding salts in a similar manner. Preparation 327.— Acet-p-Chlorauilide (l-Chlor-4-acetamino-benzene). Cl<^ ^>NH.COCH 3 . C 8 H 8 0NC1. 169-5. 20 gms. of alcohol and 20 gms. glacial acetic acid are mixed, and to this is added 10 gms. (1 mol.) of acetanilide, which is dissolved by gentle heat. After 20 c.cs. of water have been added the solution is heated to 50°, when 200 c.cs. of a cold 10% solution (a slight excess) of bleaching powder are added gradually with continuous stirring. A white precipitate is formed which is filtered off, washed with water, and then recrystallised from alcohol, animal charcoal being added, if necessary. Cl 2 C 6 H 5 NH.COCH 3 -> C 6 H 5 NCl.COCH 3 ~> C1C 6 H,NH.C0CH 3 . Colourless needles ; M.P. 179° — 180° ; soluble in alcohol, ether, and carbon disulphide. (G., 28, II., 313.) Preparation 328.— 2.6-Dichlor-4-Nitraniline. CI NHN0 2 . C 6 H 4 0 2 N 2 C1 2 . 207. Cl~ 35 gms. of p-nitraniline are dissolved in 312 c.cs. cone, hydrochloric acid at 50°. A solution of 20-5 gms. of potassium chlorate in 437 c.cs. of water at about 25° are slowly added. When all the chlorate has been added the solution is diluted with a large quantity of water ; the precipitate formed is removed by filtration and well washed. It can be further purified by crystallisation from glacial acid or from a mixture of glacial acetic acid and alcohol. CI NH,/ ^>N0 2 + Cl 2 -> NH 2 / \>N0 2 . CI Yield. — 87% theoretical (42 gms.). Lemon-yellow needles ; M.P. 185°— 188°. (B., 36, 4391.) 33G SYSTEMATIC ORGANIC CHEMISTRY Preparation 329. — Chloranil (Tetra-chloro-^-benzquinone). Cl_ CI 0 = / y=0. C 6 0 2 C1 4 . 246. CT~C1 30 gms. of 2.6-diclilor-4-nitraniline are boiled with 750 c.cs. of cone, hydrochloric acid and 33 gms. of tin, and thus reduced to the corresponding diamine. 25 gms. of crystallised potassium chlorate are added slowly, without cooling, the whole being kept gently boiling. The boiling is carried on for a short time after the whole of the chlorate has been added ; the liquid is then diluted and filtered. The precipitate is washed well with water, dried, and purified by recrystallisation from toluene or by sublima- tion. CI CI CI CI NH 2 / \N0 2 -> NH 2 / )NH 2 -> 0=/ \ = 0. ci cr cr~ci Yield. — 90% theoretical (32 gms.). Yellow leaflets ; sublimes on heating. (B., 36, 4390.) Reaction CLXV. Replacement of Hydrogen by the Use of Halogen Com- pounds. — The halogen compounds used are those of phosphorus, sulphur, antimony and iodine, and also sulphuryl chloride and bleaching powder. When phosphorus pentachloride is used the halogen does not enter the nucleus until the hydrogen of the side chain has been completely replaced. A mixture of red phosphorus and bromine is used in place of phosphorus bromide ; with yellow phosphorus the reaction is much too vigorous. As red phosphorus generally contains traces of free phosphoric acid it should be previously washed with water until acid free, and dried before using. Sulphur bromide and iodide are used in presence of nitric acid ; with these the halogen enters the nucleus, and only mono-derivatives are formed. Antimony pentachloride yields two atoms of halogen for chlorination. Iodine monochloride in glacial acetic acid or dilute hydro- chloric acid replaces hydrogen by iodine. Sulphuryl chloride chlorinates aromatic compounds, both in the side chain and in the nucleus ; when a carbonyl or carboxyl group is present the hydrogen in the a-position to this group is substituted. Bleaching powder is used as a chlorinating agent owing to the ease with which it gives up its available chlorine. Preparation 330. — a-Bromo-stearic Acid (2-Brom-octa-decan acid). CH 3 (CH 2 ) 15 CHBrCOOH. C ls H 35 0 2 Br. 363. 30 gms. (3 mols.) of stearic acid and 1-1 gms. (1 atom) of red phosphorus are placed in a flask fitted with a reflux condenser and dropping-funnel. The flask is immersed in a water bath containing water at 60° — 70°, so that the stearic acid melts, and 22-5 gms. (4 mols.) of dry bromine are added gradually from the dropping-funnel. When addition is complete the mixture is heated on a boiling water bath for about 3 hours. The product THE LINKING OF HALOGEN TO CARBON 337 is poured into water, and the monobromo stearic acid filtered of! and dried on a porous plate. It is recrystallised from carbon disulphide. 3CH 3 (CH 2 ) 16 COOH + P + 4Br 2 = 3CH 3 (CH 2 ) 15 CHBrCOBr + HP0 3 + 2HBr. CH 3 (CH 2 ) 15 CHBrCOBr + H 2 0 -> CH 3 (CH 2 ) 15 CHBrCOOH. Colourless plates ; M.P. 61° ; the materials used in this preparation must be pure and dry (see preparation of mono-bromacetic acid). (B., 24, 2903 ; 25, 482.) Preparation 331. — Mono-bromacetic Acid (Mono-brom-ethan acid). CH 2 BrCOOH. C 2 H 3 0 2 Br. 139. The materials for this preparation must be pure and dry. The acetic acid is purified, as on p. 234 ; the bromine is shaken with cone, sulphuric acid, and the phosphorus warmed with dilute ammonia, washed well with water, and dried in a steam oven. 20 gms. (3 mols.) of pure glacial acetic acid and 3 gms. (1 atom) of red phosphorus are placed in a round-bottomed flask of about 300 c.cs. capacity. (N.B. — Rubber stoppers should not be used.) 71 gms. (4 mols.) of bromine are added from a dropping funnel very gradually at first, the flask being cooled by immersion in cold water. The reaction proceeds with great vigour, but moderates after about half of the bromine has been added, when the remainder may be run in more quickly. The flask is then warmed on a boiling water bath until the colour of bromine vapour in the interior of the flask disappears. After cooling, the brom-acetyl bromide is poured into a distilling flask and distilled under diminished pressure. The product is weighed, and the theoretical amount of water required to convert it into bromacetic acid added gradually (1-8 gms. for 20 gms. of the acyl bromide). The mixture solidifies to a white crystalline mass. This is purified by distilling under ordinary pressure from a small distilling flask provided with an air condenser, the portion distilling at 190° — 210° being retained. 3CH 3 COOH + P + 8Br = 3CH 2 BrCOBr + HP0 3 + 2HBr CH 2 BrCOBr + H 2 0 ~> CH 2 BrCOOH. Yield.— Variable. Colourless crystals; M.P. 50°— 51° ; B.P. 208°. Note. — The bromacetyl bromide and bromacetic acid must not be allowed to touch the hands as they cause serious wounds. (B., 20, 2026 ; A., 242, 141.) Preparation 332. — Mono-bromsuccinic Acid (2-Brom-butan-diacid). COOH.CH 2 .CHBrCOOH. C 4 H 5 0 4 Br. 197. A tubulated retort is sealed to a Liebig's condenser, and the latter connected to an apparatus to absorb hydrobromic acid. 18 gms. (3 mols.) of carefully dried succinic acid are intimately mixed with 3-5 gms. (excess) of red phosphorus. This is placed in the retort, and 80 gms. (excess) of bromine is added slowly from a dropping-funnel through the tubulus. rhe bromine must be very carefully added at the beginning as the reaction 338 SYSTEMATIC ORGANIC CHEMISTRY is violent, and again added only when the reaction subsides. When all the bromine has been added, the whole is heated on a water bath until the bromine disappears. The retort now contains mono-bromsuccinyl bromide ; the free acid is obtained by pouring slowly the contents of the retort into 100 c.cs. of boiling water, the flame being withdrawn. It is then filtered, and repeatedly extracted with ether, the latter removed on the water bath, and the residue recrystallised from water. CHo.COOH CH.Br.COBr 3 1 + 2P + 8Br 2 — > 3 I + 2HP0 3 + 7HBr. CH 2 .COOH CH 2 .COBr CHBr.COBr CH.Br.COOH | + 2H 2 0 -> | CH 2 COBr CH 2 COOH. Yield,— 85% theoretical (25 gms.). Colourless crystals ; M.P. 160° ; soluble in water. (A., 242, 145 ; B., 14, 892.) Preparation 333. — 2.4,1-Iod-nitraniline (l-Amino-2-iod-4-nitroben- zene). C 6 H 3 (NH 2 )(N0 2 )I. C 6 H 5 0 2 N 2 .I. 264. 15 gms. (1 mol.) of finely ground ip-m tramline are agitated with cold glacial acetic acid in quantity just sufficient to bring all into solution. A solution of 26-5 gms. (1 mol.) of iodine monochloride in glacial acetic acid is then slowly added to the well-stirred solution, which after the addition is allowed to stand 1 hour. It is then poured into 1-5 litres of boiling water, filtered and allowed to cool. After some time crystals of iod-nitraniline separate which are filtered off and dried. C 6 H 4 (NH 2 )(N0 2 ) + IC1 -> C 6 H 3 (NH 2 )(N0 2 )I + HC1. Long, yellow needles ; soluble in hot water ; M.P. 105°. (B., 34, 3344.) Preparation 334. — Mono-chlor-malonic Acid (2-Chlor-propan-diacid). CH.Cl(COOH) 2 . C 3 H 3 0 4 C1. 138-5. 8 gms. (1 mol.) of malonic acid from a sample which had been dried in a steam oven and cooled in a desiccator are dissolved in 250 c.cs. of anhydrous ether. The solution is cooled in ice water, and 10 gms. (1 mol.) of sulphuryl chloride slowly added. The ether is removed on a water bath, and the residue left in a vacuum desiccator containing sulphuric acid until crystal- lisation of mono-chlor-malonic acid is complete. CH 2 (COOH) 2 + S0 2 C1 2 -> CHCl(COOH) 2 + HC1 + S0 2 . Yield.— Theoretical (10-5 gms.). Colourless crystals; M.P. 133°. (B., 35, 1814.) Reaction CLXVI. Replacement of the Amino Group by Halogen. — The amino group can easily be replaced by halogen : — (a) By means of the Sandmeyer reaction. The amine is diazotised and the resulting diazonium solution added to a warm solution of cuprous halide. E.NH 2 -> R.N : NCI -> R.C1 + N 2 . THE LINKING OF HALOGEN TO CARBON 339 (b) By Gattermann's method, in which copper powder is added to an acid solution of the diazonium salt. (c) By heating a solution of the diazonium compound with hydriodic acid or potassium iodide. Preparation 335. — o-Brom-toluene. C 6 H 4 (CH 3 ).Br. C 7 H 7 Br. 171. 6 gms. or^o-toluidine are dissolved in a mixture of 35 c.cs. hydro - bromic acid of constant boiling point, and 40 c.cs. of water. The solution is cooled to 0°, and diazotised by the addition of 5 gms. sodium nitrite dissolved in 12 c.cs. of water ; during this addition a drop is frequently removed, diluted with water on a watch-glass, and tested with starch iodide paper for free nitrous acid (see p. 365). Copper powder (prepared from 40 gms. copper sulphate, see p. 504) is then added in small quantities at a time to the diazonium solution, which should be continuously stirred ; an effervescence — due to the escape of nitrogen — takes place. When addition of copper produces no further effervescence, the bromo-toluene forms the lower layer. This layer is separated, steam-distilled and the distillate extracted with ether. The ethereal solution is dried over solid calcium chloride, and fractionated. CH 8 .C 6 H 4 .NH 2 -> CH 3 .C 6 H 4 N : N -> CH 3 .C 6 H 4 .Br. Br Yield.— 70% theoretical (6 gms.). B.P. 181°. (G. (1890), 29, 631.) Preparation 336. — jo-Chlor-toluene (l-methyl-4-chloro-benzene). CH 3 .C 6 H 4 .C1. C 7 H 7 C1. 126-5. 20 gms. (1 mol.) of jo-toluidine are dissolved in 100 c.cs. of a mixture of equal volumes of water and cone, hydrochloric acid, and diazotised in the usual way (see p. 365) with sodium nitrite. 15 gms. of moist copper powder (see p. 504) are then added in small portions to the well- stirred solution. When the evolution of nitrogen has ceased, the product is steam-distilled, the distillate extracted with ether, and the ethereal solution dried over anhydrous sodium sulphate. The sodium sulphate is filtered off and the filtrate distilled. p-Chloi -toluene passes over at 163°. CH 3 .C 6 H 4 .NH 2 -> CH 3 .C 6 H 4 N 2 C1 -> CH 3 .C 6 H 4 C1 + N 2 . Colourless oily liquid ; M.P. 7-4° ; B.P. 163°. (B., 23, 1218.) Preparation 337. — Chlorobenzene. ' C 6 H 5 .C1. 112-5. 20 gms. aniline are dissolved in 130 c.cs. water and 37 c.cs. cone, hydrochloric acid, and diazotised (see Preparation 378) at 0° — 5° by the addition of 15 gms. sodium nitrite dissolved in 40 c.cs. water. 140 c.cs. of a 10% solution of cuprous chloride (p. 504) are heated nearly to boiling in a flask and the diazonium solution run in gradually, the contents of the flask being occasionally shaken, and maintained near boiling during the addition. z 2 340 SYSTEMATIC ORGANIC CHEMISTRY The yellow precipitate which appears on the introduction of the diazonium solution decomposes almost immediately, yielding chloro- benzene and nitrogen. The contents of the flask are submitted to steam distillation until no more oily drops of chlorobenzene pass over. The distillate is extracted with ether, the ethereal solution dried oyer calcium chloride and fractionated. G 6 H 5 N 2 C1^C 6 H 5 .C1 + N, Yield.— 75% theoretical (18 gms.). Colourless liquid; B.P. 132°. (B., 23, 1880 ; 23, 1628 ; A., 272, 141.) Preparation 338 .— ^-Iodo-toluene. CH 3 .C 6 H 4 .1. C 7 H 7 I. 171. 20 gms. of ^-tohridine are boiled with hydrochloric acid to dissolve the base, the solution being distinctly acid. The solution is diazotised as usual, and when diazotisation is complete 31 gms. potassium iodide dissolved in water are then run in from a tap-funnel with continuous stirring. The mixture is allowed to stand for a time when a dark brown mass is formed which is filtered off and recrystallised from alcohol. CH 3 C 6 H 4 NH 2 -> CH 3 C 6 H 4 N 2 C1 -> CH 3 C 6 H 4 I. Yield.— 80% theoretical (25 gms.). Yellow plates ; M.P. 35° ; B.P. 211°. Reaction CLXVII. Replacement of Halogen by Halogen. — The substi- tution of bromine by chlorine can be effected through the use of the pentachlorides of antimony or phosphorus. Iodine is still more readily replaced by chlorine, not only by direct action of the latter but also by double decomposition with certain metallic chlorides (HgCl 2 , SbCl 5 , AgCl) or iodine trichloride. The substitution of chlorine by the direct action of bromine is rarely effected. Aluminium bromide, cupric bromide in alcoholic solution or boron tribromide under pressure, convert many alkyl chlorides into alky! bromides. Mono-chloracetic acid heated to 150° in a sealed tube with hydrobromic acid or potassium bromide yields mono-bromacetic acid. Iodine may be replaced by bromine by direct action or by heating under pressure with bromides of copper, mercury, silver or boron. Bromine and iodine can be replaced by iodine through double decom- position with hydriodic acid or iodides of potassium, calcium or aluminium. Preparation 339. — Iod-acetic Acid. CHJ.COOH. C 2 H 3 0 2 r. 186. 25 gms. (1 mol.) of chloracetic acid dissolved in 125 c.cs. of absolute alcohol and 50 gms. (excess) of finely-powdered potassium iodide are refluxed on a water bath for 1 hour. The product is well cooled in ice water, and filtered from potassium chloride and iodide. The filtrate is decolorised (if necessary) by passing in a stream of sulphur dioxide, and afterwards evaporated to a small bulk on a water bath. On cooling, a THE LINKING OF HALOGEN TO CARBON 341 product separates which is collected, dried by exposure in air, and recrystallised from a large volume of petroleum ether. CH 2 Cl.COOH -f KI -> CHJ.COOH + KC1. Colourless leaflets ; M.P. 84° ; the solid Causes painful blisters in contact with the skin, and the vapours irritate the eyes. (Z. Ch., 1868, 484 ; B., 41, 2853.) Preparation 340. — Propenyl Tribromide (1.2.3-Tribrom-propan). CH 2 .Br.CHBr.CH 2 Br. C 3 H 5 Br 3 . 281. 75 gms. (slight excess) of bromine are slowly added to 50 gms. (1 mol.) of allyl iodide contained in a flask, fitted with an air condenser, and well cooled in a freezing mixture ; the whole apparatus being set up in a fume cupboard. The liquid is allowed to stand 24 hours, and filtered from the iodine which has crystallised out. The brown filtrate is repeatedly washed with dilute caustic soda solution, and finally with sodium thio- sulphate, and then with water, dried over fused calcium chloride and distilled. The distillate is again treated with sodium thiosulphate solution and with water, dried and distilled. The fraction 200° — 220° is allowed to stand in a freezing mixture, and the mother liquor is then poured off from the crystals which form. The product is purified by repeated distillations. CH 2 : CH.CH 2 I + 3Br = CH 2 Br.CHBr.CH 2 Br + L Colourless glistening prisms ; insoluble in water ; M.P. 16° ; B.P. 219° — 220°. (A. Ch., [3], 48, 304 ; [3], 51, 91 ; C. r., 70, 638 ; A., 156, 168.) Reaction CLXVIII. Replacement of Hydrogen by Molecular Halogen. — Chloro- and bromo-derivatives of the aliphatic hydrocarbons are obtained by the action of chlorine and bromine on these hydrocarbons in presence of light, the reaction being more energetic in sunlight than in diffused light. The corresponding iodo-derivatives cannot be obtained in this way, due, it is supposed, to the energetic reducing action of hydriodic acid, which converts the iodo-derivative into the original paraffin. CH 4 + I 2 -> CH 3 I + HI -> CH 4 + I 2 . In the case of aromatic bodies the temperature has an important influence on the part of the molecules the chlorine or bromine will attack ; in the cold in the presence of carriers, the halogen enters the nucleus, while at the boiling point the side chain is attacked. The carriers most frequently used are : iron, aluminium-mercury couple, iodine, halides of phosphorus antimony, iron or aluminium, sulphur. The halogen is always more active in sunlight, or in ultra-violet light. A solvent is frequently employed, either to dissolve the compound or to moderate the action of the halogen ; those commonly employed are carbon tetrachloride, glacial acetic acid, carbon disulphide, ethylene dichloride, chloroform, ether, water, hydrochloric acid, sulphuric acid. It is not always a matter of indifference what solvent is selected. 342 SYSTEMATIC ORGANIC CHEMISTRY In some cases the operation has to be conducted in a sealed tube under pressure, and if a solvent is also employed carbon tetrachloride is generally the most suitable. Preparation 341. — Dibrom-sulphanilic Acid (2.6-Dibrom-l-amino-4- benzene sulphonic acid). C 6 H 2 Br 2 (NH 2 )(S0 3 H). C 6 H 5 0 3 NBr 2 S. 331. 10 gms. (1 mol.) of sulphanilic acid are dissolved in about 1 litre of warm water. The solution, when cold, is placed in a large bottle or flask which is connected to a suction pump on one side, and to a wash-bottle containing 18-5 gms. (2 mols.) bromine on the other. In this way a stream of air laden with bromine vapour is drawn through the solution. When the bromine has completely disappeared, the liquid is filtered, and concentrated on a water bath until a sample yields a large crop of crystals on cooling. The whole is allowed to cool, the crystals separated and dried. The mother liquor may yield a second crop after further concentration. C 6 H 4 (NH 2 )(S0 3 H) + 2Br 2 -> C 6 H 2 Br 2 (NH 2 )(S0 3 H) + 2HBr. Yield. — 90% theoretical (16 gms.). Colourless needles ; soluble in hot water ; decomposes at 180°. (A., 120, 138.) Preparation 342.— Chlor-benzene (Phenylchloride). C 6 H 5 C1. 112-5. 100 gms. of pure, dry benzene are heated to boiling with 1 gm. wrought iron powder in a large round-bottomed flask with reflux condenser attached. A stream of dry chlorine is passed through at a temperature of 79° with vigorous stirring. It is essential that the chlorine should be dried, and at least three wash-bottles of cone, sulphuric acid and a calcium chloride tube are recommended. The hydrochloric acid evolved during the reaction may be absorbed in a flask which contains a layer of water. Chlorine is passed in until about 90% of the calculated quantity is used up. The chlorination lasts about 5 hours, and the weight should be increased by 43 gms. The gas should be well regulated, otherwise unchanged benzene will be carried off. If the chlorine inlet tube becomes stopped up with dichlor-benzene, the stream of gas should be interrupted for a time when the solid will dissolve again. The chlorination mixture is allowed to stand, and is poured off from the iron sludge. The mixture is rectified by means of a fractionating column. Approximately, the following fractions will be obtained : — B.P. 0/ /o Composition. 79°- -81° 3 Benzene. 81°- -125° 10 Benzene and chlor-benzene. 126°- -133° 85 Chlor-benzene. 133° -180° 5 Chlor-benzene and dichlor-benzene. 5 Resinous matter and loss. THE LINKING OF HALOGEN TO CARBON 343 The fraction 126° — 133° is redistilled through the column, and the fraction 131°— 132° collected. C 6 H 6 + Cl 2 -> C 6 H 5 C1 + HC1. Yield.— 90% theoretical (130 gms.). Colourless liquid ; B.P. 132° ; D. ( » 1-1284. (B., 11, 117 ; 26, 1053.) Preparation 343. — j9-Bromophenol. OH<^ ^>Br. C 6 H 6 OBr. 174. 100 c.cs. of carbon disulphide and 100 gms. of phenol are placed in a round-bottomed flask fitted with a mechanical agitator, and to which is attached a reflux condenser and a dropping-funnel through a rubber stopper. 170 gms. of bromine (54-6 c.cs.) dissolved in 50 c.cs. of carbon disulphide are placed in the dropping-funnel. The flask is cooled below 5° in a freezing mixture, and after starting the agitation the bromine is slowly run in, the addition requiring about 2 hours. The mixture is distilled to remove the carbon disulphide. The residue is distilled in vacuo, using a Claisen flask and a good fractionating column. The fraction 145° — 150° at 25 — 30 mms. is collected, and on cooling sets to a solid white mass, which may be dried by pressing. OH<^ Br 2 -> OH<^ ^>Br. F^R— 80— 84% theoretical (145—155 gms.). M.P. 63°— 64°. Note. — The jobromophenol should not be allowed to come in contact with the stopper. (A., 137, 200; B., 7, 1176; "Organic Syntheses," Vol. I., Roger Adams, and others.) Preparation 344. — Benzal Chloride (Phenyl-dichlor-methan). <^ ^>CHC1 2 . C 7 H 6 C1 2 . 161. 445 gms. toluene and 10 gms. phosphorus pentachloride are heated to boiling in a litre flask provided with a reflux and agitator. Dry chlorine is passed in through the liquid until the increase in weight is 355 gms. The chlorination is facilitated by bright sunlight, or by ultra-violet light. The chlorination mixture is then fractionally distilled and the fraction between 160° — 225° collected. This fraction is further fractionated, and the fraction between 200° — 210° collected and purified by distillation. The impurities present after chlorination are unchanged toluene, benzyl-chloride and benzo-trichloride. ^>CH 3 + 2C1 2 -> <^ ^>CHC1 2 + 2HC1. Yield.— 85% theoretical (660 gms.). Colourless liquid ; B.P. 206° ; D. 1-2557. (A., 116, 336 : 146, 322 ; 139, 318.) 344 SYSTEMATIC ORGANIC CHEMISTRY Preparation 345 —Benzyl Chloride (Phenyl-chlor-methan). C 6 H 5 .CH 2 .C1. C 7 H 7 C1. 126-5. 50 gms. of toluene are placed in a tared retort (see Fig. 52), the tubulus of which is sloped upwards and connected to a water reflux condenser carrying a straight calcium chloride tube at the end. 2 gms. phosphorus pentachloride or phosphorus trichloride to act as chlorine carrier are also placed in the retort. The toluene is boiled and a stream of dry chlorine is led through the liquid by a delivery tube fixed by a cork (an ordinary cork, previously soaked in melted paraffin wax should be used) in the neck of the retort. The retort is weighed periodically, and the stream of chlorine continued until an increase in weight of 18-5 gms. takes place. The product is distilled, the fraction 165° — 185° being collected ; this is Fig. 52. redistilled, collecting the fraction 176° — 180°, which is practically pure benzyl chloride. C 6 H 5 .CH 3 + Cl 2 C 6 H 5 CH 2 C1 + HC1. Yield.— 60% theoretical (40 gms.). B.P. 176°. (A, 1853, 88, 129 ; B., 18, 606 ; A, 272, 149.) Preparation 346. — j>Nitrobenzyl Bromide. N0 2 .C 6 H 4 .CH 2 Br. C 7 H 6 0 2 NBr. 216. Method I. — 5 gms. pure ^-nitrotoluene, 2 c.cs. of bromine, and a crystal of iodine are placed in a sealed tube. The tube is placed in a bomb furnace and gradually heated up during 40 minutes to 130°, at which temperature it is maintained for 160 minutes. After cooling, the tube is opened and the product extracted with about 60 c.cs. of hot alcohol. From the resulting solution crystals separate on cooling, which are filtered off ; a second crop is obtained after concentrating and cooling THE LINKING OF HALOGEN TO CARBON 345 the mother liquor. Water is added to the final mother liquor to precipitate a small quantity of the nitrobenzyl bromide, which is filtered off, dried, and purified by recrystallisation from petroleum ether. The first and second crops should be washed with cold petroleum ether. Yield. — 75% theoretical (6 gms.). Method II. — 10 gms. of ^-nitrotoluene dissolved in 100 c.cs. of carbon- tetrachloride and a crystal of iodine are placed in a silica flask provided with a reflux condenser. The solution is covered with a layer of water (about 50 c.cs.) and heated to gentle boiling, while situated about 15 cms. from a mercury vapour lamp. A solution of 15 gms. bromine in 50 c.cs. carbon tetrachloride is then run in drop by drop from a dropping-funnel at the top of the condenser. When all the bromine is in, boiling is con- tinued until the solution becomes almost colourless. The contents of the flask are cooled, transferred to a separating funnel, and the lower carbon tetrachloride layer run into a distilling flask. Carbon tetrachloride is distilled off over a water bath, and the residue of ^-nitrobenzyl bromide reCrystallised from alcohol or petroleum ether. N0 2 .C 6 H 4 CH 3 + Br 2 -> N0 2 C 6 H 4 CH 2 Br + HBr. Yield.— 80% theoretical (12-6 gms.). Needles ; M.P. 99°— 100°. (See also Am. Soc, 40, 406.) Preparation 347. — Tetrabrom-diphenylamine (2.4,2. 4-Tetra-brom-l- l'-diphenylamine). Br.f YBr Brf )Br C la H 7 NBr 2 . 485. 4 gms. (1 mol.) of finely powdered diphenylamine are agitated with a sufficient quantity of cold glacial acetic acid to dissolve it. The solution is stirred while 5 c.cs. (4 mols.) of bromine dissolved in 50 c.cs. glacial acetic acid are slowly run in. The tetrabrom-diphenylamine formed separates as a precipitate, which is filtered off and recrystallised from alcohol. (C 6 H 5 ) 2 NH + 4Br 2 -> (C 6 H 3 Br 2 ) 2 NH + 4HBr. Yield. — Theoretical (12 gms.). Colourless needles ; M.P. 182°. (A., 132, 166 ; B., 8, 825.) Preparation 348. — m - Bromobenzoic Acid (1 - Carboxyl - 3 - brom- benzene). Br <^ ^>COOH. C 7 H 5 0 2 Br. 201. 6 gms. (1 mol.) of benzoic acid, 8 gms. (1 mol.) of bromine, and 40 gms. of water are heated together in a thick-walled sealed tube to about 140° — -150° in the usual type of furnace for 9 hours. After cooling, the tube is opened with the usual precautions, and the colourless crystals of bromobenzoic acid washed out, filtered, and boiled with 100 c.cs. of water 346 SYSTEMATIC ORGANIC CHEMISTRY in a basin for 1 hour to remove unchanged benzoic acid. The residual bromobenzoic acid is then recrystallised twice from hot water. C 6 H 5 .COOH + Br 2 = C 6 H J .Br,CO.OH -f HBr. Yield— 80% theoretical (8 gms.). . Colourless needles ; soluble in hot water ; M.P. 155°. (A., 149, 131.) Preparation 349. — Dibrom-succinic Acid (2.3-Dibrom-butan-diacid). CHBrCOOH C 4 H 4 0 4 Br 2 . 276. CHBrCOOH 12 gms. (1 mol.) of succinic acid, 32 gms. (1 mol.) of bromine, and 12 gms. of water are heated in a sealed tube for 6 hours at 170° (see p. 38). The tube is then opened in the usual way. The greyish-white mass with which the tube is now filled is recrystallised from boiling water, with the addition of a little animal charcoal. CH 2 .COOH CHBrCOOH j + 2Br 2 = j + 2HBr. CH 2 .COOH CHBrCOOH. Yield. — Theoretical (27 gms.). Colourless glistening crystals ; soluble in hot water, soluble in alcohol and in ether ; decomposes at 200° with formation of hydrobromic acid and brom-maleic acid. (A., 117, 120 ; A. Spl., 1, 351 ; BL, 18, 168.) Preparation 350. — a-Bromonaphthalene. Br 116 gms. of naphthalene (flakes) and 125 c.cs. of water are placed in a pot fitted with a good mechanical agitator and heated to 40°- — 50°. 145 gms. (45 c.cs.) of bromine are then gradually dropped in from a dropping- funnel dipping to the bottom of the pot, at such a rate that the temperature is maintained at 40° — 50°. The addition takes 8 — 9 hours. After all the bromine has been added, stirring is continued until the colour has practically disappeared. The mixture is allowed to cool, and a heavy oil separates. The oil is steam-distilled on an oil bath at 145° — 150°, this process removing the hydrobromic acid and some unchanged naphthalene. The oil is distilled in vacuo, the fraction 132°— 133° at 12 mms. (145°— 148° at 20 mms.) being collected. The lower fractions contain naphthalene, and the higher, 1.4-dibromo- naphthalene. C 10 H 8 + Br 2 = C 10 H 7 Br + HBr. Yield.— 55— 60% theoretical (100—110 gms.). (A, 135, 40 ; 147, 166 ; " Organic Synthesis," Vol. I., Roger Adams, and others.) THE LINKING OF HALOGEN TO CARBON 347 Pkeparation 351 . — Tribrom-s-xylenol. (CH 3 ) 2 C 6 Br 3 (OH). C 8 H 7 OBr 3 . 359. A few gms. of xylenol are placed in a large test tube, or small beaker, and covered with about 20 times their weight of water. Bromine is gradually added drop by drop until an excess is indicated by a reddish- brown colour which does not disappear. Sulphur dioxide, either as aqueous solution or gas, is added until the excess of bromine is removed. The precipitate is filtered off, washed with water, and recrystallised from alcohol. CH = C(OH) C.Br = C.OH CH 3 C^ ^CH + 3Br 2 CH 3 C<^ ^- Br + 3HBr. CH — C.CH 3 X CBr C.CH 3 Yield.— 90% theoretical. Fine needles ; M.P. 166°. (B., 18, 2679 ; A., 281, 122.) Preparation 352. — Tribromophenol (1 - Hydroxy - 2.4.6 - tribromo- benzene). C 6 H 2 (OH)Br 3 . C 6 H 3 OBr 3 . 331. 5 gms. (1 mol.) of phenol are dissolved in 100 c.cs. of water, and to the cold solution 8-3 c.cs. (3 mols.) of bromine in aqueous solution are added. The precipitate, which is almost insoluble in water, is filtered off, washed with water, and recrystallised from dilute alcohol. C 6 H 5 (OH) + 3Br 2 -> C 6 H 2 Br 3 (OH) + 3HBr. Yield.— Theoretical (17 gms.) Colourless needles ; M.P. 95°. (A., 43, 212 ; 137, 208.) Preparation 353 . — /y-Brom-dimethylaniline. C 6 H 4 BrN(CH 3 ) 2 . C 8 H ie NBr. 200. 10 gms. dimethylaniline are dissolved in glacial acetic acid, and 6-6 gms. bromine dissolved in glacial acetic acid gradually added. When the solution is diluted with water, the ^-brom-dimethylaniline is precipitated, filtered off, and recrystallised from alcohol. C 6 H 5 N(CH 3 ) 2 -> C e H 4 Br.N(CH 3 ) Yield.— Ahaost theoretical (16—17 gms.). White plates ; M.P. 55°. (B., 8, 715.) Preparation 354. — Benzoyl Chloride. C 6 H 5 C0C1. C 7 H 5 0C1. 140-5. Dry chlorine is led into cold benzaldehyde (for apparatus see p. 344). The chlorine is easily absorbed with evolution of heat, torrents of hydro- chloric acid being given off. When the reaction has moderated some- what, heat is applied in order to keep the liquid boiling briskly, the stream of chlorine being continued until the evolution of hydrochloric acid ceases. The excess chlorine is removed by passing a stream of dry 348 SYSTEMATIC ORGANIC CHEMISTRY air or carbon dioxide through the apparatus. The product is then distilled. X H \C1. I teld. — Almost theoretical. Colourless, fuming liquid, with irritating smell ; B.P. 198° ; D. " 1-214. (A., 3, 1262.) * Preparation 355. — Chloral, CCl 3 CHO C 2 H0C1 3 . 147-5. 100 c.cs. absolute alcohol are placed in a retort, with the side tube on the slant and attached to a reflux, and which can be cooled. A current of dry chlorine is passed into the alcohol, the temperature being kept below 10°. The gas is quickly absorbed at first, but the absorption slackens off. The contents of the retort are heated to 60°, while chlorine is still passed, as long as it is absorbed. The liquid is then boiled gently and cooled— its specific gravity should now be 1-400. An equal volume of cone, sulphuric acid is now cautiously added, ethyl chloride and hydrochloric acid being evolved. The mixture is distilled from a water bath. The distillate is neutralised with chalk and again distilled and finally fractionated, the fraction boiling at 93°— 96° being retained.' CI CI CH 3 CH 2 OH -> CH 3 CHO -> CCI3CHO. Colourless liquid ; characteristic odour ; B.P. 94-5°. (Z Ch 1870 172; A., 279, 293.) K ' . ' When chloral is mixed with J its weight of water, the mixture gradually solidifies to a crystalline mass of chloral hydrate. CCI3CHO + H 2 0 -> CC1 3 CH(0H) 2 . Colourless crystals; M.P. 57°; B.P. 97°. with decomposition: is converted into chloral by sulphuric acid. (Z., 1870, 172, 351.) Preparation 356.— Mono-chloracetic Acid. CH 2 Cl.COOH. C 2 H 3 0 2 C1. 94-5. 100 grns. glacial acetic acid and 10 gms. of sulphur are placed in a small flask and the whole weighed. The flask is fitted with a two-holed cork, one hole being fitted with an adapter, to which is attached a reflux con- denser, while the other is fitted with a delivery tube reaching down into the acid. The flask is heated on a boiling water bath, and a steady current of chlorme passed into the acid, until (about 6 hours) a gain m weight of 50 gms. has taken place. As it has a catalytic accelerating effect on the operation it is important to place the apparatus in direct sunlight. When the required increase has taken place, the liquid is decanted from the sulphur into a distilling flask and distilled through an air condenser. Acetyl chloride, sulphur chloride and acetic acid come over at first. The fraction 150°— 190° is collected separately ; this yields crystals of mono-chloracetic acid, on cooling ; the liquid is drained off THE LINKING OF HALOGrEN TO CARBON 349 Tom the crystals, the latter redistilled, and the fraction 180° — 190° jollected. CII a .COOII + Cl 2 CH 2 Cl.COOH + HCL Yield. — 45—60% theoretical (75—100 gms.). Colourless crystals. tf.P. 62°— 63°; B.P. 185°— 187°. (Bl. [3], 2, 145.) Preparation 357 . — Trichloraniline. Cl_ NH,^ ^>C1. C 6 H 4 NC1 2 . 196-5. Cl 10 gms. of dry aniline are dissolved in 200 gms. dry carbon tetrachloride, md placed in a flask fitted with a mechanical agitator (see Fig. 37). Fhe flask is surrounded by an efficient freezing mixture, so that the emperature is about — 10°. Through one of the side tubes is passed Iry chlorine mixed with dry carbon dioxide (equal volumes). A white srystalline deposit of trichloraniline is thrown down, but if the tempera - ure is allowed to rise or the materials used not absolutely dry, the product s contaminated with aniline black. The crystals are filtered off and ecrystallised from alcohol. _CI <^ )nh 2 -> ci<( )nh, Cl Yield. — Almost theoretical (21 gms.). White needles; M.P. 77-5°: 3.P. 262°. CHAPTER XXIII THE LINKING OF HYDROGEN TO NITROGEN Amino Compounds Reaction CLXIX. Action of Metals on Nitro Compounds in Acid Solution. — N0 2 -> NH 2 . The metals used are iron, zinc, tin ; and the acids, hydrochloric, sulphuric, and in some cases acetic. As a rule, the best temperature for the reduction is about 100°, and in some cases the nitro compound may be dissolved in a suitable solvent. In all cases, good mechanical agitation is essential to prevent the metal settling to the bottom of the pot. When iron is used along with hydrochloric acid, the acid acts as a catalyst, and very little need be used in the reaction (see note under aniline). The amine is obtained in the form of its salt, the base being liberated by caustic soda. The amine, if volatile in steam, is separated by steam distillation ; solid amines are separated by filtration. Sometimes the amine may be extracted with ether, but before this is done the metal should first be removed. Where zinc and tin are used, double salts of the general formula, R.NH 2 .HC1.MC1 2 , sometimes separate out when the reductim is com- plete, e.g., chlor-anilines. These salts may be decomposed my excess of caustic soda, and the base isolated as before. The reaction is applicable to both aliphatic and aromatic nitro com- pounds. Preparation 358. — Aniline (Amino-benzene). C 6 H 5 NH 2 . C 6 H 7 N. 93. I This compound should be made in a closed pot, to which very efficient agitation is fixed, and attached to a reflux condenser, as shown in Fig. 36. The metal used in this reduction is iron, and should be in as fine a state as possible. * 60 c.cs. of water and 120 gms. of iron powder, are placed in the reduction pot, agitation being maintained during the addition. The pot is then heated to 90° — 95°, and 10 c.cs. cone, hydrochloric acid (D. 1-18) is poured in ; 100 gms. nitrobenzene are then added, a few c.cs. at a time. The temperature must be held at 100° C, and this can be conveniently done by regulating the addition of the nitrobenzene. When all the latter has been added, the reduction is continued at about 100° C. until no smell of nitrobenzene remains, or until a sample dissolves completely in hydrochloric acid. 350 THE LINKING OF HYDROGEN TO NITROGEN 351 If the agitation is not powerful enough to carry through this process, the following may be adopted : 100 gms. of nitrobenzol and 60 c.cs. water and 10 c.cs. of cone, hydrochloric acid (D. 1-18) are heated in the pot up to 95° C. 1 20 gms. iron powder is then added carefully, the temperature being maintained at about 100° C. After all the iron has been added, the temperature is maintained at 100° C. by external heat, and agitation continued until all the nitrobenzene has been reduced. Steam Distillation. — If direct steam can be led into the reduction pot, this process is simplified, for, by merely altering the condenser to the usual sloping position, the aniline can be distilled off. If no direct steam can be lead into the reduction pot, the contents, after the reduction is finished, are poured into a large round-bottomed flask, and steam from a steam generator led into it, the products of vaporisation being condensed in the usual way (see Fig. 14). Separation. — The condensate is poured into a separating funnel and allowed to stand until separation into two layers is complete. This may be assisted by applying heat or by adding salt. The aniline is then poured off and dried over solid caustic soda and then distilled. C e H 5 N0 2 + 3Fe + 6HC1 -> C 6 H 5 NH 2 + 3FeCl 2 + 2H 2 0. Yield.— 95% theoretical (70 gms.). B.P. 184° ; D. 1-026 ; important intermediate for dyestuffs. Note. — The quantity of hydrochloric acid used in an acid reduction where iron is employed is only about ^ of the quantity required by theory. This is explained by the fact that the hydrochloric acid acts as a catalytic agent. (1) Fe -f 2HC1 -> FeCl 2 + H 2 . (2) FeCl 2 + 2H 9 0 -> Fe(OH) 2 + 2HC1. (3) 2.RNH 2 .HC1 + Fe -> 2.ENH 2 + FeCl 2 + H 2 . Equation (1) shows the first reaction between Fe and HC1. Equation (2) shows the formation of Fe(OH) 2 , which is itself a powerful reducing agent. It is possible to reduce nitrobenzene to aniline with alkaline ferrous sulphate (Fe(OH) 2 ). Equation (3) shows the regeneration of FeCl 2 and H by the action of the metal on the hydrochloride. It is possible to reduce nitrobenzene with a non-substituted ammonium salt, e.g., ammonium chloride and a metal (D.R.P., 89978). (A., 55, 200 ; B., 19, 903 ; 13, 1298 ; 19, 2916.) Peeparation 359. — o- and £>-Toluidine (1*2 and 1'4-Methyl amino benzene). eH 3 <^ \andCH 3 / ^>NH 2 . C 7 H 9 N. 107. The reduction of nitrotoluene is similar to that given for nitrobenzene under aniline (p. 350). The steam distillation is similar, the ortho- and ??ara-compounds formed in the reduction passing over. Separation cfo- and p-Toluidine (a).— The oil is separated from the water and ice and salt added and the mixture stirred. A whitish-yellow 352 SYSTEMATIC ORGANIC CHEMISTRY crystalline compound will appear, which is the hydrate of the jo-compound . This is filtered off through an ice filter, and the hydrate well pressed to remove any adhering oily or^o-compound. The or^o-compound passes through the filter along with the water, and is separated, as in the separa- tion of aniline. The £>ara-compound is recrystallised from alcohol. (J. S. C. I., 27, 258.) Separation of Pure o-Toluidine (b). — The mixture containing the o- and ^-compounds is dissolved in hydrochloric acid until slightly acid to Congo Red, and water added until the solution is saturated at ordinary tempera- ture. Saturated aqueous sodium ferrocyanide is then gradually added with shaking, when the greenish-white needles of o-toluidine hydro- ferrocyanide come down. The solution, after precipitation is complete, is still slightly acid. The o-compound is filtered off, washed with a little water, and a very little dilute hydrochloric acid. It is dried, and the base obtained from it by decomposing with caustic soda and extraction with ether. After drying the ethereal solution with potassium carbonate, and removing the ether, the base distils at 198°. NQ 2 NH 2 CH 3 <^ ^ > CH 3 <^ ^) Yield— 90— 95% theoretical (total o and p). b, B.P. 198° ; D. 1-003 ; p, M.P. 45° ; B.P. 200° ; D. 1-046 ; important intermediate for dves. (J. C. S., 121, 1294.) Pkeparation 360. — a-Naphthylamine. NH 2 '[ ) j C 10 H 9 N. 143. The reduction is similar to that of nitrobenzene (Preparation 358), but no condenser need be used in this case. 120 gms. iron powder and 60 c.cs. water are placed in the reduction pot, and the temperature raised to 95°. 10 c.cs. of cone, hydrochloric acid are then poured in and 100 gms. a-nitronaphthalene added gradually. The reduction is continued until a sample is completely soluble in hydrochloric acid. Separation. — The steam distillation is carried out as in Preparation 358, using in this case superheated steam. A convenient apparatus for producing superheated steam is shown in Fig. 15. The naphthylamine is then filtered off and crystallised from benzene or toluene. Yield.— 80— 85% theoretical (65—70 gms.). M.P. 51° ; B.P. 300° ; D. 1-23. A small percentage of ^-naphthylamine is formed in the reduction. (J. pr., 27, 140 ; A., 92, 401 ; 275, 217.) Preparation 361 . — m-Phenylene-Diamine (Hydrochloride) . NH 2 <^ ^>NH 2 .HC1. C 6 H 9 N 2 CJ. 144-5. This process is carried out in the usual reduction pot with reflux attached (see Fig. 36). THE LINKING OF HYDROGEN TO NITROGEN 353 150 c.cs. water are placed in the reduction pot and heated up to 95° C, and 100 gms. m-dinitrobenzene (M.P. 91° C.) are then added. 10 c.cs. of cone, hydrochloric acid, and about 120 gms. of fine iron powder are added gradually, care being taken that the contents do not froth over. This process is carried on until the solution loses its yellow colour, as may be shown by spotting on filter paper. A solution of sodium carbonate is then added until an alkaline reaction is obtained. It is boiled and filtered from the iron residue. The iron residue is again boiled with water and filtered. The combined filtrates are evaporated to a convenient bulk and cone, hydrochloric acid added to precipitate the hydrochloride. This is allowed to cool, and is filtered and dried. NO, NH 2 Yield.— 90% theoretical (77 gms.). M.P. 61° ; B.P. 283°. (J., 1861, 512 ; 1863, 422 ; Z. Ch, 1865, 51.) Preparation 362. — /9-Phenylene-Diamine. NH 2 <^ ^>NH 2 . C 6 H 8 N 2 . 108. The process is similar to that used for making the meto-compound. In this case, however, j9-nitraniline (M.P. 148°) is added to the mixture of iron powder, water, and acid. The following quantities are used : — 100 gms. iron powder ; 5 c.cs. cone, hydrochloric acid ; 100 c.cs. water. These are heated to 95° 0. and 100 gms. ^-nitraniline gradually added. Cooling may have to be applied to regulate the action. The reduction is continued as in Preparation 361 until the liquid loses its yellow colour. Sodium carbonate is added, as before, until alkaline. After the iron residue is filtered of! the filtrate is concentrated until the base crystallises. NQ 2 <( )NH 2 -> NH 2 ( )NH 2 . Yield.— 90% theoretical (57 gms.). M.P. 147° ; B.P. 267°. (J., 1863, 422 ; B., 7, 871 ; 28, 250.) Preparation 363.— Metanilic Acid (Aniline m-sulphonic acid). SQ 3 H. NH 2 / y C 6 H 7 0 3 NS. 173. Nitrobenzene m-sulphonic acid is prepared as on p. 306. The reduction is carried out, using iron powder, as in H acid (p. 307). After the reduc- tion is neutralised and filtered, the filtrate is concentrated to about 600 c.cs. Hydrochloric acid is added until an acid reaction to Congo is obtained. The metanilic acid then crystallises out. The separation may be assisted by adding common salt. Yield. — 80% theoretical. (Crystallises with |H 2 0 of crystallisation ; intermediate for dyestuffs. (Z. a., 9, 686.) S.O.C. A A 354 SYSTEMATIC ORGANIC CHEMISTRY Preparation 364— Diamido Stilbene Disulphonic Acid. SQ 3 H SO3H NH 2 <^ ^>CH = CH<^ ^>NH 2 . C 14 H 14 0 6 N 2 S 2 . 370. The sodium salt of the dinitro acid from Preparation 294 is dissolved in 300 c.cs. hot water, and hydrochloric acid is added to neutralise any free sodium carbonate. The solution is run on to 200 gms. of iron turnings, which have been previously etched by standing in 20 c.cs. of 40% acetic acid. The reduction proceeds in the normal way. The clear solution is made strongly acid to Congo with hydrochloric acid, and the diamido stilbene sulphonic acid separates as yellow crystals. After 10 hours it is filtered of! and washed. Yield. — About 40% (calculated on ^9-nitrotoluene). Important inter- mediate for dyestuffs. (B., 30, 3100.) Preparation 365. — 4- Amino m-Hydroxy Benzoic Acid. OH COOH^ ^NH 2 . C 7 H 7 0 3 N. 153. 10 gms. 4-nitro-m-hydroxy benzoic acid (see p. 262) and 200 c.cs. cone, hydrochloric acid are heated on a water bath, and 30 gms. of tin slowly added. After the reaction is complete the double tin salt separates out, and is filtered. The precipitate is dissolved in 200 c.cs. of warm water and hydrogen sulphide passed until all the tin is separated. The filtrate from the tin is concentrated until crystals of the hydrochloride begin to separate. When cold, the hydrochloride is filtered, dissolved in a little water, and the free base precipitated by the addition of a cone, solution of sodium acetate. It is filtered, washed with water, and recrystallised from hot water or dilute alcohol. COOH COOH OH<^ ^NO, -> OH<^ \NH 2 . Yield.— 60% theoretical (5 gms.). M.P. 115°— 116°. (J. C. S., 119, 1429.) Preparation 366. — ^-Amino-acetanilide. NH 2 <^ ^>NH.COCH 3 . C 8 H 10 ON 2 . 150. 93 gms. of aniline are converted into acetanilide, and then to nitro- acetanilide, as shown in the preparation of jo-nitraniline (p. 268). The moist nitro-compound is then added in small portions to a vessel fitted with good agitation (see Fig. 36), and containing 125 gms. iron filings, 8 c.cs. 40% acetic acid and 500 c.cs. water heated to boiling. Boiling is continued for 10 minutes after the last addition, when the solution " spotted " on filter paper should be colourless. The liquid is then cooled to 70°, and sodium carbonate is added until the reaction is alkaline.* The precipitation of the iron is completed by adding the minimum * If the sodium carbonate is added at 100° or in excess, hydrolysis of the nitroacetanilide takes plac^. THE LINKING OF HYDROGEN TO NITEOGEN 355 quantity of ammonium sulphide until a drop on filter paper gives no coloration with sodium sulphide. The whole is then filtered, and the filtrate evaporated to 400 c.cs., when, on cooling, the amino -ace tanilide crystallises in long needles. A further crop of crystals may be obtained by evaporating the mother liquor. N0 2 <^ ^>NH.COCH 3 -> NH 2 / ^>NH.CO.CH 3 . Yield.— 55% theoretical (80—90 gms.). M.P. 162-5° ; on hydrolysis gives ^-phenylene diamine. (B., 17, 343 ; A., 293, 373.) Preparation 367— ^-Phenetidine (l.Ethoxy-4.amino-benzene). C 2 H 5 0<^ ^>NH 2 . C 8 H n ON. 137. 1. ip-Nitrophenetole. — 14 gms. ^-nitrophenol are dissolved in 40 gms. of 10% caustic soda solution, and the solution is placed in an enamel-lined autoclave fitted with a stirrer. 7 gms. ethyl chloride are introduced, and the mixture heated for 7 — 8 hours at 90° — 100°. After cooling, the ^-nitrophenetole is filtered oil and washed with dilute caustic soda to remove unchanged nitrophenol, and then with water. 2. ip-Phenetidine. — 10 gms. ;p-nitrophenetole, 20 c.c. water and 1 c.c. cone, hydrochloric acid are placed in a flask or a sulphonating pot fitted with a good mechanical agitator (see Fig. 36). The temperature is raised to 60°, and iron filings (10 gms.) are gradually introduced over 3 — 4 hours. When all the iron has been added the temperature is raised to 90°, where it is maintained until the reduction is complete. The supernatant aqueous liquor is poured or siphoned off, and the sludge is steam-distilled with superheated steam at 160° — 180°, when the jo-phene- tidine passes over, and is separated from the aqueous distillate by extraction with ether, and purified by distillation. HO^ \NO a -> C 2 H 5 0<^ ^>N0 2 -> C 2 H 5 0<^ ^>NH 2 . Liquid ; B.P. 244°. (Am. Soc. ; 1, 272 ; B., 22, 1782.) Reaction GLXX. Action of Metals on Nitro Compounds in Alkaline Solution. — The metal usually employed is zinc, although iron powder can be used in some cases. The reaction is usually carried out in caustic soda solution, Zn + 2NaOH — > Zn(ONa) 2 -f H 2 , and the reaction takes place in several stages. RN0 2 R — N x R.N = N.R + 6H -> i >0 azoxy— or || RN0 2 R— N'/ O R— N x R — N i > O + 2H -> || azo— R— N/ R . N R — N R.NH || + 2H -> | hydrazo— R . N R.NH A slight excess of metal is required, and each stage can be isolated by 356 SYSTEMATIC ORGANIC CHEMISTRY using the required amount of metal, e.g., § for the azoxy stage, f for the azo stage. Good agitation is essential, and a solvent may be used in some cases. This, however, is not always necessary if the agitation is efficient. The compounds are separated by dissolving out the zinc with ice-cold hydro- chloric acid. The hydrazo compounds, when heated with mineral acids, undergo a rearrangement (benzidine conversion). K.NH — NH.R — > NH 2 K— K.NH 2 . the NH 2 groups taking the ^-position, although a certain amount of o-p- ompound is formed, NH 2 <^__^>NH— NH<( ^> -> )>NH 2f as well as o- and ^-semidines (see p. 155). The sulphates of these last compounds are soluble in water, and they can, therefore, be separated from the ^p-^-compounds by means of sodium sulphate or sulphuric acid. Preparation 368. — Benzidine (4.4 y -Diamino-diphenyl). H 2 N^~ < \nH 2 . C^H^N,. 184. 1. Hydrazobenzene.-— 100 gms. nitrobenzene, 100 gms. of cone, caustic soda (30% solution) and 100 gms. water are placed in the reduction pan (see Fig. 36) and heated to 95° Q'., and all external heat cut off. Zinc dust of good quality (over 85% metallic zinc) is then added, a few gms. at a time. The heat of reaction will raise the temperature to 100° C, and when it cools to 98° C. a few more gms. of zinc dust are added, the temperature being allowed to drop to 98° C. before any further addition of zinc is made. During the course of the reduction small samples are abstracted by means of a rod. It will be noticed that at first a yellowish-red crystalline solid is formed on the rod, then a red crystalline solid, and ultimately all trace of red disappears and a lemon-yellow crystalline solid is formed. When this stage is reached further addition of zinc is stopped, and the whole is allowed to run for \ hour, external heat being applied. In all about 160 gms. of zinc dust will be necessary, the amount, of course, depending on the metallic content of the dust. The whole is quickly cooled by adding a large bulk of cold water to the reduction pot, agitation being maintained. When cooled to 30°, the contents of the pot are poured into a large enamelled bucket. A large quantity of ice is added, and cone, hydro- chloric acid is poured in, with stirring. The temperature should not rise above 5° C. Acid is added until the liquid in the bucket gives an acid reaction to Congo paper. The hydrazobenzene is then filtered off and washed with cold water. 2. Benzidine. — It is then removed to a basin where it is boiled up slowly \ with 500 c.cs. water and 120 c.cs. cone, hydrochloric acid and filtered from THE LINKING OF HYDROGEN TO NITROGEN 357 zinc residue. A saturated solution of sodium sulphate is then added until the benzidine sulphate is completely precipitated (test). This is filtered off and is well washed with warm water until free of acid. The moist benzidine sulphate is removed, heated to 50° C. with a little water, and caustic soda solution (30%) added with stirring until the liquid is just alkaline (test with phenolphthalein). When cold, the free base is filtered off and dried at 50° C. It may be crystallised from benzene or alcohol or from hot water (not boiling). \ / N ° 2 H \ /?\ \ A no,. \ ~\nh Azoxy Azo Hydrazo (yellow -red) (red) (white) M.P. 36°. M.P. 68° M.P. 131° <^ ^NH- NH<^ ^> C1H.H 2 N<^ ^>— <^ ^>NH 2 .HC1. H 2 S0 4 / v / \ , NaOH > H 2 N<^ y— / >NH 2 .H 2 S0 4 > H 2 N<( >NH 2 . Yield. — 75 — 80% theoretical (55 — 60 gms.). Lustrous plates; M.P. 128° ; B.P. over 400°, with decomposition ; slightly soluble in hot water ; soluble in alcohol and in benzene. Important intermediate for dyestuffs. (Z. a, 6, 67.) Pkeparatton 369. — o-Tolidine. CH 3 CH 3 H 2 N<^ )NH, C 14 H 16 N 2 . 212. The process is exactly the same as for benzidine except that 100 gms. of distilled nitrotoluene (containing no more than 4% j9-nitrotoluene) are used. CH 3 CH 3 CH 3 CH 3 / N NH — NH / \ -> Nh/ NnH.. Yield.— 65% 0 theoretical (48 gms.). Plates; M.P. 128°; slightly soluble in water ; soluble in alcohol and in benzene ; salts about 5 times more soluble than those of benzidine ; intermediate for dyestuffs. (B., 17, 467 ; 20, 2017.) Reaction CLXXI. Action of Alkali Sulphides and Hydrosulphides on Nitro Compounds. R.N0 2 -> R.NH 2 . The hydrogen is generated in the solution of alkali sulphide. Na 2 S + 3H 2 0 -> Na 2 S0 3 + 3H 2 . Excess of Na g S is used, which dissolves the sulphur always formed in 358 SYSTEMATIC ORGANIC CHEMISTRY the reaction, due to oxidation. The reaction is specially useful in cases of nitro compounds containing more than one nitro group, and conditions can be chosen such that only one nitro group is reduced, e.g., acid ™, < >N0 2 + 12H > / )>NH 2 . \ ' solution ^ ' Na 2 S ™. The reaction is really an extension of that on alkaline reduction, since the solution of sodium sulphide in water is alkaline. The complete equations are : R.N0 2 + Na 2 S + H 2 0 R.NH 2 + Na 2 S0 3 . 4R.N0 2 + 6NaSH + H 2 0 -> 4R.NH 2 + 3Na 2 S 2 0 3 . Preparation 370. — m-Nitraniline. N0 2 NH 2 / V C 6 H 6 0 2 N 2 . 138. This experiment should be performed in a fume cupboard. 100 gms. m-dinitrobenzene are placed in a beaker with 500 c.cs. water and heated to 85°. The stirring should be very brisk. 245 gms. sodium sulphide (Na 2 S.9H 2 0) dissolved in 200 c.cs. water is then allowed to drop in from a funnel during 10 minutes. The dinitrobenzene is reduced to m-nitraniline. The end of the reaction may be recognised by " spotting " the solution on filter paper, and touching with iron or copper sulphate solution. When the black stain remains for 20 seconds, the reduction is finished and the mixture is cooled down to 20° by adding ice. After standing for several hours the m-nitraniline is filtered off, and may be recrystallised from boiling water. _N0 2 . N0 2 NO / \ -> NH /_J> Yield.— 70% theoretical (58 gms.). M.P. 112-4° ; B.P. 285° ; inter- mediate for azo dyestuffs. (C. Z., 37, 299.) Preparation 371. — Picramic Acid. NH 2 OH<^ ^N0 2 . C 6 H 5 0 5 N 3 . 199. not - 10 gms. picric acid and 10 gms. caustic soda, 35%, are dissolved in 600 c.cs. water in a large flask and heated up to 55° with vigorous stirring, when a solution of 40 gms. crystalline sodium sulphide (Na 2 S.9H 2 0) in 100 c.cs. water is gradually added. 127-5 gms. of powdered picric acid are then added by degrees, concur- THE LINKING OF HYDROGEN TO NITROGEN 359 rently with 220 gms. sodium sulphide in 400 c.cs. of water. The addition of the picric acid should end at the same time as the sulphide solu- tion. The temperature should not rise above 65°, ice being added, if necessary. Stirring is continued for about 10 minutes after all has been added, and then 400 gms. ice are quickly added. The sodium salt of picramic acid is immediately precipitated. After standing for 10 hours it is filtered of! and washed with brine. The free acid is obtained by stirring up the sodium salt with 500 c.cs. water, heating to 80°, and acidifying with dilute sulphuric acid until just acid to Congo Red. Yield. — Almost theoretical (8-5 gms.). Red needles, soluble in water ; M.P. 168°— 169°. (See also A., 88, 281 ; 96, 83.) Reaction CLXXII. Action of Reducing Agents on Azo Compounds. — H 2 X— N : N — Y -> X.NH 2 + H 2 N.Y. This reaction is useful for determining the composition and constitution of azo dyes. The reducing agents employed are usually metal and acid, zinc-dust and water or ammonia, stannous chloride, or sodium hydro- sulphite in alkaline solution. The reaction is carried out with or without heat, until the suspended or dissolved colour gives place to a colourless product. Preparation 372. — a-Amino-/?-Naphthol. NH 2 iOH. C 10 H 9 ON. 159. 50 gms. Orange II. (see Preparation 385) are dissolved in 500 c.cs. boiling water, and to this is added 65 gms. tin dissolved in 375 c.cs. cone, hydrochloric acid. When decolorisation is complete the solution is filtered quickly and on cooling the hydrochloride of amino-naphthol separates out as colourless crystals. Oil OH _ / \_N = N<" ^>S0 3 H J* <( )>NH 2 + H 2 N<^ ^>S0 3 H. / \ / \ \ / \ / Fine needles, slightly soluble in dilute hydrochloric acid and in alcohol. (B., 25, 980.) Preparation 373. — Amino Salicylic Acid. OH COOH^ y C 7 H 7 0 3 N. 153. NH 2 A mixture of 50 gms. of aniline hydrochloride, 60 gms. of cone, hydro- chloric acid, and 300 gms. of ice is diazotised by adding a solution of 360 SYSTEMATIC ORGANIC CHEMISTRY 29 gms. of sodium nitrite in 100 c.cs. of water to the mixture. After 15 minutes the diazonium salt is run into a solution of 53-3 gms. of salicylic acid in 220 gms. of crystallised sodium carbonate and a litre of water. The sodium salt separates, is filtered and washed with a little water. The azo-compound is next boiled with about a litre of water, sodium hydroxide solution added until alkaline and dry sodium hyposulphite (about 135 gms.) added until the reduction is complete. After the aniline is removed by steam distillation, acid is added, and the free amino- salicylic acid separates. )NH 2 -> ( >NNC1 -> ( >N = N< >OH COOH , -f H 2 N^ ^>OH COOH Decomposes at 280°. (B., 32, 81.) Reaction CLXXIII. Action of Reducing Agents on Nitroso Compounds. E.NO -> E.NH 2 . The reduction is usually carried out in acid solution, or with bisulphite. For example, see Preparation 392. Reaction CLXXIV. Reduction of Oximes to Amines with Metallic Sodium or Sodium Amalgam. \ 4H v : NOH > ^>CH.NH 2 + H 2 0. The reaction serves for the production of amines from aldehydes or ketones through the oximes of these bodies. Reduction with metallic sodium is usually carried out in absolute alcoholic or moist ethereal solution. Methyl, ethyl or amyl alcohol may be used, but for various reasons absolute ethyl alcohol is the most frequently employed, the reaction being conducted at or near the boiling point of the alcohol. When ordinary alcohol (about 90%) is used, the sodium spurts about on the surface of the liquid, and most of the hydrogen escapes as gas. With the absolute alcohol, the sodium — with the excep- tion of the first portions added — melts to a ball which remains largely, and at times completely, immersed in the liquid, and hence the hydrogen generated is more liable to react. In some cases the sodium alcoholate formed also acts as a reducing agent, and is thereby converted into the sodium salt of the corresponding acid. When the reduction is carried out with sodium amalgam the oxime is dissolved in aqueous alcohol, and acetic acid and amalgam added at intervals so that the solution is slightly acid throughout the reduction. Preparation 37 4. — a-Phenylethylamine. C 6 H 5 CH(NH 2 )CH 3 . C 8 H n N. 121. 