THE PREPARATION OF ORGANIC COMPOUNDS BY E. DE BARRY BARNETT B.Sc.(Lond.) A.I.C. WITH 50 ILLUSTRATIONS PHILADELPHIA P. BLAKISTON'S SON & CO. 1012 WALNUT STREET 1912 Printed in Great Britain PREFACE IN the present volume the Author has aimed at giving a general outline of the methods actually employed in preparing organic compounds, and thus providing not only a laboratory manual, but also a book which may be used as a companion volume to the usual theoretical text -books. In the first chapter will be found a short description of the most common apparatus and reagents u'sed in preparative organic work ; and although some of the apparatus described may be regarded as rather crude for academic practice, it must be borne in mind that the average works laboratory, at all events in this country, is not fitted with all the latest refinements, and that one of the chief difficulties experienced by the young chemist on first entering works is to adapt himself to his environment. Although to some minds the idea of carrying out chemical preparations in sauce- pans, jam-pots, &c., may seem rather bizarre, experience will show that such apparatus is quite as satisfactory and considerably less expensive than the more con- ventional and more brittle beakers and basins. The description of the processes given is less full than in most books on organic preparations, but the details given are sufficient to enable the average student to carry out the preparations successfully, without being so exhaustive as to reduce his work to mere 281596 vi PREFACE mechanical routine. The book is not intended for those who are endeavouring to study chemistry by correspondence lessons, and those working in a univer- sity or technical college laboratory can usually refer to a senior student or to a member of the staff when in difficulties. The nomenclature used is, in most cases, the same as that employed in Beilstein's " Handbuch." In cyclic compounds the substituent with the lowest molecular weight is placed at i. In calculating the molecular weight of groups, NHR and NR 2 are regarded as equivalent to NH 2 , OR is regarded as equivalent to OH, COOR as equivalent to COOH, and so on, where R is an organic radical, halogen atom, &c. Thus C 6 H 3 [i]CH 3 [3]NO 2 [4]OH is 3. nitro- ^-cresol, C 6 H 3 [i]NMe 2 [2]OH[4]NO is 2. oxy-#-nitroso- dimethylaniline. A full description of this system will be found in the introduction to vol. i of Beilstein's " Handbuch." A considerable number of the preparations have been taken from the patent literature, and by this means it is hoped to familiarise the academic chemist with a much neglected branch of the literature. German specifications are more readily accessible than English, and will be found in Friedlander's " Fortschritte der Teerfarben-fabrikation," vols. i-ix, 1877-1910, or in Winther's " Patente der Organischen Chemie," vols. i-iii, 1877-1905. Abstracts of the more recent patents will be found in the " Chemisettes -Zentralblatt," the " Journal of the Chemical Society," and in the various technical publications. The Author wishes to acknowledge his indebtedness to the classical works of Lassar-Cohn (" Arbeit s- methoden ") and Theodor Weyl (" Methoden der PREFACE vi organischen Chemie "), and to express the hope that this small volume may be the means of causing their treatises to be better known in this country. Where other authorities have been consulted, an acknowledg- ment will be found in the footnotes. The Author also wishes to express his thanks to Mr. A. M. Hutchison, B.Sc., Mr. H. J. Page, B.Sc., and to Mr. W. G. Prescott, B.Sc., A.I.C., for much valuable help while the book was passing through the press. His thanks are also due to Messrs. Baird and Tatlock for kindly lending some of the blocks used for the illustrations. E. DE BARRY BARNETT 9 COLLINGHAM ROAD, S.W. CONTENTS CHAPTER I APPARATUS, METHODS OF MANIPULATION, REAGENTS APPARATUS PAGE Flasks ! Basins 2 Beakers Dropping funnels Condensers ^ Stirring ? Baths g Freezing mixtures 3 Filtration 3 Vacuum pumps I r Work under pressure ! l MANIPULATION Solvents and crystallisation I e Drying solids 2 j Extracting liquids 2I Distillation 22 Sublimation 2 - Melting-points 2 3 Boiling-points 2 p REAGENTS Sulphuric acid 3O Hydrochloric acid 30 Nitric acid Ammonia -j Caustic soda |j Aluminium chloride Cuprous chloride ^ : Cuprous bromide ^ 2 Sodium ethoxide , ~ Test-papers || ix x CONTENTS CHAPTER II THE HYDROCARBONS (i ) From the halogen compounds FAGE (a) Retrogressive substitution 35 (b) Action of metals 35 (c) Loss of halogen acid 3 8 (ii) From the alcohols (a) Loss of water 39 (6) Reduction 4i (iii) From the aldehydes and ketones 4 1 (iv) From the unsaturated compounds 4 2 (v) By Friedel-Craft's reaction 42 (vi) From the diazo-salts (a) By replacing the diazo-group by hydrogen 44 (6) By the linking of the aryl residues 45 (vii) From the carboxylic acids 46 (viii) From the lower hydrocarbons by oxidation 47 CHAPTER III THE HALOGEN COMPOUNDS (i) By the replacement of hydrogen by halogen (a) Molecular halogen 49 (b) Nascent halogen 54 (c) Halogen compounds (1) Phosphorus halides 56 (2) Sulphur halides 57 (3) Antimony pentachloride 59 (4) Sulphuryl chloride 59 (5) Iodine chloride 60 (6) Bleaching powder 61 (ii) By the addition of halogen or halogen acid (a) Addition of halogen 61 (b) Addition of halogen acid 63 (iii) By the replacement of oxygen or hydroxyl by halogen (1) Phosphorus pentachloride 64 (2) Phosphorus oxy chloride 66 (3) Phosphorus trichloride 68 (4) Halogen acid 69 (5) Thionyl chloride 71 (6) Sulphuryl chloride 73 (7) Chlorsulphonic acid 73 (8) Benzene sulphochloride 74 (9) Carbonyl chloride 74 (iv) By the replacement of the diazo-group by halogen (a) Method of Griess 74 (b) Method of Sandmeyer 75 (c) Method of Gattermann 75 CONTENTS xi ADDENDA PAGE Chloroform 78 lodoaryldichlorides 78 Replacement of chlorine or iodine by bromine 76 Replacement of bromine or iodine by chlorine 79 Replacement of chlorine or bromine by iodine 80 Phosgene 80 CHAPTER IV THE ALCOHOLS, PHENOLS, AND MERCAPTANS A. THE ALCOHOLS AND PHENOLS (i) By the hydrolysis of the esters 82 (ii ) From the halogen compounds 82 (iii) From the sulphonic acids 85 (iv) By Grignard's reaction 85 (v) From the amines 88 (vi) By the reduction of the aldehydes and ketones 91 (vii) From the unsaturated compounds 96 (viii) From the aldehydes by condensation (a) Aldol condensation 97 (b) Benzoin condensation 97 (c) Lederer-Manasse condensation 97 (d) Diaryl-carbinol synthesis 100 (ix) From the hydrocarbons by oxidation 101 (x) From the quinones by the addition of phenols 102 (xi) By the rearrangement of the a-diketones 104 B. THE MERCAPTANS 104 CHAPTER V THE ALDEHYDES, KETONES, QUINONES (AND QUINONE- IMIDES), AND SOME DERIVATIVES OF THE SAME A. THE ALDEHYDES (i) By the oxidation of primary alcohols 109 (ii) By the oxidation of aromatic hydrocarbons 1 i ) Chromyl chloride 112 (2 ) Chromic acid 112 (3) Cerium dioxide 113 (4) Indirect oxidation 114 (iii) By the reduction of the acids 1 16 (iv) By the aldol condensation 117 (v) By condensation with ethyl formate 1 1 9 (vi) By the replacement of hydrogen by CHO 120 B. THE KETONES (i) From the acids 122 (ii) By the oxidation of the alcohols 123 (iii) By the oxidation of the methylene group 126 xii CONTENTS PAGE KETONES continued (iv) By Friedel-Craft's reaction 127 (v) From phthalic anhydride 129 (vi) By the hydrolysis of the t'so-nitroso compounds 1 30 (vii) By the benzoin condensation 13 (viii) By Claisen's reaction (acetoacetic-ester synthesis) 131 C. THE QUINONES By the oxidation of (a) Hydrocarbons 137 (b) Primary amines i3 8 (c) Ami no -phenols 139 (d) Dihydric phenols i4 2 D. DERIVATIVES OF ALDEHYDES AND KETONES Oximes H3 Semicarbazones 1 44 Thiosemicarbazones 145 Aminoguanidine derivatives 145 Phenylhydrazones 146 Osazones 146 CHAPTER VI THE ETHERS AND SULPHIDES A. THE ETHERS 148 B. THE SULPHIDES 150 CHAPTER VII THE CARBOXYLIC ACIDS, THEIR ANHYDRIDES AND ESTERS A. THE CARBOXYLIC ACIDS (i) By the hydrolysis of the nitriles, chlorides, and amides 153 (ii) By the oxidation of the alcohols, aldehydes, and ketones 1 5 5 (iii) By the oxidation of alkyl groups 1 57 (iv) By Grignard's reaction 161 (v) By Kolbe's method 161 (vi) From the aldehydes and ketones by condensation (a) Perkin's reaction 164 (b) Claisen's reaction 167 (vii) From acetoacetic ester and malonic ester 169 ADDENDA The benzylic acids i7 2 The o.-benzoyl benzoic acids 173 The syw-diphenylmethane dicarboxylic acids 173 CONTENTS xiii B. THE ACID ANHYDRIDES PAGE (i) By heating the acid with acetic anhydride 174 (ii) By heating the acid chloride with the sodium salt 175 (iii) By treating the acid chloride with quinoline or pyri- dine 175 C. THE CARBOXYLIC ESTERS (i) Esterification of the acid by the alcohol 177 (ii) By the action of the acid chloride on the alcohol 178 (iii) By the action of the acid anhydride on the alcohol 180 (iv) Esterification with dimethyl sulphate 1 80 (v) By the action of the silver salt on the alkyl iodide 181 D. ESTERS OF INORGANIC ACIDS 182 CHAPTER VIII THE NITRILES OR CYANIDES (i) From the acid amides 185 (ii) From the halogen compounds 186 (iii) From the diazo-compounds 187 (iv) By the addition of hydrocyanic acid to aldehydes and ke tones 188 (v) By the addition of hydrocyanic acid to quinones 191 CHAPTER IX THE NITROSO- (AND iso-NITROSO-) AND NITRO- COMPOUNDS A. THE NITROSO-COMPOUNDS (i) By the oxidation of the amines 193 (ii) By the oxidation of the hydroxylamines 194 (iii) By the addition of N 2 O 3 or NOC1 195 (iv) The nitroso-phenols and aromatic nitroso-tertiary amines 195 (v) The nitrosamines 197 (vi) The fc'so-nitroso-compounds 198 B. THE NITRO-COMPOUNDS ALIPHATIC NITRO-COMPOUNDS (i) By direct nitration 199 (ii) By the replacement of halogen 199 AROMATIC NITRO-COMPOUNDS Nitration with (1) Nitric acid alone 201 (2) Nitric acid and an organic solvent 201 (3) Mixed acids 202 xiv CONTENTS ADDENDA PAGE The picrates 206 The nitrodiphenyl methanes 207 CHAPTER X - THE AMINO-COMPOUNDS A. PRIMARY COMPOUNDS (i) By the reduction of the nitro -compounds (1) Metal and acid 208 (2) Alkali sulphides 211 (3) Hydro sulphite 213 (ii) By the reduction of the azo -compounds 214 (iii) By the benzidine and semi dine change 217 (iv) By the replacement of halogen atoms 218 (v) By the replacement of hydroxyl groups 220 (vi) By the disruption of the acid amides (Hofmann's reaction) 223 (vii) From the nitriles 224 B. THE SECONDARY AND TERTIARY COMPOUNDS (i) From the halogen compounds 225 (ii) By heating the primary base with its hydrochloride 231 (iii) By heating the amines with iodine 231 (iv) By the rearrangement of the oximes (Beckmann change) 232 ADDENDA The benzylidene derivatives 233 Urea 233 Thioamides and thioanilides 234 CHAPTER XI THE DIAZO-, DIAZOAMINO-, DIAZOIMINO-, AZO-, AZOXY- AND HYDRAZO-COMPOUNDS A. THE DIAZO-COMPOUNDS 237 B. THE DIAZOAMINO-COMPOUNDS 242 C. THE DIAZOIMIDES 245 D. THE AZO-COMPOUNDS 247 E. THE AZOXY-COMPOUNDS 254 F. THE HYDRAZO-COMPOUNDS 255 G. THE HYDRAZINES 256 CONTENTS xv CHAPTER XII THE SULPHINIC AND SULPHONIC ACIDS PAGE A. THE SULPHINIC ACIDS 258 B. THE SULPHONIC ACIDS (i) By direct sulphonation 260 (ii) By the oxidation of the sulphinic acids 266 CHAPTER XIII MISCELLANEOUS TYPES A. THE PYRAZOLONES 268 B. THE ACRIDONES 269 C. THE XANTHONES 270 D. THE THIOXANTHONES 270 E. THE PHENOXAZINES 271 F. THE THIAZINES 274 G. THE AZINES 276 H. THE QUINOLINES AND ISOQUINOLINES (i) Skraup's synthesis' 279 (ii) Baeyer's synthesis 283 (iii) Niementowski's synthesis 287 I. THE TRIPHENYLMETHANE GROUP 288 (i) The malachite-green dyes 288 (ii) The rosaniline dyes (a) Condensation of -aminobenzaldehydes with ami no -compounds 291 (6) Phosgene process 293 (c) New-fuchsin process 294 (iii) The rosolic acid dyes 296 (iv) The phthaleins and pyronines 297 J. INDIGO 298 K. THE INDAMINES AND INDOPHENOLS 300 ABBREVIATIONS A Annalen der Chemie. A. Ch. Annales de Chimie et de Physique. Am. American Chemical Journal. Am. Soc. Journal of the American Chemical Society. B. Berichte der Deutschen Chemischen Gesellschaft. Bl. Bulletin de la Societe Chimique de Paris. C. Chemisches Zentralblatt. C. r. Comptes rendues de 1' Academic des Sciences. Ch. Z. Chemiker-Zeitung (Cothen). D.R.P. Patentschrift des Deutschen Reiches. E.P. English Patent Specification. F.P. French Patent Specification. G. Gazetta chimica itialiana. H. Hoppe-Seyler's Zeitschrift fur physiologische Chemie. JJahresbericht der Chemie. . pr. Journal fiir praktische Chemie. .R.C.S. Journal of the Russian Chemical Society. M. Monatshefte der Chemie. Pat. Anm. Patent Anmeldung. Proc. Proceedings of the Chemical Society. R. Recueil des travaux chimique des Pays-Bas. Soc. Journal of the Chemical Society. Z. Zeitschrift fur Chemie. Z. a. Ch. Zeitschrift fiir angewandte Chemie. Z. El. Ch. Zeitschrift fiir Elektrochemie. With one or two exceptions, the above abbreviations are those used in Beilstein's " Handbuch " and Richter's " Lexikon." xvi CHAPTER I APPARATUS, METHODS OF MANIPULATION, REAGENTS APPARATUS FLASKS. The ordinary flat-bottomed flasks, round flasks, and conical (Erlenmeyer) flasks are all suitable for organic preparations. The last -mentioned have the great advantage that they are readily cleaned. Cork rings or wicker baskets (Fig. i) should be provided for standing round-bottom flasks on the bench. Flasks can sometimes be replaced by enamelled-ware cans, but these suffer from the great dis- advantage of not allowing the liquid to be seen. They are useful, however, when a liquid bumps heavily. For experi- ments at the ordinary tem- perature bottles are preferable to flasks, as there is less like- lihood of breakage. Bottles of good glass will stand heating to 100 on the water-bath, provided the temperature is raised slowly. Experiments with concentrated sulphuric acid or oleum are best carried out in cast-iron or lead vessels (Fig. 2), provided, of course, no oxidising agent is present. Lead vessels can easily be made from lead pipe by any lead-burner. No solder must be used, all joints being " burned." A convenient size is 15 cm. deep by 6 cm. diameter. They must always be heated FIG. i. 2 % PREPARATION OF ORGANIC COMPOUNDS by means of an oil-bath. The lid is held in position by nieans of four thumb-screws. Distilling Flasks are discussed on p. 23. BASINS. Porcelain basins can be replaced in prac- tically all cases by enamelled basins, saucepans, &c. These should be of the best quality, and once the enamel FIG. 2. FIG. 3. FIG. 4. has begun to chip care must be taken not to use them for acid liquids. BEAKERS. Ordinary thin glass beakers are not much used as they can generally be replaced by sauce- pans. For experiments which do not require heating thick glass beakers are very convenient. These are especially useful when the liquid has to be stirred ; for example, in preparing diazo-solutions. Jam-pots make excellent thick glass beakers. APPARATUS, METHODS, REAGENTS 3 DROPPING FUNNELS. Dropping funnels are illus- trated on p. 22. A very convenient form is the Walter funnel (Fig. 3), as this allows the rate at which the liquid is being added to be seen with great ease. CONDENSERS. The Liebig condenser (Fig. 4) is the most usual form, but spiral condensers (Fig. 5) are very efficient. An inexpensive spiral condenser is readily made by coiling lead gas- pipe and arranging it with the lower end passing through the top of an inverted bell-jar (Fig. 6). The cooling water is led in by the pipe A and is FIG. 5. FIG. 6. FIG. 7. removed by the siphon-tube B. These condensers should not be used when the distillate is apt to solidify. Reflux Condensers are condensers arranged so that the condensed liquid flows back into the flask. They are either arranged in a vertical position (Fig. 7) or sloped (Fig. 8). The latter arrangement is the more convenient when a retort is being used. The bulb condenser shown in the diagram is more efficient than the ordinary Liebig condenser, but is not suitable for distillations. Double -surf ace condensers are very 4 PREPARATION OF ORGANIC COMPOUNDS suitable for refluxes, especially when a Soxhlet extrac- tion apparatus is being used. Several forms are on the market, of which two are shown in the illustrations (Figs. 9 and 10). FIG. 8. When an agitator is used in conjunction with a reflux condenser, a mercury seal (Fig. n) must be used. The tube A passes through the cork of the flask and is attached to the wide tube B by means of a cork. The tube c is attached to the agitator and reaches very nearly to the bottom of the tube B, which is then filled with mercury. When it is desired to keep the water in the condenser at a definite temperature, the arrangement shown in Fig. 12 is simple and effective. The water from the tap enters the bucket A at B. It leaves by the siphon-tube E, the rate of flow being regulated by the screw clip D. The temperature at JT IG . 9 . which it enters the condenser is taken at c as shown. The large bulk of water in the bucket prevents any rapid variation in the temperature. By keeping ice in A this arrangement can be used when very easily volatile liquids are being APPARATUS, METHODS, REAGENTS 5 distilled and it is desired to have the condenser water as cold as possible. STIRRING. Most reactions proceed best when the reacting mixture is well stirred. The most effec- tive source of power in the laboratory for driving agitators is Rabe's turbine (Fig. 13). It is convenient to connect this with the water-supply by means of thick-walled rubber tubing or flexible metal tubing, as it can then be readily adjusted to any desired position. For most pur- Jluifier band* FIG. 10. Burgess condenser. FIG. ii. poses the agitator is simply made by bending a piece of thick glass rod as shown (Fig. 14). It is fixed in the pulley A by means of corks, and is held in position by clamping the loose brass tube B. When, however, the 6 PREPARATION OF ORGANIC COMPOUNDS liquid contains a heavy precipitate, such as zinc dust, the agitator shown in Fig. 15 is more effective. The agitator is driven from the turbine by means of an endless, round rubber band. In order to join the ends of this so that it will not " jump " the wheel, FIG. 12. they are cut off at as accurate an angle as possible, and the tapering ends then bound firmly together with stout thread. Liquids can also be agitated by blowing air through them, or by sucking it through by means of a water-pump (Fig. 16). BATHS. Cast-iron saucepans make the best baths. For temperatures up to 100 of course water is used. APPARATUS, METHODS, REAGENTS 7 For temperatures above 100 an oil- or fusible -metal bath must be employed. As an oil, castor oil, cylinder oil, or paraffin wax is suitable, and can be used for temperatures up to about 300. As fusible metals, Wood's alloy, melting at 71 (i to 2 parts Cd, 2 parts Sn, 7 to 8 parts Sb), and Rose's metal, melting at 95 (2 parts Sb, I part Pb, i part Sn), are the most suitable. When using a metal-bath it is advisable to coat the flask with lamp-black in order to prevent the metal adhering to the glass. Metal-baths FIG. 13. have the advantage of being cleaner than oil-baths, and, owing to the high conductivity of the metaL FIG. 14. FIG. 15. are less liable to local overheating, but they have the disadvantage that considerable force is required to immerse the flask in the relatively dense metal, and hence there is increased liability of breakage. PREPARATION OF ORGANIC COMPOUNDS If steam is available, a steam-bath can be con- veniently substituted for a water - bath. A simple and easily constructed form is shown in Fig. 17. The steam is led in at A and the con- densed water passes out at B. These steam-baths are espe- cially useful when very easily inflammable liquids, such as car- bon bisulphide, which ignites when brought in contact with metallic surfaces at 160, are being heated, as the steam can be generated at a distance. FREEZING MIXTURES. Powdered ice and common salt FIG. 1 6. (3 parts ice, i part NaCl) gives a temperature of about 18 ; ice and crystallised calcium chloride (7 parts ice, 10 parts CaCl 2 6H 2 O) about - 48. Ice and hydrochloric acid also form an efficient freezing mixture. If lower temperatures are desired, solid carbon dioxide ( 78) or liquid air ( - 180) must be used. The former is most effec- tive when mixed to a slush with alcohol or ether. FILTRATION. Organic pre- parations are not often filtered through an ordinary conical funnel. These are useful, how- ever, when solutions which crys- taDise readily on cooling are being dealt with, as they can be readily " jacketed." A simple FIG. 17. and quite effective jacket is made by wrapping the funnel round with a spiral of rather narrow lead pipe, FIG. 1 8. APPARATUS, METHODS, REAGENTS 9 the turns of the spiral being made as close as possible, and then blowing steam through during the nitration. A more convenient form is shown in Fig. 18. It con- sists of a double - walled copper cone which carries the glass funnel. The annu- lar space is filled with water which is heated as shown. Before filtering inflammable liquids such as alcohol, ben- zene, &c., the burner must be removed. The most effec- tive form of filter jacket is that shown in Fig. 19. It consists of a double-walled glass funnel, arrangements being made for passing steam through the annular space. The advantage of this type lies in the fact that the paper is in actual contact with the heated surface. Usually liquids are filtered through a Buchner (Fig. 20) or Hirsch (Fig. 21) funnel. The paper is placed on the perforated porce- lain disc A, moistened with the liquid to be fil- tered, and well pressed down. The funnel is connected with a thick- walled flask by means of a rubber cork, and the side-tube of the FlG flask connected to the pump. Thin glass flasks must not be used as they collapse. The Hirsch model is chiefly used when small quantities are being dealt with. As filtering media Schleicher and Schull's hardened FIG. 20. 10 PREPARATION OF ORGANIC COMPOUNDS paper No. 575 white band is the most generally useful and will stand fairly strong cold acids. It is somewhat expen- sive, but after use can be cleaned with a nail-brush and used again. It is not suitable for filtering organic solvents such as ben- zene, nitrobenzene, aniline, &c., through a Buchner funnel, as when moistened with oily liquids it will not adhere to the surface of the plate. For such liquids Schleicher and Schiiirs 595 white band will be found satis- factory. Cloth also makes an excellent medium, unbleached calico being the most satisfac- tory. It is either cut into circles and used with a Buchner funnel in the ordinary way, or it is suspended from a wooden frame as shown (Fig. 22). The precipitate can be effec- tively freed from mother-liquor by folding up the cloth just as a parcel is wrapped up, and then pressing either in an ordi- nary ledger press, or, if this is not available, by piling bricks on it. When pressing precipi- tates it is advisable to use a double thickness of cloth. Highly corrosive liquids such as concentrated sulphuric acid, caustic alkali, &c., must be filtered through glass-wool or asbestos. Glass-wool is used in the form of a small plug in an ordinary conical funnel, but care must be taken not to pack it too tight. An asbestos filter is prepared on a Buchner funnel just FIG. 21. APPARA1US, METHODS, REAGENTS n as in a Gooch crucible. It is much more satisfactory than glass-wool. VACUUM PUMPS. There are numerous forms of water-pumps on the market, of which that shown in the diagram (Fig. 23) is one of the most effective. It is connected with the water-supply by thick-walled rubber tubing and must be carefully wired on. With a good water-pressure, a vacuum of about 10 mm. of mercury can be obtained. To obviate the danger of FIG. 22. the water running back, an extra thick-walled flask is interposed between the pump and the vessel which is being exhausted. For measuring the pressure a mercury manometer as shown in Fig. 24 is most suitable. When the experi- ment is finished great care must be taken to admit air very slowly, as if the air be admitted rapidly the mer- cury will rush up and break the top of the tube. WORK UNDER PRESSURE. *When experiments are to be carried out under only slightly elevated pressure (not more than one atmosphere), soda- water bottles or beer bottles can be used. These 12 PREPARATION OF ORGANIC COMPOUNDS must be wrapped up in stout cloth and heated very slowly on a water-bath. It is not safe to heat them FIG. 24. FIG. 23. FIG. 25. above 100. For higher pressures a bomb tube or an autoclave must be used. Bomb tubes are made of good quality glass tubing about 16 mm. internal diameter and about 3 mm. thickness of wall. It is APPARATUS, METHODS, REAGENTS 13 not necessary to use hard glass, Jena " resistance " glass (blue line and stamped " R ") or Jena " normal glass " (red line) being the most suitable, as they are easily worked in an ordinary gas-air blowpipe. One end of the tube is carefully sealed off in the ordinary way, care being taken to avoid leaving a " blob " of glass. The tube is then filled (it must not be more than half full), the open end carefully cleaned and dried, FIG. 26. and then drawn off to a thick capillary. To do this it is gradually heated in the blowpipe until soft and a piece of glass rod about 6 in. long attached as shown (Fig. 25) . The blast flame is then lowered until it is about 4 in. long, made as hot as possible, and allowed to play on the bomb tube about in. below the end. The tube is held in as horizontal a position as its contents will allow and continually revolved, the open end being supported by holding the glass rod with the left hand. Under this treatment the glass soon thickens and begins to fall together (Fig. 26). When almost closed the tube is removed from the flame, allowed to cool for 14 PREPARATION OF. ORGANIC COMPOUNDS a moment, and then slowly and steadily drawn out to a capillary. This is then sealed off and the whole carefully annealed in the smoky flame. The finished tube should present the appearance as shown in Fig. 27. The seals are quite simple to make, but require a little practice. Points to remember are : (i) Do not draw out the capillary until the sides have thickened and fallen in so that the tube is almost closed ; (2) allow the tube to cool for a moment before drawing out, and draw out slowly ; (3) reject any seal in which the walls of the capillary and the shoulder are not thick ; FIG. 27. (4) anneal the tube thoroughly in the smoky flame. Well-sealed tubes will stand a very high pressure. Bomb tubes are wrapped in paper (to prevent their being scratched), placed in a cast-iron pipe, and then heated in a special furnace such as shown (Fig. 28) . After cooling and without removing the tube, the end of the capillary is heated with a flame until the glass softens and any pressure is blown off. When there is no longer any pressure in the tube the end is cut off in the usual way, but tubes must never be removed from the furnace until it is quite certain that they contain no pressure. As the capacity of bomb tubes is limited, it is often more convenient to use an autoclave. These are constructed of steel or bronze, and if desired can be lined with enamel, lead, &c. The lid should be provided with a tube to carry the thermometer, a APPARATUS, METHODS, REAGENTS 15 pressure gauge, and a screw valve. An agitator can also be added, but under high pressure the stuffing- box almost invariably leaks. The autoclave itself is provided with a lead ring and the lid is screwed into this by means of bolts. The autoclave is heated either by a direct flame or by an oil-bath. FIG. 28. SOLVENTS AND CRYSTALLISATION. The majority of reactions proceed best when the reacting substances are in solution, and solvents are also added to moderate an otherwise too violent reaction* The purification of crude solids is usually carried out by recrystallisation. In choosing a solvent one should be chosen in which the desired substance dissolves readily on heating, but in which it is almost insoluble in the cold, and in which the impurities are either 1 6 PREPARATION OF ORGANIC COMPOUNDS insoluble or are very soluble. The usual procedure is to dissolve the substance in the boiling solvent, filter the hot solution from any insoluble impurities, and then cool the nitrate as rapidly as possible with violent shaking. Crystallisation can often be induced by scratching the sides of the vessel with a glass rod. As substances sometimes separate slowly from their solutions, it is often advisable to allow the whole to stand over-night before collecting the crystals. These should be washed with the solvent from which they were crystallised. If the substance separates in an oily state it can often be obtained crystalline by re- crystallising from more dilute solutions. If it does not separate at all the solution must be concentrated. Mixed solvents, especially alcohol and water, are often very useful. They are* employed as follows. The substance is dissolved in some boiling solvent, e.g. alcohol, in which it is readily soluble. A second solvent, e.g. water, which is miscible with the first solvent, but in which the substance is insoluble, is then slowly added until a slight permanent turbidity appears, the whole being kept gently boiling. On cooling, the substance will usually separate in the crystalline form. A modification of this method which often gives excellent results is carried out as follows. The substance is dissolved in some cold solvent, e.g. water; another miscible solvent, e.g. alcohol, in which the substance is insoluble, is then added until a slight permanent turbidity appears. The solution is then filtered and placed in a vacuum desiccator over some substance which takes up the first solvent but not the second ; in the above case, for example, soda -lime or solid potash would be used. The solution thus becomes less and less rich in the solvent which has the power of dissolving the sub- stance, and the latter separates out, usually in the crystalline form. As a last resort substances which are insoluble in water, but soluble without change in concentrated sulphuric acid, can be crystallised by dissolving in the concentrated acid and then setting APPARATUS, METHODS, REAGENTS 17 the solution aside in a moist place, e.g. in a desiccator containing water. The acid gradually becomes more dilute, and the substance usually separates out crystalline. The following list gives the solvents most generally used, together with their boiling-points : Inorganic Solvents Water, 100 Cone. H 2 SO 4 Cone. HNO 3 Cone. HC1 Alcohols Methyl alcohol, 66 Ethyl alcohol, 78 Amyl alcohol, 1 30 Hydrocarbons Petroleum ether, 70' Ligroin, 120 Benzene, 79 Toluene, 1 10 w.-Xylene, 139, Naphthalene, M.P. 80, B.P. 218 Ethers Ether, 35 * Anisole, 152 Bases Aniline, 182 Pyridine, 115 Quinoline, 239' Acids Formic acid (90 %) ' 100 Acetic acid, 119 Miscellaneous Compounds Acetone, 56 Carbon bisulphide, 47 Nitrobenzene, 210 Ethyl acetate, 77 Ethyl benzoate, 213' Phenols Phenol, M.P. 43, B.P. 181 w.-Cresol, 202 Halogen Compounds Chloroform, 61 Carbon tetra- chloride, 78 Dichlorethylene, 55 Trichlorethylene, 88 Tetrachlor- ethylene, 121 Tetrachlor- ethane, 147 Pentachlor- ethane, 159 Epichlorhydrin, 117 Chlorobenzene, 132 Bromobenzene, iS5 c a-Chlor- naphthalene, 263 a-Brom- naphthalene, 279 Cone. H 2 S0 4 is only used as described on p. 16. Cone. HNO 3 is sometimes useful with highly nitrated compounds. 1 8 PREPARATION OF ORGANIC COMPOUNDS Alcohol. In most laboratories absolute alcohol, containing 96-98 per cent. C 2 H 5 OH, can be obtained duty-free. In a large number of cases, especially when used as a solvent, it can be replaced by the less expensive methylated spirit. There are two kinds of methylated spirit on the market, viz. " ordinary methylated spirit/' which contains 10 per cent, of wood- naphtha and not less than 0.385 per cent, of mineral- naphtha ; and " industrial spirit," which contains 5-10 per cent, of wood-naphtha but no mineral-naphtha. The latter of these is the more suitable for laboratory purposes, but can only be obtained under a special licence. Before use methylated spirit should be purified by boiling it for an hour under a reflux con- denser with a little solid caustic potash. The purified spirit is then distilled from the alkali and resin. Phenol has great solvent power, but suffers from the disadvantage that it is solid at the ordinary temperature. It can be used diluted or can be replaced by w.