50 gms. acetophenone oxime dissolved in 100 c.cs. absolute ethyl alcohol are placed in a litre round-bottomed flask having a long neck. THE LINKING OF HYDROGEN TO NITROGEN 361 The flask is fitted with, a cork carrying an addition tube (p. 46), and the sloping limb of the latter is attached to a reflux water condenser, while the vertical limb is closed with a cork. A bottle containing benzene and pieces of bright sodium (about 50 gms.) of such a size that they slip easily down the addition tube, is prepared. The flask is heated on a water bath until the alcohol boils. Pieces of sodium (one at a time) are introduced through the vertical limb of the addition tube, a piece of drawn-out glass rod being used to remove the sodium from the bottle, and the benzene adhering need not be removed with filter paper. The first pieces of sodium cause vigorous reaction, but the reaction soon becomes moderate. The alcohol is kept actively boiling all the time. When the reaction becomes sluggish a further 100 c.cs. absolute alcohol are added, and addition of sodium to the boiling solution is continued, as before. Altogether about 500 c.cs. absolute alcohol and 40 gms. sodium are required. The addition of sodium is continued until a test, carried out in the following way, shows that reduction is complete : — A sample (about 2 c.cs.) is withdrawn, diluted with an equal volume of water, and about 2 c.cs. cone, hydrochloric acid added. The mixture is boiled for a minute, and a portion added to hot Fehling's solution (see p. 496). If no reduction of the Fehling's solution takes place the reduction of the oxime is complete. When reduction is complete the flask is cooled in ice water, while the contents are neutralised by the gradual addition of cone, hydrochloric acid — through a tube leading underneath the surface so as to avoid loss of fumes. The sodium chloride, which is precipitated, is filtered off and washed with about 50 c.cs. of 15% hydrochloric acid, the washings being added to the filtrate, which is then placed in a porcelain basin and evaporated nearly to dryness. The residue, when cold, is agitated for some time with an excess of cone, caustic soda solution ; phenyl- ethylamine separates on the surface, and the lower layer contains solid sodium chloride. The liquors are decanted from the solid sodium chloride into a separating funnel ; the sodium chloride is agitated with a little ether, which is also decanted into the funnel. The upper layer of ether and phenylethylamine is separated, and the aqueous layer extracted a second time with ether. The ethereal extracts are mixed and dried over anhydrous sodium sulphate. After standing overnight the sodium sulphate is filtered off, and the phenylethylamine recovered in one of the following ways : — 1. By distillation. The ether is first removed, and the phenylethyl- amine (B.P. 186°) comes over at 180°— 190°. Owing to the fact that phenylethylamine is volatile to a considerable extent in ether vapour, this separation is not so efficient as might be expected. Yield.— 80% theoretical. 2. A current of dry carbon dioxide is passed into the cold, dry ethereal solution, which after some time goes almost solid, owing to the precipita- tion of the carbamate of the amine. The precipitate is filtered off, well pressed down on the funnel, and washed with a little pure dry ether. Carbon dioxide is again passed into the filtrate and any carbamate formed, 362 SYSTEMATIC OKGANIC CHEMISTEY filtered off, and so on, until the final nitrate yields no precipitate on pro- longed passing of carbon dioxide. The total yield of carbamate is pressed out on a porous plate to dry. If it is desired to keep for some time it should be preserved in a stoppered bottle. C 6 H 5 C(NOH).CH 3 -> C 6 H 5 .CH(NH 2 ).CH 3 . 2C 6 H 5 CH(NH 2 )CH 3 + C0 2 -> C 6 H 5 CH(CH 3 )NHCOONH 3 CH(CH 3 ).C 6 H 5 . Yield of Carbamate. — 95% theoretical (calculated on oxime). Since the carbamate is very soluble in alcohol, pure ether should be used for the extraction when the base is recovered as carbamate. The carbamate may be used directly for the resolution of the base (see p. 401). a-Phenylethylamine. — B.P. 186° ; easily soluble in organic solvents ; moderately soluble in water ; strong base ; absorbs carbon dioxide when exposed to air. a-Phenylethylamine Carbamate. — M.P. 101° — 102° ; easily soluble in water or in alcohol ; on heating, dissociates into amine and carbon dioxide. (J. C. S., 83, 1147.) CHAPTER XXIV hydrogen to nitrogen Hydroxylamines and Hydrazines. Reaction CLXXV. — Action of Metallic Zinc on Nitro Compounds in Neutral Solution. E.N0 2 + 4H -> E.NHOH e.g., nitrobenzene gives phenylhydroxylamine. Although the reaction may be carried out by generating the hydrogen by the interaction of zinc and water, better yields are obtained by adding a neutral salt, such as ammonium chloride. In order to prevent the reduction going too far, it is necessary to keep down the temperature. Preparation 375. — Phenylhydroxylamine ( (Hydroxy-amino)-benzene). C 6 H 5 NHOH. C 6 H 7 ON. 109. 12 gms. of nitrobenzene are mixed in a beaker with 250 c.cs. of water containing 6 gms. of ammonium chloride and well stirred, the temperature being kept below 15°. 18 gms. of good zinc-dust are added in four equal parts after intervals of J hour. When the smell of nitrobenzene has disappeared the stirring is stopped. The mixture is filtered at the pump, the filtrate being put on one side, and the precipitate washed, by adding 200 c.cs. of water at 45° while the pump is not working, and then the water gradually sucked through by means of the pump. The filtrate and the washings are separately saturated with sodium chloride, and cooled to 0°. After a short time the phenylhydroxylamine separates out ; it is filtered and dried without washing. / \N0 2 -> / ^NH.OH. Yield. — Almost theoretical (10 gms.). Colourless crystals ; M.P. 81° C. (D.R.P., 89978.) Reaction CLXXVI. Action of Reducing Agents on Diazonium Compounds. EN = NCI + 4H -> R.NH.NH 2 . The reaction is somewhat similar to that of reducing agents on azo- compounds. The hydrazines are universally obtained by this reaction, the same reducing agents being used as in the case of azo-compounds. Preparation 376 . — £>-Nitrophenylhydrazine. N0 2 <^ ^>NH.NH 2 . C 6 H 7 0 2 N 3 . 153. 10 gms. of j9-nitraniline are diazotised (see p. 367). The filtered diazo- 363 364 SYSTEMATIC ORGANIC CHEMISTRY solution is slowly added, with stirring, to 40 cues, of a cold saturated solution of ammonium sulphite (see p. 508) containing 8 c.cs. of cone, ammonia solution. Ammonium nitrophenylhydrazine disulphonate soon separates, and after standing for about an hour in a freezing mixture, is filtered, and the precipitate heated on the water bath with 20 c.cs. cone, hydrochloric acid for a few minutes at 70° — 80°. The solution thus obtained is cooled in ice, and the precipitate which separates is dissolved in a small quantity of water. To this solution a cold concen- trated solution of sodium acetate is added ; the nitrophenylhydrazine separates and is recrystallised from alcohol. N0 2 <^ \NH 2 -> N0 2 <^ \n 2 C1 -> N0 2 <^ ^>NH.NH 2 . Yield. — 15 — 20% theoretical (2 gms.). Orange red needles; M.P. 157°, with decomposition ; soluble in alcohol and in ligroin. (J. C. S., 121, 719.) Peepaeation 37 7 . — Phenylhydrazine. C 6 H 5 NH.NH 2 . C 6 H S N 2 . 108. Method I. — 10 gms. freshly distilled aniline are added to a solution of 30 gms. cone, hydrochloric acid in 75 c.cs. water and diazotised with 8 gms. sodium nitrite in 30 c.cs. water, the temperature being kept about 0°. 30 gms. common salt are added with shaking, and the solution cooled in a freezing mixture. 60 gms. stannous chloride in 25 gms. cone, hydrochloric acid are then added, and after standing for some hours L the hydrochloride of phenylhydrazine separates, is filtered off and washed with a little saturated salt solution. It is transferred to a flask and treated with excess of caustic soda solution, when the free base is extracted with ether. The ethereal solution is dried with caustic potash, and the ether removed by evaporation. The phenylhydrazine may be purified, if desired, by freezing or by distilling in vacuo. . H 2 C 6 H 5 NH 2 -> C 6 H 5 N 2 C1 > C 6 H 5 NH.NH 2 .HC1. Yield. — 90% theoretical (10 gms.). Method II. — 10 gms. aniline are dissolved in acid and water and diazotised as before. The diazo solution is poured into a saturated solution of sodium sulphite containing 34 gms. Na 2 S0 3 . The liquid is now heated with zinc dust and a little acetic acid till it becomes colourless, when it is filtered hot. Sodium phenylhydrazine sulphonate passes into the filtrate, and is immediately mixed with one-third of its volume of fuming hydrochloric acid (caution !) which converts it into phenyl- hydrazine hydrochloride, which is thrown out of solution, filtered, and well pressed. The free base is liberated as before. Yield. — 75% theoretical (8 gms.). Colourless crystals ; M.P. 23° ; B.P. 763 243-5° (decomposition); B.P. 12 120°; soluble in alcohol, ether, benzene. (B. 3 16, 2976 ; 26, 19 ; 31, 346.) CHAPTER XXV the linking of nitrogen to nitrogen Diazonium Compounds. Reaction CLXXVIX. — Action of Nitrous Acid on Primary Aromatic Amines. Diazonium compounds are formed in this way. C 6 H 5 NH 2 + HN0 2 + HC1 C 6 H 5 NH 2 + NaN0 2 + 2HC1 Diazonium compounds are usually prepared in mineral acid solution, and the nitrous acid generated from sodium nitrite. Sufficient acid must be used to generate nitrous acid and to form the salt of the base, and still leave the solution acid. In practice 2| — 2J mols. of hydrochloric acid are generally employed. In most cases it is essential that the reaction should be carried put at about 0°, as many diazo solutions decompose above this temperature. The reaction goes very readily in some cases ; but in others, and especially where an acid group is present, e.g., naphthylamine sul- phonic acids, the reaction is only carried out with difficulty. It is possible to diazotise a solid, but the reaction is very slow, and if the solid is dissolved and reprecipitated in a fine state of division the action goes much quicker. In the case of acidic substances, the compound is dissolved in sodium carbonate or caustic soda solution, and reprecipitated with the requisite amount of acid and then diazo tised. Compounds such as [1.2.4] amido-hydroxy-sulphonic acid of naphthalene and its isomers cannot be diazotised in mineral acid, as quinone com- pounds are formed, due to oxidation. They are diazotised in neutral solution in presence of copper or zinc salts, or in weak acid solution, such as acetic acid. (D.R.P., 171024.) Diazotisation.— In the ordinary process of diazotisation the base is dissolved in the requisite quantity of acid, with heating if necessary, and excess of ice is added to bring the temperature down to 0°— 5°. Sodium nitrite in the form of a 10% solution is then run in until the end point is reached. The End Point. — The reaction is complete when on stirring after each addition, and testing with starch iodide or starch iodide paper, a distinct 365 -> C 6 H 5 NC1 + 2H 2 0. ill N C 6 H 5 NC1 + NaCl + 2ELO. I 366 SYSTEMATIC OEGANIC CHEMISTRY blue colour is obtained at once. A drop of the solution is removed on a glass rod at intervals and placed on the starch iodide paper, or on a piece of dry filter paper near a drop of starch-iodide solution (see p. 501) . When- ever the blue colour is obtained, and this colour persists when another test is made after 3 minutes, the reaction is complete. A blue colour developed on the starch paper after a time is discarded. The nitrite should be added at such a rate that no free nitrous acid is evolved. It is essential that the starch iodide solution or paper should be tested previously by a very dilute acidified solution of sodium nitrite before any test is made. It is not usually necessary to isolate the diazo salt from solution, although in some cases this separates out as the reaction proceeds. If sufficient acid is not present, an amido azo compound may be precipitated, due to the " coupling " (see p. 275) of the diazonium compound with the excess of base. In fact, this is one method of forming amido azo com- pounds — by diazo tising in presence of about half the quantity of acid necessary for the complete diazotisation. Some diazonium compounds are quite stable, e.g., o-anisidine, while 2>-nitraniline is stable up to 30°. Stable Diazonium Compounds. — Many methods have been devised for preparing stable diazonium compounds for use in the dyeing industry. For example, diazotised j?-nitraniline, when treated with alkali, forms a compound, N0 2 <^ ^)>N — NONa, which is perfectly stable, and can be converted back to the diazonium compound with hydrochloric acid. When the diazonium compound is treated with /? -naphthalene sulphonic acid (Na salt) a stable diazonium compound is produced (Thann and Becker). R — N CI + Na SO Preparation 378. — Diazonium Compounds (in Solution). 1. Aniline. C 6 H 5 NNC1. 9-3 gms. aniline are run into 100 gms. of water and 45 gms. cone, hydro- chloric acid. 100 gms. ice are added, and the whole is stirred till tempera- ture reaches 0°. 7 gms. sodium nitrite (as a 10% solution) are then gradu- ally added, preferably by a tube leading under the surface of the solution. The temperature should not rise above 7° — 8°. Slow stirring is continued all the time, except when tests are being made. When a distinct blue colour is obtained on starch iodide paper at once, which persists after another test in 3 minutes, the diazotisation is complete. 2. Benzidine and Tolidine. C1N 2 C 6 H 4 — C 6 H 4 N 2 C1. The process is similar to above, 184 gms. benzidine o^l-2 gms. tolidine being dissolved by heating in 300 gms. water and 90 gms. cone, hydro- THE LINKING OF NITROGEN TO NITROGEN 367 chloric acid. After cooling to 0°, the diazotisation is carried out as before. In these cases tetrazonium compounds are formed. 3. p-Nitraniline. N0 2 C 6 H 4 N 2 C1. (a) 13-8 gms. j9-nitraniline are powdered and added to a mixture of 150 gms. water, 45 gms. cone, hydrochloric acid, and 150 gms. ice, and stirred for 15 minutes, the temperature being under 5°. 7 gms. sodium nitrite (10% solution) is introduced quickly, the usual test with starch- iodide being applied after all of the nitrite solution has been added. (6) 13-8 gms. jo-nitraniline are added to 70 gms. water and 45 gms. cone, hydrochloric acid, and heated to dissolve. The solution is then cooled and diazotised, as before. 4. H Acid. OH NNC1 34-1 gms. H acid are introduced into 400 gms. water and 6 gms. sodium carbonate at a temperature of 40° — 50°. The solution should be alkaline. This is run into a mixture of 55 gms. hydrochloric acid and 500 gms. water. 7 gms. sodium nitrite (10% solution) are then added — as before — slowly towards the end. 5. Dinitroanihne. NO,/" ^N 2 C1. N0 2 Sodium nitrite (1^ mols.) is dissolved in cone, sulphuric acid by heating to about 50°. It is then cooled to 20°, and finely powdered dinitroanihne (1 mol. ) is gradually added. When all has been added, stirring is continued for 2 hours at 20° — 30°. The solution is then poured on to ice and filtered. The diazonium compound is thus isolated as a paste. Preparation 379. — Diazoaminobenzene. C 6 H 5 N = N.NH.C 6 H 5 . C 12 .H n N 3 . 197. 6 gms. of sulphuric acid and 600 c.cs. of water are placed in a litre beaker, and 20 gms. of aniline added. The solution is warmed to 30°, and a solution of 7-5 gms. of sodium nitrite dissolved in a little water added with constant stirring. The solution is maintained at 30° for 15 minutes, after which it is left to stand for 30 minutes at laboratory temperature. The diazoamino benzene is then filtered off, washed with water, and dried on a porous plate. It may be recrystallised from warm petroleum, but the solution should not be boiled for any length of time as the compound is thereby decomposed. C 6 H 6 N : N.H$0 4 + NH 2 .C 6 H 5 -> C 6 H 5 N : N.NHC 6 H 5 + H 2 S0 4 . 7^.-80% theoretical (17 gms.). Golden-yellow plates ; M.P. 28° ; explodes when heated slightly above its M.P. 368 SYSTEMATIC ORGANIC CHEMISTRY Preparation 380. — Diazobenzene Sulphate (Benzene Diazonium Sul- phate). C 6 H 5 .N(: N).S0 4 H. C 6 H 6 0 4 N 2 S. 202. 15 gms. (1 mol.) of aniline and 140 gms. of absolute alcohol are mixed, and 30 gms. (2 mols.) of cone, sulphuric acid run in, slowly and with constant shaking. The precipitate of aniline sulphate, which first appears, redissolves. The mixture is kept at 30° — 35° (thermometer in liquid), out of direct sunlight, while 20 gms. (1 mol.) of amyl nitrite are dropped in from a tap-funnel. The whole is then left in ice water for \ hour, and the crystals which have separated filtered off at the pump and washed with a little alcohol. As diazobenzene sulphate is explosive the precipitate must be kept moist. In that state it can be used for the various reactions described below.* (C 6 H 5 NH 2 ) 2 H 2 S0 4 + 2C 5 H u ONO + H 2 S0 4 = 2C 6 H 5 N( i N)S0 4 H + 2C 5 H n OH + 2H 2 0. Colourless needles ; soluble in water and methyl alcohol ; slightly soluble in ethyl alcohol ; on heating decomposes explosively at about 100°. (A, 137, 47 ; B., 28, 2049.) Preparation 381. — Diazobenzene Nitrate (Benzene Diazonium Nitrate). C 6 H 5 .N(;N).N0 3 . C 6 H 5 0 3 N 3 . 167. Owing to the highly explosive nature of the diazobenzene nitrate, its preparation should never be undertaken except the compound is wanted for research or some special purpose. 20 gms. of aniline are placed in a beaker, well cooled, and "boiled-out" nitric acid, previously diluted with half its volume of water carefully added, till the mixture sets to a thick crystalline paste — aniline nitrate. The crystalline mass is filtered off at the pump, and washed with a little cold water. 5 gms. of the moist salt are finely powdered and placed in a small flask with enough water just to cover the substance. The flask is now well cooled in ice- water, and nitrous fumes (for preparation, see p. 509) are led in with frequent agitation until all the aniline nitrate has disappeared. At no time must the temperature of the flask rise above 10°. Should there not be sufficient water to keep all the diazobenzene nitrate formed in solution, its crystalline form will easily enable it to be distinguished from the aniline salt. When the reaction is finished the contents of the flask are poured into 3 times their volume of absolute alcohol, and ether is added to this mixture as long as crystals separate. If too much water has been added to the aniline nitrate from the beginning, a thick aqueous solution of diazobenzene nitrate separates out in place of the crystals. If this occurs, the ether-alcohol is decanted off, and the residue redissolved in absolute alcohol, and reprecipitated with ether. On no account must large quantities of the preparation be allowed to dry. If it has to be * Any of the diazo -compound which remains over should hd dissolved inl wuter and poured away. THE LINKING OF NITROGEN TO NITROGEN 369 preserved it must be kept moist, or, better, in aqueous solution. The usual diazo reactions can be carried out with the latter. C 6 H 5 .NH 2 + HN0 3 = C 6 H 5 NH 3 .N0 3 . 2C 6 H 5 .NH 3 .N0 3 + NO + N0 2 = 2C 6 H 5 .N( \ N).N0 3 + 3H 2 0. Colourless needles ; extremely explosive in the dry state ; very soluble in water ; insoluble in ether ; on heating decomposes explosively. (A., 137, 41.) Reactions of Diazonium Compounds. The following reactions are performed in test tubes with about 1 gm. of the substance. Most of these reactions are also given on the large scale. 1. The substance is heated with a few cubic c.cs. of ethyl alcohol, when vigorous effervescence takes place, and the liquid turns red. On adding water an oil consisting of benzene and a little phenetole separates on the surface. C 6 H 5 .N 2 .S0 4 H + C 2 H 5 OH = C 6 H 6 + N 2 + CH 3 .CHO + H 2 S0 4 . C 6 H 5 .N 2 .S0 4 H -f C 2 H 5 OH = C 6 H 5 .O.C 2 H 5 + N 2 + H 2 S0 4 . 2. A solution of about 1 gm. of- the substance in a little water is cooled in ice, made alkaline with caustic soda, and treated with a cold, alkaline solution of stannous hydrate, made by dissolving about 4 gms. of stannous chloride in twice its weight of water, and adding 40% caustic soda solu- tion until the precipitate redissolves. Effervescence occurs, nitrogen is liberated, and benzene separates on the surface of the liquid. C 6 H 5 .N 2 .ONa + Sn(ONa) 2 + H 2 0 = C 6 H 6 + 0 : Sn(ONa) 2 + N 2 + NaOH. 3. An aqueous solution of the substance is gently warmed, when a vigorous evolution of nitrogen occurs, and a dark-coloured oil, smelling strongly of phenol, separates. It can be extracted with ether and tested for phenol (see p. 347): If a solution of diazobenzene nitrate be used, the liberated nitric acid acts on the phenol as it is formed, and nitrophenol is produced. C 6 H 5 .N 2 .S0 4 H + H 2 0 = C 6 H 5 OH + H 2 S0 4 + N 2 . C 6 H 5 .N 2 .HN0 3 + H 2 0 = C 6 H 5 OH + HN0 3 + N„ C 6 H 5 OH + HN0 3 = C 6 H 4 (OH)(N0 2 ) + H 2 0. 4. An aqueous solution of the substance is mixed with a solution of bromine in hydrobromic acid or potassium bromide, when a reddish- brown oil separates. This solidifies to a mass of leafy crystals, if the aqueous layer be poured off the oil, and the latter washed with a little ether. The crystals are diazobenzene perbromide. C 6 H 5 .N 2 .S0 4 H + KBr + Br 2 = C 6 H 5 NBr.NBr 2 + KHS0 4 . C 6 H 5 .N 2 .S0 4 H + HBr + Br 2 = C 6 H 5 .NBr.NBr 2 + H 2 S0 4 . If a sufficient quantity of the crystals has been prepared, it may be divided into two portions. One portion is covered with cone, ammonia. A violent reaction sets in, the crystals disappear, and a dark oil, possessing S.O.C. B B 370 SYSTEMATIC ORGANIC CHEMISTRY a peculiar narcotic odour, is produced, consisting principally of diazo- benzene imide. C 6 H 5 NBrNBr 2 + NH 3 - C 6 H 5 N 3 + 3HBr. The other portion of the perbromide is warmed with a little alcohol. Nitrogen and bromine are given off, and bromobenzene is formed. C 6 H 5 .NBr.NBr 2 = C 6 H 5 Br + N 2 + Br 2 . 5. Potassium iodide solution is added to an aqueous solution of the diazonium salt. Nitrogen is evolved, and a dark-coloured oil, iodobenzene, separates. C 6 H 5 .N 2 .S0 4 H + KI = C 6 H 5 I + N 2 + KHS0 4 . For large scale reaction see Praparation 338. 6. The solution of the diazonium salt is mixed with an aniline salt and excess of sodium acetate, or the solution is shaken up with a few drops of aniline. In either case a yellow crystalline precipitate of diazoamino- benzene is obtained. C 6 H 5 .N 2 .S0 4 H + C 6 H 5 NH 2 .HCJ] + CH 3 €OONa = C 6 H 5 N : N.NHC 6 H 5 + NaHS0 4 + CH 3 COOH + HC1. C 6 H 5 .N 2 .S0 4 H + C 6 H 5 NH 2 = C 6 H 5 N 2 .NHC 6 H 5 + H 2 S0 4 . For* large scale reaction see p. 367. 7. A solution of phenol in caustic soda is added drop by drop to an aqueous solution of the substance. An orange crystalline precipitate of * sodium hydroxyazobenzene is formed. If /?-naphthol be used in place oT phenol a scarleT^precipitate of sodium hydroxy-^-naphthaleneazo- benzene is obtained (Sudan Dyes). C 6 H 5 .N 2 .S0 4 H + C 6 H 5 (ONa) = C 6 H 5 N : NC 6 H 4 (ONa) + Na 2 S0 4 + 2H 2 0. G 6 H 5 .N 2 S0 4 H + C 10 H 7 (ONa) = C 6 H 5 N : NC lo H 6 (ONa) + Na 2 S0 4 + 2H 2 0. 8. An acetic acid solution of dimethylaniline is added to a solution of the substance. A magnificent red colour is produced in a short time through the formation of dimethylaminoazobenzene sulphate. C 6 H 5 N 2 S0 4 H + C 6 H 5 N(CH 3 ) 2 .HOOC.CH 3 = C 6 H 5 N : N.C 6 H 4 N(Ca 3 ) 2 .H 2 S0 4 + CH 3 COOH. A sulphuric acid solution of m-phenylene diamine is added to the solution of the diazonium salt. The orange colour is due to diaminoazobenzene sulphate (Chrysoidine). C 6 H 5 N 2 S0 4 H + C 6 H 4 (NH 2 ) 2 (H 2 S0 4 ) = C 6 H 5 N : NC 6 H 3 (NH 2 ) 2 (H 2 S0 4 ) + H 2 S0 4 . For large scale reaction see Preparation 384. 9. A \ grn. at the most of the moist diazobenzene sulphate is allowed to dry spontaneously on filter paper in some safe place, and when dry exploded by kindling the paper. THE LINKING OF NITROGEN TO NITROGEN 371 Reaction CLXXVIII. Action of Alkaline Reducing Agents on Aromatic Nitro Compounds. — Azoxy and azo compounds are first formed. 2R.N0 2 and The final reduction product is a hydrazo compound. In order to isolate the azoxy and azo compounds, the requisite quantity of reducing agent is employed. For example, if zinc is used, then three-fifths and four-fifths of the quantity necessary for complete reduction will give the azoxy and azo compounds respectively, the conditions being the same (see Preparation 368). R.N — N.R and R — N = N.R 0 0 Azoxy R — N = N.R. Azo B B 2 CHAPTER XXVI DYES 1. Azo Dyes. These dyestuffs are formed by coupling diazonium compounds with phenols or aromatic bases. The characteristic group is — X = X — . and the general formula X— X = X— Y. Mono-azo dyes contain one — X = X— group, while dis-azo dyes contain two, and so on. For the general laws of coupling see Eeaction CXXII. Mono-azo dyes are acid \ or basic in reaction, according to the nature of the auxochrome present W».e p. 275). They are soluble in alkali and in cone, sulphuric acid if they contain a phenol or a sulphonic group. They are decomposed by cone, nitric acid and halogens. Reducing agents decompose them, with the formation of amines, a reaction which serves to determine their composition and constitution. X— X = X— Y -h 4H -> X.XH 2 + XH 2 .Y. Preparation 382. — Methyl Orange (Helianthine). S0 3 Xa/ \n = NNH^-> S0 3 H<^ \N 2 C1 dimethyl aniline S0 3 H<^ \x = N<( .^>N(CH 3 ) 2 . Yield. — Almost theoretical. (B., 10, 528.) The yellow crystals are the sodium salt, and when acid is added to a solution a red colour is obtained. The dyestuff is, therefore, used as an indicator in acidimetry and alkalimetry. 372^ DYES 373 If anthranilic acid is used in place of sulphanilic, the dyestuff formed is Methyl Red. (See " Organic Syntheses," Vol. II. (1922), J. B. Conant and others.) _COOH <^ ^>N = _\n(CH 3 ) 2 . Preparation 383.— Congo Red. NH 2 NH 2 \ / \_/ I I I C 8 aH 26 0 6 N 6 S 2 . 653. 184 gms. benzidine are dissolved in 300 c.cs. of water and 20 c.cs. cone, hydrochloric acid, heat being applied, if necessary. Ice is added till the temperature is below 5° C. 30 c.cs. cone, hydrochloric acid are then added, and about 144 gms. sodium nitrite in 10% solution until diazotisation is complete (see p. 365). 150 gms. sodium naphthionate are dissolved in as little water as possible. The diazo solution is rim into the sodium naphthionate, with stirring, and after \ hour a solution of 35 gms. sodium carbonate is added gradually, so that during further stirring the solution is always alkaline. The contents of the beaker will appear brown at this stage. The whole is then slowly heated up to about 80° C. and common salt added to saturate the solution. After cooling, the reddish-brown Congo Red is filtered off, washed with saturated common salt solution, and dried. Dyes cotton, direct from alkaline bath, red. In order to obtain a good yield a large excess of sodium naphthionate is employed, the excess being recovered as the free acid on acidifying the mother liquor after filtering off the dyestuff. (B., 19, 1719.) If o-tolidine is used in place of benzidine, the dyestuff formed is Benzo- purpurin 4=B. (D.R.P., 84893.) Preparation 384. — Chrysoidine Y. \N = NN = NCI. NH 9 ~ NH / \N = NCI + / \NH 2 -> / ^>N = N— / (B., 10, 388.) If m-tolylenediamine is used in place of m-phenylenediamine, the dyestuff formed is Chrysoidine R. Peeparation 385. — Orange II. OH SOoH<^ \_N = N— / C 16 H 12 0 4 N 2 S. 328. 17-3 gms. sulphanilic acid are dissolved in water and a little caustic soda. Ice is added until the temperature is below 5° C. 30 c.cs. hydrochloric acid are then added, and about 7-2 gms. sodium nitrite in 10% solution gradually run in until diazotisation is complete (see p. 365). The diazo compound usually separates out as fine needles, but these are not isolated. 144 gms. /?-naphthol are dissolved in 15 c.cs. water, to which 4-5 gms. caustic soda have been added. This solution is made up to about 180 c.cs. by adding water. It is then cooled, if necessary. The diazo solution is carefully added, with stirring, until coupling is complete (see p. 490). The mass should now give a slight alkaline reaction. After stirring for about an hour the dyestuff separates out, a little salt being added to complete the precipitation. The orange powder is filtered off and dried. Dyes wool orange from an acid bath. (J. S. C. I., 6, 591.) If a-naphthol is used in place of ^-naphthol, the dyestuff formed is Orange I. (J. S. C. I., 6, 591.) so«h/ \n = n/ Noh. 2. Di- and Tri-Aryl Methane Dyes. These dyes may be regarded as derivatives of C 6 H5 C 6 H 5 CH 2 and CH— C 6 H 5 C 6 H5 C 6 H 5 Diphenylme thane. Triphenylmethane. The dyes are obtained from their amido and alkylamido derivatives, these groups being usually present in the _p-position. DYES 375 Preparation 386. — Auramine. NH 2 CI (CH 3 ) 2 N<^ _ _ \— C— <^ \n.(CH 3 ) 2 . C 17 H 22 N 3 C1. 303-5. 242 gms. pure dimethyl aniline are mixed with 140 c.cs. water and 260 gms. cone, hydrochloric acid, and heated to 30°. 60 gms. 40% formaldehyde are then added, and the mixture heated to 85°, with occasional stirring, for 5 hours. The base is then precipitated by adding 120 gms. sodium carbonate dissolved in a little water. The product, tetramethyl-diamino-diphenylmethane, is filtered after cooling to 20°, and washed with water. It is dried at 50°. The yield of this base is almost quantitative. 127 gms. diamino base, 32 gms. sulphur, 70 gms. ammonium chloride, and 1,000 gms. common salt are heated in an auto- clave with stirrer and exit tube to 110°. The substances should all be finely powdered, and absolutely dry. The temperature is raised to 130° during 2 hours, and a rapid stream of dry ammonia passed through. At 140° a vigorous evolution of hydrogen sulphide begins, which lasts from 5 — 7 hours, according to the speed of the stream of ammonia. The tem- perature is raised to 145° during 5 hours, stirring being continued. The ammonia stream should pass at a speed of about 5 bubbles per second, and it is advisable to have a slight excess pressure of ^ atm. measured by a manometer, which can be conveniently done by throttling the exit tube. When the evolution of hydrogen sulphide has ceased, the contents of the autoclave are placed in a large basin and treated with 3 litres of water to dissolve out the salt. The dye is then filtered off, and dissolved in 1 J litres of water at 60°. The solution is filtered, and a litre of saturated salt solution added, when the auramine comes down in glistening, golden leaflets. It is filtered and dried. _^>N(CH 3 ) 2 .HC1 + CH 2 0 -> (CH 3 ) 2 N<^ \_CH 2 — ( )>N(CH 3 ) 2 NH 2 ■ + S + NH 4 C1 + NH 3 -> (CH 3 ) 2 N<^ )>— C-<^ )>N(CH 3 ) 2 . di Yield — Up to 175 gms. Dyes cotton mordanted with tannin or tartar emetic a pure yellow. (B., 33, 318.) Preparation 387. — Magenta. CH 3 \nh 2 C 9n H, n N,CL 337-5. 7 gms. aniline and 27 gms. commercial toluidine (containing 64% ortho,, and 36% para) are heated with 34 gms. cone, hydrochloric acid to 130'' 376 SYSTEMATIC ORGANIC CHEMISTRY in a 250-c.c. flask. 3 gms. aniline, 13 gms. commercial toluidine, and 27-5 gms. nitrobenzene are then added. The flask is transferred to an oil bath at 100°, and 1-5 gms. iron powder dissolved in the minimum quantity of hydrochloric acid (2 mols.) slowly added. An air condenser is attached, and the temperature raised to 180°, and maintained at this temperature for about 5 hours. When a sample, withdrawn on & glass rod, solidifies on cooling, the action is finished. The mixture is then steam-distilled to remove the nitrobenzene and \excess amines. The melt is then poured into 250 c.cs. boiling water,) with stirring, and 6 c.cs. cone, hydrochloric acid added slowly. As s$on as an acid reaction is obtained, 13 gms. common salt are added, and tne whole boiled for a few minutes. The aqueous solution (containing the hydro- chlorides of aniline and toluidine) is poured off and the residue allowed to cool, when it solidifies to a green mass. This mass is broken up and extracted with 750 c.cs. boiling water containing 6 c.cs. cone, hydrochloric acid, which dissolves the magenta. The solution is filtered hot, and, after cooling to 60°, is again filtered. The magenta is then " salted out " with common salt, and after standing some time, is filtered off and recrystallised from water containing a little hydrochloric acid. The hydrochloride forms green, glistening crystals, giving a red solution in water. It dyes silk and wool bluish-red, and mordanted cotton. / \ C 6 H 5 N0 2 / v CH 3 / )NH 2 + 0 2 OHC<^ )>NH 2 . A CH 3 CH 3 , W Vh 2 / \nil NH/ ^CH O C1I ( \ 7 NH, >NH, \ / Leuco base. CH 3 >H 2 O / HC1 HO.C— > ~" \ / Carbinol base. C ( \NH 2 NHo.Cl. \NH 2 Magenta. is also formed. \ )= NH 2 .C1 Para-rosaniline chloride. (J. S. C. I., 5, 163; 7, 118.) DYES 377 Peeparation 388. — Malachite Green. >N(GH 3 ) C C 23 II 25 N 2 C1. 364-5. >: N(CH 3 ) 2 C1. Method I. — 50 gms. of dimethylaniline, 20 gms. of benzaldehyde and 20 gms. of pulverised anhydrous zinc chloride (see p. 506) are heated in a porcelain dish, with frequent stirring, on a water bath for 4 hours. The mass is then melted by the addition of hot water and transferred to a large flask, where it is steam-distilled until no more dimethylaniline passes over. The leuco-base of the dye remains in a viscous form on the sides of the flask after cooling ; the aqueous solution is decanted and the base washed a few times by decantation with cold water. The base is dissolved in boiling alcohol, the solution filtered hot, and the filtrate left overnight in an ice chest. Colourless crystals separate, which are collected and dried in air on filter paper. A second crop may be obtained by concentrating the mother liquor. If the base separates as an oil, instead of crystals, more alcohol should be added, and heat applied until the oil redissolves. A small portion of the leuco-base is weighed, dried at 100°, and weighed again in order to determine its moisture content. The equivalent of 10 parts by weight of the anhydrous base is dissolved by heating with a quantity of dilute hydrochloric acid, corresponding to 2-7 parts by weight of hydrogen chloride. The colourless solution of the leuco-base is diluted in a large beaker with 800 parts of water, and 10 parts of 40% acetic acid added. The solution is cooled to about 0° by the addition of lumps of ice, and a freshly prepared lead dioxide paste (for preparation and estima- tion, see p. 504), corresponding to 7-5 parts Pb0 2 , added gradually during the course of 10 minutes, the mixture being stirred and cooled during the addition. Stirring is continued for 2 hours, after which the unchanged lead peroxide is filtered off, and the lead in the filtrate precipitated by the addition of 10 parts of sodium sulphate dissolved in 50 parts of water. Lead sulphate is filtered off, the filtrate is heated to boiling, and 15 gms. of sodium chloride added for each 100 c.cs. of dye solution ; while still hot, 8 parts of zinc chloride, dissolved in a small quantity of water, are also added. On cooling, the zinc chloride double salt of the dye is filtered off, washed with saturated sodium chloride solution, and dried on a porous plate. If the mother liquors are coloured, owing to some of the dye still remaining in solution, a further crop may be obtained by adding more sodium chloride and zinc chloride. C 6 H 5 CHO + 2C 6 H 5 N(CH 3 ) 2 -> C 6 H 5 CH{C 6 H 4 N(CH 3 ) 2 } 2 + H 2 0 (Leuco base) \0 /C 6 H 4 N(CH 3 ) 2 HCl C 6 H 5 -C/ + H 2 0 < C 6 H 5 C(OH){C 6 H 4 N(CH 3 ) 2 } 2 V 6 H 4 = N(CH 3 ) 2 C1 (Carbinol base.) Malachite green hydrochloride. 378 SYSTEMATIC ORGANIC CHEMISTRY The formula of the zinc chloride double salt is — 2C 23 H 25 N 2 C1 + 2ZnCl 2 + H 2 0. Brass yellow prismatic needles ; soluble in hot water to a bluish-green solution ; dyes silk, wool, jute and leather, a bluish-green directly, and cotton which has been previously mordanted with tannin and tartar emetic. Method II. — 50 gms. dimethylaniline, 20 gms. benzaldehyde, and 45 gms. of cone, hydrochloric acid are placed in a flask fitted to a reflux condenser, and the mixture heated at 100° for 24 hours. The product is then made alkaline with caustic soda, and steam-distilled to remove traces of benzaldehyde and dimethylaniline. After this the procedure is the same as in Method I. (J. S. C. I., 6, 433.) 3. Pyrone or Phthalein Dyes. Preparation 389. — Eosin. Na Bl '\ A //\ /Br. COONa. C 20 H 6 O 5 Br 4 Na 2 . 692. Into a mixture of 15 gms. of fluorescein and 60 gms. of alcohol (about 95%), contained in a flask, are added with frequent shaking 11 c.cs. of bromine, drop by drop, from a burette. When half the bromine has been added the dibromide which is then formed is in solution ; on further addition of bromine the tetrabromide separates out in the form of brick- red leaflets. After all the bromine has been added, the mixture is allowed to stand for 2 hours. The precipitate is filtered off, washed first with alcohol, then with water, and converted into the sodium salt by mixing with a little hot water, carefully neutralising with caustic soda (avoiding excess), and evaporating to dryness on a water bath. Bluish-red crystals or brownish-red powder. In water, bluish-red solution ; dilute solution has green fluorescence. In alcohol, easily soluble, with bluish-red colour and yellowish-green fluorescence. Dyes wool and silk yellowish-red. (J. S. C. L, 1893, 513.) Preparation 390. — Fluorescein. HQ/ V V ^OH DYES 379 A mixture of 15 gms. of phthalic anhydride and 22 gms. of resorcinol is ground in a mortar. It is then transferred to a nickel or cast-iron vessel, and heated in an oil bath to 180°. At this temperature 7 gms. of powdered fused zinc chloride (see p. 506) are added, with stirring, during the course of 10 minutes. The temperature is raised to 210°, and maintained at this point until the liquid, which gradually thickens, becomes solid, for which 1 — 2 hours are required. The cold melt is removed from the vessel with a knife or chisel, powdered, and boiled 10 minutes with 200 c.cs. of water and 10 c.cs. of cone, hydrochloric acid. This treatment causes the solution of zinc oxide and basic zinc chloride. The fluorescein is filtered off, washed with water until the nitrate no longer shows an acid reaction ; it is dried on a water bath. Yield. — Almost theoretical (32 gms.). Red powder ; slightly soluble in water ; soluble in alcohol ; soluble in alkalies with intense green fluorescence ; dyes animal fibres a fast vellow. OH II OH > .CO _j_ / 0' CO- OH OH rA \oh A ,0 CO \0 + 2H 2 0. p> Free acid. ^OH |2NaOH ONa K Sodium salt. (J. S. C. I, 22, 513.) COONa ' s O 4. Nitro Dyes. Preparation 391.— Naphthol Yellow S. (2 : 4-Dinitro-l-naphthoI-7 sulphonic acid (K Salt) ). OK SO„K. NO. C 10 H 4 O 8 N 2 SK 2 . 390. NO? 100 gms. of cone, sulphuric acid are warmed to 100° in a small flask. 50 gms. of powdered a-naphthol are added in one instalment. The mixture is raised to 120° by heating in an oil or sand bath and maintained at this temperature for 3 — 4 hours. The sulphonation mixture is then poured into 600 c.cs. of water, which are stirred mechanically. When the temperature of the mixture falls to 30° it is poured into a mixture of 23 gms. of cone, nitric acid and 8 c.cs. of water, which is well stirred mechanically ; the temperature is kept below 35° by cooling in water, 380 SYSTEMATIC OKGANIC CHEMISTRY if necessary. A further 21 gms. of cone, nitric acid are added at such a rate that the temperature does not rise above 40°. The nitration mixture is filtered through woollen cloth and washed free from acid with 10% sodium chloride solution. The drained precipitate is stirred with 200 c.cs. of hot water at 80°, solid sodium carbonate added until neutral, and the dyestuff precipitated by adding 20 gms. potassium chloride. OH OH + 2HN0 3 + H 2 S0 4 S0 3 H + 3H 2 0. N0 2 (Free acid). Orange-yellow powder ; dyes wool and silk from an acid bath. (A., 152, 299.) 5. Thiazine Dyes. Peeparation 392. — Methylene Blue (Hydrated zinc double chloride of tetramethyl-diamido-phenazthionium) . N(CH 3 ) , ZnCL.HoO. Nitroso-dimethyl-aniline. — 16 gms. of dimethylaniline are dissolved in 53 gms. of cone, hydrochloric acid (30%) and 100 gms. ice added. 10-5 gms. of sodium nitrite previously dissolved in 40 c.cs. water are then slowly run in from a dropping- funnel, the solution being agitated during the addition. The temperature must be kept below 5° by the addition of ice, when necessary. When the nitrite is added, the agitation is stopped, and a test for the presence of free nitrous acid applied. A sample of the liquor is withdrawn, diluted with 3 times its volume of water, and tested with starch-iodide paper. If test does not indicate free nitrous acid, more nitrite must be added until a positive indication is obtained. The solution should be acid to Congo paper, and of a yellow colour ; if not acid it is somewhat green. After the addition of all the nitrite the mixture is allowed to stand for 2 hours, and at the end of this time it should just give a slight indication of free nitrous acid. The greater part of the nitroso-dimethylaniline hydrochloride separates out as yellow crystals. ^-Amino-dimethylaniline. — The above mixture is well agitated, 100c.es. of water and 70 gms. of cone, hydrochloric acid added ; this is followed by 20 gms. iron filings, and sufficient ice added from time to time to keep the temperature below 30°. The reduction is complete when a drop spotted on filter paper is quite colourless. The liquor, which is generally acid, is treated with lime-paste until it is only faintly acid to Congo paper ; the neutralisation is completed by the addition of chalk until frothing stops. The residue of iron and chalk is filtered off and washed, the washings being added to the nitrate. DYES 381 Thiosulphonic Acid and Dye. — Before entering on this stage of the preparation the following solutions are prepared : — Solution I.— 33-5 gms. sodium thiosulphate in 40 c.cs. water.— Solution II. — 26-4 gms. sodium bichromate in 40 c.cs. water. Solution III. — 14 gms. dimethylaniline in 24 gms. cone, hydrochloric acids. Solution IV. — 26-4 gms. sodium bichromate in 40 c.cs. water. Solution V. — 1-5 gms. copper sulphate in 20 c.cs. water. The clear neutral solution of ^-amino-dimethylaniline is vigorously agitated. Solution I. is added all at once, and immediately following it Solution II. during the course of 2 minutes. After an interval of 2 minutes Solution III. is added all at once, and immediately following it Solution IV. during the course of 2 minutes. Agitation is continued for 7 minutes before Solution V. is added. The mixture is then transferred to a large vessel and heated ; it soon assumes a bronze appearance, and much frothing takes place. Heat is withdrawn until the froth settles ; when this occurs, the mixture is heated up again and filtered almost boiling. The black precipitate of chromium hydroxide is washed with boiling water until the filtrate is only faintly coloured. The total filtrate is heated almost to boiling, then treated with 150 gms. common salt, 40 gms. of 50% zinc chloride solution and 10 gms. cone, hydrochloric acid. On cooling, the double zinc salt of methylene blue separates out as a coppery powder, which is filtered off and washed with a little 10% brine solution ; it is dried at a temperature not exceeding 50°, a yield of about 30 gms. being obtained. If " zinc-free " methylene blue is desired, the nitrate from the chromium hydroxide is heated to 80°, 15 gms. of common salt added for each 100 c.cs. of solution, also 10 c.cs. of cone, hydrochloric acid. On cooling, the " zinc-free " methylene blue separates in fine crystals. /\no /Nneu (CH 3 ) 2 N, Dimethylaniline. -NIL (CH 3 ) 2 N! j?-Nitroso- dimethyianiline. (CH 3 ) 2 N (CH 3 ) 2 n! (CH 3 ) 2 N^ p -Amino - dimethylaniline. N(CH< SO ? H Thiosulphonic acid of p - amino - dimethylaniline . S0 3 H Thiosulphonic acid of Bindschedler's Green, N (A., 251, 1.) (CH 3 ) 2 N X/ )^ g/ l xy N(CE k Methylene Blue. 382 SYSTEMATIC ORGANIC CHEMISTRY Methylene blue is of a very pure shade, and is much used for dyeing tannined cotton ; the " zinc-free " dye is used for medicinal purposes, and also for the production of discharge effects in silk printing. Preparation 393 —Methylene Green (Nitro-methylene blue). 30 gms. methylene blue (Zn salt) are made into a paste with 35 c.cs. water and 16 gms. of 60% nitric acid ; to this are added at 25° 3-5 gms. of sodium nitrite dissolved in the minimum quantity of water. The temperature is raised slowly to 50° (rate 1° per minute) with good agitation, and kept there for 2 hours. 160 gms. of saturated brine are then added, and the precipitate filtered off after 12 hours. The product is purified by dissolving in 800 c.cs. water at 60°, filtering to remove residue, and reprecipitating the dye with 105 gms. common salt along with 35 gms. of 50% zinc chloride solution. After standing for 12 hours, the dye is filtered off, pressed, and dried at 45°. Yield— About 25 gms. Used in conjunction with iron-mordanted logwood, or with tin phosphate for dyeing black on silk, also for cotton and calico printing. (E.P., 8992 (1886).) Preparation 394. — Primuline. I ySv /SO a Na CfiHo/ >C.C fi H; C 28 H 17 0 3 N 4 S 4 Na. 608. 6 XX 3< 20 gms. £>-toluidine and 14 gms. sulphur are well mixed together and heated in a jar in an oil bath to 250° C. The mass turns yellow, and the reaction is finished when no more H 2 S is evolved. The mass, after cooling, is powdered and heated with 4 times its weight of fuming sulphuric acid (30% S0 3 ) to 70° — 80° C. for a few minutes until a sample dissolves in caustic soda. The sulphonation mixture is poured into ice-water, and the sulphonic acid of the primuline base which is precipitated filtered and washed free of acid. The paste is stirred up with dilute ammonia until alkaline, filtered and washed with cold water. The residue is the ammonium salt of dehydro-thio-j9-toluidine sulphonic acid, and the filtrate contains the primuline. The filtrate is saturated with common salt, when the primuline separates out and is filtered and dried. Dyes cotton direct from alkaline or neutral bath primrose-yellow (see Preparation 300). (D.R.P., 56606.) 6. Indigoid Dyes. Preparation 395. — Indigo. >C = C( I I C 16 H 10 O 2 N 2 . 262. -CO v / CO- >C = C< -NH/ \NH- 14 gms. anthranilic acid are suspended in 50 c.cs. benzene. 7 gms. DYES 383 finely powdered potassium cyanide are added, and after shaking, 7-5 c.cs. of 40% formaldehyde. The temperature rises, and the potas- sium salt of co-cyanmethyl anthranilic acid is formed in the aqueous liquid. The benzene is removed, and 20 c.cs. of 40% ca ustic soda solution are added. The mixture is carefully heated over a wlregauze until ammonia begins to be evolved. After the reaction has subsided, heating is con- tinued until all the ammonia is driven off, water being added, if neces- sary, to prevent the contents of the flask becoming solid. The mix- ture, when cold, is carefully neutralised with cone, hydrochloric acid (/using ph^noljo]^ and then acidified with about 15 cxsT^FgE^aTacetic Tacid. The yellowish- white precipitate of phenyl- glycine-o-carboxylic acid is filtered off, washed with water, and dried on a porousplate. 10 parts of phenylglycine-o-carboxylic acid, or the corresponding amount of the sodium or potassium salt, are added to a solution of 10 — -12 parts of pure caustic soda in 4 — 6 parts of water. The mixture is then quickly evaporated, being stirred continuously until dry. It is powdered, and added to 8^=J^aTts_ol^solio^^ The mixture is heated to 250° — 270°, and stirred with the thermometer, steam being evolved. The end of the reaction is indicated by the strong yellow colour of the fusion. The homogeneous paste is cooled, and boiled with water containing a little sodium hydrosulphite to prevent oxidation. The liquid is filtered from paraffin, and oxidisj^byjiajssing air, when indigo is precipitated as a dark blue powder. /\NH 2 LoOH NH.CH 2 CN COOK /\NH.CH 2 CN COOH 2NaOH /\NH.CH 2 .COONa + NH 3 . COONa /\NHCBLCOONa COONa /\NH- NaOH _> | | C1F -C(ONa)' Sodium indoxyl. >CH + O, -C(ONa)' -NH > NH -CO x x CO- Indigo dissolves in reducing agents to give a colourless leuco-compound. Cotton, wool and silk are dyed by soaki ig in the leuco-compound and exposing to air. (D.K.P., 125916.) 384 SYSTEMATIC ORGANIC CHEMISTRY 7. Anthraqtuinone Dyes. Preparation 396. — Algol Yellow. C 6 H 5 CONH^ CO NH.COC 6 H 5 ill! C 28 H 18 0 4 N 2 . CO 446. 7 gms. of 1.8-dinitro-anthraquinone (Preparation 231) are added to a solution of 35 gms. sodium sulphide (Na 2 S.9H 2 0) in 200 c.cs. water, and heated gradually to boiling. The mass becomes dark blue and thick, owing to the separation of sulphur and diamino-anthraquinone. The precipitate is filtered off and extra yield recovered by adding common salt to the filtrate. The diamino compound is then extracted from the precipitate by boiling up with alcohol and filtering from sulphur. The diamine is precipitated from the alcoholic solution by adding water. It is filtered and dried on the water bath. Scarlet red powder ; M.P. 262° C. Benzoylation. — 1 gm. of the diamino compound is treated with 4 gms. benzoyl chloride and 10 gms. dimethylaniline and boiled for 1 hour, when the benzoyl derivative separates out as a yellow-brown powder. The unchanged base and the dimethylaniline are extracted with dilute hydrochloric acid. It is then filtered. Yellowish powder ; M.P. 234° C. Preparation 397. — Alizarin. /CO x /OH(l) C 6 H4\ /C 6 H 2 \ , C 14 H 8 0 4 . 240. x CO x x OH(2) 100 gms. 100% /?-anthraquinone sulphonate (silver salt) (see p. 307) are mixed with 260 gms. 100% caustic soda, 28 gms. sodium chlorate, and sufficient water to make volume up to 670 c.cs. The mixture is placed in an autoclave and heated up to 185° with continuous stirring, the pressure attaining 5 — 6 atms. After 48 hours, the melt is allowed to cool, and the following test applied : 2 c.cs. of the melt are treated with sufficient cone, hydrochloric acid to precipitate the alizarin. The nitrate is then extracted twice with a little ether to remove traces of alizarin. The liquid is now diluted to 15 c.cs., and the fluorescence, which is due to unchanged silver salt, and the mono-hydroxy-sulpho acid observed. If the reaction is complete, only a very faint fluorescence should develop. If the reaction is not complete, the mixture is heated up again in the autoclave to 190° for 24 hours. It is then diluted with 2 litres of water, and the alizarin precipitated at the boil with 50% sulphuric acid. It is cooled to 50°, filtered and washed. It is not dried, as when once dry it no longer dyes properly. DYES 385 CO OH ; SO,H NaOH To! ;OH CO Yield. — About 70 gms. A polygenetic dyestuff, i.e., dyes mordanted cotton various colours, depending on the mordant used, e.g., iron oxide gives a violet colour, alumina a red colour, chromium a brown colour, etc. (J. S. C. I., 2, 213 ; E.P., 1948 (1869).) Prepaeation 398. — Anthracene Brown (Anthragallol). 1.2.3-Tri- hydroxy Anthraquinone. C 14 H 8 0, 256. 36 gms. pure benzoic acid are dissolved in 300 gms. sulphuric acid (mono- hydrate) in a glass or porcelain beaker with good stirring. The mixture is heated slowly to 90°, at which temperature 50 gms. pure, dry gallic acid * (dried at 110°) are added in small portions during an hour. The tempera- ture is then raised to 118°, and kept there for 6 hours, after which the melt is allowed to drop cautiously into a litre of boiling water, with con- tinuous stirring. The product is filtered boiling through a hot filter, and the dye well washed with hot water. The excess benzoic acid crystallises out in the mother liquor. OH nn OH I J COOhI JoH \ J\ J\ /OH Yield. — 70—80% theoretical (70 — 80 gms.). Dyes wool brown with chrome mordants, chromium fluoride giving the best shades. (J. S. C. L, 3, 141.) * Good quality gallic acid may be obtained by hydrolysing tannin with 40% caustic soda solution at 70° with the addition of a little sodium bisulphite to protect the acid from oxidation. The gallic acid is then precipitated by cone, hydrochloric acid and crystallised from water. (Note. — Sulphuric acid must not be used.) s.o.c. CHAPTER XXVII DRUGS Preparation 399. — Chloral Formamide (Chloralamide). CCl 3 .CH(OH)NH.CHO. C 3 H 4 0 2 NC1 3 . 192-5. 74 gms. freshly distilled chloral are added, with, stirring, to 22-5 gms. cooled formamide (see Preparation 265). Much heat is evolved, and the mixture sets on cooling to a crystalline mass of chloral formamide. It is purified by recrystallisation from dilute alcohol, the solution not being heated above 48° (see below). CCI3CHO + HCONH 2 -> CCl 3 CH(OH).NH.CHO. Colourless crystals ; M.P. 114° — 115° ; a hypnotic ; above 48°, is reconverted to chloral and formamide. (D.R.P., 50586 ; E.P., 7391 (1886).) Preparation 400. — Aspirin (Acetyl Salicylic Acid). y.cocHg C 9 H 8 0 4 . 180. COOH. 100 gms. acetyl chloride in 25 gms. glacial acetic acid are added to 69 gms. salicylic acid in a retort. The retort is gently heated until the reaction commences, when heating is discontinued. Hydrochloric acid is evolved, and acetyl chloride commences to pass over. When the reaction slackens, the temperature is raised gradually to 60°, and when the action has ceased, to 70°, to remove acetyl chloride as far as possible. This can be much facilitated by the application of a slight vacuum. When the distillation has ceased the contents of the retort are poured into an enamelled basin and allowed to crystallise. The crystals are then filtered off, washed with water, and dried at 30° — 40°. They are recrystalhsed by dissolving in ethyl alcohol at about 40°, and throwing out of solution by the addition of cold water. \COOH[2] \COOH [2] Rhombic plates ; M.P., which varies according to rate of heating, is given by British Pharmacopoeia as 134° — 135° ; should give no violet coloration with ferric chloride ; the most important analgesic and anti- pyretic. (BL, 1915, 17, 186.) 386 OH [1] /OCOCH 3 [l] DRUGS 387 Peeparation 401. — Chloramine T. CH 3 .C 6 H 4 S0 2 N.NaCl + H 2 0. C 7 H 9 0 3 NClSNa. 245-5. jt?-Toluene-sulphonyl chloride (see Preparation 285) is treated with 4 times its weight of dilute ammonia solution, and stirred for several hours, until all the powdered sulphonyl chloride is converted into the crystalline sulphonamide. A little of the mixture is filtered, and the crystals boiled with water. When no acidity is developed the reaction is complete. The crystals are then filtered off, washed with a little water, and recrystaliised from a small quantity of water. Needles ; M.P. 64°. CH 3 C 6 H 4 S0 2 C1 -> CH 3 C 6 H 4 S0 2 NH 2 . 171 parts of _p-sulphonamide are treated with 525 parts of a 2N solution of sodium hypochlorite (see p. 508) containing 40 parts NaOH. A white precipitate is immediately formed, which, on heating and subsequent cooling, deposits crystals of Chloramine T, which are washed with brine and recrystaliised from water. CH 3 C 6 H 4 S0 2 NH 2 + NaOCl -> CH 3 C 6 H 4 S0 2 N.NaCl. Colourless needles ; a very powerful disinfectant. (J. S. C. I., 1918, 37,288.) Preparation 402. — Arsanilic Acid (^-Amino-phenylarsinic acid). NH 2 C 6 H 8 0 3 NAs. 217. AsO(OH) 2 . 100 c.cs. arsenic acid (technical— 76%) are heated for 12 — 15 hours at 140°, to concentrate to 100%. It is then cooled, and into it are stirred 140 c.cs. of dry ice-cold aniline. Aniline arsenate is formed, which is ground up and heated to 160° until molten, then under a reflux con- denser for 1—1-1 hours at 160°— 170°, and then for 1 hour at 180°— 185°. It is allowed to cool somewhat, and 45 c.cs. N. caustic soda solution added to decompose any arsenate still remaining. The aniline liberated is separated by extraction with ether. The aqueous layer is shaken up with Kieselguhr or animal charcoal, and the arsenilic acid precipitated from the clear solution by adding a sufficient quantity of dilute hydro- chloric acid. It is then filtered and washed with cold water. NH,~~|(H 3 As0 4 ) a NH 2 NH 2 -> 2. j + \/ AsO(OH) 2 Of. Sulphanilic acid. The sodium salt, NH 2 .C 6 H 4 .AsO(OH)(ONa) + 5H 2 0, prepared by neutralising 1 mol. of the acid with 1 mol. caustic soda, is known as " Atoxyl." (Am. Soc, 41, 451.) 388 SYSTEMATIC ORGANIC CHEMISTRY Preparation 403— Antipyrine, Phenazone (l-Phenyl-2*3-Dimethyl Pyrazolone). CH 3 .C = CH „ L I CO CH^ON,. 