-cresol, but is not much used. Naphthalene is an excellent solvent, but on account of its high melting-point it finds but little use in recrystallising. Ether, in spite of its high solvent power, is not exten- sively used for recrystallisation, as substances often do not separate nicely. This can be remedied to a certain extent by dehydrating the ether over sodium, but its low boiling-point is a great objection. Pyridine and Quinoline are both excellent solvents and are usually used in the crude form as obtained from coal tar. Ethyl benzoate is an excellent solvent, but must be used with care, as it is apt to benzoylate phenols and bases. A similar objection applies to all esters with high boiling-points. A high boiling-point solvent is best removed from the crystals by washing with some low boiling-point liquid with which it is miscible, e.g. ether. If the crystals are insoluble in water, it is often convenient to remove the solvent by distillation in steam. APPARATUS, METHODS, REAGENTS 19 DRYING SOLIDS. Solids which do not melt or decompose at 100 are best dried in the steam oven unless they are very readily vola- tile, e.g. quinone. The Victor Meyer oven (Fig. 29) forms a convenient method of drying solids at any given temperature. It consists of a double-walled copper box, pro- vided with a lid, the annular space being provided with a reflux con- denser and containing a liquid which boils at the temperature at which it is desired to dry the substance. If a substance cannot FIG. 29. be heated it is best dried in a vacuum desiccator (Figs. 30 and 31). If the type shown in Fig. 30 is used, one should be chosen in which the tap is in the side and not in the lid, as if the tap is in the lid it is very apt to get broken. Hempel's desiccator (Fig. 31) is the FIG. 30. FIG. 31. more rapid in its action, as the desiccating substance is placed both on the bottom of the apparatus and in the space A. As desiccating substances, concentrated sulphuric 20 PREPARATION OF ORGANIC COMPOUNDS acid, anhydrous calcium chloride, soda-lime, and solid caustic potash or caustic soda are most used. If the liquid to be removed is an acid, such as acetic acid, a basic desiccating agent such as potash is used, whereas if it is desired to remove a base, such as pyridine, the desiccator is charged with concentrated sulphuric acid. The ground-glass rim of the desiccator must be well greased with lard or vaseline. Pure vaseline is rather thin for the purpose and can be advantageously re- placed by the crude article (mineral jelly). When admitting air to an evacuated desiccator, the tap must be opened very cautiously, as otherwise the dried substance will be blown about and lost. DRYING LIQUIDS. When only a small quantity of a liquid is to be dried, it is best first to dissolve it in some neutral solvent such as ether, ligroin, benzene, &c., from which it is readily separated by distillation, as by this means loss is avoided. The liquid is dried by adding a dehydrating agent (anhydrous calcium chloride, potassium carbonate, sodium sulphate, caustic potash, copper sulphate, &c.), allowing it to stand for some time, and then filtering and distilling. With the exception of caustic potash, it is very convenient to add the finely powdered dehydrating agent slowly, shaking well after each addition. Under these cir- cumstances, an oily layer consisting of a solution of the dehydrating agent in the water present first separates. On the addition of more dehydrating agent this becomes very viscous and adheres to the sides of the vessel, so that the dried liquid can be poured off at once. This method is particularly applicable when ethereal solu- tions are being dried with calcium chloride. In preparing absolute ether, sodium should be added, and the whole allowed to stand until no more gas is given off. The ether is then decanted and distilled over fresh sodium. Alcohol can be rendered almost anhydrous by dis- tilling over burnt lime. The last traces of water can then be removed by means of metallic calcium. In drying aldehydes and ketones it must be borne APPARATUS, METHODS, REAGENTS l \ 21 in mind that they readily undergo the aldol conden- sation under the influence of dehydrating agents. EXTRACTING SOLIDS. Solids are best extracted in a Soxhlet apparatus (Fig. 32). The sub- stance is placed in the thimble of filter-paper A, the top of which is closed with a very loose plug of cotton-wool or glass-wool. The liquid is boiled in the flask B, the vapour ascends to the reflux-con- denser, and the condensed liquid falls into the thimble. When the level of the liquid reaches c it is automatically returned to the flask by the siphon D. The action of the apparatus is purely mechani- cal, and it can be left running for hours without attention. It is ad- visable to tie a piece of asbestos paper round the extractor to pre- vent undue condensation in c. More rapid extraction takes place if the substance is mixed with bits of broken glass before being placed in the thimble. EXTRACTING LIQUIDS. When a substance is shaken with two liquids in which it is soluble, it divides itself between the two sol- vents according to its solubility in each, and according to the amount of each solvent present. The theory of this will be found discussed in any text-book of physical chemistry. This partition of a substance between two immiscible solvents is one of the most frequently used methods of isolating organic preparations, especially for removing ether-soluble substances from aqueous solutions. The extraction is carried out simply by shaking the solution FIG. 32. 22 PREPARATION OF ORGANIC COMPOUNDS in one solvent with the second solvent and then separating the two layers. The extraction is carried . out in a separating funnel J L - -, (Figs. 33 and 34), the layers being separated by drawing off the lower one by means of the tap. Both forms of apparatus illustrated are convenient ; the pear-shaped form, however, is perhaps the more generally useful, as it is the more convenient shape for use as a dropping FIG. 33 . FIG. 34. funnel. In carrying out ex- tractions it must be borne in mind that it is more effec- tive to extract several times with small quantities of sol- vent than to extract once with a large quantity, and that the less soluble the sub- stance is in the extracting liquid, the more difficult it will be to extract. It some- times happens that an emul- sion is formed which does not separate into two layers on standing. " Breaking " such emulsions requires some expe- rience, but it can often be done by adding more of one of the solvents. Water-ether emulsions are usually most readily broken by adding a little alcohol. The addition of calcium chloride and of sodium sulphate is also some- times effective. DISTILLATION. Distillation at atmospheric pres- sure is carried out from an ordinary distilling flask FIG. 35. APPARATUS, METHODS, REAGENTS 23 (Fig. 35), the side-tube being connected with the condenser. The neck of the flask carries a thermo- meter, the bulb of which should be on a level with the side-tuba. A few pieces of porous pot should always be added to prevent bumping. When distillation is to be carried out under reduced pressure, a Claisen flask (Fig. 36) is most suitable, and the pear-shaped variety is more convenient than the round. The side- tube is connected to the condenser, and the neck to which it is sealed carries the thermometer. The main FIG. 36. neck of the flask carries a glass tube drawn out to a capillary at both ends, one end reaching right to the bottom of the flask. By this means a slow stream of air is drawn through the liquid during distillation, and "bumping" thereby greatly lessened. t By carefully drawing oif the top capillary the flow of air can be easily adjusted during the distillation. The receiver is connected by an air-tight joint to the condenser, and, if only one fraction is to be collected, may consist of an ordinary distilling .flask, the side-tube of which is connected to the gauge and pump. This arrangement can also be used for distillation at atmospheric pressure 24 PREPARATION OF ORGANIC COMPOUNDS when it is desired to protect the distillate from atmo- spheric moisture, the side-tube in this case being connected with a calcium chloride tube. A large number of devices have been proposed from time to time for enabling several fractions to be col- lected from a distillation in vacuo without destroying the vacuum. Of these, that illustrated in Fig. 37 is by far the most convenient. The condenser is connected to A and the gauge and pump to B. The tap D is closed, c and E opened, and the distillate collected in F. When it is desired to change the receiver, c and E are closed and D opened. The receiver F is then changed, the tap D closed, and first E, and then after a minute c, opened. During these operations there is no need to interrupt the dis- tillation, as the distillate collects in G. In carrying out distilla- FIG. 37. tions in vacuo the burner should be held in the hand and continually moved about. All rubber or cork joints should be made air-tight by painting them with paraffin wax, or, if they are liable to become hot, with collodion, after the apparatus has been exhausted. With a good head of water there should be no difficulty in carrying out distillations at 10 to 12 mm. when only a water -pump is used. Distillation in steam is frequently resorted to as a means of purifying preparations. The amount of substance which passes over depends on its vapour pressure at 100 and upon its molecular weight. The method of carrying out the operation is obvious from APPARATUS, METHODS, REAGENTS 25 the diagram (Fig. 38). The sloping position of the flask is adopted in order to avoid splashing, and the heat applied to the flask is merely to prevent undue conden- sation. It is often advantageous to employ superheated FIG. 38. steam. The superheating is brought about by interpos- ing a copper spiral heated by a Fletcher burner, or a lead spiral heated in an oil-bath, between the boiler and the flask. Steam is best generated in an ordinary tin-plate can pro- vided with a safety tube reaching to the bottom. A convenient arrangement for continuously sepa- rating the two layers is shown in Fig. 39. The condenser is con- nected to A and the heavier layer drawn off from time to time at B. The lighter layer continuously flows over by the tube c. Fractional distillation of mix- tures of liquids whose boiling-points lie close together is greatly facili- tated by using a column appa- ratus. Numerous forms of these FIG. 39. have been proposed, three of which are shown in the illustration (Fig. 40). The principle on which they are constructed is to condense the less volatile portions and cause them to be distilled by the ascending 26 PREPARATION OF ORGANIC COMPOUNDS vapours. Thus, for example, the least volatile portions will condense at A. The drop of liquid which collects is heated by the ascending vapours when the more volatile portions evaporate and condense at B. These at FIG. 40, are in turn heated by the vapours, which, however, are somewhat cooler than at A, and lose their more vola- tile portions, which condense at c, and so on. It will thus be seen that by the time the vapours reach the condenser they have undergone several distillations. In systematic fractionations the liquid is distilled APPARATUS, METHODS, REAGENTS 27 so that the distillate collects at a regular speed of about two drops a second, the receiver being changed about every 5. The first fraction is then redistilled until the temperature has risen, say, 3. The second fraction is then added, the receiver changed, and the distillate collected until the temperature has risen, say, another 3. The receiver is then again changed, the third fraction added, and this process continued. FIG. 41. FIG. 42. The whole process is then repeated until fractions with constant boiling-points are obtained. The tem- perature intervals cited above are, of course, merely illustrative, the intervals actually chosen depending on how rapidly the boiling-point of the mixture rises. SUBLIMATION. Solids often pass into the gaseous state without melting, and when this is the case sublima- tion frequently affords a ready means of purification. Substances which readily condense are placed in a crucible which is fixed in a hole in a sheet of asbestos, covered with a bell-jar or large conical funnel, and the crucible then very slowly heated (Fig. 41). The i 28 PREPARATION OF ORGANIC COMPOUNDS sublimed substance condenses on the sides of the jar or funnel. More readily volatile substances are heated in a wide-necked flask on a sand- bath, the flask being provided with a tube in which cold water is made to circulate in the direc- tion shown by the arrow-heads (Fig. 42). The sublimed sub- stance condenses on the cold surface of this tube. To sublime a substance in vacuo it is placed in a tube provided with a rubber cork and a tap. After evacuation the tap is closed, the tube immersed to about half its length in an oil- or air-bath, and heated. The sublimed sub- stance condenses in the cool, upper part of the tube. MELTING-POINTS. Capillary tubes about 3 in. long are made by drawing out thin-walled glass tubing and cutting the capillary thus formed into pieces of the required length. These are sealed at one end. In order to determine the melting-point of a substance it is carefully dried, finely powdered, and then a little of it shaken down to the sealed end of one of the capil- laries. The capillary is then attached to a thermometer by F IG 43 means of a rubber band (made by cutting a thin slice off a piece of rubber tubing) in such a way that the sub- stance is opposite the bulb of the thermometer. The bulb is then immersed in concentrated sulphuric APPARATUS, METHODS, REAGENTS 29 acid contained in a small flask or in a special tube, as shown in Fig. 43. The acid is then heated until the substance is seen to melt, the whole being well stirred by moving the stirrer A up and down. This stirrer can be omitted if the bath is heated slowly, but more accurate figures are obtained if the bath is well stirred. The use of a P-tube (Fig. 44) FIG. 44. FIG. 45. also eliminates the use of the stirrer, the heat being applied at A. These tubes, however, are very apt to break at high temperatures. BOILING-POINTS. These are best determined by distilling a portion of the liquid from a small distilling flask. If sufficient liquid is not available for this, it 30 PREPARATION OF ORGANIC COMPOUNDS is placed in a not too narrow glass tube sealed at one end. A capillary tube sealed at the upper end is dropped in and the whole then attached to the ther- mometer (Fig. 45), and heated as described in the above paragraph. The air contained in the capillary tube expands and the bubbles passing through the liquid prevent superheating. REAGENTS Chemicals of technical purity are quite suitable for carrying out preparations and are a great deal less expensive than pure substances. They often come on to the market in lumps and are best ground in an ordinary coffee-mill. Sulphuric Acid. Pure sulphuric acid for analysis is a distilled acid. Its density is about 66 Be', and it contains 96 to 98 per cent, of H 2 SO 4 . Monohydrate is 100 per cent. H 2 SO 4 , and is prepared by adding oleum to a more dilute acid until the right strength is obtained. The commercial article is often quite opaque owing to the presence of flue-dust. This, as a rule, does not have any bad effect, but if desired can be removed by filtration through asbestos. Oleum (fuming sulphuric acid) can be obtained of any strength, but an acid containing about 66 per cent, of free SO 3 is most suitable, as it does not freeze readily. It is diluted down to the required strength with mono- hydrate. Hydrochloric Acid. Pure concentrated hydrochloric acid contains about 38 per cent, of HC1. For organic preparations it can in almost all cases be replaced by the less expensive commercial acid (spirits of salt, Tower salts). This is coloured yellow by the presence of iron and contains from 25 to 30 per cent. HC1. Nitric Acid. The ordinary concentrated nitric acid has a density of 1*4, and contains 63 per cent, of HNO 3 . The ordinary fuming nitric acid has a density of 1-5 and contains 94 per cent, of HNO 3 . An acid of density 1-52 corresponding to 997 per cent. HNO 3 can also be purchased. All concentrated nitric acids rapidly APPARATUS, METHODS, REAGENTS 31 acquire a red colour owing to the liberation of oxides of nitrogen. Ammonia. Concentrated aqueous ammonia has a density of O'88o and contains about 35 per cent, of NH 3 . Ammonia gas is obtained by warming this solution and drying the evolved ammonia by passing it over quicklime or soda-lime. It is more convenient to obtain the gas from a cylinder of anhydrous, liquid ammonia. Caustic Soda. Caustic soda containing 98 per cent. NaOH can be bought in powder in tins and is more convenient than the fused sticks. As a rule it is convenient also to keep the commercial solution. This can be obtained in any strength, a 33 per cent. solution being most suitable for laboratory purposes. Buying the commercial solution is considerably more economical than buying the solid alkali and then dissolving it in water. Anhydrous Aluminium Chloride. It is usually best to buy this reagent, the most satisfactory brand being that sold in sealed bottles by Kahlbaum. If desired, however, it can be prepared by passing dry chlorine over aluminium foil packed in a hard glass tube. The reaction is started by warming the end of the tube nearest the source of chlorine. The aluminium chloride sublimes and is collected in a flask provided with a calcium chloride tube to exclude atmospheric moisture. Cuprous Chloride. Cuprous chloride can be bought at a reasonable price, or it can be prepared by one of the two following methods : (a) l Cupric chloride is dissolved in boiling water and the calculated quantity of copper powder (Natur- kupfer C) slowly added to the boiling solution. At the end of two or three minutes the solution will have become completely colourless. The cuprous chloride is then filtered off as rapidly as possible, and dried out of contact with the air. (b) Two hundred and fifty grammes of crystallised 1 B. 29, 1878. 32 PREPARATION OF ORGANIC COMPOUNDS copper sulphate, 120 grm. of common salt, and 500 c.c. of water are heated to boiling. One kilogramme of concentrated hydrochloric acid and 130 grm. of copper turnings are added, and the whole gently boiled until decolorised, oxidation by the air being avoided as far as possible by closing the mouth of the flask with a loose plug of glass-wool. The solution is rapidly poured off from unchanged copper and then well- boiled water added until no more cuprous chloride is precipitated. As cu- prous chloride is most fre- quently used in solution in hydrochloric acid, e.g. in carrying out Sand- meyer's reaction (p. 75), it is convenient not to precipitate it, but to weigh the solution poured off from the excess of copper and then to dilute it with concentrated hydrochloric acid until the total weight is 2036 grm. The result- ing solution contains about 10 per cent, of Cu 2 Cl 2 . Cuprous Bromide. Cuprous bromide is obtained by boiling 125 grm. of crystallised copper sulphate with 360 grm. of potassium bromide, 800 c.c. of water, 200 grm. of copper turnings, and no grm. of concentrated sulphuric acid until the whole is decolorised. Sodium. Oil should be removed from the surface of the sodium by means of dry blotting paper, and the metal then cut into thin slices or pressed into wire by means of a sodium press (Fig. 46). After use the die should be at once removed and placed in alcohol. It should not be thrown into water, as if this is done any sodium adhering to the inside may give rise to an explosion. Granulated sodium is obtained as follows. 1 i B. 21, 1464; 35, 3516; J. pr. [2] 54, 116. FIG. 46. APPARATUS, METHODS, REAGENTS 33 The metal is covered with a fairly deep layer of dry paraffin or xylol and heated to 120. The flask is then corked, wrapped up in a thick cloth, and well shaken for a minute or two. The metal is thus obtained in the form of a powder. Quantities up to about 50 grm. can be safely dealt with in one operation. The paraffin or xylol can then be replaced by any desired neutral solvent, such as anhydrous ether, ligroin, &c., by washing several times by decantation. Sodium Ethoxide. An alcoholic solution of sodium ethoxide is very readily obtained by slowly adding thin strips of sodium to excess of absolute alcohol. The heat given out during the reaction causes the alcohol to boil, and the preparation should, therefore, be carried out under a reflux condenser. In order to isolate the solid ethoxide free from alcohol, the alcoholic solution must be distilled in a current of hydrogen from a copper retort, the last traces of alcohol not being lost below 200. When the dry product is required it is best to prepare sodium powder as fine as possible by the method given above, using 250 c.c. of xylol, &c., to each 23 grm. of sodium. The xylol and sodium are then placed in a flask provided with a reflux condenser and agitator, cooled with ice, and the calculated quantity of alcohol, diluted with two volumes of xylol, &c., added slowly. When all the alcohol has been added, and the violent reaction has subsided, the whole is heated gently on the water-bath for a time in order to complete the reaction. The ethoxide thus obtained forms a snow-white, flocculent precipitate which shows greater reactivity than that prepared by other methods. TEST-PAPERS. Litmus paper is affected by both inorganic and organic acids, and can usually be conveniently replaced by Congo paper. This is pre- pared by steeping filter -paper in a solution prepared by dissolving 3 grm. of Congo red in a litre of boiling water to which a few drops of sodium carbonate have been added. It is turned blue by inorganic acids and brown by organic acids. The blue colour is, 3 34 PREPARATION OF ORGANIC COMPOUNDS however, also produced by concentrated organic acids. Alkalis are best detected by Brilliant Yellow paper. This is prepared by steeping filter-paper in a solution of 1-5 grm. of Brilliant yellow in 1000 c.c. of boiling water containing two or three drops of acetic acid. It is turned red by caustic alkalis, alkali carbonates, and ammonia. Nitrous acid is detected by means of starch-iodide paper. To prepare this, 10 grm. of starch are ground to a thin cream with cold water and then poured slowly into one litre of boiling water. The whole is boiled for two to three minutes and then cooled as rapidly as possible. When cold a solution of 3-5 grm. of potassium iodide is added. Filter-paper is steeped in the solution thus obtained, and dried in as clean an atmosphere as possible. It should be preserved in well-stoppered bottles, and if properly prepared should give a pure blue colour with nitrous acid and other oxidising agents. CHAPTER II THE HYDROCARBONS IN this chapter no attempt can be made to mention all the methods employed in the preparation of hydro- carbons, but the most important reactions will be discussed briefly. It should be pointed out that the artificial preparation of hydrocarbons is in most cases of theoretical rather than practical im- portance, the majority of important hydrocarbons being obtained from natural sources, viz. petroleum (paraffin), coal tar (benzene and its homologues, naphthalene and anthracene), and turpentine oil (terpenes). The most important synthetic hydro- carbon is acetylene, obtained by the action of water on calcium carbide, and is too well known to require further mention. FROM THE HALOGEN COMPOUNDS. Hydro- carbons can be obtained from the halogen compounds by three methods, viz. : (a) Retrogressive Substitution. This consists in replacing the halogen atom by one of hydrogen and is usually accomplished by heating (under pressure if necessary) with concentrated hydriodic acid and red phosphorus. The method is often useful for reducing alcohols, aldehydes, and ketones, the hydroxyl group, or aldehydic or ketonic oxygen atom having been previously replaced by halogen. (6) Action of Metals. This method was originally proposed by Wiirtz for the synthesis of the paraffins by treating the alkyl halides with metallic sodium, and was extended to the aromatic series by Fittig. The 35 36 PREPARATION OF ORGANIC COMPOUNDS reaction consists in the removal of the halogen as sodium halide and union of the two radicals : 2RHlg + 2Na = R - R + aNaHlg. The synthesis can be varied by employing a mixture of two halides, e.g. bromobenzene and ethyl bromide, when treated with sodium, give ethyl benzene. The reaction is carried out by heating the halogen compounds with rather more than the calculated quantity of sodium in the form of thin slices, wire, or powder (p. 32) in some neutral solvent, such as ether, ligroin, benzene, &c. In some cases, however, the reaction is best carried out without a solvent (see sy m. -diphenyl ethane, below) . Also recent experiments made by the author point to liquid ammonia (in which sodium dissolves to give a deep blue solution) being a useful solvent in some cases. PREPARATION OF ETHYL BENZENE (C 6 H 5 . C 2 Hs) .1 Fifty grammes of bromobenzene and 45 grm. of ethyl bromide are dissolved in about 100 c.c. of anhydrous ether, and 25 grm. of sodium in thin slices or as wire added through a reflux condenser, the flask being cooled with ice. The whole is allowed to stand over-night and the supernatant liquid then decanted from the sodium bromide and unchanged sodium. Owing to the presence of this latter the residue must be destroyed by adding it little by little to cold water. The ethyl benzene is isolated from the ethereal solution by fractional distillation. It forms a colourless liquid boiling at 134. The yield is about 60 per cent. PREPARATION OF syw.-DIPHENYL ETHANE (Dibenzyl) (C 6 H 5 .CH 2 .CH 2 .C 6 H 5 ).2 A slight excess of sodium is added to benzyl chloride (12 parts sodium, 50 parts benzyl chloride) alone or dissolved in two volumes of dry toluene, and the whole heated under a reflux condenser on the water-bath until no further change takes place. If no toluene has been added the whole is extracted with anhydrous ether and the ethereal extract fractionated. If the reaction has been carried out in the presence of toluene, the toluene solution 1 A. 131, 303, 310. 2 A. 121, 250 ; 137, 258. THE HYDROCARBONS 37 is poured off, the residue washed once or twice by decantation with toluene, and the united liquors then fractionated. The dibenzyl is finally recrystallised from alcohol. Colourless needles melting at 5i-52 and boiling at 248. A large number of symmetrical diphenyl derivatives have been prepared by heating aromatic halogen compounds with copper powder. 1 The reaction is a very general one so far as the iodo-compounds are concerned, but the chloro- and bromo-compounds only react when nitro-groups are present in the ortho- or para-positions. Thus o- and ^-nitrobromobenzene give 2.2' and 44'-dinitrodiphenyl in good yield, whereas 3.3'-dinitrodiphenyl can only be obtained from w.-nitro- iodobenzene. The reaction is carried out by heating the iodo-compound with about its own weight of copper powder to a temperature of 230 to 280, and hence it is frequently necessary to work in closed vessels. The reaction takes place a great deal more readily when nitro-groups are present in the ortho- or ^)ra-positions. Thus 2.4-dinitro-i-chlorobenzene is converted into the corresponding diphenyl derivative by boiling with copper powder in nitrobenzene solution. The yields are usually 60 to 80 per cent. PREPARATION OF DIPHENYL (C a H 5 .C 6 H 5 ). Twenty grammes of iodobenzene and 20 grm. of copper powder are heated for three hours in a sealed tube to 230. The contents of the tube are then extracted with ether, and the ethereal extract filtered and fractionated. The diphenyl (B.P. 250- 255) is finally purified by recrystallisation from alcohol. Colourless leaflets melting at /o -?! . The yield is 82 per cent. PREPARATION OF 2.4.2'. 4'-TETRANITRODIPHENYL (N0 2 ) 2 [2.4]C 6 H 3 [i.i / ]C 6 H 3 (N0 2 ) 2 [2 / .4 / ]. 2 . Ten grammes 2.4- dinitro-chlorobenzene and 10 grm. of copper powder are boiled for an hour under a reflux condenser with 20 c.c. of nitrobenzene. After cooling, the solution is diluted with ether, filtered, and ligroin slowly added to the filtrate. An oil separates which becomes crystalline when the vessel is i B. 34, 2176. 2 B. 34, 2177. 38 PREPARATION OF ORGANIC COMPOUNDS scratched. It is collected and recrystallised from benzene. Yellowish prisms melting at 163. The yield is 66 per cent. (c) By the Loss of Halogen Acid. This method gives rise to unsaturated compounds : -CH 2 -CHHlg- -CH = CH- + HHlg and has proved particularly useful in the study of the terpenes. The reaction is carried out by heating the halogen compound with alcoholic (best methyl alco- holic) caustic potash, with alkali phenolates, or with organic bases such as aniline, dimethylaniline, quino- line, 1 &c. PREPARATION OF MENTHENE (C 10 H 18 ). 2 One hundred grammes of phosphorus pentachloride are covered with dry petroleum ether and 100 grm. of menthol added little by little, the whole being cooled with ice, and care being taken not to add further portions of menthol until no more hydro- chloric acid is evolved. The petroleum ether is then distilled off and the residue fractionated, the menthyl chloride (about 70 grm.) being collected at 2O5-2i5. This is added to a hot solution of 75 grm. of caustic potash in 320 grm. of phenol, the whole heated to 150 for ten to twelve minutes and then distilled until a thermometer immersed in the liquid registers 200. The distillate is washed with aqueous caustic potash until free from phenol and then distilled over metallic sodium. Colourless liquid boiling at i6o-i66. The rather indefinite boiling-point is due to the substance not being quite pure. CH(CH 3 ) 2 CH(CH 3 ) 2 CH(CH 3 ) 2 I I I CH CH C / \ / \ S\ CHOHCH 2 CH.C1CH 2 CH CH 2 I '-II II CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH CH CH I I I CH 3 CH 3 CH 3 Menthol Menthyl chloride Menthene 1 A. 227, 286 ; 245, 196 ; B. 40, 603 ; Soc. 85, 1403. 2 B. 29, 1843 ; 25, 686. THE HYDROCARBONS 39 PREPARATION OF DIPENTENE ([d +1] Limonene).i (C 10 H 16 ). Ten grammes of dipentene dihydrochloride and 20 grm. of aniline are cautiously warmed until a reaction sets in, and the heating then continued for two or three minutes. Glacial acetic acid (20 c.c.) is then added and the whole steam-distilled. The distillate is next steam-distilled with oxalic acid (mineral acids must not be used), and this process repeated until no more aniline comes over. The hydrocarbon is separated from the aqueous portion of the distillate, dried over solid caustic potash, and finally distilled over sodium. It forms a colourless liquid boiling at 178-! 80. CH 3 CH 3 CH 2 CH 3 NX c.ci CH, CH 2 CH CH 2 NX \/ C.CI C C Dipentene dihydrochloride Dipentene FROM THE ALCOHOLS. Hydrocarbons can be obtained from alcohols by two methods ; (a) By Loss of Water. This gives rise to unsaturated compounds, e.g. : CH 3 .CH 2 OH = CH 2 : CH 2 + H 2 O. The preparation of pyruvic acid by heating tartaric acid with acid potassium sulphate (p. 125) : f'HiCOH.COOH COH.COOH CO.COOH j | II -| + H 2 + C0 2 iHOJ CH . jCOOjH CH 2 CH 3 Enolic form Ketonic form Tartaric acid Pyruvic acid 1 B. 40, 603 ; A. 245, 196; 350, 150. 40 PREPARATION OF ORGANIC COMPOUNDS and of acrolein by heating glycerine with potassium bisulphate 1 : ['HO|CH 2 CH 2 CH 2 I Hi <- iOHi _* 2 H 2 O + C = CH "II II /OH | HO.HCjH ! C< CHO Enolic Ketonic Acrolein are the best-known examples of this reaction. The reaction is also frequently carried out by heating the alcohol with sulphuric acid, zinc chloride, phosphoric acid, &c. The last-named substance has the advantage over sulphuric acid that no sulphur dioxide is formed. PREPARATION OF ETHYLENE (CH 2 : CH 2 ). (a) A mixture of 25 grm. of alcohol and 150 grm. of concentrated sulphuric acid is placed in a capacious flask together with some dry sand (to lessen frothing), and the whole heated on a sand-bath until a steady stream of gas is evolved. A mixture of 100 grm. of alcohol and 200 grm. of concentrated sulphuric acid is then slowly run in from a dropping funnel, the end of which should be drawn out to a point. The evolved gas is led off through a delivery tube in the usual way and is freed from carbon dioxide and sulphurous acid by passing it through caustic potash solution. It is finally dried by passing through concentrated sulphuric acid. The gas can only be liquefied by means of liquid air. (b) 2 About 50 c.c. of syrupy orthophosphoric acid (D = i -75) are heated to 2OO-22O (thermometer bulb in liquid) and maintained at this temperature while alcohol is run in very slowly by means of a dropping funnel drawn out to a point and reaching right to the bottom of the flask. The gas is dried by passing through concentrated sulphuric acid. This is the best method of preparing ethylene, and is recommended for use in the preparation of ethylene di- bromide (p. 62). 1 B. 20, 3388. 2 Proc. 17, 147 ; J.R.C.S. 32, 76 ; C. 1900 L, noi. THE HYDROCARBONS 41 Camphene and menthene are obtained in 90 per cent. yield when borneol and menthol are heated on the water-bath for six to eight hours with continual stirring with dilute sulphuric acid (i acid, 2 water). (b) By Reduction. The alcohols as a rule are best reduced by prolonged heating under pressure with concentrated hydriodic acid and red phosphorus. Primary and secondary alcohols of the type ArCH 2 OH can be reduced by sodium and alcohol, the hydrocarbon ArCH 3 being the sole product. Alcohols of the type ArCH : CHOH are only partially reduced by this reagent, a mixture of ArCH 2 CH 3 and ArCH 2 .CH 2 OH being produced, the latter only being capable of reduc- tion by treatment with hydriodic acid. The tertiary alcohols, including the phenols, can be reduced by distillation over hot zinc-dust. The triaryl carbinols, Ar 3 COH, are particularly easily reduced, boiling with glacial acetic acid and zinc being sufficient treat- ment. 1 FROM THE ALDEHYDES AND KETONES. Both classes of substances on exhaustive reduction give the corresponding hydrocarbon, but the aldehydes are best first converted into the dichlor-compounds by the action of phosphorus pentachloride, and these then reduced by the methods cited on p. 35 : R.CHO -> R.CHC1 2 - RCH 3 . This procedure is also best when it is desired to reduce a fatty ketone. The mixed aliphatic-aromatic ketones are smoothly reduced by passing their vapour mixed with hydrogen over finely divided nickel (prepared by reducing nickel oxide with hydrogen at a low temperature) at a temperature of 190 to 195. The aromatic ketones are readily reduced by sodium (i part) and boiling alcohol (10 parts). PREPARATION OF DIPHENYL METHANE (C 6 H 6 ) 2 CH 2 . 2 Twenty grammes of benzophenone are boiled under a reflux 1 B - 35. 3137 ; M. 22, 613. 2 B. 31, 999- 42 PREPARATION OF ORGANIC COMPOUNDS condenser with 200 grm. of alcohol; and 20 grm. of metallic sodium slowly added to the boiling solution. When all the sodium has dissolved, the contents of the flask are satu- rated with CO 2 and then poured into cold water and the whole extracted with benzene. The benzene solution is dried over calcium chloride, the benzene distilled off from the water-bath, and the distillation then carried on under reduced pressure. The diphenyl methane passes over at 174-: 76 at 80 mm. and solidifies in the receiver to a mass of colourless needles melting at 25-26. The yield is about 90 per cent. The quinones are best reduced by dry distillation with zinc dust (10 to 50 parts). FROM UNSATURATED COMPOUNDS. Ethylenic bonds can be saturated by heating the substance in an atmosphere of hydrogen in the presence of a contact substance such as platinum-black or finely divided nickel. Palladium and its hydroxide also act as hydro- gen carriers and their use has been suggested as a commercial method x of reducing the unsaturated fatty acids obtained from Soya bean oil, fish oils, &c. (oleic acid, linolic acid, &c.), thus rendering it possible to obtain a hard soap from these fats. Ethylenic bonds can also be reduced by sodium and alcohol or by sodium amalgam. 2 THE FRIEDEL-CRAFTS REACTION. This is one of the most generally known methods of obtaining aromatic hydrocarbons and consists in condensing the alkyl halide with an aromatic hydrocarbon in the presence of anhydrous aluminium chloride, e.g. : C 6 H 6 + RHlg = C 6 H 5 .R + HHlg. The reaction is not limited to alkyl halides, acyl halides reacting in exactly the same way to produce ketones (p. 127). The reaction is carried out either by mixing the hydrocarbon with the alkyl halide and then slowly adding the aluminium chloride, or the aluminium chloride is mixed with the hydrocarbon and the alkyl halide slowly added. The reaction as a rule takes 1 E.P. 5188". 2 A. 121, 375. THE HYDROCARBONS 43 place without the application of heat. The product is finally isolated by pouring the reaction mixture into water, separating, and fractionating the product. As a rule a large excess of the hydrocarbon is used in order to moderate the reaction, but this effect can also be brought about by the use of some neutral solvent such as ligroin, carbon bisulphide, or nitro- benzene. The last of these substances is often espe- cially useful owing to its power of dissolving anhydrous aluminium chloride. The action of the aluminium chloride is catalytic, a small quantity being, as a rule, capable of converting a large quantity of hydrocarbon into its homologue. In the case of ketones, however, the aluminium chloride often forms a compound, and, therefore, in condensing an acid chloride with an aromatic compound it is usually necessary to use a molecular quantity of aluminium chloride. Aluminium chloride can often be advantageously replaced by aluminium foil and anhydrous hydro- chloric acid gas * or mercuric chloride, by aluminium mercury couple, 2 or by anhydrous ferric chloride. PREPARATION OF TRIPHENYL METHANE, (C 6 H 5 ) 3 CH. 3 Forty grammes of chloroform, previously dried with calcium chloride, are dissolved in 200 grm. of dry benzene, the whole placed in a flask fitted with a reflux condenser, and 25 grm. of anhydrous aluminium chloride added little by little. The reaction sets in at the ordinary temperature, causing brisk ebullition and evolution of hydrochloric acid. When all the aluminium chloride has been added the whole is boiled for forty minutes, cooled, and then poured slowly into cold water. The benzene layer is separated, dried over calcium chloride, and then distilled at the ordinary pressure until the temperature reaches 200. The residue is then fractionated under reduced pressure. Some diphenyl methane (B.P. 175 at 80 mm.) first passes over, and then the triphenyl compound. The distillation is continued as long as the 1 B. 28, 1136. 2 Soc. 67, 826. 3 B. 26, 1961 ; A. 235, 207. 44 PREPARATION OF ORGANIC COMPOUNDS distillate solidifies on cooling. The hydrocarbon is then recrystallised twice from benzene, from which it separates with one molecule of benzene of crystallisation. This benzene is driven off by heating on the water-bath, and the pure hydrocarbon recrystallised from alcohol. It forms colourless plates melting at 92 and boiling at 358. The yield is about 35 per cent. PREPARATION OF DIPHENYL METHANE (C 6 H 5 ) 2 CH 2 .i One gramme of aluminium foil in thin strips is treated for one to two minutes with a concentrated solution of mercuric chloride and then rinsed thoroughly, first with cold water, then with absolute alcohol, and finally with benzene. These operations must be carried out as rapidly as possible, and the couple at once added to 65 grm. of benzene contained in a flask fitted with a reflux condenser. Thirty grammes of benzyl chloride are then slowly run in during an hour, when a brisk reaction sets in with rise of temperature and evolution of hydrochloric acid. When all the benzyl chloride has been added, the whole is boiled on the water-bath for fifteen minutes, cooled, shaken up with dilute caustic soda, and the benzene layer separated. The aqueous portion is extracted with benzene, the benzene solutions united, dried over calcium chloride, and the benzene then removed by distillation from the water-bath. The residue is then fractionated under reduced pressure, the diphenyl methane passing over at 174-! 76 at 80 mm. Colourless needles, M.P. 25, B.P. 262. The yield is about 20 per cent. FROM THE DIAZO-COMPOUNDS. This method is limited to the aromatic series, and can be carried out in two directions, viz. : (a) The diazo-group is replaced by hydrogen. The classical method of reducing a diazo-compound is by heating it with alcohol : R.N : N.C1 -j-C 2 H 5 OH = RH + N 2 + HC1 + CH 3 CHO but the phenolic ether is often obtained simul- taneously : R.N 2 C1 + C 2 H 6 OH = R.OC 2 H 5 + N 2 + HCL i Soc. 67, 826. THE HYDROCARBONS 45 Hypophosphorous acid, HPO 2 , often gives excellent results. It is applied either in the form of the com- mercial solution (D = 1-15) or as the calcium salt with the calculated quantity of sulphuric acid. The diazo-compounds can also be reduced by sodium stannite 1 or alkaline solutions of sodium hydro- sulphite, 2 but the yields are usually poor. Those diazo-compounds which contain negative groups in the ortho- or ^am-position usually give the best yields on reduction. PREPARATION OF DIPHENYL (C 6 H 5 . C 6 H 5 ) . 3 Thirty grammes of benzidine are dissolved in 70 grm. of concentrated hydrochloric acid and 400 c.c. of water, and diazotised in the usual way (see p. 238) with sodium nitrite (23 grm.) . A filtered, ice-cold solution of hypophosphorous acid, obtained by digest- ing 150 grm. of finely powdered calcium hypophosphite with 45 c.c. of concentrated sulphuric acid and 500 c.c. of water for some time at 80 or a corresponding amount of the com- mercial acid, is then added and the whole allowed to stand in the ice-chest for several days until no more solid separates. The diphenyl is then filtered off, suspended in dilute caustic soda, and distilled in steam. M.P. 71, B.P. 254. The yield is 60 per cent. (b) The diazo-group is eliminated and two aryl groups linked together. This method is confined to the preparation of symmetrical diaryl compounds. The reaction is carried out either by adding a hydrochloric acid solution of cuprous chloride to the diazo-salt, 4 in which case part of the diazo-compound is simul- taneously converted into the corresponding chloro- derivative (Sandmeyer's reaction, see p. 75), or the diazo-chloride is treated with copper powder 5 (best, the copper paste described on p. 75). The latter reaction proceeds most smoothly in alcoholic or aqueous alcoholic solution. The copper powder can be replaced by zinc dust or iron powder, but the yields are usually not so good. i B. 22, 587. 2 B. 40, 858. 3 B. 35, 162. 4 B. 34, 3802 ; 38, 725. 5 B. 23, 1226. 46 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF s.s'-DINITRODIPHENYL (NO 2 [3J C 6 H, i [i.i / ]C 6 H 4 [3 / ]NO 2 ). 1 Thirty grammes of m.-m tramline are dissolved or suspended in 45 grm. of concentrated sulphuric acid and 60 c.c. of water, and diazotised as usual with 15-3 grm. of sodium nitrite. The diazo-solution thus obtained is run slowly and with continual stirring into a cold solution of 22 grm. of cuprous chloride in 100 c.c. of concentrated hydrochloric acid. When the solution has become green the reaction product is filtered off and distilled in steam. m.-Chlornitro- benzene (6 grm.) passes over and dinitrodiphenyl remains in the flask, and it is collected and recrystallised from glacial acetic acid. Yellow needles. M.P. 200. The yield is 87 per cent. PREPARATION OF DIPHENYL (C 6 H 5 .C 6 H 5 ). 2 Thirty-one grammes of aniline are dissolved in 150 c.c. of water and 40 grm. of concentrated sulphuric acid, and diazotised in the usual way with 23 grm. of sodium nitrite. One hun- dred grammes of 90 per cent, alcohol are added and then slowly 50 grm. of copper powder. The temperature of the solution rises to 30 40 and nitrogen is evolved. After stirring for an hour the whole is distilled in steam and the distillate collected whenever a sample gives solid matter on dilution with water. M.P. 71. The yield is about 25 per cent. FROM THE CARBOXYLIC ACIDS. The carboxyl group is not easily reduced, but may be eliminated by distilling the sodium salt of the acid with soda-lime. Thus sodium benzoate distilled with soda-lime gives benzene in good yield. The sulphonic group is often similarly eliminated. Hydrocarbons are also often obtained by the electrolysis of the sodium salts of the acids. Thus potassium acetate on electrolysis gives ethane : 2CH 3 COOK + 2H 2 O = CH 3 . CH 8 + 2CO 2 + 2KOH + H 2 , and potassium succinate gives ethylene : CH 2 .COOK CH 2 I + 2 H 2 = || + 2C0 2 + 2KOH + H 2 . CH 2 .COOK CH 2 i B, 38; 726. 2 B. 23, 1226. THE HYDROCARBONS 47 These methods, however, are of theoretical rather than practical importance. FROM THE LOWER HYDROCARBONS BY OXIDATION. This reaction is, as a rule, of no great importance as a preparative method, but is worthy of mention. The reaction only takes place in the ali- phatic series in a few cases, and then only to a very minor extent (yields i to 2 per cent.). Unsaturated compounds, however, react more readily than satu- rated ones. Thus the copper acetylides are oxidised by shaking their alkaline solutions with air or on treating them with potassium ferricyanide. The best-known case of this reaction is the oxidation of the copper salt of o.-nitrophenylacetylene to the corresponding di-acetylene : NO, NO, =C C=C NO 2 NO 2 and this is one of the steps in an earlier indigo synthesis. In the aromatic series the reaction takes place with greater ease and is usually carried out by heating the hydrocarbon with an aqueous solution of potassium persulphate. PREPARATION OF DIBENZYL (C6H 5 .CH 2 .CH 2 .C6H 5 ).i Thirty grammes of toluene are heated with continual stirring for four hours on the water-bath with a solution of 44 grm. of potassium persulphate in 500 c.c. of water. The oily 32, 432, 2531. 48 PREPARATION OF ORGANIC COMPOUNDS layer is then collected, dried with calcium chloride, and fractionated. Toluene and benzaldehyde pass over first, and then between 270 and 280 a mixture of benzoic acid and dibenzyl. This portion of the distillate is dissolved in ether, washed with dilute caustic soda (to remove benzoic acid), the ether removed, and the residue recrystallised from dilute alcohol. Yield about 15 per cent. CHAPTER III HALOGEN COMPOUNDS THE chief methods of preparing halogen compounds are : (i) Replacement of hydrogen by means of (a) mole- cular halogen, (b) nascent halogen, (c) halogen compounds. (ii) Addition of halogen or halogen acid to unsatu- rated compounds. (iii) Replacement of hydroxyl by halogen. (iv) Replacement of the diazo-group by halogen. (i) (a) REPLACEMENT OF HYDROGEN BY MEANS OF MOLECULAR HALOGEN. Chlorine reacts with methane in direct sunlight with explosive violence, carbon being deposited and hydrochloric acid formed. In diffused daylight the hydrogen atoms are successively replaced, carbon tetrachloride being the final product. As a rule, however, chlorine and bromine only replace hydrogen slowly. With iodine the reaction is usually too sluggish to be of any great practical importance. The reaction can be greatly accelerated by adding a halogen " carrier." The most frequently used carriers are, iron and anhy- drous iron halides, aluminium halides, sulphur, iodine, chlorides of antimony, and phosphorus pentachloride. Of these, iodine, phosphorus pentachloride, and the chlorides of antimony all direct the halogen to the side chain when employed in halogenating aromatic com- pounds. Heat and direct sunlight also have a beneficial effect on the course of the reaction. 49 4 50 PREPARATION OF ORGANIC COMPOUNDS It is often necessary to dissolve the substance which is to be halogenated, and the best solvents are water, sulphuric acid, chloroform, carbon tetrachloride, and glacial acetic acid. In the case of bromine, aqueous potassium bromide is sometimes a convenient sol- vent, as bromine is more soluble in this than in water. As a source of chlorine either a cylinder of the com- pressed gas can be used or the gas can be generated by allowing concentrated hydrochloric acid to drop on solid potassium, or better, calcium permanganate. No heating is required at first, but when the stream of gas begins to slacken the flask should be warmed. Chlorine is best dried by passing it through concen- trated sulphuric acid. All corks, rubber or otherwise, when exposed to the action of chlorine or bromine should be protected by coating with paraffin wax or collodion. PREPARATION OF MONOCHLORACETIC ACID (CH 2 C1COOH). One hundred grammes of glacial acetic acid and 10 grm. of sulphur are placed in a tubulated glass retort and the whole weighed. The retort is then supported on a sand-bath with the neck sloping upwards. A condenser is attached to the neck so as to form a sloping reflux and is provided with a calcium chloride tube. A fairly rapid stream of dry chlorine is led in by a tube passing through the tubulus and reaching almost to the bottom of the retort. The acid is kept gently boiling and the stream of chlorine continued until an increase in weight of about 38 grm. has taken place. This usually takes about 10 hours but the reaction is greatly facilitated by direct sunlight. The liquid is then poured off from the sulphur and distilled. The first portions consist of acetyl chloride, acetic acid, &c., and are rejected. The fraction boiling at about i6o-i9O is collected and, after cooling, any liquid portion poured off and the solid then redistilled. Colourless sharp-smelling crystals. M.P. 63, B.P. i85-i87. Yield about 70 to 80 grm. In halogenating fatty acids the halogen always attaches itself to the a-carbon atom. The reaction possibly takes place in the following stages : HALOGEN COMPOUNDS CH,.COOH /OH CH 2 : C< X OH Enolic form. ^- O;H| - X OH ' -> CH 2 C1.G( +HC1 X3H When halogens act on aromatic compounds at the ordinary temperature it is the hydrogen of the nucleus that is attacked, whereas at elevated temperatures the halogen enters the side chain. According to Brunei and Vorbrodt, 1 when bro- minating aromatic com- pounds in solution, the greater the ionising power of the solvent the more readily the halogen enters the nucleus. PREPARATION OF BROMO- BENZENE (C 6 H 5 Br). 2 Fifty grammes of benzene containing about J grm. of pyridine (to act as a halogen carrier) are placed in a flask fitted with an upright condenser and trap as shown in Fig. 47. One hundred and twenty grammes of bromine (40 c.c.) are then added and the whole heated gently on a water-bath to 25- 30. At this temperature a FIG. 47. vigorous reaction sets in with evolution of hydrobromic acid. When the reaction has moderated, the temperature is slowly raised to 65~7O and maintained at this point until the evolution of hydro- bromic acid has almost ceased. After cooling, the contents 1 Ch. Z. 33, 557. 2 Soc. 76, 894- 52 PREPARATION OF ORGANIC COMPOUNDS of the flask are well washed with dilute caustic soda (the washings must react alkaline), dried over calcium chloride, and then distilled. Unchanged benzene passes over at about 8o-ioo and is rejected. The higher boiling portions are collected and fractionated. Heavy colourless oil. B.P. 155. Yield 60 grm. PREPARATION OF BENZYL CHLORIDE (C^CH^Cl). 1 One hundred grammes of toluene and 5 grm. of phosphorus pentachloride (to act as chlorine carrier) are placed in a tubu- lated retort connected with a reflux condenser carrying a calcium chloride tube at the end (Fig. 8). The toluene is boiled and a stream of dry chlorine is led into the boiling liquid through the tubulus. This treatment is continued until 37 grm. of the gas have been taken up. The liquid is then fractionated and the fraction boiling between 165 and 185 collected and repeatedly refractionated (best with a column apparatus, see p. 26), until a fraction is obtained boiling at 176-! 80. Colourless liquid with an irritating smell. B.P. 176. Yield 80 to 90 grm. The portions boiling above 185 consist chiefly of benzal chloride, C 6 H 5 CHC1 2 , and benzotrichloride (phenylchloroform), C 6 H 5 CC1 3 . PREPARATION OF BENZOYL CHLORIDE (C 6 H 6 COC1). 2 Dry chlorine is led into 100 grm. of cold benzaldehyde in the apparatus described in the previous preparation. The gas is readily absorbed with evolution of heat, and torrents of hydrochloric acid are given off. When the reaction has moderated heat is applied so as to keep the liquid boiling briskly, and the stream of chlorine is continued until no more hydrochloric acid is evolved. A stream of dry air or carbon dioxide is then passed through the apparatus in order to drive out excess of chlorine. Finally the product is distilled. Colourless fuming liquid with a very irritating smell. Yield almost quantitative. This is the technical method of pre- paring benzoyl chloride, and thus obtained it always contains rather more chlorine than required by theory. This is due to some slight substitution having taken place in the nucleus. Hydroxyl- or amino- groups attached to the nucleus greatly facilitate the entrance of halogen. The B. 18, 606; A. 272, 149. 2 A. 3, 1262. HALOGEN COMPOUNDS 53 halogen first enters the para- and then the two ortho- positions. PREPARATION OF TRIBROMOPHENOL. Ten grammes of phenol are dissolved in 200 c.c. of cold water, and 52 grm. of bromine in aqueous solution added. The precipitated tri- bromophenol is collected, washed with water, and recrystallised from dilute alcohol. Long slender needles melting at 95. Yield quantitative. Other phenols behave in the same way and the reaction has been applied to their quantitative estimation. 1 In brominating or chlorinating primary amines it is usually necessary to protect the amino-group from the oxidising action of the halogen by replacing one of the hydrogen atoms. This is best done by forming an acety /-derivative (see p. 228). PREPARATION OF 5-BROM ACET-o.-TOLUIDE. 2 Twenty grammes of acet-o.-toluide are dissolved in 130 grm. of glacial acetic acid, and bromine-laden air is drawn through the solution by means of a filter- pump until the whole solidifies to a white, crystalline mass. The acetic acid is then removed as completely as possible by draining on a Buchner funnel at the pump, and the bromacet-o.-toluide recrystallised from alcohol. Yield 15 grm. M.P. I56-I57. The acetyl group can be removed by boiling with hydrochloric acid. The acetic acid mother-liquors from the above preparation contain 5-brom-0.-toluidine, which has been formed by the saponification of the bromacettoluide by the hydrobromic acid liberated during the reaction. The hydro bromide of the base crystallises out in pearly leaflets when the acetic acid is removed by distillation. The free base can be obtained by steam-distilling this from slightly alkaline solution. M.P. 58. Secondary and tertiary amines can usually be directly halogenated. 1 Hans Meyer, "Analyse u. Konstitutionsermittlung, " 2nd ed. (1909), p. 467. 2 B. 25, 868. 54 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF TETRABROMDIPHENYLAMINE. Eight grammes of diphenylamine are dissolved in alcohol and 65 grm. of bromine dissolved in 100 c.c. of the same solvent slowly added with continual stirring. The whole is then poured into about 500 c.c. of water, filtered, well washed, and recrystal- lised from alcohol. Colourless needles. M.P. 182. Yield quantitative. (i) (b) REPLACEMENT OF HYDROGEN BY MEANS OF NASCENT HALOGEN. Substitution often takes place more readily when molecular halogen is replaced by the nascent element, and in addition the method has the advantage of allowing the amount of halogen used to be more accurately regulated. The nascent halogen can be generated by the action of an oxidising agent (K 2 Cr 2 O 7 , or, better, HHlgO 3 , where Hlg stands for chlorine, bromine, or iodine) on the halogen acid or one of its salts in the presence of sulphuric acid, e.g. : 5NaBr + NaBr0 3 + 3H 2 SO 4 = 3 Na 2 S0 4 + 6Br + 3H 2 O, or by the action of halogen acid on a salt of the type HHlgO, or the halogen can be liberated electrolytically. In the case of bromine the element is sometimes liberated simply by the action of sulphuric acid on potassium bromide : 2KBr + 2H 2 SO 4 = K 2 S0 4 + 2H 2 O + SO 2 + 2Br. The mixture of bromide and bromate, &c., can either be prepared by weighing out the individual salts or excess of halogen is added to aqueous caustic soda and the solution evaporated to dryness : 6KOH + 3Br 2 = sKBr + KBr0 3 + 3H 2 O. The residue is then dissolved in water and the active halogen estimated by titration in the ordinary way. It is convenient to prepare a solution of such a strength that on acidifying i c.c. liberates o-i grm. of halogen. HALOGEN COMPOUNDS 55 Bromination and iodination of aromatic compounds can often be conveniently brought about by means of the corresponding sulphur halides in the presence of nitric acid (see p. 57). PREPARATION OF 2-6 - DICHLOR - 4 - NITRANILINE. 1 Twenty-eight grammes of /?.-nitraniline are dissolved in 250 c.c. of concentrated hydrochloric acid at 50. To this is gradually added a solution of 16-4 grm. of potassium chlorate in 350 c.c. of water at about 25. When the whole of the chlorate has been added the solution is diluted with a large volume of water, and the resulting precipitate removed by nitration and well washed. It may be further purified by crystallisa- tion from glacial acetic acid or a mixture of this solvent and alcohol. Yield 87 per cent. Lemon-yellow needles. M.P. i85-i88. PREPARATION OF a-BROMNAPHTHALENE. Seventy grammes of bromine are dissolved in 350 c.c. of 10 per cent. caustic soda. Twenty-five grammes of finely powdered naphthalene, and then with continual stirring 250 c.c. of 10 per cent, hydrochloric acid, are added slowly through a tube reaching to the bottom of the vessel. Oily a-bromnaphthalene forms and is collected and washed, first with 10 per cent. sodium carbonate solution and then with water. The oil is then heated to 200 until no more hydrobromic acid (present as an addition compound) is evolved. It is finally distilled, and the distillate passing over between 200 and 210 collected. Colourless liquid. B.P. 208. PREPARATION OF 2.6-DIBROMSULPHANILIC ACID. Seventeen grammes of sulphanilic acid are dissolved in 500 c.c. of hot water, and to the solution thus obtained a solution of 10 grm. of bromine in 125 c.c. of 13 per cent, caustic soda is added. By means of a tube reaching to the bottom of the vessel 21 grm. of concentrated hydrochloric acid are then slowly run in with continual stirring. When all the acid has been added, the solution is carefully neutralised with caustic soda and a concentrated solution of 25 grm. of crystal- lised barium chloride added. The precipitated barium salt, which contains two molecules of water of crystallisation, is * B. 36, 43 Qi. 56 PREPARATION OF ORGANIC COMPOUNDS collected by filtration after the solution has cooled. To obtain the free acid the barium salt is suspended in water and decom- posed with the calculated amount of sulphuric acid. The precipitated barium sulphate is removed by filtration and the clear filtrate concentrated until crystallisation sets in. On cooling, 2.6-dibromsulphanilic acid separates out in long needles containing two molecules of water. It is easily soluble in cold water and hot alcohol. When heated it decomposes at about 180. (i) (c) REPLACEMENT OF HYDROGEN BY MEANS OF HALOGEN COMPOUNDS. Hydrogen is often conveniently replaced by halogen by means of halogen compounds. The most frequently employed of these latter are the halides of phosphorus and sulphur, antimony pentachloride, sulphuryl chloride, and iodine chloride. Further, in the case of quinonoid compounds, prolonged heating with halogen acid sometimes causes the entrance of halogen into the ring, but this method is only of theoretical interest. Bleaching powder has also been employed as a chlorinating agent, the most notable case being in the preparation of chloroform (see p. 78). PHOSPHORUS HALIDES. The halogen first enters the side-chain and does not enter the nucleus until the hydrogen of all the side-chains is completely replaced. Thus o- and ^>-xylene, when heated with PC1 5 under pressure at 200, give CCl 3 C 6 H 4 CHCl 2 and (CC1 3 ) 2 C 6 H 4 . 1 For chlorinating, however, the method is of but minor importance, but is sometimes of great use in bromi- nating. In this case it is usual not to employ separately prepared phosphorus bromide, but rather a mixture of bromine and red phosphorus, and care must be taken to use a good sample of the latter, as red phosphorus often contains considerable quantities of the yellow variety, and this reacts with bromine with extreme violence. Also it is usually necessary to have the reagents perfectly dry, and as red phosphorus nearly always contains phosphoric acid, it must be well 1 C. r. 102, 689. HALOGEN COMPOUNDS 57 washed with water until the wash-liquors are no longer acid in reaction, and then carefully dried. The bro- mine must be dried by shaking with concentrated sulphuric acid. PREPARATION OF MONOBROMSUCCINIC ACID. CH 2 .COOH(i) This preparation is best carried out in a CHBr.COOH. tubulated retort the neck of which is sealed into a Liebig's condenser. The end of the condenser should be connected with an absorption apparatus as shown in Fig. 47 (p. 51), in order to prevent the escape of the hydrobromic acid and bromine fumes into the air. An intimate mixture of 18 grm. of carefully dried succinic acid and 3-5 grm. of red phosphorus is placed in the retort and 80 grm. of bromine are added slowly by means of a dropping funnel through the tubulus. At first each drop of bromine causes a very violent reaction, and there- fore care must be taken not to add more than a drop at a time. When all the bromine has been added the whole is heated on the water-bath until the bromine has disappeared. The retort now contains monobromsuccinyl bromide formed according to the equation : CH 2 .COOH 3 | + 2P + 8Br 2 = CH 2 .COOH CHBr.COBr 3 | + 2HP0 3 + 7HBr. CH 2 .COBr In order to decompose this and obtain the acid, the contents of the retort are poured slowly into 100 c.c. of boiUng water contained in a basin from which the flame has been withdrawn. When all the bromide has been added, the whole is filtered, cooled, and repeatedly extracted with ether. The united ethereal extracts are distilled on the water-bath, and the solid residue of monobromsuccinic acid recrystallised from a little water. It melts at 160. The yield is 80 to 90 per cent. SULPHUR HALIDES. The chlorides of sulphur have met with no success as chlorinating agents, but excel- i A. 242, 145; 6.14,892. 58 PREPARATION OF ORGANIC COMPOUNDS lent results are often obtained by using the bromide or iodide in the presence of nitric acid. The halogen exclusively enters the nucleus and only monobrom- or monoiodo-compounds are obtained. 1 The reaction is carried out as follows. The hydrocarbon to be halogenated is dissolved in about 4 parts of ligroin, and the solution thus obtained poured on to about 3 parts of nitric acid (D 1-4). Excess of sulphur bromide is then slowly added with careful cooling during about three hours. The upper layer is then separated, washed first with dilute caustic potash and then with water, the ligroin distilled off, and the brominated compound distilled with steam and then fractionated. When preparing iodine compounds by this method it is usually necessary to heat the reaction mixture, and a more dilute acid (D 1-34) is employed. The yields are usually from 80 to 95 'per cent, of theory. In some cases nitration takes place simultaneously to a small extent. PREPARATION OFa-BROMNAPHTHALENE. Fifty grammes of naphthalene are dissolved in 200 c.c. ligroin and the solution poured on to 200 c.c. of nitric acid (D = 1-4). The vessel is then surrounded with a freezing mixture of ice and salt, and when the temperature has fallen to o, 120 grm. of sulphur bromide are slowly added during about three hours. The ligroin layer is then separated, washed with dilute caustic soda and then with water. The ligroin is distilled off, and the residue, which contains about 5 per cent, of nitronaphthalene, reduced with tin and hydrochloric acid (10 grm. of tin and about 200 c.c. of 20 per cent, acid), and then steam-distilled. The naphthylamine remains behind as the hydrochloride, whereas the bromonaphthalene passes over. It is separated from the water and redistilled over a little solid potash. It forms a colourless oil boiling at 280. PREPARATION OF 4-IODO-W.