188. N C 6 H 5 Phenylmethyl pyrazolone (see Preparation 249) is methylated with a methyl alcoholic solution of methyl chloride or bromide at 90° — 100°, a slight excess of methylating agent being employed. The methylation can be conveniently carried out in an autoclave fitted with an agitator. The alcohol is distilled off, and the reaction product dissolved in water made slightly alkaline with caustic soda. The antipyrine is then extracted with benzene, and crystallised from benzene, and finally from water, animal charcoal being used to decolorise. CH 3 C = CH— CO CH 3 C = CH — CO HN N.C 6 H 5 CH 3 N N.C 6 H 5 . White crystalline scales ; M.P. 113° ; odourless ; possesses bitter taste ; a valuable analgesic and antipyretic. (D.R.P., 69883, 26429.) Preparation 404. — Veronal, Barbitone (Diethyl-malonyl urea, diethyl- barbituric acid). y CO— NH V (C 2 H 5 ) 2 C< >CO. C 8 H 12 N 2 0 3 . 184. \CO— NH/ 16 gms. sodium are dissolved in 300 gms. absolute alcohol. To the cooled solution are added 20 gms. dry urea and 50 gms. diethyl malonic ester (see Preparation 199). The mixture is heated in an autoclave for 4 — 5 hours at 100°— 110°. On cooling, the sodium salt of diethyl barbituric acid separates, is filtered off, dissolved in water, and the free acid precipi- tated by the addition of hydrochloric acid. The acid is filtered and recrystallised from water, using animal charcoal if necessary. /COOC 2 H 5 NH 2X .CO— NH X (C 2 H 5 ) 2 C< + >CO _> (C 2 H 5 ) 2 C< >CO. \COOC 2 H 5 NH/ \CO— NH/ Colourless crystals ; M.P. 191° ; an important hypnotic. (D.R.P., 146496 ; Am. Soc, 40, 725.) Preparation 405. — Sulphonal (Diethyl-sulphone-dimethyl-methane). C2H 5 S0 2 \ ..CH3 >C< C 7 H 16 0 4 S 2 . 228. C 2 H 5 S0 2 / \CH 3 1. Acetone Ethyl Mercaptol. — 50 gms. ethyl mercaptan (see Preparation 305) are added to 20 gms. acetone and 6 gms. anhydrous calcium chloride. Dry hydrochloric acid gas is passed in, the temperature being DRUGS 389 kept below 25° by external cooling. When saturated with HC1 the mixture is allowed to stand overnight, and washed with water. The layer of mercaptol is separated and dried over calcium chloride, and fractionally distilled. Unchanged ethyl mercaptan passes over first, and then the mercaptol at 190°. 2C 2 H 5 SH + OC.(CH 3 ) 2 (C 2 H 5 S) 2 C(CH 3 ) 2 + H 2 0. 2. Sulphonal. — 33 gms. acetone ethyl mercaptol are added with brisk agitation to 1 litre of 5% potassium permanganate solution. The mixture gradually warms up as oxidation proceeds. About 85 gms. solid permanganate are gradually added at intervals. Stirring is continued until the permanganate is reduced, when the solution is boiled and decolorised with animal charcoal. Sulphonal separates out on cooling, is filtered, and recrystallised from aqueous alcohol. (C 2 H 5 S) 2 .C(CH 3 ) 2 _> (C 2 H 5 S0 2 ) 2 .C.(CH 3 ) 2 . Colourless, odourless, tasteless, prismatic crystals ; M.P. 125-5° ; a hypnotic. (B., 19, 280.) Preparation 406. — Phenacetin (Aceto-^-phenetidine). C 2 H 5 0^ ^NH.COCHg. C 10 H 13 O 2 N. 179. (1) . 13-7 gms. ^-phenetidine (see Preparation 367) are dissolved in 200 c.cs. water and 37-5 gms. 20% hydrochloric acid, and diazotised below 6° with 6-3 gms. sodium nitrite. The diazo solution is then run into a solution of 9-5 gms. phenol in 350 c.cs. of 2% sodium carbonate solution. The azo compound separates out in about 1 hour, and is filtered off and dried. C 2 H 6 0<^~ \NH 2 -> C 2 H 5 0<^ \n = NCI -> C a H 5 0<^" ^>N = N N / ^OH. Yield.— Theoretical. M.P. 104-5°. (2) . 24 gms. of the azo compound are dissolved in 100 c.cs. alcohol and 4 gms. caustic soda. The solution is then placed in an enamel-lined autoclave, 7 gms. ethyl chloride are added, and the whole is heated under pressure for 5 — 6 hours at 90° — 100°. On cooling, the diethoxyl azo compound separates, and is filtered off (M.P. 156°). C 2 H 5 0<^ ^>N = ~~yOH ^C 2 H 5 0<^ ~^>N = NOC 2 H 5 . (3) . 10 gms. of the diethoxy azo compound are mixed with 50 gms. 20 % hydrochloric acid, and 6 gms. of granulated tin are added. When all has gone into solution, caustic soda solution is added to make alkaline, and the p-phenetidine distilled over by superheated steam at 160° — 180°. C 2 H 5 0/ ^>N N<^ )>OC 2 H 5 -> 2.C 2 H 5 0<^ ^NH, 2 mols. of ^9-phenetidine are thus prepared from the initial 1 mol. of j9-phenetidine. (D.R.P., 48453.) 390 SYSTEMATIC ORGANIC CHEMISTKY (4). Equal weights of distilled ^-phenetidine and glacial acetic acid are heated under a reflux with the addition of a little fused sodium acetate until no free base remains (test with alkaline ^-naphthol solution). The excess of acetic acid is then removed by distillation in vacuo, and the residue dissolved in boiling water to which animal charcoal is added, and after cooling and filtering, phenacetin separates out. It is filtered, washed, and recrystallised from water or 60% alcohol, a little sulphur dioxide solution being added to prevent oxidation. C 2 H 5 0 C 2 H 5 0<^ ^NH.COCHg. White glistening scales ; M.P. 134° ; a very important analgesic and antipyretic. (D.R.P., 139568.) CHAPTER XXVIII ELECTEOLYTIC PREPARATIONS Preparation 407. — Benzaldehyde. C 6 H 5 .CHO. 106. The apparatus for this preparation consists of a narrow glass beaker, or a wide-mouthed bottle. The beaker is corked, and an efficient glass stirrer passing through the centre is attached to a small turbine or motor. Four electrodes are fixed in position so that they are clear of the stirrer. Two anodes, each of sheet platinum of about 1 sq. dcm. surface, are placed diametrically opposite one another, while the two cathodes, spirals of platinum wire and each of 2 cms. surface, are placed between them near the sides of the beaker. 50 gms. toluene, 200 c.cs. of 10% sulphuric acid and 250 c.cs. of acetone are placed in the cell, which is surrounded by cold water. The current density should be 1-5 — 2 amperes, the E.M.F. 5—6 volts, and the temperature under 20°. 3 The stirring must be vigorous to keep the mixture in a thorough emulsion. From the equation C 6 H 5 .CH 3 + 20 = C 6 H 5 .CHO + H 2 0 50 gms. of toluene require 58 ampere hours, but in order to ensure complete oxidation 65 ampere hours should be passed. The contents are then transferred to a flask, and made slightly alkaline with sodium carbonate. The acetone is removed by distillation, and the residue steam distilled, when benzaldehyde and unchanged toluene pass over. Benzaldehyde is separated as its bisulphite compound, formed by shaking up with sodium bisulphite, allowing to stand to crystallise and filtering. Dilute caustic soda is then added, the benzaldehyde separated by steam distillation, dried, and redistilled. Yield. — 7 — 8 gms. (see p. 219). The procedure for o- and ^-xylene is similar. (Am. Soc, 22, 723.) Preparation 408. — Iodoform (Tri-iod Methane). CHI 3 . 394. 20 gms. of anhydrous sodium carbonate and 20 gms. (8 mols.) of potassium iodide are dissolved in 20 c.cs. of water, 50 c.cs. (excess) of absolute alcohol added, and the whole poured into a beaker. The anode is a sheet of platinum foil, 8 by 10 cms., the cathode of platinum wire wound into a spiral of 1 cm. diameter. The solution is warmed to 60° or 70°, and a current of 3 amperes per sq. dcm., counting both sides of the anode, is passed through the 391 392 SYSTEMATIC ORGANIC CHEMISTRY solution, while carbon dioxide is bubbled into the liquid to neutralise the caustic potash formed. After 1 hour the iodoform which has separated is filtered off and washed with cold water. 2KI + H 2 0 + C0 2 -> K a CO s + H 2 + I 2 . I 2 3I 2 CH 3 CH 2 OH > CH3CHO > CI3CHO -> CHI3. Yield. — 75% theoretical. Yellow crystals ; insoluble in water ; soluble in alcohol and ether ; volatile in steam ; M.P. 119°. (C, 1897, IL, .695.) Preparation 409. — Methyl Alcohol. CH3OH. 32. A solution in 500 c.cs. water is made from 110 gms. potassium acetate, 26 gms. potassium carbonate and 28 gms. potassium bicarbonate, and poured into a lead cell or glass beaker, which need contain no anode chamber. The beaker should be placed in a basin of cold water, and the cathode should take the form of a thin lead pipe, with a copper connection soldered to it, wound in the form of a coil, and placed close to the inner walls of the beaker. Through this pipe a supply of cold water is run, so that the temperature is maintained at 25° — 30° during the electrolysis. The anode is of platinum, and should be so arranged that it can be rotated. The current densitv is 20 — 25 amperes per sq. dcm., and the E.M.F. 7—8 volts. As the electrolysis proceeds, acetic acid is dropped in at such a speed that the solution does not become acid. When 50 — 60 ampere hours have passed the electrolysis is stopped. The contents of the cell are then distilled to remove the methyl alcohol, and some formaldehyde, which is also produced. The alcohol is dried and redistilled in the usual way. CH3COO- 1 - + OH' -> CH3OH + C0 2 Yield.— 50— 60% theoretical (see p. 206). (A., 323, 304.) Preparation 410. — j9-Phenylene-Diamine. H 2 N.C 6 H 4 .NH 2 . 108. 20 gms. ^-nitraniline are dissolved in 150 c.cs. of alcohol, and to this is added a solution of 5 gms. sodium acetate in 100 c.cs. hot water. This mixture is then placed in a beaker, which acts as a cathode cell. The anode cell, which is a porous pot, contains a 20% solution of sodium carbonate. The cathode and the anode are both of nickel gauze. The mixture is first warmed to 75°, and the high current keeps it boiling. Alcohol may be added from time to time to replace that evapo- rated. The current density is 15 amperes, and the E.M.F. 7 — 8 volts. After about 20 ampere hours have passed, the current density is cut down to 2 amperes. After 24 ampere hours have passed, the current is stopped ; the hot cathode liquid is then poured into a mixture of 50 c.cs. of sulphuric ELECTROLYTIC PREPARATIONS 393 acid and 100 c.cs. of water, and allowed to stand. The j9-phenylene diamine sulphate is filtered and dried on a porous plate. Yield. — 75% theoretical (20 gms.). o-Nitraniline gives by same method o-phenylene diamine ; m-nitraniline gives by same method m-diamido- azo-benzene. (B., 28, 2350.) Pkepakation 411. — Borneol. C 10 H 18 O. 154. A 10% solution of camphor in alcohol and half its volume of 75% sulphuric acid is placed in the cathode chamber and 70% sulphuric acid placed in the anode chamber. The current density is 12 amperes, and the E.M.F. 10 — 15 volts. The current is allowed to pass for 5 hours, the temperature being kept below 20°. The product is then poured into water, and the solid filtered off, dried and recrystallised from petroleum ether ' Yield.— 40% theoretical. M. P. 204°— 205°. (Z.e., 8, 288.) Pkepakation 412. — Di-ethyl Adipate (Di-ethyl ester ol hexan di-acid). COOC 2 H 5 .(CH 2 ) 4 .COOC 2 H 5 . C 10 H 18 O 4 . 202. Ethyl Acrylate. CH 2 : CH.COOC 2 H 5 . C 5 H 8 0 2 . 100. A nearly saturated solution of potassium ethyl succinate (1*5 parts of salt to 1 part of water) is placed in a tall beaker, which must not be more than half full, and which should be cooled in ice water. An anode of stout platinum wire, made into a spiral, is introduced. The cathode consists of a piece of sheet platinum. A current of 50 — 75 amperes per sq. dcm. of anode surface is then passed through. Much frothing takes place. At the end of the reaction — 70 c.cs. of solution require 20 ampere hours — the mixture with the adipic ester floating on the surface is diluted with water in a separating funnel, and extracted twice with ether. The ethereal extract is dried over calcium chloride and placed in a distilling flask. After removing ether, the fraction distilling up to 120° containing ethyl acrylate is separately collected. The residue containing diethyl adipate is distilled under reduced pressure. COOC 2 H 5 .CH 2 CII 2 COOK COOC 2 H 5 .CH 2 .CH 2 j ; ' | -;- 20() 2 -f 2K '". COOC 2 H 5 .CH 2 .CH 2 COO:K COOC 2 H 5 .CH 2 .CH 2 Yield of Diethyl Adipate.— 30— 35% theoretical ; B.P. 760 245° ; colour- less liquid with characteristic odour. Ethyl acrylate, which is a by- product, is only obtained in very low vield ; B.P. 760 101° — 102°. (T. R. S. E., 36, 211.) CHAPTER XXIX PRODUCTS FROM NATURAL SOURCES Preparation 413. — Quinine Sulphate. 80 — 100 gms. of powdered cinchona bark are placed in a mortar and ground up with about 250 c.cs. of milk of lime. The whole is evaporated to dryness on the water bath, and the mass powdered up when cold. This residue is shaken up with about 200 c.cs. of chloro- form, and allowed to stand in a flask for about 12 hours. It is then filtered and washed with chloroform. The quinine is removed from the chloroform extract by shaking up 2 or 3 times with dilute sulphuric acid and then with water, until the aqueous solution no longer exhibits a blue fluorescence. The acid and aqueous extracts are carefully neutralised with ammonia, and the whole is evaporated on the water bath until quinine sulphate begins to separate out; it is filtered off, on cooling. Another crop of crystals may be obtained by concentrating the mother liquor. The quinine sulphate may be recrystallised from water. Yield. — 1 — 2 gms. The free base may be isolated by dissolving the sulphate in water slightly acidified with dilute sulphuric acid. Excess of sodium carbonate solution is then added, when the quinine is precipitated. It is filtered off, washed and dried. M.P. 175°. Preparation 414. — Caffeine (Theine). CH 3 .N — CO rn CO.C— N< + H 2 0. 212. I II >CH CH 3 N— C— NX J lb. of tea is boiled up with 600 c.cs. of water for 15 minutes, and filtered through fine cotton, the leaves being washed with about 300 c.cs. of boiling water. The filtrate is heated to boiling, and basic lead acetate (made by boiling lead acetate with litharge and water, and filtering) is added until no further precipitation of the albumens and tannins present takes place. This is filtered and the residue washed with hot water. The lead in the filtrate is precipitated by adding dilute sulphuric acid. The clear liquor is decanted from the lead sulphate, and concentrated to about 300 c.cs., animal charcoal being added. After filtering and cooling, the filtrate is extracted several times with chloroform. The chloroform is removed by distillation on the water bath, and the crude product boiled up with water and animal charcoal, and filtered. The filtrate is then concentrated until crystallisation takes place. 394 PRODUCTS FROM NATURAL SOURCES 395 Yield. — 1 — 2 gms. Fine needles, containing 1H 2 0 ; M.P. 132°— 133°. Caffeine may be synthesised from uric acid. (D.R.P., 121224.) Peeparation 415. — D- Alanine (D-2-Amino-propan acid). CH 3 .CH(NH 2 )COOH. C 3 H 7 0 2 .N. 89. Glycocoll-ester Hydrochloride (Hydrochloride of ethyl ester of amino ethan acid). CH 2 (NH 2 .HCl.).COOC 2 H 5 . C 4 H 10 0 2 .N.C1. 139-5. The raw material employed is the cheap waste of raw Milan silk, 500 gms. of which are treated with 2 litres of fuming hydrochloric acid (D. 1-19) and frequently shaken until, in the course of an hour, the threads have fallen to pieces. The flask is warmed, with frequent shaking, on a steam bath ; the liquid foams considerably, and a dark violet solution is produced. This is boiled under a reflux condenser for 6 hours ; it is advisable to add a few gms. of animal charcoal. When quite cold, the acid liquor is filtered through a coarse but strong filtering cloth, and evaporated under reduced pressure (10 — 15 mm.) at 40° — 45° to a thick syrup. This is treated while still warm with 3 litres of absolute alcohol, and a very rapid current of dry hydrogen chloride passed in without cooling and with frequent shaking, until the liquid is saturated. In this process complete solution must occur, and the alcohol must boil. The operation is usually finished in 1J hours. If the current of hydrogen chloride, and consequently the rise in temperature, is too small, the mixture must be boiled afterwards for \ hour on the water bath, in order to render the esterification as complete as possible. The very dark brown liquid is now cooled to 0°, and " inoculated " with a few small crystals of glycocoll-ester hydrochloride, and the greater part of the glycocoll-ester hydrochloride separates in the course of 12 hours at 0° in the form of a thick paste of crystals. The mass is filtered at the pump through coarse linen, well pressed, and washed with a little ice-cold alcohol. The acid alcoholic solution is evaporated as completely as possible under low pressure from a bath at 40° — 45°, and the residual syrup is again esterined with \\ litres of alcohol and hydrogen chloride, as before. The cold solution is " inoculated," and allowed to stand for 2 days at 0°, when the, remainder of the glycocoll is for the most part precipitated as ester hydrochloride. The solution, after filtration, is again evaporated under reduced pressure. The syrup left behind contains the hydro- chlorides of the other amino-acid esters. In order to liberate the esters, the residue is dissolved by vigorous shaking at ordinary temperature in the smallest quantity of water (about \ volume). To the solution is added about twice its volume of ether, and the whole is carefully cooled in a freezing mixture. Strong caustic soda is then cautiously added until the free acid is almost neutralised, and, finally, a saturated solution of potassium carbonate. On vigorous shaking, a considerable part of the liberated esters goes into solution in the ether. The ether is now poured off and replaced by fresh ether. The whole is carefully cooled, then an excess of concentrated alkali is added, and immediately afterwards 396 SYSTEMATIC ORGANIC CHEMISTEY potassium carbonate in small portions, until the whole mass has become a thick paste. The ether is repeatedly renewed during the operation. The extraction with ether is continued until the extracts are colourless. This requires 4 — 5 litres of ether. The united ethereal solutions, which are brown in colour, are shaken for 5 minutes with potassium carbonate, then poured off, and dried for 12 hours over anhydrous sodium sulphate. When the greater part of the ether has been evaporated at ordinary pressure on a water bath, the distillation is continued under a pressure of 10 — 12 mms. At ordinary temperature, ether first passes over. The distilling vessel is now warmed in warm water, when a first fraction is obtained, which still contains alcohol and ether, and also some glycocoll ester and alanine ester. When the temperature of the bath has risen to 55°, the main part of the alanine ester begins to boil. The operation is discontinued when, at a bath temperature of 80°, nothing more distils over. In this way 110 — 125 gms. distillate are obtained, consisting for the most part of alanine ester. To obtain free alanine the alanine ester is heated for about 6 hours with 5 times its weight of water on a water bath, until the alkaline reaction has disappeared. The solution is evaporated on a water bath till crystallisation begins. The liquid is allowed to stand at 0°, when about 30 gms. alanine separate ; optical examination shows this to consist of almost pure ^-compound. From the mother liquor a second crop of 20 — 25 gms. may be obtained, and this still consists of fairly pure active amino-acid, so that the total yields amount to 50 — 55 gms. The last mother liquor still contains a fair amount of active alanine, but it is mixed with so much racemic substance that it cannot be separated from it by mere recrystallisation from water. The first two crops are dissolved once more in hot water, and the liquid evaporated on the water bath till it begins to crystallise. At 0° a large quantity of the pure, active amino- acid separates out. Glycocoll-ester hydrochloride : Colourless needles ; soluble in hot alcohol ; very soluble in water ; M.P. 144°. D-alanine : Needles ; soluble in water ; decomposes on heating ; [a] 2 D ° = + 9-55° (HC1). (J. pr., [2], 37. 160 ; B., 27, 60; 32,2459.) Preparation 416. — Cystine (Di-(2-amino-2-carboxyl-ethanyl-(l) )- disulphide). HOOC.CH(NH 2 ).CH 2 S v > C 6 H 12 0 4 N 2 S 2 . 240. HOOC.CH(NH 2 ).CH 2 S/ 500 gms. of horsehair are boiled in a flask of 3 litres capacity with 1J litres of cone, hydrochloric acid (about 30% strength) for 6 hours under a reflux condenser. The dark-coloured liquid is diluted with 4 litres of water, and, while kept fairly cool, is treated with cone, potassium hydroxide solution (33%) until the reaction is only faintly acid. To clarify the liquid it is warmed and vigorously stirred for some time with about 40 gms. of animal charcoal, and filtered. PRODUCTS FROM NATURAL SOURCES 397 The filtrate is exactly neutralised with potassium hydroxide, and set aside to crystallise at low temperature, preferably in the ice chest, for 5 — 6 days. The cystine which separates is filtered at the pump, washed with, cold water, then dissolved in the smallest possible quantity of warm 10% ammonia, again treated with animal charcoal in the warm, and finally precipitated from the filtrate by the addition of acetic acid. This operation is repeated once more ; the final product is quite colourless and free from tyrosine. Yield. — 15 gms. Colourless crystals. (E. Fischer, " Organic Prepara- tions," 1908.) Peepaeatton 417. — Glucosamine Hydrochloride (Hydrochloride of 2-amino-tetrol-(3.4.5.6-hexanal-(l) ) ). CH 2 OH.(CHOH) 3 CH(NH 2 : HCl).CHO. C 6 H 13 0 5 . 165. The carapaces and claws of lobsters, which have been cleaned, as far as possible mechanically, are digested for 24 hours with cold dilute hydrochloric acid. They may then be cut up easily, and freed from adherent fibres and flesh. 100 gms. of the material thus prepared are covered in a porcelain dish with fuming hydrochloric acid, and heated to gentle boiling on a sand bath. The chitin quickly goes into solution, and the liquid becomes dark in colour. The liquid is evaporated until a considerable crystallisation of glucosamine hydrochloride has taken place, then allowed to cool, filtered at the pump through linen or hardened paper, and washed with a little cold hydrochloric acid. The mother liquor, on further evaporation, yields a second crop of crystals. To purify the salt it is dissolved in warm water, and the solution concentrated till crystal] isation begins. Colourless crystals ; soluble in hot water. (B., 17, 213.) Peeparation 418. — Tyrosine (2-Amino-3-(j9-hydroxyphenyl)-propan acid). HO.C 6 H 4 .CH 2 .CH(NH 2 ).COOH. C 9 H n O s . 167. 100 gms. of silk waste are boiled for 6 hours under a reflux condenser with 300 c.cs. of fuming hydrochloric acid (D. 1-19). The greater part of the hydrochloric acid is removed by evaporating the brown-coloured solution under reduced pressure ; the residue is dissolved in water, filtered, and made up to a known volume. The percentage of hydrochloric acid is determined by titration of an aliquot part of the liquid, and the amount of sodium hydroxide calculated for the whole solution is then added, with ice cooling and constant stirring. A brownish-black precipitate is at once produced. After it has stood for an hour in ice water, it is filtered ofE at the pump, dissolved again in hot water, and boiled vigorously with about 10 gms. of animal charcoal. The filtered liquid is now colourless, and deposits pure tyrosine on cooling. By concentrating the mother liquor a second crop of crystals may be obtained. Yield. — 5 — 6 gms. Colourless crystals : soluble in hot water. (Z. ph., 48, 528.) 398 SYSTEMATIC OKGANIC CHEMISTKY Preparation 419. — Furfurol. CH CH \ C 5 H 4 0 2 . 96. CH\ /C.CHO. A mixture of 200 gms. of bran, 200 gms. of cone, sulphuric acid, and 600 gms. of water is distilled from a large flask till the distillate measures about 600 c.cs. The latter is neutralised with caustic soda, mixed with 150 gms. of common salt and again distilled, till about 200 c.cs. have passed over. This distillate is again saturated with common salt, extracted with ether, the extract dried over anhydrous sodium sulphate, the ether removed on the water bath, and the residue distilled, the fraction 160° — 165° being collected separately. Yield. — 6 gms. Colourless liquid ; burnt smell ; darkens on standing ; B.P. 162°. (A., 74, 280 ; 116, 258.) Preparation 420. — Oleic Acid (9-Octadecen acid). CH 3 (CH 2 ) 7 CH = CH(CH 2 ) 7 COOH. C 18 H 34 0 2 . 282. 10 gms. of potassium hydroxide in 100 c.cs. of alcohol are heated with 30 gms. olive oil for 1 — 2 hours under a reflux. The alcohol is removed on a water bath, and dilute acetic acid is added to the residue until it is neutral to phenolphthalein. 30 gms. of cone, lead acetate solution are then added, which precipitates a mixture of the lead salts of oleic, palmitic, and stearic acids. The mixture is filtered and washed with alcohol to remove unchanged oil. It is then extracted in a Soxhlet apparatus with ether, which dissolves lead oleate. When the ether is evaporated lead oleate remains. Pure dilute nitric acid is added, and oleic acid separates as an oil. The oil is removed by means of a separating funnel, dried over calcium chloride, and distilled under reduced pressure. C 3 H 5 (O.COC 17 H 3 3)3 + 3KOH -> 3C 17 H 33 COOK + C 3 H 5 (OH) 3 . Yield.— 50% theoretical (14 gms.). Colourless oil ; M.P. 14° ; B.P. 10 223° ; decomposes on heating at ordinary pressures ; D.\ 5 0-895. (B., 27, 172.) CHAPTER XXX STEREOCHEMICAL REACTIONS Preparation 421. — a-Brom-cinnamic Acid (3-Phenyl-2-brom-2-propen acid) 0 C 6 H 5 .CH : CBr.COOH. C 9 H 7 0 2 Br. 227. 5 gms. (1 mol.) of pure a-brom-allocinnamic acid are placed in a test tube with a thermometer immersed in the substance. The tube is immersed in a bath of cone, sulphuric acid heated to 200° — 210°, and kept there for 10 minutes. After cooling, the product is dissolved in dilute alkali, and after neutralising the excess of alkali the solution is treated with a solution of barium chloride, which precipitates the barium salt of a-brom-cinnamic acid. The free acid can be liberated in the usual way. C 6 H 5 CH C 6 H 5 CH ll ^ II Br.C.COOH COOH.C.Br a-Brom-cinnamic acid. a-Brom-allocinnamic acid. M.P. 131°. M.P. 120°. Yield. — 80 — 85% theoretical (4 — 4-2 gms.). Colourless prismatic needles ; soluble in hot benzene ; M.P. 131°. (J. C. S., 83, 686.) Preparation 422. — Mesaconic Acid (£mws-3-Carboxy-2-buten acid). CCOOH. C 5 H 6 0 4 . 130. II HOOC.C.H 20 gms. of citraconic acid (see p. 236) are dissolved in the minimum quantity (about 25 c.cs.) of pure dry ether in a quartz flask. 5 gms. of chloroform and a few drops of a moderately strong solution of bromine in chloroform are then added. The solution is exposed to strong sunlight, or to the rays of a mercury vapour lamp. Mesaconic acid soon begins to separate on the side of the flask nearest the light. The flask is occasion ally turned, and drops of bromine are added at intervals until no further separation takes place. The pasty mass is filtered, washed with ether, and dried. CH 3 CH 3 ! I CCOOH -> CCOOH II II CH.COOH HOOC.C.H Yield. — 73% of complete conversion (15 gms.). Colourless crystals ; 399 400 SYSTEMATIC ORGANIC CHEMISTRY M.P. 202° ; somewhat soluble in water ; insoluble in ether and in chloroform. (A., 188, 73.) Preparation 423. — Benz-^-aldoxime (/5-Benzaldoxime). C 6 H 5 CH || C 7 II 7 ON. 121. N.OH 12 gms. a-benzaldoxime are dissolved in 50 c.cs. pure anhydrous ether. Dry hydrogen chloride is passed into this solution, using a rather wide delivery tube, since the hydrochloride of the /S-oxime, which separates quickly, is liable to block the end of the tube. The precipitate is filtered off, washed with ether, transferred to a separating funnel and mixed with 50 c.cs. of ether. Cone, sodium carbonate solution is then added, with shaking, until effervescence ceases. The ethereal layer, which con- tains the /?-oxime, is separated from the lower aqueous-sodium chloride layer, dried over anhydrous sodium sulphate, and the ether removed in a vacuum desiccator. The residue forms a mass of small needles, which are pressed out on a porous plate. Yield.— Almost theoretical (10 gms.). M.P. 128°— 130° (on quick heating) . (B., 23, 1684.) C 6 H 5 CH C 6 H 5 .CH II -> II HON N.OH. Preparation 424. — Resolution of Inactive Mandelic Acid into its Optically Active Components. COOH I H— C— OH. C 8 H 8 0 3 . 152. I CeHs 20 gms. (less than 1 mol.) of crystallised cinchonine, 10 gms. (1 mol.) of mandelic acid (recrystallised from benzene) and 500 c.cs. of water are heated with agitation in a flask on a boiling water bath for an hour. After cooling to laboratory temperature, the undissolved material is filtered off, but not washed. The nitrate is left in an ice chest to cool to 6° — 8°, and then seeded with a few crystals of ^-cinchonine mandelate ; if this seeding material is not available, a small quantity may be prepared in one of the following ways : — 1. The point of a glass rod is dipped in the filtrate, then withdrawn and allowed to dry in the air ; during this slow evaporation some crystals of (Z-cinchonine mandelate form on the rod. The rod is again immersed in the cold solution, and occasionally rubbed against the sides of the containing vessel. 2. A few c.cs. of the filtrate are treated with saturated brine solution until a slight precipitation takes place, then heated to redissolve, and finally left to stand several days in a cool place until crystals separate. These crystals contain some e£-cinchonine mandelate, and serve for seeding material. STEREOCHEMICAL REACTIONS 401 After seeding, the nitrate is left for a few days at 6° — 8°, until no more crystals of ^-cinchonine-^-mandelate separate out. These are filtered off, dried on a porous plate, and the nitrate A reserved for the preparation of Z-mandelic acid. When dry, the crystals are dissolved in 25 times their weight of water by heating in a flask on a boiling water bath for an hour ; the undissolved portion is filtered off, but not washed ; the nitrate is seeded with a few crystals of cZ-cinchonine-<#-mandelate (reserved from the first product if purer material is not available), and left to stand at 6° — 8° for a few days until no further crystallisation takes place. The crystals are filtered off, redissolved in 30 parts of water, and the solution treated with a slight excess of ammonia to precipitate the cinchonine, which is filtered off. The nitrate containing ammonium e£-mandelate is acidified with hydrochloric acid and extracted with ether. The ether is evaporated off, the residue is heated for some time on a water bath, and then, after cooling, crystals of ^-mandelic acid separate. These are pressed on a porous plate, and recrystallised from benzene. Colourless needles ; M.P. 133° — 134° ; easily soluble in hot, somewhat soluble in cold water ; [d]% )0 = + 157° in aqueous solution. A sample of mandelic acid showing lsevo-rotation may be obtained from filtrate A by liberating the free acid, after the manner described for the d-acid. (B., 16, 1773 ; 32, 2385.) Pkepakation 425. — Resolution of a-Phenylethylamine. (p. 360.) C 6 H5\ >CH.NH 2 . C 8 H n N. 121. Commercial dry malic acid (1 part — 1 mol.) is covered with 4 parts of cold water in a beaker. The quantity of racemic a-phenylethylamine (1 mol.) necessary to form the acid salt is then added, during a few minutes with constant stirring. Both base and acid dissolve, but before the acid has completely disappeared the solution becomes slightly syrupy, and a crystalline powder begins to separate. The mass is stirred with a glass rod until the malic acid is all dissolved, and then left to stand overnight. The crude £-malate of ^a-phenylethylamine is filtered off with suction, well pressed down, and washed with a little cold water. [The mother liquor A, containing chiefly the Z-malate of I- a-phenylethylamine, is reserved for the preparation of the famine (see below).] The crude salt, which, when dry, is approximately equal in weight to that of the phenyl - ethylamine used, is recrystallised 3 or 4 times from water. The following method is convenient (p. 14) : the crude salt is divided into two portions, B and C. B is dissolved in the minimum of hot water on a boiling water bath, filtered hot, if necessary, and set aside to crystallise ; the formation of small crystals should be induced by cooling in ice water and scratching with a glass rod. When no more crystals separate, the crop B x is filtered off, and the nitrate and small quantity of washings used to recrystallise C from which crop C x is obtained. B x is recrystallised in the minimum of boiling water, yielding crop B 2 and a mother liquor, which is used to recrystallise C x . The recrystallisation is continued in this manner until 402 SYSTEMATIC ORGANIC CHEMISTRY crops B 4 and C 4 are obtained. B 4 is pure c?-amine-£-malate, and is set aside. The mother liquors from C l5 C 2 , C 3 and C 4 , are combined and evaporated to about \ of their volume, then cooled in ice water, and the resulting crop of crystals D filtered off. C 4 is recrystallised once more from fresh boiling water, and the mother liquor from C 5 is used to recrystallise D. C 5 is pure, and T> 1 is recrystallised 4 more times from water, after which it is pure. If large quantities of salt are being recrystallised, the mother liquors of J) 1 — D 5 should be worked up after the above manner to yield more ^-amine Z-malate. The yield of pure cZ-amine £-malate should be about 70% of the crude product. The pure salt is dissolved in water, the solution placed in a separating funnel, and cone, caustic soda solution added so long as any turbidity of the aqueous layer is produced. The upper layer of base is separated, and the lower aqueous layer extracted with ether to recover any dissolved base. The ethereal extract is united with the base and dried over anhydrous sodium sulphate. The ethereal solution is introduced, in portions at a time, to a Claisen distilling flask of appro- priate size, and the ether distilled off (see p. 32). The residue is then distilled in an apparatus filled with hydrogen, the fraction 180° — 190° being collected. For polarimetric observations the amine should be distilled directly into a polarimeter tube, as it is a strong base which absorbs carbon dioxide with avidity. Yield. — 90% theoretical (calculated on pure malate), or 30% of the weight of racemic base used. In the above resolution an equivalent amount of the carbamate of the base can be used in place of the free base. For the isolation of the l-base the solution A (referred to above) is treated with an excess of caustic soda to liberate the base, which is extracted with ether. The ethereal extract is dried over anhydrous sodium sulphate, and after the removal of the ether the base passes over at 185° — 190°. This base, which is lasvo-rotatory, is treated with tartaric acid, just as the racemic base was with malic acid, and the pure ?-base obtained after six recrystallisations of the salt. a-Phenylethylamine : B.P. 186°— 187° ;«]>=- + 38-28° and [a] D - + 40-27 at 15°. ' (J. pr., 72, 307.) B. Bj^ B 2 B 3 B 4 C O2 O3 0 5 CHAPTER XXXI DECOMPOSITIONS Peeparation 426.— Butyric Acid (Butan acid). CH s .CH 2 .CH 2 .COOH. C 4 H 8 0 2 . 88. 10 gms. of ethyl malonic acid (p. 234) are introduced into a small dis- tilling flask, which is placed in an oil bath with the side tube sloping upwards. A cork, carrying a thermometer with bulb immersed in the substance, is inserted in the neck of the flask. The substance is heated at 180° until no further carbon dioxide is evolved. The side tube of the flask is then sloped downwards and the product (butyric acid) distilled, the fraction 160° — 165° being collected. CH s .CH a CH(COOH) 2 -> CH 2 .CH 2 .CH 2 .COOH + C0 2 . Yield.— 85% theoretical (5-5 gms.). Colourless liquid ; rancid odour ; B.P. 162-3° ; D. 16 [ 5 0-8141. (A., 138, 218 ; J., 1868, 514.) Preparation 427. — Pyrogallol (1.2.3-Trihydroxy benzene). 10 gms. of gallic acid and 20 gms. of powdered pumice are mixed and placed in a retort. A cork, carrying a delivery tube, is inserted through the tubulus to serve for the entrance of carbon dioxide. The retort is then heated on a sand bath with a stream of carbon dioxide passing through, the stem of the retort sloping downwards into a receiver. Crystals of pyrogallol condense in the stem, which should be warmed with a small flame to cause the product to melt and flow down into the receiver. Yield.— 40% theoretical (3 gms.). Colourless crystals ; M.P. 133° ; soluble in alcohol, ether and water. (A., 101, 48.) Preparation 428. — Diethyl Collidine Dicarboxylate (2.4.6 -Trimethyl- 3.5-dicarbethoxy pyridine). C 6 H 3 (OH) 3 . 126. C 6 H 2 (OH) 3 .COOH C 6 H 3 (OH) 3 + C0 2 . CH 3 C C 2 H 5 OOC.Ci ■C.COOC 2 H 5 C 14 H 19 0 4 N. 265. [C.CH 3 20 gms. of ethyl dihydrocollidine dicarboxylate (see Preparation 91) and 403 d d 2 404 SYSTEMATIC ORGANIC CHEMISTRY 20 gms. alcohol are placed in a small flask, which is immersed in a bath of cold water. Nitrous fumes (p. 509) are led into the mixture until a test sample dissolves to a clear solution in dilute hydrochloric acid. The alcohol is then evaporated off on a water bath, the residue treated with sodium carbonate until alkaline, and the oil which separates extracted with ether. The ethereal extract is dried over potassium carbonate, the ether evaporated, and the residue distilled. The fraction 290° — 310° is collected and redistilled, the pure ester distilling at 308° — 310°. C 5 H 2 N(CH 3 ) 3 (COOC 2 H 5 ) 2 + O C 5 N(CH 3 ) 3 (COOC 2 H 5 ) 2 + H 2 0. Yield.— 80% theoretical (16 gms.). Yellow oil; B.P. 308°— 310°. (A., 215, 8.) Preparation 429. — Collidine (2.4.6 -Trimethyl pyridine). CH 3 CH 3 <^ ^>N C 8 H n N. 121. " CH 3 10 gms. of powdered dry di-potassium collidine dicarboxylate (see Preparation 178) are intimately mixed with 20 gms. of slaked lime, and the mixture introduced into a 50-cm. length of combustion tubing, closed at one end. A loose plug of asbestos is placed in the open end of the tube, the tube is tapped horizontally on the bench to make a passage for gas and then connected by means of an adapter to a small receiver. The tube is placed in a sloping combustion furnace, so that the sealed end is slightly elevated. The closed end is first heated, the rest gradually,, and finally the whole length is strongly heated with the tiles in position. The distillate is taken up with ether, the extract dried over solid potassium hydroxide and distilled, the fraction 169° — 174° being separately collected. C 5 N(CH 3 ) 3 (COOK) 2 + 2Ca(OH) 2 -> 2CaC0 3 + 2KOH + C 5 NH 2 (CH 3 ) 3 . Yield. — Almost theoretical (4 gms.). B.P. 172° ; greenish-yellow liquid with an obnoxious odour. (A., 215, 32.) Preparation 430. — Thiophen (1.3 - Di-en -1.4- butylene sulphide). CH— CH II II CH CH C 4 H 4 S. 84. 100 gms. (less than 1 mol.) of phosphorus trisulphide (p. 507) and 100 gms. (1 mol.) of thoroughly dry sodium succinate are intimately mixed and placed in a retort, which is of such a size that the mixture does not more than half fill it. The retort is connected to a condenser, and the latter passes through a cork into a receiver cooled in a freezing mixture. A wash bottle containing dilute caustic soda and fitted with a cork carrying two delivery tubes is connected on the one side to the receiver, and on the other to a draught chamber (or a very slight suction DECOMPOSITIONS 405 from a pump). On heating the retort gently with a small flame a reaction soon commences, and the mass swells up with the evolution of much sulphuretted hydrogen. At this stage the flame is withdrawn and the reaction allowed to proceed spontaneously until completion (e.g., till gas ceases to bubble through the wash bottle). The contents of the receiver j are distilled from a water bath, washed with dilute caustic soda, dried over metallic sodium and redistilled. (CH 2 .COONa) 2 + 4H 2 S -> C 4 H 4 S + Na 2 S + 2S + 4H 2 0. Yield. — 33% theoretical (40 gms.). Colourless liquid ; faint smell resembling that of benzene ; B.P. 84°. (B., 18, 454.) Preparation 431. — Thioxene (1. 4-Dimethyl-thiophene). CH— CH II II (CH 3 )C C(CHo) C 6 H 8 S. 118. Y 6 gms. (1 mol.) of acetonyl-acetone (see p. 188) are heated with 4 gms. (excess) of finely powdered phosphorus pentasulphide in a sealed tube at 140° — 150° for an hour. On cooling, a colourless liquid and a solid are obtained ; the former is poured off and fractionally distilled. The distillation is repeated over metallic sodium, the fraction 132° — 136° being retained. CH 2 .CO.CH 3 CH = C(CH 3 ) ( + P2S5 ^ j /S. CH 2 .CO.CH 3 CH = C(CH 3 ) Yield. — 50% theoretical (3 gms.). Colourless, mobile liquid ; charac- teristic odour ; B.P. 135° ; D. 1 ^ 5 0-9755 ; gives a cherry-red colour with a solution of isatin in concentrated sulphuric acid ; this colour changes to reddish-brown on warming. (B., 18, 2251 ; 20, 1747.) Preparation 432— Phenyl Isothiocyanate (Phenyl mustard oil). C 6 H 5 NCS. C 7 H 5 NS. 135. 64 c.cs. cone, hydrochloric acid and 20 gms. thiocarbanilide are boiled for 30 minutes in a flask attached to a reflux condenser, when the phenyl isothiocyanate separates as an oil. 40 c.cs. water are added and the whole distilled until about 15 c.cs. remain in the flask. The distillate is extracted with ether, which is then dried with calcium chloride. The ether is removed by distillation, and the fraction boiling at 197° — 222° collected. This is redistilled, and the fraction 218° — 222° retained. HC1 (C 6 H 5 NH) 2 CS > C 6 H 5 NCS + C 6 H 5 NH 2 (HC1). Yield — 55% theoretical (7 gms.). Colourless liquid with pungent odour ; B.P. 222° ; D 15 5 1-135. (Z. Ch., 1869, 589.) Preparation 433. — Trimethylethylene (2-Methyl-2-buten). (CH 3 ) 2 : C : CH.CH 3 . C 5 H 10 . 70. 20 gms. (1 mol.) of amyl alcohol (from fusel oil) are mixed with 30 gms. 406 SYSTEMATIC OKGANIC CHEMISTRY of anhydrous zinc chloride in the form of small lumps, left for 24 hours, then heated on a sand bath, the low-boiling distillate being collected and carefully fractionated. The product is a mixture of several isomeric amylenes, but consists mainly of tri-methyl-ethyiene. (CH 3 ) 2 : C : CH.CH3. The receiver must be cooled in ice. C 5 H n OH — H 2 O->C 5 H 10 . Volatile liquid ; B.P. 370°. (A., 128, 225.) Peepaeation 434. — Citraconic Anhydride (Anhydride of c^-3-carboxyl- 2-buten acid). CH3CCO J )>0. C 5 H 4 0 3 . 112. HCCO 250 gms. of crystallised citric acid are dehydrated by heating in a porcelain basin to a temperature not exceeding 150°. When the acid has become fluid the whole is allowed to cool, removed from the basin and coarsely powdered. The anhydrous acid is then placed in a retort and rapidly distilled. The distillate separates into two layers, the upper layer consisting of water and citraconic acid and the lower layer of impure citraconic anhydride. The layers are separated and the upper layer fractionated, the fraction 190° — 210° being collected and added to the anhydride layer. This mixture is distilled under 30 mms. pressure, the fraction 110° — 114° being retained. CH 2 .COOH I COH.COOH I CH 2 .COOH 7^.-22—25% theoretical (30—35 gms.). Colourless liquid : B.P. 30 110°— 114° ; B.P. 760 213°— 214°. (A., 188, 73.) Peepaeation 435. — Ethylene (Ethen). CH 2 : CH 2 . C 2 H 4 . 28. 50 c.cs. of syrupy or^o-phosphoric acid (D. 1-75) are heated until a thermometer in the liquid indicates 210°, and alcohol run in very slowly by means of a dropping funnel drawn out to a point and reaching to the bottom of the flask. During the addition the temperature must be kept between 200° and 220°. The gas is dried by bubbling through cone, sulphuric acid. C 2 H 5 OH — H 2 0 = C 2 H 4 . Colourless gas with sweet smell ; sparingly soluble in water, more readily in alcohol and ether ; liquifies at 10° and 60 atms. (P. C. S., 17, 147.) CH 3 ! C.CO + C0 2 + 2H 2 0. I )o CHCO DECOMPOSITIONS 407 Preparation 436— Acetonitrile (Methyl cyanide). CHgCN. C 2 H 3 N. 41. 15 gms. of phosphorus pentoxide are introduced into a 200-c.c. dis- tilling flask attached to a short condenser. As the pentoxide absorbs moisture rapidly and becomes sticky, it is convenient to push the neck of the distilling flask through a cork, which fits the phosphorus pentoxide bottle, and then to shake the oxide until the required weight is introduced. 10 gms. of powdered acetamide are immediately introduced, the mixture shaken up, and distilled over a small flame, which is constantly moved about. To the distillate is added about half its volume of water, and then solid potassium carbonate, until no more dissolves. The upper layer of liquid, which consists of methyl cyanide, is separated and distilled over a little fresh phosphorus pentoxide. CH 3 .CO.NH 2 — H 2 0 = CH 3 CN. Yield. — 70% theoretical (5 gms.). Colourless liquid ; characteristic odour ; B.P. 82°. (A., 64, 333 ; 65, 297.) Preparation 437. — Acrolein (2-Propenal). CH 2 : CH.CHO. C 3 H 4 0. 56. 200 gms. of glycerine previously dehydrated by heating in an open basin to 170° are mixed with 400 gms. of potassium bisulphate broken to the size of small shot in a glass flask, or better, a metallic retort of at least 4 litres capacity. The delivery tube of the retort is connected to a long condenser to the lower end of which a distillation flask is fastened on tightly (e.g., by means of an adapter). This latter is surrounded by a freezing mixture, and its side tube con- nected to a draught pipe. The whole apparatus is fitted up in a fume cupboard. The mixture is allowed to stand in the closed retort for several days, and then slowly heated and distilled, a gas-ring being used to heat the retort. Water first distils, then the contents of the retort swell consider- ably, and acrolein mixed with water and sulphurous acid passes over. The distillation is continued till, after several hours, practically no more liquid distils. The distillate consists of two layers, the upper one being acrolein, the lower an aqueous solution of sulphur dioxide. The latter is removed by shaking with powdered litharge till no more white lead sulphite is formed. The whole mass is again distilled on a water bath, the receiver being cooled, as before, and the same precautions taken to prevent the escape of uncondensed vapours. The distillate is dried over calcium chloride and again distilled on a water bath. All these operations must be carried out in a good fume cup- board, and, to prevent loss by polymerisation, as quickly as possible. CH 2 OH.CHOH.CH 2 OH -> CH 2 = CH.CHO + 2H 2 0. Yield. — 30% theoretical (35 gms.). Colourless mobile liquid ; pene- trating odour ; attacks the eyes ; polymerises on keeping to a white trans- lucent solid (disacryl) resembling porcelain ; a small quantity of alkali or a 408 SYSTEMATIC OKGANIC CHEMISTRY solution of potassium cyanide brings about the change in a few minutes ; B.P. 52°. (BL, 36, 550 ; A. Ch., [6], 26, 367 ; A. SpL, 3, 180 ; B., 5, 810.) Preparation 438. — Pyruvic Acid (2-Oxy-propan acid). CHg.CO.CO.OH. C 3 H 4 0 3 . 88. 200 gms. of potassium hydrogen sulphate and 100 gms. of tartaric acid are finely powdered and intimately mixed. The mixture is distilled in a short-necked, 2-litre, round-bottomed flask, attached to a moderately long condenser, from a paraffin bath heated to 220°. The apparatus is fitted up in a fume cupboard. The mass froths a great deal at first, and j it is necessary to interrupt the heating when the flask is half full of froth, as otherwise it may boil over. When the temperature of the bath has fallen to about 120° the heating is recommenced. The distillation is continued until no more liquid distils. The distillate is at once fraction- ated under reduced pressure, the fraction 68° — 70° at 20 mms. being separately collected. It may also be fractionated at ordinary pressures, the fraction 130°— 180° being redistilled and collected at 165°— 170°, but it is difficult to obtain it colourless in this way. COOH.CH(OH).CH(OH).COOH = CH 3 .CO.COOH + H 2 0 + C0 2 . Yield— 30% theoretical (20 gms.). Colourless liquid ; polymerises on keeping ; has a characteristic odour somewhat resembling that of acetic acid ; MP. 10° ; B.P. 20 68°— 70° ; B.P. 760 165° ; K = 0-56. (A., 242, 268.) Preparation 439. — Acetaldehyde (Ethanal). CH3.CHO. C 2 H 4 0. 44. The apparatus is set up as shown in sketch (Fig. 53). To the lj-litre , 1 round-bottomed flask is atttached a slanting condenser with a long delivery tube dipping into 30 c.cs. dry ether in a flask surrounded by ice-water, a further delivery tube passing into a second flask containing ether. A tap-funnel is also attached to the flask. 100 gms. (1 mol.) potassium dichromate (or an equivalent quantity of sodium dichromate) and 420 c.cs. of water are placed in the flask and gently warmed on a sand bath. The flame is removed and a warm mixture of 100 gms. (excess) of absolute alcohol and 140 gms. (1 mol.) of cone, sulphuric acid slowly run in from the tap-funnel, the flask being occasionally shaken. Much heat is evolved, and the alcohol which distils is returned by the reflux condenser. When all the alcohol-acid mixture has been added, the flask is heated on a sand bath and warm water (30°) is passed through the condenser. The aldehyde passes over into the ether. Anhydrous sodium sulphate is added to- the ethereal solution, which is still kept in the ice-water. After a time the solution is decanted and the residue washed with a little dry ether. The solutions are combined and dry ammonia gas (for preparation, see p. 503) passed through until the solution is saturated. After standing for an hour, the solution deposits crystals, which are filtered off and washed with a little dry ether. The yield of aldehyde ammonia is about 40% theoretical, calculated on the alcohol used. The crystals are dissolved in an equal weight of \ water, and distilled on a water bath with a mixture of 1J parts cone. DECOMPOSITIONS 409 sulphuric acid and 2 parts water, the receiver being well cooled in a freezing mixture. The temperature of the water bath is gradually raised until the water begins to boil, when the distillation is interrupted. The Fig. 53. distillate is dried with anhydrous calcium chloride, and redistilled from a water bath heated to 30°. The aldehyde is kept in a well-stoppered bottle. 3C 2 H 5 OH + K 2 Cr 2 0 7 + 4H 2 S0 4 -> 3CH 3 .CHO + K 2 S0 4 + Cr 2 (S0 4 ) 3 + 7H 2 0. CH 3 CHO + NH 3 -> CH 3 CH(OH)NH 2 . 2CH 3 CH(OH)NH 2 + H 2 S0 4 -> 2CH 3 CHO + (NH 4 ) 2 S0 4 , Yield. — 40% theoretical (19 gms.). Colourless liquid; sharp odour; B.P. 21° ; J). I 0-807 ; miscible with water, alcohol and ether. (A., 14, 133 ; J. pr., [1], 76, 54.) For modifications of the above method, see Am. Soc. 44, 2658. Dehydrogenation of Primary Alcohols to Yield Aldehydes. When ethyl alcohol is passed over reduced copper at 300° — 400°, decomposition takes place into acetaldehyde and hydrogen, the reaction being reversible. CH 3 .CH 2 OH CH 3 .CHO + H 2 . Methyl alcohol as well as the higher aliphatic and the aromatic alcohols behave similarly. The copper acts catalytically, and while cobalt, nickel, iron, zinc, platinum, also serve, copper is the most suitable. At high temperatures two -side reactions accompany the main reaction. 410 SYSTEMATIC ORGANIC CHEMISTRY 1. The aldehyde formed is split up into hydrocarbon and carbon monoxide. R.CHO — > EH + CO. 2. Dehydration of the alcohol takes place. R.CH 2 .CH 2 OH -> RCH : CH 2 + H 2 0. The operation should, therefore, be conducted at the lowest temperature at which dehydrogenation proceeds. A margin of 20° above this point is generally not unfavourable. Preparation 440. — Acetaldehyde. CH 3 CHO. C 2 H 4 0. 44. A combustion tube 1 metre long is loosely packed for three-quarters of its length with copper oxide (either small lumps or wire form), the layer being held in position with loose asbestos plugs. The tube is placed in a long cylindrical air bath (Fig. 43) fitted with 2 thermometers, preferably nitrogen filled. The oxide is reduced to metal by heating to 180° — 200° in a current of specially purified hydrogen. The reduction occupies about 6 days. The hydrogen (from a Kipp) should be passed first through caustic soda solution, then through cone, sulphuric acid, then over heated copper gauze or turnings (previously washed with alcohol to remove grease) to remove arsenic, and finally through a tower containing sticks of caustic soda. On no account must any part of the apparatus be heated until all air has been expelled from the apparatus. When the reduction is finished, the side tube of a silica distilling flask is connected to the combustion tube, while a dropping funnel is inserted through a cork in the neck of the flask. The other end of the combustion tube is connected first to an empty flask, and then to a worm condenser, which in turn is connected to two suction flasks cooled in ice and salt. The silica flask is heated in an air bath to 300° while alcohol is dropped in at a moderate rate from the tap-funnel. At the same time the combustion tube is heated to 300° or even as high as 340°. The vapours from the tube, after condensation, yield unchanged alcohol, a little water, and up to 40% of acetaldehyde ; the escaping hydrogen is led to a draught pipe. After a time, when the catalyst begins to lose its activity, the temperature of the air bath is raised to near 400°. The aldehyde is separated from the condensed liquid by fractional distillation ; with an efficient column two distillations should give a pure product. The recovered alcohol, after treatment with alkali (to remove traces of acid which always develop) and redistillation, can be again passed over the catalyst. The highest conversion obtainable with one passage over the catalyst is about 40%, since an equilibrium results at this stage. The copper loses its activity after some time, but is easily regenerated by oxidation in a current of air at 300°, and subsequent reduction with hydrogen. CH 3 CH 2 OH CH3CHO + H 2 . (See p. 409.) DECOMPOSITIONS 411 Preparation 441. — Benzil. C 6 H 5 .COCO.C 6 H 5 . C 14 H 10 O 2 . 210. 20 gms. of benzoin and 50 c.cs. of cone, nitric acid (D. = 1-42) are placed in a large flask, which is then heated on an actively boiling water bath. A vigorous reaction soon commences, and torrents of nitrous fumes are evolved at first ; for this reason the operation should be con- ducted in a fume cupboard. After 2 hours' heating, the product is poured into vigorously stirred cold water, the crystalline deposit filtered off, washed with cold water, pressed out on filter paper and recrystallised from alcohol. C 6 H 5 .CO.CH(OH).C 6 H 5 + 0 -> C 6 H 5 CO.CO.C 6 H 5 + H 2 0. Yield. — 80% theoretical (16 gms.). Yellow prisms ; insoluble in water ; M.P. 95° (A., 34, 188.) Preparation 442. — a-Brom-cinnamic Acid and a-Bromallo-cinnamic Acid (Cis- and Tm/is-3-phenyl-2-brom-2-propen acid). 20 gms. (1 mol.) of cinnamic acid dibromide (p. 332) are covered with alcohol and the theoretical amount (2 mols.) of alcoholic potash (say, 70 gms. of a 10% solution) added. After heating for about 15 minutes in a small flask, the mixture is evaporated to dryness in a dish on a water bath. The residue is digested with an amount of water sufficient to dissolve about 3 parts of the potassium salts, and an excess of a 10% solution of barium chloride added. Barium a-bromcinnamate is precipi- tated, while barium a-bromallocinnamate remains in solution. The former is filtered off, washed with dilute barium chloride solution, and the free acid precipitated by treatment with hydrochloric acid ; it is filtered off, washed with water and dried on a porous plate. It is recrystallised from benzene as colourless prismatic needles ; M.P. 131° ; yield 11 gms. The brom-allo-acid is recovered in a similar manner by acidifying the solution containing it (as Ba salt). It is recrystallised from petroleum ether as prisms with a yellow tinge ; M.P. 120°. C 6 H 5 CHBr.CHBr.COOH + 2KOH -> C 6 H 5 CH : CBr.COOK + KBr + 2H 2 0 (J. C. S, 83, 673.) Preparation 443.— Menthene (l-Methyl-4-(l-methyl ethyl)-3-cyclo hexen). C 6 H 5 CH : CBrCOOH. C 9 H 7 0 2 Br. 227. CH(CH 3 ) 2 C HC; jCH 2 C 10 H 138. H 2 C l -CR 2 CH 3 70 gms. (1 mol.) of crude menthyl chloride (p. 327) are added to a warm 412 SYSTEMATIC ORGANIC CHEMISTRY solution containing 75 gms. (excess) of caustic potash dissolved in 320 gms. of phenol. The mixture (contained in a flask) is maintained at 150° for 10 — 12 minutes, and then distilled until the thermometer (still immersed in liquid) registers 200°. The distillate is placed in a funnel and shaken with dilute caustic soda until free from phenol ; it is then distilled over sodium, the fraction 160° — 170° being retained and again distilled over sodium. C 10 H 19 C1 + C 6 H 5 OK -> C 10 H 18 + C 6 H 5 OH + KC1. Colourless liquid ; B.P. 167° ; D.» 0-8064. (B, 29, 1843.) Preparation 444. — Dipentene. C_CH<^ ^CCH 3 . C 10 H 16 . 136. C 10 H 16 . Colourless liquid ; B.P. 178°— 180°. (B., 40, 603 ; A., 245, 196 ; 350, 150.) Preparation 445. — s-Xylenoi (3. 5-Dimethyl-l- hydroxy benzene). (CH 3 ) 2 C 6 H 3 (OH). C 8 H 10 O. 122. 10 gms. of dimethyl cyclohexenone (p. 77) are dissolved in 20 gms. of glacial acetic acid, and the solution cooled by ice- water, care being taken that the acid does not solidify. A solution of 13 gms. of bromine in 10 gms. of glacial acetic acid is added slowly from a dropping funnel with stirring, and the whole allowed to stand overnight in a draught cupboard ; hydrobromic acid is evolved. Next day the solution is heated on a water bath to about 50° with frequent shaking ; after being a short time at this temperature the bath is raised to boiling, and heating continued until there is but slight evolution of hyplrobromic acid. A reflux air condenser is then attached and heating continued over a wire gauze until the acetic acid commences to boil, and until the evolution of hydro- bromic acid almost ceases. The solution is cooled and poured into a cold solution of 75 gms. of caustic potash in 150 c.cs. of water. The by-products insoluble in the potash solution are extracted with ether, and the alkaline solution saturated with carbon dioxide to liberate the xylenol, which is distilled off in steam in presence of carbon dioxide. The distillation is DECOMPOSITIONS 413 stopped when a test portion of the distillate gives no precipitate of tribrom- xylenol (see p. 347) on the addition of a few drops of bromine. The dis- tillate is left in the ice chest overnight, when the greater part of the xylenol crystallises out ; this is filtered off. The xylenol in the filtrate is recovered by saturating with common salt and extracting with ether. CH 2 — CO CH 2 — CO CH 3 .CH CH 3 .CH 2HBr + CH 3 .c/ \cR ~> CH 3 — c/ ScH CH - - C.CH 3 CH — CXH 3 . Yield. — 60% theoretical (6 gms.). Crystalline substance ; M.P. 64° ; B.P. 760 220°— 221°. (Bl, [3J, 11, 702 ; B., 18, 362, 2672 ; 20, 410.) Preparation 446. — Glutaric Acid (Pentan di-acid). COOH.CH 2 .CH 2 .CH 2 .COOH. C,H 8 0 4 . 