-XYLENE. Ten grammes of w.-xylene are dissolved in 80 c.c. of ligroin, and the solution thus obtained poured on to 120 c.c. of nitric acid (D = 1-34). 1 Durol gives a dibro mo -compound. HALOGEN COMPOUNDS 59 Twenty grammes of powdered sulphur iodide are then added and the whole heated on the water-bath under a reflux con- denser for three to four hours. The ligroin layer is then separated, washed with dilute caustic soda, and the ligroin distilled off. The residue is steam-distilled, and the oil which comes over collected and distilled over a little solid potash. Colourless oil boiling at 220. Yield 75 per cent. ANTIMONY PENTACHLORIDE. Antimony penta- chloride is sometimes useful for chlorinating and is converted in the process into the trichloride. It is occasionally used in the presence of iodine for the exhaustive chlorination of aliphatic compounds of high molecular weight, such as palmitic acid. 1 It is also capable of chlorinating aromatic compounds in the nucleus. PREPARATION OF 3-4-DICHLORBENZOIC ACID. 2 Ten grammes of ^.-chlorbenzoic acid and 75 grm. antimony pentachloride are heated in a sealed tube to 200 for about eight hours. After cooling, the tube is opened and the contents treated with excess of dilute hydrochloric acid. The preci- pitated acid is collected, washed with cold water, and dissolved in dilute ammonia. After filtration the solution is evaporated to dryness and the ammonium salt decomposed with dilute hydrochloric acid. The acid is collected, washed, and dried in the usual way. It is recrystallised from dilute alcohol and forms colourless crystals melting at 2Oi-2O2. SULPHURYL CHLORIDE (SO 2 C1 2 ). Sulphuryl chloride is useful for replacing hydrogen atoms when in the a-position to carbonyl or carboxyl groups. In some cases oxidation takes place simultaneously. Thus when hydroquinone in ethereal solution at o C. is treated with sulphuryl chloride, first y-dichlorquinone and finally chloranil is formed. 3 1 B. 16, 2870 ; 24, 1025. 2 A. 179, 283. 3 G. 24, [2] 375 ; B. 28 ; R. 72. 6o PREPARATION OF ORGANIC COMPOUNDS OH O O Cl Cl/ X iCl Cl CL JC1 OH O O It has also been used for chlorinating various aromatic compounds both in the side-chain and in the nucleus. 1 PREPARATION OF MONOCHLORMALONIC ACID, CHC1(COOH) 2 . 2 Carefully dried malonic acid (10-4 grm.) is dissolved in 300 c.c. of absolute ether (dried over sodium), and 1 3 '5 grm. of sulphuryl chloride slowly added with careful cooling. When the reaction is over, the ether is removed by distillation and the residue set aside in a vacuum desiccator over concentrated sulphuric acid until crystallisation takes place. Colourless crystals. M.P. 133. Yield almost quan- titative. * In the same way, by using twice the quantity of sulphuryl chloride, dichlormalonic acid can be obtained. In this case it is best, after removing the ether, to dissolve the residue in alcohol, pass in dry hydrochloric acid gas, and then fractionate the ester thus formed. For the preparation of monochloracetic acid by heating acetic acid with sulphuryl chloride under pressure, the reader is referred to D.R.P. 146,796; 160,102 ; and 162,894 ; or at the ordinary pressure in presence of acetyl chloride, D.R.P. 157,816. The yields are said to be excellent. IODINE CHLORIDE. Iodine monochloride is used for replacing hydrogen by iodine. It is usual to work in glacial acetic or dilute hydrochloric acid solution. 1 Z. Ch. 1866, 705 ; B. 26, 2942 ; ).R.P. 139,552 ; 158,951 ; 160,102 ; 162,394. 2 B. 35, 1814. HALOGEN COMPOUNDS 61 PREPARATION OF IODONITR ANILINE (2.4.1).! Ten grammes of /?-nitraniline are dissolved in the least possible quantity of cold glacial acetic acid, and, with continual stirring, a solution of 17-8 grm. of iodine chlorine in the same solvent added slowly. When all the iodine chloride has been added the whole is allowed to stand for one hour and then poured into 1000 c.c. of boiling water. After boiling for a few minutes the solution is filtered, and on cooling, the filtrate deposits long yellow needles of 2-iodo-4-nitraniline, melting at 105. By working at a higher temperature and using double the quantity of iodine chloride, 2.6-di-iodo-4-nitraniline is obtained. BLEACHING POWDER. Bleaching powder has met with very extensive use in the preparation of chloro- form (see p. 78), and has also been used as a chlorinat- ing agent where simultaneous oxidation is not desired. PREPARATION OF ACET-.-CHLORANILIDE. 2 Five grammes of acetanilide are dissolved with gentle warming in a mixture of 10 grm. of glacial acetic acid and 10 grm. of alcohol. The solution is then diluted with 100 c.c. of water and heated to 50. At this temperature 100 c.c. of a cold, 10 per cent, solution of bleaching powder are slowly added with continual stirring. The acet-.-chloranilide is collected, washed with water, and recrystallised from alcohol or dilute acetic acid. Colourless needles. M.P. 172-5. (ii) ADDITION OF HALOGEN OR HALOGEN ACID (a) ADDITION OF HALOGEN. Chlorine and bro- mine are, as a rule, readily taken up by compounds con- taining a double or triple bond, whereas iodine but rarely reacts in this way. Compounds containing a conjugated double bond, C=C C=C , react abnormally and on the addition of halogen give a -CHk-C=C-CHlff-. substance of the type CHlg-C=C~CHlg- An explanation of this behaviour is furnished by Thiele's theory of latent valencies. 1 B - 34. 3344- 2 A. 182, 98. 62 PREPARATION OF ORGANIC COMPOUNDS When bringing about such addition-reactions the most usual solvents are CS 2 , CC1 4 , glacial acetic acid, and ether. When forming addition compounds with the ter- penes, Wallach recommends alcohol as a solvent. As a rule better results are obtained with bromine than with chlorine, as in the latter case there is more danger of substitution taking place simultaneously. PREPARATION OF ETHYLENE DIBROMIDE. 1 A fairly rapid stream of ethylene is generated from alcohol and sul- phuric or phosphoric acid {see p. 40), and after washing, first with water and then with dilute caustic soda, is passed into 100 grm. of bromine contained in a vessel surrounded by cold water or ice. The stream of gas is continued until the bromine is decolorised. The oily liquid is then washed with dilute caustic soda solution, dried with calcium chloride, and finally distilled. Colourless oily liquid, freezing at 8 and boiling at 131. PREPARATION OF CINNAMIC ACID DIBROMIDE (Ph . CHBr . CHBr . COOH) . 2 Twenty-five grammes of cinnamic acid are dissolved in 100-125 c.c. of dry ether and the whole cooled to o by surrounding with ice or a freezing mixture. Twenty-seven grammes of bromine are then slowly added, and, as the reaction is very violent in direct sunlight, care must be taken to exclude all but diffused light. When all the bromine has been added, the solution, which should be colourless, is transferred to a distilling flask and the ether removed by distillation. The residue is then recrystallised from dilute alcohol. Instead of distilling off the ether, the acid can be extracted by shaking out with dilute caustic soda solution, and then precipitated from the aqueous extract by acidifying with hydrochloric acid. Colourless leaflets. M.P. 195. Yield almost quantitative. PREPARATION OF CINNAMIC ACID DICHLORIDE. 3 This experiment must be carried out in direct sunlight. Fifteen grammes of finely powdered cinnamic acid are suspended in 120 grm. of freshly distilled carbon bisulphide, and the whole saturated with dry chlorine until of a greenish yellow colour. 1 A. 168, 64 ; 192, 244. 2 A. 195, 140. 3 B. 14, 1867. HALOGEN COMPOUNDS 63 The solution is then violently shaken until the colour has disappeared, resaturated with chlorine, and this process repeated until rather more than the calculated weight of chlorine (6-5 grm.) has been taken up. The precipitated acid is then collected by nitration and recrystallised from dilute alcohol. Colourless leaflets melting with slight decomposition at i62-i64. Yield 90 to 95 per cent. When the addition of chlorine takes place in the dark a totally different but isomeric substance is formed. For experimental details, &c., see B. 27, 2041. (b) ADDITION OF HALOGEN ACID. 1 Hydriodic acid adds on most readily, hydrobromic acid less readily, and hydrochloric acid, as a rule, only with difficulty, but the terpenes often readily form addition compounds with this last. In unsymmetrical com- pounds, e.g. CH 3 .CH : CH 2 , the halogen attaches itself to the carbon atom which is poorest in hydrogen 2 (MarkownikofFs rule). PREPARATION OF ft - PHENYL - ft - BROMPROPIONIC ACID (Ph.CHBr.CH 2 COOH). 3 Ten grammes of finely pow- dered cinnamic acid are shaken for two days with 50 c.c. of an aqueous solution of hydrobromic acid saturated with the gas at o. The precipitate is then collected, washed with a little ice-water, pressed between filter-paper, and dried in vacua over solid potash at the ordinary temperature. A more expeditious method is to saturate glacial acetic acid at the ordinary temperature with hydrobromic acid (i part of glacial acetic acid dissolves about 0-6 part of HBr), and then to heat the solution thus obtained with the cinnamic acid in a sealed tube at 100 for two hours. On cooling, the addition compound crystallises out. As bromhydrocinnamic acid is very readily decomposed by water it can only be recrystallised from anhydrous media. For this purpose carefully dried carbon bisulphide is best, as bromhydrocinnamic acid is only slightly soluble in this medium in the cold, whereas cinnamic acid itself is readily dissolved. Colourless crystals. M.P. 137. 1 Methods of generating hydrochloric and hydrobromic acid gases will be found discussed on p. 70. 2 A. 153, 256 ; 145, 274 ; B. 2, 660. 3 B. II, I22J. 64 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF LIMONENE HYDROCHLORIDE.* For the success of this experiment the total exclusion of every trace of moisture is absolutely necessary. Twenty grammes of limonene, which has been dried over metallic sodium, is dis- solved in its own volume of carefully dried carbon bisulphide. The solution is placed in a dry distilling flask, the side-tube of which is connected with a calcium chloride tube to prevent the entrance of atmospheric moisture. The flask is surrounded with ice, and a stream of dry hydrogen chloride gas led into the mixture through the neck. After the gas has been passed for about eight hours the operation is interrupted, the carbon bisulphide removed by distillation from the water-bath, and the residue then fractionated in vacuo. The monohydro- chloride passes over at 97-98 (11-12 mm.). It forms a colourless liquid : CH a Cl (iii) REPLACEMENT OF OXYGEN OR HYDROXYL BY HALOGEN The oxygen in ketones, aldehydes, and acid amides, and the hydroxyl group in alcohols and carboxylic and sulphonic acids, can usually be replaced by halogen atoms by means of a variety of substances. The most important of these will now be discussed. PHOSPHORUS PENTACHLORIDE. Phosphorus penta- chloride replaces the oxygen or hydroxyl in all types of substances mentioned above : 2ROH + PC1 5 = 2RC1 + POC1 3 + H 2 R : O + PC1 5 = RC1 2 + POC1 3 . It is used either alone or in the presence of a solvent such as acetyl chloride, chloroform, phosphorus oxy- chloride, benzene, ligroin, or ether. The phosphorus 1 A. 270, 1 88. HALOGEN COMPOUNDS 65 oxychloride formed is usually removed by fractional distillation in vacuo. This reaction is the one most frequently used for preparing ketone and acid chlorides. The use of acetyl chloride as a solvent was introduced by Emil Fischer, and has proved especially useful for preparing the chlorides of amino-acids. Phosphorus pentabromide has met with but little success for preparing bromine compounds. PREPARATION OF BENZOYL CHLORIDE (PhCOCl). Fifty grammes of dry benzole acid are mixed with 90 grm. of powdered phosphorus pentachloride. The reaction, which commences at the ordinary temperature, is completed by heat- ing for a short time on the water-bath. The phosphorus oxychloride (B.P. 110) and the benzoyl chloride (B.P. 200) are then separated by fractional distillation. Colourless, fuming oil with pungent odour. Yield 90 per cent. PREPARATION OF HIPPURYL CHLORIDE (PhCONH. CHaCOCl). 1 Ten grammes of dry hippuric acid are finely powdered, sifted through a very fine sieve, and then added to a solution of 13 grm. of phosphorus pentachloride in 100 grm. of acetyl chloride. The whole is violently agitated on a shaking- machine for two hours. The resulting crystals are collected, washed with dry petroleum ether, and dried in a vacuum desic- cator over concentrated sulphuric acid. If desired, they may be further purified by recrystallisation from warm acetyl chloride, but prolonged heating must be avoided, as otherwise decomposition will take place and a yellow substance be formed. At all stages of the preparation moisture should be avoided as far as possible. Colourless needles. On heating, it becomes yellow at about 125, then red, and finally melts indefinitely at higher temperatures. Yield 80 per cent. PREPARATION OF NAPHTHALENE SULPHO- CHLORIDES (C 10 H 7 SO 2 C1). 2 Forty grammes of sodium a- or /3-naphthalene sulphonate are dried at 150, and while still warm are gradually added to an equal weight of coarsely powdered phosphorus pentachloride. The reaction takes place without heating, and the addition of the salt is so regu- lated that it does not become too violent. When the whole has i B. 38, 612. 2 A. 275, 233. 5 66 PREPARATION OF ORGANIC COMPOUNDS been added the mixture is heated on the water-bath until it has become homogeneous, and most of the phosphorus oxy- chloride then removed by distillation under slightly reduced pressure (500 mm. 100 C.). When 20-25 g rm - of the oxy- chloride have been collected, the distillation is stopped and the contents of the flask poured into a basin and allowed to cool with continual stirring. The crystalline mass thus obtained is ground up with ice-cold water, filtered, and the precipitate melted by careful heating on the water-bath. The water it has retained rises to the surface and is removed as far as pos- sible by absorbing it with filter -paper. On cooling, the sulpho- chloride sets to a solid mass. This is powdered and dried in vacuo over sulphuric acid. It is then recrystallised from a mixture of benzene and petroleum ether. Colourless crystal- line solids. The a -chloride melts at 66, the /3-chloride at 76. Yields 60 and 70 per cent, respectively. PREPARATION OF o.-NITROBENZYL CHLORIDE (C 6 H 4 [i]NO 2 [2]CH 2 Cl).i Five grammes of o.-nitrobenzyl alcohol are dissolved in 50 grm. of dry chloroform, and 3 grm. of powdered phosphorus pentachloride added to the well- cooled liquid. When the reaction is over, the whole is shaken up with cold water, the chloroform layer collected, and the chloroform removed by distillation from the water -bath. o.-Nitrobenzyl chloride is left as a mass of pale yellow needles which melt at 49. It may be recrystallised from chloroform. PREPARATION OF BENZOPHENONE CHLORIDE (Ph 2 CCl 2 ) . 2 Twenty-four grammes of benzophenone are mixed with 40 grm. of phosphorus pentachloride and the whole heated under a reflux condenser on the oil-bath to a tempera- ture of 220-240 for four hours. The resulting mixture is then submitted to fractional distillation in vacuo, the benzo- phenone chloride passing over at 193 at 30 mm. pressure. PHOSPHORUS OXYCHLORIDE. Phosphorus oxy- chloride does not attack ketonic groups except when these are capable of reacting in the enolic form, e.g. uric acid. It does not form acid chlorides from carboxylic acids, but only from their sodium salts. It replaces alcoholic hydroxyl and can, therefore, be 1 B. 18, 2402. 2 B. 3, 752 ; 29, 2944. HALOGEN COMPOUNDS 67 used for preparing chloro-acids from the corresponding oxy-acids, the carboxyl group remaining intact. It leaves no volatile phosphorus compound as it is changed into phosphoric acid, and in cases where the required halogen compound can be distilled this considerably facilitates the separation. PREPARATION OF DIPHENYL CHLORACETIC ACID (Ph 2 CClCOOH) .1 Twenty grammes of benzylic acid, Ph 2 C(OH> COOH, are gently warmed with an equal weight of phos- phorus oxychloride until the acid goes into solution and a red colour begins to make its appearance. The whole is then allowed to cool and the crystalline mass thus obtained shaken with a litre of cold water until the acid has become quite solid and hard (one to two hours). It is then collected, washed with water, dried, and recrystallised from a mixture of benzene and ligroin. Colourless rhombic tablets. M.P. n8-ii9 (decomp.). Yield 65 per cent. PREPARATION OF 2.6-DICHLORURIC ACID. 2 Twenty grammes dry potassium urate are heated with 24 grm. of phosphorus oxychloride for six hours in a sealed tube at a temperature of i6o-i7O. After cooling, the tube is opened (there is considerable pressure) and the dark-coloured mass poured into water, filtered, and the precipitate dried and powdered. It is then added slowly to 5 parts of nitric acid (D = 1-4), and the whole boiled for twenty to thirty minutes. The greater part of the dichloruric acid remains undissolved and the rest is recovered by precipitating with water. The crude acid is now well washed, suspended in 24 parts of boiling alcohol, and aqueous ammonia added little by little until the whole goes into solution with the exception of a few brown flocks. These are removed by nitration and the nitrate boiled with animal charcoal, and again filtered. On sharply cooling the nitrate, the ammonium salt separates out as large pale yellow leaflets, the yield being about 6 grm. A further quantity of the salt can be obtained by concentra- ting the mother-liquors . To obtain the free acid the ammo- nium salt is dissolved in water and then acidified with mineral acid. The 2-6-dichloruric acid is precipitated and is collected in the usual way. It should form a colourless crystalline powder which does not melt. i B. 36, 145- 2 B. 30, 2208. 68 PREPARATION OF ORGANIC COMPOUNDS PHOSPHORUS TRICHLORIDE. Phosphorus trichloride replaces alcoholic, phenolic, and carboxylic hydroxyl groups, and in the preparation of the chlorides of the lower fatty acids is usually to be preferred to the pentachloride. It has the advantage of leaving no volatile phosphorus compounds, and whereas one molecule of the trichloride gives three molecules of acid chloride, one molecule of the pentachloride gives only one molecule of the acid chloride : 3R.COOH 4- PC1 3 = sRCOCl + P(OH) 3 R.COOH + PC1 5 = RCOC1 + POC1 3 + HC1. It is especially useful for preparing derivatives from acid chlorides, e.g. acid amides, without isolating the chloride in the pure state (see p. 220). PHOSPHORUS TRIBROMIDE and TRI-IODIDE have also been used for replacing hydroxyl groups by halogen, but the yields are not so good as in the case of the chlorine compounds, and it is better to use a mixture of the halogen and red phosphorus, in which case substitution at the a-carbon atom also takes place (see p. 57). PREPARATION OF ACETYL CHLORIDE (CH 3 COC1). One hundred grammes of glacial acetic acid are placed in a distilling flask which is cooled by immersion in cold water. Eighty grammes of phosphorus trichloride are then slowly added with continual shaking. When the whole of the tri- chloride has been added, the mixture is gently warmed until no more hydrochloric acid is evolved. It is then distilled from the water-bath and the distillate further purified by a second distillation. The acetyl chloride passes over at 55 as a colour- less, strongly fuming liquid with a pungent and irritating odour. It must be carefully protected from atmospheric moisture as it is readily decomposed. The yield is about 60 to 70 per cent. PREPARATION OF ETHYL BROMIDE (C 2 H 5 Br).i Sixty grammes of bromine are slowly added to a mixture of 60 grm. of alcohol and 10 grm. of red phosphorus, the whole 1 Meyer u. Jacobsen, " Lehrbuch der Organ, Ch." (1907), p. 281, HALOGEN COMPOUNDS 69 being shaken continually and well cooled. When all the bromine has been added the mixture is shaken mechanically for some hours, and then distilled from the water-bath. The ethyl bromide which distils over is washed, first with dilute sodium carbonate solution and then several times with water. It is dried with calcium chloride and redistilled. Colourless heavy liquid boiling at 38. A better method of preparation is given on p. 71. PREPARATION OF ETHYL IODIDE (C 2 H 5 I).i Fifty grammes of iodine are slowly added in small portions to a mixture of 5 grm. of red phosphorus 2 and 40 grm. of alcohol, the whole being cooled from time to time by immersing the flask in ice-water. When all the iodine has been added, the whole is set aside at the ordinary temperature over -night and then boiled under a reflux condenser on the water -bath for two hours. The ethyl iodide is distilled off, washed with dilute caustic alkali, and then several times with water, dried with calcium chloride, and redistilled. Ethyl iodide forms a colourless, sweet-smelling oil which boils at 72 '3. On keeping, it gradually acquires a violet colour owing to the separation of iodine. Yield 95 to 98 per cent. HALOGEN ACID. Hydriodic acid usually reacts readily with alcoholic hydroxyl groups, replacing them by iodine. In the case of polyhydric alcohols only one hydroxyl is thus replaced, the others being reduced, e.g. mannite, C 6 H 8 (OH) 6 , gives a mixture of hexyl iodides, C 6 H 13 I. Hydriodic acid also reacts with ethers, giving either a mixture of iodides, or the alcohol of the higher radical and iodide of the lower, according to circumstances. On the latter reaction is based Zeisel's estimation of methoxy- and ethoxy-groups. Hydrobromic and hydrochloric acids also react with alcoholic hydroxyl, but less readily. In the case of hydrochloric acid the reaction is usually so incomplete that it is necessary to assist it by adding a dehydrating 1 Loc. cit. 2 According to Walker a considerable amount of time can be saved by using a mixture of equal parts of red and yellow phosphorus. Soc. 61, 717. yo PREPARATION OF ORGANIC COMPOUNDS agent, such as zinc chloride or sodium sulphate. The latter of these substances is to be preferred, as zinc chloride is apt to cause isomeric change, e.g. CH 3 (CH 2 )5CH 2 OH, with hydrochloric acid and zinc chloride, gives CH 3 (CH 2 ) 4 CHC1.CH 3 , the unsaturated hydrocarbon, CH 3 (CH 2 ) 4 CH : CH 2 , being formed as an intermediate product. 1 Hydrochloric acid gas is best prepared by the action of technical, concentrated sulphuric acid (" mono- hydrate " or " B.O.V.") on sal-ammoniac in a Kipp's apparatus. Such apparatus should not be shaken, as sulphuric acid dissolves some hydrochloric acid, and on agitation this is apt to come out of solution suddenly and project the concentrated acid from the top of the apparatus. The gas can also be obtained by dropping concentrated sulphuric acid into concentrated hydro- chloric acid or a mixture of this latter and common salt. If generated in this way it must be dried by passing through strong sulphuric acid. Hydrobromic acid gas is most readily obtained by the action of hydrogen sulphide on bromine : 2 H 2 S -f- Br 2 = 2HBr + S. The sulphuretted hydrogen is obtained from a Kipp's apparatus, and after washing is passed through bromine contained in a narrow wash-bottle and covered with a layer of water. The evolved gases are washed with a solution of potassium bromide in which some red phosphorus is suspended. A rapid stream of almost pure hydrobromic acid can thus be obtained. It is quite free from bromine vapours and sulphuretted hydrogen. PREPARATION OF HEXYL IODIDE (C 6 H 13 I). 3 Sixty- seven grammes of iodine and 75 c.c. of water are placed in a tubulated retort the neck of which is connected with a sloping reflux condenser. Ordinary phosphorus is then added in small pieces to the gently warmed mixture until a colourless solution is obtained. The condenser is then lowered to the 1 B. 7, 1792. 2 C. r. no, 784. 3 B. 40, 142. HALOGEN COMPOUNDS 71 normal position, 15 grm. of mannite added to the contents of the retort, and the whole distilled fairly rapidly in a current of carbon dioxide, led in by a tube passing through the tubulus. When the liquid begins to become coloured owing to the sepa- ration of iodine, the distillation is interrupted, the contents of the retort cooled, and more phosphorus added until the liquid is again decolorised. The distillate, together with another 15 grm. of mannite, is returned to the retort and dis- tilled as before. This operation is repeated once again, and finally the distillate is collected, the aqueous layer removed in a separating funnel, and the oil washed first with dilute soda and then with water. It is dried with calcium chloride and redistilled. The greater portion passes over between 165 and 170, and consists of a mixture of isomeric hexyl iodides. These can be partially separated by repeated fractionation under reduced pressure. PREPARATION OF ETHYL BROMIDE (C 2 H 5 Br). Twenty- five grammes of alcohol are added to 50 grm. of concentrated sulphuric acid with continual shaking. When the mixture has cooled it is poured on to 60 grm. of finely powdered potassium bromide, and the whole allowed to stand over-night. The mixture is then distilled from the water-bath and the ethyl bromide purified as described on p. 68. PREPARATION OF ETHYL CHLORIDE.* The reaction is carried out in the apparatus shown (Fig. 48). One hundred grammes of alcohol and 50 grm. of fused zinc chloride are placed in the flask A, and dry hydrochloric acid gas led through the boiling mixture. The ethyl chloride formed is washed with water in B and concentrated sulphuric in c. The spiral condenser D is surrounded by a freezing mixture of ice and salt, as is also the receiver E. As ethyl chloride boils at 12 it must be preserved in thick, sealed glass tubes. The yield is almost quantitative. THIONYL CHLORIDE (SOClg). Thionyl chloride serves chiefly for the preparation of acid chlorides, 2 and for this purpose has the advantage over phos- 1 B. 7, 741 ; A. 174, 372 ; J. pr. [2] 14, 195. 2 B. 16, 1627 ; 37, 2951, 3217 ; 38, 605 ; 40, 2649; M. 22, 109. 72 PREPARATION OF ORGANIC COMPOUNDS phorus pentachloride that aldehydic and ketonic groups are unaffected by it, and that it gives rise only to gaseous by-products : SOC1 2 + 2R.COOH = S0 2 + H 2 + 2R.COC1. Any excess of the reagent is readily removed by FIG. 48. distillation (B.P. 78), or the excess can be destroyed by adding formic acid : SOC1 2 + 2HCOOH = SO 2 + 2CO + 2HC1 + H 2 O. Thionyl chloride has found its chief use in the pre- paration of the chlorides of complicated amino-acids, 1 i B. 36, 2094. HALOGEN COMPOUNDS 73 but in this case one of the hydrogen atoms of the amino -group must first be replaced by the carbethoxy group by treatment with chlorcarbonic ester. Otherwise the amino-group will also be attacked. It has also proved very useful for preparing the chlorides of the pyridine carboxylic acids. 1 Some ketonic acids, such as pyruvic acid, do not react with thionyl chloride, and the ^.-oxybenzoic acids only react when there is a negative group in the meta-position to the carboxyl. Alcoholic hydroxyl 2 is also sometimes attacked by thionyl chloride, e.g. : (C 6 H 5 CH 2 )(C 6 H 5 )(C 2 H 5 )COH - (C 6 H 6 CH 2 )(C 6 H 5 )(C 2 H 5 )CC1. The reaction is usually carried out with a slight excess of thionyl chloride and no solvent, and either takes place at the ordinary temperature or on gentle warming. SULPHURYL CHLORIDE (SO 2 C1 2 ). Sulphuryl chloride is but little used in the laboratory, but is employed to a large extent technically for preparing acid chlorides from the corresponding salts 3 (cf. p. 60). The calcium salts give the best results. The reaction takes place at the ordinary temperature, but very intimate mixing is required. CHLORSULPHONIC ACID (SO 2 OHC1). Chlorsulphonic acid, obtained by passing dry hydrochloric acid gas into oleum, is chiefly used for preparing the chlorides of sulphonic acids directly from the aromatic hydro- carbons. A large excess of the acid is used and rise in temperature prevented. The yields are excellent. 4 1 M. 22, III. 2 B. 37, 1453. 3 D.R.P. 151,864, 63,593. 4 D.R.P. 98,030 ; B. 12, 1848 ; 42, 1802, 2057. This method is used technically for the preparation of toluene- 74 PREPARATION OF ORGANIC COMPOUNDS BENZENE SULPHOCHLORIDE l and CARBONYL CHLORIDE 2 can also be employed for replacing hy- droxyl by chlorine. The latter substance also reacts with benzaldehyde to form benzal chloride : C 6 H 6 CHO + COC1 2 = C 6 H 5 CHC1 2 + CO 2 . (iv) REPLACEMENT OF THE DIAZO-GROUP BY HALOGEN Most primary aromatic amines when treated with nitrous acid are readily converted into diazo-salts : 3 ArNH 2 + HNO 2 + HC1 = ArN :N.C1 + H 2 O. The diazo-compounds when isolated are exceedingly explosive, but numerous methods are known whereby the diazo-group can be replaced by other groups or elements without actually isolating the explosive substance. For replacing the diazo-group by halogen three methods are known, viz. : (i) Method of Griess. This consists in heating the diazo-salt with the halogen acids. The method usually goes very well with hydriodic acid, and is the standard method of preparing aromatic iodides, but is far less satisfactory with the other halogen acids. o.-sulphochloride, an intermediate compound in the manufac- ture of saccharin : S0 2 C1 CH 3 NHj COOH NH Saccharin 1 F.P. 328,120. 2 J. pr. [2] i, 412. 3 For experimental details the reader is referred to p. 238. HALOGEN COMPOUNDS 75 (ii) Sandmeyer's Method. This consists in treating the diazo-salt with halogen acid and cuprous halide. It is of very general application, and as a rule gives excellent results. The base is diazotised in the ordinary way (see p. 238), except that when preparing bromine or iodine compounds it is best to replace the hydrochloric acid by sulphuric acid. The resulting diazo-solution or suspension is then slowly run into a boiling solution of the cuprous salt l in the correspond- ing halogen acid. The resulting halogen compound is separated by steam distillation or by other methods according to circumstances. (iii) Gattermann's Reaction. This consists in adding copper powder to the diazo-salt of the corresponding halogen acid. The reaction takes place at the ordinary temperature and the yields are as good as or better than those obtained by Sandmeyer's method. The method has the advantage that less bulky solutions have to be dealt with. For the preparation of the copper powder, zinc dust is sifted through a fairly fine sieve into a cold saturated solution of copper sulphate until the latter is decolorised. The liquid is then poured off from the precipitated copper and the latter washed once or twice with water. It is then shaken up with dilute hydrochloric acid to remove excess of zinc dust, and when no more hydrogen is evolved the acid liquors are poured off and the residue washed with water until neutral. The copper powder thus obtained is very readily oxidised by the air and is best preserved as a paste in well-stoppered bottles. Instead of the powder obtained as above, the commercial copper bronze can be used, the best form being that sold by Kahlbaum under the name of " Naturkupfer C." Before use this should be freed from traces of oil by washing with ether or ligroin. PREPARATION OF IODOBENZENE (C 6 H 5 I). (a) Method of Griess. 2 Forty-eight grammes of aniline are dissolved in 1 The preparation of cuprous chloride and cuprous bromide will be found described on p. 31. 2 A. 241, 35. 76 PREPARATION OF ORGANIC COMPOUNDS 700 c.c. of water and 85 c.c. of concentrated hydrochloric acid. Ice is added until the temperature falls below o and the solution diazotised in the usual way with a solution of 35 grm. of sodium nitrite, the temperature being kept below 10. A cold, concentrated solution of 85 grm. of potassium iodide is then slowly run in with continual stirring. At first rapid evolution of nitrogen takes place, but towards the end the reaction becomes less vigorous and must be assisted by gentle warming on the water-bath. When no more nitrogen is evolved, the solution, which has become coloured owing to the separation of iodine, is decolorised by the addition of caustic soda, the heavy oil collected, washed with water, and steam-distilled. The oil which passes over is collected, dried with calcium chloride, and distilled. lodobenzene forms a colourless, heavy oil which boils at 1 88. Yield almost quantitative. (b) Gattermann's Method. 1 Thirty-one grammes of aniline are dissolved in 400 grm. of 50 per cent, sulphuric acid, and the solution cooled below o by the addition of ice. The aniline is then diazotised as usual with 23 grm. of nitrite in concen- trated solution. One hundred and twenty-six grammes of potassium iodide and 40 grm. of copper paste or powder are then added. When the reaction is over the copper sinks to the bottom of the vessel. The iodobenzene is purified as above. Yield 70 per cent. PREPARATION OF CHLOROBENZENE (C 6 HsCl). (a) Sandmeyer's Method. Thirty-one grammes of aniline are dissolved in 200 c.c. of water and 57 c.c. of concentrated hydrochloric acid, and then diazotised in the ordinary way with 23 grm. of sodium nitrite dissolved in 60 c.c. of water. The solution thus obtained is slowly run into 350 c.c. of an almost boiling 10 per cent, cuprous chloride solution prepared as described on p. 31. When the whole has been added the greater part of the aqueous liquid is poured off, and the residual oil steam-distilled. The oil which passes over is collected, washed with dilute sodium carbonate, then with water, dried over calcium chloride, and finally distilled. Colourless liquid boiling at 132. Yield 73 per cent. (b) Gattermann's Method. 2 Thirty-one grammes of aniline are added to 150 c.c. of water and 225 c.c. of concentrated 1 B. 23, 1222. 2 B. 23, 1220. HALOGEN COMPOUNDS 77 hydrochloric acid. Complete solution does not take place. The resulting liquid is diazotised as before with 23 grm. of nitrite. Forty grammes of copper paste or powder are added, and the whole allowed to stand until the reaction is over (about half an hour). When this is the case the copper will sink to the bottom of the vessel. The chlorobenzene is purified as before. Yield about 73 per cent. o.-Chlortoluene can be prepared in exactly the same way as the above, but in this case, whereas Sandmeyer's method gives a yield of only 30 per cent., Gattermann's method gives a yield of 66 per cent. The proportions to use are : 36 grm. o.-toluidine, 200 c.c. cone. HC1, 150 c.c. H 2 O, 23 grm. NaNO 2 , 40 grm. Cu paste. B.P. 179. PREPARATION OF BROMOBENZENE (C 6 H 5 Br).i i ce is added to 130 grm. of concentrated sulphuric acid until the temperature falls to o. Thirty-one grammes of aniline are then added, and the solution diazotised as usual with 23 grm. of nitrite. One hundred and twenty grammes of potassium bromide and 40 grm. of copper paste are then added, and, when the reaction is over, the bromobenzene steam-distilled off, and purified as described under chlorobenzene. Colourless oil boiling at 155. Yield 42 per cent. PREPARATION OF o.-BROMBENZOIC ACID (C 6 H 4 [i] Br[2]COOH). 2 Thirty -five grammes of crystallised copper sulphate, 100 grm. of sodium bromide, and 30 grm. of copper turnings are boiled under a reflux condenser with 300 c.c. of water and 33 grm. of concentrated sulphuric acid until almost decolorised. Forty grammes of anthranilic acid are then added and the whole allowed to cool. Ice is added until the temperature falls to o, and then a cold, concentrated, aqueous solution of 21 grm. of sodium nitrite slowly run in. During the addition the temperature should not exceed 5, more ice being added from time to time if necessary. When all the nitrite has been added the whole is allowed to stand over- night at the ordinary temperature. The precipitated o.- brombenzoic acid is then collected, washed with cold water, and recrystallised from water. It forms long colourless needles melting at 147-! 50. Yield 82 per cent. 1 B. 23, 1222. 2 A. 276, 56. 78 PREPARATION OF ORGANIC COMPOUNDS ADDENDA In many cases when halogen compounds are being prepared simultaneous oxidation takes place. The best-known examples of this are the preparation of chloroform and iodoform by the action of bleaching powder or hypoiodite on alcohol. The preparation of chloranil (see p. 139), and of chloropicrin, C1 3 CNO 2 , from picric acid and bleaching powder are also well- known examples of simultaneous oxidation and chlori- nation. So also is the preparation of chloral, CC1 3 CHO, by the action of chlorine on alcohol. PREPARATION OF CHLOROFORM (CHC1 8 ). Two hun- dred grammes of fresh bleaching powder are ground up to a thin cream with 800 c.c. of water, and the whole then trans- ferred to a large flask fitted with a condenser. Forty grammes of acetone (or alcohol) are then added and the whole cautiously heated until the reaction sets in. The flame is then withdrawn until the frothing ceases, when the whole is distilled until no more chloroform comes over. The lower layer of the distillate is collected, washed with dilute caustic soda, dried over calcium chloride, and then redistilled from the water-bath. Heavy colourless liquid with a sweet smell. B.P. 61. Yield about 40 grm. ACTION OF CHLORINE ON AROMATIC IODO- COMPOUNDS. When chlorine acts on aromatic iodo- compounds in which the iodine atom is attached directly to the nucleus, a derivative of iodine trichloride is formed in which the iodine is trivalent. Aliphatic iodine compounds or compounds in which the iodine is situated in a side-chain do not act in this way. PREPARATION OF IODOBENZENE BICHLORIDE (PhlCy. 1 Twenty grammes of iodobenzene are dissolved in 50 grm. of dry chloroform and a stream of dry chlorine passed into the liquid. After a minute or two pale yellow needles begin to separate. When these no longer increase in quantity, they are filtered off and washed with a little chloroform. 1 J- pr. [2] 33, 155- HALOGEN COMPOUNDS 79 Yield almost quantitative. The compound is rather unstable and readily loses chlorine. When shaken with cold, 10 per cent, caustic soda it is readily changed into iodosobenzene l (C 6 H 5 I : O), a white amorphous mass insoluble in all the usual solvents. On oxidation (heating to 100 in air or boiling with water in a current of air or oxygen) it gives iodoxybenzene 2 (C 6 H 5 IO 2 ). This may be recrystallised from water or glacial acetic acid ; it explodes violently at 230. REPLACEMENT OF THE HALOGENS BY EACH OTHER. Chlorine or iodine can be replaced by bromine, (a) By treatment with cupric bromide 3 in alcoholic solution : 2CuBr 2 + 2C 3 H 5 I = 2C 3 H 5 Br + Cu 2 I 2 + Br 2 . In order to remove the bromine liberated during the reaction some copper powder is added, (b) Sometimes treatment with bromine is sufficient, e.g. methylene iodide treated with bromine water reacts at once with the evolution of heat to form methylene bromide and iodine. 4 (c) Heating, usually under pressure, with boron tribromide often gives excellent results. In this way phosgene is converted into a mixture of COClBr and COBr 2 . 5 Bromine and iodine can be replaced by chlorine, (a) By the direct action of chlorine with or without a solvent (water, chloroform, &c.). Thus chlorine reacts with boiling bromobenzene to form chlorobenzene and higher halogenated products. 6 (b) By the action of antimony pentachloride, iodine trichloride, mercuric chloride, or best silver chloride. Sometimes the reaction takes place in the cold, sometimes heating with or without pressure is required. 7 1 It should be noted that in German iodobenzene (C 6 H 6 I) is Jodbenzol, whereas PhIO 2 is Jodobenzol. Iodosobenzene is the same in both languages. 2 B. 25, 3500 ; 26, 358. 3 A. 100, 124. 4 A. Ch. 30, 266. 5 C. r. 120, 190. 6 Z. 1868, 451 ; B. 17, 795 ; 30, 1208. 7 C. r. 97, 1491 ; A. 141, 207 ; B. 22, 74. 8o PREPARATION OF ORGANIC COMPOUNDS Chlorine or bromine can be replaced by iodine by treatment with hydriodic acid, or the iodides of alu- minium, boron, calcium, sodium, or potassium. As aliphatic iodine compounds are, as a rule, less readily obtained than the chlorine or bromine analogues, the method is often useful. Thus carbon tetrachloride is readily obtained from carbon disulphide and chlorine, whereas carbon tetra-iodide can only be obtained conveniently by the action of boron tri-iodide on the tetrachloride. 1 The most convenient method of replacing chlorine or bromine by iodine is by treatment with sodium or potassium iodide 2 in aqueous, or, better, in alcoholic solution, or in the case of sodium iodide, in acetone solution. The reaction often takes place at once with precipitation of sodium chloride or bromide, but some- times requires standing and warming. The bromine compounds react more easily than the chlorine com- pounds, and tertiary more easily than secondary or primary. PREPARATION OF IODO ACETIC ACID (CH 2 ICOOH). 3 Twenty-five grammes of chloracetic acid are dissolved in water containing 42 grm. of potassium iodide, and the whole heated on the water-bath to a temperature of 50 for two to three hours. The solution is then decolorised by passing in a stream of sulphur dioxide, and, after cooling, is extracted with ether. The ethereal extract is shaken with calcium chloride for half an hour, filtered, and then the ether removed by distillation. The crystalline residue is recrystallised from a large quantity of petroleum ether, best by means of a Soxhlet apparatus. Colourless leaflets melting at 83. In contact with the skin it causes very painful blisters. PREPARATION OF CARBONYL CHLORIDE (Phosgene) (COC1 2 ) . 4 Phosgene is most readily obtained in the laboratory by the action of strongly fuming sulphuric acid on carbon tetrachloride. Five hundred grammes of carbon tetrachloride 1 C. r. 113, 19. 2 A. 3, 266 ; 112, 125 ; B. 29, 1558 ; 30, 2506 ; 43, 1528. 3 B. 41, 2853, 4 B. 26, 1990. HALOGEN COMPOUNDS 81 are placed in a flask fitted with a reflux condenser and delivery tube, as shown in Fig. 49, and heated to boiling on a water- bath. About 1 20 c.c. of 80 per cent, oleum are then slowly dropped in through the tap funnel, the end of which has been drawn out to a fine point. A regular stream of phosgene is evolved and is washed by passing it through concentrated FIG. 49. sulphuric acid. This acid should be kept cold by means of cold water or ice. The gas can be collected in toluene or it can be liquefied by a freezing mixture. When all the oleum has been added the flask is warmed for five minutes over a naked flame. The yield is about 90 per cent. B.P. 8. CHAPTER IV THE ALCOHOLS, PHENOLS, AND MERCAPTANS THE number of methods whereby alcohols and phenols can be obtained is very large, and only those which are most useful for preparing these compounds in the laboratory will be considered. (i) BY THE HYDROLYSIS OF THE ESTERS. The saponification is usually carried out by boiling the ester with aqueous or alcoholic caustic alkali solution. As the esters of organic acids are usually prepared from the alcohols, the method is of little importance for preparative purposes except in the case of the higher alcohols, which are obtained by saponifying the natu- rally occurring waxes, and in the preparation of glyce- rine by saponifying the vegetable and animal oils and fats (soap manufacture). The method is, however, of great importance for obtaining alcohols from the esters of the haloid acids (the alkyl and aryl halides) and this case will be considered in a separate section. (ii) FROM THE HALOGEN COMPOUNDS. In the aliphatic series halogen atoms are much less firmly bound than is usually the case in the aromatic series, and, as a rule, can be replaced by hydroxyl groups by merely boiling with water, or dilute alkali, or alkali carbonate solution. If the carbon atom to which the halogen is attached is tertiary, the reaction takes place with the greatest ease. Thus triphenyl methyl chloride is decomposed by merely warming with water. The reaction is also facilitated when more than one halogen atom is attached to the same carbon atom, but in this case, of course, the products of hydrolysis are aldehydes, 82 ALCOHOLS, PHENOLS, AND MERCAPTANS 83 ketones, or carboxylic acids. It should be noted that when compounds containing the structure Hlg are hydrolysed, the product is not the corresponding unsaturated alcohol, but the tautomeric ketone : OH v - > CH - CO \ When hydrogen and halogen are in the 1.2-position, there is a danger of a simultaneous loss of water taking place with the formation of an unsaturated compound : \ / \ / \ / J>CH CHlg \CH C^-OH OCC/ + H 2 O. For this reason it is sometimes found best to bring about hydrolysis with moist silver oxide, or to convert the halogen compound into the corresponding acetate by means of silver acetate, and then to saponify this with as mild a saponifying agent as possible : H-I-OH R| Hlg AgiO. COCH 3 RO.!COCH 3 _* ROH + CH 3 C0 2 H The saponification of the halogen compounds is often especially useful in connection with the Lederer- Manasse synthesis, and will be further discussed in this connection on p. 97. PREPARATION OF BENZYL ALCOHOL (C 6 H 5 CH 2 OH). Benzyl chloride is boiled under a reflux condenser with 10 parts of a 10 per cent, potassium carbonate solution until the smell of the chloride has disappeared (about twelve hours). After cooling, the whole is extracted with ether, the ether extract dried with potassium carbonate or sodium sulphate, and then 84 PREPARATION OF ORGANIC COMPOUNDS distilled. The benzyl alcohol passes over at 206 and forms a colourless liquid. See also pp. 97-100. PREPARATION OF GLYCOLLIC ACID (CH 2 OHCOOH) 1.1 One hundred grammes of chloracetic acid are dissolved in 800 c.c, of water, and the solution thus obtained boiled under a reflux condenser with 112 grm. of very finely ground marble until carbon dioxide is no longer evolved (two to three days). On cooling, three layers of crystals are usually formed, viz. a top layer consisting of Ca(C 2 H 3 O 3 )2.4H 2 O (microscopic hair- like needles), a middle layer, sometimes absent, consisting of Ca(C 2 H 3 O 3 )2 (six-sided rods), and a bottom layer consisting of CaClC 2 H 3 O 3 . 3H 2 O (octahedra). The flask is carefully warmed without shaking until the top layer has gone into solution, the whole filtered, and the precipitate boiled out several times with water. The united filtrates are allowed to stand for several days, when crystallisation usually takes place. Should this not happen the solution must be concentrated. The crystals are filtered off and well pressed down in order to free them, as far as possible from mother -liquor, ground up with their own weight of cold water, and again filtered and pressed. This treatment is continued until chloride can no longer be detected in the filtrate. The yield of the calcium salt is about 66 per cent. It is dried in the air or by pressing between filter- paper. In order to obtain the free acid, the calcium salt is decomposed with oxalic acid, and as any excess of oxalic acid hinders the crystallisation of the glycollic acid, before proceeding it is necessary to estimate accurately the calcium content of the above salt. The calcium is then precipitated from the boiling solution by slowly adding the calculated quantity of oxalic acid dissolved in boiling water. The calcium oxalate is removed by filtration, and the filtrate concentrated until a crystallisation sets in. On cooling, glycollic acid separates in colourless leaflets which melt at 80. It is very soluble in water. The yield is about 75 per cent, of theory (reckoned on the calcium salt). In the aromatic series the halogen atoms are very firmly bound and, as a rule, can only be replaced with the greatest difficulty. Negative substituents, however, especially nitro-groups, in the ortho- or para- position, 1 B. 16, 2954. ALCOHOLS, PHENOLS, AND MERCAPTANS 85 render the halogen atom more reactive. Thus picryl chloride (syw.-trinitrochlorobenzene) acts as a true acid chloride (just as picric acid is a strong acid), and is rapidly hydrolysed by water. In the naphthalene and anthraquinone derivatives the halogen atom is more readily replaced than is the case in the benzene compounds. 1 PREPARATION OF 2.4-DINITROPHENOL, C 6 H 3 [i] OH[2.4](NO 2 ) 2 - Twenty grammes of chlordinitrobenzene are boiled under a reflux condenser with 21 grm. of sodium carbonate (anhydrous) and 225 c.c. of water until complete solution is obtained. After cooling, the solution is acidified with hydrochloric acid and the precipitated dinitrophenol collected, washed with cold water, and dried between filter- paper or in a vacuum desiccator. It melts at 114. The yield is about 90 per cent. (iii) FROM THE SULPHONIC ACIDS. The aro- matic sulphonic acids on fusion with caustic alkali are converted into phenols, and this forms one of the most important methods of obtaining the phenols both in the laboratory and on the large scale. Caustic potash is the best alkali to employ, as when caustic soda is used there is more likelihood of simultaneous oxidation taking place. In some cases it is found advantageous to carry out the reaction by heating with alcoholic caustic potash solution under pressure. In the case of di- or poly-sulphonic acids, one or more groups can be replaced by carefully regulating the conditions of the experiment. Halogen groups, if present, are usually simultaneously replaced by hydroxyl. It must be borne in mind that when polyhydric phenols are heated to a high temperature with caustic alkali, a rearrangement takes place, the hydroxyl groups taking up the meta- position to each other. Hence all the benzene disulphonic acids when fused with potash give resorcinol. 1 The halogen in haloid phenols can be replaced by hydroxyl by heating under pressure with alkaline earth hydroxides. Pat. Anm. Kl. 12. q. F. 31,351. '86 PREPARATION OF ORGANIC COMPOUNDS In the naphthalene series the method is very im- portant for preparing the technically valuable naphthol and amino-naphthol sulphonic acids, and the following general rules are worth remembering : Sulphonic groups in the a- position are more readily replaced than those in the ft- position. When a-naphthylamine-a-sulphonic acids are fused with caustic, the amino-group is only unattacked when on a different ring from the sulphonic group. If on the same ring it is replaced by hydroxyl. Of the a-naphthylamine- or a-naphthol-, a-sulphonic acids, the sulphonic group in the peri- position is the most readily replaced, e.g. : S0 3 H OH OH OH S0H S0 3 H Of the a-naphthylamine- or a-naphthol-, /5-sulphonic acids, the groups in the epi- or kata- positions are most readily replaced, e.g. : OH OH S0 3 H S0 3 H S0 3 H OH HO/\/\ /\/SO,H S0 3 H If the amino or phenolic group is in the ft- position, then the /3-sulphonic groups in the kata- and 2.3- positions are the most readily replaced. In carrying out the fusion the caustic potash (from 1 1 to 15 parts) is melted in a nickel basin with a little water, the sulphonic acid gradually added, and the ALCOHOLS, PHENOLS, AND MERCAPTANS 87. whole well stirred with a thermometer which is pro- tected from the action of the alkali by a tube of metal or hard glass, the annular space round the bulb being filled for preference with mercury or paraffin wax. PREPARATION OF PHENOL (C 6 H 5 OH) .* Thirty grammes of caustic potash and about 5 c.c. of water are melted at a low temperature in a nickel basin, and then 20 grm. of potassium benzene sulphonate added and stirred in. The temperature is then raised to 252 and maintained at this point for one hour. After cooling, the melt is dissolved in a little water and then acidified with concentrated hydrochloric acid, care being taken not to allow the solution to get too hot, as in that case considerable quantities of phenol will be lost by volatili- sation. The solution is then extracted several times with ether, the ethereal extract dried with anhydrous sodium sulphate, and the ether removed by distillation. The residual phenol passes over at about 1 80 and solidifies in the receiver. Colourless needles. M.P. 42. B.P. 182. Yield 96 per cent. PREPARATION OF a- AND /3-NAPHTHOL (C 10 H 7 OH). Thirty parts of caustic soda and i part of water are fused in a nickel basin and heated to 280. Ten parts of sodium naphthalene a- or /3-sulphonate are slowly added, and the temperature raised to 300, and then to 3io-32O for ten minutes. After cooling, the melt is dissolved in water, acidified as above with hydrochloric acid, the naphthol filtered off from the cold solution, washed, and recrystallised from water. a-Naphthol melts at 95; /3-naphthol at 122. Yields about 80 per cent. (iv) BY GRIGNARD'S METHODS. When a halogen compound, preferably the iodide, is treated in absolute ethereal solution with magnesium, a magnesium alkyl or aryl compound is formed : R.Hlg + Mg = MgRHlg. To obtain a carbinol from this it may be allowed to react on a variety of compounds, of which the following may be mentioned : 1 J-pr. [2] 17, 394; 20,300. 88 PREPARATION OF ORGANIC COMPOUNDS Oxygen and water : RMgl + O + H 2 = R.OH + MglOH. Aldehydes : RMgl + R'.CHO= R'CHOHR + MglOH. Ketones : RMgl + R'R"CO = RR'R"COH -f MglOH. And a similar reaction takes place with acid chlorides, acid anhydrides, &c. PREPARATION OF PHENYL METHYL CARBINOL (C 6 H 5 CHOHCH 3 ).i The ether used in this experiment must be pure and perfectly dry (distil over sodium or phosphorus pentoxide), and all apparatus must be scrupulously dry. Thirty-six grammes of methyl iodide are dissolved in 50 c.c. of absolute ether, and 20 c.c. of the mixture added to 6 grm. of clean magnesium ribbon in a dry flask provided with a reflux condenser. If a brisk reaction does not set in at once it may be started by adding a trace of iodine. When the reaction has subsided, 70 c.c. of absolute ether are added and then the rest of the iodide solution drop by drop. The whole is boiled for half an hour, a little more methyl iodide being added, if necessary, to complete the solution of the magnesium. The whole is then cooled by surrounding with ice, and a solution of 26 grm. of benzaldehyde in its own volume of absolute ether added slowly with constant shaking. After standing over- night the flask is cooled with water, and dilute hydrochloric acid added slowly until, on shaking, the whole of the solid matter dissolves (250 c.c. of 2N acid). The ethereal layer is then removed, washed first with sodium bicarbonate solution, then with sodium bisulphite (to remove iodine), and again with sodium bicarbonate. It is dehydrated over potassium carbonate, the ether removed by distillation, and the carbinol distilled in vacua. It boils at 100 at 15 mm. The yield is about 65 per cent. (v) FROM THE AMINES. This replacement is of great importance in the aromatic series, and may be carried out either directly or indirectly. 1 Cohen, " Practical Organic Chemistry " (1908), p. 206. ALCOHOLS, PHENOLS, AND MERCAPTANS 89 As a rule, amino-groups are only replaced by hydroxyl groups by the action of caustic alkali when a negative substituent, such as a nitro-group, is in the ortho- or para- position. Thus aniline on boiling with caustic alkali gives no trace of phenol, whereas the nitrophenol is readily obtained in good yield by boiling ortho- and />tfnz-nitraniline with caustic potash. 1 Secondary and tertiary bases having a nitroso-group in the para- position also easily give the nitroso-phenol (see p. 196). In the naphthalene series amino-groups are more readily replaced, e.g. a-naphthylamine salts on heating with water to 200 give a-naphthol. A more important method, and one which has been applied technically for the preparation of some of the naphthol sulphonic acids, consists in heating the amino-compound with sodium bisulphite. Under these circumstances a sulphite ester is first formed, which is then hydrolysed to the corresponding phenol : ArNH 2 ArO.SO 2 H ArOH. The reaction takes place most readily with a-naph- thylamine sulphonic acids. PREPARATION OF i-NAPHTHOL-4-SULPHONIC ACID (Neville and Winther's Acid). 2 Thirty -two grammes of sodium naphthionate, 20 c.c. of water, and 75 c.c. of sodium bisulphite solution (40 Be.) are heated for twenty-four hours with continual stirring to 85-9O. After cooling, the solution is acidified with hydrochloric acid (use Congo paper) and unchanged naphthionic acid filtered off (about 3 to 4 grm.). The ni- trate is made alkaline with caustic soda and boiled until no more ammonia is evolved. It is then again acidified with hydrochloric acid and boiled until the smell of sulphur dioxide has vanished. Finally, the required sulphonic acid is precipi- tated as its sodium salt by saturating the hot solution with common salt. The indirect replacement of the amino-group is * B. 7, 77. a D.R.P. 109,102. 90 PREPARATION OF ORGANIC COMPOUNDS brought about by boiling solutions of the diazo- salts : ArN : NHSO 4 + H 2 O = ArOH + H 2 SO 4 + N 8 . This method is also applicable to the aliphatic series, but as the aliphatic diazo-compounds are not formed by the action of nitrous acid on the primary amines, it is only necessary to add sodium nitrite to an acid solution of the base : R.NH 2 + HO 2 N = R.OH + N 2 + H 2 O. As a preparative method, the reaction is not much applied except in the aromatic series. As the diazo-sulphates give the best yield of the phenol, it is usual to use sulphuric acid for diazotising. The diazo-salt is not isolated, but its solution either heated to boiling or slowly added to boiling, dilute sulphuric acid, and the whole boiled until no more diazo-compound is present (test with an alkaline solution of R-salt or /3-naphthol) . The yields in some cases, especially with amino-phenols, are very poor, but can often be improved by boiling the diazo-sulphate with copper sulphate. PREPARATION OF DI-.-OXYDIPHENYL (HO.C 6 H 4 . CsH^.OH). 1 Fifty grammes of benzidine are dissolved in a litre of water and 60 c.c. of concentrated hydrochloric acid. The solution is diluted to 5 litres, 200 grm. of concentrated sulphuric acid added, and the whole diazotised in the usual way (see Chapter XI) with a solution of 37 grm. of sodium nitrite in 200 c.c. of water. The clear solution is then heated to boiling by blowing in steam, and maintained at this tempera- ture until a sample gives no colour with alkaline R-salt solu- tion (about twenty minutes). The solution is filtered hot, and the diphenol crystallises out on cooling. It forms colour- less needles melting at 272. Yield 80 per cent. PREPARATION OF PYROCATECHOL (C 6 H 4 [i. 2 ](OH) 2 ).2 Fifty grammes of o.-amino phenol are diazotised in the ordinary way and the diazo-solution slowly run into 100 c.c. of boiling, i B. 22, 335. 2 D.R.P. 167,211. ALCOHOLS, PHENOLS, AND MERCAPTANS 91 10 per cent, copper sulphate solution. When the reaction is complete the solution is cooled and the pyrocatechol extracted with ether. Hydroquinone is obtained from .-amino phenol, and o.-cresol from o.-toluidine in exactly the same way, except that for 50 grm. of amine a solution of 200 grm. of crystallised copper sulphate in its own weight of water should be used. If a diazo-nitrate is boiled with water, nitration takes place simultaneously in the ortho- position. PREPARATION OF s-NITRO-CRESOL (C 6 H 3 [i]CH 3 [3] NOa^jOH). 1 Seventy-five grammes of .-toluidine are dis- solved by gently warming in 380 c.c. of water and 93 grm. of nitric acid (D = i'33). The whole is then cooled below o (crystallisation takes place, but this does not interfere with the reaction) and diazotised in the usual way with a solution of 49 grm. of sodium nitrite in 100 c.c. of water. During the diazotisation the temperature must not exceed 10. After standing for two hours at a low temperature, about 100 c.c. of the solution are transferred to a litre flask and slowly heated to boiling under a reflux condenser. A very violent reaction sets in, and unless a very efficient condenser is used, considerable quantities of the nitro-cresol will be lost. When the reaction is over, the rest of the diazo-solution is slowly dropped in by means of a dropping-funnel. When the whole has been added, the boiling is continued for a few minutes, and the nitro-cresol then distilled over with steam. It usually collects in the receiver as an oil which soon solidifies to a yellow crystalline mass. M.P. 36-5. Yield 60 to 70 per cent. (vi) BY THE REDUCTION OF THE ALDEHYDES AND KETONES. A very large number of reducing agents have been employed for reducing the aldehydes and ketones to the corresponding primary and secon- dary alcohols. The best results, however, are usually obtained with sodium and alcohol, sodium amalgam and water, aluminium amalgam and water, zinc dust and caustic soda or ammonia, or zinc dust and glacial acetic acid. Of these the most generally used 1 B. 24, 1960. 92 PREPARATION OF ORGANIC COMPOUNDS is sodium amalgam, and the reduction is usually carried out by dissolving the ketone in moist ether and then shaking with the amalgam. Instead of ether, benzene can be used, small quantities of water being added from time to time, or the amalgam can be allowed to act on the moist ketone without employing a solvent. The reduction with sodium and alcohol, which is particularly useful in the aromatic series, is carried out by dissolving the ketone (i part) in alcohol (10 parts) and then slowly adding sodium wire (i part). Other methods applicable to special cases will be found discussed at the end of this section. The reduction of the ketones is usually accompanied by intermolecular condensation, a pinacone (ditertiary glycol) being formed : 2(CH 3 ) 2 .CO + 2H = (CH 3 ) 2 .COH.COH.(CH 3 ) 2 . Acetone Pinacone In the aliphatic series the pinacone is invariably formed to a greater or less extent, but by choosing suitable conditions the aromatic ketones can usually be reduced without any pinacone formation. As a rule, pinacone formation takes place with greater ease when an acid reducing agent is used than when the reduction is carried out in alkaline solution. PREPARATION OF METHYL PHENYL CARBINOL (CH 3 . CHOH . C 6 H 5 ) .* Twenty grammes of acetophenone are dissolved in 200 grm. of alcohol and the whole warmed on the water-bath. Twenty grammes of sodium are rapidly added, and when this has dissolved, the solution neutralised by passing in a current of carbon dioxide. The whole is then diluted with about 250 c.c. of water and the alcohol removed as far as possible by distillation from the water-bath. The residue is extracted with ether, the ether distilled off, and the residue distilled in vacuo. The carbinol passes over at 118 at 40 mm. or at 100 at 1 5 mm. At atmospheric pressure it boils at 198. The yield is about 40 per cent. 1 B. 31. 1003. ALCOHOLS, PHENOLS, AND MERCAPTANS 93 PREPARATION OF BENZHYDROL (C 6 H 5 ) 2 CHOH.i One part of benzophenone is dissolved in 10 to 20 parts of alcohol and about 5 parts of concentrated, aqueous, caustic potash. Five to ten parts of zinc dust are then added, and the whole allowed to stand in a warm place for five to seven days . The solution is then saturated with carbon dioxide, filtered, and the filtrate evaporated until crystallisation sets in. On cooling, the benzhydrol separates out in colourless needles which melt at 68. The yield is about 70 per cent. PREPARATION OF BENZPINACONE, (C 6 H 5 ) 2 .COH.COH (C 6 H 5 ) 2 . 2 One part of benzophenone, 2 parts of zinc foil, and 10 parts of 85 per cent, acetic acid are boiled for fifteen minutes, the whole being well shaken at frequent intervals. The liquid is then poured off from the unattacked zinc, cooled, and filtered. The filtrate is again boiled up with zinc, and this process repeated a third time, the solutions being filtered through the same filter each time. Finally the benzpinacone is washed with acetic acid (5 acid : i water) and then recrystal- lised from 13 parts of boiling glacial acetic acid. It melts with decomposition at 168. The yield is 90 per cent. The a-diketones are best reduced with zinc dust and sulphuric acid, iron and acetic acid, stannous chloride and hydrochloric acid, or sodium hydrosulphite in alcoholic solution. 3 PREPARATION OF HYDROBENZOIN (C 6 H 5 CHOH. CHOHC 6 H 5 ). 4 Twenty grammes of benzoin are dissolved in 200 c.c. of alcohol and the solution heated on the water-bath with 22 grm. of stannous chloride in 60 c.c. of hydrochloric acid (D == 1*17) until decolorised (about half an hour). The whole is then cooled, filtered, and the precipitate washed with a little alcohol. M.P. 134. Colourless leaflets from glacial acetic acid or aqueous alcohol. Yield almost theoretical. The indigoid and anthraquinonoid dyes are best reduced to their hydroxy compounds (the " vats ") by 1 J- pr. [2] 33, 184. 2 B. 14. R. 1402. C. 1881, 150. 3 J-pr. [2] 76, 137. 