132. A mixture of 20 gms. of methylene dimalonic ester, 20 gms. of cone, hydrochloric acid and 20 c.cs. of water is heated for 6 hours in a flask under reflux. At the end of this time the product is evaporated to dryness, and the residue (glutaric acid) distilled under reduced pressure ; it distils at 185° — 195° under 10 mms. pressure. The small quantity of anhydride formed is eliminated by warming with a little water. After drying, the product is recrystallised from benzene. CH 2 {CH(COOC 2 H 5 ) 2 } 2 -> COOH.CH 2 .CH 2 .CH 2 .COOH + 4C 2 H 5 OH + 2C0 2 . Yield. — 75% theoretical (6 gms.). Soluble in hot benzene ; M.P. 97°. (B., 27, 2346.) Preparation 447. — 2.6-Dibromaniline (2.6-Dibrom-l-amino benzene). C 6 H 3 (NH 2 )Br 2 . C 6 H 5 NBr 2 . 251. 45 gms. of cone, sulphuric acid, 13 c.cs. of water and 10 gms. of dry dibromsulphanilic acid (p. 342) are placed in a flask, which is fitted with a cork bored with three holes. Through one hole a glass tube, sealed at the lower end and passing down into the mixture, is inserted ; inside this tube a thermometer is placed. The other holes hold glass tubes to convey superheated steam through the flask. The mixture is heated to 170° in an oil bath, and superheated steam is blown through. The temperature rises gradually, but must not be allowed to exceed 180°. Some of the dibromaniline formed is carried over by the steam, but most of it remains in the flask. After about 90 minutes, steam is shut off and the contents of the flask poured into a large volume of cold water. The precipitate is filtered off, dried on filter paper, and recrystallised from petroleum ether. NH 2 .C 6 H 2 Br 2 S0 3 H + H 2 0 -> NH 2 C 6 H 3 Br 2 + H 2 S0 4 . Yield.— 83% theoretical (6 gms.). Colourless needles ; M.P. 83°— 84°. (A., 253, 275.) 414 SYSTEMATIC ORGANIC CHEMISTRY Preparation 448. — Benzene Sulphuric Acid. C 6 H 5 .S0 2 H. C 6 H 6 0 2 S. 142. 40 c.cs. water are placed in a 300-c.c. flask provided with a reflux condenser and dropping-funnel and heated to boiling. 10 gms. of good quality zinc dust are added, the source of heat is withdrawn, and 10 gms. of benzenesulphonic chloride, in small portions at a time, are added from the funnel. A vigorous reaction follows each addition, and this is allowed to subside before more is added. When all is in, the flask is heated for a short time over a small flame, then cooled, and the precipitate of zinc dust and zinc benzenesulphinate filtered off. The precipitate is then mixed with a solution of 10 gms. anhydrous sodium carbonate in 50 c.cs. of water, and the whole heated for 10 minutes on a boiling water bath ; by this means sodium benzenesulphinate is formed and goes into solution. The precipitate is filtered off. The filtrate is evaporated to half its volume, then cooled and acidified with dilute sulphuric acid. After standing, and scratching the sides of the containing vessel with a glass rod, colourless crystals of benzenesulphinic acid separate. These are filtered off and recrystallised from a little water. 2C 6 H 5 S0 2 .C1 + 2Zn -> (C 6 H 5 S0 2 ) 2 Zn + ZnCl 2 . Colourless crystals ; insoluble in water ; M.P. 83°— 84°. (B., 9, 1585.) CHAPTER XXXII MISCELLANEOUS PREPARATIONS Preparation 449. — Epichlorhydrin. CH 2 C1CH.CH 2 . C 3 H 5 0C1. 92-5. V 100 gms. of glycerine are dehydrated by heating on a sand bath until the temperature registers 175°. After cooling to ordinary temperature, it is mixed with an equal volume of glacial acetic acid. Dry hydrogen chloride is passed into the cold solution until saturated (2 hours). The mixture is heated on a water bath, and after standing overnight, is again treated with hydrogen chloride for about 6 hours. The liquid is then distilled. Hydrochloric and acetic acids first pass over ; the fraction 160° — 210°, which contains chiefly dichlorhydrin, is separately collected and used for the next stage. (Yield, about 60 gms.) To the dichlorhydrin is added, with constant stirring, a cooled solution of 50 gms. caustic potash in 100 c.cs. water. The temperature must not be allowed to rise. The epichlorhydrin is then extracted with ether, and the ethereal solution washed with water in a separating funnel, and dried over calcium chloride. The ether is removed on a water bath and the residue fractionally distilled, using a column (see p. 21). The fraction 115° — 125° is then collected. Above this temperature aceto- dichlorhydrin distils. CH 2 OH.CHOH.CH 2 OH + HC1 CH 2 Cl.CHOH.CH 2 OH + HC1 CH 2 C1CH0HCH 2 C1 + KOH Yield — 12 — 15% theoretical (12 — 15 gms.). Colourless mobile liquid, with ethereal smell ; B.P. 117° ; D. 1-203. (A. Spl. a 1, 221.) Preparation 450.— Benzamide. C 6 H 5 CONH 2 . C 7 H 7 ON. 121. 10 gms. of benzonitrile are mixed with 150 c.cs. of 3% aqueous hydrogen peroxide, and about 3 c.cs. of 2N caustic soda added. The mixture is warmed to 40°, and shaken until all the oil disappears and a white solid 415 CH 2 Cl.CHOH.CH 2 OH + a-Monochlorhydrin. CH 2 C1CH0HCH 2 C1 + H. aa-Dichlorhydrin. CH 2 CHCH 2 C1 + KC1 + I O E pichlorhy drin . 416 SYSTEMATIC ORGANIC CHEMISTRY (benzamide) is formed. The solid is filtered off, washed with water, and recrystallised from alcohol. C 6 H 5 CN + H 2 0 2 -> C 6 H 6 CONH 2 + 0. Yield.— Theoretical (12 gms.). M.P. 128°. (B., 18, 355.) Preparation 451.— Cupferron (NH 4 salt of nitrosophenylhydroxyl- amine). .NO C 6 H 5 N< C 6 H 9 0 2 N 3 . 155. \ONH 4 . » 725 gms. phenylhydroxylamine, obtained from the .reduction of nitro- benzene (see Preparation 375), is treated with 3 litres ether. The ether insoluble material (sodium chloride) is filtered off and weighed, this weight being deducted from the weight of crude phenylhydroxylamine. The filtrate is placed in a 5-litre round-bottomed flask, cooled to 0°, and stirred with an efficient mechanical stirrer, while a rapid stream of ammonia gas is passed into the solution. After about 15 minutes the theoretical quantity of freshly-distilled amyl nitrite (107 gms. for each 100 gms. phenyl- hydroxylamine) is added through a dropping funnel. The addition of amyl nitrite requires about 30 minutes, during which time the stream of ammonia is continued, so that ammonia will remain in excess (other- wise a coloured product results). The temperature should not exceed 10° during this addition. After the addition of the nitrite the mixture is stirred for 10 minutes to ensure complete reaction. The cupferron is then filtered off, washed several times with ether, and dried by exposure on sheets of filter paper. It is stored in a bottle, where it is exposed to the vapours of ammonia ; this is effected by placing a small tube con- taining solid ammonium carbonate, and which is drawn out to a fine capillary, inside the bottle of cupferron. /NO yO C 6 H 5 NHOH -> C 6 H 5 N<; or C 6 H 6 NC \ONH 4 ^NO.NH 4 . Yield.— 80— 90% theoretical (800 gms.). This reagent is much used for the estimation of copper and iron (hence its name). See text-books on inorganic analysis. (Am. Soc, 41, 276.) Peeparation 452. — Benzene Sulphonyl Chloride. C 6 H 5 S0 2 C1. 176-5. 150 gms. of sodium benzene sulphonate, which have been dried for 3 hours at 140°, are mixed with 85 gms. of finely divided phosphorus pentachloride in a round-bottomed flask provided with a reflux condenser. The mixture is heated at 17 0° — 180° in an oil bath. The flask should be removed every 4 hours, stoppered, and vigorously shaken until the mass becomes pasty. The mass is poured into a mixture of ice and water, when the benzene sulphonyl chloride sinks to the bottom ; it is separated, washed with water, and distilled in vacuo, the fraction 145° — 150° at 45 mms. MISCELLANEOUS PREPARATIONS 417 being collected. The phosphorus pentachloride may be replaced by 60 gms. phosphorus oxy chloride. 3C 6 H 5 S0 2 .ONa + PC1 5 = 3C 6 H 6 S0 2 C1 + 2NaCl + NaP0 3 . 2C 6 H 5 S0 2 .ONa + POCl 3 = 2C 6 H 5 S0 2 C1 + NaCl + NaP0 3 , Yield.— 75— 80% theoretical (110—120 gms.). Colourless oil; M.P. 14-5° ; B.P. 760 2 46° (decomposition). (B., 42, 1802, 2057 ; " Organic Syntheses," Vol. I., Roger Adams, and others.) Preparation 453.— a-Naphthalene Sulphonyl Chloride. S0 2 C1. C 10 H 7 O 2 ClS 226-5. 30 gms. (1 mol.) of sodium a-naphthalene sulphonate previously dried at 150° are gradually added while warm to 30 gms. (slight excess) of phosphorus pentachloride contained in a basin or beaker. The reaction commences on the addition of the first portions, and further addition is regulated so that the reaction does not become too vigorous. After the final addition the whole is heated on a water bath until homogeneous. After- wards it is transferred to a flask and distilled under reduced pressure until the distillate — which consists at first of phosphorus oxy chloride — weighs 15 — 20 gms. The residue in the flask is poured into a mortar and stirred as it solidifies ; when solid it is mixed with ice water, ground up and filtered. It is then well pressed for a short time on a porous plate, and after complete drying in vacuo over sulphuric acid, is recrystallised from a mixture of benzene and petroleum ether. C 10 H 7 SO 2 OH + PC1 5 -> C 10 H 7 SO 2 Cl + HC1 + POCl 3 . Yield.— 60% theoretical (17-5 gms.). M.P. 66°. f} -Naphthalene sulphonyl chloride is prepared in a similar manner from sodium ^-naphthalene sulphonate. (A., 275, 233.) Preparation 454. — Ethyl Potassium Sulphate. C 2 H 5 O.S0 3 K. C 2 H 5 0 4 SK. 164. To 100 c.cs. ethyl alcohol in a J-litre round-bottomed flask are carefully added with cooling 40 c.cs. cone, sulphuric acid. A reflux condenser is attached and the mixture heated for an hour on the water bath, and then allowed to cool. The liquid is poured into \ litre of water in a porce- lain basin, and to this is added chalk, with stirring, until effervescence ceases.. The calcium sulphate is filtered off, and washed with a little warm water. To the filtrate, which contains ethyl calcium sulphate, is added saturated potassium carbonate solution until the liquid gives a faint alkaline reaction to phenolphthalein. The calcium carbonate is filtered off and washed with a little hot water. The filtrate is then evapo- rated until crystallisation begins, when it is set aside to cool. The crystals s.o.c. E E 418 SYSTEMATIC ORGANIC CHEMISTEY of ethyl potassium sulphate are filtered off and dried, and a further crop obtained hy concentrating the mother liquor. C 2 H 5 OH + H 2 S0 4 -> C 2 H 5 O.S0 3 H > (C 2 H 5 O.S0 3 ) 2 Ca -> C 2 H 5 O.S0 3 K. Yield. — 15% theoretical (45 gms.). Deliquescent, monoclinic plates ; soluble in water ; insoluble in alcohol or ether. (BL, 19, 295.) Preparation 455— Quinol (1.4-Dihydroxybenzene). C 6 H 4 (OH) 2 . C 6 H 6 0 2 . 110. 10 gms. of finely powdered ^-benzoquinone are suspended in about 100 c.cs. of water, and sulphur dioxide passed in until the odour of the gas still remains after standing for some hours. Should the odour disappear saturation is repeated until the solution retains the smell of the gas on standing overnight. The solution is then extracted a few times with ether, the ether distilled off, and the residue recrystallised from a little water containing sulphurous acid and animal charcoal. Yield. — Theoretical (10 gms.). Colourless plates; M.P. 169°; soluble in alcohol, water and in ether ; insoluble in. benzene ; decomposes when quickly heated. (B., 19, 1467 ; C, 1898 (2), 1007.) Preparation 456 . — Amino-azo-benzene. C 6 H 5 N : N.C 6 H 4 NH 2 . C 12 H n N 3 . 197. 10 gms. of finely ground diazoamino-benzene, 5 gms. of aniline hydro- chloride, and 20 gms. of aniline are heated in a beaker at 40° for an hour. After standing overnight at ordinary temperature, the mixture is treated with an excess of dilute acetic acid to dissolve the aniline ; aminoazo- benzene remains undissolved. It is filtered off, washed with water, and recrystallised from dilute alcohol. C 6 H 5 N : N.NH.C 6 H 5 -> C 6 H 5 N : N.C 6 H 4 NH 2 . Yellow needles ; M.P. 126° ; stable basic substance. (B., 19, 1953 ; 20, 372.) Preparation 457. — Nitrosobenzene, C 6 H 5 NO. 107. 4-6 gms. potassium dichromate (or an equivalent quantity of sodium dichromate) are dissolved in 200 c.cs. water and the solution cooled to 0° in a freezing mixture. A mixture containing 4 gms. finely powdered phenylhydroxylamine, 30 gms. cone, sulphuric acid, and 270 c.cs. of water is also cooled in ice water, and to it the dichromate solution is added quickly. The nitrosobenzene which separates is removed by steam distillation, and if any solidifies in the condenser, the water should be run out of the latter until the solid melts and flows down into the receiver. The nitrosobenzene is filtered off from the distillate, pressed on a porous plate until dry, and washed with a little petroleum ether. C 6 H 5 NH.OH + O -> C 6 H 5 NO + H 2 0. M.P. 68° ; colourless or yellow crystals. (D.K.P., 89978 ; 105875.) MISCELLANEOUS PREPARATIONS 419 Preparation 458. — Aniline Nitrate (Phenyl-ammonium nitrate). C 6 H 5 NH 3 .N0 3 . C 6 H 8 0 3 N 2 . 156. Aniline Hydrochloride (Phenyl-ammonium chloride). C 6 H 5 NH 8 .C1. C 6 H 8 NC1. 129-5. The preparation of aniline nitrate is fully described on p. 368 under the preparation of diazobenzene nitrate. The crude product therein obtained is recrystallised by dissolving in a little absolute alcohol and precipitating therefrom with ether. The preparation and purification of aniline hydrochloride is exactly similar. C 6 H 5 NH 2 + HN0 3 = C 6 H 5 NH 3 .N0 3 . C 6 H 5 NH 2 + HC1 = C 6 H 5 NH 3 .C1. Yields. — Aniline Nitrate. — 80% Theoretical (13 gms. from 10 gms. of aniline). Aniline Hydrochloride. — 80% Theoretical (10 gms. from 10 gms. of aniline). Colourless crystals ; soluble in water and alcohol ; insoluble in ether ; aniline hydrochloride melts at 192° ; aniline nitrate transforms to nitraniline at 190°. (A. Ch., [6], 21, 355 ; J., 1861, 495 ; B., 14, 1083.) Aniline Sulphate (Di-phenyl-ammonium) Sulphate. (C 6 H 5 NH 3 ) 2 S0 4 . C 12 H 16 0 4 N 2 S. 284. To 10 gms. (2 mols.) of aniline 15 c.cs. (an excess) of dilute (5N) sulphuric acid are added. The precipitate is recrystallised from a little water. 2C 6 H 5 NH 2 + H 2 S0 4 = (C 6 H 5 NH 3 ) 2 S0 4 . Yield. — 90% theoretical (13 '5 gms.). Colourless crystals ; soluble in water ; slightly soluble in absolute alcohol ; insoluble in ether. (A. Ch., [6], 21, 355 ; B., 18, 3313.) Preparation 459. — Aniline Hydroferrocyanide (Phenyl ammonium ferrocyanide). Aniline is dissolved in cone, hydrochloric acid until only slightly acid. Water is then added until the whole is a saturated solution of aniline hydrochloride at ordinary temperature. A saturated solution of sodium ferrocyanide is then added until precipitation is complete. The solution should be slightly acid after this stage has been reached. The white precipitate is filtered off, washed first with a little alcohol and then ether, and dried by suction. 2C 6 H 5 NH 2 + H 4 Fe(CN) 6 -> 2C 6 H 5 NH 2 .H 4 Fe(CN) 6 [.2H 2 OJ. Yield. — Theoretical. White rhombohedral crystals with greenish tinge ; infusible ; almost insoluble in water, solution being decomposed on boiling with evolution of hydrocyanic acid ; insoluble in alcohol or in ether. Many other aromatic organic bases yield similar compounds. (J. C. S., 121, 1293.) E E 2 420 SYSTEMATIC ORGANIC CHEMISTRY Preparation 460.— ^-Benzoquinone Dichlorimide. C1N<^ ^>NC1. C 6 H 4 N 2 C1 2 . 175. Chlorine is passed into 250 c.cs. water containing 45 gms. caustic soda until the total weight is 332 gms. 750 c.cs. of ice-water are then added, and into the cold solution are slowly run 27 gms. j9-phenylenediamine hydrochloride in 300 c.cs. of water and 60 c.cs. of cone, hydrochloric acid. After the blue colour disappears the dichlorimide separates, is filtered and washed with water until the filtrate is free from chlorine ; it is then recrystallised from 70% alcohol or petroleum ether (40° — 60°). NH 2 / ^NH 2 + 3C1 2 -> C1N<^ ^>NC1 + 4HC1. Colourless needles, which explode at 126° (caution /). (B., 12, 47.) Preparation 461. — Alkyl Nitrophenols (l-Methoxy-2-nitrobenzene), etc. NQ 2 NQ 2 CH 3 0<^ \andCH 3 0<^ ^>N0 2 , C 2 H 5 0^ ^> etc. o-Mtro-anisole. o-Mtro-phenetole. 70 gms. of ortho- or jpara-mtvo phenol, 20 gms. caustic soda, and 40 gms. sodium carbonate are dissolved in 200 c.cs. water. To this solution is added 250 c.cs. methyl (or ethyl) alcohol, 90%, and the whole cooled to 10° and placed in an autoclave. 1-75 gm. mols. methyl (or ethyl) chloride (both are gases at ordinary temperature) are then added, and the temperature is raised to 100° for 8 hours — the pressure being 4—5 atms. The product is poured into water and the alkyl ether separated. The alcohol is then recovered. The alkyl compound is washed with a little caustic soda solution to remove free nitrophenol. It is purified by distillation. / \OH > <^ ^>OCH 3 , etc. Yield.— 75— 80% theoretical (55 gms.). o-Nitroanisole : M.P. 9° : B.P. 265° ; jo-nitroanisole : M.P. 54° ; B.P. 258°. o-Nitrophenetole : M.P. 78° ; B.P. 268° ; ^-nitrophenetole : M.P. 60° ; B.P. 283°. (Z. Ch., 1913, 12, 171.) Preparation 462. — Potassium Phthalimide. / co \ C 6 H 4 < )NK. C 8 H 4 0 2 NK. 185. 2-4 gms. phthalimide (previously dried in a steam oven) are dissolved in 80 c.cs. ethyl alcohol (distilled from lime), the solution is heated to boiling, and a hot solution of 1 gm. (1-| atoms) of potassium in 30 c.cs. of ethyl alcohol added. [The potassium ethoxide is prepared by dissolving the potassium in alcohol diluted with dry ether, which is afterwards MISCELLANEOUS PEEP AR ATI ONS 421 driven off when the solution is raised to boiling on a water bath.] When cold, the white precipitate is filtered off, washed with dry ether, and dried in an oven. 7^.-68% theoretical. Sodium phthalimide may be prepared in a similar manner, the yield being 50% theoretical. Bv using amyl alcohol in place of ethyl alcohol the yields may be improved to above 90% theoretical. (J. C. S., 121, 2362 ; A., 215, 181.) Preparation 463. — Phenyl-hydrazone of cZ-Mannose (+ + -f- + Pentolhexanal). CH 2 (OH)(CH(OH)) 4 CH : NNH.C 6 H 5 . C 12 H 18 0 5 N 2 . 270. To 4 gms. (1 mol.) of mannitol dissolved in 20 c.cs. of water, and a solution of 1 gm. of ferrous sulphate in cold water is added, and then gradually, 12 c.cs. (1 atom of 0) of hydrogen peroxide solution (20 vols.), or more if solution is weaker, are dropped in. The solution must be well cooled throughout. Sodium carbonate solution is added till just alkaline, the whole filtered, and a portion of the filtrate tested for mannose by Fehling's solution, and by ammoniacal silver nitrate. To the bulk of the filtrate 1 c.c. (excess) of phenylhydrazine dissolved in a slight excess of dilute acetic acid is added, the solution allowed to stand, and the precipitate of mannose phenylhydrazone filtered ofT. It is recrystallised from dilute alcohol. CH 2 OH(CHOH) 4 CH 2 OH + O - CH 2 OH(CHOH) 4 CHO + H 2 0. Yellow crystals ; M.P. 198°. Preparation 464. — Diphenyl Disulphide. C 6 H 5 S.SC 6 H 5 . C 12 H 10 S 2 . 218. 0-5 c.c. (2 mols.) of thiophenol are dissolved in alcohol, 0-5 c.c. of cone, ammonia added, and the whole evaporated to dryness on a water bath in a good fume cupboard. 2C fi H 5 SH + O = C 6 H 5 S.SC 6 H 5 + H 2 0. Yield. — Theoretical. Colourless needles ; M.P. 61°. Preparation 465. — lodoso-benzene ( ( Oxy-iod) -benzene). C 6 H 5 .I : O. C 6 H 5 OI. 220. By-product. — Diphenyl lodonium Iodide (Phenyliodide derivative of iod-benzene). (C 6 H 5 ) 2 : LI. C 12 H 10 I 2 . 408. 10 gms. (1 mol.) of phenyliodide dichloride are carefully rubbed with a solution of 5 gms. of sodium hydroxide in 40 gms. of water in a mortar and allowed to stand overnight. The iodosobenzene is filtered off, washed with water, and pressed on a porous plate. The alkaline filtrate 422 SYSTEMATIC ORGANIC CHEMISTRY is saturated with sulphur dioxide, and the precipitated diphenyl iodonium iodide crystallised from a small quantity of hot water, or from alcohol. C 6 H 5 I : CL + 2H 2 0 = C 6 H 5 I(OH) 2 + 2HC1 = C 6 H 5 .I : 0 + H 2 0 + 2HC1. A small portion of the iodosobenzene is probably oxidised to iodoxy- benzene, C 6 H 5 I0 2 , which reacts with the hypothetical hydroxide, C G H 5 .I(OH) 2 , to give diphenyl iodonium hydroxide and iodic acid. This base is present in the alkaline filtrate from the iodosobenzene. The sulphur dioxide reduces the iodic acid to hydriodic acid, which, combining with the iodonium base, forms an iodide insoluble in cold water. C 6 II 5 -I.;OH I0 2 jC 6 H 5 = C 6 H 5 .I(OH).C 6 H 5 + HI0 3 . OH + HI0 3 + 3S0 2 + 3H 2 0 = HI + 3H 2 S0 4 . (C 6 H 5 ) 2 I.OH + HI = (C 6 H 5 ) 2 I.I + H 2 0. Yields. — Iodosobenzene. — 75% theoretical (9 gms.). White amorphous substance ; soluble in water, yielding a neutral solution ; decomposes when heated to above 240°. Diphenyl Iodonium Iodide. — Crystallises from alcohol in long, yellow needles ; M.P. 175° — 176° ; on melting decomposes completely into iodobenzene. (B., 25, 3495 ; 26, 1307, 1354 ; 27, 506.) Preparation 466. — lodoso-lbenzene Acetate (Di-acetyl derivative of phenyl-di-hydroxy iodine). C 6 H 5 I : (O.CO.CH 3 ) 2 . C 10 H n O 4 I. 322. 5 gms. (1 mol.) of iodosobenzene are dissolved with heat in the smallest possible quantity of glacial acetic acid, the solution evaporated to dryness on a water bath, and the powdered residue recrystallised from a little benzene. C 6 H 5 I : 0 + 2CH3COOH = C 6 H 5 I : (O.CO.CH 3 ) 2 + H 2 0. Yield.— Theoretical (7 gms.). Colourless prisms ; M.P. 156°— 157°. Preparation 467. — Iodoxy-benzene (Phenyl iodite). C 6 H 5 .I0 2 . C 6 H 5 0 2 L 236. 10 gms. (1 mol.) of iodosobenzene are mixed in a flask with sufficient water to form a thin paste, and steam-distilled until no more iodobenzene comes over, and until all the iodosobenzene has completely reacted. If the iodoxybenzene formed does not dissolve completely, water is added until solution takes place. The residue is then filtered and concentrated on a water bath until a test portion, on cooling, gives a copious precipitate. 2C 6 H 5 I : 0 = C 6 H 5 I.0 2 + C 6 H 5 I. Snow-white powder ; decomposes suddenly on heating to 210° — 230°. Preparation 468. — Diphenyl Iodonium Iodide (Phenyl-iodide of iod- benzene). (C 6 H 5 ) 2 I.I. C 12 H 10 I 2 . 408. 10 gms. (1 mol.) of iodosobenzene and 11 gms. (1 mol.) of iodoxybenzene MISCELLANEOUS PREPARATIONS 423 are, treated with water and with 20 gms. (excess) of freshly precipitated silver oxide in a stout, well-stoppered bottle, shaken mechanically for 4 hours, and filtered. The filtrate, which contains free diphenyliodonium hydroxide, has a strongly alkaline reaction.* The base has not been obtained in a pure form, but its salts are readily prepared from the solution. The solution contains part of the base in the form of its iodate, and is therefore first treated with sulphur dioxide, and then with excess of potassium iodide solution, when the iodide separates out completely. It is recrystallised from alcohol. C 6 H 5 1 : 0 + C 6 H 5 I0 2 + AgOH -> (C 6 H 5 ) 2 I.OH + AgI0 3 . (C 6 H 5 ) 2 I,OH + KI -> (C 6 H 5 ) 2 I.I. Yield. — 93% theoretical (17 gms.). Yellow needles from alcohol ; M.P. 175° — 176° ; on melting decomposes completely into iodobenzene. (B., 27, 426 ; 502, 1592.) Preparation 469— Phenyl-iodide Dichloride. C 6 H 5 .I : Cl 2 . C 6 H 5 C1 2 I. 275. 10 gms. (1 mol.) of iodobenzene are dissolved in 20 c.cs. of dry chloro- form, and a current of chlorine, dried by bubbling through two concentrated sulphuric acid wash bottles, is led into the solution through a very wide delivery tube. During the passage of the gas the solution is cooled by ice water ; when no more gas is absorbed the yellow crystals are filtered off, washed with chloroform, spread out in a thin layer on a pad of filter paper, and allowed to dry in the air. C 6 H 5 I + Cl 2 = C 6 H 5 I : Cl 2 . Yield. — Almost theoretical (13 gms.). Very unstable yellow crystals ; decompose on heating. (J, pr., 33, 154 ; B., 26, 357 ; A., 369, 119.) Preparation 470. — ^-Naphthalene Sulpho-glycine. C 10 H 7 .SO 2 .NH.CH 2 .COOH. C 12 H n 0 4 NS. 265. 2 gms. (1 mol.) of glycocoll are dissolved in 27 c.cs. (1 mol.) of normal sodium hydroxide, and to this an ethereal solution of 12 gms. (2 mols.) of /3-naphthalene-sulphonyl chloride is added. The mixture is shaken in a stoppered bottle in a shaking machine at ordinary temperature. Three times, at intervals of about an hour, the same amount of normal alkali is again added. After about 4 hours the aqueous liquid, which still reacts alkaline, is separated from the ethereal layer in a funnel, filtered, and acidified with hydrochloric acid. The oil which is precipitated soon crystallises. For complete purification it is recrystallised from hot water C 10 H 7 .SO 2 Cl + NH 2 .CH 2 .COOH = C 10 H 7 SO 2 .NHCH 2 .COOH + HC1. Colourless laminse, M.P. 156° (159° corr.). (B., 35, 3780.) * Test solution for an iodate. 424 SYSTEMATIC ORGANIC CHEMISTRY Preparation 471. — Thiophenol. C 6 H 5 SH. C 6 H 6 S. 110. This experiment should be performed in a good draught chamber. 240 gms. cone, sulphuric acid and 720 gms. crushed ice are placed in a litre round-bottomed flask. The mixture is cooled by placing the flask in a freezing mixture ; the temperature should be kept below 0°. Stirring is commenced, and 60 gms. benzene sulphonyl chloride (see p. 416) are gradually run in during \ hour. 120 gms. of zinc-dust are then added as quickly as possible without allowing the temperature to rise above 0° ; this requires about \ hour. The stirring is continued for 1 — \\ hours, the temperature being kept below 0°. A reflux condenser is now attached, the freezing bath is removed, and the temperature allowed to rise spontaneously or by the application of a little heat, the agitation being maintained. A vigorous action ensues after a time, and much hydrogen is evolved, at which stage cooling should be applied. The mixture is then heated to boiling until the solution becomes clear (about 4 — 7 hours). The thiophenol is steam-distilled, separated from the water, and dried with calcium chloride. It is distilled, the fraction boiling at 166°— 175° (71° at 15 mms.) is collected. C 6 H 5 S0 2 CI + 6H -> C 6 H 5 SH + 2H 2 0 + HC1. Yield.— 90% theoretical (34 gms.). Colourless liquid ; B.P. 173° ; characteristic unpleasant odour ; produces burns on the skin : vapour irritates the eyes. (A., 119, 142 ; B., 28, 2319 ; 51, 751.) Peeparation 472. — Lead and Mercury Salts of Thiophenol. (C 6 H 5 S) 2 Pb. (C 6 H 5 S) 2 Hg. C 12 H 10 S 2 Pb. 425. C 12 H 10 S 2 Hg. 418. 1 gm. (excess) of lead acetate or mercuric chloride is dissolved in alcohol by the application of heat, and the solution cooled and filtered. 0-5 c.c. (2 mols.) of thiophenol are then added drop by drop when a precipitate of the required salt is obtained. It is washed with a little alcohol. 2C 6 H 5 SH + (CH 3 COO) 2 Pb = (C 6 H 5 S) 2 Pb + 2CH 3 .COOH. 2C 6 H 5 SH + HgCl 2 = (C 6 H 5 S) 2 Pb + 2HC1. Yield. — Theoretical (1 gm.). Crystalline substances ; insoluble in alcohol. Preparation 473. — Lead and Calcium Salts of Glyceric Acid. (Pb or Ca)[O.CO.CH(OH)CH 2 OH] 2 . Pb Salt. — A dilute aqueous solution of glyceric acid (p. 242) is neutralised with lead carbonate containing a small quantity of lead oxide. The mix- ture is heated to boiling and filtered hot. The filtrate, on concentrating and cooling, yields the required salt in crusts, which adhere to the sides of the vessel. A further crop may be obtained by concentrating and cooling the mother liquors. The product may be recrystallised from hot water. MISCELLANEOUS PREPARATIONS 425 Yield. — -Theoretical (twice the weight of acid taken). Ca Salt. — A dilute aqueous solution of glyceric acid is boiled with excess of calcium carbonate and filtered hot. The nitrate, on concentrating and cooling, yields colourless crystals of the required salt, which may be recrystallised from hot water. (A., 120, 226.) Peepaeation 474. — Triphenyl - chloromethane (Triphenylmethyl chloride). (C 6 H 5 ) 3 CC1. C 19 H 15 C1. 278-5. 12-5 gms. of freshly prepared, finely divided anhydrous aluminium chloride (see p. 503) are added in 4 equal portions to a mixture of 10 gms. (1 mol.) of redistilled carbon tetrachloride, which has stood for 48 hours over calcium chloride, and 35 gms. (excess) of pure similarly treated benzene, in a flask fitted with a long reflux condenser. When the reaction moderates, it is completed by heating on a water bath for 1 hour. On cooling, the contents of the flask are very slowly poured with mechanical stirring on to ice surrounded by a freezing mixture. Three times during the addition benzene is added, sufficient to dissolve the triphenyl-chloro- me thane as it separates. The benzene solution is separated, washed with dilute hydrochloric acid, then with water, dried over calcium chloride, and evaporated on a water bath until triphenyl-chloromethane crystallises, on cooling a sample. After filtration, a further yield may be obtained by removing the benzene under reduced pressure at 40°, and washing the residue with ether. The whole is purified by retreatment with benzene, as above. 3C 6 H 6 + CC1 4 -> C1C(C 6 H 5 ) 3 + 3HC1. Yield. — 80% theoretical (14 gms.). Colourless crystals ; somewhat soluble in benzene ; M.P. 108°— 112°. (A., 194, 253.) Prepaeation 475— Thianthren (Di-thio-di-phenylene), C 6 H 4 <^>C 6 H 4 . C 12 H 8 S 2 . 216. To the catalyst prepared as described on p. 57, from 25 gms. of aluminium powder, 45 gms. of mercuric chloride and 25 gms. (excess) of pure dry benzene, 10 gms. (4 atoms) of flowers of sulphur are added under good mechanical stirring, and the mixture heated on a water bath until hydrogen sulphide is no longer evolved. The product, on cooling, is decomposed by adding ice, filtered, and the residue repeatedly extracted with chloroform, from which the thianthren is obtained on concentration. It is recrystallised from acetone. AlCl 3 HgCl .S v 2C 6 H 6 + 2S > C 6 H 4 / g/ >C 6 H 4 . Yield. — 80% theoretical (14 gms.). Colourless crystals ; soluble in chloroform ; insoluble in cold acetone ; M.P. 160°. (J. C. S., 117, 1335.) This is an extension of the Friedel-Craft's Reaction (see p. 56). 426 SYSTEMATIC ORGANIC CHEMISTRY The Hydration of Unsaturated Hydrocarbons to Yield Oxy-compounds. The recent developments in the production of acetaldehyde from acetylene have given a new stimulus to this type of reaction ; hitherto such examples of hydration were of comparatively little importance. In the presence of moderately dilute sulphuric acid isobutylene is con- verted into trimethyl carbinol, a reaction which represents one step in the purification of hydrocarbon oils. (CH 3 ) 2 C : CH 2 + H 2 0 -> (CH 3 ) 3 C.OH. For the preparation of acetaldehyde, acetylene is led into 20 — 45% sulphuric acid, or 30 — 35% phosphoric acid or 96% acetic acid, or a strong organic sulphonic acid, all in presence of a mercury salt. The action probably consists (1) in the formation of a double compound between acetylene and the mercury salt, and (2) the decomposition of this compound with formation of acetaldehyde. In addition to acetalde- hyde there is likely to be formed some of its condensation products and polymerides. For further consideration of such reactions, the monographs on catalysis by Henderson, and by Rideal and Taylor, should be consulted. Preparation 476. — Acetaldehyde. CHg.CHO. C 2 H 4 0. 44. Acetylene prepared from calcium carbide and purified by passing (1) through copper sulphate solution, and (2) through a tower packed Fig. 54. with bleaching powder, is led into a flask containing 300 c.cs. of 96% acetic acid and 9-5 gms. mercuric sulphate in solution, the temperature of which is kept at 30° (see Fig. 54). The exit tube from the flask is connected (1) to a cold water condenser, and (2) to two wash-bottles containing ether, and cooled in ice. The gas should be passed at a very moderate rate for 1 or 2 days, and a little water (1 — 2 c.cs.) added at MISCELLANEOUS PKEPARATIONS 427 intervals to replace that taken up in the reaction. When it is decided to discontinue the reaction the flask is warmed to 60° — 70° to drive all the aldehyde over into the ether. The ethereal solution is dried over anhydrous sodium sulphate, then decanted, and saturated with dry ammonia". A very good yield of aldehyde-ammonia results. CH ; CH 4 H 2 0 -> CH 3 .CHO. CH3.CHO + NH 3 -> CH 3 CHOH.NH 2 . The experiment shows, with the use of simple apparatus, the preparation of acetaldehyde from acetylene. With more elaborate apparatus involving thorough agitation of the gas with the catalyst, and also a circulatory system by which the escaping acetylene can be repeatedly passed through, the catalyst, excellent yields can be obtained. Preparation 477. — Paracetaldehyde. (CH 3 CHO) 3 . C 6 H 12 0 3 . 132. A paste, consisting of 10 gms. mercuric sulphate, and 40 gms. of ammo- nium hydrogen sulphate with 20 c.cs. of water is introduced into a strong glass bottle of 1,500 c.cs. capacity. The bottle is three parts filled with glass beads and thoroughly shaken ; it is then fitted with a one-holed cork carrying a delivery tube, which passes down through the beads. j A current of acetylene, prepared from calcium carbide and water, and purified by passing first through copper sulphate solution, and then through a tower packed with bleaching powder, is led into the bottle, which has no outlet and which is periodically shaken. In about 2 hours the beads adhere together somewhat ; then para- cetaldehyde begins to collect at the bottom of the bottle. Water is i added, 2 — 3 c.cs. at a time, at intervals during the formation. The yield i is good, and there is practically no escape of acetylene or acetaldehyde from the apparatus. The action consists in the formation of a mercuric sulphate acetylene compound and its subsequent decomposition giving paracetaldehyde. The passage of acetylene should be continued for about 2 days. The contents of the bottle are finally shaken up with ether, the j ethereal solution separated, dried over anhydrous sodium sulphate, and distilled. Paracetaldehyde passes over as a colourless liquid, boiling point 124°. 3C 2 H 2 + 3H 2 0 -> (CH 3 CHO) 3 . (Am. Soc, 43, 2071.) Preparation 478. — Chloroform (Trichlormethan). CHC1 3 . 119-5. 100 gms. of fresh 35% bleaching powder, or an equivalent quantity, are j ground up in a mortar to a paste with water and washed with water into a 2-litre flask, 400 c.cs. of water being used altogether. (Note. — As com- mercial bleaching powder is rather variable, the sample should be analysed, and the correct equivalent quantity taken, otherwise poor yields are obtained.) 20 gms, rectified spirit (or acetone) are placed in the flask. 428 SYSTEMATIC ORGANIC CHEMISTRY which is connected to a long condenser and receiver. The flask is gently warmed on a sand bath until a reaction commences, when the flame is withdrawn until the reaction subsides ; much frothing takes place at this stage if the reaction is going properly. Heat is again applied and dis- tillation continued so long as any oily drops of chloroform pass over. The distillate is placed in a separating funnel, and the bottom layer of chloro- form run off. This is washed with dilute sodium hydroxide, dried over granular calcium chloride and distilled. Yield. — (20 gms.). Colourless liquid ; B.P. 61° ; when made from alcohol it contains a little ethyl chloride. The ultimate changes are represented by the following equations : — 4C 2 H 5 OH + 8Ca(OCl) 2 — > 2CHC1 3 + 3Ca(COOH) 2 + 5CaCl 2 + 8H 2 0. CH 3 .CO.CH 3 + 3C1 2 -> CH3COC.CI3 + 3HC1. 2CH3.CO.CCl3 + Ca(OH) 2 -> (CH 8 COO) a Ca + 2CHC1 3 . (A., 23, 244 ; J. Eng., 1912, IV., 345 and 406.) Preparation 479.— Iodoform. CHI3. 394. From Alcohol. — 32 gms. potassium carbonate are dissolved in 80 gms. water and 16 gms. 95% alcohol, and the solution heated to 70°. 32 gms. powdered iodine are then added gradually with stirring. Iodoform gradu- ally separates out, and when the solution has become completely decolor- ised, is filtered off, washed with water, and dried at ordinary tempera- ture. A further yield is obtained by adding 2 — 3 gms. potassium bichro- mate and 16 — 24 gms. cone, hydrochloric acid, neutralising and adding 32 gms. potassium carbonate, 16 gms. 95% alcohol and 6 gms. iodine, and carrying out as before. The iodoform is then recrystallised from alcohol. C 2 H 5 OH + 4I 2 + 6KOH -> CHI 3 + HCOOK + 5KI + 5H 2 0. Lemon yellow hexagonal crystals ; M.P. 115° ; characteristic odour and taste ; sparingly soluble in water. (J., 1894, 317.) From Acetone. — 100 gms. iodine are dissolved in 320 gms. warm 10% caustic soda solution, and after cooling, 20 gms. of acetone added. 100 gms. powdered iodine are added with stirring and then caustic soda solution gradually, until the iodine disappears. The iodoform separates and is filtered off. 20 gms. acetone are added to the filtrate, which has been acidified with hydrochloric acid, and then made alkaline with caustic soda and a further yield of iodoform obtained. Yield.— (180 gms.). (A. Spl., 7, 218, 377.) Preparation 480. — Thiourea (Thiocarbamide). NH 2 S : C< CH 4 N 2 S. 76. X NH 2 . 50 gms. of ammonium thiocyanate are melted in a round-bottomed flask in a paraffin bath and kept at a temperature at which the mass STEOCJS ' PREPARATIONS 429 remains just liqu, M0° — 150°) for 5— G hours, or at 170° for 1 hour. The former metho> /es the better yield. The cooled melt is powdered and ground up with i alf its weight of cold water, which dissolves unchanged ammonium thiocyaLite, but little of the thiourea. The residue is re- crystallised from hot water. CNS.(NH 4 ) ^ CS(NH 2 ) 2 . Yield. — 14 — 16% of complete conversion (7 — 8 gms.) ; slightly soluble in cold water (1 in 11) ; soluble in hot water and alcohol ; almost insoluble in ether or benzene ; M.P. 172°. (J. C. S., 22, 1 ; 83, 1 ; J. pr. [2], 9, 10.) Preparation 481. — Urea (Carbamide). CO< CH 4 ON 2 . 60. X NH 2 . Volhard's Method. — 39 gms. potassium cyanide and 10 gms. caustic potash are dissolved in 100 c.cs. of water in a large flask. 63 gms. potassium permanganate dissolved in 1 litre of water are then added, drop by drop, from a funnel, the flask being placed in a freezing mixture. The tem- perature should not rise above 8°. This is filtered, and a solution of 80 gms. ammonium sulphate is added, and the whole evaporated to dry- ness. The residue is powdered and extracted with 80 c.cs. absolute alcohol under a reflux at boiling point for | hour. It is then filtered and the residue washed with boiling alcohol. The alcohol is removed by distillation until the volume is about 50 c.cs. It is then placed in a glass dish and allowed to stand. The crystals which separate are filtered, washed with alcohol, and dried. A second crop of crystals can be obtained from the mother liquor. Prisms ; M.P. 132° ; verv soluble in water ; insoluble in chloroform. (J., 1880, 393.) Preparation 482. — Methylamine Hydrochloride. CH3.NH2.HCl. CH 6 NC1. 67-5. 125 gms. ammonium chloride and 250 gms. 40% aqueous formaldehyde solution are placed in a distilling flask with thermometer well below surface of liquor. The flask is attached to a water condenser, and slowly heated until the thermometer registers 104°, at which it is main- tained constant until no further liquid distils over. Weight of distillate — - 54 gms. The product in the flask is cooled and filtered from ammonium chloride which separates. The filtrate is evaporated on a water bath to half its original volume, cooled and a second crop of ammonium chloride filtered off. The liquid is then concentrated at 100° until a crystalline scum forms on the surface. On cooling, methylamine hydrochloride separates, and is filtered off. After further evaporation and cooling, a second crop of methylamine hydrochloride is similarly obtained. The filtrate is again concentrated, and left for 24 hours over solid caustic soda in a vacuum desiccator ; the semi-solid residue is extracted with warm 430 SYSTEMATIC OKGAMO ^ ~ chloroform which dissolves out ai, ulu' irochloride, and a further quantity of methylamine hvdr^Moride is .red off. The total yield is treated with boiling chloroform , washed with warm chloroform, and dried in a desiccator. /OH H.CHO + NHg.HCl -> H.CH< -> H.CH : NH.HC1 + H 2 0. \NH 2 .HC1 CH 2 : NII.HC1 + H 2 0 + H.CHO -> CH 3 .NH 2 . HC1 + H 2 0. Yield. — 85% theoretical (50 gms.). Large deliquescent plates ; in- soluble in chloroform. (J. C. S., Ill, 844.) Pkepakation 483. — /i/)-Dinaphthylamine. (C 10 H 7 ) 2 NH. C 20 H 15 N. 269. 100 gms. of ^-naphthylamine and 0-5 gms. of iodine are heated to 230° for 4 hours. The melt is then cooled and recrystallised from benzene. 2C 10 H 7 NH 2 -> (C 10 H 7 ) 2 NH + NH 3 . Yield. — Almost theoretical (185 gms). Silver glistening plates ; M.P. 170-5° ; sparingly soluble in hot alcohol ; easily soluble in hot glacial acetic acid. (C, 1900, II., 1093.) Preparation 484. — Phenyl-/? -naphthylamine. C 10 H 7 NH.C 6 H 5 . C 16 H 13 N. 219. 90 gms. of /?-naphthol and 112-5 gms. of aniline are heated for 7 hours to 100° — 190° with 1 gm. of iodine. The melt is boiled out first with dilute hydrochloric acid and then with dilute caustic soda. The residue is dried and distilled in vacuo. The phenylnaphthylamine passes over at 237° (15 mms.). It is recrystallised from methyl alcohol. C 10 H 7 OH + H 2 N.C 6 H 5 -> C 10 H 7 NH.C 6 H 5 + H 2 0. Yield.— Almost theoretical. Needles ; M.P. 108°. (B., 13, 1850.) Peeparation 485. — Thiocarbanilide. CS(NHC 6 H 5 ) 2 . C 13 H 12 N 2 S. 228. 50 gms. carbon disulphide and 40 gms. aniline are dissolved in 60 c.cs. alcohol and 10 gms. powdered caustic potash are added. The whole is heated (caution /) on a boiling water bath for 3 — 4 hours under a long reflux condenser. (Carbon disulphide boils at 46°.) The carbon disulphide and alcohol are then distilled off and the residue is washed with water and with dilute hydrochloric acid to remove unchanged aniline. It is then filtered, washed with water, and recrystallised from alcohol. Yield.— 70% theoretical (35 gms.). Colourless plates; M.P. 151°; sparingly soluble in water. (A. 70, 142 ; B., 33, 2726.) Preparation 486. — Phenylglycine. C 6 H 5 NH.CH 2 COOH. C 8 H 9 0 2 N. 139. 20 gms. of chloracetic acid are dissolved in 20 c.cs. of water, and 16 gms. MHCELLANEOUS PREPAEATIONS 431 of calcium hydroxide added, the whole being kept cool : a mixture of 20 c.c. of methyl or ethyl alcohol and 60 gms. of aniline is next added, and the whole stirred and warmed until the reaction is complete. The alcohol and aniline are distilled off with steam ; the calcium salt is filtered off and is converted into the sodium salt when cold (see p. 303). The calculated amount of a mineral acid is added to the concentrated solution of the sodium salt and the phenyl glycine thus obtained. ^>NH 2 + C1CH 2 .C00H — > <^ ^NH.CH 2 .COOH + HOI. Small crystals. M.P. 126°— 127°. (D.R.P., 167698.) Preparation 487. — Phenylglycine-o-carboxylic Acid. /COOH C 6 H 4 < C 9 H 9 0 4 N. 195. \NH.CH 2 COOH. 11-2 gms. of caustic potash are dissolved in 100 c.cs. water, and to this is added 9-4 gms. chloracetic acid and 13-6 gms. anthranilic acid. The solution is warmed on a water bath under a reflux for 2 hours at 60° — 80°. Hydrochloric acid is then added to neutralise and after standing the phenylglycine-o-carboxylic acid separates out and is filtered off and recrystallised from water. A further yield can be obtained by evaporating the filtrate. /COOH /COOH C 6 H 4 < + C1CH 2 C00H -> C 6 H 4 < \NH 2 \NH.CH 2 COOH. Colourless crystals. M.P. 200° (with decomposition). Sparingly soluble in water. Solution in alcohol shows a blue fluorescence. (B., 23, 3432.) Preparation 488. — Glycine (Glycocoll). CH 2 NH 2 COOH. C 2 H 5 0 2 N. 75. 104 gms. of chloracetic acid are dissolved in an equal weight of water, and this solution slowly run into 1,248 c.cs. of 25% ammonia, the whole being stirred well. When all the acid has been added the solution is set aside for 24 hours and then boiled until no more ammonia is evolved. It is made neutral while hot with a slight excess of copper carbonate, filtered, and the filtrate evaporated until it begins to crystallise. On allowing to cool the copper salt of glycocoll separates as blue needles, is filtered and washed first with dilute, and then with more concentrated alcohol. The salt is dissolved in water, and the copper precipitated by sulphuretted hydrogen from the boiling solution. The sulphide is filtered off and washed well, and the filtrate concentrated to small bulk. On cooling, the glycocoll separates. CH 2 ClCOOH + NH 3 — > CH 2 NH 2 COOH + HC1. Monoclinic crystals ; M.P. 232° — 236° with decomposition ; soluble in 4 parts cold water, almost insoluble in alcohol and ether. (A., 266, 295.) 432 SYSTEMATIC ORGANIC CHEMISTRY Peepaeation 489— Glycocoll Ester and Glycine J Anhydride (Ethyl ester of amino-ethan acid) and (2.5-diketopiperazine). NH 2 .CH 2 .COOC 2 H 5 and .CO — CH 2X HN< )NH. (C 4 H 9 0 2 N and)C 4 H 6 N 2 0 2 . (103 and) 114. \CH 2 — CO/ Glycocoll Ester. — 50 gms. (1 mol) gylcocoll-ester hydrochloride (see p. 395) are treated with 25 c.cs. of water, which only suffice for partial solution. 100 c.cs. ether are then added, and the whole well cooled in a freezing mixture and treated with 40 c.cs. (excess) of sodium hydroxide (33%). Finally, such an amount of dry, granulated potassium carbonate is added with cooling and shaking as to form a thick paste. After vigorous shaking, the ethereal solution is poured off, the residue is shaken two or three times with ether, and the united extracts, after filtration, are allowed to stand, with frequent shaking, first for ten minutes with dry potassium carbonate and then for several hours with anhydrous sodium sulphate. The ether is evaporated and the residue is distilled under diminished pressure. At 10 mms. it boils at 51-5° — 52-5°, and so the receiver must be well cooled. NH 3 Cl.CH 2 COOC 2 H 5 + NaOH = NH 2 .CH 2 COOC 2 H 5 + NaCl + H 2 0. Yield. — 65% theoretical (25 gms.) B.P. 718 148°— 149°. with decomposi- tion. (A., 127, 97 ; J. pr., [2], 37, 166.) Glycine Anhydride. — 20 gms. (2 mols.) of glycine-ester are cooled and treated with 12 gms. of water, and the mixture is then allowed to stand at room temperature for some days. The anhydride separates out during this time in beautifully crystalline form. It is filtered, washed with a little cold water, and dried under reduced pressure over sulphuric acid. /CO— CH 2 2NH 2 CH 2 COOC 2 H 5 = HN\ >NH + 2C 2 H 5 OH. X CH 2 — CO Yield. — 60% theoretical (7 gms.) Colourless plates ; turns brown at 245° ; melts with blackening at 275°. Sublimes on rapid heating. (J. pr., [2] 37, 173.) For the direct preparation of glycine-anhydride from glycocoll ester hydrochloride see B., 39, 2930. Peepaeation 490. — Racemic Phenylalanine (3-Phenyl-2-amino-propan- acid). C 6 H 5 .CH 2 .CH(NH 2 ).COOH. C 9 H n 0 2 N. 165. 50 gms. (1 mol.) of benzylmalonic acid (see p. 235) are dissolved in 250 gms. of dry ether, and 50 gms. (1^ mols.) bromine are gradually added in daylight. At first the halogen rapidly disappears, and clouds of hydrobromic acid are evolved. At the end the liquid is coloured reddish- brown by the excess of bromine. When it has stood for half an hour the ethereal solution is shaken with a little water, sulphuric acid being gradually added until the red colour of the bromine disappears. The MISCELLANEOUS PREPARATIONS 433 ethereal layer is then separated, again washed with a little water, and carefully evaporated. The solid residue is recrystallised from about 250 c.cs. of hot benzene. Yield, 95% theoretical (65 gms.). The benzyl- brommalonic acid when dried under reduced pressure at 80° melts at 137° (corr.). The benzylbrommalonic acid containing water is now heated in an oil bath to 125° — 130°, and the fused mass evolves carbon dioxide and a certain amount of hydrobromic acid. The reaction is complete in the course of 30 — 45 minutes. The residue is a yellow oil, which even at a low temperature does not crystallise, and which in the main consists of phenyl- a-brompropionic acid. For the purpose of purification it is washed with water, taken up in ether, and dried with anhydrous sodium sulphate ; the ether is then distilled off. The mobile, almost colourless oil remaining is dissolved in 5 times its volume (excess) of 25% aqueous ammonia, and either heated for 3 hours to 100° in a sealed tube or allowed to stand for 3 to 4 days at ordinary temperature. On evaporation of the ammo- niacal solution an almost colourless residue is left, and this chiefly consists of ammonium bromide and phenylalanine. On boiling with absolute alcohol the amino-acid is left undissolved and is recrystallised from hot water. C 6 H 5 .CH 2 CH(COOH) 2 + Br 2 = C 6 H 5 CH 2 CBr(COOH) 2 + HBr. C 6 H 5 CH 2 CBr(COOH) 2 -> C 6 H 5 CH 2 .CHBrCOOH + C0 2 . C 6 H 5 .CH 2 CHBr.COOH + 2NH 3 = C 6 H 5 CH 2 .CH(NH 2 )COOH + NH 4 Br. Yield. — 55% theoretical (24 gms.) Colourless crystals ; soluble in hot water. M.P. 263°— 265° with decomposition. (B., 37, 3064.) Pkeparation 491. — Diazobenzene Sulphonic Acid (Inner salt o! diazo- nium benzene hydroxide-4-sulphonic acid). /N = N [1 : 4]C 6 H 4 < / C 6 H 4 O a N a S. 168. . 20 gms. (1 mol.) of sulphanilic acid, previously dried on a water bath and finely powdered, are dissolved, in the heat, in 58 c.cs. (1 mol.) of 2N sodium hydrate ; and the solution is diluted until, on cooling to 50°, no crystallisation occurs. This solution is now treated with 10 gms. (rather more than the calculated amount) of sodium nitrite, and the mixture is poured, with constant stirring, into an excess of cold, dilute sulphuric acid. In a short time the diazo -compound separates out as a white, crystalline mass. To favour crystallisation the liquid is cooled, and after it has stood for some time the substance is filtered off. This compound can be kept in the. dry state, but must not be dried at 100°. In dealing with the dry pro- duct care is, however, always necessary, for it sometimes explodes violently when rubbed. >N = N C 6 H 4 (NH 2 )(S0 3 H) -> C 6 H 4 (N : NC1)(S0 3 H) -> C 6 H 4 < / \so 2 Yield. — 80% theoretical (16 gms.). Colourless crystals ; stable enough to be recrystallised frorcf water at 60°. s.o.c. 434 SYSTEMATIC ORGANIC CHEMISTRY Preparation 492. — Diazomethane. CH 2 N 2 . 42. 1. Methylurethane is prepared from methylamine and chloroformic ester. CICOOEt + NH 2 CH 3 = CH 3 NHCOOEt + HCL 2. Nitrosomethylurethane is prepared by treating methylurethane with a mixture of sodium nitrite and sulphuric acid. But if large quantities are required it is better to lead nitrous fumes (see p. 509) into pure methyl- urethane diluted with an equal volume of ether until the liquid has assumed a dirty colour. The whole is washed with water and soda, dried over anhydrous sodium sulphate, and distilled under reduced pressure. If required for diazomethane this is not necessary. This substance attacks the skin, lungs and eyes. It seems to be hydrolysed to diazomethane in the body. HN0 2 N0 CH 3 NHCOOEt > CH 3 NCOOEt. One part (1 — 5 c.cs. ; not more has been used to the present) of the nitrosourethane are placed in a flask fitted with a descending condenser, 30 — 50 c.cs. of pure ether and 1 — 2 parts of 25% methyl alcoholic potash are poured in. The flask is warmed on a water bath. A yellowish vapour comes over and soon the ether begins to distil. The operation is continued until the remaining ether in the flask is colourless. The ethereal solution is yellow even at 3- -5% concentration. NO CH 3 NCOOEt + KOH -> CH 2 N 2 + KHC0 3 + C 2 H 5 OH. Yield. — 50%. Yellow, odourless, poisonous gas, soluble in dry ether. (B., 27, 1888 ; 28, 855 ; 35, 897.) PART III CHAPTER XXXIII ORGANIC ANALYSIS Detection of Elements present in Carbon Compounds. Carbon and Hydrogen. — Some fine copper oxide is heated in a porcelain crucible for a few minutes to drive off all moisture, and afterwards left to cool in a desiccator. A small amount — 0-1 — 0-2 gm. — of the compound is mixed with about 10 times its weight of the dry copper oxide and placed in a dry, clean test tube 10 — 12 cms. long. 4 — 6 cms. of dry copper oxide are then added, and the tube closed with a cork carrying a delivery tube bent at a right angle. The tube is supported in a horizontal position and gradually heated, beginning first at the unmixed copper oxide and raising it to a high temperature before the compound is appreciably heated. The oxygen of the copper oxide acts as oxidising agent, and if the compound contains hydrogen, water collects on the cooler portions of the tube ; if it also contains carbon, the issuing gas, when passed into lime or baryta water, causes turbidity. Nitrogen, Halogens, Sulphur and Phosphorus. — A piece, about 0 5 c.c. of bright sodium or potassium is placed in a small, hard glass test tube about 8 cms. long and 1 cm. in diameter. (In testing easily volatile com- pounds, a longer tube, to act as a condenser, should be used.) The end of the tube is gradually heated at some distance above a small flame until the sodium (or potassium) just melts. The tube is withdrawn from the flame, and a small quantity of the compound dropped on to the surface of the molten metal. Generally a brisk reaction, often accompanied by detonations, takes place, and when this subsides the end of the tube is gradually heated to bright redness, at which it is maintained until decom- position is complete, and any excess of sodium is oxidised. By this treat- I ment there is formed : sodium cyanide if nitrogen is present ; sodium halide if halogen is present ; sodium sulphide if sulphur is present ; per- haps, sodium sulphocyanide if both nitrogen and sulphur are present, but when sulphur is present, an excess of sodium should be used in order to prevent the formation of sulphocyanide. While still hot, the tube is plunged into 10 c.cs. of distilled water contained in a small beaker or dish ; by this the tube is shattered, and alkali metal remaining reacts briskly, a quantity of carbon remains suspended in the liquid, and any cyanide, halide, sulphide or sulphocyanide formed, passes into solution. The mixture is boiled for a minute, then cooled and filtered through a pre- viously wetted filter paper. The filtrate should be water clear ; if not 435 f f 2 436 SYSTEMATIC ORGANIC CHEMISTRY the fusion must be repeated and more care taken to ensure the complete decomposition of the organic compound by longer heating. The filtrate is divided into portions which are tested as follows : — (a) For Nitrogen. — To one portion, about 1 c.c. of ferrous sulphate solution and a few drops of ferric chloride solution are added. Hydroxides of iron are precipitated. (If no precipitation occurs, a little caustic soda solution must be added.) The mixture is boiled for 1 — 2 minutes, and if alkali cyanide — equivalent to nitrogen in the original compound — is present, sodium ferrocyanide is formed. After cooling under the tap, the alkaline mixture is acidified with hydrochloric acid, which dissolves the precipitated ferrous and ferric hydroxides, and the resulting ferric salt reacting on the sodium ferrocyanide forms Prussian Blue. Accordingly a blue or bluish-green precipitate indicates the presence of nitrogen. At times a blue or bluish-green solution is obtained, which only gives a blue precipitate after standing a few hours, or perhaps overnight. (The addition of a little potassium fluoride is often very helpful in bringing down the blue precipitate.) When the test is doubtful, it should be repeated, using more of the alkaline solution, or if the compound contains only a small percentage of nitrogen, it may be necessary to repeat the fusion, using a larger quantity of the compound. Compounds (e.g., diazo- compounds) which evolve nitrogen at moderate temperature generally fail to give a positive reaction by this method, and in such cases nitrogen can be detected by heating the compound with cupric oxide in an atmo- sphere of carbon dioxide after the manner of a Dumas determination of nitrogen (p. 450), and finding amongst the products a gas which is not absorbed by caustic potash. For volatile or unstable nitrogen com- pounds, a mixture consisting of 138 parts of ignited potassium carbonate and 72 parts of magnesium powder may be used in place of sodium (or potassium). Small quantities of this mixture and of the compound are intimately mixed and heated in a glass tube. The mass is extracted with water, filtered, the filtrate made alkaline and tested for cyanide. (b) For Halogens. — If nitrogen has been proved absent by (a), a portion of the solution is acidified with nitric acid, and silver nitrate added. A curdy white or yellow precipitate indicates the presence of a halogen. If nitrogen is present, the solution, after acidification with nitric acid, must be boiled until all hydrocyanic acid is expelled before silver nitrate is added. Halogens may also be detected by Beilstein's test. — A piece of pure copper oxide, held by means of a platinum wire around it, is heated in a Bunsen flame until it ceases to colour the flame green. It is then allowed to cool, and a little of the compound is placed on it. If, on heating again, there appears a bright green flame accompanied by a blue zone round the oxide (due to the volatilisation of copper halide), the presence of a halogen is indicated. A third test for the presence of halogens consists in heating the com- pound along with an excess of pure lime in a glass tube. The mass is afterwards extracted with water, and tested with silver nitrate. (c) For Sulphur.