4 B. 37, 1677. 94 PREPARATION OF ORGANIC COMPOUNDS treatment with alkaline sodium hydrosulphite. The reduction compounds are difficult to isolate in a pure state, as they are very rapidly oxidised by the air. 1 If, however, the reduction is carried out with zinc dust and boiling acetic anhydride in the presence of anhydrous sodium acetate, the vats can be readily isolated in the form of their stable acetic esters. PREPARATION OF DIACETYLOXYANTHRANOL, 2 C.OCOCH 3 y \C 6 H 4 . One part of anthraquinone is boiled for C.OCOCH 3 a short time with 10 to 15 parts of acetic anhydride, 2, parts of anhydrous sodium acetate, and 3 parts of zinc dust. The solution after cooling is filtered, the residue dissolved in a little boiling glacial acetic acid, filtered hot, and the filtrate allowed to cool. The diacetyl-oxyanthranol is collected, and recrystal- lised several times from glacial acetic acid. It forms colourless needles which melt at 260. The more fully reduced anthraquinones, the anthranols, ,CH . C 6 H / | >C 6 H 4 X COH/ are more stable than the oxy anthranols. /CH . PREPARATION OF ANTHRANOL, C 6 H 4 <( >C 6 H 4 . \/ (a) 3 Ten grammes of anthraquinone are boiled with 400 c.c. of glacial acetic acid and 25 grm. of granulated zinc. Con- centrated hydrochloric acid is added to the boiling liquid in quantities of a few cubic centimetres at a time until further addition no longer causes the appearance of a transitory brown colour and hydrogen is continuously evolved. The reduc- tion requires about a quarter of an hour, and on cooling the solution should not deposit crystals. When cold, the whole 1 Vide J. pr. [2] 76, 141, and D.R.P. 204,568 (indigo white) ; B. 40, 390, 924. 2 B. 21, 1172. 3 B. 20, 1854. ALCOHOLS, PHENOLS, AND MERCAPTANS 95 is poured into dilute hydrochloric acid, and the precipitate recrystallised from glacial acetic acid. Colourless needles melting with decomposition at i63-i7O. Yield 80 per cent. (b) l Ten grammes of anthraquinone are dissolved in 150 grm. of concentrated sulphuric acid, and 25 grm. of aluminium powder (" aluminium bronze ") slowly added, care being taken that the temperature does not rise above 3o-4O. When almost colourless, the solution is poured into i litre of water and the precipitate collected and recrystallised from glacial acetic acid. Instead of aluminium powder, copper powder may be used (10 parts anthraquinone, 160 H 2 SO 4 , 7 Cu at 20 to 40). In order to avoid oxidation when crystallising anthranol, it is advantageous to add a little hydrochloric acid and a trace of aluminium powder to the acetic acid. The true quinones are usually reduced by sulphurous acid, but are more rapidly attacked by hydroxylamine or phenylhydrazine. The latter reagent reduces alcoholic solutions of quinone with almost explosive violence. PREPARATION OF HYDROQUINONE (Quinol) (C 6 H 4 [i.4](OH) 2 ). 2 For this preparation either pure, very finely ground quinone suspended in water, or, more usually, the suspension of crude quinone obtained by the oxidation of aniline as described on p. 138 is used. In either case the cold liquid is saturated with gaseous sulphur dioxide until it retains the smell of the gas after standing over-night. The solution is then extracted several times with ether, the ether removed by distillation, and the residue recrystallised from water containing sulphurous acid and animal charcoal. The hydroquinone forms colourless needles which melt at 169. In the above reduction the first product is the highly coloured quinhydrone (see p. 103), which is then further reduced by the sulphurous acid to the quinol. Aromatic aldehydes, in which the aldehydic group is directly attached to the nucleus, undergo simul- taneous reduction and oxidation when heated with 1 D.R.P. 201,542. 2 A. 215, 127. 96 PREPARATION OF ORGANIC COMPOUNDS aqueous caustic alkali, an alcohol and a carboxylic acid being formed : 2ArCHO + KOH = ArCH 2 OH + ArCOOK. (vii) FROM THE UNSATURATED COMPOUNDS. The unsaturated compounds may be converted into hydroxyl compounds by the addition of water, hypo- chlorous acid, &c., or by oxidation. The addition of the elements of water can, in some cases, be effected in the presence of acids or alkalis, but the reaction only takes place with great difficulty in the case of ethylenic compounds, and will not be further considered. It may be remarked, however, that the addition takes place most readily when the double bond is adjacent to a carboxyl group. The addition takes place somewhat more readily in the case of acetylenes. Thus acetylene itself when passed into concentrated or dilute sulphuric acid gives acetaldehyde : H 2 O Tautomeric CHjCH CH 2 :CHOH CH 3 .CHO. change Attempts have been made to apply this reaction to the production of acetaldehyde on the large scale, in order to obtain ethyl alcohol by its reduction. Such attempts, however, have not been commercially successful. As certain metals, 1 such as platinum, and some salts, 2 notably mercury salts, act as catalysts in the above reaction, it is not impossible that it may become commercially successful at a future date. Of greater importance than the above addition re- actions is the oxidation of ethylenic bonds to vic-dioxy- compounds. The oxidation is usually carried out by very dilute (i to 2 per cent.) potassium permanganate solution. In some cases alkali-hypobromites, ferric chloride in acetone solution, Caro's acid (p. 193), or nitric acid can be used. Potassium permanganate, however, usually gives the best results. i C. 1095 I, 1585. 2 B. 14, 1540. ALCOHOLS, PHENOLS, AND MERCAPTANS 97 PREPARATION OF /3-PHENYL GLYCERIC ACID (C 6 H 5 .CHOH.CHOH.COOH).i Sixty grammes of cinnamic acid are dissolved in 5 to 6 litres of water and the solution made strongly alkaline with sodium carbonate or caustic soda. It is then cooled with ice, and treated slowly, and with continual stirring and cooling, with 90 grm. of potassium permanganate in 2 per cent, aqueous solution. During the oxidation the temperature should not rise above o. The solution is filtered from precipitated manganese hydroxide, and dilute hydrochloric acid added to the clear filtrate until it is only slightly alkaline. It is then boiled down to about half its volume, neutralised with hydrochloric acid, and concentrated on the water-bath to a small volume. A good deal of salt separates out, but this does not interfere with the isolation of the acid. After cooling, the solution is repeatedly extracted with ether (eight to ten times) . The ethereal extracts are extracted with cold water and the dissolved ether removed from the aqueous portion by blowing air through it. A slight precipitate separates and is discarded. The filtrate is heated almost to boiling and neutralised with chalk. On cooling, the calcium salt of /3-phenyl glyceric acid separates out and is purified by recrystallisation. The free acid can be obtained by decomposing the calcium salt with hydrochloric acid and then extracting with ether. As, however, the acid is very soluble in water and only slightly soluble in ether, it is better to decompose the calcium salt with the exact amount of oxalic acid, filter off the calcium oxalate, and concentrate the filtrate until crystallisation sets in. The acid crystallises from water in colourless needles which melt with decomposition at 141. (viii) FROM THE ALDEHYDES BY CONDENSA- TIONS, (a) The aldol condensation is discussed on p. 117, and, therefore, it is merely necessary to point out that if the condensation is carried out in the presence of magnesium amalgam, the aldehydic group of the aldol is simultaneously reduced, a dihydric alcohol resulting. (b) The benzoin condensation is discussed on p. 131, and leads to aromatic ketonic alcohols. (c) The Lederer-Manasse synthesis is of considerable 1 B. 21, 919 ; A. 268, 27. 98 PREPARATION OF ORGANIC COMPOUNDS importance, but is confined to the production of phenolic carbinols. When formaldehyde is condensed with a phenol, either a diphenyl methane derivative or a benzyl alcohol is produced : 2C 6 H 5 OH +H.CHO = HOC 6 H 4 .CH 2 .C 6 H 4 OH + H 2 O C 6 H 5 OH + H.CHO = HOC 6 H,.CH 2 OH the entering group taking the para- or ortho- position to the hydroxyl group, the para- position being prefer red. The former of the above reactions takes place when the more powerful condensing agents are used, but it is impossible to foretell in any definite case which reaction any given condensing agent will give rise to. As a rule, the caustic alkalis, alkali carbonates, alkaline earth oxides, lead oxide, or hydrochloric acid are used to bring about the condensation. When hydrochloric acid is used, the corresponding benzyl chloride is fre- quently produced ; from it the alcohol can be obtained by heating with water or dilute alkalis. Occasionally two oxymethyl groups can be introduced. PREPARATION OF o.- AND .-OXYBENZYL ALCOHOLS (HOC 6 H 4 CH 2 OH) - 1 Sixty grammes of phenol are dissolved in 300 c.c. of 10 per cent, caustic soda, 70 grammes of 40 per cent. formaldehyde solution added, and the whole allowed to stand at the ordinary temperature for several days. The solution is then neutralised with hydrochloric acid, extracted several times with ether or ethyl acetate, and the solvent then removed by distillation. If unchanged phenol is present in the residue, it is removed by distillation in steam. Finally the o.- and ^.-oxybenzyl alcohols are separated by fractional crystallisation from benzene. The ortho- compound being much more soluble than the para- compound, a fairly complete separation can be effected by shaking the mixture with cold benzene. o.-Oxybenzyl alcohol (saligenin) melts at 82 ; ^.-oxybenzyl alcohol at ni-ii2 . PREPARATION OF .-CRESOLDIMETHYLOL (C 6 H 2 [i] OH[2-6](CH 2 OH) 2 [4]CH 3 ). 2 Twenty-two grammes of />.-cresol i B. 27, 2411 ; D.R.P, 85,588 2 B. 40, 2524. ALCOHOLS, PHENOLS, AND MERCAPTANS 99 are dissolved in 150 c.c. of 15 per cent, caustic soda solution, and 30 grm. of 40 per cent, formaldehyde solution are added. After standing for several days at the ordinary temperature, the solution is acidified with acetic acid or saturated with carbon dioxide and the precipitate filtered off and recrystallised. It melts at 133. PREPARATION OF s-NITRO-4-OXYBENZYL ALCOHOL (C 6 H 3 [i]CH 2 OH[3]NO 2 [4]OH).i Forty grammes of o.-nitro- phenol, 100 grm. of 40 per cent, formaldehyde, and 200 c.c. of concentrated hydrochloric acid are boiled under a reflux- condenser for six hours. After cooling, the supernatant liquor is decanted from the heavy brown oil, and the latter distilled in steam to remove unchanged nitrophenol. The residue is extracted several times with boiling water, and the united extracts filtered hot and then allowed to cool. Long yellow needles are deposited, which after being recrystallised from water several times melt at 97. In exactly the same way . -nitrophenol yields 2-oxy-5-nitro- benzyl alcohol, which forms colourless needles melting at 128. PREPARATION OF HEXAOXYDIPHENYL METHANE DICARBOXYLIC ACID. 2 One hundred grammes of gallic acid are dissolved in 1125 c.c. of hot water, and 375 c.c. of hot concentrated hydrochloric acid and 60 grm. of 40 per cent. formaldehyde added. The whole is heated on the water-bath under a reflux condenser until no further precipitation takes place, filtered hot, and the precipitate well washed with boiling water, then with alcohol, and finally with ether. The acid forms a crystalline powder which does not melt. The yield is 57 per cent. PREPARATION OF s-CHLOR-4-OXYBENZYL CHLORIDE (C 6 H 3 [i]CH 2 Cl[3]Cl[4]OH). 3 Five parts of o.-chlorphenol and 6 parts of 40 per cent, formaldehyde are mixed, well cooled with ice, and then saturated with hydrochloric acid gas. The solution is set aside for about two weeks with frequent shaking, when an oil separates out which soon becomes crystalline. It is then pressed on a porous plate and recrystallised several times from benzene, and from anhydrous 1 B. 34, 2458 ; D.R.P. 136,680. 2 B. 25, 946 ; 31, 260. 3 B. 34, 2459. ioo PREPARATION OF ORGANIC COMPOUNDS petroleum ether. It melts at 93. The corresponding alcohol, 3-chlor-4-oxybenzyl alcohol, is obtained when the above compound is boiled with water. After cooling, it is extracted with ether, and the ether removed by distillation. A clear yellow oil remains which becomes crystalline when the sides of the vessel are scratched. It is recrystallised from benzene, and forms colourless needles which melt at 123. Similar to the above reactions is the condensation of chlormethyl alcohol with phenols, which sometimes takes place without the addition of a condensing agent, e.g. chlormethyl alcohol and salicylic acid when boiled in aqueous solution yield saligenic acid, 1 or in the presence of hydrochloric acid 2 or zinc chloride. (d) Diaryl carbinols can often be obtained when an aromatic aldehyde is condensed with a phenol or an aromatic base. Here the normal course of the reaction is the formation of a triphenyl methane derivative : Ar.CHO + 2C 6 H 5 NMe 2 = ArCH(C 6 H 4 NMe 2 ) 2 + H 2 O but by working in dilute solutions the reaction can be arrested when only one molecule of the phenol or base has condensed. Just as in the Lederer-Manasse synthesis, the para- position is preferred, but if this is occupied the entering group often takes the ortho- position. The reaction takes place in the presence of hydro- chloric acid. When an aldehyde is being condensed with a base it is usually sufficient simply to employ the base in the form of its hydrochloride. PREPARATION OF 4 - NITRO - 4'- DIMETHYLAMINO BENZHYDROL (NO 2 .C 6 H 4 CHOHC 6 H 4 .NMe 2 ). 3 Fifteen grammes of ^.-nitrobenzaldehyde and 12 grm. of dimethyL aniline are boiled under a reflux condenser for 40 hours wrTfT 300 c.c. of concentrated hydrochloric acid. The solution is then diluted, unchanged nitrobenz aldehyde removed by 1 D.R.P. 113,512. 2 D.R.P. 113,722. 3 D.R.P. 45,8o6. ALCOHOLS, PHENOLS, AND MERC APT ANS 101 filtration, and the filtrate neutralised. The benzhydrol separates as yellow flocks which are collected, washed, and freed from small quantities of dimethyl aniline by steam- distillation. It is finally recrystallised from dilute alcohol and forms fine yellow needles which melt at 96. The yield is 80 per cent. The corresponding compound from benzaldehyde and dimethyl aniline, ^.-dimethylamino benzhydrol, is formed in the same way, but the preparation does not go as smoothly as in the above example. For further information regarding this reaction the reader is referred to the original literature. 1 (ix) FROM THE HYDROCARBONS, ETC., BY DIRECT OXIDATION. In the aliphatic series this reac- tion can only take place if the hydrogen is attached to a tertiary carbon atom, as in triphenyl methane. The reaction is of very minor importance, as although the carbinol is probably the first product obtained when the leuco-derivatives of the triphenyl methane dyes are oxidised, it is not isolated, but at once loses a molecule of water to form the dyestuff, e.g. : OH (C 6 H 5 ) 2 CH.C 6 H 4 NMe 2 - [(C 6 H 6 ) 2 .C.C 6 H 4 .NMe 2 .HCl] (C 6 H 5 ) 2 .C : C 6 H 4 : NMe 2 Cl Leucomalachite Green Possibly the free bases possess the carbinol structure, but for further information on this subject the reader is referred to works on tinctorial chemistry. See also pp. 288-297. PREPARATION OF TRIPHENYL CARBINOL (C 6 H 5 ) 3 C.OH. 2 Twelve grammes of triphenyl methane are dissolved in 60 grm. of glacial acetic acid and the solution warmed on the water-bath. Twelve grammes of chromic acid are slowly added, and the warming continued until a sample 1 B. 21, 3292 ; 42, 4163 ; D.R.P. 45,8o6, 119,461. 2 B. 14, 1944. 102 PREPARATION OF ORGANIC COMPOUNDS poured into water gives a precipitate which does not melt when the water is boiled (about i to i^ hours). The whole is then poured into water, and the precipitate recrystallised from benzene. M.P. 159. Yield 80 to 90 per cent. The hydrogen atoms in aromatic compounds can occasionally be oxidised to hydroxyl by the action of hydrogen peroxide in glacial acetic acid. 1 In the case of anthraquinone, oxidation takes place more readily, and the technical preparation of alizarine consists in heating the /3-sulphonic acid with caustic soda and potassium chlorate in closed vessels : CO CO S0 3 Na CO OH /\/V\ QH CO Alizarine Anthraquinone can also be oxidised to oxyanthra- quinones by heating with oleum or nitrosyl sulphuric acid in the presence of boric acid, the boric acid forming boric esters and hence allowing the oxidation to be carried out at a higher temperature than would be otherwise possible. 2 (x) FROM THE QUINONES BY THE ADDITION OF PHENOLS. The true quinones, such as benzo- quinone, readily add on two molecules of a phenol to form an addition compound, e.g. : HO O : C 6 H 4 : O + 2 C 6 H 5 OH = H0/ /OH 4 <^ X OC 6 H 5 Phenoquinone With hydroquinones only one molecule is taken up, a quinhydrone being formed : 1 Soc. 97, 1659. 2 D.R.P. 65,375,68,114, 68,123, 64,418, 81,481, &c. ALCOHOLS, PHENOLS, AND MERCAPTANS 103 O C 6 H 4 O O : C 6 H 4 : O + C 6 H 4 (OH) 2 = ^>C 6 H 4 <^ HO OH The reaction takes place very readily, the highly coloured addition products being produced when the solutions of the two components are mixed. Hence the quinhydrones are the first products formed when the quinones are prepared by oxidising the hydroquinones, or when the quinones are reduced to the hydro- quinones, and by using only half the quantity of the reducing or oxidising agent demanded by the equation : C 6 H 4 (OH) 2 ^ 0:C 6 H 4 :0 H 2 they may be readily isolated. PREPARATION OF PHENOQUINONE, 1 C 6 H 5 X xOC 6 H 5 ^CeH^ . 1 One part of benzoquinone and H(X X OH 2 parts of phenol are heated under a reflux condenser in ligroin solution for a few minutes. On cooling (the solution having been concentrated if necessary), the phenoquinone separates out as red needles with a green reflex. M.P. 71. Resorcin-quinone is best prepared in benzene solution. Almost black needles with green reflex. Decomposes at about 90. Pyrogallol-quinone (purpurogallein) is similar. PREPARATION OF QUINHYDRONE, 2 O /64 v / This compound can be obtained by warming quinone and hydroquinone in aqueous solution, but is most readily pre- pared by warming hydroquinone in aqueous solution with half the quantity of ferric chloride necessary for its oxidation to quinone. It forms green prisms with a strong metallic lustre. M.P. 171. 1 A. 200, 251 ; 215, 134. 2 B. 24, 1341- io 4 PREPARATION OF ORGANIC COMPOUNDS (xi) FROM THE a-DIKETONES BY INTRA- MOLECULAR REARRANGEMENT. This rearrange- ment of the aromatic a-diketones into derivatives of glycollic acid under the action of caustic alkalis is discussed on p. 172. It may be pointed out that phenanthraquinone undergoes a similar rearrange- ment : '\ /\ COOH \/ Phenanthraquinone Diphenylene glycollic acid THE MERCAPTANS The mercaptans, or thioalcohols, form a rather unimportant class of compounds, and, on account of their disgusting odour, are unpleasant to deal with. The aliphatic members are usually best obtained by distilling the sodium salts of alkyl sulphuric acids with sodium sulphydrate in aqueous solution. 1 The corresponding sulphide is formed simultaneously, but the mercaptan is readily separated by washing with caustic potash solution, in which it dissolves to form a mercaptide, and then decomposing the alkaline solu- tion with mineral acids. The mercaptans can also be obtained by reducing the sulphochlorides with zinc and sulphuric acid, or from the halogen compounds by double decomposition with sodium sulphydrate or sodium disulphide, the disulphide formed in the latter case being subse- quently reduced with zinc and hydrochloric acid. * B. 20, 3409. ALCOHOLS, PHENOLS, AND MERCAPTANS 105 PREPARATION OF THIOGLYCOLLIC ACID (HS.CH ? . COOH). (a) 1 One hundred grammes of chloracetic acid are dissolved in 500 c.c. of water and accurately neutralised with potassium carbonate or caustic potash. To the cold solution 500 c.c. of aqueous potassium sulphydrate, containing 80 grm. KSH, are added slowly with continual agitation, and the whole then heated for fifteen minutes on the water-bath. A concentrated aqueous solution of 250 grm. of crystallised barium chloride and 100 c.c. of 25 per cent, ammonia are added, and the whole then set aside. After standing several hours crystallisation can be induced by violently shaking the liquid and scratching the sides of the vessel. The barium salt is filtered off and forms shining monosymmetric tablets having the formula : S CH 2 CO \ / +3H 2 BaO In order to obtain the free acid, the barium salt is ground up with 3 parts of 12 per cent, hydrochloric acid, extracted several times with ether, the ethereal extract dried, and the ether then removed by distillation from the water-bath. The residue is finally fractionated in vacuo, when the free acid passes over as a colourless oil boiling at iO7-io8 at 16 mm. (b) 2 Chloracetic acid (9*45 grm.) is dissolved in 40 c.c. of water and neutralised with 5-5 grm. of sodium carbonate. A cold solution of sodium disulphide, obtained by boiling 12 '8 grm. crystallised sodium sulphide with 3-2 grm. of sulphur and 35 c.c. of water, is then slowly added, the temperature being allowed to rise to about 40. The whole is digested for one hour at 95, cooled, filtered, and the filtrate treated at 70 with 7-7 grm. zinc dust and 41 grm. concentrated hydrochloric acid. After filtering, the liquid is neutralised with sodium carbonate, and the sodium salt salted out with sodium chloride, or it is made alkaline with ammonia, barium chloride (25 grm.) added, and the barium salt treated as in the first preparation. Thioglycollic acid is of increasing importance for the manufacture of the thioindigoid vat-dyes. Even halogen atoms attached to a benzene nucleus 3 1 B. 39, 733. 2 D.R.P. 180,875. 3 When nitro-groups are present in the ortho- or para- position, the halogen atom is much more readily replaced. Cf. p. 152. io6 PREPARATION OF ORGANIC COMPOUNDS can sometimes be replaced by the mercaptan group, but in this case a contact substance, such as a copper salt, must be added. PREPARATION OF TH IOS ALIC YLIC ACID 1 Fifty grammes of o.-chlorbenzoic acid are mixed with a little water and then 38-5 grm. of caustic soda of 40 Be. (13-5 grm. NaOH in 25 c.c. water), 100 grm. of sodium sulphydrate, and 0-5 grm. of crystallised copper sulphate carefully mixed in. The whole is then heated with continual stirring to i5o-2OO. The mass soon becomes dark red and melts. The temperature is then raised to 250, when the mass becomes thick, heats spontaneously, and gradually solidifies. The cooled melt is dissolved in a litre of water and the thio- salicylic acid precipitated from the filtered solution with hydrochloric acid. The yield is almost quantitative. Thiosalicylic acid is also of importance as an inter- mediate product in the manufacture of thioindigoid dyes. Another important method for producing aromatic mercaptans is by the replacement of the diazo-group. This replacement can be brought about in several ways, viz. : (i) The diazo-chloride is treated with potassium xanthate, and the xanthic ester then hydrolysed : 2 Ar.N:N.Cl + KS.C^ = ArS.C< + KC1 + N 2 X OEt \OEt + 5H 2 O = ArSH + EtOH + H 2 S + CO 2 \OEt (ii) The diazo-salt is treated with potassium and copper thiocyanates and the aryl thiocyanate thus formed hydrolysed. 3 (iii) The diazo-solution is treated with potassium sulphydrate, when the mercaptan is formed directly. 4 i D.R.P. 189,200. 2 J. pr. [2] 41, 184. 3 B. 23, 738, 770. 4 B. 20, 349. ALCOHOLS, PHENOLS, AND MERCAPTANS 107 (iv) The diazo-solution is treated with sodium poly- sulphide and the polysulphide then reduced. 1 PREPARATION OF TH I OS ALI CYLIC ACID 2 Ten parts of anthranilic acid are dis- solved in 1 50 to 200 parts of dilute hydrochloric acid containing 5 parts of HC1, ice (20 parts) is added, and the whole diazotised in the usual way with 6-7 parts of sodium nitrite. Sulphuretted hydrogen is then passed into the diazo-solution until the yellow precipitate which at first separates becomes bright red. This is due to the formation of N : N.SH COOH The still moist precipitate is dissolved in sodium carbonate solution, and the whole warmed until a sample gives a pure white precipitate with hydrochloric acid. The solution is then made acid (Congo paper) with hydrochloric acid, and the precipitated thiosalicylic acid filtered off and washed with cold water. 1 Pat Anm. Kl. 12. q. 30,607, 32,070. 2 D.R.P. 69,073. CHAPTER V ALDEHYDES, KETONES, QUINONES (AND QUINONE-IMIDES), AND SOME DERIVA- TIVES OF THE SAME A. THE ALDEHYDES BEFORE discussing the various methods of preparing the aldehydes, a few words must be said on the methods employed for isolating and purifying the same. For this purpose it is usual to convert the aldehyde into a derivative which crystallises well, and which can be readily decomposed into the original aldehyde. Such derivatives are numerous, and some of the most important will be found discussed at the end of this chapter. Ammonia is occasionally used (see p. 109) and the resulting aldehyde-ammonia decomposed by distilling with acids : X H 2R.C-OH + H 2 S0 4 - 2R.CHO + (NH 4 ) 2 SO 4 . More commonly the crude aldehyde is shaken up with a concentrated solution of sodium bisulphite, and the resulting bisulphite compound decomposed by distilling with sodium carbonate solution : +Na 2 C0 3 =2R.CHO + 2 Na 2 SO 3 +CO 2 +H 2 O. This method is fairly general, but is inapplicable in some cases, especially in the terpene series, where the aldehyde is very sensitive to acids. In such cases the aldehyde can be combined with an amino-carboxylic 108 ALDEHYDES, KETONES, QUINONES 109 or amino-sulphonic acid, the resulting compound being usually decomposed by steam distillation, without the addition of acids : R.CH :NR'SO 3 Na +H 2 O -R.CHO + NH 2 R'SO 3 Na. The most usual amino-sulphonic acid to use is naph- thionic acid (a-naphthylamine-4-sulphonic acid) either in the form of its sodium or its barium salt. The latter salt has the advantage of giving condensation products which are practically insoluble. Sugars are best isolated as their phenylhydrazones, e.g. : CH 2 OH(CHOH) 4 .CH rN.NHPh. I. OXIDATION OF PRIMARY ALCOHOLS. This method is most frequently employed in the aliphatic series, especially for oxidising polyhydric alcohols to the corresponding polyoxyaldehydes (the aldoses). For the oxidation of monohydric alcohols, potassium bichromate and sulphuric acid are usually employed, but the oxidation can often be brought about by atmospheric oxygen in the presence of contact sub- stances. Thus formaldehyde is prepared technically by passing methyl alcohol vapour and air over copperised asbestos, the heat of the reaction being sufficient to keep the asbestos at a dull red heat. PREPARATION OF ACET ALDEHYDE (CH 3 CHO). Two hundred cubic centimetres of water and 60 c.c. of concentrated sulphuric acid are placed in a flask fitted with a condenser * and tap-funnel, and heated to boiling. The flame is then removed and a solution of 200 grm. of sodium dichromate in 200 c.c. of water and 125 c.c. of alcohol slowly added through the tap-funnel. Considerable heat is given out, and the bichromate solution should be added at such a rate as to keep the whole boiling fairly briskly. The distillate, which consists chiefly of aldehyde, alcohol, and water, is then distilled from the water -bath through a sloping reflux condenser (Fig. 50) into 100 c.c. of dry ether, which is kept cold by means 1 The water in the condenser should be as cold as possible and r the receiver should be cooled with ice. no PREPARATION OF ORGANIC COMPOUNDS of ice or a freezing mixture. The water in the condenser should be maintained at a temperature of 3o-35 in order to condense the alcohol and water, but not the aldehyde. The bulb A is to prevent the ether being sucked back. The aldehyde dissolves in the ether, and the solution thus obtained is saturated with dry ammonia gas (see p. 31) and then allowed to stand for an hour. The colourless crystals of alde- hyde ammonia, CH 3 .CH (OH) (NH 2 ), which separate are collected, washed with ether, and dried between filter-paper FIG. 50. at the ordinary temperature. Yield about 30 grm. The compound is dissolved in its own weight of water, 3^- parts of cold, 40 per cent, sulphuric acid added, and the whole distilled from the water -bath. As aldehyde boils at 21, ice-water should be run through the condenser, and the receiver should be cooled in a freezing mixture. The distillate is dried with calcium chloride and redistilled from a water-bath heated to 30. It forms a colourless liquid with a pleasant smell. Alcohol can also be oxidised by treating it with a stream of chlorine gas. Simultaneous chlorination takes place, trichloracetaldehyde (chloral), CC1 3 CHO, being ALDEHYDES, KETONES, QUINONES in formed. This unites with excess of alcohol to form the alcoholate, CC1 3 CH(OH)(OC 2 H 5 ). The reaction commences in the cold and is completed by raising the temperature to the boiling-point. The oxidation of polyhydric alcohols to aldoses is best brought about by dilute nitric acid, sodium carbonate and bromine, or hydrogen peroxide in the presence of traces of ferrous sulphate (Fenton's reagent) . The sugars, which are troublesome to obtain in the free state, are isolated as their phenylhydrazones. PREPARATION OF MANNOSE PHENYLHYDRAZONE (CH 2 OH (CHOH) 4 CH : N . NHPh) .1 Sixty grammes of mannite are added to 400 c.c. of water and 200 c.c. of concentrated nitric acid (D = 1-41), and the whole heated to a temperature of 40 to 45. After two or three hours red fumes appear, and the liquid must then be tested every twenty minutes by withdrawing a small sample, neutralising with crystallised sodium carbonate, and then adding a little phenyl hydrazine dissolved in acetic acid, care being taken that the whole shows an acid reaction. When a sample so treated deposits a heavy yellow precipitate on standing for a few minutes, the heating is stopped and the reaction mixture cooled as rapidly as possible. It is rendered alkaline by the addition of crystal- lised sodium carbonate, the carbon dioxide evolved sweep- ing the liquid clear of nitrous acid. It is then acidified with acetic acid, and 20 grm. of phenyl hydrazine dissolved in dilute acetic acid added. On standing over-night the hydrazone is deposited as pale yellow needles. M.P. 195. Yield 6 grm. The testing every twenty minutes is very necessary, as if the oxidation is carried too far the aldehyde will be oxidised to the corresponding carboxylic acid. The sugar itself can be obtained by boiling the hydrazone with concen- trated hydrochloric acid, but it is very troublesome to isolate. The oxidation can also be carried out as follows. 2 Twenty grammes of mannitol are dissolved in 100 c.c. of water contain- ing 5 grm. of crystallised ferrous sulphate. The solution is well cooled and then 60 c.c. of 20 volume (6 per cent.} hydrogen dioxide slowly run in. The whole is made just alkaline with sodium carbonate, acidified with acetic acid, and then treated with 6 grm. of phenyl hydrazine dissolved in dilute i B. 22, 365. 2 Soc. 75, 9. ii2 PREPARATION OF ORGANIC COMPOUNDS acetic acid. After standing, the hydrazoneis collected, washed, ground up with acetone, and recrystallised, first from boiling water, then from 60 per cent, alcohol, and finally twice from water containing animal charcoal. II. OXIDATION OF AROMATIC HYDRO- CARBONS. For the direct oxidation of aromatic hydro- carbons to aldehydes a variety of oxidising agents is available. (a) Chromyl chloride (Etard's reaction) . The hydro- carbon is dissolved in 10 parts of carbon bisulphide, and the chromyl chloride dissolved in the same solvent slowly added with continual cooling. A brown com- pound, RCH(OCrCl 2 OH) 2 , is precipitated and is finally decomposed with water. This method is not often used as the reaction is often dangerously violent and the intermediate compounds are very explosive. (b) Chromic acid. As chromic acid oxidises the aldehydes to carboxylic acids, the aldehyde must be protected at the moment of its formation. To bring about this result the oxidation is carried out in acetic anhydride solution in the presence of concentrated sulphuric acid. Under these conditions the aldehyde is at once converted into its diacetate, and as this is not attacked by chromic acid it can be isolated and subsequently hydrolysed by boiling with acids R.CHO + (CH 3 CO) 2 = RCH(OCOCH 3 )s R.CH(OCOCH 3 ) 2 '+ H 2 = RCHO + 2CH 3 COOH. PREPARATION OF ISO-PHTHALALDEHYDE, C 6 H 4 (CHO) 2 [i'3]. 