— To a portion of the alkaline filtrate a few drops of a ORGANIC ANALYSIS 437 freshly prepared solution of sodium nitroprusside are added. A violet or purple coloration indicates the presence of sulphur. Other methods — in all of which the resultant sulphate is precipitated with barium chloride — for the detection of sulphur in compounds, are : (a) oxidation with sodium peroxide (see p. 463) ; (6) oxidation with sodium carbonate and potassium nitrate ; (c) oxidation with fuming nitric acid in sealed tubes. (d) For Phosphorus. — About 1 c.c. of the alkaline filtrate is heated with 3 c.cs. of cone, nitric acid for a few minutes. To this solution after cooling, ammonium molvbdate solution is added, and the whole warmed. A crystalline yellow precipitate of ammonium phosphomolybdate on standing, indicates the presence of phosphorus. Other methods for the detection of phosphorus involve oxidation to phosphoric acid by means of (a) sodium peroxide ; (b) sodium carbonate and potassium nitrate ; (c) fuming nitric acid in sealed tubes. The presence of phosphorus may also be ascertained by heating the compound with magnesium powder, and moistening the cold product with water, whereby phosphine (recognised by its smell) is liberated from the magnesium phosphide. Metallic Radicles. — The organic matter in the compound, is destroyed either (a) by heating to redness for some time in contact with air in a quartz or porcelain crucible, or (b) by oxidising with a mixture of cone, nitric and sulphuric acids. After decomposition is complete, the residue is examined by the usual tests for inorganic radicles. In (a) volatile radicles such as mercury, arsenic and ammonium will be lost. CHAPTER XXXIV QUANTITATIVE ESTIMATION OF CAKE ON AND HYDROGEN The principle involved is the complete oxidation of these elements to carbon dioxide and water. A weighed quantity of the substance is heated along with cupric oxide in a stream of air or oxygen, and the carbon dioxide and water formed are absorbed separately and weighed. From these data the percentages of carbon and hydrogen in the compound are calculated. Oxygen and Air Supplies. — The air or oxygen used is purified from acidic or aqueous vapours, as otherwise these would be absorbed along with the products of combustion ; this purification is effected by passing the gas through soda lime and sulphuric acid. The purified gas then enters the combustion tube and carries along with it the products of com- bustion, namely, carbon dioxide and water ; the mixture of gases next enters an apparatus containing sulphuric acid, which absorbs the water formed, while the carbon dioxide is carried along to be absorbed in an apparatus containing caustic potash solution. In order to convey a pre- liminary idea of the apparatus used and procedure adopted, the following diagrammatic representation is given. Soda lime to remove C0 2 H 2 S0 4 pumice to remove H 2 0 Oxygen Soda lime to H 2 S0 4 pumice supply remove C0 2 — > to remove H 2 0 H 2 S0 4 bubbler to indicate rate of flow of gas Glass tube con- taining CuO and substance placed in com- bustion furnace H 2 S0 4 pumice to absorb H 2 0 KOH to absorb C0 2 Guard tube of CaCl 2 + soda lime. These gases can be conveniently supplied from tinned iron containers by displacement with water. Such containers should have a capacity of about 30 gallons, and when once filled will serve for several combustions. In case the laboratory is not equipped with containers of this type, the gases can be suitably supplied from glass aspirating vessels, and the oxygen may be generated by heating potassium permanganate. Or, the oxygen may be supplied direct from a pressure cylinder provided the latter 438 ESTIMATION OF CARBON AND HYDROGEN 439 is equipped with two gauges— one to register the pressure in the cylinder, and the other the pressure at which the gas is delivered. The operating pressure is generally from 1—4 lbs. Oxygen prepared by electrolysis must not be used in the method here described, as it often contains as much as 1% of hydrogen. Purifying Apparatus.— There are several forms of apparatus in use, most of which give good results when properly manipulated. The follow- ing (Fig. 55) is simple, and gives excellent results. It consists of two pairs of large U -tubes, which are fixed by wiring to a wooden stand. They are so arranged that oxygen can be passed through one pair, and air through the other. The outlet from the second tube of each pair is joined to a T-piece. The connections are made by means of glass tubes and well-fitting rubber stoppers. In case any connections are made with rubber tubing, it should be thick walled, and should be pushed over the glass tubes until they meet. In order that one filling will serve for several combustions large U -tubes, 3 cms. internal diameter and 15 cms. high, are used. The first of each pair is filled with soda lime, and the second with pumice moistened with pure cone, sul- phuric acid. The pumice and soda lime should be sifted free from powder and should be 12 — 20 mesh size. As pumice occasionally contains calcium carbonate, it should be treated with hydrochloric acid, well washed, and dried before being placed in the U -tubes. As cone, sulphuric acid often contains oxides of nitrogen, it is important to use pure acid, and then only as much of it as will moisten the pumice. In order to prevent dust being carried over into the glass delivery tubes, a layer of absorbent cotton or asbestos is placed over the soda lime in the limbs of the tubes which con- tain it. The entrance of each gas to the purifying train is controlled by a screw pinchcock on the rubber tubing, which connects each gasholder to the purifying train. Granular (but not fused) calcium chloride, or aluminium oxide on pumice, can be used instead of sulphuric acid pumice as drying agent. These should be sifted free from powder and filled into a larger U-tube, after the manner in which the soda lime tube is filled. Whatever reagent is selected here for drying the air and oxygen, should also be used for absorbing the water formed in the combustion. In other words, the dry- ing agents used in each instance should have the same absorption capacity. However, owing to the fact that commercial calcium chloride often con- tains basic substances which absorb carbon dioxide, the use of sulphuric acid pumice is preferable. Gas Bubbler. — The object of the bubbler is not only to give an idea as to how fast the gas is passing through the apparatus, but also to enable a comparison to be made between the amount of gas entering the combus- 440 SYSTEMATIC ORGANIC CHEMISTRY tion tube and the amount entering the potash apparatus. A convenient form of bubbler is shown in Fig. 56. It is attached by means of thick walled rubber tubing to the T-piece of the purifying <=^, apparatus and contains a few drops of pure cone. QjZJ sulphuric acid. Fig. 56. Combustion Tube and Furnace. — The type of furnace generally used consists essentially of a series of Bunsen flames impinging on an iron or nickel trough lined with asbestos which serves as a bed for the combustion tube. While the gas is supplied from a common main, each burner is so constructed that its air and gas supply can be independently regulated. Above the tube a row of fireclay tiles, to serve as muffles, are arranged so as to regulate the temperature and assist in the heating of the various parts of the tube. Though their use has not yet become general, electrically heated furnaces may be used ; the principle is the same as that of the gas furnace, namely, that they consist of a series of heating units, each of which can be controlled by its own rheostat. Such a furnace has advantages over the gas furnace since it is cleaner and does not render the atmosphere unpleasant either by radiated heat or by products of combustion. The length of the combustion furnace should be 70— 75 cms. The combustion tube should be of difficultly fusible glass, 10 — 15 mms. internal diameter and walls 1-5 mm. thick. It should be cut of such a length that it projects at least 5 cms. beyond the furnace at either end. In order that the sharp edges of the tube may not cut the rubber stoppers, the extreme ends are heated first in a smoky and afterwards in a blowpipe flame, until the edges are just rounded, care being taken to avoid any deformation of the tube. After cooling, the tube Is washed thoroughly and dried. Cutting Hard Glass Tubing.— To cut hard glass tubing a deep file mark is made at the desired length. Around the tube, one on each side of the file mark, are folded two strips of wet filter paper. These rolls of paper are moved to within 0-5 cm. of each other and bound on the tube by pieces of cord. The space between the rolls of paper is then heated in a small pointed blowpipe flame, directing the flame so as to strike only the top of the tube while the latter is turned. If the tube does not crack across at first, it is strongly heated, and a few drops of water from a tap allowed to fall on the file mark. This generally effects a neat cut. Filling the Tube. — The simplest case of combustion is that involving the analysis of a substance containing carbon and hydrogen, or carbon, hydrogen and oxygen. For such a combustion the tube is filled in the following manner (Fig. 57). A loose plug of asbestos, or a spiral of copper gauze 0-5 cm. wide is placed in the tube 5 cms. from one end ; coarse copper oxide (about 10 mesh size) or " wire form " copper oxide is poured in through a wide funnel from the other end of the tube until there is a layer about 45 cms. long. A second plug of asbestos or narrow spiral of copper gauze is introduced to keep this copper oxide in position. A spiral of copper oxide is prepared by rolling tightly a strip of copper gauze (40 mesh) 15 cms. wide round a stout copper wire until the roll neatly fits ESTIMATION OF CAKBON AND HYDROGEN 441 the tube. The projecting ends of the wire are bent into loops close to the gauze, and the spiral oxidised by heating strongly in a blowpipe flame. When cold the spiral is pushed into the tube to a distance of 5 cms. from one end, the loops enabling it to be moved backwards and forwards in the tube by means of a stout hooked copper wire. The combustion tube is fitted with two good red indiarubber one-holed stoppers ; these should fit accurately, and the parts which come into contact with the glass should be smeared with the faintest trace of vaseline to prevent sti clang to the Fig. 57. tube when hot. The stopper next the copper oxide spiral carries a glass delivery tube ; this tube is provided with a ground -glass stopcock and serves as inlet for the purified air and oxygen. In case wire-form copper oxide is used the tube should be tapped horizontally on the bench to make a passage for the gas. Care should also be taken that the asbestos plugs are not too tightly packed. The tube is now laid on the trough of the furnace, and over each end projecting beyond the furnace a square of asbestos having a circular hole in the centre is placed ; these protect the rubber corks from the heat of the furnace during the combustion. Absorption Apparatus for Water.— Granular (not fused) calcium chloride, alumina pumice and pumice moistened with cone, sulphuric acid are efficient absorbents for water. On the whole the last mentioned has the most advantages when used as depicted in the apparatus Fig. 58. The apparatus consists of a U-tube, one limb drawn out, bent at a right angle and sealed to a bulb tube ; the other limb is open as shown by dotted lines at ° E, and carries a side tube, F. The bend ^ ^ and parts of the limbs of the tube are filled with pumice (sieved and purified) moistened with cone, sulphuric acid. A wad of asbestos is arranged above the pumice in limb E. This done, the open end E is wiped dry and sealed off as shown. During the combustion the side tube 0 is in position through the cork in the exit end of the combustion tube, while the side tube F is connected to the potash absorbent apparatus by means of rubber pressure tubing. At other times the two side tubes 0 and F are closed by pieces of rubber pressure tubing 2 cms. long in each of which is inserted a glass rod rounded at both ends and 1 — 1-5 cm. long. It is important that the edges of all glass tubes to be joined by rubber connections should be rounded in a flame. After Fig. 58. 442 SYSTEMATIC ORGANIC CHEMISTRY about twelve combustions, when this apparatus becomes inefficient through the absorption of water, the water in the bulb is poured out through the side tube 0 and D, and dried by means of folded filter paper ; cone, sulphuric acid is introduced from a pipette through the side tube F, and after inclining the tube so as to " wash " all the pumice, the acid is poured out through F. When this operation is repeated twice and F dried by means of folded asbestos paper, the apparatus is ready for further use. When calcium chloride is used as absorbent it is placed in a U-tube similar to that just described. Since calcium chloride often contains basic chlorides which absorb carbon dioxide, a stream of dry carbon deoxide should be passed through the filled U-tube for 2 hours before use in order to neutralise any basic substances present. The excess of the gas is afterwards driven out by means of a current of dry air. Absorption Apparatus for Carbon Dioxide.— Several forms of potash apparatus are in use. That of Geissler (Fig. 59) is perhaps the most commonly employed, though the apparatus (Fig. 60), since it is not so liable to breakage and also since it contains four bubbling com- partments, is more durable and efficient. The bulbs in each case are filled with a solution of caustic potash containing 50 gms. potash to 50 F IG> 59. Fig. 60. c - c s. of water. Caus- tic soda is not used owing to the sparing solubility of sodium carbonate in caustic soda solutions. The removable side tube is filled with granular calcium chloride, and has a loose plug of cotton-wool at each end. In order to fill the bulbs with potash solution the side tube is removed and a length of rubber tubing attached in its stead ; the other end of the apparatus is dipped into a basin containing the potash solution, suction is applied, until a quantity of liquid, almost sufficient to fill the bulbs, is transferred. After filling the bulbs, that part of the apparatus immersed in the potash solution is dried with pieces of rolled filter paper, the ground-glass joint of the calcium chloride tube is smeared with vaseline and the side tube replaced. Stoppers of pressure rubber tubing and glass rod are attached, and these are only removed when the apparatus is in use. When in use, the arm tube is joined by pressure rubber to a straight calcium chloride guard tube and the other end is similarly joined to the sulphuric acid pumice U-tube. As both types of apparatus, but particularly the Geissler, are fragile, it is most important when making the rubber connections to grip the apparatus by the glass tube over which the rubber is about to be pushed ; any pressure across the bulbs is thus avoided. The passage of rubber is rendered easier by breathing on the glass tube. In connecting the apparatus the importance of using rubber pressure tubing and of ESTIMATION OF CAKBON AND HYDROGEN 443 bringing the ends of the glass tubes closely together may be gathered from Leiben's remark, " that if long rubber tubes are employed the effect is almost the same as if the gas had been bubbled through water again." The potash solution should be renewed after every two combustions. Guard Tube of Calcium Chloride and Soda Lime.— This consists of a straight calcium chloride tube, one half filled with calcium chloride and the other half filled with soda lime, a plug of cotton-wool being placed at each end It is connected to the arm tube of the potash apparatus when the latter is in use, and serves to prevent the entrance of acidic or aqueous vapours. It is also used to prevent the ingress of aqueous or acidic vapours to the combustion tube when the latter is disconnected from the absorption train. Copper oxide is hygroscopic and it is necessary to protect it from the moisture of the air. Having prepared all the apparatus as indicated in the foregoing, the whole is assembled as shown in Fig. 61. The gas bubbler, as well as the absorption train, is supported by wires suspended from a horizontal support. This removes any weight from the ends of the combustion tube, and consequently prevents bending of the heated tube. At this stage notice is taken that all walls, connections and supports fulfil the conditions already specified. The absorption apparatus is then disconnected from the combustion tube and its stoppers of rubber tubing and glass rod replaced. The rubber stopper in the exit end of the combustion tube is also removed. Preliminary Heating of the Combustion Tube.— Air is turned on, and its rate of flow adjusted so that 2 or 3 bubbles per second pass through the bubbler. The gas jets under the combustion tube are lighted and gradually turned up until the tube attains a dull red heat, at which it is maintained for about an hour, the tiles being in position over the tube. In this way any organic impurities are oxidised and removed along with any moisture present in the tube. At the beginning of the heating moisture condenses in the open end of the tube, due to the fact that copper oxide is hygroscopic. The greater quantity of this moisture can be removed with a piece of folded filter paper. As soon as moisture has ceased to collect the open end is closed by its cork bearing the straight calcium chloride-soda lime tube. After about 20 minutes' further heating the burners are turned down and finally extinguished, and the current of air cut off. Weighing the Absorption Apparatus prior to Blank Experiment. — A cardboard box or large beaker half filled with cotton-wool should be used to carry the absorption apparatus from one room to another, as by this means the dangers of breakage and contamination by grease are largely avoided. While the combustion tube is cooling the absorption apparatus is removed to the balance room, wiped free from dust and grease with a clean cloth which is free from lint and does not contain sizing or starch. After standing 30 minutes inside the balance case the stoppers are removed and each member separately weighed. The weighing should be done quickly and the stoppers replaced. Blank Experiment. — The guard tube is removed from the combustion Hi SYSTEMATIC ORGANIC CHEMISTRY tube and the entire absorption train connected as shown in Fig. 61. Before proceeding with any quantitative experiments it is necessary to make certain that the apparatus is airtight. To do this, a piece of stout rubber tubing carrying a screw clip is affixed to the exit limb of the potash apparatus. The screw clip is not closed at first. A stream of air is turned on, and if it bubbles freely at the same rate through the bubbler and potash bulbs it is certain there is no undue obstruction to the passage of gas through the apparatus. The screw clip attached to the potash appara- tus is then closed and the full pressure of the air gradually turned on. After the first few bubbles of air have passed through the potash apparatus, no further movement of gas should appear in any part of the apparatus. If it withstands this test the screw clip is released, and, while air is passed through at the rate of 2 — 3 bubbles per second, the tube is gradually heated to a dull red heat for 30 minutes. The absorption train is disconnected Fig. 61. and stoppered, and the guard tube inserted again in the combustion tube. The burners are gradually turned down and the absorption apparatus weighed according to the scheme already outlined. The increase in each absorbent should not exceed 0-0003 gm. If the increase is greater than this, it is possible that the copper oxide was not thoroughly dehydrated at the commencement of this blank run. A second blank run will show whether the copper oxide has been completely dehydrated during the course of the first blank run. If necessary a third " blank " is run. In case the sulphuric acid pumice absorbing apparatus continues to gain, the purifying apparatus for the removal of water is probably inefficient and should be refilled. If the potash apparatus loses weight the calcium chloride arm tube has become saturated with moisture and should be refilled. Finally the apparatus is tested by means of blank experiments until all sources of error are traced and eliminated ; the increase or decrease in the weight of the absorption apparatus will not then amount to more than the error in weighing. Weighing the Boat and Substance. — When the blank experiments have been completed the combustion tube is allowed to cool with the straight drying tube inserted in its exit end. During this time the boat is prepared and the substance weighed out in it. A porcelain, or preferably a platinum, boat 7 cms. long is used. It should be treated with nitric acid, washed with water, heated in a blast flame and cooled in a desiccator. When cold, it is weighed, 0-15 to 0-2 gm. of the substance to be analysed ESTIMATION OF CARBON AND HYDROGEN 445 is introduced and weighed again. It is then replaced in the desiccator which is carried to the combustion room. In general, liquids of boiling point above 170° may be weighed directly in the boat. The Combustion. — When the inlet end of the combustion tube is cold, the cork at that end is removed and the copper oxide spiral withdrawn by means of a hooked wire. The boat is pushed into the tube as far as the coarse copper oxide, the spiral is replaced and the cork bearing the glass delivery tube with stopcock closed, inserted. The straight calcium chloride tube is removed from the exit end of the combustion tube, and the absorption train connected as in Fig. 61. At this stage the apparatus is again tested in the manner already described to make sure that it is air- tight. After closing the screw pinchcock which admits the air to the purifying train, the glass cock is opened, and a slow stream of air — 2 — 3 bubbles per second — is admitted to the tube by carefully opening the pinchcock. Small flames from the burners under the copper oxide are lighted, beginning with those at the exit end of the tube and lighting one by one until a point about 10 cms. from the boat is reached. Two or three burners under the copper oxide spiral, but not within 5 cms. of the boat, are also lighted. The flames from these burners are gradually increased in size until the tube above them attains a dull red heat when the corre- sponding tiles are in position. Next follows that part of the operation the successful carrying out of which is essential in order to obtain accurate results, namely, the gradual combustion of the substance. Some informa- tion as to how the substance is likely to behave may be obtained before- hand by gently heating some of it on a piece of platinum foil and noticing if it is easily volatile or if it leaves a charred residue difficult to burn off. Until experience in this portion of the combustion has been acquired, the further heating should be done very slowly, as any sudden rush of vapour, which might lead to imperfect combustion, is to be avoided. The remaining burners, beginning with those farthest from the substance, are lighted and gradually turned on. The first indication of combustion is the appearance of moisture on the exit end of the tube, and an increase in the speed of the gas passing through the potash apparatus. With easily volatile substances the boat is heated at the beginning by means of hot tiles, brought from an already heated part of the furnace. The heating should be conducted in such a way that the gas bubbles in the potash apparatus can easily be counted ; if the rate exceeds this limit, the heat on the substance must be reduced either by lowering of flames or removal of tiles, until the approved speed is again reached. When the combustion is nearly finished, that is, when the rate of gas passing through the potash apparatus approximates to that in the bubbler, the stream of air is shut off by closing first the glass stopcock and then the screw pinchcock. A stream of oxygen is immediately turned on, the screw pinchcock admitting it being first opened and then the glass stopcock. In this way, any back diffusion of gas from the com- bustion tube to the purifying train is avoided. The passing of oxygen often results in an increased speed of bubbles in the potash apparatus. If not done previously, the tiles over the boat ar now closed and the whole tube heated to dull redness until all moisture is 446 SYSTEMATIC ORGANIC CHEMISTRY driven from the exit end, and the gas issuing from the apparatus rekindles a glowing splinter. The tiles over the boat should be occasionally raised and notice taken if any carbon (graphite) remains in the boat. Many substances have a carbon residue which only burns off very slowly, and of course the heating must be continued until combustion is complete. The removal of moisture from the tube is generally a matter of some difficulty, but it may be greatly accelerated by holding a very small flame or hot tile beneath the moist parts, and at the same time passing an increased current of gas through the apparatus. Care must be taken that there is no danger of the cork in the tube being burnt, and it should always be possible to hold the glass surrounding the cork between the finger and thumb. In general the time occupied from when the tube is first heated until all traces of moisture are driven over into the absorption apparatus is 60 — 75 minutes. Volatile substances, which must be heated more cautiously, and those which leave a residue of carbon, require longer time. As soon as the combustion is complete, the burners are lowered, and the stream of oxygen is replaced by one of air in order to displace oxygen from the absorption apparatus. After about 20 minutes the absorption appara- tus is disconnected from the combustion tube and stoppered. The straight ^uard tube is again introduced into the exit end of the combustion tube, the burners are extinguished and the stream of air shut off. The absorp- tion apparatus is wiped free from dust, etc., allowed to stand 30 minutes beside the balance and then weighed. From the difference in the weights of the absorption apparatus, before and after the combustion, the per- centages of carbon and hydrogen are calculated from the following formulae : — % of carbon == ^ Weight of substance 11 o/ ,r \ Weight of HoO 101 % of hydrogen = oi Vivace X m The error for each element should not exceed 0-2%. Discussion oi Results. — The difficulty of obtaining an accurate " blank determination " reveals how liable the analysis is to slight errors. Even in the best conducted analyses it is found that, as a rule, the percentage of carbon is a little low owing to the loss of moisture from the potash apparatus, whilst the hydrogen is a little high. The formation of carbon monoxide without complete oxidation to carbon dioxide leads to an error, as the carbon monoxide which is not absorbed by the potash escapes from the apparatus. If low results are being obtained for carbon, the escaping gas should be bubbled through palladious chloride solution or some other reagent which detects carbon monoxide. Substances which yield carbon monoxide readily should be burnt with a very long layer of copper oxide. Modifications of the Method and other Notes. — The combustion may also be conducted entirely in a current of oxygen. It is still an open question whether it is preferable to use oxygen from the beginning or only towards ESTIMATION OF CAKBON AND HYDROGEN 447 ,'the end of the combustion. Both methods lead to the same result, though i the second is the more economical, a little quicker and not so conducive to ; the formation of graphite. The purification required for the oxygen depends on the impurities con- ! tained in it, and these again vary according to the source and preparation of the gas. For instance, oxygen prepared by electrolysis contains gener- ally from 0-1 — -1% of hydrogen, and obviously the purification already : described would not be sufficient when electrolytic oxygen is used. Such oxygen should be passed through a tube containing copper oxide heated to dull redness. This tube, a piece of combustion tubing about 30 cms. long, containing a roll of copper oxide gauze, or layer of copper oxide, 12 cms. long, is inserted between the oxygen supply and the purifying apparatus. It is most conveniently heated in a short furnace of the regular combustion type, but if this is not available, it can be heated with a few Ramsay or other flat-flame burners. Cerium dioxide on pumice acts as a very active oxidising agent, and a short layer of it placed between the boat and the copper oxide enables the combustion to be carried out in a much shorter time, as the h eating may be done more rapidly without danger of incomplete combustion. To prepare this cerium dioxide pumice, enough pumice to fill 5 cms. of the combustion tube, 5 gms. of pure cerium nitrate crystals and enough water to cover the pumice are heated to dryness on a water bath in a dish. When used, this is first placed in the combustion tube ; it is kept in position by i two very narrow spirals of copper gauze. The decomposition of the cerium nitrate to cerium dioxide is completed by heating in the combustion furnace with oxygen passing through, first at low temperature, until all moisture is driven off, and finally at dull red heat, until the cerium nitrate is decomposed. Combustion ol Volatile and Hygroscopic Substances. — If the substance is hygroscopic, the boat must be enclosed and weighed in a dry stoppered tube, to which two small pieces of glass have been fused, in order to prevent it rolling when on the pan of the balance. /^V_ If the substance is a volatile liquid, it must be weighed in a V_X"~ small glass bulb (Fig. 62), drawn out to a wide capillary. Fig. 62. JThe bulb is first weighed. It is then heated, and while still hot, the capillary end is immersed in the liquid. As the bulb cools, the air inside it contracts, and some liquid is drawn into the bulb. If sufficient liquid is not introduced, the operation must be repeated. The tube is then sealed and re-weighed. When the bulb is ^about to be introduced into the combustion tube, the end of the capillary i is filed and broken off, the bulb is placed in the boat with its open end i elevated and directed towards the exit end of the combustion tube. In the combustion of a moderately volatile substance, such as naphthalene, the heat from the copper oxide spiral is sufficient to volatilise the greater part, and hence it is only necessary to light the burners under the boat i towards the end of the combustion. In the case of highly volatile sub- stances, a combustion tube is used which projects at least 15 cms. beyond he furnace at the inlet end. The boat containing the bulb is placed just 448 SYSTEMATIC ORGANIC CHEMISTRY outside the furnace, and then the copper oxide spiral in contact with the boat. A Bunsen flame is placed under the spiral, and the heat from it regulated so as to vaporise the substance at a convenient speed. Combustion of Substances containing Nitrogen. — A modification of the foregoing procedure must be adopted for the combustion of substances containing nitrogen, since oxides of nitrogen are formed to some extent, and these are liable to be absorbed in the potash solution. A spiral of metallic copper is introduced into the exit end of the tube and this, when red hot, reduces the oxides of nitrogen with the liberation of nitrogen, which passes through the apparatus unabsorbed. The first plug of asbestos is introduced, not 5 cms. but 15 cms. from the exit end of the combustion tube, and this space of 1 5 cms. is reserved for a reduced copper spiral. The layer of copper oxide is shortened by 10 cms., but no other changes are made in the filling of the tube. The copper spiral is prepared by rolling a strip of copper gauze, about 13 cms. wide, round a copper wire until the roll neatly fits the tube. To give the spiral a clean metallic surface, it is gripped with a pair of crucible tongs and heated to bright redness in a somewhat roaring blowpipe flame. It is then quickly pushed into a stout test tube containing, in addition to a pad of asbestos at the bottom, about 1 c.c. of pure methyl alcohol. During this operation the test tube should either be supported in a clamp, or wrapped, in a duster if held in the hand. The methyl alcohol reduces the film of oxide on the gauze, and is oxidised at the same time to formaldehyde. The vapours from the tube should be lighted, and when the flame recedes within the tube, a good cork bearing a delivery tube is inserted and connection made to a suction pump. Gentle suction is applied and as the copper spiral is still fairly hot, practically all the remaining alcohol is quickly removed. After a time, the test tube and its contents are allowed to cool, and the spiral removed to a vacuum desiccator containing calcium chloride, where it is kept until required for insertion in the combustion tube. It is important to carry out the combustion in such a manner that the copper spiral is not oxidised to any appreciable extent. The preliminary heating of the copper oxide is performed as already described, but the reduced copper spiral is put in position last — just before connecting the combustion tube to the absorption apparatus. The combustion may be carried out in either of the following ways — | (a) The same burners of the furnace are lighted as for non-nitrogenous substances, and air is passed in until no more water collects at the exit end of the tube ; the burners under the reduced copper spiral are then extin- guished, and the current of air replaced by one of oxygen. The current of oxygen is continued until a glowing splinter is rekindled by the gas issuing from the absorption train ; the oxj^gen is finally displaced from the apparatus by air. (b) The glass stopcock on the inlet end of the combustion tube is closed, and the combustion is performed without the passage of either air or oxygen through the tube. Oxygen is only admitted towards the end, and at the same time the burners under the reduced copper spiral are extinguished. The operation is completed as indicated in (a). Sub- ESTIMATION OF CARBON AND HYDROGEN 449 stances which have a difficultly combustible nitrogenous residue should be previously mixed with fine copper oxide. Combustion of Substances Containing Sulphur or Halogen.— The com- bustion of these substances is carried out similarly to that of non-nitro- genous substances, with the exception that half of the layer of copper oxide is withdrawn from the exit end of the tube and replaced by chips of fused lead chromate. The lead chromate retains the sulphur and halogens as lead sulphate or lead halide, and thus prevents them reaching the potash apparatus. The following precautions must be taken : (a) the lead chromate must not be heated so strongly as the copper oxide, other- wise it fuses to the glass, causing the latter to crack on cooling ; (b) the lead chromate above the last three burners at the exit end of the combus- tion tube should not be heated so strongly as the rest of the layer, since lead sulphate is slightly unstable and lead halide slightly volatile at a high temperature. The combustion of halogen-containing substances may be carried out by means of copper oxide alone, if a silver spiral is inserted at the exit end of the combustion tube in order to retain the halogen. Metallic Radicles. — When a metallic radicle is present in an organic compound, it is advisable to destroy the organic matter by ignition before making an estimation of the metal. The organo compounds of some metals on ignition give carbonates, while others give ^"^ T ^ 7 oxides. In certain cases where nitrogen is present, cyanides are formed. The FlG - 63 - metal in the residue is then estimated by the ordinary methods. In many cases the ignition of an organo-metallic compound may be carried out concurrently with the combustion of the compound. For this purpose a special type of boat (Fig. 63), is advan- tageous. The boat is made of transparent quartz tubing drawn out at both ends and upturned ; these ends provide an entrance and exit for the air or oxygen, while none of the residue is carried over by the current of gas. (J. C. S., 121, 1292.) s.o.c. G G CHAPTER XXXV QUANTITATIVE ESTIMATION OF NITEOGEN- Dumas Method. — The substance is completely burned by copper oxide in a tube filled with, carbon dioxide ; the nitrogen evolved is collected over caustic potash and its volume measured ; while the carbon and hydrogen, being oxidised to carbon dioxide and water respectively, are retained by the caustic potash solution. The combustion may be carried out in two ways — (a) in a tube sealed at one end, the carbon dioxide being generated from materials inside the tube, and (6) in a tube open at both ends, the carbon dioxide being generated in a second vessel and passed into the combustion tube. Method (a) is the more convenient when estimations are only conducted occasionally, and method (b) when estimations are frequently or continuously conducted. Method (a). — 500 gms. of coarse or wire-form and 100 gms. of fine copper oxide are placed in a nickel and a porcelain boat respectively. The first is heated to a dull red heat in a muffle furnace, and the second is heated over a Bunsen flame. While they are heated, the combustion tube is prepared. A combustion tube, 80 — 85 cms. long, and similar to that used for the estimation of carbon and hydrogen, is selected. A glass rod is sealed to one end, and the tube is heated near this end in a blowpipe flame until the glass softens, when it is quickly drawn out. Heat is again applied to the shoulder of the tube until the glass softens, when it is again drawn out. If a good blowpipe has been used, and the glass well softened each time, only a small capillary should now emerge from the shoulder of the tube ; this is sealed off close to the shoulder and the latter rounded by alternately heating it and blowing into the open end of the tube. The sealed end should be annealed by holding it in a smoky flame before setting it aside to cool (see p. 38). When cold, it is thoroughly washed out and dried. The coarse and the fine copper oxide are now allowed to cool somewhat before being introduced into two clean dry flasks, which are closed with ground-glass stoppers, or corks coated with tinfoil. When the tube is about to be filled, it should be clamped in a vertical position at the side of the bench, and at a suitable height for filling. A funnel with a short but wide stem should be inserted in the open end of the tube to assist in the filling. As shown in Fig. 64, sufficient magnesite to fill 12—13 cms. is first placed in the tube ; it should be in pieces the size of a pea, and sifted free from powder ; dark or discoloured grains should be rejected. It is important to use only the best qualities of magnesite. A plug of asbestos is then inserted and pushed home with a long glass rod. Enough coarse 450 QUANTITATIVE ESTIMATION OF NITROGEN 451 SI 2 T £ « v- oT Sid Fig. 64. copper oxide is then poured in through the funnel to fill approximately 8 cms. of the tube ; this is followed by a 2-cm. layer of fine copper oxide. For mixing the substance with fine copper oxide it is convenient to use a weighing bottle of shape indicated in Fig. 64a; the neck should be small enough to enable it to be inserted in the end of the combustion tube. Enough fine copper oxide to fill about 5 cms. of the com- bustion tube is placed in this bottle, about 0-2 gm. of the powdered substance to be analysed is accurately weighed out from another weighing bottle (which should contain the approxi- mate quantity) and placed on top of the copper oxide in the first bottle ; some more fine copper oxide, sufficient to cover the substance, is added, and the whole gently mixed by shaking the bottle with stopper inserted. The contents are now poured into the combustion tube, and the bottle " rinsed " a few times with fine copper oxide, the " rinsings " being poured into the combustion tube. The layer of fine copper oxide and substance should be approximately 10 cms. in length. A 30-cm. layer of coarse copper oxide is then poured in, and an asbestos plug inserted to keep it in position. A reduced copper spiral 10 cms. long is prepared as described on p. 448 ; as in the estimation of carbon and hydrogen in nitrogenous compounds, it serves to decompose oxides of nitrogen with the liberation of free nitrogen ; it is placed in position as shown in Fig 64. Before commencing to fill the tube, the subdivisions should be marked off on it against a meter stick ; the various lengths should not differ much from the figures given, as otherwise the layer of coarse copper oxide may be too short or the copper spiral out of position. When the tube is filled, it is fitted with a good rubber stopper carrying a bent delivery tube, and whilst placed in a horizontal position on the bench, it is gently tapped along one side in order to make a passage for gas above its contents. The tube is now placed in a furnace possessing a flame surface of 75 cms. ; the furnace should be tilted so that the sealed end of the tube is somewhat higher than the other, and the 5 cms. free space should just lie outside the furnace. This arrangement prevents any moisture which collects in the cooler protruding part of the tube from running back into the hotter portion. In order to protect the rubber stopper, a square of asbestos board, having a circular hole in the centre, is placed over the tube between the furnace and the stopper. For the collection of the nitrogen a graduated SchifFs azotometer (Fig. 65) is used. Into this a quantity of mercury sufficient to fill it 4 — 5 mms. above the lower side tube, is first placed. A solution of potash, previously G G 2 Fig. 64a. 452 SYSTEMATIC ORGANIC CHEMISTRY prepared by dissolving caustic potash (about 150 gms.) in an equal weight of water in a porcelain dish, is then poured into the pear-shaped reservoir. By opening the tap and raising the reservoir, the apparatus becomes filled and remains so on closing the tap and lowering the reservoir. The tap should be greased and examined to see that it is thoroughly air-tight. The lower bent tube of the azotometer is connected to the delivery tube Fig. 65. extending from the combustion tube by means of thick pressure rubber tubing on which a screw pinchcock is placed. The Combustion. — The tap of the azotometer is opened and the pear- shaped reservoir lowered so that it contains practically all the potash solution. The pinchcock is opened, leaving the apparatus ready for flooding with carbon dioxide. The burners under the one-half of the magnesite layer next the sealed end of the tube are lighted and gradually turned on until the flames all but meet over the tube ; the tiles over these burners are then closed down. A rapid stream of carbon dioxide is thus produced, which quickly drives the air out of the tube before diffusion has time to take place. After a rapid current of carbon dioxide has been evolved for ten minutes, the burners under the spiral and the layer of coarse oxide to within 10 cms. of the fine copper oxide are lighted in order to drive out any occluded gases (hydrogen and air). In another 15 minutes the current of carbon dioxide is allowed to slow down a little ; the azotometer is filled with potash solution by raising the reservoir and closing the tap. The gas entering the azotometer is now largely absorbed on passing up the column of potash ; the bubbles should decrease in size as they ascend, and appear as mere specks on approaching the top. If, however, this is not the case, owing to the combustion tube still containing an appreciable quantity of air, the tap should be opened and the reservoir lowered, and a rapid current of carbon dioxide passed for 5 minutes longer. The test is QUANTITATIVE ESTIMATION OF NITROGEN 453 again repeated ; if after 2 minutes only a trace of foam has collected, the azotometer is filled with potash solution, the tap closed and the reservoir lowered as far as possible. The current of carbon dioxide is lessened, all but one burner under the magnesite being either extinguished or lowered. The copper spiral and the part of the coarse copper oxide already heated should now be at a dull red heat. The burners under the coarse oxide on both sides of the fine oxide are now lighted, beginning with those farthest away from the substance, and lighting two at a time — one on each side. ! Each burner, the tiles above it being closed, should heat the tube above it to a dull red heat before its neighbour is lighted, but the flames should not meet above the tube. When the flames approach the fine oxide mixed with the substance, the gas passing into the azotometer should be carefully watched, and as soon as any nitrogen collects, the further heating of the ! substance should be done very gradually. As described in the estimation of carbon and hydrogen, a little of the substance should be examined beforehand to ascertain whether it is easily volatile or not. If the sub- stance is easily volatile, it should be heated at first with very small flames or with hot tiles brought from an already heated part of the furnace.* The success of the analysis largely depends on the gradual heating of the substance ; only one burner at a time should be lighted under the sub- stance, and when the amount of unabsorbed gas evolved at this heat slackens, another burner is lighted. The rate of gas bubbles passing up the azotometer should not be greater than can be easily counted ; irregular bursts of gas may cause the potash solution to be sucked back into the combustion tube. When the substance, having been heated in this fashion up to a dull red heat, ceases to evolve nitrogen, the burners under the magnesite layer are lighted, and a not too rapid stream of carbon dioxide passed through the apparatus for about 15 minutes in order to drive all traces of nitrogen into the azotometer. The absorption apparatus is then closed by the pinchcock and discon- nected from the combustion apparatus at the rubber tubing. The burners under the spiral and oxide are gradually turned down so that the combustion tube cools with a slow stream of carbon dioxide passing through it ; this prevents the copper spiral being oxidised. The reservoir is raised until the liquid in it is at the same level as the liquid in the azotometer and a thermometer is hung beside the azotometer. The levels of the liquid in the reservoir and azotometer are adjusted occasionally, and in about an hour the volume of the nitrogen is read off, and the temperature and atmospheric pressure noted. The percentage of nitrogen is calculated from the formula : — 100 _ I 0-0012562 w ( P) 760(1 + 0-003665-0 where w is the weight in grams of the substance taken, V the observed volume of nitrogen, P the barometric pressure in mm. of mercury, and * If the carbon dioxide is so slowly absorbed that it tends to„drive the potash out of the azotometer, fresh potash solution should be placed in the cup at the top and admitted by opening the stopcock very slightly. 454 SYSTEMATIC ORGANIC CHEMISTRY p the vapour pressure of the potash solution at the temperature t ; when 50% potash solution is used its vapour tension is negligibly small. Instead of reading the volume of nitrogen in the azotometer it is often customary to transfer it, after all traces of carbon dioxide have been absorbed, to a graduated tube standing over water. This gives a result free from any errors due to incorrect vapour tension or to the presence of foam on the surface of the potash in the azotometer. When it is intended to transfer the nitrogen after this fashion, an azotometer having a delivery tube above the tap should be used ; a truncated funnel is attached on this delivery tube by means of a piece of rubber tubing or cork so as to form a cup surrounding the delivery tube (Fig. 66). At the time the azotometer is filled just prior to the collection of the nitrogen evolved during the com- bustion, the pear-shaped reservoir should be raised sufficiently high to fill the delivery tube with potash solution. To transfer the nitrogen the cup at the top of the azotometer is filled with water above the end of the delivery tube, and any bubbles of air in the delivery tube are expelled by allowing water to enter it through a glass tube drawn out Yto a capillary. A graduated tube, completely full of water, is closed by the finger and inverted in the water in the cup in such a position that the end of the capillary enters the mouth of the graduated tube. The nitrogen is expelled from the azotometer by raising the reservoir and opening the stopcock. The graduated tube containing the nitrogen — is then transferred, after closing the open end with the 4 finger, to a long glass cylinder containing cold water ; here it is clamped and allowed to stand 20 minutes in order to ^ attain room temperature. The volume of the gas is read off Fig. 66. after adjusting the tube so that the level of the water is the same inside and outside, the tube being held with a wooden or paper holder, but not with the hands. The barometric pressure is noted, and the temperature of the gas is taken as that of the water with which it is in contact. The percentage of nitrogen is calculated from the same formula as before, p representing the vapour tension of water in this case. A third method of measuring the nitrogen is to let it remain in the azotometer and displace the potash solution by water. About 20 c.cs. of potash solution is placed in the cup. The reservoir is lowered, the stop- cock is partially and carefully opened to allow the solution from the cup to run down the inside walls and absorb any traces of carbon dioxide that may be present. The stopcock is closed before all the solution has left the cup. The operation is repeated, using cold distilled water to wash the gas until the potash solution is out of the azotometer and reservoir. While the potash solution is being displaced into the reservoir it should be poured out a little at a time, care being taken that air is not admitted to the azotometer through the rubber tube. Method (b). — The combustion tube used is in every way similar to that used in connection with the estimation of carbon and hydrogen. The short tube (Fig. 67) is partially filled with powdered sodium bicar- QUANTITATIVE ESTIMATION OF NITROGEN 455 bonate or magnesite in pieces the size of a pea, and a loose plug of glass-wool is inserted to retain solid particles ; the tube should be tapped horizontally to provide a channel for gas ; it is heated either in a short furnace or by flat name Bunsen burners. The two tubes are connected by rubber stoppers and a trap which prevents any drops of moisture arising from the decom- position of the bicarbonate from passing into the heated combustion tube. The method of filling the combustion tube is indicated in the general diagram (Fig. 67). The mixture of fine copper oxide and substance is placed in a long boat which may be porcelain, quartz or copper. The copper oxide spiral takes the place of the short layer of copper oxide mentioned in method (a) and serves to oxidise any vapours which diffuse backwards. The reduced copper spiral is inserted after the rest of the tube is filled. The manner of connecting the combustion tube to the azotometer as well as the manner of conducting the combustion is the same as described in method (a). It is particularly important that the evolution of carbon dioxide from the smaller tube should not cease altogether at any time, since otherwise vapours may diffuse backwards into the trap. The convenience of this method for carrying out a number of consecutive "<-5cms-x7<:nis B 11 H=^g_^=(XE 40cms- Fig. 67. estimations is obvious ; the oxidised spiral can be quickly removed and replaced, and the short tube can be quickly recharged and connected. Before starting a second combustion, however, the boat and the reduced copper spiral should be removed from the tube and a current of dry oxygen passed through while the tube is heated to dull redness for about 15 minutes ; any reduced copper is thus reoxidised. After this preliminary heating the tube should be allowed to cool in a current of dry carbon dioxide generated from a Kipp apparatus. Copper oxide which occludes a small quantity of air when heated and cooled in air does not occlude the gas so readily when cooled in carbon dioxide. Length of Time for an Analysis. — From the beginning of the heating of the magnesite to the appearance of a rapid current of carbon dioxide requires about 10 minutes ; the first test as to whether air is still present in the tube should be made 15 minutes later ; length of time for further tests, 5 minutes. The heating of the spiral and coarse oxide to dull redness occupies about 15 minutes ; further heating to start the com- bustion of the substance 5 minutes. The combustion proper requires 30 minutes. Displacement of the last traces of nitrogen by heating the magnesite occupies 10 minutes. The total time required for these periods of heating is, therefore, 90 minutes. Further Notes. — More heating is required to generate carbon dioxide 456 SYSTEMATIC ORGANIC CHEMISTRY from magnesite than from sodium bicarbonate. A mixture of potassium bichromate and sodium carbonate has been recommended for the genera- tion of carbon dioxide by direct heating. Manganese carbonate has also been recommended. Carbon dioxide may also be obtained by the action of acid on marble in a Kipp apparatus ; the marble must be previously boiled for a long time with water to expel occluded air, and even then it is almost impossible to get rid of the last traces. The acid should also be boiled. Sodium hydroxide should not be used in the azotometer as the carbonates formed crystallise out easily owing to their sparing solubility in caustic soda solutions. Cupric oxide, when heated and cooled in an atmosphere of air or oxygen, absorbs some of these gases which it only gives off very slowly when reheated ; this causes an error in the estimation of nitrogen. With com- pounds containing much nitrogen the percentage error due to this cause is very small, but with compounds containing little nitrogen the error is appreciable. The Dumas method is applicable to every type of organic nitrogen compound and gives accurate results. In a few cases the method gives results which are too high owing to the formation of methane, which is not completely oxidised by copper oxide in absence of oxygen, and collects in the azotometer. To obviate this difficulty the coarse copper oxide should be replaced by a long layer of lead chromate and the substance mixed with 'fine copper oxide and powdered lead chromate. (J. C. S., 89, 570.) If any nitric oxide escapes decomposition by the reduced copper spiral its presence is detected when the gas in the azotometer is mixed with air. Nitrogen as nitric oxide occupies twice the volume of the same amount of nitrogen in the free state. Kjeldahl's Method of Estimating Nitrogen. — The majority of organic nitrogen compounds in which nitrogen exists in a non-oxidised form, when heated with concentrated sulphuric acid are completely destroyed, with formation of ammonium sulphate. Compounds containing methyl groups attached to nitrogen are seldom completely destroyed, but give rise to methylamines ; this, however, causes no error, since the methylamines are strong bases. From the resulting solution the ammonia (or methyl- amine) is liberated by means of alkali ; the gas is distilled off and collected in standard acid. A weighed quantity — generally about 0-5 gm., but varying from 0-2 gm. to 1-0 gm., according to the percentage of nitrogen — of the finely powdered substance is placed with about 10 gms. of pure potassium hydrogen sulphate in a long-necked, round-bottomed Jena flask of 500 c.cs. capacity, and 30 c.cs. of pure concentrated sulphuric acid are introduced from a pipette. The object of the potassium hydrogen sulphate is to promote oxidation by raising the boiling point of the liquid. The flask is clamped over a sand bath and the contents boiled briskly until the liquid, which first darkens in colour, becomes clear and colourless or slightly yellow. At this stage the active evolution of sulphur dioxide ceases. This initial decomposition generally requires 30 — 60 minutes' heating. Should it QUANTITATIVE ESTIMATION OF NITROGEN 457 prove difficult to effect, pure precipitated manganese dioxide which has been dried at 150° is added in small quantities to the hot liquid at intervals of about 3 minutes, with thorough agitation of the contents of the flask after each addition, until a pale yellow or pink colour is attained. The oxidation is effected very rapidly by the addition of the manganese dioxide, generally not occupying more than 15 minutes when the mixture is at a sufficiently high temperature. Instead of adding manganese dioxide, a crystal (about 0-5 gm.) of copper sulphate or a drop of mercury may be added to serve as an oxygen carrier, but the oxidation is not effected so quickly as when manganese dioxide is used. When the decomposition is complete the flask is allowed to cool, the contents are diluted with 2 — 3 vols, of dis- tilled water, and a few pieces of porous earthenware, which later serve to induce regular ebullition, added. The flask is now attached to the distilling apparatus shown in Fig. 68. Through one hole of the doubly bored rubber stopper a bulb adapter, widen serves to retain any alkali carried upwards, is inserted. The end of the adapter is con- nected with an upright condenser, the end of which just dips below the surface of 25 c.cs. of a semi-normal solution of hydro- chloric or sulphuric acid, contained in a conical flask. A tap-funnel, bent as shown, is inserted in the neck of the flask through the second hole in the cork. A solution containing 30 gms. of caustic soda in 60 c.cs. of distilled water is slowly run in through the funnel while the contents of the flask are gently agitated. The flask is then heated, cautiously at first, to avoid too rapid evolution of ammonia, and vigorously after a few minutes. Distillation is continued until the volume of liquid is reduced by one- third, when all the ammonia should have passed over. At this Stage the distillate is tested with red litmus paper, and if no further ammonia is being evolved the conical receiver is removed and the excess of standard acid in it determined by titrating with semi-normal sodium carbonate, using Methyl Orange as indicator. If there is any doubt about the purity of the reagents used, a blank "experiment should be performed, using the same quantities of the same reagents under the same conditions. The volume of the standard acid neutralised in the blank experiment is deducted from the volume of acid neutralised in the determination — • Fig. 68. % of nitrogen N Volume of ^ acid neutralised X 0-007 X 100 Weight of substance taken. CHAPTER XXXVI QUANTITATIVE ESTIMATION OF HALOGENS AND SULPHUR Carius Method. — The method of Carius, which is applicable to practically all types of organic halogen compounds, consists in oxidising the substance with fuming nitric acid, under pressure in presence of silver nitrate. The silver halide formed is then separated by filtration and weighed. The following are required for the analysis : 1. A tube of thick walled soft tubing about 50 cms. long, 12 — 13 mms. inside diameter, and walls 2 — 3 mms. thick. Tubes of hard potash glass with walls 2 mms. thick may also be used. The tube is carefully sealed at one end, in the manner described on p. 38, after which it is thoroughly washed and dried. 2. A weighing tube, about 10 cms. long, sealed at one end and of such a diameter that it slips easily into the thick walled tube. 3. A funnel tube or thistle funnel, about 40 cms. long, which fits into the sealed tube and serves to convey the silver nitrate and fuming nitric acid to the bottom of this tube. 4. Pure fuming nitric acid, the purity of which should be tested by diluting 2 c.cs. of it with 50 c.cs. of distilled water and adding a few drops of silver nitrate solution. The liquid should remain perfectly clear. If it contains chlorine, it must be redistilled over a few crystals of silver nitrate. 5. A tube furnace (bomb furnace). (See p. 40.) 6. Solid silver nitrate. Filling and Sealing the Tube. — The exact weight of the weighing tube is determined. Into it is placed about 0-2 — 0-3 gm. of the substance to be analysed, finely powdered, and the tube plus its contents exactly weighed again. By means of the funnel tube, a quantity of finely pow- dered silver nitrate varying from 0-5 — 1-0 gm. — according to the per- centage of halogen-- is introduced into the sealed tube. This is followed by 2 c.cs. of fuming nitric acid. The funnel tube is then removed, care being taken not to touch the sides of the sealed tube with it, and while the latter is held at a slight angle, the weighing tube is allowed to slide gently down to the bottom of it, but the substance must not come into contact with the acid. The open end of the sealed tube is then sealed in the blow- pipe, as described on p. 40, care being taken that during the sealing the substatice does not come in contact with the acid. When the substance to be analysed is a liquid, it is placed in a bulb tube with an open capillary (for filling, see p. 447), which is introduced, bulb foremost, into the tube after the silver nitrate and nitric acid have been inserted. 458 ESTIMATION OF HALOGENS AND SULPHUR 459 Heating the Tube. — When cold, the tube is placed in an iron protecting cylinder, and the whole transferred to a tube furnace, where it is heated according to the directions given on p. 41. The temperature and duration of heating depend on the greater or less resistance of the sub- stance towards decomposition. With many compounds that oxidise easily, 2 — 4 hours at 150° — 200° is sufficient, while substances which do not easily oxidise, especially those containing sulphur, must be heated 8 — 10 hours and as high as 250° — 300°. It is advisable to commence the operation in the morning, and to raise the temperature gradually to 200° during the first four hours, and to 250° or 300° during the second period of 4 hours. Practically all substances are decomposed by this treatment. For any particular substance, experiment will show whether the duration of heating and the temperature may be reduced. Opening the Sealed Tube. — The tube is allowed to remain in the furnace until perfectly cold. The iron protecting case containing the tube is then removed from the furnace, and the capillary end of the tube allowed to project 3 or 4 cms. Before heating the capillary to softening in a large name, care must be taken to drive back into the tube, by gently heating over a small flame, any liquid which may have collected in the capillary. Fall directions are given on p. 41 for opening the capillary. After opening the capillary, the tube is removed from the case, and examined to see if it still contains crystals or oily drops of the undecomposed sub- stance. If it does, the capillary is again sealed, and the tube reheated in the furnace ; but if it does not, a deep file scratch is made in the wide part of the tube about 3 cms. below the shoulder of the capillary and the end broken off according to the second method of opening sealed tubes (p. 42). The tube is then held almost in a horizontal position, and the conical end removed ; any fragments of broken glass are carefully wiped off, and not allowed to become admixed with the contents of the tube. The part broken off is washed free from any liquid or precipitate which may have adhered to it, with distilled water into a beaker. The contents of the tube are diluted with distilled water and poured into the beaker, care being % taken that the fall of the weighing tube does not injure the beaker. The tube is held in an inverted position over the beaker, and the outer ■ edges of the open end washed with distilled water. The precipitate still remaining in the tube is washed out by repeated shakings with small quantities of distilled water, any precipitate which is attached to the tube may be loosened by rubbing with a long piece of glass rod, over the end of which is placed a short piece of rubber tubing.* The short end of a thin piece of glass rod bent at a right angle is then inserted in the mouth of the weighing tube, and while the latter is removed just above the surface of the liquid, the outside is washed with distilled water. It is then held in the fingers and the inside washed with distilled water into the beaker. Estimation oi the Silver Halide. — The contents of the beaker are now heated to boiling, until the silver halide settles and the supernatant liquid * The last traces of silver halide may be removed from the tube by washing out with ammonia into the beaker. Extra nitric acid must in this case be added to the contents of beaker. 460 SYSTEMATIC ORGANIC CHEMISTRY is clear. Any lumps amongst the precipitate are crushed from time to time to ensure that the silver nitrate is completely dissolved out. A Gooch crucible, fitted with a paper disc, is prepared ; a quantity of dilute nitric acid, approximately the same in volume and concentration as that in the beaker, is filtered through it. It is then washed well with distilled water and dried in an air oven at 140° — 150°, after which it is weighed. The contents of the beaker are then filtered with suction through the crucible, washed free from silver nitrate with distilled water, and finally dried, until constant in weight, at 140° — 150° in an air bath (30 minutes). The weight of silver halide is then determined. °/ of halo en — X °^ na ^°S en x of Ag halide /o o la ogen — wt# 0 f SUD stance taken X M. W. of Ag halide A method — somewhat more liable to error — of estimating the silver halide consists in filtering the contents of the beaker through the usual paper and funnel, washing the precipitate thoroughly with distilled water, and drying in the steam oven. The paper and precipitate are then incinerated in the usual way. Notes.—- It sometimes happens that, even after taking the precautions advised, the silver halide is mixed with fragments of glass. If this happens in the case of silver chloride, the precipitate after filtering and washing should be digested in the Gooch with warm dilute ammonia solution, which dissolves out the silver chloride. Any fragments of glass are then filtered off, and the pure silver chloride in the filtrate precipitated by acidifying with hydrochloric acid.* When fragments of glass are mixed with silver iodide, the separation is much more difficult. The silver iodide plus glass is first estimated, and afterwards left in contact with dilute sulphuric acid and a piece of chemically pure zinc ; after several hours the silver halide is reduced to metallic silver. The supernatant liquors are decanted from the silver and glass, which are washed several times by decantation with water. The silver is dissolved in dilute nitric acid and the fragments of glass collected on a filter, dried and weighed. The only chlorine and bromine compounds which fail to give good results by this method are the highly halogenated aromatic derivatives, such as hexachlorobenzene. Iodine compounds often give unreliable results, since silver iodide is appreciably soluble in a nitric acid solution of silver nitrate. Free iodine is also formed in some instances (see note on next method). Method of Pira and Schiff. — This method is only applicable to those organic substances which are not highly volatile. Liquids which combine directly with lime or sodium carbonate may also be analysed in this way. About 04 — 0-3 gm. of the substance is weighed into a very small platinum crucible, which is then filled up with an intimate mixture of sodium carbonate (1 part) and pure powdered quicklime (4 — 5 parts). The crucible is then placed in an inverted position in a larger platinum crucible, the space between the two being completely filled with the * Silver bromide, though much less soluble in ammonia than silver chloride, may also be freed from glass in this manner. ESTIMATION OF HALOGENS AND SULPHUR 461 same mixture of sodium carbonate and lime, so that the small crucible is entirely covered. The large crucible is now heated in a large Bunsen or blowpipe flame, so that the outer portions attain a high temperature before the substance in the smaller crucible begins to decompose. The whole is finally raised to a red heat. The crucibles and contents are allowed to cool, then digested with water in a strong beaker. Dilute nitric acid is cautiously added until the solution reacts acidic, care being taken that the temperature does not rise to any extent. External cooling is advisable. The solution is filtered to remove any carbonaceous matter, and the halogen precipitated with silver nitrate and estimated as described in the Carius method. When the substance contains iodine, the method requires modification ; sodium carbonate is then employed alone, as calcium iodate would be formed were lime present. If any iodine appears after acidification with nitric acid, it is reduced to hydriodic acid with the minimum quantity of sul- phurous acid. r \ = x Bromine and Chlorine = J | (Robertson). — The prin- J ciple underlying the f \ . , method is that organic substances containing these elements give them up entirely in a volatile form when heated with a mixture of chromic and sulphuric acids ; bromine compounds yield a mix- ture of bromine and hydrogen bromide, which is absorbed in alkaline F IG> 69. hydrogen peroxide as alkali bromide. Chlorine compounds yield chlorine, hydrogen chloride and chromyl chloride ; these are absorbed in alkaline hydrogen peroxide with the formation of alkali chloride and chromates ; and after reduction of the chromate, which would mask the end point, the chlorine in the solution is estimated in the usual way with silver nitrate and thiocyanate. The Apparatus (Fig. 69). — The reaction vessel, a flask of about 70 c.cs. capacity, fitted with a ground-glass joint, to which are attached an inlet and an exit tube, is heated by radiation from an asbestos gauze placed 2-5 cms. beneath it. The absorption apparatus consists of a bulb tube fitted to the exit tube of the reaction flask by a ground-glass connection, and a second smaller U-tube which serves as a guard. The reagents required are pure redistilled sulphuric acid, chromic acid, 10% sodium hydroxide solution, and hydrogen peroxide solution free from chloride. 462 SYSTEMATIC ORGANIC CHEMISTRY The Method. — Enough of the substance to give halogen equivalent to about 9 c.cs. of ^ silver nitrate is weighed from a small tube (or, if a liquid, either from a Sprengel pipette or in a bulb tube) into the reaction vessel. 4 — 6 gms. of chromic acid are then introduced. The ground-glass joint, lubricated with syrupy phosphoric acid, is fixed in position, and the flask is connected to the absorption apparatus. To the large U-tube are added 10 c.cs. of the sodium hydroxide solution, and the same volume of hydrogen peroxide solution (or water and 1 — 2 c.cs. of perhydrol). The smaller U-tube contains a little sodium hydroxide solution. Then by means of a small funnel or pipette, 25 — 30 c.cs. of sulphuric acid are poured down the inlet tube into the reaction vessel, and a slow current of dry air is blown or aspirated through the apparatus. In many cases the decomposition begins at once, and should be moderated by external cooling in case it tends to become violent. In other cases heating should be commenced with a small flame, but the source of heat should be immediately removed if the evolution of gas becomes too vigorous. After about 10 minutes, the initial vigour of the reaction will have subsided, and the heating may be increased, and the stream of air made more rapid. When adjusted at this stage, the appa- ratus may be left without further attention, and in 45 — 60 minutes the colour of bromine or chromyl chloride will have disappeared from the reaction vessel, and the operation will be complete. It is advisable to shake round the contents of the flask towards the end of the experiment, as sometimes particles of partly decomposed substance are projected above the level of the sulphuric acid. The contents of the absorption tubes are now washed into a conical flask. In the case of a bromine estimation, the solution is acidified with N nitric acid, and 10 c.cs. of — silver nitrate are added from a pipette ; the contents of the flask, cooled if necessary, are now titrated with thiocyanate in the usual manner. If chlorine is being estimated, it is necessary to destroy the highly coloured chromate, which would obscure the end point. For this purpose, the liquid is heated to boiling, and then neutralised with nitric acid. In the presence of hydrogen peroxide, the chromate is reduced to a chromic salt, which at the dilution of the experiment, is practically colourless. 10 c.cs. of standard silver nitrate are added, the solution is filtered free from silver chloride (which reacts with thiocyanate), cooled, and the excess of silver in the filtrate estimated. Standardisation of Reagents. — In order to obtain accurate results, it is necessary to standardise the silver nitrate and thiocyanate solutions with pure potassium bromide under exactly the same conditions as those of the experiment. For this purpose potassium bromide equivalent to about N . . . 9 c.cs. of silver nitrate is dissolved in a little water, and sodium hydroxide and hydrogen peroxide are added to the solution ; after acidification with nitric acid, 10 c.cs. of the silver nitrate solution are: ESTIMATION OF HALOGENS AND SULPHUR 463 N added, and the excess of silver is titrated with ^— ^ thiocyanate. By this method any errors caused by the presence of traces of chloride in the reagents or due to the very slight influence of hydrogen peroxide are all eliminated. It should be noticed that in presence of hydrogen peroxide, the red colour of ferric thiocyanate disappears in the course of several minutes. Except in the case of a few bromohydrocarbons the method gives excellent results. It is advisable to carry out a blank determination under exactly the same conditions as an actual determination. For a discussion of results, see original paper (J. C. S. 107, 902.) Quantitative Estimation of Sulphur Method of Carius. — The process is almost the same as that described under the estimation of halogens. The compound is oxidised in a sealed tube with fuming nitric acid, but neither silver nitrate nor barium chloride are placed in the tube. The resulting sulphuric acid is precipitated and weighed as barium sulphate. Similar quantities of substance and of fuming nitric acid are taken, and the processes of sealing, heating and opening the tube are conducted in the same way as for halogens. The contents of the tube, after being washed out into a beaker, are filtered free from fragments of glass. The filtrate is diluted to about 300 c.cs. with water, heated to boiling, and the sulphuric acid precipitated as barium sulphate by the addition of barium chloride solution. A large excess of barium chloride should not be added owing to the sparing solubility of barium nitrate in aqueous mineral acids ; this can be avoided by allowing the precipitate to settle before adding more of the solution. The liquid is heated over a small flame until (sometimes 1 — 2 hours) the precipitate settles and the supernatant liquid is clear. It is then filtered either through an ordinary funnel, or through a Gooch crucible (see Halogen Estimation), and the precipitate washed well with hot water. The weight of barium sulphate is finally determined. °/ of sul hur - Wt ' ° f BaS ° 4 x 32 x 100 ^ 233 X wt. of substance taken Frequently in this method a considerable amount of gas is evolved, and the tube is liable to burst. In such cases the sealed tube should be heated only to 200° for 2 hours, after which it is allowed to cool, and the capillary opened to allow the gases to escape. It is then resealed and heated to 300°. Many sulphur compounds, especially aliphatic sulphides, do not give accurate results, as the sulphones formed by the action of nitric acid are generally so stable as to resist further decomposition by the acid. When stable sulphones are formed, the contents should be washed out into a nickel basin, made alkaline with caustic potash, and evaporated to dry- ness. The residue is then treated as described in the Estimation of Sul- phur by Fusion. Fusion Method. — This method is applicable only to substances which 464 SYSTEMATIC ORGANIC CHEMISTRY are not easily volatile. A quantity of the substance — 0-2 to 0-4 gm. — is intimately mixed with 4 gms. sodium peroxide and 7 gms. sodium carbonate in an iron crucible.* It is heated very cautiously with a small flame which does not touch the crucible at first. The flame is very gradually increased until the crucible is ultimately raised to a red heat, at which it is maintained for half an hour. (Note. — Great care is necessary in the early stages of the heating, in order to avoid explosive reaction.) The melt is allowed to cool, taking care to avoid loss of any material which may have crept up the sides of the crucible. It is then digested with water, a few c.cs. of bromine water added, and the resulting solution with the crucible and lid in it warmed on the water bath for half an hour. The crucible and lid are then removed, washed thoroughly, and the solution acidified with hydrochloric acid and filtered. The sulphur in the filtrate is finally precipitated and estimated as barium sulphate. Simultaneous Determination of Halogens and Sulphur. — The operation 1 is conducted as described under the Estimation of Halogens (Carius). The sealed tube is charged with silver nitrate, fuming nitric acid and sub- stance. After the heating, the silver halide is filtered off and estimated. The filtrate, which contains the excess of silver nitrate in addition to the sulphuric acid formed by oxidation, is warmed, and to it is added a boiling solution of barium nitrate (free from chloride). The solution should be very dilute — about 500 c.cs. for 0-3 — 0-4 gms. substance originally taken — and an excess of barium nitrate, owing to its sparing solubility, is to be avoided. The barium sulphate is estimated as described under Deter- mination of Sulphur. * The reagents used must be pure. OHAPTEE XXXVII MOLECULAR WEIGHT DETERMINATION The methods mostly employed in organic chemistry for the deter- mination of molecular weights are the vapour density method of Victor Meyer and the freezing point method of Raoult ; the former being simple and rapid in practice is almost universally employed where possible. The boiling point method is sometimes employed. Method of Victor Meyer. — This method, which is used for substances which volatilise without decomposition, involves the use of the apparatus shown in Fig. 70. The inner vessel A consists of an elongated glass bulb with a long narrow stem ; it is carked at the top, near to which point a side tube, which serves to deliver gas into a measuring tube C full of water and standing in a trough of water, is sealed. Before commenc- ing the operation, A is thoroughly cleaned and dried, and a small quantity of previously ignited sand or asbestos — to break the fall of the Hoffmann bottle when it is dropped in — is placed at the bottom of the bulb. The bulb of the outer jacket B is half filled with a liquid whose boiling point is 20° — 30° above that of the substance whose molecular weight is to be determined ; a few pieces of broken porcelain are also added to induce regular boiling. B may be of glass, copper or tinplate, the last two being more durable. The inner vessel is fixed in the outer by means of a split cork which has been suitably bored (before splitting) to accommo- date the neck of A, and a bent glass tube which conveys away the vapours of the boiling liquid. While the liquid in B is being heated to boiling, about 0-1 gm. of the s.o.c. 465 h h Fig. 70. 466 SYSTEMATIC ORGANIC CHEMISTRY substance to be determined is weighed out in the Hoffmann bottle H. As the air in A expands on heating (A being corked) it is allowed to escape through the capillary tube without entering the measuring tube. But as soon as a constant temperature is reached, no further expansion of the air in A takes place, as indicated by no further escape of bubbles from the capillary. (It is important to protect the burner and the apparatus from draughts.) When this point is reached, the graduated measuring vessel is placed over the end of the delivery tube, and the cork in A is momen- tarily withdrawn while the loosely-corked Hoffmann bottle is dropped in. The substance is quickly converted into vapour, which expels its own volume of air into the measuring vessel. In the course of a minute or two, when no more bubbles pass into the measuring cylinder, it is transferred while closed by the thumb to a deep cylinder filled with water. It is left for 15 minutes prior to adjusting the internal and external liquids to the same level, when the volume V of air is read off. The temperature t, indicated by a thermometer immersed in the deep cylinder, and the barometric pressure P are at the same time noted. Then if W = weight of substance employed, and p == vapour tension of water at the tem- perature t } Freezing Point Method oi Raoult. — The depression of the freezing point of a solvent, caused by the presence of a liquid or solid in solution, is directly proportional to the amount of substance dissolved, and inversely proportional to its molecular weight. Thus if d = depression of the freezing point, w — weight of substance of molecular weight M, dissolved in 100 gms. of solvent, and k = a constant called the molecular depression, which is constant for each solvent and which may either be determined or obtained from tables, then This rule does not apply, however, to substances which dissociate in certain solvents, nor to substances which form molecular aggregates in solution. Thus, strong electrolytes should not be determined in aqueous solution, nor should the solvent be such that mixed crystals of solvent and solute separate. The values of k for the following solvents are : — the molecular weight = W X 22,400 X 760 (273 + t) V(P-p) X273 gms. d = k^f. And hence M = k-j. Water Benzene Acetic acid . Nitrobenzene Phenol Naphthalene M.P. 0° 5-5° 17° 5-3° 40° 79-6° k 18-5 50 39 69 72 69 MOLECULAR WEIGHT DETERMINATION 467 The Apparatus. — The diagram, Fig. 71, shows the form of apparatus generally used for the determination. The freezing point tube (inner tube) has a side tube through which the solute is introduced, and is fitted with a rubber stopper A perforated with two holes. Through one of these a piece of glass tube passes, in which a platinum stirrer moves up and down. Through the other the stem of a Beckmann thermometer passes. The £2 Fig. 71. freezing point tube is fitted by means of a rubber stopper into a larger tube which serves as an air bath and prevents the freezing point tube from coming into contact with the freezing mixture contained in the large glass bath. A syphon B, for emptying the cooling bath, is shown. Beckmann Thermometer : — This specially constructed thermometer has only a range of 6°, which are divided into hundredths. The amount of mercury in the bulb and stem can be varied by transferring some to the reservoir at the top or by adding some from the reservoir, and hence it is possible to adjust the thermometer so as to get a scale reading at a desired H H 2 468 SYSTEMATIC ORGANIC CHEMISTRY temperature. The numbers on the scale do not, therefore, represent Centigrade temperatures, but are merely relative temperatures, the freezing point of the solvent and that of the solvent plus solute being determined on the same adjustment of the thermometer. Adjustment of the Bechnann Thermometer. — If it is desired to work with a solvent whose freezing point is t°, it is necessary that the amount of mercury in the bulb is such that when the temperature is f or 1° — 2° lower, the top of the mercury thread can be read off on the scale. The value of the mercury thread in degrees between the top of the scale and the orifice of the reservoir is first determined by warming the bulb side by side with an ordinary thermometer in a stirred water bath until a little bead of mercury issues into the orifice ; the burner is withdrawn, the head of the Beckmann thermometer is given a slight tap to cause the bead of mercury to fall from the orifice into the reservoir, and the temperature on the ordinary thermometer noted. The bath is allowed to cool, and the Centigrade temperature again read when the mercury in the Beckmann thermometer has fallen to the top of the scale. Suppose the value of the thread between scale and orifice of reservoir to be equivalent to x°, then an amount of mercury in the bulb which will just fill the thread up to the orifice at t + x° would give a reading of 6 (the top of the scale) at f. If there is too little mercury in the bulb to reach to the orifice at t + some more is added from the reservoir in the following way. The bulb of the thermometer is immersed in a bath or held in the hand, and warmed until the mercury reaches from bulb to reservoir ; the thermometer is then inverted and some mercury from the reservoir caused to unite with that of the thread at the orifice ; the temperature is then allowed to fall and when it reaches t -j- x° the thermometer is returned to its original vertical position, and the excess of mercury at the orifice caused to fall into the reservoir by gently tapping. At t° the top of the mercury thread should be on the scale and, if so, the thermometer is ready for use. In a similar manner an excess of mercury in the bulb can be transferred by warming to t + ^° and removing at that temperature the excess of mercury at the orifice by gently tapping. Determination. — The inner tube is cleaned and dried, then fitted with corks and weighed. Sufficient solvent (generally 15 — 20 c.cs.) is intro- duced to cover the bulb of the Beckmann thermometer when it is immersed nearly to the bottom of the tube. The tube is again corked and weighed. A suitable freezing mixture is introduced into the outer cooling bath, the temperature of which should not be more than 3° below the freezing point of the solution. The apparatus is assembled as shown in sketch (Fig. 71), and the solvent allowed to cool well below its freezing point without stirring. The solution is then stirred for a moment, and as soon as crystals begin to separate, it is noticed that the mercury thread in the thermometer rises. Continuous and moderately rapid stirring is employed, and the maximum temperature indicated by the thermometer read off. This gives an approxi- mate determination of the freezing point, and serves as a guide in the repeat determinations. The inner tube is removed and the crystals melted by the heat of the hand or water bath, after which it is replaced in MOLECULAR WEIGHT DETERMINATION 469 the apparatus and the freezing point again determined — cooling this time not more than 0-5° below the freezing point, before stirring. Two or three determinations, which should agree to within 0-01°, are made in this manner, and the average taken as the freezing point of the solvent. If the substance whose molecular weight is to be determined is a solid, it is convenient to fuse it. or to press it into pellets by means of a small bullet mould. A lump or a pellet, 0-1 — 0-2 gm., is weighed out, and introduced into the inner tube, which is removed from the bath while the substance dissolves. The freezing point of the solution is then determined, and the operation repeated a few times — as in the case of the pure solvent. The difference between the freezing point of the solution and that of the pure solvent is the depression of the freezing point. Example. — Naphthalene in benzene : Weight of benzene == 20 gms. ,, naphthalene = 0-195 gm. Depression of freezing point = 0-78° tvt t i - n * -l . t i 100 X 50 X 0-195 .". Molecular weight or naphthalene = Q 78 x 10 = Boiling Point Method. — The boiling point of a pure solvent is raised by the addition of a solute, the amount of such increase being proportional to the amount of solute added. Molecular proportions of different solutes produce the same increase in boiling point for a particular solvent ; this increase is known as the molecular increase for the solvent. If e° is the observed increase in boiling point and w the weight of substance dissolved in W gms. of solvent, and K the constant for the particular solvent, then the molecular weight of the substance M = K e. W The following table gives the value of K for the more common solvents. Solvent. B.P.° K. Water Ethyl alcohol Ether Acetone Benzene 100-0 520 78-3 1,150 34-9 2,100 56-3 1,700 80-3 2,700 The apparatus, Fig. 72, consists of a boiling tube with arms on opposite sides. The one arm, A, acts as an addition tube while the other, B, acts as a reflux condenser for the solvent, which is placed in the boiling tube C. The small outlet tube D is provided to allow access to the atmosphere. A Beckmann thermometer E is inserted through a cork in the neck of C. The bulb of the tube C is surrounded by an air jacket F and by a further air jacket G, which are simply hollow cylinders, sitting on an asbestos plate II and covered with a mica plate K. By this means heating is 470 SYSTEMATIC ORGANIC CHEMISTRY made more uniform, and the tube is protected against loss of heat by radiation. The Beckmann thermometer is first set (see p. 467), so that the boiling point of the solvent to be used is registered near the middle of the scale. A weighed quantity of the solvent, 15—20 gms., is quickly introduced into the boiling tube, and a few glass beads or similar material are also added to induce regular boiling. The thermometer is then quickly inserted, so that its bulb is just above the beads and entirely surrounded by liquid. The condenser is also quickly placed in position, and heating is com- menced. The Bunsen should be regulated so that the liquid boils vigor- ously, and the same rate of ebullition should be maintained throughout the experiment. The boiling point of the pure solvent is noted, and the final reading of the thermometer should not be taken until the mercury has remained stationary, which usually requires about half an hour, the thermometer being slightly tapped before taking any reading. When the substance of which the molecular weight is to be determined is a solid, a number of tabloids, each about 0-2 gm., are made with a press. The first piece is carefully weighed and introduced through the addition tube. The temperature is again noted when it has become constant for MOLECULAR WEIGHT DETERMINATION 471 5 minutes ; a second piece is introduced and again the temperature read, and so on, and the molecular weight is calculated for each con- centration. 0-2 gm. should be subtracted from the weight of solvent when this is ether, acetone, alcohol or benzene, and 0-35 gm. when the solvent is water, to allow for the quantity of solvent clinging to the condenser, etc. When the substance is liquid, it is introduced into the boiling tube by means of a pyknometer with a long side tube, which discharges the liquid so that it falls direct into the solvent. Since the boiling point is a function of the pressure, the barometer should be read both at the beginning and at the end of the experiment, and a correction made if necessary. Example. — Anthracene in benzene. Observed increase Weight of solvent ,, anthracene K = 2,700 = 0-180° = 17-7 - 0-2 = 17-5 gms, e — 0-21 gm. .-. M - CHAPTER XXXVIII Determination of the Equivalent of an Acid. N By Titration with Standard Alkali. — — aqueous and alcoholic potash N . as well as ^ baryta solution are used for titrating organic acids, phenol- phthalein being in all cases the best indicator. Baryta solution is the most suitable alkali since it can be prepared and kept free from carbonate. The baryta solution is contained in the apparatus. Fig. 73. The storage bottle is con- nected to the top and bottom of a burette having a 2-way stopcock, and the baryta solution is protected from atmospheric carbon dioxide by a soda-lime tube inserted through the cork in the top of the storage bottle. The baryta solution is prepared from pure crystal- line barium hydroxide, Ba(OH) 2 .8H 2 0, by dissolv- ing in distilled water. Any carbonate is allowed to sub- side and the clear super- natant liquid syphoned into the storage bottle after the latter has been filled with air free from carbon dioxide. To determine the equiva- lent of an acid, a suitable quantity of it — determined by trial titrations — is dis- solved in distilled water if soluble in water, and if insoluble in water in aqueous alcohol, or in alcohol free from acid. The average of a few re* lings which should agree 472 to within 0-5% is taken, DETERMINATION OF EQUIVALENT OF AN ACID 473 and the amount of acid necessary to neutralise 85-5 gms. of barium hydroxide calculated. Preparation and Analysis of a Silver Salt. — The preparation and analysis of metallic salts is the chief method, of determining the equivalent of an organic acid. Salts of silver, calcium, barium, sodium or potassium may be used, and a few preliminary tests will reveal which salt is the most suitable. Generally the silver salt, when sparingly soluble in water, is selected, since its isolation, purification, and decom- position can be readily effected. Silver salts of organic acids usually crystallise without water of crystallisation, but some have the dis- advantage of being easily attacked by light. A small quantity of the acid is neutralised with pure aqueous ammonia, and the excess of the latter boiled off. Sufficient silver nitrate is then added and the liquid cooled. Crystals of the sparingly soluble silver salt separate and are filtered off. These are recrystallised when possible from hot water, collected, well washed, dried in a steam oven for 30 minutes, and allowed to cool in a vacuum desiccator. 0-2 — 0-3 gm. of the dry silver salt is weighed into a porcelain crucible and gently ignited until all organic matter is destroyed, and until the crucible containing the residue of silver is of constant weight — care being taken that heat is not applied too strongly, since silver is volatile at a high temperature. The equivalent of the acid = 108 f — °^ ^.; r — l) \ wt. oi silver / and the M.W., when monobasic =108 °^ s ^ v ^ r sa ^ _ iq7. wt. oi silver When the silver salt of an acid is soluble, the calcium or barium salt may be employed. These are prepared, either by adding a soluble calcium or barium salt to a soluble salt of the acid, or by neutralising the acid itself with pure lime or baryta water. Ignition of a calcium salt is carried out either gently to the carbonate, or strongly to the oxide. A barium salt is first ignited until decomposition of organic matter is com- plete, then cooled and converted into the sulphate by addition of a few drops of cone, sulphuric acid, and finally ignited as sulphate. Calcium and barium salts often contain water of crystallisation and hence may require great care in drying. When the sodium or potassium salt is available in a pure state, a known J weight is ignited until only a residue of pure carbonate remains. A few drops of cone, sulphuric acid are then carefully added, and heat from a small flame applied until the excess of sulphuric acid is driven off. If any specks of carbon remain the last process is repeated. Finally the residue is weighed as alkali sulphate. I When an acid contains halogen, and the silver salt method is employed, the residue after ignition is treated with a few drops of nitric acid and a little ammonium halide to ensure complete conversion into silver halide. 474 SYSTEMATIC ORGANIC CHEMISTRY Determination of the Equivalent of a Base. By Titration. — A crystalline salt of the base with, some mineral or organic acid is prepared and purified, and the acid present in a weighed quantity of the salt titrated with standard alkali (preferably baryta solu- tion, p. 472) in presence of phenolphthalein. From the average of several readings the amount of the salt which contains one equivalent of the acid is calculated, and from this is subtracted the weight of one equivalent of the acid, leaving the weight of one equivalent of the base. Preparation and Decomposition of the Platini-chloride. — Most organic bases form well-defined crystalline double salts with platinic and auric chlorides of the general formulse BgH^Pt.Clg and B 2 H 2 AuCl 4 , where B represents one equivalent of the base. (Iridio-chlorides and cupri-chlorides are sometimes used.) These salts are prepared by adding platinic or auric chloride to a solution of the base in dilute hydrochloric acid. The double salt is filtered off, recrystallised (generally from alcohol), and dried on a porous plate in a vacuum desiccator. When dry, a weighed quantity (0*5 — 1-0 gm.) is heated in a porcelain crucible, gently at first with the lid on, and afterwards strongly until all organic matter is burnt away. The residue is weighed as platinum or gold. Taking a platinum salt as example, the equivalent weight of the base is calculated as follows : — M , t . t , r xl nil wt. of salt taken X 195 Molecular weight of the double salt = — ; - e — t—-. ^ — . ° wt. oi platinum residue M.W. of the salt — 409-9 (i.e., M.W. of H 2 PtCl 6 ) = twice the equivalent of the base. CH s I. The resulting methyl (or ethyl) iodide is converted into silver iodide by GROUP ESTIMATIONS 477 the action of alcoholic silver nitrate, and the number of methoxyl (or ethoxyl) groups calculated from the weight of silver iodide, formed. The hydriodic acid used is prepared by fractional distillation, selecting for the determination the fraction of constant B.P. 126° and D. 1-68. The alcoholic silver nitrate, which is prepared by dissolving 4 gms. of silver nitrate in 10 c.cs. of water and adding 90 c.cs. of absolute alcohol, is preserved in a well-stoppered bottle in the dark, and it should be filtered and acidified, with one drop of nitric acid immediately before use. The simplest modification of the process is due to Perkin (J. C. S., 83, 13G7). The appara- tus employed is shown in Fig. 74. A Wiirtz flask, having a long neck (8 ins. or more) is used to contain the mixture of substance and hydriodic acid ; the flask is im- mersed in a glycerine bath in such a manner that the side tube is tilted upwards to serve as a reflux condenser ; and through the cork in the neck of the flask there passes a carbon dioxide delivery tube reaching almost to the surface of the reaction mixture. The side tube of the Wiirtz flask is connected to two smaller flasks, the first of which contains 20 c.cs. and the second 15 c.cs. of alco- holic silver nitrate. The connecting tube between these two flasks acts as a syphon, dipping just below the liquid in the second flask and reaching just above the liquid in the first flask. 0-2 — 0-3 gm. of the substance is weighed and placed in the Wiirtz flask, and 15 c.cs. of hydriodic acid of D. 1-68, along with a few porcelain chips added. The cork bearing the delivery tube is replaced in the neck of the flask, and a slow current of carbon dioxide, purified by passing first through aqueous silver nitrate and then through cone, sulphuric acid, is forced through the apparatus. The temperature of the glycerine bath is raised to 130° or 140°, the first temperature being for methoxyl compounds, and the second for ethoxyl compounds. When the upper portion of the liquid in the first small flask remains perfectlv clear after the resultant silver iodide has settled, the temperature of the glycerine bath is raised Fig. 74. 478 SYSTEMATIC ORGANIC CHEMISTRY until the hydriodic acid boils gently, and it is kept thus for an hour. The silver nitrate flasks are then replaced by the V-shaped tube containing a few c.cs. of alcoholic silver nitrate, and the heating continued for 15 minutes. If no precipitate forms the operation is finished, but if a precipitate forms, the liquid in the V-tube is added to the contents of one of the small flasks and replaced by fresh alcoholic silver nitrate, the heating being continued for another 15 minutes, and so on until no more alkyl iodide passes over. The contents of the two small flasks are diluted with water, allowed to stand for 5 minutes to ensure decomposition of the last traces of alkyl iodide, and finally poured gradually into 50 c.cs. of boiling water acidified with nitric acid, which is boiled until the alcohol is driven off. The pre-, cipitate is collected in a weighed Gooch crucible, washed, and dried in an air oven at 120°. The percentage is calculated as follows : — Methoxvl Ethoxyl wt. of silver iodide wt. of substance wt. of silver iodide wt. of substance X 3102 234-9 4504 234-9 Cummings Modification. (J. S. C. I., 41, 20.)— A convenient appa- ratus for the estimation of methoxyl groups by the Zeisel method is that used by Robertson for the esti- mation of halogens (p. 461). This consists of a long-necked round- bottomed flask attached by a ground- glass joint to a bulbed U-tube. The methyl iodide generated by the inter- action of hydriodic acid and the methoxy group is absorbed in alco- holic silver nitrate. Pyridine may also be used as absorbent (J. C. S., 117, 193). The apparatus shown in the sketch (Fig. 75) gives very good results. The flask is of 250 c.cs. capacity, and its neck, from bulb to the ground- glass joint, 25 cms. long. The delivery tube, to which is fixed a side tube, is attached to the flask by means of a ground-glass joint. A thermo- meter is fixed as shown with its bulb opposite the delivery exit. To the delivery tube is attached also by a ground-glass joint an absorber which contains about 10—15 c.cs. of pyridine. The apparatus is easily filled, emptied and washed. When the apparatus is in use, the bulb of the flask containing the hydriodic acid and the substance is heated in a water bath at 100° C. The methyl iodide is carried over into the absorber by a slow current of Fig. 75. GROUP ESTIMATIONS 479 dry carbon dioxide, passing in at the side tube. The temperature on the thermometer should not be higher than 35° — 40° C. for methoxy, and 40° C. for ethoxy compounds. At these temperatures no hydriodic acid is distilled over. As a further precaution, the neck of the flask is slanted away from the source of heat. The absorption is complete in about one hour. The pyridine and its methiodide are then washed out with water, acidified with nitric acid, a known volume of silver nitrate added and the excess of the latter estimated by thiocyanate, using ferric alum as indicator. Estimation of Esters. 1. By hydrolysis with standard alcoholic potash. A weighed quantity, 1 — 2 gms., of the ester is placed in a flask containing 50 c.cs. of semi- normal alcohol potash. The flask is fitted with a reflux condenser, and the mixture boiled on a water bath for 2 — 3 hours until hydrolysis is complete. A little water is then run down the inner surface of the con- I denser into the flask, and the excess of potash in the flask titrated with standard hydrochloric acid, using Methyl Orange as indicator. The quantity of potash used in the hydrolysis gives a measure of the value of the ester (see p. 524). R-COORi + KOH == R.COOK + RiOH. 2. By use of benzene sulphonic acid or phosphoric acid. When the ester yields on hydrolysis products which become coloured in presence of alkali and air, the above method is inapplicable. If the acid produced on hydrolysis is volatile in steam, benzene sulphonic or phosphoric acid may be used as hydrolytic agent, and the acid (from the ester) after separation by steam distillation is titrated with standard alkali. (See Estimation of Acetyl Group, p. 476.) Estimation of Amides. Amides are estimated by hydrolysis with alkalis (generally aqueous or alcoholic potash) or with acids (sulphuric, phosphoric or benzene sulphonic). In the former case the ammonia set free is absorbed in standard acid (as in the Kjeldahl estimation of nitrogen) and the excess of acid titrated. In the latter the estimation is conducted similarly to a Kjeldahl estimation of nitrogen, the ammonium salt formed on hydrolysis being afterwards decomposed by alkali and the liberated ammonia collected in standard acid. Estimation of Aldehydes (other than Formaldehyde). The method depends on the combination of alkali bisulphites with aldehydes. 25 c.cs. of the solution to be examined, which must not contain more | than 0-5% of total aldehyde, are run into 50 c.cs. of a solution of potassium j bisulphite containing 12 gms. of KHS0 3 per litre, placed in a 150-c.c. flask which is then well corked and allowed to stand for 15 minutes. 480 SYSTEMATIC ORGANIC CHEMISTRY During this time another 50 c.cs. of the potassium bisulphite solution is N . titrated with iodine. The excess of bisulphite added to the aldehyde solution is then determined with the same iodine, and from the difference the bisulphite absorbed by the aldehyde, and hence the aldehyde present can be calculated. The strength given for the bisulphite solution should be adhered to, otherwise the quantities of hydriodic acid liberated in more concentrated solutions reduce the sulphuric acid formed — the reverse reaction coming into play. The bisulphite method gives an accurate figure also for dilute solutions of mixed aldehydes ; combining it with the cyanide method (see p. 481), the amount of formaldehyde and of another aldehyde in a solution of the two can be estimated. N 1 c.c. ~r iodine = 1-5 mgs. CH 2 0 - 2-2 mgs. CH3.CHO mol. wt. of aldehyde in enxis. = 20 — mgs - Aldehydes insoluble in water should be dissolved in dilute alcoholic solution, the concentration of alcohol being kept below 5%. Estimation o£ Formaldehyde. Many methods are available for the estimation of formaldehyde. 1. For pure dilute solutions the following is recommended. 10 c.cs. of the formaldehyde solution which must, if necessary, be diluted so that it is not more than a 2% solution, is mixed with 25 c.cs. of N/10 iodine solution. 10% caustic soda solution, pure and free from nitrite, is added, with shaking, drop by drop from a burette until a clear yellow liquid is obtained ; after standing for 10 minutes, an equal quantity of 10% hydrochloric acid, plus an extra 5 c.cs., is added to liberate the excess N of iodine which is back titrated with ^ thiosulphate using freshly made starch paste as indicator. N 1 c.c. jq iodine = 1-5 mg. formaldehyde 6NaOH + 3I 2 = NaI0 3 + 5NaI + 3H 2 0 3 CH 2 0 + NaI0 3 = 3CH 2 0 2 + Nal 5NaI + NaI0 3 + 6HC1 = 6NaCl + 3I 2 + 3H 2 0. This method is very satisfactory for formaldehyde provided other aldehydes be absent. In a solution containing 1 gm. CH 2 0 per litre, two N titrations should not differ by more than 0-1 c.c. of — thiosulphate and the method will show 1 part of formaldehyde in 100,000 parts of water. It is necessary for such consistency that the quantities of acid and alkali employed be carefully controlled as described ; on no account must a GROUP ESTIMATIONS 481 great excess of alkali be used, as there then is a danger of some of the formaldehyde being converted to iodoform. 2. For impure dilute solutions of formaldehyde, especially those con- taining other aldehydes, the cyanide method should be used. The iodine method is not reliable in this case, as all aldehydes present are attacked. But while aldehydes, other than formaldehyde, combine similarly with potassium cyanide in the cold, they do so slowly ; if the excess of cyanide is removed immediately with silver nitrate, only formaldehyde is esti- mated. The addition product of formaldehyde and potassium cyanide reduces silver nitrate in the cold. If the silver nitrate solution, however, be acidified with nitric acid before adding the aldehyde-cyanide mixture, no precipitate results if the aldehyde in the latter be in excess. If the cyanide be in excess, 1 mol. of formaldehyde combines with 1 mol. of cyanide, whilst the excess precipitates silver cyanide from the silver nitrate solution in the usual way. N The details are as follows : 10 c.cs. of silver nitrate acidified with 6 drops of 50% nitric acid are mixed with 10 c.cs. of potassium cyanide solution (prepared by dissolving 3-1 gms. of 96% salt in 500 c.cs. distilled water), the whole diluted to 50 c.cs., well shaken, filtered, and 25 c.cs. of N the nitrate titrated with ^ ammonium thiocyanate. Another 10 c.cs. of the potassium cyanide solution, to which 10 c.cs. of the aldehyde solution has just been added, are run in, the whole made up to 50 c.cs., shaken, rapidly filtered, and 25 c.cs. of the filtrate immediately titrated as before. The difference between this and the blank titration gives the amount of potassium cyanide not precipitated by the formaldehyde. N 1 c.c. thiocyanate = 3 mgs. CH 2 0 CH 2 0 + KCN = KO.CH 2 CN. s.o.c. CHAPTER XL Estimations based on the Use of Titanous Chloride. This energetic reducing agent can be maintained at constant strength in aqueous hydrochloric acid solution for a reasonable period. It is advisable, however, to re-standardise it after 24 hours' standing. It serves for the reduction of aromatic nitro compounds, some nitroso bodies, many azo dyes and of nearly all the dyes which yield leuco-compoimds. It is easily standardised against a ferric salt— say ferric alum — using potassium thiocyanate as indicator. The equation — ■ TiCl 3 + FeCl 3 = TiCl 4 + FeCl 2 shows that 1 mol. titanous chloride is equivalent to 56 gms. iron, and also that its abilitv to reduce A "HI is due to the metal (Ti) passing from the tri- to the tetra-valent condi- tion. Preparation and Stor- age of Titanous Chloride Solution for Analysis. — 50 c.cs. of the commer- cial titanous chloride solution (20%) are boiled with 100 c.cs. of cone, hydrochloric acid for 1 minute, and then made up to about 2 litres in a storage bottle A (Fig. 76). The solu- tion when freshly pre- pared, should fill the bottle completely; otherwise air remains which must be displaced by hydrogen. A is con- nected to both top and bottom of a burette by means of glass and rubber tubing. The burette has a 2-way glass stopcock at B, so that it can receive solution from A, or deliver solu- Iff' Fig. tion through its orifice. The second tube from the top of A leads to a 482 ESTIMATIONS BASED ON USE OF TITANOUS CHLORIDE 483 hydrogen generator H, which consists of 2 parts, (a) an inner tube, made by- drawing a test-tube out to a fine point ; this contains granulated zinc, and is connected by means of a rubber stopper and delivery tube to A ; (b) an outer vessel containing hydrochloric acid (15%). To replace all the air in the apparatus by hydrogen, the stopcock is turned to allow solution from A to fill the tube leading to the bottom of the burette. The stopcock is then turned as for delivery from the burette, and hydrogen allowed to escape from the apparatus for 5 minutes. The burette is filled, emptied and refilled, after which the apparatus is ready for use. Standardisation. — 3-5 gms. of pure ferrous ammonium sulphate are dissolved in distilled water, 100 c.cs. of 5N sulphuric acid added, and the whole made up to 250 c.cs. 25 c.cs. of this are oxidised with potassium N permanganate solution of approximately — strength, until a faint pink ou colour persists. A large excess of potassium thiocyanate (0*2— -0-3 gm.) is added, and titan ous chloride solution run in from the burette until the red colour due to ferric thiocyanate just disappears. If 25 c.cs. of iron solution require x c.cs. of titanous chloride solution to reduce it, then each c.c. of the latter is equivalent to— ^ gm. iron. A solution of iron alum, containing about 14 gms. per litre, and acidified with sulphuric acid until the solution assumes a pale straw colour, is pre- pared. By titrating 25 c.cs. of this with titanous chloride, using potassium thiocyanate as indicator, its strength is determined, and as it will retain its strength for a long period, this alum solution may be used in all subsequent cases for standardising the titanous chloride solution. Nitro Compounds. — (a) Those Soluble in Water.— A known amount of nitro-body is dissolved in water in a conical flask, hydrochloric acid is added, and the solution is boiled with a stream of carbon dioxide passing through. Heating is momentarily stopped, and a large excess of titanous chloride solution run in. The contents are boiled for 10 minutes to ensure complete reduction. Carbon dioxide is passed through the flask during the entire operation. The solution is then cooled and the excess of titanous chloride determined by titration with ferric alum solution, using potassium thio- cyanate as indicator. A control experiment without nitro compound present is performed under exactly the same conditions. 6 equivalents of titanous chloride (6 H atoms) are required for the reduction of each N0 2 group. Example. — 0-4979 gm. ^-nitraniline is dissolved in hydrochloric acid on the water bath, and made up to 500 c.cs. 20 c.cs. of this solution are reduced with 50 c.cs. titanous chloride as described above, and the excess of the latter titrated back with ferric alum. Excess TiCl 3 = 9-7 c.cs. A control experiment having no ^-nitraniline used 0-76 c.c. TiCl 3 . TiCl 3 used = 39-54 c.cs. 1 c.c. TiCl 3 = 0-0012228 gm. Fe. 138 ^-mtraniline require 336 Fe. A Aa ~ a , • 0-0012228 X 39-54 X 138 X 25 . „. .*. 0-4979 gm. contains - ^—^ — - ^-nitramhne = 99-7%. i i 2 484 SYSTEMATIC ORGANIC CHEMISTRY Picric acid and Naphthol Yellow S may be estimated in a similar manner. (b) Those insoluble m water mnst first be sulphonated by beating with 20 parts by weight of fuming sulphuric acid on a water bath for 2 hours. The product is then made up to a definite volume with water and an aliquot part titrated with titanous chloride as described for soluble nitro com- pounds. Example. — 1-01 gms. nitrobenzene are sulphonated as described above, then cooled and the volume carefully made up to 1 litre. 20 c.cs. are with- drawn and reduced with 50 c.cs. TiCl 3 solution (as for ^-nitraniline). Excess TiCl 3 = 18 c.cs. Control experiment = 0-8 c.c. TiCl 3 . Vol TiCl 3 used = 31-2 c.cs. = 31-2 X 0-001700 gm. Fe. 123 nitrobenzene = 336 Fe ' . 0-0017 X 31-2 X 123 X 50 . Q7AQ .-. 1-002 gms. contain ^ =0 -9709 = 96-1%. (c) Nitro compounds insoluble and yet not easily sulphonated, e.g., dinitrobenzene or dinitronaphthalene, are dissolved in alcohol, and the solution poured into a known volume of titanous chloride solution acidified with hydrochloric acid, through which carbon dioxide is passed. The mixture is boiled, allowed to cool, and the excess of titanous chloride estimated with ferric alum. Example. — 0-110 gm. commercial dinitronaphthalene is dissolved in 250 c.cs. alcohol. 50 c.cs. TiCl 3 solution are placed in a conical flask, 10 c.cs. cone. HC1 added, carbon dioxide passed through, and 25 c.cs. of the dinitronaphthalene solution run in. The mixture is boiled, then allowed to cool, and the excess of TiCl 3 titrated. Excess TiCl 3 = 31-60 c.cs. Control experiment 0-90 c.c. TiCl 3 . Vol. TiCl 3 used = 17-5 c.cs. = 17-5 X 0-001750 Fe. 218 dinitronaphthalene = 672 Fe. mm /• 0-00175 x 17-5 x 10 x 218 . nonQQ 0-110 gm. contains ^ = 0-09933 = 90-3%. Nitroso Compounds. — Owing to the intense colour which these com- pounds yield in hydrochloric acid solution they may be titrated directly with titanous chloride until the yellow colour disappears. A weighed quantity is dissolved in hydrochloric acid and made up to a known volume. An aliquot part of this solution is warmed to 40° — 50° in a conical flask with carbon dioxide passing through, and titanous chloride solution is run in until the yellow colour disappears. 4 equivalents of titanous chloride are required for each nitroso group. Example. — 1-005 gms. nitrosodimethy] aniline are dissolved in 20 c.cs. ESTIMATIONS BASED ON USE OF TITANOUS CHLORIDE 485 cone, hydrochloric acid and sufficient water to make volume up to 500 c.cs. 10 c.cs. of this solution required 17-5 c.cs. TiCl 3 solution. 1 c.c. TiCl 3 = 0-001700 gm. Fe. 150 nitrosodimethvlaniline = 224 Fe. .-. 