1 Twenty-five grammes of w.-xylene are dis- solved in a mixture of 1000 grm. of acetic anhydride, 400 grm. of glacial acetic acid, and 15 grm. of concentrated sulphuric acid. One hundred grammes of chromic acid are then slowly added, the temperature being kept at about 5. When all the chromic acid has been added, the whole is allowed to stand at the above temperature until a sample gives a copious white precipitate when shaken with cold water until the acetic anhydride is destroyed. The whole is then poured on to excess i D.R.P. 121,788 ; A. 311, 353. ALDEHYDES, KETONES, QUINONES 113 of ice and stirred mechanically until the oily substance at first precipitated becomes solid. The ^so-phthalaldehyde tetrace- tate is then collected and recrystallised from methyl alcohol. It forms colourless prisms melting at 101. To obtain the free aldehyde, the tetracetate is boiled for a short time with 4 parts of 5 per cent, hydrochloric acid. On cooling, the aldehyde separates out in long needles melting at 89. It may be purified by recrystallisation from water. (c) Cerium dioxide. The oxidation is carried out in the presence of fairly strong sulphuric acid : Ce0 2 + H 2 S0 4 = CeS0 4 + H 2 O + O. Technical cerium dioxide is usually a brown powder containing 60 to 70 per cent, of CeO 2 . The amount of active oxygen is readily estimated by treating with hydrochloric acid and potassium iodide and then titrating the liberated iodine in the usual way. PREPARATION OF BENZ ALDEHYDE (C 6 H 5 CHO).i One litre of 60 per cent, sulphuric acid and 30 grm. of toluene are heated to 60 in a flask provided with a reflux condenser and mechanical stirrer. Two hundred grammes of technical cerium dioxide are then gradually added, and the tempera- ture allowed to rise to 90. When the brown dioxide has changed to the white sulphate the whole is steam-distilled, a mixture of unchanged toluene and benzaldehyde passing over. These may be separated by fractional distillation, but it is better to shake the whole on a shaking-machine for some hours with concentrated sodium bisulphite solution. If any crystals separate, water is added until they dissolve. The aqueous layer is then removed and solid sodium carbonate added until an alkaline reaction is obtained. The whole is again steam-distilled, the benzaldehyde separated by means of a tap-funnel, dehydrated over calcium chloride, and finally distilled in a current of hydrogen. It forms a colourless oil with a pleasant smell. B.P. 179. On the manufacturing scale the following oxidising agents have met with great success, but for further details the reader is referred to the literature : (a) i D.R.P. 158,609. n 4 PREPARATION OF ORGANIC COMPOUNDS manganese dioxide and sulphuric acid, D.R.P. 101,221 ; (b) ammonium manganese alum, Mn 2 (SO 4 ) 3 .(NH 4 ) 2 SO 4 , prepared by the electrolysis of ammonium manganese sulphate and sulphuric acid, D.R.P. 189,178; (c) man- ganese persulphate, Mn(SO 4 ) 2 , prepared by the elec- trolysis of manganous sulphate and sulphuric acid, D.R.P. 163,813; (d) ozone. This last reagent is used for preparing aldehydes by the rupture of a double bond. Ozonides (highly explosive bodies) are formed as intermediate compounds, and then undergo decom- position into two molecules of aldehyde or one molecule of aldehyde and one of ketone : HR.CH : CR 2 + 3 =R.CH - CR 2 = RCHO + R 2 CO + O. For the preparation of vanillin from isoeugenol by this method, see D.R.P. 97,620 : CH:CH.CH 3 CHO OCH, OCH, L 3 OH OH Isoeugenol Vanillin What is probably a modification of this method consists in blowing fine streams of air through isoeugenol which is simultaneously submitted to the action of ultra-violet light. The yield is said to be about 95 per cent. D.R.P. 224,071. For the indirect oxidation of side-chains three methods are available, viz. : (i) The di-halogen compound is prepared and then boiled with water, sodium carbonate solution, or chalk : R.CHC1 2 ->(RCH(OH) 2 )->R.CHO + H 2 O. PREPARATION OF BENZALDEHYDE (PhCHO). Fifty grammes of benzalchloride, C 6 H 6 CHC1 2 , are heated under a ALDEHYDES, KETONES, QUINONES 115 reflux condenser on the oil-bath (temperature of bath, 130) with 250 c.c. of water and 80 grm. of precipitated calcium carbonate. At the end of four hours the whole is steam-dis- tilled. The distillate is worked up as described on p. 113. (ii) The mono-halogen compound is condensed with a primary aromatic amine (e.g. aniline or, better, sulphanilic acid) , and the benzylaniline derivative thus obtained oxidised to the corresponding benzylidene com- pound. This latter is then split by heating with hydrochloric acid : ArCH 2 Cl + HNHC 6 H 5 = ArCH 2 .NHC 6 H 5 + HC1 ArCH 2 NHC 6 H 5 + O = ArCH : NC 6 H 5 + H 2 O ArCH : N.C 6 H 5 + H 2 O = ArCHO + C 6 H 6 NH 2 PREPARATION OF o.-NITROBENZALDEHYDE (C 6 H 4 [i]NO 2 [2]CHO). 1 Twenty-three grammes of o.-nitro- benzylaniline are dissolved in acetone, and the solution cooled to 10. A cold saturated solution of 12-5 grm. potassium permanganate is then slowly added, the whole being con- tinually and vigorously stirred. The solution is then filtered and the acetone removed by distillation. The resulting o.-nitrobenzylidene aniline is hydrolysed by mixing with 15 parts of cold, concentrated hydrochloric acid. The aldehyde crystallises out and can be further purified by steam-distilla- tion and recrystallisation from water. Long, pale-yellow needles. M.P. 46. (iii) In some cases where negative groups, such as nitro-groups, are present in the 0.- and p.- positions to the side-chain, the hydrogen of the latter is rendered sufficiently active to condense with ^>.-nitroso-di- methylaniline. The anil, ArCH : NC 6 H 4 NMe 2 , is then split by treatment with acids. PREPARATION OF 2.4-DINITROBENZALDEHYDE (C 6 H 3 [i ]CHO [2 .4] (NO 2 )2) .* Forty-five grammes of 2.4-dinitro- toluene, 40 grm. of .-nitroso-dimethylaniline, and 75 grm. of 1 D.R.P. 91,503, 92,684. B. 35, 1228 ; D.R.P. 121,745. n6 PREPARATION OF ORGANIC COMPOUNDS crystallised sodium carbonate are heated under a reflux condenser on the water-bath for five hours with 250 c.c. of alcohol. The anil separates out in dark green granules, which are collected and washed with several litres of boiling water. Yield 86 per cent. (67 grm.). A sample may be purified by recrystallisation from a little acetone. The whole is then shaken for some hours with 250 c.c. of 27 per cent. nitric acid and 250 c.c. of benzene. The very dark-coloured liquid thus obtained is filtered, and then readily separates into two layers. The benzene layer is removed and the benzene distilled off. An oil is left which solidifies on cooling. It is dissolved in alcohol, boiled with animal charcoal, filtered, and water added to the filtrate until a slight cloudiness appears. The whole is then set aside at the ordinary temperature in an evaporating basin, when long yellow needles gradually separate. These contain one molecule of alcohol of crystallisa- tion, which is lost on heating to 90. Dinitrobenzaldehyde melts at 72. Another 6 grm. can be obtained from the aqueous layer by again shaking up with benzene and nitric acid, thus making the total yield 88 per cent. III. REDUCTION OF THE ACIDS. The reduction may be brought about by distilling the barium or calcium salt of the acid with barium or calcium for- mate, but this method is not much used. The phenol carboxylic acids of the benzene series are readily reduced by the action of sodium amalgam and boric acid, and as the yields are good, this often forms a convenient means of obtaining the phenolic aldehydes. PREPARATION OF SALICYLALDEHYDE (C 6 H 4 [i] OH^jCHO). 1 Fifteen grammes of salicylic acid are dissolved in hot water and accurately neutralised with sodium carbonate. The solution is then diluted to I litre, heated to boiling, 1 8 grm. of ^.-toluidine added, and the whole then allowed to cool with continual stirring. Two hundred and fifty grammes of common salt and 15 grm. of boric acid are added, and then gradually and with continual stirring, 340 grm. of 2 per cent, sodium amalgam. During the addition of the amalgam the solution must be kept faintly acid by the addition of more boric acid from time to time (about 120 grm. will be required). The reduction is complete when a filtered sample i B. 41, 4147. ALDEHYDES, KETONES, QUINONES 117 gives no precipitate of salicylic acid on the addition of hydro- chloric acid. The condensation product with the toluidine (C 6 H 4 CH 3 N : CHC 6 H 4 OH) is then removed by nitration, mixed with dilute sulphuric acid, and steam-distilled. The aldehyde passes over and is extracted from the distillate with ether. The ethereal solution is dried with calcium chloride, and the ether distilled off. The residual aldehyde is finally purified by distillation. Colourless pleasant-smelling oil boiling at 196. Yield 7-5 grm. An electrical modification of this method has been described. D.R.P. 196,239. For the electrolytic reduction of oxalic acid to glyoxylic acid, see B. 37, 3188. IV. THE ALDOL CONDENSATION. This conden- sation allows of the building up of the higher aldehydes from the lower members. The condensation takes place between the aldehydic group of one molecule and the a-hydrogen atom of another molecule : 2R.CH 2 .CHO = R.CH 2 .CHOH.HCR.CHO and, hence, is limited to aldehydes containing at least one a-hydrogen atom. The reaction can also take place between two different aldehydes, and in this case only one of them need contain an a-hydrogen atom : R.CH 2 .CHO + R'.CHO = R'.CHOH.HCR.CHO. In both cases the condensation is usually accom- panied by a simultaneous loss of water, the unsaturated aldehyde being the result : CH 3 CHOH.CH 2 .CHO = CH 3 .CH ICH.CHO. The condensation is brought about by a variety of reagents, such as hydrochloric acid, sodium acetate, sodium carbonate, sodium sulphite, and potassium cyanide. This last has the special advantage of not causing the loss of water. PREPARATION OF ALDOL (CH 3 .CHOH.CH 2 .CHO).i One hundred grammes of freshly prepared acetaldehyde are slowly added to 200 c.c. of ice-water, care being taken that the 1 A. 306, 323. n8 PREPARATION OF ORGANIC COMPOUNDS temperature of the mixture does not exceed o. The solution thus obtained is cooled to - 12, and then 100 c.c. of an ice-cold, 2\ per cent, solution of potassium cyanide slowly added. During the addition of the cyanide the whole must be well stirred and care must be taken to keep the temperature below - 8. When all the cyanide has been added the whole is allowed to stand for two hours in a freezing mixture, and then for thirty hours at o. At the end of this time the solution, which should be of a syrupy consistency and pale yellow in colour, is saturated with common salt (to render the aldol less soluble) and then extracted at least four times with ether, the ethereal extracts dried with calcium chloride, and the ether removed by distilla- tion from the water -bath. The crude aldol, which is often red in colour, is then obtained by continuing the distillation in vacua; it passes over at 8o-9O at 20 mm. pressure. In carrying out the distillation it is advisable to insert a flask containing concentrated sulphuric acid between the receiver and the pump in order to absorb aldehyde vapours, which would otherwise prevent a high vacuum being obtained. The yield is 40 to 50 per cent. For the use of potassium carbo- nate as a condensing agent in the above preparation the reader is referred to the original paper. 1 In connection with the aldol condensation, attention may be drawn to the interesting synthesis of sym.- triphenyl benzene by passing dry hydrochloric acid gas into acetophenone. The hydrocarbon is deposited after standing several days in a warm place, and by resaturating the mother-liquors yields of over 50 per cent, are said to be obtained. 2 H 2 jCH Ph C HC C Ph ii'l o OL 1 'V CH / k 1 M. 13, 516. CH PhC CPh CH CH C Ph 2 B. 7, 1123. ALDEHYDES, KETONES, QUINONES 119 V. CONDENSATION WITH ETHYL FORMATE. A condensation, analogous to the formation of aceto- acetic ester, takes place under the influence of sodium ethoxide between ethyl formate and compounds con- taining the group CH 2 CO : CHO I R.CH 2 .CO.R + EtO.CHO - R.CH.CO.R + EtOH. PREPARATION OF ACETYL ACETALDEHYDE (CHgCO.CHg.CHO). 1 Thirty-four grammes of dry, freshly prepared sodium ethylate (for preparation, see p. 33) are sus- pended in dry ether or ligroin, and the whole cooled with ice. A mixture of 29 grm. of well-dried acetone and 37 grm. of ethyl formate are then slowly run in, the whole being well stirred during the process. An immediate precipitation of the white sodium salt of acetyl acetaldehyde : CH 3 .C :CH.CHO ONa takes place. This is collected, washed with ether or ligroin, and dried in a vacuum desiccator. The free aldehyde cannot be isolated as it at once condenses to sym.-tri acetyl benzene : CH 3 .CO CH 3 CO oi CH CH 3 COC!H 2 i CH C.CO.CHg CH CH 3 COC \, CH C.COCH 3 PREPARATION OF CAMPHOR ALDEHYDE (Oxy- methylene Camphor) , 2 C a H 1A c I Twelve and a half 1 D.R.P. 45,367, l \ I \CH.CHO. 2 D.R.P. 49,165. i2o PREPARATION OF ORGANIC COMPOUNDS grammes of sodium wire or powder are added to a solution of 176 grm. of camphor dissolved in toluene. The whole is well cooled with ice, and then 37 grm. of ethyl formate added. After standing in the ice-chest for at least a day the whole is poured into ice-water and well shaken. The aqueous layer is removed, acidified with acetic acid, and then extracted with ether. The ethereal extract is dehydrated with calcium chloride, and the greater part of the ether removed by dis- tillation. The residue is then transferred to a basin, and allowed to evaporate at the ordinary temperature. An oil remains which on standing sets to a solid, crystalline mass melting at 76-? 8. VI. REPLACEMENT OF HYDROGEN BY CHO. In the last section a method was described whereby the hydrogen in certain aliphatic compounds could be replaced by the aldehydic group. In the aromatic series this result can also be brought about in some cases. The oldest and best-known method consists in treating the phenols with chloroform and caustic soda (Reimer's reaction). 1 Phenolic aldehydes are thus formed, the aldehydic group going to the ortho-, and to a less extent to the para-, position with regard to the phenolic group. PREPARATION OF o.- AND .-OXYBENZ ALDEHYDE (C 6 H 4 (OH)CHO). 2 Two hundred grammes of caustic soda are dissolved in 320 c.c. of water and 100 grm. of phenol added. The whole is heated to 5O-6o under a reflux condenser, and then 150 grm. of chloroform slowly dropped in. When all the chloroform has been added, the whole is boiled for an hour and then excess of chloroform removed by distillation. The contents of the flask are made strongly acid with dilute sulphuric acid, and then steam-distilled. The distillate, which consists of salicyl aldehyde and phenol, is extracted with ether, and the ethereal extract well shaken with concentrated sodium bisulphite solution. The bisulphite compound is collected, washed with alcohol, and steam-distilled with dilute sulphuric acid or sodium carbonate. The aldehyde is isolated from the distillate as described on p. 1 1 6. Yield about 20 grm. The .-oxyaldehyde is in the residue from the first steam- i Cf. also p. i6|. 2 B. 9, 824. ALDEHYDES, KETONES, QUINONES 121 distillation. This is filtered hot, and the nitrate, after cooling, extracted with ether. The ether is removed by distillation, when the aldehyde remains as a mass of pale yellow needles. These may be purified by recrystallisation from water, and melt at ii5-ii6. The following methods of inserting the aldehyde group into the benzene nucleus are exceedingly interesting, but are not suitable for laboratory prepara- tions : (i) The benzene compound is treated with mercury fulminate in the presence of anhydrous aluminium chloride containing some hydrated chloride. The reaction takes place as if an addition compound of fulminic and hydrochloric acids were formed : C1 \ / H C 6 H 6 + )C : NOH - C 6 H 5 C/ + HC1. H/ The oxime is then saponified. B. 32, 3492 ; 36, 322. (ii) The phenol or phenolic ether is treated with anhydrous hydrochloric and hydrocyanic acids in the presence of aluminium chloride. The reaction takes place as if an addition compound of the acids were formed : H \ / H C 6 H 5 OH + >C : NH = C 6 H 4 (OH)(X : NH + HC1. CK The imide is finally saponified. The group -C enters the para- position to the hydroxyl. D R.P. 101,333- (iii) The hydrocarbon is treated with carbon monoxide and hydrochloric acid in the presence of cuprous and aluminium chlorides. Here the reaction takes place as if the unknown formyl chloride were first formed. The aldehydic group enters the para- position. Cl C 6 H 6 CH 8 + >CO = C 6 H 4 (CH 3 )CHO + HC1. H/ T22 PREPARATION OF ORGANIC COMPOUNDS Benzene only reacts when hydrobromic acid is used, and can, therefore, be used as a solvent. D.R.P. 126,421. B. THE KETONES I. FROM THE ACIDS. The calcium or, better, the barium salts of the carboxylic acids when sub- mitted to destructive distillation yield ketones. Mixed ketones can also be obtained by this method by distilling an intimate mixture of the salts of two different acids. When preparing the higher members the distillation is best carried out in vacuo. PREPARATION OF ACETONE (CH 3 ) 2 CO. Five hundred grammes of anhydrous barium acetate are placed in a hard glass or, better, a metal retort connected with a condenser, and heated with a free flame as long as any liquid distils. The distillate is shaken for four or five hours with two to three volumes of saturated sodium bisulphite solution. The resulting crystals are collected, dissolved in water, and anhy- drous sodium carbonate added until an alkaline reaction is obtained. The whole is then distilled from the water-bath, the distillate dried with calcium chloride, and redistilled. Colourless mobile liquid with characteristic smell. B.P. 56. II. OXIDATION OF SECONDARY ALCOHOLS. The best oxidising agent for this purpose is chromic acid or potassium bichromate, but chlorine water and nitrous acid both give excellent results in the prepara- tion of camphor from borneol or iso-borneol. The oxidation of polyhydric alcohols to the corre- sponding ketones is best carried out with lead peroxide and sulphuric acid, or Fenton's reagent (H 2 O 2 and FeSO 4 ). The aldose phenylhydrazones when boiled with phenyl hydrazine are oxidised to osazones : CH 2 OH(CHOH) 4 .CH : N.NHPh + 2PhNH.NH 2 = CH 2 OH(CHOH) 3X >C:N.NHPh + PhNH 2 + H 2 O + NH 3 . PhNHN : CHK The osone, CH 2 OH(CHOH) 3 .CO.CHO, can then be ALDEHYDES, KETONES, QUINONES 123 liberated by boiling with acids. Like most sugars, however, they are troublesome to isolate. PREPARATION OF sym.-DICHLORACETONE, (CH 2 Cl) 2 CO.i One hundred grammes of a-dichlorhydrin, (CH 2 C1) 2 CHOH, are mixed with 80 grm. of finely powdered potassium bichromate, and the whole well cooled with ice. A cold mixture of 120 grm. of concentrated sulphuric acid and 150 c.c. of water are then slowly added during about eight hours. The reaction mixture should be worked up at once and not allowed to stand over-night. It is extracted with warm concentrated sodium bisulphite solution, and the bisulphite compound which separates on cooling collected, pressed between filter -paper, and washed with a little ether. It is suspended in a little water, ether added, and then the calculated quantity of sodium carbonate in concentrated aqueous solution slowly added in several portions. The liquid must be well shaken after the addition of each portion, and the ether removed and replaced by fresh ether. The united ethereal extracts are dried over calcium chloride, and the ether distilled off from the water- bath. The residue is allowed to stand in vacua over con- centrated sulphuric acid until crystallisation takes place, and is then pressed between filter-paper, dissolved in ether, and the ether allowed to evaporate at the ordinary tempera- ture. The ketone then separates as transparent tablets which melt at 25. PREPARATION OF BENZIL (C 6 H 5 .CO.CO.C 6 H 6 ).2 Twenty-one grammes of benzoin, C 6 H 5 CO.CHOHC 6 H 5 , are mixed with 36 c.c. of concentrated nitric acid (D = 1-41) and heated on the water-bath for two hours under a reflux condenser. The whole is then poured into water, the preci- pitated benzil filtered off, washed, and finally recrystallised from alcohol. Yellow prisms melting at 95. Yield about 75 pev cent. PREPARATION OF MENTHONE. 3 Sixty grammes of potassium bichromate are dissolved in 300 c.c. of hot water containing 50 grm. of sulphuric acid. The solution is cooled to 30 (at which temperature crystallisation begins) and 45 grm. of finely powdered menthol added all at once. The whole is i A. 208, 353. 2 A. 34, 188. 3 A. 250, 325. 12 4 PREPARATION OF ORGANIC COMPOUNDS violently agitated, and soon becomes dark in colour, and crystals of a chromium-menthol compound separate out. The temperature rises spontaneously and is maintained at 53 by cooling or warming as may be necessary. The double compound gradually decomposes, a precipitate of menthone being deposited. After cooling, the whole is extracted with ether, the ethereal solution washed with dilute caustic soda, and the ether removed by distillation from the water-bath. The residual menthone is steam-distilled in quantities not exceeding 10 grm. at a time, collected, and dried over anhydrous sodium sulphate. It forms a colourless oil boiling at 206. It is laevo-rotatory ([a] D = - 28), and is converted into the dextro- variety by concentrated sulphuric acid. It is in order to avoid this change that less than the calculated quantity of sulphuric acid is used in the oxidation, and that the temperature must not exceed 53. Me. H Me. H / \ CH 2 CH 2 CH 2 CH 2 CHOH CH 2 CO CH 2 \ / \ / CH CH I I CHMe 2 CHMe 2 Menthol Menthone PREPARATION OF CAMPHOR, (a) 1 Fifteen grammes of borneol are dissolved in 16 grm. of benzene and the solution thus obtained shaken with 900 c.c. of water containing 7- 1 grm. of chlorine until the smell of chlorine has disappeared. The benzene layer is then separated and the benzene removed by distillation from the water-bath. Camphor remains behind in almost quantitative yield. (b) 2 Nitrogen trioxide is led over powdered borneol until the whole is liquid and has assumed a greenish blue colour. (This should be done under a reflux condenser, the flask being cooled towards the end of the treatment.) The liquid is then set aside, and after a short time evolves oxides of nitrogen, care being taken that the temperature does not exceed 70. 1 D.R.P. 177,290, 177,291, 179,738. 2 Ibid. 182,300. ALDEHYDES, KETONES, QUINONES 125 When the reaction is over, the whole is poured into water, and the camphor collected by filtration. It can be recrystallised from alcohol. M.P. 175. Yield 95 per cent. CH 2 CH CH 2 CH 2 CH CH 2 CMe 2 CMe 9 CH 2 CMe CHOH CH 2 CMe CO Borneol Camphor Ketonic compounds can sometimes be obtained from polyhydroxy-compounds by loss of water. The reac- tion is usually carried out by heating the hydroxyl compound with acid potassium sulphate. PREPARATION OF PYRUVIC ACID (CH 3 CO.COOH).i Two hundred grammes of finely powdered acid potassium sulphate and 100 grm. of tartaric acid are intimately mixed by grinding them together. The mixture is then placed in a large flask and distilled from an oil -bath at 220 (no higher). Con- siderable frothing takes place and some care is required to prevent boiling over, and for this reason the apparatus should be arranged so that the flask can be instantly raised clear of the oil-bath. The distillation is continued until nothing more passes over, and the distillate then fractionated under reduced pressure. The pyruvic acid passes over at 68-7O at 20 mm. and forms a colourless liquid boiling at 165. The yield is about 50 per cent. JHolCHJCOO^H CH 2 :COH.COOH 1C . OH . COOH Enolic form or CH 3 .CO.COOH Ketonic form CH 2 OH(CHOH) 3 \ PREPARATION OF d.-GLUCOSAZONE,2 PhNHN : C PhNHN : CH 1 A. 242, 268. 2 B. 17, 579. 126 PREPARATION OF ORGANIC COMPOUNDS Ten grammes of glucose, fructose, or mannose, or a corre- sponding amount of the phenylhydrazones of these sugars, are mixed with 20 grm. of phenyl hydrazine, dissolved in 20 grm. of 50 per cent, acetic acid and 200 c.c. of water, and the whole heated on the water-bath for i to 2 hours. The d.-glucosa- zone separates out in yellow needles and is collected and washed. Yield about 9 grm. It may be recrystallised from dilute alcohol, and melts at 205. One molecule of the phenyl hydrazine is reduced to aniline, which may be recognised in the filtrate by the bleaching-powder reaction. See p. 122. III. OXIDATION OF CH 2 TO CO. This reaction, as a rule, can only take place when the CH 2 group is attached to two aromatic residues. The oxidation is best carried out with chromic acid. For indirect method via the zsonitroso compounds, see p. 130. / C \ PREPARATION OF FLUORENONEi (C 6 H 4 C 6 H 4 ). Ten grammes of fluorene, 30 grm. of coarsely ground sodium bichromate, and 40 grm. of glacial acetic acid are boiled under a reflux condenser for two to three hours. The whole is then poured into water, and the precipitated fluorenone collected and washed. It is finally recrystallised from rather dilute alcohol. It forms long yellow needles melting at 83. / C \ PREPARATION OF ANTHRAQUINONE (C 6 H 4 < >C 6 H 4 ) . \XK Ten grammes of anthracene are dissolved in 120 c.c. of glacial acetic acid by boiling under a reflux condenser. A solution obtained by dissolving 20 grm. of chromic acid in 15 c.c. of water and then diluting with 75 c.c. of glacial acetic acid is slowly added from a tap-funnel during an hour, the liquid in the flask being kept boiling. When all the chromic acid has been added, the boiling is continued for ten minutes and the deep green solution, after cooling, poured into half a litre of water. The precipitated anthraquinone is collected, well washed, first with hot water, then with warm dilute caustic soda, and finally again with water. It is then dried in the steam-oven. Yield about 10 grm. It is best purified by i A. 279, 258. ALDEHYDES, KETONES, QUINONES 127 sublimation at 250. Yellow needles. M.P. 277. If crude anthracene is used, the crude anthraquinone should be purified by heating to 110 for ten minutes with 3 parts of 5 per cent. oleum in a basin. The whole is then allowed to stand in a damp place for twenty-four to forty-eight hours, poured into water, filtered, washed with boiling dilute caustic soda, and then with water, dried, and finally sublimed. IV. CONDENSATION OF ACID CHLORIDES WITH BENZENE DERIVATIVES. This condensation forms a standard method for preparing aromatic ketones and takes place under the influence of anhydrous aluminium or ferric chlorides. The reaction usually occurs without the application of heat and is carried out with or without a solvent. In the former case carbon bisulphide, ligroin, ether, or nitrobenzene may be used. Further discussion will be found on pp. 42, 162. PREPARATION OF ACETOPHENONE (C 6 H 5 CO . CH,) .1 Thirty grammes of benzene are poured on to 50 grm. of pow- dered aluminium chloride contained in a flask provided with a reflux condenser. Thirty-five grammes of acetyl chloride are then slowly added from a tap -funnel, the flask being cooled with ice. The whole is then set aside for an hour, poured on to ice, and extracted with a small quantity of benzene. The benzene layer is washed, first with dilute caustic soda and then with water. It is dehydrated with calcium chloride and dis- tilled. The fraction boiling at i9O-2io is collected and redistilled. The acetophenone then passes over as a sweet- smelling oil boiling at 202, and on standing solidifies to a crystalline mass melting at 20. Yield about 50 per cent. PREPARATION OF ACET-SALICYLIC ACID (C 6 H 3 [i]OH[2]COOH[4]COCH 3 ).2 Eighty grammes of sali- cylic acid are mixed with 100 grm. of acetyl chloride, and 100 grm. of sublimed ferric chloride added little by little. A brisk reaction takes place and the O. -acetyl derivative, "aspirin," C 6 H 4 (OCOCH 3 ) (COOH), is first formed. Further addition of ferric chloride causes the mass to become liquid again and to assume a dark brown colour. When the evolution of hydrochloric acid slackens the whole is cautiously warmed i A. Ch. [6] I, 507 ; 14, 455. 2 B. 30, 1776. 128 PREPARATION OF ORGANIC COMPOUNDS over a free flame, the flask being continuously shaken, to iio, but care must be taken not to exceed this temperature. The heating is continued for a quarter of an hour after all the ferric chloride has been added, and the melt then poured into a basin and allowed to cool. It is washed three times with cold water, the residue dissolved in boiling water and filtered hot. Hydrochloric acid is added to the hot filtrate until the deep red colour disappears. The acet-salicylic acid separates out on cooling in yellow needles, which after standing for twenty-four hours are collected, washed, and recrystallised from alcohol. If still coloured it should be boiled with a little water to which a crystal of potassium permanganate has been added. M.P. 210. Yield about 25 per cent. PREPARATION OF . 2 -DIMETHYL BENZOPHENONE (CH 3 [4]C 6 H 4 [i]CO[i / ]C 6 H4[4 / ]CH 3 ).i A litre flask is provided with a double-bored cork carrying a wide glass tube, or, better, a wide-stemmed ordinary conical funnel closed with a well- fitting cork, and a reflux condenser provided with an absorp- tion apparatus as in Fig. 47, p. 51. The absorption liquid consists of toluene, and should be cooled with ice or a freezing mixture. Two hundred grammes of a technical 20 per cent. toluene solution of carbonyl chloride are placed in the flask, and 100 grm. of powdered aluminium chloride slowly added through the wide glass tube or funnel. The addition requires about four hours, and the funnel should be closed after each portion has been added, in order that the carbonyl chloride driven off by the reaction may be collected in the toluene. During the addition the flask should be cooled in a water-bath. When all the aluminium chloride has been added, the flask is warmed very gently for a short time, and the contents then slowly poured into water and distilled in steam until nothing more passes over. The aqueous part of the residue is then poured off as far as possible and discarded, very dilute hydro- chloric acid added to the solid matter, and the whole distilled in steam for half an hour. The aqueous portion is again discarded, the solid matter well washed, and then either fractionally distilled or recrystallised several times from dilute alcohol. The ketone forms colourless needles melting at 94-95 and boiling at 333. The yield is 50 to 80 per cent. i A. 312, 92 ; B. 7, 1183 ; IO, 2173 ; J. pr. [2] 35, 466. ALDEHYDES, KETONES, QUINONES 129 V. CONDENSATION OF PHTHALIC ANHYDRIDE WITH BENZENE, ETC. Phthalic anhydride condenses readily with benzene and its derivatives to form benzoyl benzoic acids : /CO X A1C1 3 C 6 H 4 Nxx C 6 H 5 CO.C 6 H 4 COOH and these readily lose water to form the corresponding anthraquinone : /\/ C \ \ -co \/\ COjOHj /\/" W \/\ \/\CO/\/ H0. This method may become of considerable technical importance, as phthalic anhydride can be obtained cheaply from naphthalene, and anthraquinone is in increasing demand for the preparation of the new vat- dyes, such as indanthrene. PREPARATION OF o.-BENZOYL BENZOIC ACID (C 6 H 5 CO[i]C 6 H 4 [2]COOH).i Fifty grammes of finely pow- dered phthalic anhydride are added to 175 grm. of dry benzene, and 90 grm. of powdered aluminium chloride then added all at once. The whole is gradually warmed on the water- bath in a flask fitted with a reflux condenser and mechanical stirrer. The reaction starts at 30, and is prevented from becoming too violent by regulating the temperature of the water-bath. When the mass has become too viscous for the stirrer to revolve, the temperature is gradually raised to 70 and maintained at this point until no more hydrochloric acid is evolved. The condenser is then inverted and cold water slowly added. Considerable heat is evolved and the greater part of the unchanged benzene distils off. The rest is removed with steam, and the residue boiled for several hours with excess of sodium carbonate. The alumina is then filtered off and well washed with boiling water. On treating the cooled nitrate with hydrochloric acid, benzoyl benzoic acid is precipitated in almost 1 A. 291, 9 ; C, r. 119, 139. 