1-005 gms. contain - ^ = 0-9983 gm. = 99-3%. Azo Dyes. — (1). Azo dyes which are soluble in dilute hydrochloric acid may be titrated directly, the disappearance of the colour indicating the end point. (2) . Many azo dyes which are insoluble in dilute hydrochloric acid can be titrated directly in presence of Rochelle salt. Since Rochelle salt forms a compound with titanium, which is pale yellow in dilute solution, this method is inapplicable for the estimation of yellow dyes. (3) . A number of azo dyes which cannot be estimated according to (1) or (2), may be estimated indirectly. A weighed quantity of dye is boiled in aqueous solution in a flask through which a stream of carbon dioxide is passing. After adding hydrochloric acid an excess of titanous chloride is run into the boiling mixture. The reduction is usually complete in about 2 minutes, after which the flask is cooled under the tap with the current of carbon dioxide still passing. When cold, the excess of titanous chloride is estimated with ferric alum solution using potassium thio- cyanate as indicator. The azo group requires 4 equivalents of titanous chloride. Example of(l). — 1-003 gms. of Orange II. (C 16 H n N 2 0 4 SNa) are dissolved in water and made up to 500 c.cs. 50 c.cs. are withdrawn into a conical flask, 5 c.cs. cone, hydrochloric acid added, and after boiling for 1 minute, titrated with titanous chloride. Vol. TiCl 3 required = 29-15 c.cs. = 29-15 X 0-00165 gm. Fe. 350 Orange II. = 224 Fe. i aaq 4. • 29-15 X 0-00165 X 10 X 350 . _ no .-. 1-003 gms. contain ^24 = 0*7522 gm. = 75%. Example of (2). — 1-10 gms. of Diamine Black (C 34 H 24 0 14 N 6 S 4 Na 4 ) are dissolved in 250 c.cs. water. 50 c.cs. of this solution are withdrawn, 25 c.cs. of Rochelle salt solution (about 20%) added, and titrated with titanous chloride until the colour of the dye disappears. Vol. TiCl 3 used = 20-22 c.cs. = 20-22 X 0-00165 gm. Fe. 960 diamine black = 448 Fe. - 1A 20-2 X 0-00165 X 5 X 960 . , . .-. 1-10 gms. contain —r^ — = 0-44 gm. = 40%. Example of (3). — 0-99 gm. of Chrysophenine G (C 30 H 26 N 4 0 g S 2 Na 2 ) is 486 SYSTEMATIC ORGANIC CHEMISTRY dissolved in a litre of water. 100 c.cs: of this solution are withdrawn and boiled, with a current of carbon dioxide passing through ; 10 c.cs. of cone, hydrochloric acid and 50 c.cs. of titanous chloride are then added, and the mixture boiled until the precipitate dissolves and the solution turns a slight violet colour. After cooling, the excess of titanous chloride is titrated with ferric alum. Excess TiCl 3 = 34-2 c.cs. Vol. TiCl 3 used = 15-8 c.cs. = 15-8 X 0-00165 gm. Fe. 680 chrysophenine = 448 Fe. , . 15-8 X 0-00165 X 10 X 680 ft w .-. 0-99 gm. contains j-^ = 0-396 gm. & 448 & = 40%. Dyes which Yield Colourless Leuco Compounds. — Approximately 1 gm. is dissolved in 250 c.cs. water ; 50 c.cs. of this solution and about 2 c.cs. cone, hydrochloric acid are introduced into a conical flask fitted with a rubber stopper having 3 holes. Through one hole a current of carbon dioxide is introduced, another serves for the escape of this gas, and the third is left for the delivery tube of the titanous chloride burette. The solution is boiled, and then titrated with titanous chloride, until the colour just disappears. Example. — 1 gm. crystallised zinc-free Methylene Blue (C 16 H 18 N 3 S,C1) is treated as described above. 50 c.cs. of this solution required 41-64 c.cs. titanous chloride solution, of which 1 c.c. = 0-00165 gm. Fe. 319-5 Methylene Blue = 112 Fe. , . 41-6 X 0-00165 X 5 X 319-5 . no /. 1 gm. contains — ^ = 0-98 gm. 11^ = 98 %. The zinc double chloride of Methylene Blue has the formula 2C 16 H 18 N 3 . S.C1, ZnCl 2 , H 2 0, and is much less soluble in dilute hydrochloric acid. A drop of weak Methylene Blue solution may be used as indicator in the direct titration of substances with titanous chloride where a selective reduction takes place. The end point is perfectly sharp if the solution is warmed to 35°. Of other examples which yield leuco compounds, Indigo may be esti- mated by titrating the sulphonated dye in presence of Rochelle salt : Magenta in Rochelle salt solution ; Eosin and Rhodamine in presence of Rochelle salt and alcohol, the latter to keep the leuco compound in solution. All these titrations are carried out on the boiling dye solution and in presence of carbon dioxide. For many other valuable applications of the use of titanous chloride, see Knecht and Hibbert, " New Reduction Methods in Volumetric Analysis" (Longmans, Green & Co.). CHAPTER XLI ESTIMATIONS BASED ON DIAZOTISATION OR COUPLING. Preparation of Standard Reagents. (a) Sodium Nitrite. — Sodium nitrite is often estimated by the use of permanganate and oxalic acid. When impure sodium nitrite is estimated in this manner, the values obtained are often too high, owing to the presence of other oxidisable substances. For reactions such as those which follow, it should be estimated with pure sulphanilic acid or with pure benzidine. Commercial sulphanilic acid is purified by dissolving in sufficient aqueous sodium carbonate to give an alkaline solution, which is boiled until all trace of aniline disappears. The solution is filtered and acidified with hydrochloric acid, and after 12 hours the product is filtered off and washed with a little water. It is again dissolved by means of hot water and sodium carbonate to a neutral solution ; the solution is quickly cooled along with stirring to 0°, and the sodium sulphanilate filtered off. These crystals are dissolved in distilled water, and acidified with pure cone, hydrochloric acid. The crystals which separate are filtered off and washed free of sodium chloride with distilled water ; they are once more recrystallised from distilled water, and afterwards dried until of constant weight in an air oven at 120°. The product should be preserved in a bottle having a ground-glass stopper. To prepare a semi-normal solution, exactly 86-5 gms. are dissolved in 50 c.cs. pure (20%) ammonia, and made up to 1 litre ; the solution when preserved in the dark will keep for many months. To prepare semi-normal nitrite solution, about 37*5 gms. of commercial sodium nitrite (or rather less of the purer salt) are dissolved in water, N N filtered, and made up to 1 litre. 50 c.cs. of the sulphanilic acid or benzidine solution are then titrated with it in the following manner : — The solution is measured by means of a pipette into a 500-c.c. beaker ; 200 gms. of ice and 13 gms. of cone, hydrochloric acid are also added. The beaker is slightly tilted to one side, and the nitrite solution, run in from a burette, is allowed to trickle down the side of the beaker and thus to sink quickly to the bottom. When about 45 c.cs. nitrite have been added, the solution is stirred with a glass rod, and more nitrite is run in, drop by drop, (tests being carried out at intervals), until a drop of the solution just causes an immediate blue coloration on starch-iodide paper.* After * A certain amount of practice is necessary to judge the end point accurately, as the paper when moistened with diazonium solution generally 487 488 SYSTEMATIC ORGANIC CHEMISTRY standing a few minutes, a test is again applied to see if the excess of nitrite still remains, and if not, more nitrite is added, until a slight positive test is obtained after a few minutes' standing. It is advisable to repeat the operation, all but 1 c.c. of the total volume of nitrite used in the previous test being run in at once along the side of the beaker ; this obviates as much as possible the escape of free nitrous acid on mixing. The remainder of the nitrite is run in, drop by drop, as before. From the volume of nitrite necessary, a cal- culation is made to ascertain what volume of water must be added to make the remaining nitrite exactly semi-normal. Fig. 77 shows a convenient type of burette for use in cases where many titrations have to be per- formed. The burette is fixed to the storage bottle and the liquid is blown up into the burette by compressed air from the hand bulb, the bead at A being opened by pressure between the fingers. The titration is done at C by opening the bead at B. N Aniline Solution. — About Fig. 77. 250 c.cs. of the purest commercial aniline are carefully redistilled, and the fraction passing over within half a degree at its boiling point reserved for the preparation of the standard solution. Exactly 4-6-5 gms. of the above fraction are weighed ; to this is added 50 c.cs. ice-water, and 75 c.cs. of cone, hydrochloric acid, the object of the ice-water being to prevent the escape of fumes when the acid and amine come together. The solution is then made up to 1 litre with distilled water ; when prepared in this way, it is generally accepted as exactly semi-normal, and many use it as such for the standardisation of sodium nitrite solution ; however, if any doubt exists, it is standardised against the previously prepared sodium nitrite. develops a blue colour on standing a short time. Approaching the end point the eye detects a brief interval between the moistening of the test paper and the development of the colour ; at the end point this interval disappears and the colour develops instantaneously. ESTIMATIONS BASED ON DIAZOTISATION OR COUPLING 489 N N (c) 2q Phenyldiazonium Solution. — 50 c.cs, of the aniline solution are measured out into a 500-c.c. flask, 25 c.cs. of cone, hydrochloric acid are added, and the flask immersed in ice- water. When thoroughly cold, N . 50 c.cs. of ^ sodium nitrite are run in from a burette, the contents of the flask being gently rotated at intervals. After standing for 15 minutes, the solution is made up to 500-c.c. ; it may be preserved for a few hours at 0° in the dark, but should always be freshly prepared for use. N (d) — R Salt Solution. — 20 gins, of commercial " R Salt " (^-naphthol- 3.6-disodium-disulphonate) are dissolved in water and made up to 1 litre N.N to give an approximately solution. A ^ phenyldiazonium solution is prepared and 100 c.cs. of it poured into a 100-c.c. measuring cjdinder which had been previously cooled in an ice chest. The cylinder is then immersed in a vessel containing ice-water. 50 c.cs. of the R salt solution are measured out into a beaker, 8 gms. sodium carbonate added, and stirred to dissolve. 15 c.cs. of the phenyldiazonium solution are then added from the measuring cylinder. A red dye is formed which is thrown out of solution by the addition of common salt. After adding sufficient salt, a drop " spotted " on filter paper leaves a sediment of dye in the centre, and the outspread is colourless. A small quantity of diazonium solution from the stock solution is poured into a small beaker to be used for testing. If the outspread on filter paper of a drop from the solution containing the dye is touched with a glass rod dipped in the diazonium test solution, a red dye is formed, provided a sufficient quantity of diazonium solution has not been added already — which is not intended. Proceeding in this way, and testing after each addition, small quantities of diazonium solution from the measuring cylinder are added until a drop tested on filter paper no longer forms a red dye. Since 1 mol. of R salt couples with 1 mol. of diazo compound, the strength of the R salt solution can be easily calculated, and hence the N quantity of water which must be added to make it Standard " R salt " is used for estimating amines (p. 490). Estimation of Amines. (a) By Diazotisation. — Many amines which diazotise readily can be accurately estimated with standard nitrite. The principle of the method is exactly the same as that underlying the standardisation of sodium nitrite with sulphanilic acid, benzidine or aniline. As a general rule 1/100 mol. wt. of the amine is dissolved along with rather more than three times its acid equivalent of hydrochloric acid in water ; the solution N is cooled to 0° by the addition of ice, and -~ sodium nitrite solution is run 490 SYSTEMATIC ORGANIC CHEMISTRY in until an end point is indicated by starch-iodide paper (see preparation of standard sodium nitrite). N % purity = c.cs. of ^- nitrite X 5. Certain diazonium salts such as those of the nitranilines and chloranilines decompose starch iodide in the same way as free nitrous acid ; such com- pounds should be estimated by coupling (Method (b) ). (b) By Diazotiwtion and Coupling. — Exactly t Jq mol. wt. of the amine is diazotised as described under (a). 8 gms. sodium carbonate are added to the diazotised solution and stirred until dissolved. The solution is diluted and cooled, so that its strength is equivalent to about 1% amino N . . and its temperature about 5°. ^ R salt solution is then run in until an excess of diazo solution no longer appears on spotting on filter paper (see p. 489), the dye being first salted out by the addition of common salt. By the above method, two values are obtained — a " nitrite " value, and an " R salt " value, and these should agree. The above outline is general, but is subject to variation for the par- ticular amine under estimation. For instance, the amount of sodium car- bonate — the essential point is to have the mixture alkaline during the coupling — depends on the acidity of the diazonium solution, and the presence of acid groups, such as sulphonic. When the coupling is carried, out in acetic acid solution, sodium acetate is added in place of sodium carbonate and in three times the quantity. Estimation of Phenolic Compounds. Phenolic compounds which couple readily and completely, with diazonium compounds, can be estimated by titration with a standard diazonium solution. The standardisation of R salt affords one example of the method. Example. — /?-Naphthol. — 1'44 gms. ( T J^ mol.) of ^-naphthol are dissolved in 4 c.cs. caustic soda solution (15%) ; to this is added 100 c.cs. water and 3 gms. of solid sodium carbonate. The whole is then made up to 200 c.cs. N in a flask. 50 c.cs. of this are placed in a beaker, and ice-cold ^ phenyl- diazonium solution run in until a drop on filter paper no longer shows an excess of /?-naphthol when tested with diazonium solution. (For end point see R salt, p. 489.) % purity = c.cs. of diazonium solution X 2. Estimation of H Acid (Acid Sodium Salt). (a) By Diazotisation. — 3-41 gms. ( t Jq mol.) are dissolved in 5 c.cs. of 10% sodium carbonate solution and diluted to 250 c.cs. 25 c.cs. of ESTIMATIONS BASED ON DIAZOTISATION OR COUPLING 491 cone, hydrochloric acid are then added, and the solution diazotised at 5° N with w sodium nitrite. Li % of H acid = c.cs. of nitrite X 5. (b) By Coupling. — 3-41 gms. H acid are dissolved in 50 c.cs. of 10% N sodium carbonate and diluted to 300 c.cs. phenyl diazonium solution is then added until the end point is obtained as determined by " spotting ? ' (see p. 489). o/ f Ti — c " cs * °^ diazonium solution. /q oi 1 1 acid — For a good quality of H acid, the percentage determined by diazotisa- tion should only be slightly higher than that determined by coupling. CHAPTER XLII MISCELLANEOUS ESTIMATIONS Estimation of ^-Phenylenediamine. The para- diamines cannot be estimated by means of the diazo reaction. The following estimation is based on the formation of benzoquinone dichloro-imide when j9-phenylenediamine in hydrochloric acid solution is added to a solution containing excess of sodium hypochlorite and sodium carbonate. A solution of sodium hypochlorite is prepared by diluting 50 c.cs. of a commercial solution containing about 12 — -15% available chlorine, to 1000 c.cs. Or, a corresponding solution may be prepared by passing chlorine into caustic soda (p. 508). 50 c.cs. of this solution are titrated . ' N with sodium arsenite solution, using starch-iodide paper as indicator. 100 c.cs. of hypochlorite solution are then measured out, diluted with an equal volume of cold water, and about 1 gm. of solid sodium carbonate added. 10 c.cs. of the solution to be determined, containing 2 — 6% of ^-phenylenediamine dissolved in slight excess of hydrochloric acid, is added slowly with stirring. The mixture should then give a strong reaction with starch-iodide paper, otherwise the experiment must be repeated, using either less diamine or more sodium hypochlorite solution. On the addition of the diamine solution, the dichloro-imide is rapidly precipitated as an almost colourless solid. C 6 H 4 (NH 2 ) 2 + 3C1 2 -> C 6 H 4 : (NCl) a + 4HC1. . N ' The turbid solution is then titrated, without nitration, with sodium arsenite solution, using starch- iodide paper as external indicator, the end point being sharply defined by the disappearance of the blue colour on spotting. At the end of the titration the solution should be alkaline, since the dichloro-imide in alkaline solution has no action on the test- N paper. The difference in the volume of the ^ arsenite solution required for the titration of the sodium hypochlorite itself and for the titration of the hypochlorite plus diamine is equivalent to the amount of active chlorine removed from the solution as benzoquinone dichloro-imide, each c.c. N of |- arsenite solution corresponding to 0-0018 gm. of diamine. The method gives good results, the error varying from 0*3 — 0-7%. (J. S. C. I., 38, 408.) 492 MISCELLANEOUS ESTIMATIONS 493 Estimation of Thiophen in Benzene. 2 c.cs. of commercial benzene and 20 c.cs. of Denige's reagent (see below), are introduced into a strong test-tube (2 cms. X 15 cms.), which is after- wards closed with a good wet cork, and placed in a shaking machine for 3 hours. (Even without shaking, the reaction takes place to some extent.) At the end of this time, the precipitate is collected in a weighed Gooch crucible, washed with hot water until neutral to litmus, dried at 110°— 115° C. until constant, and weighed as 2(H 9 O.H 9 S0 4 )C 4 H 4 S. The weight of the precipitate X 0-0757 gives the weight of thiophen. To prepare the above reagent, 20 c.cs. of pure cone, sulphuric acid are poured into 100 c.cs. distilled water, 5 gms. of finely powdered mercuric oxide are added and the mixture stirred until almost all dissolves. The solution is then filtered and the nitrate preserved in a stoppered bottle. The Gooch crucible is prepared with a filtering layer of good fibrous asbestos on top of which is placed a perforated porcelain plate. The asbestos should be previously purified by boiling up first with aqua regia for a short time, and then with cone, hydrochloric acid for a week, the acid being renewed each day. (J. S. C. I., 38, 189.) Estimation of Enol Modification in a Compound exhibiting Keto-enol Tautomerism. The enolic form reacts instantly with an alcoholic solution of bromine, and the amount of bromine used corresponds with the formation of a dibromide, which body, however, cannot be isolated since it decomposes as soon as formed into hydrogen bromide and a bromo-ketone. — C.OH — C.Br.OH — C:0 || -> | -> | + HBr. — CH — CH.Br —C.H.Br The amount of enolic compound can be estimated by adding a standard solution of bromine in alcohol, until the yellow colour just persists, but the method has the disadvantage that such a solution of bromine is unstable. In the following method a slight excess of an alcoholic solution of bromine is added to an alcoholic solution of the tautomeric compound ; the excess of bromine is immediately removed by the addition of a few drops of alcoholic ^-naphthol solution ; potassium iodide solution is next added, and the hydrogen iodide formed by interaction with the hydrogen bromide present reduces the bromo-ketone with liberation of free iodine which is estimated by titration with standard thiosulphate (in absence of starch). As one molecule of iodine is equivalent to one molecule of enolic compound, the percentage of this form is easily calculated. —CO 2HI —CO I > I + I 2 + HBr. — C.HBr — CH 2 Example. — Ethyl Aceto-acetate. — The following reagents are prepared : — N 1. An approximately alcoholic bromine solution; the bromine 494 SYSTEMATIC ORGANIC CHEMISTRY itself being previously purified by shaking up with sulphuric acid, then separating and distilling. 2. A 10% solution of potassium iodide. N 3. yq sodium thiosulphate solution. 4. 1 gm. of ^-naphthol dissolved in 20 c.cs. alcohol. 1-625 gms. ester are dissolved in 100 c.cs. alcohol in a flask, and cooled to — 7°. The contents are given a swirling motion, and ice-cold bromine solution (21 c.cs.) added until a faint yellow colour is produced. Alco- holic /?-naphthol sufficient to remove colour is then added. The time for the addition of bromine and /?-naphthol should not exceed 20 seconds. 5 c.cs. of the potassium iodide solution are added, and the contents N titrated with — thiosulphate. Volume of thiosulphate = 18*7 c.cs. which is equivalent to 18-7 X 0-0127 gm. iodine, or to 18-7 X 0-0065 gm. enolic ester o/ T7 i 100 X 18-7 X 0-0065 _ , n -•- % Enol = ^ = 749. Estimation of Anthracene in Commercial Anthracene. The estimation of anthracene depends on its oxidation by means of chromic acid to anthraquinone. 1 gm. of the sample is dissolved in 45 gms. of glacial acetic acid by heating on a sand bath under a long reflux condenser. When the contents of the flask are boiling, 15 gms. of crystallised chromic acid dissolved in 50% acetic acid are very gradually added (2 hours). When the addition of chromic acid is complete, the mixture is boiled for another 2 hours. After cooling, the contents are treated with 400 c.cs. water, and the precipitated anthraquinone filtered off, washed with cold water, then with boiling dilute alkali and finally with boiling water, until the washings are free from alkali. The residue is then washed into a small porcelain basin and dried at 100°. 10 gms. of Nordhausen sulphuric acid (about 5% S0 3 ) are added, and the mixture heated for 10 minutes at 100°. After cooling, it is carefully poured (caution !) into 200 c.cs. of cold water, the anthra- quinone filtered, washed with dilute alkali, and finally with water as before. It is then dried and weighed. The anthraquinone is volatilised by heating on a sand bath and the residue is weighed. The difference gives the weight of anthraquinone. 178 Wt. of anthraquinone X = weight of anthracene. Estimation of Acetone. 1. Volumetrically. — Iodine in alkaline solution reacts with acetone to give iodoform, a reaction which is used in the estimation of the ketone. 1 mol. acetone = 3 mols. iodine. CH3COCH3 + 3KIO -> CH3COCI3 + 3KOH CH3COCI3 + KOH -> CHI3 + CH3COOK. MISCELLANEOUS ESTIMATIONS 495 The excess of iodine may be decomposed as follows : — I 2 + 2K0H - KIO + KI + H 2 0 KIO + KI + 2HC1 = I 2 + 2KC1 + H 2 0 and is titrated with thiosulphate solution. A weighed quantity (about 2 c.cs.) of acetone is made up to 500 c.cs. with water. 15 c.cs. of this solution are shaken with 50 c.cs. of approx- imately normal caustic potash in a 250-c.c. stoppered flask. About N 100 c.cs. of ^ iodine solution are then run in from a burette, and the mixture shaken for 10 minutes. It is then acidified with about 50 c.cs. of approximately normal sulphuric acid. The excess of iodine which is ... N thereby liberated is titrated with ^ thiosulphate ; this amount deducted from the quantity of iodine originally added gives the amount of iodine used. N 1 c.c. of iodine = 0-000968 gm. acetone. Example. — Weight of acetone =2-0 gms. Volume of acetone solution = 15 c.cs. N iodine added =82-5 c.cs. N „ — thiosulphate = 21*0 c.cs. N . iodine used up = 61-5 c.cs. Wt. of acetone in 15 c.cs. solution = 61-5 X 0-000968 gms. , , 61-5 X 0-000968 X 500 ,, 500 c.cs. solution — ^ gms. n/ . 61-5 X 0-000968 X 500 X 10 .-. % Acetone = 15 2 = 99-38. 2. Gravimetricatty. — Mercuric sulphate combines with aliphatic ketones to give insoluble precipitates which, when dried in vacuo, have the general formula (2HgS0 4 .3HgO).4COK 2 . These compounds have such high molecular weights that very small quantities of the ketone need be used. 5 gms. of mercuric oxide are dissolved in 120 c.cs. of cold 30% sulphuric acid. 25 c.cs. of this solution and 25 c.cs. of the acetone solution con- taining about 0-05 gm. of acetone, are placed in a strong glass bottle of about 200 c.cs. capacity. The glass stopper is wired in, and the bottle heated to 100° on a water bath for 10 minutes. When cold, the whole is filtered through a weighed filter paper, and the residue washed with cold water, dried in vacuo for 12 hours and weighed. Wt. of acetone == weight of precipitate X 0-0584. 496 SYSTEMATIC ORGANIC CHEMISTRY Example. — Wt. of acetone in 25 c.cs. of water = 0-052 gm. „ precipitate = 0-886 „ .% „ acetone = 0-886 X -0584 = 0-0517 gm. 0-0517 X 100 •'• % acetone = = 99-4 Estimation of Glucose or Cane Sugar in Solution by means of Fehling's Solution. Fehling's Solution consists of two parts. The first, a solution of 69-28 gms. of pure crystalline copper sulphate dissolved in water with the addition of 1 c.c. of pure sulphuric acid, and the whole made up to 1 litre ; the second, a solution of 350 gms. of Rochelle salt (sodium potassium tartrate) and 120 gms. of sodium hydroxide (purified from alcohol) dissolved in water and made up to 1 litre. Equal volumes of these two parts are mixed just before use. Each c.c. of the resulting solution is equivalent to 0-005 gm. glucose or to 0-00475 gm. cane sugar. The solution deteriorates after a time, and should be standardised frequently against pure glucose or pure cane sugar. Standardisation. — Some pure glucose is dried for 12 hours in a vacuum desiccator over sulphuric acid and a solution of known concentration (0-5—1%) made. 5 c.cs. of each part of the Fehling's solution are measured out into a porcelain dish, diluted with 40 c.cs. of dilute caustic soda solution, and gently boiled. Glucose solution, about 1 c.c. at a time, is then run from a burette, and the mixture boiled after each addition until the blue colour is finally discharged. The titration is then repeated, all but 2 c.cs. of the volume of glucose solution used in the first determination being run in at once, and the remainder in drops until the blue colour just vanishes. The end point is more easily observed when the dish is slightly tilted. Several deter- minations are made until concordant results are obtained. If the end point is indistinct, a dilute acetic acid solution of potassium ferrocyanide " spotted " on a white plate may be used as external indicator. A brown coloration is observed so long as copper is present in solution. Alternately the standardisation may be carried out with a solution of " invert sugar " prepared by heating 4-75 gms. of cane sugar with 50 c.cs. of 2% hydrochloric acid to boiling for 10 to 15 minutes, then cooling, neutralising exactly with sodium carbonate, and diluting to 1 litre. Estimation of Glucose or Cane Sugar in Solution. — The estimation of glucose or inverted cane sugar solution is carried out similarly to the fore- going standardisations. The concentration must be of the order of 0-5 — 1%, otherwise reliable results are not obtained. As cane sugar does not reduce Fehling's solution until inverted, a mixture of cane sugar and' glucose may be estimated by determining the glucose prior to inversion, MISCELLANEOUS ESTIMATIONS 497 and then the total glucose and fructose after inversion. Fructose, galac- tose, mannose, maltose, lactose, may be estimated similarly, but the results are not satisfactory in all cases. Instead, of measuring the volume of the Fehling's solution, the hot solution of sugar may be mixed with an excess of Fehling's solution, heated in a boiling water bath for 15 minutes, and the precipitated cuprous oxide estimated in either of the following ways : — 1. By filtration through a weighed " asbestos " Grooch crucible, washing first with hot water, then with alcohol, and finally with ether, and drying for 30 minutes in a steam oven. 2. By filtration (as in 1.), washing with hot water, then dissolving N the Cu 2 0 in a known volume of permanganate solution previously diluted with 4 times its volume of 25% sulphuric acid, and titrating the N excess of permanganate at 40° — 50° with an solution of oxalic acid. N 1 c.c. of -pr permanganate is equivalent to 0-01426 gm. cuprous oxide, or to 0-01426 x 0'5045 gm. glucose or to 0*01426 X 0-4793 gm. cane sugar. (J. S. C. L, 16, 981.) PART IV CHAPTER XLIII INORGANIC SECTION Reagents. Sulphuric Acid.— The acid used in the laboratory is the commercial, 96—98% acid. The 100% acid (monohydrate) can be made from this by adding the requisite amount of oleum (see p. 306). Usual impurities : lead sulphate and oxides of nitrogen. Oleum. — Oleum is supplied in all strengths up to 70% free S0 3 . From 0—40% free S0 3 it is liquid ; from 40—60% free S0 3 , it is solid ; from 60—70% free S0 3 it is liquid ; above 70% it is solid. The acid should be kept in well stoppered, stout glass bottles, and when it is necessary to melt the acid, the stopper is withdrawn, a watch-glass placed on the mouth of the bottle, and the bottle, while placed on a layer of sand in a large vessel, is warmed with a small flame. The bottle is then fitted with a wash-bottle attachment, and any desired quantity of oleum is forced out by gentle air pressure from hand or foot bellows (the mouth must not be used). For the preparation of oleums of definite strengths, see p. 306. Usual impurities : ferric sulphate, sulphur dioxide and lead sulphate. For estimation, see p. 305. Hydrochloric Acid. — The pure concentrated aqueous acid contains about 38% HOI. The commercial acid containing about 30% HC1 serves for most organic preparations. The yellow colour is due to iron. Usual impurities : chlorine, sulphuric acid and iron. Hydriodic Acid.— Both the cone, acid and the acid of constant boiling point (D. 1-7, 57% HI) (see p. 502) are on the market. Usual impurity : iodine. Nitric Acid. — The commercial cone, acid generally contains about 70% HN0 3 . Fuming nitric acid (see p. 508) containing about 95% HN0 3 (D. 1-5) is available commercially. Usual impurities : oxides of nitrogen, sulphuric acid, hydrochloric acid, chlorine and iodine. Phosphoric Acid.— The commercial acid (D. 1*5) contains 65% H 3 P0 4 ; syrupy phosphoric acid contains about 90% H 3 P0 4 . Usual impurities : sulphuric acid and iron. Anhydrous Aluminium Chloride. — It is best to buy this reagent from a reliable manufacturer. As a high pressure frequently exists in bottles containing this reagent, such bottles should be opened with care, a cloth being wrapped round the bottle during the operation. If the commercial 498 INORGANIC SECTION 499 product is not available, it may be prepared (see p. 503). Usual impurity : water. Titanous chloride comes on the market in the form of a 20% solu- tion (see p. 482). Usual impurities : oxidation products. For the many reducing reactions in which titanous chloride is used it may be replaced by titanous sulphate, which must be used when there is danger of chlorination. Copper Bronze (Kahlbaum, " Natur Kupfer "). — This product can be used for the Gattermann reaction (p. 150) in place of copper powder (p. 504). The bronze should be washed with ether to remove oil and grease. Zinc-Dust. — Commercial varieties vary much in character and are subject to deterioration ; they contain usually 90 — 95% Zn (for estima- tion, see p. 506) ; they should be preserved in an airtight vessel and should be occasionally estimated. Two other forms of zinc for reducing purposes are on the market — a ground zinc, made by grinding metallic zinc, and a variety in the form of powder containing 2% of lead, which gives specially good results. Usual impurities : zinc oxide, iron and arsenic. Caustic Soda. — This is supplied in powder, flake and stick forms, the former two being more convenient to use. The pure variety comes on the market in the form of sticks. In weighing out a quantity, the sticks should not be handled. Pieces of a desired size can be broken of! by elevating one end and dealing a sharp blow with a knife or file at the desired point. The same remark applies to caustic potash sticks. 30 — 40% solutions of caustic soda are available in commerce. Usual impurities : sodium chloride and sodium carbonate. Ammonia.— A solution, D. 0*88, containing 35% NH 3 comes on the market. Cylinders of anhydrous liquid ammonia are also available. Sodium Nitrite. — The commercial product contains 97—98% NaN0 2 , and is suitable for most organic reactions. For estimation see p. 487. Usual impurity : sodium nitrate. Sodium Sulphide (Na 2 S,9H 2 0). — The commercial variety consists of dirty brown deliquescent crystals. It can be used for most purposes. Usual impurities : poly sulphides and sulphate. For estimation see p. 508. Sodium Bisulphite (see p. 506). — This is available in the solid form, and as a 30% solution commercially. The product as prepared on p. 506 is the most reactive in many cases. Usual impurity : bisulphate. Sodium Hypochlorite (see p. 508).— The commercial solution (about 30%) is available. Usual impurities : caustic soda, sodium chloride and sodium chlorate. Iron Filings and Iron Powder. — These are recommended for many operations in place of zinc and tin, on account of cheapness. Usual impurities : oxides. Stannous Chloride.— The product should be obtained from a reliable .firm. It should be frequently estimated, as it deteriorates through oxidation. Tables of the gravities and strengths of some reagents are given on pp. 500, 509-511. K K 2 500 SYSTEMATIC ORGANIC CHEMISTRY It is important that the common bench reagents should be of a definite strength. The following table shows the approximate strengths of the ordinary bench reagents, which have been found convenient in practice : — Approximate Concentration of Reagents. Beagent. D. Approx. Nor- mality. 1 litre 1ST solution equivalent to c.c. 100 gms. contain 100 CCS contain 1 -84. ou Q5»fi cms 1 75'Q cms H 2 S0 4 H 2 S0 4 IT SO rlil XI 20U^ tXXX . I 10 O 900 1 • t\ rrm a 94. ^ nrm q Z/rt 0 gins. (11.+ 6-4 1. water). H 2 S0 4 H 2 S0 4 XlV_yl cone. 1 9 1I1 0 i a gms. ii\ji tt 0 gms. UP] Hil XXVyl 1111. i Uo K O 900 ID O glllb. 1 8.9 frmc AO £1 glllo. (1 ] _l l.U waters HC1 HC1 TT1STO oawo J.Ill \J ^ \J\JX.\.\J» 1 -4 D«7 U«J O glXXUs Q 1 . 4 rem a VI rt gXXXb. UNO XX 1\| \J 3 HN0 3 dil. 1-17 5 200 27-1 gms. 31-5 gms. (11. +2 1. water). HNO3 HNO3 C 2 H 4 0 2 cone. 1-06 18 56-5 100 gms. C 2 H 4 0 2 106 gms. C 2 H 4 0 2 C 2 H 4 0 2 dil. 1-04 5 203 28 gms. C 2 H 4 0 2 29-5 gms. C 2 H 4 0 2 KOH 1-19 5 195 22 gms. 28-8 gms. (280 gms. in 1 1.). KOH KOH NaOH 1-17 5 200 15 gms. 20 gms. (200 gms. in 1 1.). NaOH NaOH NH 4 OH 0-96 5 200 9-5 gms. 8-5 gms. (1 1. strong + 31. water). NH 3 NH 3 Test Papers and Solutions. 1. Litmus Paper. — Used as an indicator for all weak and strong acids and bases. Turned red by acids and blue by alkalis. Cubes of best quality litmus containing 50 — 90% calcium sulphate are ground and washed with benzene, then with alcohol. 4 — 5 gms. of the residue are then dissolved in 1 litre of water ; good quality filter paper is soaked in the solution and dried by hanging on threads. It is then cut into small pieces. For red litmus a few drops of acetic acid are added to the solution, and for blue litmus, ammonia is used. 2. Phenolphthalein Paper. — Used in acidimetry and alkalimetry. Turned red by alkalis, reacting with ammonia and sodium carbonate, but not with bicarbonate. Used chiefly in analytical work. 0-5 gm. of phenolphthalein is dissolved in 500 c.cs. of hot water, and filter paper is soaked in the hot solution and dried. A few drops of a very dilute alcoholic solution may be used as an internal indicator. INORGANIC SECTION 3. Congo Paper.— Used as an indicator for acids. Turner by mineral acids and violet by strong organic acids. 1 gm. Congo Red is dissolved in 1 litre of water to which a fev of ammonia have been added. Filter paper is soaked in the w solution and dried. 4. Brilliant Yellow Paper. — Used as an indicator for alkalis. Turned red by alkalis and by alkali carbonates and ammonia. 1 gm. of the dye is dissolved in 1 litre of water and filter paper dipped in the solution and dried. The alkali salts of phenols and naphthols also give an alkaline reaction, so that free alkali must be tested for in the following way. A crystal of ammonium chloride is added to a few drops of the solution placed on a watch-glass, and the latter warmed with a very small flame. Another watch-glass with a piece of moistened red litmus paper adhering to its concave side, is placed over the other one, and if the liquid is alkaline the litmus paper will Be turned blue. This method can also be used where the colour or solubility of the substance to be tested prohibits the direct use of test papers. 5. Thiazole Paper (Mimosa Paper). — Used as an indicator for free alkali and is preferable to turmeric. Turned red by alkalis, but not influenced by ammonia even in high concentrations. Prepared similar to Congo Red paper, the dye thiazole yellow (Clayton Yellow) being employed. 6. Starch-Iodide Paper. — Used as an indicator for nitrous acid, and for halogens and other oxidising agents. Turned bluish violet by a trace of oxidising agent and brown by excess. 10 gms. of pure starch are ground up with 100 c.cs. of cold water and the mixture poured slowly into 2 litres of boiling water with good stirring. The whole is boiled for a few minutes, then cooled rapidly. 2 gms. of potassium iodide are added and 1 gm. of cadmium iodide. When all is in solution, filter paper is dipped in and dried in an atmosphere free from fumes. The solution does not keep and should be freshly prepared. The solution may be used as an indicator by " spotting " on filter paper. When the paper is used, a drop of the test solution is removed on a glass rod, and lightly drawn across the paper. The papers should be tested each time they are used by treating with a 1% solution of hydrochloric acid containing 1 drop of normal sodium nitrite solution. 7. Lead Acetate Paper. — Used for detecting H 2 S, with which it gives a brown coloration. ^Filter paper is soaked in a solution of 5 gms. lead nitrate or acetate or ferrous sulphate per litre, and dried in an atmosphere free from H 2 S. Ferrous sulphate paper does not keep. 8. Methyl Orange.— Used as an internal indicator in acidimetry and alkalimetry. Turned red with acid and yellow with alkali. Can be used in the presence of carbonates to detect free alkali. Is acted upon by bicarbonate. 1 gm. of methyl orange is dissolved in 1 litre of water. ,/STEMATIC ORGANIC CHEMISTRY ji Red. — Used as an internal indicator like methyl orange, _ore sensitive. a. of methyl red is dissolved in 1 litre of water. < ote. — All test papers and solutions should be preserved in well .coppered bottles. Inorganic Preparations, etc. Chlorine. — Manganese dioxide is placed in a flask and just covered with cone, hydrochloric acid. On heating, a regular current of chlorine is obtained which is passed through water and through cone, sulphuric acid. Chlorine can also be prepared by heating a mixture of cone, hydrochloric acid (5 parts) with ground potassium dichromate (1 part). Another con- venient method, which does not necessitate the use of heat, consists in treating good bleaching powder — cubes consisting of bleaching powder and plaster of Paris are sold for this purpose — with 4onc. hydrochloric acid. Bromine. — When nascent bromine is required, a mixture of sodium bromide and bromate is added to the solution of the substance. The quantity of sulphuric acid required by the following equation is then added. 5NaBr + NaBr0 3 + 6H 2 S0 4 = 6NaHS0 4 + 3H 2 0 + 6Br. For most purposes commercial bromine is used, although this form sometimes contains as much as 10% of impurities, the chief of which is bromoform. It may be purified by shaking up with cone, sulphuric acid. Hydrochloric Acid. — Gaseous hydrochloric acid is conveniently prepared in a Kipp apparatus charged with fused ammonium chloride in lumps, and cone, sulphuric acid. Another convenient method is to run cone, commercial hydrochloric acid (about 30% HC1) into cone, sulphuric acid from a dropping funnel contained in a suction flask or Woulff bottle. Hydrobromic Acid. — Sulphur dioxide is passed on to the surface of a mixture of 35 c.cs. of bromine and 200 c.cs. of water until a uniform pale yellow solution remains, which is distilled. S0 2 + Br 2 + 2H 2 0 = 2HBr + H 2 S0 4 . The sulphuric acid remains behind, and the distillate which may contain traces of sulphuric acid is redistilled over barium bromide. When large quantities of hydrobromic acid are required, it is advisable to pass sulphur dioxide into a mixture of crushed ice and bromine until a uniform pale yellow solution is obtained. Hydriodic Acid. — 11 parts by weight of iodine are placed in a small round-bottomed flask, and 1 part of yellow phosphorus, cut into small pieces and dried, is gradually added. The addition of each piece causes a flash of light and the contents of the flask become liquid. When all the phos- phorus has been added, solid phosphorus tri-iodide separates on cooling. The product is treated with 1J parts of water and, when gently heated, INORGANIC SECTION 503 evolves hydrogen iodide, which is passed over some red phosphorus moistened with a little water in a U-tube. Heating is continued until the liquid just becomes colourless ; otherwise, if heating is continued further, phosphine and phosphonium iodide are formed, which may cause explo- sion. If a solution of hydriodic acid is required, the gas is led through an inverted funnel into a small quantity of cold water. This solution, if dilute, may be concentrated by distillation. At 127° a solution of con- stant boiling point passes over containing 57% of hydrogen iodide and of density 1-70. Ammonia. — Ammonia gas can be conveniently obtained by gently heating cone, ammonium hydroxide solution (D. 0-88) which contains 35% of the gas. The evolved gas is dried by passing it over quicklime or soda-lime. A very convenient method consists in dropping cone, ammonia solution on to solid caustic potash or soda packed in a drying tower or in a flask. If a relatively large quantity of alkali is used the gas evolved is dry. Zinc- Ammonium Chloride. — This compound is formed by passing a current of dry ammonia gas into molten zinc chloride, ZnCl 2 .2NH 3 . It can also be obtained by passing the gas over pulverised anhydrous zinc chloride. This compound gives up ammonia on heating and is used in place of the concentrated solution in certain reactions. Aluminium-Mercury Couple. — -Aluminium foil is cut in small strips and formed into rolls. It is then placed in a saturated solution of mercuric chloride. After about a minute the foil becomes coated with a film of metallic mercury. The liquid is poured off and the couple well washed with water, then alcohol, and finally benzene. It is then ready for use. The couple should always be freshly prepared when required. Zinc-Copper Couple. — Granulated zinc is treated several times with a 2% solution of copper sulphate, the decolorised solution being poured off each time. The couple is washed first with water and then with alcohol, after which it is ready for use. Anhydrous Aluminium Chloride. — Aluminium shavings are freed from oil by boiling with alcohol, and then dried in an air bath at 120°. These are then packed in a thoroughly dry, hard glass tube, and kept in position by asbestos plugs. To one end of the tube is attached a drying apparatus consisting of two sulphuric acid wash-bottles. To the other end is attached a receiving apparatus in the form of a wide-mouthed bottle, which is closed with a cork suitably bored to admit the hard glass tube and a calcium chloride tube. The air is displaced from the apparatus by passing a stream of hydrochloric acid from a Kipp apparatus through the drying apparatus. This is accomplished when the gas issuing from the calcium chloride tube of the receiver is completely soluble in water. The hard glass tube is heated in a small furnace, or by means of a few Ramsay burners, the heating being gradual at first, and commencing at the end nearer the hydrochloric acid generator. White vapours of aluminium chloride condense in the receiver, and it is necessary to main- tain a rapid current of hydrochloric acid. The reaction is finished when there is only a small dark coloured residue of aluminium left in the tube. 504 SYSTEMATIC ORGANIC CHEMISTRY The aluminium chloride should be preserved in well stoppered bottles (see p. 498), or in a desiccator. Cuprous Chloride.— 100 gms. of crystallised copper sulphate, 48 gms. common salt and 200 c.cs. water are heated to boiling. 400 gms. of cone, hydrochloric acid and 72 gms. of copper turnings are added, and the whole is gently boiled until decolorised. It is important to exclude air from the flask, which may be done by using a plug of glass-wool or a Bunsen valve. The solution is rapidly decanted from unchanged copper, and then distilled water added until no more cuprous chloride is precipitated. The precipitate is filtered and washed, first with S0 2 solution, and then with glacial acetic acid until the filtrate is colourless. It is removed from the filter and dried on a water bath until all the acetic acid is driven off. It is preserved in a well stoppered bottle. For the Sandmeyer reaction it is not necessary to isolate the solid product. The solution, after removing the copper, is treated with cone, hydrochloric acid until the total weight is 815 gms. This solution contains about 10% cuprous chloride. Cuprous chloride can also be made by bubbling sulphur dioxide through a strong solution of cupric chloride and filtering off the white precipitate of the desired substance. Cuprous Bromide. — 100 gms. of crystallised copper sulphate, 288 gms. potassium bromide, 640 c.cs. of water, 160 gms. of copper turnings, and 88 gms. of cone, sulphuric acid are boiled until the whole is decolorised. The solution is decanted from unchanged copper. Lead Peroxide. — 100 gms. of bleaching powder are shaken up with 1500 c.cs. of water and filtered. The filtrate is added gradually to a hot solution of 50 gms. lead acetate in 250 c.cs. of water ; the addition is continued until the precipitate turns dark brown, and until no precipitate is formed by further addition of bleaching powder solution to a filtered test portion. The liquid is decanted, and the precipitate washed several times with water, then filtered and washed with water. It is preserved in a well stoppered bottle in the form of a thick paste. Evaluation. — 0*5 to 1 gm. of the paste is treated (with cooling) with hydrochloric acid (approximately 15% solution). The chlorine liberated on heating is passed into a solution of 4 gms. of potassium iodide in water, N and the iodine liberated is titrated with sodium thiosulphate. 1 c.c. of this thiosulphate solution is equivalent to 0-012 gm. of pure lead peroxide. Copper Powder. — 100 gms. of crystallised copper sulphate are dissolved in 350 gms. of water in a beaker, to which is attached a mechanical agitator. After cooling to laboratory temperature, the stirrer is set in motion, and 35 gms. (or more if necessary) of good quality zinc-dust are gradually added until the solution is decolorised. The precipitated copper is washed by decantation with water. Dilute hydrochloric acid is added to the precipitate (to remove excess zinc), and agitation continued until evolution of hydrogen ceases. The powder is filtered off and preserved in a moist condition in a stoppered bottle. INORGANIC SECTION 505 Sodium Amalgam —Weighing of Sodium. — A lump of sodium is removed from a storage bottle and the surface cleaned with a knife. The bright lump is covered with petroleum ether (60° — 80°) in a porcelain dish, and cut into small pieces. A second dish (or beaker) containing petroleum ether is weighed. Small lumps of sodium are removed from the first dish, quickly dried with filter paper, and added to the second until the required weight of sodium is obtained. Sodium amalgam is usually made to contain 2J% of sodium, as such a product is solid and easily pulverised. Pure dry mercury is placed in a porcelain mortar and warmed in an oven to 60° — 70°. It is then removed to a fume cupboard, and the metallic sodium, removed a piece at a time from the petroleum ether, quickly dried with filter paper, and plunged under the surface of the mercury with a pointed glass rod. The hand should be covered with a towel during the operation. When preparing a large quantity of amalgam it is advisable to place only a portion of the mercury in the mortar at first, and to charge this with sodium before adding another portion of mercury to the contents. Proceeding in this way the sodium dissolves quietly, and there is practically no spluttering with the second or later instalments of mercury. The usual way of introducing sodium into a liquid is in the form of wire. A sketch of a press for this purpose is shown in Fig. 78. Silver Nitrite. — A warm concen- trated aqueous solution of silver nitrate containing 24 gms. is mixed with a warm concentrated solution of potassium nitrite containing 15 gms. The mixture is allowed to cool and the silver nitrite which separates filtered off and rapidly washed with water. Sodium Ethylate (or Ethoxide). — 100 c.cs. of absolute alcohol are placed in a flask and clean metallic sodium in small strips added until it no longer dissolves. Gentle heat is then applied to effect solution of the last particle of metal: The excess of alcohol is then distilled off up to 200°, and the dry residue warmed for some time in a current of hydrogen. It is then preserved in a well stoppered bottle. It is not always necessary to isolate the dry sodium ethoxide, the alcoholic solution being sufficient for most purposes. A very reactive sodium ethylate can be obtained by adding the calcu- lated quantity of absolute alcohol diluted with 2 vols, of dry xylene to granulated sodium under xylene (see p. 506). During the addition the whole is well cooled and shaken. The xylene is then distilled off in a current of dry hydrogen. Fig. 78. 506 SYSTEMATIC ORGANIC CHEMISTRY Granulated Sodium. — 1 part of sodium is covered with 10 parts of dry xylene and heated to 120°. The flask is then corked and wrapped in a thick dry cloth and well shaken for a short time. The metal is thus obtained in the form of a powder. No more than 20 gms. of sodium should be granulated at one time. A dry bucket should be kept at hand to drop the flask into in case of breakage. (B., 21, 1464 ; 35, 3516 ; J. pr. [2], 54, 116.) Anhydrous Sodium Acetate. — Crystallised sodium acetate (CH 3 .COONa. 3H 2 0) is heated in a basin over a small flame. The salt melts and for some time steam is evolved until all the water of crystallisation is driven off, at which stage the mass becomes solid. The flame is then increased, and heating continued until the mass melts again. Care must be taken not to char the product by using too large a flame. On cooling, the mass solidifies ; it is broken up into small lumps and preserved in a stoppered bottle. Anhydrous Zinc Chloride. — Crystallised zinc chloride is fused in a porce- lain basin for a short time until no more steam is evolved, then cooled and broken up into small pieces which are preserved in a well stoppered bottle. Sodium Bisulphite. — Sodium carbonate is covered with a layer of water — insufficient to dissolve it — and sulphur dioxide is passed into the mixture. After a time the solid disappears and an apple-green solution remains which smells strongly of sulphur dioxide. Sulphur dioxide may be obtained from a siphon of the liquid or generated by the action of cone, sulphuric acid on sodium sulphite. Sodium bisulphite solution may be obtained by dissolving the sodium bisulphite in water, but the solution so prepared does not act as readily with aldehydes and ketones as the syrupy apple-green solution described above. Sodamide. — This is prepared by the action of ammonia gas on sodium heated to 300° — 400°. For the preparation of quantities of 20 gms. or more the most convenient apparatus consists of some form of closed iron pot provided with inlet and outlet tubes for ammonia. The appa- ratus, Fig. 36, or an autoclave from which any copper fittings have been removed can easily be adapted to suit the purpose. If the apparatus is free from rust, the sodium may be- placed directly on the bottom of the pot. Or, it may be contained in a large nickel or iron crucible. Before commencing to heat, the air should be displaced from the pot by am- monia, after which the temperature is raised to and maintained at 300° — ■ 400° while a current of the dry gas is passed over the molten metal. The reaction takes place readily. If, after cooling and opening the pot, any soft lumps of sodium remain on the surface, these can be picked out with a knife, or else the apparatus may be closed again and more ammonia passed over the heated metal. The sodamide forms a hard mass which is chipped out with a knife or chisel. It should be preserved in stoppered bottles. Evaluation of Zinc-Dust.— 0 5 gm. of zinc-dust is quickly weighed out and placed in a dry 250 c.cs. graduated flask and 50 c.cs. of saturated solution of ferric alum added. The flask is stoppered and vigorously INORGANIC SECTION 507 shaken until the zinc-dust disappears. The reaction is represented by the equation — Zn + Fe 2 (S0 4 ) 3 = ZnS0 4 + 2FeS0 4 . 25 c.cs. of cone, sulphuric acid are then added gradually, cooling being applied. When all the acid is added, the volume is made up to 250 c.cs. with distilled water. 50 c.cs. of this solution are then withdrawn and N titrated with -permanganate, o N 1 c.c. j KMn0 4 = 0 00654 gm. Zn. Sulphur Monochloride (S 2 C1 2 ). — In a dry retort is placed 100 gms. of sulphur, which is melted by gentle heating. The retort is connected to a receiver having an exit tube. Chlorine, dried by passing through cone, sulphuric acid and fused calcium chloride, is passed into the melted Fig. 79. sulphur. Sulphur monochloride distils over, and the passage of gas is continued until very little sulphur remains. The brownish yellow liquid which collects is redistilled, the fraction 138° — 139° being collected, and preserved in a sealed bottle. Phosphorus Di-iodide (PI 2 ). — 5 parts of phosphorus are dissolved in carbon disulphide, and to the well cooled solution 41 parts of dry, powdered iodine are added. The carbon disulphide is then distilled off from the phosphorus di-iodide. Phosphorus Trisuiphide (P 2 S 3 ). — The calculated quantities of dry amorphous phosphorus and sulphur are carefully melted together in a fireclay crucible. It is then cooled and broken up. Chlorosulphonic Acid (S0 3 HC1). — A mixture of common salt and cone, hydrochloric acid is placed in a flask and hydrochloric acid gas produced by dropping cone, sulphuric acid on to it. The gas is dried and passed into fuming sulphuric acid in a retort until no further absorption takes place, cooling being applied to the retort, if necessary. The retort is then heated to 140° — 153°, when chlorosulphonic acid distils over. A pure acid can be obtained, if necessary, by a further distillation, the fraction boiling at 149° — 151° being retained. The yield is nearly 508 SYSTEMATIC ORGANIC CHEMISTRY theoretical. Fig. 79 shows a convenient form of apparatus. A dilute chlorosulphonic acid can be readily obtained by adding common salt to fuming sulphuric acid. Fuming Nitric Acid. — This can be prepared by distilling 2 mols. sodium nitrate with 1 mol. cone, sulphuric acid at over 200° ; or by distilling a mixture of strong nitric acid and cone, sulphuric acid. The addition of 3 — 5% starch is effective. Its specific gravity at 15° is 1-533. Sodium Hypochlorite (NaOCl). — 1. Excess of sodium carbonate is added to a solution of bleaching powder. The filtrate, after removing the CaC0 3 , contains 5% available chlorine, and the solution can be kept for some time. 2. Chlorine gas is passed into a cold solution of caustic soda until nearly all the soda is chlorinated. The solution is usually made to contain 10—15% available chlorine. (J. S. C. I., 18, 1096.) Sodium Hyposulphite (Na 2 S 2 0 4 ). — S0 2 is passed into a strong solution of NaHSOg until saturated, and the mixture reduced with zinc-dust. NaHS0 3 + S0 2 + Zn = ZnS0 3 + Na 2 S 2 G 4 x H 2 0. Milk of lime is then added to precipitate ZnO and CaS0 3 , and the liquor is saturated with salt at 50°, and cooled to crystallise the hyposulphite. By adding excess of caustic soda to a cone, solution of the crystals at 50°, the anhydrous salt is precipitated as a powder, which may be filtered and washed with alcohol. Various hyposulphite preparations containing aldehydes, zinc compounds (Rongalite), etc., are on the market, which are more stable. Ammonium Sulphite. — S0 2 from a siphon is passed in a vigorous stream into 2 parts of cone, ammonia solution (D. 0-880) and 1 part of ice, sur- rounded by a freezing mixture. The solution gradually assumes a light- yellow colour. When no more S0 2 is absorbed the solution is neutralised with cone, ammonia solution. This solution is a saturated solution of ammonium sulphite and sometimes deposits crystals on standing. Sodium Sulphide (Na 2 S). — Evaluation. — The crystalline variety is Na 2 S.9H 2 0. 5 gms. sodium sulphide is dissolved in water up to 250 c.cs. and care- fully neutralised with dilute acetic acid in presence of phenolphthalein until the latter is colourless. A -JN solution of crystallised zinc sulphate (57-514 gms. ZnS0 4 .7H 2 0 per litre) is run in from a burette until all the soluble sodium sulphide is converted into zinc sulphide. A cone, solution of cadmium sulphate is spotted on thick blotting-paper, and a drop of the liquid being analysed is placed near it. A yellow stain will be produced as long as any soluble sulphide remains. The zinc sulphate is added until no yellow colour is given. Example. — Volume of zinc sulphate - 9-3 c.cs. AT a • OK 9 ' 3 >< 0,078 A i.M Na 2 S m 25 c.cs. = = 0-1451 gm. % Na 2 S = X 5 10 X 100 = 29-02. INORGANIC SECTION 509 Carbonyl Chloride (Phosgene). — 100% sulphuric acid, to which is added 2% dry ignited kieselguhr, is placed in a flask which is attached to a small reflux condenser and a dropping funnel. Carbon tetrachloride is placed in the funnel, and from the top of the condenser is led a delivery tube passing through an empty wash-bottle, and then under the surface of toluene contained in a Buchner flask, the side tube of which is led to a draught duct. The sulphuric acid is heated to 140°, when the carbon tetrachloride is allowed to drop slowly. After the reaction commences the temperature may be lowered to about 120°, and this temperature maintained by gentle heat. The carbonyl chloride passes over and is absorbed in the toluene, while the hydrogen chloride which is formed passes over. The whole operation should be conducted in a good draught chamber as phosgene is very poisonous. 2H 2 S0 4 + 3CC1 4 —> 3C0C1 2 + 4HC1 + S 2 0 5 C1 2 . Nitrous Fumes. — Arsenious acid (As 2 0 3 ) is broken into small pieces and placed in a flask with a two-holed cork, which carries a dropping funnel and a delivery tube. The delivery tube is connected to an empty wash- bottle surrounded by cold water to condense any nitric acid which passes over. Nitric acid (D. 1-3) is dropped in gradually from the funnel, while the flask is gently heated ; a stream of nitrous fumes is readily evolved. Chromic Anhydride (Cr0 3 ). — 1'5 vols, of cone, sulphuric acid is added gradually, and with shaking to 1 vol. of a saturated solution of potassium chromate. The mixture is allowed to cool, when the anhy- dride separates out as scarlet crystals. The crystals are filtered off, washed with a little nitric acid, and dried in a desiccator. The crystals are hygroscopic, and should be preserved in a well stoppered bottle. K 2 Cr0 4 + H 2 S0 4 = K 2 S0 4 + Cr0 3 + H 2 0. Chromyl Chloride (Cr0 2 Cl 2 ). — A mixture of 4 parts sodium chloride. 5 parts potassium dichromate and 9 parts fuming sulphuric acid, is placed in a retort and distilled until coloured liquid no longer passes over. The chromyl chloride is then redistilled (B.P. 116°). K 2 Cr 2 0 7 + 4NaCl + 3H 2 S0 4 .S0 3 = 2Cr0 2 Cl 2 + 2KHS0 4 + 4NaHS0 4 . Specific Gravities and Concentrations op Aqueous Acid Solutions. Hydrochloric. Nitric. Sulphuric. Acetic. % D.15 % D. 15 % D. is % D. 15 0-15 1-005 1-000 1-005 4-49 1-030 1-0 1-0007 2-14 1-010 1-90 1-010 10-19 1-070 5 1-0067 3-12 1-015 2-80 1-015 15-71 1-110 10 1-0142 4-13 1-020 3-70 1-020 20-91 1-150 15 1-0214 5-15 1-025 4-60 1-025 26-04 1-190 20 1-0284 6-15 1-030 5-50 1-030 31-11 1-230 25 1 0350 510 SYSTEMATIC ORGANIC CHEMISTRY Specific Gravities and Concentrations of Aqueous Acid Solutions — continued. Hydrochloric. Nitric. Sulphuric. Acetic. % D.15 % D.is % D.15 % D.15 715 1-035 6-38 1-035 35-71 1-270 30 1-0412 8-16 1-040 7-26 1-040 40-35 1-310 35 1-0470 9-16 1-045 8-99 1-050 44-82 1-350 40 1-0523 10-17 1-050 9-84 1-055 50-11 1-400 45 1-0571 11-18 1-055 10-68 1-060 55-03 1-450 50 1-0615 12-19 1-060 11-51 1-065 60-65 1-510 55 1-0653 13-19 1-065 12-33 1-070 65-08 1-560 60 1-0685 14-17 1-070 13-95 1-080 70-32 1-620 65 1-0712 15-16 1-075 15-53 1-090 75-42 1-680 70 1-0733 16-15 1-080 17-11 1-100 80-68 1-740 75 1-0746 17-13 1-085 18-67 1-110 85-70 1-790 80 1-0748 18-11 1-090 22-30 1-120 90-05 1-820 85 1-0739 19-06 1-095 22-54 1-135 90-40 1-822 90 10713 20-01 1-100 24-08 1-145 91-00 1-825 91 1-0705 20-97 1-105 26-36 1-160 91-50 1-827 92 1-0696 21-92 1-110 28-63 1-175 92-10 1-830 93 1-0680 22-86 1-115 31-30 1-185 92-52 1-832 94 1-0674 23-82 1-120 32-36 1-200 93-05 1-834 95 1-0660 24-78 1-125 34-55 1-215 93-43 1-835 96 1-0644 25-75 1-130 36-78 1-230 94-20 1-837 97 1-0625 26-70 1-135 39-05 1-245 94-60 1-838 98 1-0604 27-66 1-140 41-34 1-260 95-00 1-839 99 1-0580 28-61 1145 44-41 1-280 95-60 1-840 100 1-0553 29-57 1-150 46-72 1-295 95-95 1-8405 30-55 1-155 49-07 1-310 97-00 1-8410 31-52 1-160 52-37 1-330 97-70 1-8415 32-49 1-165 55-79 1-350 98-20 1-8410 33-46 1-170 58-48 1-365 98-70 1-8405 34-42 1-175 61-27 1-380 99-20 1-8400 35-39 1-180 63-23 1-390 99-45 1-8395 65-30 1-400 99-70 1-8390 67-50 1-410 99-95 1-8385 69-80 1-420 Specific Gravities and Concentrations of Aqueous Alkaline Solutions. Caustic Soda. 0-61 2- 00 3- 35 4- 26 D.15 1-007 1022 1-036 1-052 Caustic Potash. Ammonia. % D.15 /o 1 1-009 0-45 0-998 3 1-025 1-37 0-994 5 1-041 2-31 0-990 7 1-058 3-30 0-986 INORGANIC SECTION 511 Specific Gravities and Concentrations of Aqueous Alkaline Solutions— continued. Caustic Soda. Caustic Potash. Ammonia. % D.15 % % D.i r > 5-87 1-067 9 1-074 4-30 0-982 6-55 1-075 11 1-092 5-30 0-978 7-31 1-083 13 1-110 6-30 0-974 8-68 1-100 15 1-128 7-31 0-970 9-42 1-108 17 1146 8-33 0-966 10-97 1-125 19 1-166 9-35 0-962 12-64 1-142 21 1-188 10-47 0-958 14-37 1-162 23 1-209 11-60 0-954 15-91 1-180 25 1-230 12-74 0-950 16-77 1-190 27 1-252 13-88 0-946 17-67 1-200 29 1-276 14-46 0-944 19-58 1-220 31 1-300 15-04 0-942 21-42 1-241 33 1-324 15-63 0-940 23-67 1-263 35 1-349 16-82 0-936 25-80 1-285 37 1-374 18-03 0-932 27-80 1-308 39 1-400 19-25 0-928 29-93 1-332 41 1-425 20-49 0-924 32-47 1-357 43 1-450 21-75 0-920 34-96 1-383 45 1-475 23 03 0-916 36-25 1-397 47 1-499 24-33 0-912 37-47 1-410 49 1-525 25-65 0-908 38-80 1-424 51 1-552 26-98 0-904 39-99 1-438 53 1-578 28-33 0-900 41-41 1-453 55 1-604 29-69 0-896 42-83 1-468 57 1-630 30-37 0-894 44-38 1-483 59 1-655 31-75 0-890 46-15 1-498 61 1-681 32-50 0-888 47-60 1-514 63 1-705 33-25 0-886 49-02 1-530 65 1-729 34-95 0-882 67 1-754 69 1-780 Vapour Pressures. Vapour pressure of water at different temperatures. Temperature. Pressure. Temperature. Pressure. Tempera- ture. 40 gms.KOH: 100c.c.H 2 O. 49 gms.KOH: lOOc.c. H 2 0. mms. mms. mms. mms. 0° 4-6 16° 13-5 10° 6-5 5-6 2° 5-3 18° 15-4 12° 7-5 6-5 4° 6-1 20° 17-4 14° 8-4 7-3 6° 7-0 22° 19-7 16° 9-6 8-3 8° 8-0 24° 22-2 18° 10-9 9-5 10° 9-2 26° 25-0 20° 12-4 10-8 12° 10-5 28° 281 22° 13-9 12-1 14° 11-9 30° 31-6 Vapour pressure of cone. KOH solution at different temperatures. CHAPTER XLIV TESTS FOR ORGANIC ACIDS, ALKALOIDS, CARBOHYDRATES Tests for some Organic Acids — - Group I. — Calcium salts insoluble in water, therefore precipitated by CaCl 2 either in cold or on boiling : Oxalic, tartaric, citric, malic. Group II. — Iron salts insoluble in water, therefore precipitated by Fe 2 Cl 6 from neutral solutions : Benzoic, succinic. Group III. — Acids not precipitated by CaCl 2 or Fe 2 Cl 6 in the cold but precipitated by AgN0 3 from neutral solutions : Acetic, formic, hydro- cyanic, cyanic, hydroferrocyanic, hydroferricyanic, sulphocyanic. Group IV. — Acids not precipitated by foregoing reagents : Salicylic hippuric, stearic, uric, gallic, tannic, lactic. TABLE I. Preliminary Examination of Common Organic Acids. 1. Heat solid substance in test tube. 2. Heat solid substance with cone. H2SO4. (a) No charring. White ) Oxalic, sublimate. > Benzoic. Acetic ) Acetic, odour. } Formic. Irritating -\ odour and (Succinic. white j sublimate. ' Odour of | bitter [ Hydrocyanic, almonds, j °IZJ. } salicylic. (b) Immediate charring, i Odour of ) burnt y Tartaric. Sugar, j Odour of \ burnt - Uric, feathers, j Odour of ^ bitter V Hippuric. almonds. / Blackens \ after a I Citric, time. ) (a) No charring. | Formic. CO evolved, j Succinic. ( Ferrocyanic. salts formed ) ^ amG - (b) Charring at once. Tartaric. Gallic. Tannic. (c) Charring after a time Citric. Malic. Uric. Lactic. TABLE II. Tests in Neutral Solutions. To neutral solutions add : — j White precipitate /in the cold . . • . . Oxalic. P1 j Do. in the cold on standing . . Tartaric. l ^ l2 j Do. Ion boiling Citric. \ Do. Ion continued boiling . . . Malic. 512 TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC. 513 TABLE II. — Tests in Neutral Solutions — continued. To neutral solution add : — /Buff precipitate I Brownish -red precipitate Prussian blue precipitate Fe 2 Cl 6 - Blueblack precipitate Violet coloration . Greenish-brown coloration 'Red coloration ( White ppt. insol. in HN0 3 , sol. in NH 4 OH Do. do. do. Do. do. insol. Orange ppt. sol. in NH 4 OH White ppt. sol. in HN0 3 and NH 4 0H AgNO; Do. do. do. Do. do. NH 4 OH . Do. do. do. Do. do. do. Do. do. do. Do. do. do. Do. reduced to metallic silver Do. decomposed by HN0 3 Do. sol. in NH 4 OH Benzoic. Succinic. Ferrocyanic. Tannic, Gallic. Salicylic. Ferricyanic. Acetic, Formic, SuTpho cyanic. Hydrocyanic. Sulphocyanic. Ferrocyanic. Ferricyanic. Oxalic. Tartaric. Citric. Malic. Acetic. Benzoic. Succinic. Salicylic. Formic. Cyanic. Preparation o£ Neutral Solutions of Salts ol Organic Acids. Soluble acids should be dissolved in water and treated solution until phenolplithalein is just turned pink. with Na 2 C0 3 Insoluble acids or salts are treated with excess of Na 2 C0 3 solution. The excess of alkali is then removed by addition of mineral acids until neutral to phenoiphthalein. Neutral solutions should be of about 10% concentration. ^ Ammoniacal silver nitrate solution is made by adding ammonia carefully to a solution of AgN0 3 until the precipitate at first formed is just re dissolved. GROUP I. on heating, give carbonates. H 2 S0 4 , on heating, usually no Oxalic,; COOH.COOH + 2H 2 0.— White crystalline solid. Loses 2H 2 0 at 100°, /tjien melts and sublimes partly with decomposition, giving off C0 2 angH.COOH. Alkafcjbxalates are soluble in water. All palates are insoluble in alcohol. Oxalates of alkalis and alkaline earths, Othei/metallic oxalates give oxides. Cone. chaiMng ; CO and C0 2 evolved. Solutions of oxalates give with — 1. KaCl 2 , white precipitate — CaC 2 0 4 , soluble in HCi and HN0 3 , almost insoMble in acetone and ammonia. 2. J?AgN0 3 , white precipitate — Ag 2 C 2 0 4 , soluble in HN0 3 and ammonia. 3j§KMn0 4 in dilute H 2 S0 4 solution, decolorised and C0 2 given off. S.0.C. L L SYSTEMATIC ORGANIC CHEMISTRY Tartaric, CHOH.COOH CHOH.COOH. Colourless crystals. M.P. 167°— 170°. Readily soluble in water, moderately in alcohol, sparingly in ether. Alkali tartrates are soluble in water. All tartrates insoluble in alcohol. On heating, charring takes place ; burnt sugar smell, and acid vapours evolved. Cone. H 2 S0 4 , on heating, turns brown then black, and acid vapours evolved. Neutral solutions of tartrates give with — 1. CaCl 2 , white precipitate — CaC 4 H 4 0 6 , usually only after vigorous shaking ; soluble in HO, HN0 3 and, if precipitate has not assumed the crystalline form, in acetic acid. Soluble also in cold cone. KOH after washing. Re-precipitated on boiling. 2. AgN0 3 , white precipitate — Ag 2 C 4 H 4 0 6 , soluble in HN0 3 and ammonia. Precipitate dissolved in minimum quantity of ammonia, deposits silver mirror on gently heating. 3. KC1, white precipitate — KC 4 H 5 0 6 , soluble in mineral acids and in alkalis, insoluble in acetic acid. Precipitation induced by stirring or by addition of alcohol. Citric, CH 2 COOH I COHCOOH + H 2 0 I CH 2 COOH. Colourless crystals; M.P. 100° (anhydrous acid, M.P. 153°); readily soluble in water and alcohol, sparingly in ether. Alkali salts soluble in water. Most citrates insoluble in alcohol. On heating, melts and gives off water ; no smell of burnt sugar. Cone. H 2 S0 4 , on heating, gases evolved ; solution becomes yellow and then dark. Neutral solutions of citrates give with — 1. CaCl 2 , white precipitate — Ca 3 (H 6 H 5 0 7 ) 2 on boiling; no precipitate in the cold. Precipitate soluble in NH 4 Ci, insoluble in KOH. 2. AgN0 3 , white precipitate— Ag 3 C 6 H 5 0 7 , soluble in ammonia. No mirror formed as in tartrates. 3. KC1 gives no precipitate. 4. Ca(OH) 2 on boiling, white precipitate— Ca 3 (C 6 H 5 0 7 ) 2 , which redis- solves on cooling. Malic, CHOH(COOH)CH 2 COOH.— Colourless deliquescent needles; M.P. 100° ; readily soluble in water, moderately in alcohol and in ether. Metallic malates mostly soluble in water. On heating loses water and is converted to fumaric and maleic acids. Cone. H 2 S0 4 , on heating, turns brown ; CO and C0 2 evolved. TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC. 515 Neutral solutions of malates give with — 1. CaCl 2 , white precipitate — Ca.C 4 H 4 0 5 , on boiling from cone, solutions ; precipitation assisted by alcohol. 2. AgN0 3 , white precipitate — Ag 2 C 4 H 4 0 5 , turning grey on boiling. 3. Ca(OH) 2 , no precipitate, even on boiling. GROUP II. Benzoic, C 6 H 5 COOH. — White needles or scales ; M.P. 121° : sparingly soluble in cold, fairly readily in boiling water ; readily soluble in alcohol and in ether. Mostjbenzoates soluble in water ; all give benzoic acid with mineral acids. On heating, melts and volatilises. On heating acid or salts with soda-lime, benzene evolved. Cone. H 2 S0 4 , on heating, dissolves ; no charring ; acid precipitated on dilution with water. Neutral solutions of bsnzoates give with — 1. CaCl 2 , no precipitate even on addition of alcohol. 2. Fe 2 Ci 6 , buff precipitate — Fe 2 (C 7 H 5 0 2 ) 6 , soluble in HClwith liberation of benzoic acid. 3. HC1, free acid precipitated. 4. BaCl 2 , in presence of ammonia ; no precipitate even on addition of alcohol. Succinic, COOH.CH 2 CH 2 .COOH. — Colourless prisms ; M.P. 181° ; soluble in water, sparingly soluble in cold alcohol and ether. On heating, loses water, yielding anhydride. Succinates char at high temperature. Cone. H 2 S0 4 added to succinates ; on heating, solution turns dark and sublimate forms on cold part of dry tube. Neutral solutions of succinates give with — 1. CaCl 2 , no precipitate even on boiling. 2. Fe 2 Cl 6 , brownish red precipitate ; basic ferric succinate easily soluble in HC1. 3. BaCl 2 in presence of ammonia, white precipitate on addition of alcohol. GROUP III. Formic, H.COOH.— Colourless liquid ; M.P. 8° ; B.P. 101°. Pungent odour ; vapour burns with blue flame. Miscible in all proportions with water, alcohol and ether. Most formates soluble in water, sparingly soluble in alcohol. Formates, when heated, evolve CO yielding carbonates, oxides or metals. Cone. H 2 S0 4 , CO evolved. Neutral solutions of formates give with — 1. Fe 2 Cl 6 , red coloration, which on boiling yields reddish precipitate of basic ferric formate. L L 2 516 SYSTEMATIC ORGANIC CHEMISTRY 2. AgN0 3 in cone, solutions, white precipitate — AgCH0 2 , turning dark even in cold, owing to deposition of metallic silver. This decom- position of silver formate does not take place in presence of excess ammonia. 3. HgCl 2 , on warming, white precipitate — Hg 2 Cl 2 , or grey precipitate of metallic mercury. 4. Solutions of formates or formic acid decolorise permanganate solution. 5. Solutions of formates or formic acid, with few drops alcohol and few drops cone. H 2 S0 4 , on warming, give ethyl formate, recognised by sweet smell. Acetic, CH3.COOH. — Colourless crystals ; M.P. 17° ; B.P. 119° : characteristic odour ; vapour burns with bluish flame ; miscible in all proportions with water, alcohol and ether. All acetates, except silver and mercury and the basic acetates of iron and aluminium, are soluble. Acetates, when heated, give acetone. Cone. H 2 S0 4 , on heating, liberates acetic acid. Neutral solutions of acetates give with — 1. Fe 2 Cl 6 , red coloration, which on boiling yields brownish precipitate of basic ferric acetate. The red colour is destroyed by HC1, but not by 2. AgN0 3 in cone, solutions, white crystalline precipitate — AgC 2 H 3 0 2 , soluble in hot water and in ammonia. Silver acetate is not reduced when the solution is boiled. 3. Solid acetates with cone. H 2 S0 4 and a few drops of alcohol, on heating, give ethyl acetate, recognised by pleasant odour. 4. Dry acetates mixed with a trace of As 2 0 3 , when heated, give vapours of cacodyl oxide, As 2 (CH 3 ) 4 0, recognised by smell (caution ! vapours are very poisonous). Hydrocyanic, HCN. — Colourless volatile liquid ; B.P. 26° ; burns with reddish-violet flame ; soluble in water, alcohol and ether. Aqueous solution does not redden blue litmus. Cyanides of the alkali and alkaline earth metals soluble in water. Most other metallic cyanides insoluble. Cone. H 2 S0 4 , on heating, liberates CO. Dilute HCi, in cold, liberates HCN, recognised by smell (caution !). Solutions of cyanides give with — 1. AgN0 3 , white precipitate — AgCN, insoluble in dilute HN0 3 , soluble in ammonia and KCN solution. 2. NaOH with few drops FeS0 4 and Fe 2 Cl 6 solutions, acidified with HCi, precipitate of Prussian blue. 3. Yellow ammonium sulphide, on evaporation to dryness, thiocyanate, which gives with Fe 2 Cl 6 in dilute HCi, deep red colour. Cyanic, HCNOo — Unstable liquid ; smell similar to acetic acid. Cyanates with HCI give C0 2 and NH 4 C1. TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC. 517 Aqueous solution of KCNO on standing gives NH 3 , leaving K 2 C0 3 in , solution. Solutions of cyanates give with AgN0 3 , white precipitate — AgCNO, soluble in ammonia ; decomposed by acids with liberation of C0 2 and formation of an ammonium salt. For conversion to urea, see p. 429. Thiocyanic, HONS.— Unstable liquid ; salts mostly soluble in water, and are decomposed when heated. Solid salts heated with H 2 S0 4 yield C0 2 , HCN and H 2 S. Solutions of thiocyanates give with — 1. AgN0 3 , white precipitate — AgCNS, insoluble in dilute HN0 3 , sparingly soluble in ammonia ; also soluble in KCNS. 2. Fe 2 Cl 6 to dilute solution, deep red coloration — Fe 2 (CNS) 3 , colour is unchanged by HC1, but destroyed by HgCl 2 . For conversion to thiourea, see p. 428. Hydroferrocyanic, H 4 Fe(CN) 6 .— Colourless crystalline solid, readily soluble in water. Salts of alkali and alkaline earth metals soluble in water. All ferrocyanides are decomposed by heat. Cone. H 2 S0 4 , on heating, CO evolved. Solutions of ferrocyanides give with — ■ 1. Fe^Cl 6 , dark blue precipitate — Prussian blue, Fe 4 {Fe(CN) 6 } 3 , insoluble in HC1, soluble in oxalic acid. 2. FeS0 4 , pale blue precipitate, which rapidly darkens on exposure to air. 3. AgN0 3 , white precipitate — Ag 4 Fe(CN) 6 , insoluble in dilute HN0 3 . and in ammonia, soluble in KCN. 4. CuS0 4 , chocolate precipitate — Cu 2 Fe(CN) 6 , insoluble in dilute acids. Hydroferricyanic, H 3 Fe(CN) 6 . — Yellow crystalline solid, readily soluble in water. All metallic ferricyanides are decomposed by heat. Cone. H 2 S0 4 , on heating, CO and C0 2 . Solutions of ferricyanides give with — 1. Fe 2 Cl 6 , brown or dark green coloration. 2. FeS0 4 , dark blue precipitate— Turn bull's blue, Fe 3 {Fe(CN) 6 } 2 , insoluble in acids, decomposed by KOH. 3. CuS0 4 , greenish-yellow precipitate — Cu 3 {Fe(CN) 6 } 2 . 4. AgN0 3 , orange precipitate — Ag 3 Fe(CN) 6 , insoluble in dilute HN0 3 , soluble in ammonia and KCN. GROUP IV. Salicylic, C 6 H 4 OH.COOH [1.2]. — Colourless needles ; M.P. 157° ; sparingly soluble in cold, moderately in hot water ; easily soluble in alcohol and in ether. Most salicylates are soluble in water, and give salicylic acid with mineral acids. When strongly heated gives C0 2 and phenol. Salicylic 518 SYSTEMATIC ORGANIC CHEMISTRY acid or salicylates mixed with soda-lime and heated give phenol, recognised by its smell. \. ' The acid is soluble in cone. H 2 S0 4 , and is reprecipitated on dilution with water. Neutral solutions of salicylates give with — 1. Fe 2 Cl 6 , violet coloration ; colour destroyed by acids or alkalis. 2. Bromine water, yellowish-white precipitate. 3. Dry salicylates, with few drops methyl alcohol and cone. H 2 S0 4 , on warming, methyl salicylate (oil of winter green) ; recognised by smell. Hippuric, CH 2 NH.COC 6 H 5 COOH. — Colourless, crystalline substance ; M.P. 187° ; readily soluble in hot water, or in hot alcohol ; on heating, benzonitrile (odour of oil of almonds) ; on heating with soda-lime, NH 3 evolved. Neutral solutions of hippurates give with — 1. Dilute acids, hippuric acid. With cone. HC1 at 100°, benzoic acid separates, leaving glycine in solution. 2. Fe 2 Cl 6 , brown precipitate. Uric, C 5 H 4 N 4 0 3 . — White crystalline powder ; sparingly soluble in water and all solvents ; insoluble in cold Na 2 C0 3 , but soluble in NaOH. On heating, NH 3 , HCNO, HCN and urea are formed. Cone. H 2 S0 4 , in cold, soluble ; on heating, C0 2 and S0 2 evolved. The Murexide Test. — Evaporate a little uric acid and dilute HN0 3 to dryness. Add few drops of ammonia to the red residue when cold ; purple coloration. Uric acid reduces Fehling's solution on prolonged boiling. Tannic (Gallo-tannic), C 14 H 10 O 9 + 2H 2 0. — Colourless, amorphous, glistening mass ; decomposes on heating ; very soluble in hot water. Can be " salted " out of solution by NaCl. Tannates are sparingly soluble in water. Action of caustic alkalis same as for gallic acid. Cone. H 2 S0 4 , on warming, dark-green coloration, and brownish-black precipitate on dilution. Neutral solutions of tannates give with — 1. Fe 2 Cl 6 , bluish-black precipitate, soluble in HC1, but reprecipitated by ammonia. 2. KCN, no coloration. 3. Tartar emetic, precipitate. 4. Pb(CH 3 COO) 2 , acidified with acetic acid, white precipitate. 5. Gelatin, greyish precipitate. 6. AgN0 3 , metallic silver. 7. NH 4 C1 and ammonia, precipitate. Gallic, C 6 H 2 (OH) 3 COOH [3.4.5.1].— Colourless, silky needles ; decom- poses on heating, giving pyrogallol and leaving charred residue ; sparingly soluble in cold water ; readily soluble in hot water, and in alcohol. Most gallates are sparingly soluble in water, and when mixed with caustic alkalis oxidise in air, giving coloured solutions. TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC!. 519 Cone. H 2 S0 4 , on warming, dark-red solution, and dark-red precipitate on dilution with water. Neutral solutions of gallates give with— 1 . Fe 2 Clg, bluish-black precipitate, soluble in excess to a green solution. The precipitate is also soluble in HC1. 2. KCN, pink coloration, which disappears on standing. 3. Pb(CH 3 C00) 2 acidified with acetic acid, no precipitate. 4. Solution of gelatin, no precipitate. 5. Fehling's solution, precipitate of Cu 2 0. 6. AgN0 3 , metallic silver. 7. NH 4 C1 and ammonia, no precipitate. Lactic, CHg.CHOH.COOH. — Syrupy liquid ; decomposes on heating, giving acetaldehyde. Neutral solutions of lactates give with — ■ 1. AgN0 3 , no precipitate. 2. ZnS0 4 , zinc salt on crystallising — star-shaped groups. 3. CaCl 2 , no precipitate. 4. KMn0 4 acidified, on warming, decoloration. Alkaloids Caffeine Quinine Cinchoninc Morphine Codeine Narcotine Strychnine Bruoine Nicotine Conine Atropine Common Types. M.P. 234° B.P. m!p. Source. Tea, coffee. 179° ) 9 ^^ 0 j Cinchona bark. 230° \ 155° ' Opium. 176° ) 268° j 168° j Strychnos nux vomica. 247° Tobacco. 167° Hemlock. 115° Deadly nightshade. Most of the alkaloids, with the exception of conine and nicotine, are crystalline solids ; they are usually insoluble or sparingly soluble in water, but being nitrogen bases they dissolve in acids, forming soluble salts, from which the base is precipitated by dilute NaOH or Na 2 C0 3 . The majority are optically active and possess a bitter astringent taste, as well as an extremely poisonous character. General Tests. — 1. Solution of iodine in KI — brown amorphous ppt. 2. Nessler's solution — white or discoloured amorphous ppt. 3. Potassium mercuric iodide — white or yellowish- white ppt. 4. Phosphomolybdic acid — light to brownish-yellow gelatinous ppt. 5. Chloroplatinic acid — yellow crystalline solid. 6. Tannic acid or picric acid in aqueous solution — precipitates almost all the alkaloids. 520 SYSTEMATIC ORGANIC CHEMISTRY Separation of the Alkaloids. — Geoup I.— Precipitated by NaHC0 3 . Morphine, cinchonine, quinine, narcotine. Group II.— Not precipitated by NaHC0 3 . Strychnine, brucine. Group III. — Liquid alkaloids, volatile in steam. Conine, nicotine. Group IV.— Alkaloids not contained in I., II., or III., but which may be extracted from alkaline solution by an organic solvent (CH.C1 3 ). Caffeine (theine), atropine, codeine, cocaine. GROUP I. Morphine, C 17 H 19 0 3 N + H 2 0.— White amorphous or crystalline sub- stance, sparingly soluble in cold water and in ether ; M.P. 230°. To colourless solution in cone. H 2 S0 4 add — 1. Cone. H 2 S0 4 containing a few drops HN0 3 — A violet coloration on standing. 2. Cone. HN0 3 — Red coloration, changing to yellow on warming. 3. Crystal of K 2 Cr 2 0 7 — Bright-green coloration. 4. One drop of formalin — Purple colour, changing to blue. To aqueous solution of salt add — 1. NaOH — Base precipitated, soluble in excess. 2. Fe 2 Cl 6 (neutral solution) — Blue coloration. 3. HI0 3 solution — Iodine liberated, test with starch. Cinchonine, C 19 H 22 ON 2 . — White powder or crystalline compound ; almost insoluble in water ; c/-rotatory ; M.P. 255°. Solutions of salts do not exhibit fluorescence. Cone. H 2 S0 4 dissolves ; becomes brown or black on heating. To aqueous solution of salt add — 1. NaOH — Base precipitated, insoluble in excess. 2. Chlorine water, and then a few drops of NH 4 OH — Light- yellow ppt. 3. K 4 Fe(CN) 6 to neutral or slightly acid solution — Yellowish-white ppt., soluble in excess on warming. Quinine, C 20 H 24 O 2 N 2 -f 3H 2 0. — White powder (anhydrous) or crystal- line compound ; sparingly soluble in water ; /-rotatory ; M.P. 177° (anhydrous) or 67° (hydrated). Dilute solutions of its salts, acidified with H 2 S0 4 , exhibit a bluish fluorescence, which is discharged by HC1. Cone. H 2 S0 4 dissolves ; turns yellow and brown on heating. To aqueous solution of salt add — 1. NaOH— white ppt. 2. Cone, chlorine water (J- its volume), and then excess of cone. NH 4 OH — Emerald green colour. 3. Chlorine water, K 4 Fe(CN) 6 and NH 4 OH — Red coloration. Quinine hydrochloride, on heating alone, assumes a violet colour, and gives off violet vapours. Narcotine, C 22 H 23 0 7 N.— White crystalline powder ; M.P. 176° ; sparingly soluble in hot water, soluble in hot alcohol and in ether ; salts react acid in solution ; /-rotatory in neutral solution, (/-rotatory in acid TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC. 521 1. Cone. H 2 S0 4 on warming, colour changes from blue- violet to red. 2. Dilute H 2 S0 4 and Mn(X, on heating and filtering, opianic acid (M.P. 150°) separates. 3. Cone. HN0 3 dissolves to yellow solution, turning orange-red on heating. 4. Cone. H 2 S0 4 and a trace of HN0 3 — Turns brown and then red. 5. Cone. H 2 S0 4 and ammonium molybdate — Green coloration changing to red. To a solution in dilute HC1 add — 1. NaOH — Base precipitated, insoluble in excess. 2. Chlorine water and NH 4 OH — Yellow-red colour. GROUP II. Strychnine, C 21 H 22 0 2 N 2 . — Colourless needles ; M.P. 268° ; sparingly soluble in water, alcohol, and ether ; very soluble in CHC1 3 ; ^-rotatoiy in alcohol. 1. Cone. H 2 S0 4 — Colourless solution (even at 100°) which gives bluish- violet to red with oxidising agents (Pb0 2 , K 2 Cr 2 0 7 , Mn0 2 ). 2. Cone. HNO3 — Colourless solution, turning yellow on heating. To solution of salt add — 1. NaOH — Base precipitated, soluble in excess of NH 4 OH. 2. K 3 Fe(CN) 6 or K 2 Cr0 4 — Yellow crystalline ppt. in neutral and fairly cone, strychnine salt solution. Brucine, C 23 H 26 0 4 N 2 + 4H 2 0. — Colourless needles or prisms ; M.P. 168° ; sparingly soluble in water, readily soluble in alcohol and in chloro- form ; [a] D = about - 120° (in CHC1 3 ). 1. Cone. H 2 S0 4 — Rose-red coloration, changing to yellow. 2. Cone. HN0 3 — Rose-pink coloration, turning yellow on heating, and turning to purple with SnCl 2 . 3. Cone. HC1, followed by dilution with water and addition of chlorine water — Red coloration, turning yellow with ammonia. To solutions of its salts add — ■ 1. KOH — Base precipitated, insoluble in excess. 2. Hg 2 (N0 3 ) 2 , to a neutral solution — Crimson colour on boiling. GROUP III. Conine, C 8 H 17 N. — Colourless, oily liquid, turning brown on exposure to air ; volatile in steam ; B.P. 167° ; readily soluble in water and organic solvents ; (^-rotatory. 1. Cone. H 2 S0 4 — Purple, and then an olive coloration. 2. Cone. HN0 3 — Blood-red coloration. 3. Phenolphthalein — Turned pink in 50% alcoholic solution, colour intensified by addition of a few drops CHC1 3 . 4. After standing for 5 minutes with alcoholic CS 2 , the mixture gives a brown ppt. with a drop of very dilute CuS0 4 . 5. Albumen — Coagulated. 522 SYSTEMATIC ORGANIC CHEMISTRY Nicotine, C 10 H 14 N 2 . — Colourless, oily liquid, turning brown on exposure to air ; volatile in steam ; B.P. 247° ; readily soluble in water and organic solvents ; /-rotatory. 1. Cone. HC1 — A light- violet or brown coloration on warming, changing to orange with cone. HN0 3 . 2. Cone. HN0 3 — Red coloration. 3. Phenolphthalein — Only coloured pink in very dilute alcohol. 4. Albumen — Not coagulated. 5. On warming 1 drop with 2 c.cs. epichlorhydrin gives a red colour. To solution of salt add — 1. Iodine in KI — Yellow precipitate disappearing after a time. 2. NaOH — Base liberated, but not precipitated. GROUP IV. Caffeine (Theine), C 8 H 10 N 4 O 2 + H 2 0.— Colourless needles ; M.P. 234° ; sparingly soluble in cold water and in alcohol, readily soluble in chloro- form ; sublimes unchanged. 1. Cone. NaOH — Decomposed and methylamine evolved. 2. Murexide test — Treat with a crystal of KC10 3 and a few drops of HC1, evaporate to dryness ; the red residue turns purple with ammonia. To aqueous solution add — 1. AgN0 3 — No precipitate. 2. Iodine in KI— A precipitate ; M.P. 215°. 3. K 4 Fe(CN) 6 and HN0 3 (iron free) — Yields Prussian blue on warming. Atropine, C 17 H 23 N0 3 . — Silky needles or prisms ; M.P. 115° ; very sparingly soluble in water, fairly soluble in ether or benzene, readily in alcohol or chloroform ; optically inactive. 1. Cone. HN0 3 — Boiled and evaporated to dryness, and residue treated with alcoholic potash ; yields violet colour, changing to red. 2. Bromine in HBr — Yellow crystalline precipitate. 3. Baryta water on evaporation to dryness — Odour of hawthorn blossom. 4. On heating to 108° becomes /-rotatory. Codeine, C 18 H 21 N0 3 . — Crystalline compound ; M.P. 155° ; moderately soluble in water, readily in alcohol or CHC1 3 , insoluble in petroleum ether ; /-rotatory. 1. H 2 S0 4 , followed by addition of a crystal of FeS0 4 — Blue colour. 2. FeCl 3 — No colour. 3. NaOH— Base insoluble. Hydrochloride ; M.P. 264°. Cocaine, C 17 H 21 N0 4 . — Colourless prisms ; M.P. 98° ; slightly soluble in water, readily in organic solvents ; /-rotatory. 1. Cone. H 2 S0 4 and a few drops of alcohol — Characteristic odour of ethyl benzoate. 2. Acids or alkalis (on heating) — Yields benzoic acid and ecgonine (M.P. 205°). 3. KMn0 4 — Violet precipitate. TESTS FOR ORGANIC ACIDS, ALKALOIDS, ETC. 523 4. K 2 Cr0 4 in presence of HC1— Yellow precipitate. 5. Aqueous iodine on solutions of salts yields — per-iodide, M.P. 161°; hydrochloride, M.P. 182°. Carbohydrates The carbohydrates are crystalline or amorphous solids which char on heating, and emit an odour of burnt sugar. They are non- volatile. Some are soluble in water, e.g., sugars ; some are insoluble, e.g., cellulose. General Test for Soluble Carbohydrates. — To a dilute solution of the carbohydrate in water 2 — 3 drops of a saturated alcoholic solution of a-naphthol is added, and 2 c.cs. of cone, sulphuric acid. A violet colora- tion is produced, which is discharged by alkali. Monosaccharoses. — (a) Pentoses, C 5 H 10 O 5 . — (1). 1 — 2 gms. of the carbo- hydrate is distilled with 10 c.cs. water and 5 c.cs. cone. HC1 ; the distillate contains furfurol, which gives a deep-red coloration on addition of a few drops of aniline and cone. HC1. (2). A deep-red colour is produced on heating with phloroglucinol and cone. HC1. Example. — Arabinose. M.P. 160° ; [a]^ 8 = + 105° ; reduces Fehling's solution ; osazone, M.P. 157°. (b) Hexoses, C 6 H 12 0 6 . — (1). Aldoses, which are identified by heating a small amount at 60° — 70° with 10 c.cs. of bromine water, boiling of the excess of bromine, and adding a little very dilute ferric chloride solution, when a deep-yellow coloration (due to the presence of a hydroxy acid) is produced. Example. — d-Glucose (Grape Sugar or Dextrose). M.P. 146° ; [a]^ 0 — + 52-6. Reduces Fehling's solution and ammoniacal silver nitrate ; osazone, M.P. 205° ; oxime, M.P. 137°. (2). Ketoses, which may be identified by warming 1 part with 0-5 part resorcinol, and a little dilute HC1 when a red coloration is produced, turning to a brown precipitate ; soluble in alcohol. Example. — d-Fructose (Fruit Sugar or Levulose). M.P. 95°; [a]^ 0 = — 95° ; reduces Fehling's solution and ammoniacal silver nitrate ; osazone M.P. 204° ; oxime, M.P. 118°. Disaccharoses, C 12 H 22 0 11 . — On hydrolysis by boiling with dilute acids yield monosaccharoses, usually hexoses. Examples. — (a) Sucrose (Cane Sugar or Saccharose). Colourless crystals ; M.P. 160° ; [a]!? = 66-5° ; does not reduce Fehling's solution ; does not form an osazone ; yields invert sugar [a]^ 0 = — 37-4° on boiling with dilute acids ; (osazone of invert sugar melts at 204°) . (b) Maltose (Malt Sugar). Hard, white crystals ; decomposes on heating ; [a]|? = + 137° ; reduces Fehling's solution and ammoniacal silver nitrate ; osazone, M.P. 206°. (c) Lactose (Milk Sugar). Hard, rhombic prisms ; M.P. 205° ; [ a ]f? = + 52-5° ; readily reduces Fehling's solution and ammoniacal silver 524 SYSTEMATIC ORGANIC CHEMISTRY nitrate ; is much less sweet than cane sugar, and also much less soluble in water ; osazone, M.P. 200°. Polysaccharoses, (C 6 H 10 O 5 )w. — Amorphous, tasteless solids, insoluble in alcohol and in ether ; a few are soluble in cold water ; on hydrolysis with dilute acids they yield carbohydrates of simpler constitution. Example. — Starch. Fine, white powder, which shows an organised structure under microscope ; insoluble in cold water, but on boiling yields a gelatinous opalescent solution ; aqueous solution yields a characteristic blue colour with iodine ; solution also yields precipitates with tannin, and with basic lead acetate ; does not reduce Fehling's solution or ammoniacal silver nitrate. On heating to about 200°, yields dextrin. ADDENDUM Preparation of Alcoholic Potash Method I. — 10 gms. of caustic .potash sticks are dissolved^ in an equal quantity of water and diluted with absolute alcohol to 400 c.cs. ~ The solution is agitated with 10 gms. of anhydrous sodium sulphate until clarified, after which the clear solution is decanted. Method II. — 15 gms. of caustic potash sticks are agitated with 500 c.cs. of 95 % alcohol at ordinary temperature until dissolved. After settling, the clear solution is decanted. When preparing the solution for analytical purposes, caustic potash " purified from alcohol " should be employed. The solution is standardised with hydrochloric acid, using phenolphthalein as indicator. INDEX A Absorbents, 33 for water, 441 Absorption (apparatus for carbon dioxide), 442 Accidents, 1 Acetaldehyde, 408, 410, 426 Acetaldehyde -ammonia, 300 Acetamide, 292, 293 Acetanilide, 296 Aceto-acetic ester, 132, 143, 153, 187, 188 Acet-p-chloranilide, 335 Acetic acid, 234, 241 tests for, 513, 516 I Acetic anhydride, 258 j Acetone,. 96, 88 (estimation of), 494 j Acetone-cyanhydrin, 151 I Acetone-etbyl-mercaptol, 388 Acetone-plienylhydrazone, 283 /Acetone-semicarbazone, 285 j Acetonitrile, 407 Acetonyl-acetone, 188 Acetophenone, 82, 84 Acetophenone-oxime, 280 \ (transformation of), 282 Acetyl chloride, 324 groups (estimation of), 476 Acetylene, 166 Acetylides, 115 Acetyl-mesitylene, 83 Acid solutions (specific gravities and concentrations), 509 Acrolein, 407 Acyl groups (estimation of), 476 Adams, 343, 417 jAir bath, 35 ^-Alanine. 395 Alcoholic potash, 235, 476, 524 .Aldehydes (estimation of), 479 Aldehyde-ammonia, 158 Aldime, 100 Aldol, 96 condensation, 95 Algol Yellow, 384 Alizarin, 193, 384 Alizarin Blue, 160 Alkaline reduction, 355 solutions (specific gravity and con- centration), 510 Alkaloids (tests for), 512, 519 ' Alkyl bromides, 328 Aluminium chloride. 55, 58, 80, 115, 498, 503 Aluminium -mercury couple, 55, 58, 175, 503 Amides, 292, 293 (estimation of), 479 4-Amido-hydroxy-benzoic acid, 354 Amines (estimation of), 475, 489 p -Amino -acetanilide, 354 2-Amino-anthraquinone, 296 Amino-azo-benzene, 418 o-Amino-benzaldehyde, 163 Amino compounds, 350 ^-Amino-dimethyl-aniline, 380 Amino -guani dine derivatives, 285 4-Amino-3-methyl-benzophenone, 156 a-Amino-/3-naphthol, 359 Amino-naphthol disulphonic acid, 307 Amino -naphthol sulphonic acid, 314 p -Amino -phenol, 203 Amino -salicvlic acid, 359 Ammonia, 499, 503 Ammonium sulphite, 508 Amyl nitrite, 251 Aniline, 350 standard solution, 488 hydrochloride, 419 hydroferrocyanide, 419 nitrate, 419 sulphate, 419 Anils, 220 Animal charcoal, 30 Anisole, 211 Anthracene, 170 (estimation of), 494 (purification of), 171 Anthracene Brown, 385 Anthranilic acid, 241, 291 AnthranoL 78, 79, 182 Anthraquinone, 77, 226 dyes, 384 Anthraquinone-/3-sulphonic acid, 307 Antipyrine, 388 526 INDEX Apparatus for the continuous re- moval of ether,. 22 Arabinose, 523 Arsanilic acid, 387 Asbestos, 29, 493 Aspirin, 386 Atropine (tests for), 522 Aur amine, 375 Autoclaves, 42 Auxochrome, 275 Azo compounds, 355, 371 Azo dyes, 372 (estimation of), 485 Azoxy compounds, 355, 371 B Bakelite, 66 Baking process, 311 Ball condenser, 31 Barbitone, 388 Barium hydroxide (standard). 472 Baths, 35 Beckmann thermometer, 467 transformation, 281. 282 Beilstein, 15 Bell-iar filtering apparatus, 30 Benzaldehyde, 219, 220, 224, 225, 391 semicarbazone, 284 Benzal-chloride, 343 Benzal-malonic acid, 109 ester, 138 Benzamide, 223, 294, 415 Benzanilide, 297 Benzanthrone, 79 Benz-anti-aldoxime, 281 Benz-syn-aldoxime, 400 Benzene-sulphinic acid, 319, 414 Benzene-sulphonic acid, 303, 316, 475 Benzene-sulphonyl-chloride, 416 Benzhydrol, 180 Benzil, 411 Benzilic acid, 105, 106 Benzidine, 155, 356 tetrazonium solution, 366 Benzoic acid, 113, 178, 232, 237 (tests for), 513, 515 Benzoic anhydride, 260 Benzoin, 97 Benzo-nitrile, 149, 150 Benzophenone, 82, 87 chloride, 323 £>-Benzoquinone, 229 dichlorimide, 420 Benzopurpurin, 373 Benzoyl-acetone, 91 Benzoyl-aceto-acetic ester, 136 o-Benzoyl-benzoic acid, 115 Benzoyl' chloride, 324, 348 Benzoyl-p-toluidine, 297 Benzpinacone, 66 Benzyl-aceto -acetic ester, 136 Benzyl alcohol, 178, 194 Benzyl -benzoate, 257 Benzyl-brom-malonic acid, 433 Benzyl -chloride, 344 Benzyl -cyanide, 147 Benzyl -malonic acid, 235 Benzylidine-acetone, 93 Benzylidine-acetophenone, 94 Benzylidine-aniline, 299 Bi-diphenylene ethane, 51 Bindschedler's Green, 381 Boiling point (determination of), 18, 19 of salt solutions, 35 Bomb furnace, 40 Borneol, 393 Brilliant yellow paper, 501 Brom -acetic acid, 337 n-Brom-allocinnamic acid, 399, 411 m-Brom-benzoic acid, 345 a-Brom-cinnamic acid, 399, 411 Bromine, 502 j)-Brom-dimethyl aniline, 347 a-Brom-naphthalene, 346 p-Bromophenol, 343 Brom-succinic acid, 337 a-Brom-stearic acid, 336 o -Brom -toluene, 339 Brucine (tests for), 521 Bucherer, 152 Buchner funnel, 29 Bumping, 19, 26 Butyl alcohol (tertiary), 69 Butyric acid, 403 C Caffeine, 394 (tests for), 522 Calcium phosphate (use of), 30 Camphor-aldehyde, 90, 91 Camphor -oxime, 280 Camphor -quinone, 222 d-Camphor-sulphonic acid, 304 Cane sugar (estimation of), 496 Cannizarro, 178 Capillary tube, 15 Carbamide, 429 Carbinol base, 376, 377 Carbon to carbon (linking of), 48 Carbon (detection of), 435 disulphide, 1 INDEX 527 Carbon and hydrogen (estimation of), 438 Carbonyl chloride, 83, 509 Carbohydrates (tests for), 512, 523 o-Carboxy - phenamino - acetonitrile, 153 (Jarius, 458 Carron oil, 1 Catalytic preparations (apparatus for), 46 Catechol, 201 Caustic soda, 499 Cautions, 1 Cerium dioxide, 225, 447 Chlor-acetic acid, 348 Chloral, 348 Chi oral -for mamide, 386 Chloral -hydrate, 348 Chloramiiie-T, 387 Chloranil, 229, 336 Chlor-benzene, 339, 342 Chlorhy drins, 216 Chlorine, 502 Chlor-malonic acid, 338 Chlor-nitro -benzene, 158 Chloroform, 427 m-Chloro-j9-hydroxy-benzyl alcohol, 194 Chlorosulphonic acid, 309, 507 jt?-Chlor-toluene, 339 Chromic anhydride, 509 Chro mo gen, 275 Chromophore, 275 Chromyl chloride, 224, 509 Chryso'idine, 370, 373, 374 Cinchona bark, 394 Cinchonine (tests for), 520 Cinnamic acid, 107, 109 Cinnamic acid-dibromide, 332 Cinnamic -aldehyde, 93 Cinnamic -anhydride, 255 Citraconic acid, 236 Citraconic-anhydride, 406 Citric acid (tests for), 513, 514 Claisen flask, 25 Claisen, 90, 95, 140 Cocaine (tests for), 522 Codeine (tests for), 522 Collidine, 404 Collodion, 25 Columns (fractionating), 21 Combustions, 438 Combustion of Carbon and hydrogen (notes on), j 446 Volatile and hygroscopic sub- 1 stances, 447 Cojmbustion tube and furnace, 440 Conant, 373 | Condenser (air), 19 ! Congo red, 373 paper, 501 Conine (tests for), 521 Constant boiling mixtures, 21, 22 Continuous steam distillation, 24 Control tests, 23 Cooling mixtures, 10 | Copper-benzoyl-acetone, 92 Copper bronze, 499 powder, 60, 61, 239, 339, 504 (reduced), 410 Copper-zinc couple, 175, 503 | Corks (boring of), 7 (softening of), 7 Corrected boiling points, 20 melting points, 17. Corrections (boiling point), 20 (melting point), 17 Costing (notes on), 5 Coupling, 275, 490 Cresols, 199 Croton-aldehyde, 93 Crystallisation, 7 (by cooling), 8 (by evaporation), 11 (special methods), 12 (fractional), 12 Crystals (separation of), 11 Gumming, 478 Cupferron, 416 Cuprous bromide, 504 chloride, 339, 504 Cyanhy drins, 150 Cyanic acid (tests for), 513, 516 Cyanogen, 222 Cystine, 396 D Decolorisation, 30 (use of calcium phosphate), 30 (use of SG 2 ), 30 Decomposition reactions, 403 Dehydracetic acid, 127 Dehydrogenation of primary alcohols, 409 Dehydrothiotoluidine, 318 Denige's reagent, 493 Density of liquids, 43 Desiccators, 11, 33 Detection of elements, 435 Diacet-o-toluidide, 298 Diacetoxy-anthracene, 253 528 INDEX Diamino-anthraquinone, 384 Diamino-stilbene disulphonic acid, 354 Diary 1 -methane dyes, 374 Diazoaminobenzene, 367 Diazobenzene nitrate, 368 perbromide, 369 sulphate, 368 sulphonic acid, 433 Diazomethane, 434 Diazonium compounds, 174, 275, 320, 363, 365 in solution, 366 (reactions of), 369 (stable), 366 Diazotisation, 365 (end point), 365, 487 Dibenzanilides, 156 Dibenzyl, 51, 60 2.6-Dibromaniline, 413 Dibrom -succinic acid, 346 Dibrom-sulphanilic acid, 342 Dichlor-cinnamic acid, 333 Dichlor-nitraniline (2.6.4), 335 2.6-Dichlor-uric acid, 325 Dicyano-quinol, 154 Dieithyl-acetal, 215 Diethyl-acetosuccinate, 145 Diethyl-adipate, 393 Diethyl-aniline, 298 Diethyl-collidine dicarboxylate, 403 Diethyl -dihydro collidine dicarboxyl- ate, 159 Diethyl -ether, 208 Diethyl-malonate, 251 Diethyl-tartrate, 248, 250 ^p-^'-Dihydroxy-diphenyl, 200 a-Diketones, 105, 221 1.3-Diketones, 91 Dimethyl - amino - azobenzene sul- phate, 307 Dimethyl-aniline, 298 Dimethyl-benzophenone, 83 Dimethyl-benzyl -phenyl - ammonium chloride, 286 Dimethyl -cellulose, 213 Dimethyl -cyclohexenone, 77, 412 Dimethvl-oxalate, 246 Dimethyl-sulphate, 63, 64, 211, 254 Dimethyl terephthalate, 255 Dimethyl-o-toluidine, 287 a-a-Dinaphthol, 73 ^-^-Dinaphthol, 73 ^-/y-Dinaphthylamine, 430 Dinitro -aniline, diazonium solution, 367 Dinitro-anthraquinone (1.5 and 1.8), 271 | 2 : 4-Dinitro-benzaldehyde, 221 1 m-Dinitro-benzene, 265 I 2. 2 , -Dinitro -benzidine, 271 Dinitro -chlorbenzene, 266 Dinitro -diphenyl, 158 Dinitro -methylaniline, 261 Dinitro -phenol, 198 Dinitro -stilbene disulphonic acid, 314 Dipentene, 412 Dipentene -hydrochloride, 334 Diphenyl, 48, 60, 61, 175 Diphenyl-acetic acid, 186 Diphenylamine, 289, 290 Di phenyl -chloracetic acid, 326 Diphenyl -dihydro anthracene, 57 . Diphenyl -disulphide, 421 Diphenyl -iodonium iodide, 421, 422 Diphenylmethane, 52, 58, 172 Diphenyl-methyl ethylene, 62 Disaccharoses, 223 Disacryl, 407 Distillation, 12, 18 dry, 24 fractional, 20, 26 in current of gas or under reduced pressure, 27 of small quantities, 19, 20 steam, 22 vacuum, 24 Distribution coefficient, 32 Drugs, 386 Drying of liquids, 34 solids, 33 Dvfton, 22 Dnlcitoi, 179 Dumas, 450 Dyes, 372 E Elytrolytic preparations, 391 Eosin, 378 Equivalent of a base (determination of), 474 Equivalent of an acid (determination of), 472 Esters (estimation of), 479 Estimation of acetone, 494 acetyl derivatives, 476 acyl derivatives, 476 aldehydes, 479 amides, 479 amines, 489 anthracene, 494 azo dyes, 485 bromine {Robertson), 461 INDEX 529 Estimation of — continued. carbon and hydrogen, 438 chlorine (Robertson), 461 dye-leuco compounds, 486 enol-rnodification, 493 esters, 479 formaldehyde, 480 glucose and cane sugar, 496 1 H acid, 490 halogens, 458 halogens and sulphur (simultane- ously), 464 hydro xyl groups, 475 metallic radicles, 449 methoxyl and ethoxyl groups, 476 nitro compounds, 483 nitrogen, 450, 455, 456 nitroso compounds, 484 phenolic compounds, 490 ^-phenylene-diamine, 492 primary and secondary amines, 475 sulphur, 463 thiophen in benzene, 493 Etard, 224 Ether, 208 (apparatus for removal of), 32 (extraction with), 32 (purification of). 209 Ethers, 208 Ethyl-acetate, 249, 254 Ethyl-acetoacetic ester, 135 Ethyl-acrylate, 393 Ethyl-alcohol (purification of), 206 Ethyl-argento -cyanide, 290 Ethyl-benzene, 59 Ethyl-benzoate, 250 Ethyl-bromide, 328 Ethyl-chloride, 330 Ethyl-cinnamate, 138 Ethyl-cyanide, 147 Ethyl-ether, 208 Ethyl-iodide, 330 Ethyl-hydrogen-tartrate, 247 Ethyl-isocyanide, 290 Ethyl-malonic acid, 234 Ethyl-malonic ester, 132 E^tyl-niercaptan, 321 Ethyl -nitrate, 247 Ethyl-nitrite, 274 Ethyl-orthoformate, 210 Ethyl -potassium sulphate, 417 Eth> lene, 406 Eth-'^ne-dibromide, 332 Eth^ne-dichloride, 334 Eth^iene-dicyanide, 146 Ethylene-glycol, 195 Ethfylidene-bis-acetoacetic ester, 139 Extraction of solids, 31 Extraction with ether, 32 s.o.c. F I'Y.h ling's solution, 496 Feist, 127 Filter (hot water), 10 (steam jacket), 10 Filtration, 9, 28 Filtration of corrosive liquids, 29 small quantities, 29 Findlay, 45 Fire (cautions), 1 Fischer, 164 Fittig, 58, 65, 238 Fluorescein, 378 Formaldehyde (estimation of), 480 Formamide, 293 Formic acid (tests for), 513, 515 Fractional crystallisation, 12 distillation, 20, 26 liquefaction and evaporation, 176 Fractionating columns, 21 Franldand-Duppa, 130 Freezing point method for molecular weights, 466 Friedel-Crafts, 54, 56, 80, 84, 115 Friend, 13 d-Fructose, 523 Funnel (Buchner), 29 (hot water), 10 (ice), 11 (steam), 10 Furfurol, 398 Fusion pot, 204 Gallic acid, 385 tests for, 513, 518 Gattermann, 100, 150, 319, 339 Gattermann-Koch, 85 Geissler, 442 a-d-Glucoheptonic acid, 123 a-Grlucoheptose, 184 Gluconic acid, 243 Glucosamine hydrochloride, 397 Glucosazone, 283 d-Glucose, 223, 523 (estimation of), 496 Glutaric acid, 413 Glyceric acid, 242 (Pb and Ca salts), 424 Glycerol (dehydration of), 327 Glycine, 431 anhydride, 432 M M 530 INDEX Grlycocoll ester, 432 Grlycocoll -ester hydrochloride, 395 Glycollic acid, 122, 195 Grignard, 61, 62, 63, 67, 70, 89, 112 " 128, 173 reageni (preparation of), 68 H H acid, 307 diazonium solution, 367 (estimation of), 490 Halogen compounds, 175, 190 Halogens (Beil stein's test), 436 carriers, 341 (detection of), 435 (estimation of), 458 Hanizsch, 158 Hard glass tubing (cutting of), 440 Heating under pressure, 38 Helianthin, 372 Hexahydrobenzene, 167 Hexahydrophenol, 169 Hexamethylene tetramine, 300 Hints, 3 Hippuric acid (tests for), 518 Hippuryl chloride, 324 Hofmann, 291 Hydracetyl-acetone, 97 Hydration of unsaturated hydro- carbons, 426 Hydrazines, 363 Hydrazobenzene, 356 Hydrazo -compounds, 355, 371 Hydriodic acid, 477, 498, 502 Hydrobenzamide, 300 Hydrobenzoin, 181 Hydrobromic acid, 502 Hydrochloric acid, 502 Hydrocinnamic acid, 185 Hydrocyanic acid (tests for), 513, 516 Hydroferricyanic acid (tests for), 513, 517 Hydroferrocyanic acid (tests for), 513, 517 Hydrogen compounds, 166 Hydrogen (detection of), 435 Hydrogenation of benzene, 168 Hydroxy acids, 186 aldehydes, 184 Hydroxy -benzaldehyde, 99 m-Hydroxy -benzoic acid, 200 o-Hydroxy-benzoic acid, 111 p-Hydroxy-benzoic acid, 240 o- and ^>-Hydroxy-benzyl alcohols, 67 Hydroxy compounds, 65, 178, 193 Hydroxy-oxy compounds, 232 Hydroxy -methylene-camphor, 90 l-Hydroxy-4-naphthalene sulphonic acid, 202 Hydroxylamines, 363 Hydroxyl groups (estimation of), 475 I Imides, 292, 293 Indigo, 382 Indoxyl, 383 Inorganic preparations, 502 et seq. Iod-acetic acid, 340 2.4.1-Iod-nitraniline, 338 Iodoform, 391, 428 j9-Iod-toluene, 340 /3-Iodo-propionic acid, 326 Iodosobenzene, 421 acetate, 422 Iodoxy-benzene, 422 Ionone, 76 (pseudo), 93 Iron filings, 499 Irone, 76 Iso-cyanides, 290 Iso-nitroso camphor, 222 Iso-propyl iodide, 190, 328 K Ketenes, 127 Ketimine, 103 Keto-enol tautomerism (estimation of), 493 Kjeldahl, 456 Knecht and Hibbert, 486 Knoevenegal, 152 Kolbe, 110 Kriiger, 76 L Lactic acid (tests for), 519 Lactones, 184 Lactose, 523 «< Lead acetate paper, 501 Lead peroxide, 504 (evaluation of), 504 Lederer-Manasse, 66, 106 Lens (use of), 13 Leucine, 152 Leuco base, 376, 377, 383 Leucyl -glycine, 288 Lexicon (Richter), 3 Library (use of), 3 Liebig, 95 INDEX 531 Liquids, inflammable (distillation of), 19 Litmus i>aper, 500 M Magenta, 375 Malachite Green, 377 Malic acid, 513, 514 Malonic acid, 119 Maltose, 523 Mandelic acid (resolution of), 400 Mandelonitrile, 151 Mannitol-dibenzoate, 265 Mannitol-hexacetate, 252 Manometer, 25 Mechanical agitation, 37 Melting point (baths), 16 (determination), 15 (mixed), 17 (of alloys), 36 tubes, 15 Menthene, 411 Menthyl chloride, 327 Merc apt ans, 321 Mercuric chloride, 84 Mercury vapour lamp, 345 Mesaconic acid, 399 Mesityl oxide, 93 i)[esitylene, 53 Mesitylenic acid, 238 Metal baths, 36 Metallic radicals (detection of), 437 (estimation of), 449 Metanilic acid, 353 Methane, 175 w-Methoxy-resacetophenone, 104 Methyl-alcohol, 392 (purification of), 206 Methylamine hydrochloride, 429 Methyl -aniline, 287 Methyl-benzoate, 254, 255 Methyl -celluloses, 213 Methyl -cyanide, 148 Methyl-ethyl-acetic acid, 188 Methyl-ethyl-ketone, 187 o-Methyl-glucoside, 214 Methyl -hydrogen succinate, 252 Methyl-iodide, 330 Methyl-ketol, 164 Methyl- Orange, 372, 501 Methyl -propyl -ketone, 187 Methyl-Red, 372, 502 Methyl -trinitro-benzoate, 256 Methylene Blue, 380 '(zinc free), 381 Methylene-dimalonic ester, 139 Met li.ylene (irccn, 382 Methylene-iodide, 191 Michler's ketone, 81 Microscope (use of), L3 Miscellaneous reactions, 415 Mixed acid, 262 (analysis of), 263 Mixed melting points, I 7 Mixtures (cooling), 10 Molecular weights (determination of), 465 Mono-brom-acetic acid, 337 Mono-brom-succinic acid, 337 Mono-chlor-acetic acid, 348 Mono-chlor-malonic acid, 338 Morphine (tests for), 520 Mucic acid, 244 N /3-Naphthalene-sulpho -glycine, 423 Naphthalene-/3-sulphonic acid, 304 Naphthalene -sulphonylchloride, 417 Naphthalene -1.4 -sulpho -sulphinic acid, 319 n-Naphthaquinone, 227, 230 /3-Naphthaquinone, 230 Naphthionic acid, 312 a -Naphthoic acid, 233 a-Naphthol, 202 /3-Naphthol, 204 Naphthol Yellow S, 379 #-Naphthyl-acetate, 252 a-Naphthylamine, 352 /3-Naphthylamine, 295 /^-Naphthyl-methyl-ether, 212 Narcotine (tests for), 520 Natural sources (products from), 394 Neutral reduction, 363 Nevile and Winther's acid, 202 Nickel catalyst (preparation of), 167 Nicotine (tests for), 522 m-Nitraniline, 358 ^-Nitraniline, 268 diazonium solution, 367 Nitration, 262 (rules of), 263 Nitric acid, 498 fuming, 508 Nitriles, 149, 150, 154, 232 ^p-Nitro-acetanilide, 268 o- and j9-Nitro-anisole, 420 m-Nitro-benzaldehyde, 270 Nitrobenzene, 265, 273 m-sulphonic acid, 306 o-Nitro-benzoyl chloride, 325 j9-Nitro -benzyl bromide, 344 Nitro compounds, 261 (isolation of), 264 532 INDEX Nitro dyes, 379 Nitro -ethane, 274 4-Nitro-3-hydroxy-benzoic acid, 262 Nitro -methane, 273 Nitro -methylene Blue, 382 a -Nitro -naphthalene, 267 />- Nitro -phenetole, 355 o- and ;p-Nitro -phenetole, 420 o- and ^-Nitro -phenol, 270, 272 p -Nitro -phenylhydrazine, 363 o -Nitro -quinoline, 161 ra-Nitro -salicylic acid, 272 o- and f -Nitro -toluene, 266 w-Nitro-toluidine, 269 Nitrogen compounds, 146 (detection of), 433 (estimation of), 450, 456 (notes on), 455 Nitroso -benzene, 418 iso-Nitroso-camphor, 222 Nitroso-compounds, 360 ^-Nitroso-dimethylaniline, 278, 380 p -Nitroso -methylaniline, 278 Nitroso -methylnrethane, 434 Nitroso -p-naphthol, 277 p-Nitroso -phenol, 277 Nitrous fumes, 271, 509 Noyes and Warfel, 22 0 Oil bath, 36 Oleic acid, 398 Oleum, 305 (estimation of), 305 of given strength, 306 Orange I., 374 Orange II., 374 Organic acids (tests for), 512 Oxalic acid, 237 (anhydrous), 246 (tests for), 513 Oxamide, 222 Oxide compounds, 208 Oxide-oxy compounds. 126, 246 Oximes, 279, 360 (Beckmann's transformation of), 281, 282 Oxy-compounds, 74, 219 Oxy- and hydroxy-oxy-compounds, 183 Oxygen, 438, 447 P Paracetaldehyde, 216, 427 Paraldehyde, 216 Para-rosaniline hydrochloride, 376 Perlan, 54, 107, 477 Phenacetin, 389 Phenanthraquinone, 227 Phenazone, 388 ?>-Phenetidine, 355 Phenetole, 209 Phenol, 199, 204, 369 Phenol-phthalein, 100, 500 Phenols, 170 Phenoquinone, 218 Phenyl-acetic acid, $73 r-Phenylalanine, 432 Phenyl -benzo ate, 255 #-Phenyl-/3-brompropionic acid, 333 Phenyl diazonium solution, 366 (standard), 489 Phenyl-dihydroxy -propionic acid, 205 a-Phenylethylamine, 14, 360 carbamate, 362 resolution of, 401 Phenyl -glycine, 430 Phenyl-glycine-o-carboxylic acid, 289, 383, 431 Phenyl-hydrazine, 364 Phenyl -hydrazine -f>-sulphonic acid, 313 Phenyl -hydrazone of ^-mannose, 420 Phenyl-hydrazone of pyruvic acid, 283 \ Phenyl-hydrazones, 282 v Phenyl-hydroxylamine, 203, 363 Phenyl iodide dichloride, 423 Phenyl-isothiocyanate, 405 Pheiiyl-methyl-carbinol, 68, 180 l-Plienyl-3-methyl -pyrazolone, 284 Phenyl-^-naphthylamine, 430 Phenyl-sulpho -propionic acid, 315 m-Phenylene-diamine, 352 sulphonic acid, 313 39-Phenylene- diamine, 353, 392 (estimation of), 492 Phosgene, 509 Phosphoric acid, 498 Phosphorous (detection of), 435 Phosphorus di -iodide, 507 trisulphide, 507 Phthaleins, 100 Phthalic acid, 240 iso-Phthalaldehyde, 225 Phthalic anhydride, 258 Phthalimide, 279, 294 potassium salt, 420 Picramic acid, 358 Picric acid, 267 Pinacoline transformation, 74 Pinacones, 50, 65, 74 Piperic acid, 108 INDEX 533 Piperonyl acrolein, 93 Pirn and Scliiff, 460 Platinichloride of bases, 474 Poison (cautions), 1 Polari meter, 44 Polysnlphides, 316 Potash bulbs, 442 Potassium collidino-dicarboxylate, 235 phthalimide, 420 xanthate, 320 Preparations (lists of), 4 Primuline, 317, 382 a-a-Propenyl-dichlorhydrin, 327 Propenyl tribromide, 341 Propionic acid, 112 Pumps, 27 Pyridine methiodide, 286 Pyrogallol, 403 trimethyl ether, 212 Pyrone and phthalein dyes, 378 PyTonines, 101 Pyruvic acid, 408 Q Quaternary ammonium compounds, 286 Quinaldine, 163, 164 Quinhydrone, 181, 217, 218 Quinine sulphate, 394 (tests for), 520 Quinizarin, 102 Quinol, 181, 200, 229, 418 Quinoline, 160, 161, 163 Quinones, 154, 170, 181, 227, 228 K R-salt (standard solution), 489 Baoult, 465, 466 Reactions (scheme of arrangement), 2 Reagents (approximate concentration of), 500 Receiver for distillation in a current of gas or under reduced pressure, 27 Receivers for fractional distillation, 25, 26 Reduction in acid solution. 350 alkaline solution, 355 neutral solution, 363 Reduction of jazo compounds, 359 pximes, 360 Reflux condenser, 206 Eeformatsky, 128 Reimer-Tiemann, 98, 117 Beychler's acid, 304 Richter, 4, 15 Robertson, 461 Rubber stoppers, % ■>., 25 S 8 abatier- Sender ens , 167 Saccharic acid, 243 Saccharin, 309 Salicylaldehyde, 99, 183 Salicvlic acid, 111 (tests for), 513, 517 Salting out, 30 Sand bath, 36 Sandmeyer, 149, 273, 338 Scheme of arrangement of reactions, 2 Schiff's azotometer, 451 Sehmitt, 110 Schotten-Baumami, 253, 296, 297 Sealed tubes, 38, 458 Sealing glass tubes, 38, 40 Seeding, 8, 9 Semi-carbazones, 284 Semi dine, 155 Semi-oxamazones, 285 8 enter, 23 Separating funnels, 31 Separation by extraction, 32 Separation of immiscible liquids, 31 Setting-point, 17 Silver nitrite, 505 salt, 307 salts of acids, 473 Skraup, 159 Smith, 22 Sodamide, 91, 140, 506 Sodium (granulated), 506 (weighing of), 505 Sodium acetate (anhydrous), 506 amalgam, 505 benzylate, 257 bisulphite, 499, 506 ethylate, 91. 505 hypochlorite, 499, 508 * hyposulphite, 508 nitrite, 498 (standard solution), 487 press, 505 residues, 2 sulphide, 499 (evaluation of), 508 Solution (preparation of), 9 534 INDEX Solvent (selection of), 8 Soxhlet, 12, 31 Specific gravities of solutions, 509, 510, 511 Specific rotation, 45 Spotting, 489 Sprengel pyknometer, 44 Stannous chloride, 499 Starch, 524 iodide paper, 501 Steam distillation, 23, 351 (continuous), 24 (superheated), 23 Stelzner, 15 Stereochemical reactions, 399 Still-heads, 21 Stoppers (removing fixed), 7 Strecker, 152 Strychnine (tests for), 521 Sublimation, 28 Succinic acid, 119, 186 (tests for), 513, 515 Succinic anhydride, 259 Succinimide, 292 Sucrose, 523 Sudan dyes, 370 Sulphanilic acid, 31 l x Sulphinic acids, 318 Sulphonal, 388 Sulphonation apparatus, 38, 303 Sulphone, 303, 322 Sulphonic acids, 302 (isolation of), 302 Sulphonic group (reactions of ), 316 Sulphur (detection of), 435 (estimation of), 463 monochloride, 327, 507 Sulphuric acid, 498 Sulphuryl chloride, 338 T Tannic acid (tests for), 513, 518 Tartaric acid (tests for), 513, 518 Technical products, 6 Terephthalic acid, 239 Tertiary butyl alcohol, 69 Test papers, 500 Tetra-brom-diphenylamine, 345 Tetra-chlor-ethane, 117 Tetra-methyl-diamino-di phenyl me thane, 375 3 : 5 : 3' : 5 , -Tetramethy]-2-2 / -di]i.v(h - oxy-diphenyl methane, 67 o-^-o'-^Z-Tetra-nitro-diphenyl, 157 Tetranitro -methane, 274 Theine, 394 (tests for), 522 Thermo-couple, 46 Thermometers (choice of), 15 standardising, 17, 20 Thianthren, 425 Thiazine dyes, 380 Thiazole paper, 501 Thio -acetic acid, 322 Thio-carbanilide, 430 Thio-cyanic acid (tests for),, 513, 517 Thio-diphenylamine, 317 Thio -ethers, \322 Thionyl chloride, 323 Thiophen, 404 (estimation of), 493 Thio -phenol, 424 (Hg and Pb salts), 424 Thio -salicylic acid, 320, 321 Thio -urea, 428 Thioxene, 405 Tiemann, 76 ; 152 Titanous chloride standard solution, 482, 499 Titherley, 22. o-Tolidine, 357 tetrazonium solution, 366 Toluene bath, 35 Toluene-o-sulphonamide, 310 Toluene-^ -sulphonamide, 387 o- and 17-Toluene sulphonic acids, 3 04 (separation of), 305 Toluene-o -sulphonyl chloride. 305, 309 Toluene -sulphonyl chloride, 3Cf5, 387 p-Toluic acid, 233 o- and ^-Toluidine, 351 (separation of), 351 o-Toluidine (separation of pure), 3£>2 j9-Tomnitrile, 149, 150 2 -j9-Toluoyl -benzoic acid, 116 p-Tolyl-aldehyde, 85 Triaryl methane dyes, 324 Tribrom-ethane, 195 s-Tribromo -benzene, 174 Tribromophenol, 347 Tribrom-s-xylenol, 347 Tricarballylic acid, 120 Trichlorar 349 Trimethy. vse, 213 Trimethyl-etliylene, 405 Trimethyl-/3-naphthyl-ammonium iodide, 286 Triphenyl- acetic acid, 114 Triphenyl-benzene, 54 Triphenvl-carbinol, 70, 71, 193 INDEX jTriphenyl-chlormethane, 425 fTriphenyl-methane, 55, 173 Tube capillary, 15 furnace, 40 U | Ultra-violet rays, 333 Urea. 429 Uric acid (tests for), 518 Uvitic acid, 238 V Vacuum distillation, 24 Vapour density method, 465 pressures, 511 Veronal, 388 Victor' Meyer, 465 Volhard, 429 W Walker, 22 Water baths, 35 trap, 25 Wurtz, 58 X Xanthones, 126 ^-Xylene, 63 s-Xylenol, 412 Y Young, 22 Z ZeiseL 476 Zinc alkyl, 64, 71, 90 ammonium chloride, 503 chloride ( anhydrous ), 506 Zinc -copper couple, 175, 503 Zinc dust, 499 (evaluation of), 506 PRINTED IN GREAT BRITAIN BY THE WHITEFRIARS PRESS, LTD., LONDON AND TONBRIDGE. 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