130 PREPARATION OF ORGANIC COMPOUNDS quantitative yield. It may be recrystallised from xylol or water. From the latter solvent it separates in long needles containing one molecule of water, wh,ich it loses at 1 10. The hydrated acid melts at 94, the anhydrous acid at 127. PREPARATION OF ANT H R A Q UI NO N E, 1 / C \ C 6 H 4 <' /C 6 H 4 . Twenty grammes of o.-benzoyl benzoic XXX acid are mixed with 120 grm. of concentrated sulphuric acid and heated on the oil-bath to 150 for one hour. After cooling, the whole is poured on to ice and the precipitated anthraquinone collected and purified as described on p. 126. The yield is quantitative. VI. FROM THE iso-NITROSO-COMPOUNDS. This forms a useful method for obtaining a-diketones. The ^'so-nitroso-compounds are obtained from the mono- ketones containing the group CH 2 CO as de- scribed on p. 198. /CO PREPARATION OF CAMPHORQUINONE, 2 C 8 H 14 / | \CO Nine grammes of z'so-nitroso camphor are dissolved in 15 c.c. of glacial acetic acid and a solution of 4 grm. of sodium nitrite in 8 c.c. of water very slowly added, the whole being violently stirred or shaken. The solution at first becomes brown and then greenish in colour, and nitrous oxide is evolved, but there should be no smell of nitrous acid. Heat is evolved, and much rise in temperature must be prevented at the begin- ning of the preparation by cooling from time to time in water. Towards the end of the operation the evolution of gas slackens, and the reaction must then be assisted by heating over a naked flame. When no more gas is evolved, the contents of the flask are allowed to cool and then poured into excess of cold water. The quinone is precipitated as a crystalline mass which, after washing and drying, can be purified by sublimation at 60. It forms golden-yellow sweet-smelling needles which melt at 198. Yield 50 per cent. /C : NOH /CO C e H 14 < | + HNOo = C 8 H 14 < | + N 2 + H 2 O. X CO X CO 1 Z. a. Ch. 19, 669. 2 A. 274, 71. ALDEHYDES, KETONES, QUINONES 131 VII. FROM AROMATIC ALDEHYDES. Aromatic aldehydes, in which the aldehydic group is directly attached to the ring, undergo a peculiar condensation when heated with alcoholic solutions of potassium cyanide. The action of the cyanide is catalytic, a small quantity being able to convert a large quantity of the aldehyde into the corresponding benzoin. The course of the reaction is probably the alternate forma- tion and decomposition of a cyanhydrin : X OH Ph.CHO + HCN - PhC^-H \CN /OH *O /OH /OH PhC-H + Phcf = PhC^ - C-Ph X H \CN X OH /OH ^ - C^Ph = PhCO.CHOH.Ph + HCN \CN X H It will be seen that the resulting benzoin is a hydroxy- ketone. The benzoin condensation has not been observed in the aliphatic series, but is general for aromatic aldehydes, and is also undergone by some heterocyclic aldehydes, such as furfurol. PREPARATION OF BENZOIN (C 6 H 5 CO . CHOHC 6 H 5 ) .1 Fifty grammes of benzaldehyde are dissolved in 100 c.c. of alcohol, and about 10 grin, of potassium cyanide in twice its weight of water added. The whole is then refluxed on the water-bath for an hour. On cooling, the benzoin crystallises out and is filtered off and washed with a little alcohol. Thus obtained it is quite pure enough for the preparation of benzil (p. 123), but if desired it can be recrystallised from dilute alcohol. It forms colourless prisms melting at 137. VIII. CLAISEN'S REACTION. Claisen's reaction consists in the splitting out of a molecule of alcohol from an ester and a second component which may be 1 A. 34, 186 ; 198, 151. 132 PREPARATION OF ORGANIC COMPOUNDS (a) another molecule of the same ester, (b) a different ester, (c) a ketone. RCOOEt + R.CH 2 .COOEt = RCO.CHRCOOEt RCOOEt + HCR 2 COCR 3 =RCO.CR 2 .COCR 3 where R may be hydrogen, or an alkyl or aryl group. It is only the a-hydrogen atom of the second com- ponent, i.e. the hydrogen atom on the carbon next to the carboxylic or ketonic group, that reacts, and hence, in case (a) only those esters which contain such an hydrogen atom undergo the condensation. The reaction always gives rise to /3-diketonic compounds and is the general case of the formic ester condensation mentioned on p. 119. The condensation is brought about by metallic sodium, sodium ethylate, or soda- mide. The latter reagent, which is of fairly recent application, often gives excellent results. PREPARATION OF ACETO ACETIC ESTER (CH 3 CO.CH 2 . COOEt). 1 Two hundred and fifty grammes of ethyl acetate, which have been dehydrated over calcium chloride, are placed in a flask fitted with a reflux condenser, and 25 grm. of sodium, either in, thin slices or, better, as wire, added . When the vigorous reaction which at first sets in has slackened, the whole is boiled until all the sodium has vanished. The warm liquid is then acidified with 50 per cent, acetic acid (about 160 c.c. will be required) and shaken with 400 c.c. of saturated salt solution. After standing a few minutes the liquid separates into two layers, the upper one of which is collected, and frac- tionated in vacua until a fraction boiling constantly at 71 at 13 mm. pressure is obtained. Colourless liquid with pleasant smell boiling at 181 at atmospheric pressure. Yield about 35 per cent. Propiopropionic ester is obtained in the same way, but the higher esters do not undergo the condensation. Succinic ester behaves like acetic ester, but being dibasic gives a cyclic compound. PREPARATION OF SUCCINOSUCCINIC ESTER." Ten grammes of granulated sodium (p. 33) are added to 38 grm. 1 A. 186, 161, 214. 2 A. 211, 308 ; 229, 45. ALDEHYDES, KETONES, QUINONES 133 of ethyl succinate containing two or three drops of absolute alcohol, and the whole set aside for ten days . The dry mass is then broken up, and made faintly acid with dilute hydrochloric acid. The insoluble portion is collected and recrystallised from alcohol. M.P. 126. Yield excellent. COOEt COOEt CHJH EtOJ CH CH 9 CO CH 9 CO CO CH 2 CO CH 2 \ / \ / lOEtl / CH HiCH ' ! ' | COOEt COOEt 2 molecules succinic ester Succinosuccinic ester PREPARATION OF ACETYL ACETONE (CH 3 CO. CH 2 COCH 3 ).i Ethyl acetate (120 c.c.) is dissolved in 32 c.c. of pure dry acetone, and the whole cooled in a freezing mixture. Thirty-five grammes of finely powdered sodamide are then slowly added. The reaction sets in at once and ammonia is evolved. When all the sodamide has been added the whole is allowed to stand some time at o and then over-night at the ordinary temperature. Ice-water is then added and the aqueous layer removed. This, on acidifying with acetic acid and subsequent addition to concentrated copper acetate solution, gives a deep blue precipitate of the copper salt, ( (CH 3 CO) 2 CH) 2 Cu. Yield 25 grm. The free diketone can be obtained from this by shaking it with chloroform and dilute sulphuric acid. The chloroform layer is dried, and after the chloroform has been removed on the water-bath, the diketone passes over at i35-i42. PREPARATION OF ACETYL ACETOPHENONE (CH 8 CO. CH 2 COC 6 H 6 ). 2 Twenty-four grammes of acetophenone and 19 grm. of ethyl acetate are dissolved in 150 c.c. of absolute i B. 38, 695 ; D.R.P. 49,542. 2 Loc. cit. 134 PREPARATION OF ORGANIC COMPOUNDS ether, and 16 grm. of powdered sodamide slowly added. After a few hours the whole sets to an almost solid mass of the sodium salt. It is set aside for a day and then poured on to sufficient ice-water to dissolve the whole of the precipitate. The aqueous layer is separated, and freed from dissolved ether by blowing a current of air through it. On acidifying, the acetyl benzo- phenone is precipitated in 77 per cent, yield. M.P. 6o-6i. Higher members may be built up from acetoacetic ester, &c., by condensing with alkyl or acyl halides : CH 3 CO.CH COOEt ; CH 3 CO . CH COOEt. CO.R These compounds can then condense with another halogen compound giving, for example, CH 3 COCR 2 COOEt. All these substances on boiling with dilute caustic potash undergo the " ketonic hydrolysis," forming alcohol, carbon dioxide, and a ketone : CH 3 CO.CR 2 COOEt + H 2 =* CH 3 COCHR 2 + EtOH + C0 2 . The " acid hydrolysis " with concentrated potash will be found discussed on p. 170. In the same way ketonic acids can be obtained by condensing malonic ester with one or two molecules of an acid chloride and then hydrolysing the product : R.CO.CH(COOEt) 2 +H 2 O = R.CO.CH 2 .COOH + EtOH + CO 2 . PREPARATION OF MONO- AND DI-ETHYL ACETO- ACETIC ESTER. 1 Twenty-three grammes of sodium are slowly added to 300 c.c. of absolute alcohol contained in a flask fitted with a reflux condenser. When all the sodium has dissolved, the solution is cooled with ice, and 130 grm. of acetoacetic ester added. One hundred and seventy grammes i A. 186, 188. ALDEHYDES, KETONES, QUINONES 135 of ethyl iodide are then slowly dropped in. When all the iodide has been added, the whole is heated until neutral to moist litmus paper. To bring this about it may be necessary to add a little more ethyl iodide. When neutral, the solution, which now contains monoethyl acetoacetic ester, is divided into two equal parts. From one part the alcohol is removed by distillation on the water-bath, the residue shaken with water until all the solid matter is dissolved, and then extracted with ether. The ethereal solution is dehydrated with anhydrous sodium sulphate, and the ether distilled off from the water- bath. The residue is then fractionated in vacua. B.P. 82-84 at 14 mm., 198 at 760 mm. Yield 60 to 80 per cent. The second part is converted into the diethyl compound by adding a solution of nj grm. of sodium in 150 c.c. alcohol, and then slowly, as before, 85 grm. of ethyl iodide. The whole is boiled until neutral and the diethyl compound isolated in exactly the same way as the monoethyl derivative. B.P. 94-95 at 1 6 mm., 204 at 760 mm. Yield 50 to 60 per cent. PREPARATION OF BENZOYL ACETOACETIC ESTER,* COC 6 H 5 Sodium (35-4 grm.) is slowly added to CHgCO.CH.COOEt. 600 c.c. of absolute alcohol under a reflux condenser. When all the sodium has dissolved, the liquid is cooled and 300 c.c. of it drawn off. To this is added 100 grm. of acetoacetic ester. Ninety cubic centimetres of benzoyl chloride are placed in a burette, and with continual stirring 45 c.c. allowed to run slowly into the mixture of acetoacetic ester and sodium ethylate. The addition should take fifteen minutes and the temperature must be kept below 10. The whole is allowed to stand for half an hour, and then 1 50 c.c. of the ethylate solu- tion and 22-5 c.c. of benzoyl chloride added exactly as before. This treatment is repeated, always halving the amount of ethylate and benzoyl chloride, until all the ethylate solution and chloride have been used. After twelve hours the sodium salt is filtered off and washed with ether. By treating it with ice-water and dilute acetic acid the free ketone can be obtained. It is extracted with ether, dehydrated with anhydrous sodium sulphate, and the ether removed by distillation from the water - 1 A. 226, 220 ; 291, 71. 136 PREPARATION OF ORGANIC COMPOUNDS bath. The residue is then fractionated under as high a vacuum as possible. At 12 mm. it passes over at 175 with only very slight decomposition. It forms a thick liquid. The monoalkyl acetoacetic esters prepared as above are often contaminated with the dialkyl compounds. This is due to double decomposition taking place between the unchanged sodium salt and the mono- alkyl ester : CH 3 COCHNaCOOEt + CH 3 CO.CHR.COOEt = CH 3 COCH 2 COOEt + CH 3 COCNaRCOOEt. This can be remedied to a large extent by using only half the calculated quantity of sodium and alkyl halide. Of course under these conditions half the acetoacetic ester remains unchanged, but this is readily recovered by distillation. PREPARATION OF BENZYL ACETOACETIC ESTER (CHjjCOCHBzCOOEt). 1 A solution of 5-75 grm. of sodium in 75 c.c. of alcohol is added to 65 grm. of acetoacetic ester. Benzyl chloride (31-8 grm.) is then added, and the whole, after standing for an hour at 30, boiled under a reflux condenser for an hour. The product is then fractionated in vacuo. The benzyl acetoacetic ester passes over at i64-i65 at 14 mm. The yield is about 89 per cent., allowing for the acetoacetic ester recovered. PREPARATION OF METHYL zso-AMYL KETONE (CH 3 .CO.CH(C 2 H 5 ) 2 ).2 Diethyl acetoacetic ester is boiled under a reflux condenser with saturated baryta water, or alcoholic potash. The product is carefully washed with saturated salt solution until free from alcohol, dried with calcium chloride, and distilled. The ketone forms a colourless mobile liquid boiling at 137-! 39. Methyl Propyl Ketone 3 can be prepared in exactly the same way from monoethyl acetoacetic ester. It is best purified by means of the bisulphite compound. It boils at 101. 1 B. 44, 1507. 2 A. 138, 211. 3 Loc. cit. ALDEHYDES, KETONES, QUINONES 137 C. THE QUINONES AND QUINONE-IMIDES The quinones can be roughly divided into three classes, viz. (a) ortho-quinones, (b) ^am-quinones, (c) quinones in which the quinonoid groups are on different nuclei, e.g. : O V II O Pyrenequinone These last are of but little interest and will not be further considered. The quinone-imides are quinones in which either or both of the quinonoid oxygen atoms have been replaced by the imino-group, =NH. The quinone-imides themselves are usually unstable and difficult to isolate, but their chlorides, which contain =N.C1 in place of =NH, are often easily obtained. The quinones and quinone-imides are invariably obtained by oxidation, and a large variety of sub- stances serve as starting-out points for their prepara- tion. (a) HYDROCARBONS. This method is only appli- cable to polynuclear quinones. The preparation of anthraquinone is the best-known example and was discussed on p. 126. a-Naphthoquinone can also be prepared by this method, but the procedure described on p. 140 gives better yields. 38 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF a-NAPHTHOQUINONE. 1 Ten grammes of chromic acid are dissolved in 65 c.c. of ice-cold So per cent. acetic acid. A solution of 10 grm. of naphthalene in 95 c.c. of glacial acetic acid is then slowly added, and the whole allowed to stand for three days at the ordinary temperature with occasional shaking. At the end of this time the liquid is poured into 850 c.c. of water, and the precipitated quinone filtered off. It is almost pure, but may be purified by subli- mation or by recrystallisation from alcohol. It forms golden- yellow plates which melt at 125. It possesses a biting odour and, like all true quinones, is very volatile with steam. Yield about 40 per cent. (b) PRIMARY AMINES. The oxidation of the primary amines with sodium or potassium bichromate is the standard method of preparing the quinones of the benzene series. The method is also applicable to a-naphthylamines, but does not give satisfactory yields. Sulphonic acid groups if present in the ^im- position are split out. Thus sulphanilic acid on oxida- tion gives />.-benzoquinone. PREPARATION OF BENZOQUINONE (O : C 6 H 4 : O) . 2 One hundred grammes of aniline are dissolved in 2 litres of water containing 800 grm. of concentrated sulphuric acid. One kilogramme of ice is added, and when the temperature has fallen below o, a cold saturated solution of 300 grm. of sodium dichromate is slowly run in. During this addition, which requires about five hours, the whole must be continually stirred, and the temperature must be kept below 5. When all the dichromate has been added the whole is allowed to stand quietly for an hour, at the end of which time the quinone will have risen to the surface. It is skimmed off, filtered, washed with a little cold water, and dried between filter-paper. It must not be dried in the oven or in a vacuum desiccator. It is then purified by recrystallisation from ligroin in a Soxhlet apparatus. It forms long yellow needles which have a biting odour, are very volatile, and melt at 116. Yield 60 per cent. By extracting the dark-coloured liquid with ether a further quantity can be obtained, bringing the yield up to 85 per cent. i Soc. 37, 634; A. 167, 357. 2 B. 20, 2283. ALDEHYDES, KETONES, QUINONES 139 As a rule, ^.-diamines are more readily oxidised to quinones than are the monamines. Thus i.4-naphthylene diamine on treatment with hydrochloric acid and sodium nitrite at a low tempera- ture is oxidised to a-naphthoquinone, no trace of diazo- compound being formed. In carrying out the pre- paration, it is merely necessary to filter off the quinone and then recrystallise it. The ^.-diamines are readily obtained by reducing the corresponding azo-colours. See p. 214. PREPARATION OF CHLORANIL (O :C 6 C1 4 : 0).i Twenty-four grammes of 2.6-dichlor-4-nitraniline are reduced to the corresponding diamine by boiling with 600 c.c. of concentrated hydrochloric acid and 26 grm. of tin. Without cooling, 20 grm. of crystallised potassium chlorate are slowly added, the whole being kept gently boiling. The boiling is con- tinued for a few minutes after the whole of the chlorate has been added, and the liquid then diluted and filtered. The precipitate is well washed with water, dried, and then purified either by recrystallisation from toluene or by sublimation. Yellow leaflets which sublime on heating. Yield 90 per cent. The potassium chlorate acts simultaneously as an oxidising and chlorinating agent : Cll NH 2 /\ Cl t cil + KC1+H 2 O+2NH 4 C1. Cl NH 2 || O Chloranil AMINO-PHENOLS. The o.- and ^.-amino-naphthols and the ^.-amino-phenols are very readily oxidised to the corresponding quinones, and as the amino- phenols are readily obtained from the phenols either by reducing the nitroso - compounds or by first forming an azo- colour and then reducing i B. 36, 4390. 1 40 PREPARATION OF ORGANIC COMPOUNDS this (p. 214), their oxidation forms one of the easiest methods of preparing quinones. The oxidation is usually brought about by nitrous or nitric acid, but bichromate, lead peroxide, &c., may also be used. PREPARATION OF a-NAPHTHOQUINONE (1.4).! Fifty grammes of amino-naphthol or a corresponding amount of one of its salts (obtained by the reduction of Orange I, p. 216) are suspended in 200 c.c. of 10 per cent, hydrochloric acid, and 40 grm. of sodium nitrite slowly added. The resulting yellow precipitate is collected, and purified either by steam distillation, sublimation, or by recrystallisation from ligroin or alcohol. Yellow plates melting at 125. Yield about 70 per cent. A further quantity can be obtained by extracting the mother-liquors with ether. PREPARATION OF /3-NAPHTHOQUINONE (1-2) . 2 Thirty grammes of a-amido-/3-naphthol (obtained by the reduction of Orange II Mandarin, pp. 216, 250) are suspended in 120 c.c. of water containing 30 c.c. of concentrated sulphuric acid. The whole is cooled to o by the addition of ice, and then 15 grm. of potassium or sodium bichromate dissolved in 200 c.c. of water slowly added. The mixture must be well stirred, and any rise in temperature prevented by adding more ice from time to time. The quinone separates in the pure state and only requires to be carefully washed. Red needles melting with decomposition at 115-! 20. PREPARATION OF /3-NAPHTHOQUINONE-4-SULPHONIC ACID. Twenty grammes of a-amino-/3-naphthol-4-sulphonic acid are ground up with 30 c.c. of 23 per cent, nitric acid. When the reaction is over, hot water is added until solution takes place. Some insoluble impurities are removed by nitration, and the resulting filtrate then treated with potas- sium chloride until no more precipitation takes place. The potassium salt of the quinone sulphonic acid is then filtered off, washed with cold water, and recrystallised from alcohol. Yield 84 per cent. PREPARATION OF .-BENZOQUINONE-CHLORIMIDE (Cl : N . C 6 H 4 : 0) ? Forty-five grammes of sodium hydroxide 1 A. 183, 242. 2 A. 189,153; 194, 202 ; 211,49; B. 25, 982. 3 B. 37, 1498- ALDEHYDES, KETONES, QUINONES 141 are dissolved in 250 c.c. of water, and chlorine passed into the solution until 35 grm. of the gas have been taken up. The solution is then diluted with ice and water to 500 c.c., and a solution of 43 grm. of .-amino-phenol in 500 c.c. water and 100 c.c. concentrated hydrochloric acid run in slowly. The chlorimide separates in yellow flocks, which after washing and drying are recrystallised from petroleum ether. M.P. 85. PREPARATION OF .-BENZOQUINONE - DICHLORI- MIDE (ClN:C 6 H 4 :NCl).i Ninety grammes of caustic soda are dissolved in 500 c.c. of water, and chlorine passed into the cold solution until it has gained 75 grm. in weight. It is then diluted to 1500 c.c. with ice and water. A solution of 54 grm. of ^.-phenylenediamine hydrochloride in 600 c.c. of water and 120 c.c. of concentrated hydrochloric acid is then slowly run into the cold solution thus obtained. A blue coloration at first appears, but this soon vanishes, and snow- white flocks of the dichlorimide are precipitated. These are collected, washed until the filtrates show no chlorine reaction, and finally either recrystallised from 70 per cent, alcohol, or extracted in a Soxhlet apparatus with petroleum ether of low boiling-point (ligroin, boiling at 120, should not be used). Colourless needles which explode at 126. (Take care !) PREPARATION OF AMINO-NAPHTHOQUINONEIMIDE SULPHONIC ACID. 2 i - Naphthol - 2.4 - diamino - 7 - sulphonic acid hydrochloride (by the reduction of Naphthol Yellow S, p. 213) is either warmed with excess of ferric chloride dissolved in dilute hydrochloric acid, or it is dissolved in ammonia and a rapid current of air then blown through the cold solution. In either case the quinoneimide separates in brick-red needles which only require to be collected and washed with water. The yield by both methods is about 65 per cent. The formula of the substance is : O O I! II S0 8 H/\/\ _ NH S0 3 H/\/\ NH 2 or \/X ' NH 2 1 Loc. cit. 142 PREPARATION OF ORGANIC COMPOUNDS A similar compound is obtained by oxidising the reduction compound of Martins' Yellow: 1 OH OH NH, I-I N0 2 Martius' Yellow O O or NH 2 Amino -naphthoquinoneimide NH DIHYDRIC PHENOLS. The o.-dihydric phenols of the benzene series serve for the preparation of the o.-benzoquinones. 2 The oxidation is brought about by anhydrous silver oxide in absolute ether. The o.-benzoquinones are, however, exceedingly difficult to prepare, and for the success of the experiment every trace of moisture must be excluded. The ^>.-dihydric phenols are very readily oxidised to the corresponding quinones (FeCl 3 , K 2 Cr 2 O 7 , PbO 2 , &c.), the quinhydrones (see p. 103) being formed as intermediate products : OH / OH Hydroquinone /\ OH O /\ OH Quinhydrone o Quinone 1 A. 134, 377. 2 B. 20, 1776 ; 37, 4744. ALDEHYDES, KETONES, QU1NONES 143 The method, however, is not much employed, as the hydroquinones are usually made by the reduction of the quinones. SOME DERIVATIVES OF THE ALDEHYDES AND KETONES The >CO group in the aldehydes and ketones is very reactive and readily gives rise to condensation products, and some of these are of the greatest impor- tance for isolating, purifying, and identifying the aldehydes and ketones. The condensation products with ammonia and primary aromatic amines have already been dealt with on p. 108 (see also p. 233). The very important addition products with sodium bisulphite have been discussed under benzaldehyde (p. ii3),salicyl aldehyde (p. 120), acetone (p. 122), and dichloracetone (p. 123). OXIMES. The oximes are formed by the loss of a molecule of water between one molecule of hydroxyl- amine and one molecule of the ketone or aldehyde : / R /R R C + H 2 NOH = R C : N.OH + H 2 O. ^O The hydroxylamine is applied in the form of one of its salts (usually the hydrochloride) , which may or may not be first neutralised by the addition of one molecule of a basic substance such as caustic soda, sodium acetate, sodium ethylate, or barium carbonate. This last is said to be especially valuable. Aniline is also sometimes used, e.g. in the preparation of the oxime of acetoacetic ester. 1 Alcohol is almost invari- ably used as a solvent. The aldoximes, as a rule, are formed at the ordinary temperature, whereas the formation of ketoximes usually requires the application of heat, prolonged heating under pressure often being necessary. As a class the oximes suffer from the i B. 28, 2731. 144 PREPARATION OF ORGANIC COMPOUNDS disadvantage of being liquids or solids of low melting- point which are difficult to purify. PREPARATION OF BENZOPHENONE OXIME.* Thirteen grammes of benzophenone and 3 grm. of hydroxylamine hydrochloride are heated on the water-bath under a reflux condenser for one day with 15 c.c. of 90 per cent, alcohol, to which a trace of hydrochloric acid has been added. The alcohol is then removed by evaporation and the residue recrystallised from very dilute alcohol. Fine silky needles melting at 140. The monoximes of the a-diketones are identical with the fc'so-nitroso-compounds, and are dealt with on p. 198. The quinone monoximes are identical with the nitroso-phenols, and are discussed on p. 195. THE SEMICARBAZONES. The semicarbazones are formed by the loss of water between the aldehyde or ketone and semicarbazide : R 2 CO -f H 2 N.NH.CONH 2 = R 2 C:N.NH.CO.NH 2 +H 2 0. They show great powers of crystallisation, and are very suitable for identification purposes. For their pre- paration semicarbazide hydrochloride is dissolved in a little cold water and then neutralised (Congo paper) with alcoholic potassium acetate. The ketone is then added, and the whole diluted with alcohol and water until complete solution takes place. The reaction, which takes place at the ordinary temperature, requires from a few minutes to several days, and is complete when a sample poured into water gives a hard crys- talline precipitate. Another method consists in dis- solving i part of semicarbazide hydrochloride in 3 parts of water and then adding i part of potassium acetate. Rather less than the calculated quantity of the ketone is then added, and the whole shaken mechanically. The semicarbazone usually begins to 1 B. 19, 989. ALDEHYDES, KETONES, QUINONES 145 separate almost at once, but should this not be the case its formation may be accelerated by the addition of a little acetone free from methyl alcohol. The semi- carbazones are best purified by recrystallisation from pure acetone. PREPARATION OF ^.-CAMPHOR SEMICARBAZONE.i Twelve grammes of semicarbazide hydrochloride and 15 grm. of sodium acetate are dissolved in 20 c.c. of water, and 15 grm. of camphor in 20 c.c. of glacial acetic acid added. The whole is gently warmed and warm glacial acetic acid added until a clear solution is obtained. On cooling, part of the semi- carbazone crystallises out and the rest is obtained by precipi- tating with water. After washing, the whole is recrystallised from alcohol or benzene. Colourless needles melting at 236- 238. The thio-semicarbazones, R 2 C :N.NH.CS.NH 2 , are obtained in much the same way as the semicarbazones. They have the advantage of forming insoluble salts with certain heavy metals, especially with silver : R 2 C:N.NH.C:NH I S.Ag THE AMINOGUANIDINE DERIVATIVES. Amino- guanidine combines with aldehydes and ketones with loss of water : /NHNH 2 /NHN:CR 2 R 2 CO +HN : C< = HN : C<( + H 2 O. X NH 2 X NH 2 The resulting compounds form very well crystalline picrates. The condensation takes place in the presence of mineral acid. In the aliphatic and terpene series aminoguanidine hydrochloride is dissolved in water containing a little hydrochloric acid. The ketone is added, and then alcohol until a clear solution is obtained. The whole is boiled for a short time under a reflux i B. 28, 2192, 10 146 PREPARATION OF ORGANIC COMPOUNDS condenser, poured into water, and made alkaline with caustic soda. The solution is then extracted with ether, the ether removed by distillation, and the residue suspended in hot water and treated with aqueous picric acid solution. The picrate is precipitated and is recrystallised from strong or dilute spirit according to circumstances. With aromatic aldehydes, aminoguanidine nitrate is dissolved in water and then shaken up with the aldehyde, alone or in alcoholic solution. On addition of a few drops of nitric acid condensation takes place almost at once, and the difficultly soluble nitrate of the aminoguanidine derivative is precipitated in the pure state. Quinones can be condensed with the nitrate in the same way, but in this case the whole must be boiled for a few minutes. THE PHENYLHYDRAZONES, ETC. The phenyl- hydrazones are formed according to the equation : R 2 CO + H 2 N.NHPh = R 2 C : N .NHPh + H 2 0. The phenyl hydrazine is applied in dilute acetic acid solution (dissolve the free base in one volume of 50 per cent, acetic acid and then dilute with three volumes of water), or the hydrochloride is dissolved in 8 to 10 parts of water containing excess of sodium acetate (i j- parts) . The hydrazone usually crystallises out on standing at the ordinary temperature. The pre- paration of mannose phenylhydrazone was described on p. in. The osazones, which may be regarded as bis-phenyl- hydrazones, were discussed on p. 122. Instead of phenyl hydrazine itself some of its deri- vatives are sometimes employed. Thus as.-benzyl phenyl hydrazine : /CH 2 C 6 H 5 C 6 H 5 N NH reacts more readily than phenyl hydrazine itself, and usually gives more insoluble products. The con- ALDEHYDES, KETONES, QUINONES 147 densation is brought about in warm, neutral, alcoholic solution,the hydrazone being subsequently precipitated by water. ^.-Bromphenyl hydrazine is applied in dilute acetic acid solution. as.-Methyl phenyl hydra- zine, CH 3 (C 6 H 5 )N.NH 2 , often gives osazones only from ketones, and hence serves for separating mixtures of aldoses and ketoses. 1 /H The alcoholates, R.C^-OH, and the acetals, X OR R.CH(OR) 2 , may be regarded as the ethers of the unknown gm-dihydric alcohols, and are described on p. 150. The cyanhydrins, R.CH(OH)CN, are the nitriles of the a-oxyacids, and are discussed on p. 188. 1 B. 35, 959, 2626 ; 37, 4616; H. 36, 233. CHAPTER VI THE ETHERS AND SULPHIDES WITH the exception of ethyl ether, the ethers are not of great importance. The aliphatic members are obtained by the action of concentrated sulphuric acid on the alcohols, the alkyl sulphuric acids being formed as intermediate products : R.OH + H 2 SO 4 = R.O.SO 3 H + H 2 O R.O.S0 3 H + HO.R = R 2 O + H 2 S0 4 . Ethers containing two different radicals are best obtained by treating the sodium alcoholate with the alkyl halide, preferably the iodide : R.ONa + R'l = R.O.R' + Nal. PREPARATION OF DIETHYL ETHER (C 2 H 6 ) 2 O. One hundred grammes of concentrated sulphuric acid are slowly added to an equal weight of alcohol, the whole being well shaken and cooled during the process. The mixture is then placed in a d stilling flask attached to a long and efficient condenser and provided with a tap-funnel and thermometer, the ends of both of which must dip below the surface of the acid mixture. The flask is then heated on a sand-bath. When the temperature of the mixture reaches 140 ether begins to distil, and should be collected in a receiver which is cooled with ice. During the distillation the temperature is maintained at 140, and alcohol is added through the tap-funnel at the rate at which the ether distils over. When about 1 50 c.c. of alcohol have been added the process is interrupted, and the distillate, which contains ether, sulphurous acid, and water, washed first with 50 c.c. of 10 per cent, caustic potash and then with a similar volume of saturated salt solution. The ether is then driecj \yith calcium chloride and distilled from the water- 148 THE ETHERS AND SULPHIDES 149 bath. It forms a colourless liquid which boils at 35, and is highly inflammable. As obtained above it contains traces of alcohol and water, which can only be removed by treatment with metallic sodium and subsequent distillation. The phenolic ethers, ArOAlk, are usually obtained by treating the alkali phenolates with the alkyl iodide : ArONa + Alkl = ArO.Alk + Nal. PREPARATION OF PHENETOLE (C 6 H 5 OC 2 H 5 ). One equivalent (2-3 grm.) of sodium is dissolved in 30 c.c. of alcohol, and one equivalent (9-4 grm.) of phenol and 19-5 grm. (i^ mol.) of ethyl iodide added. The whole is then boiled under a reflux condenser on the water-bath until no longer alkaline to moist litmus paper (about 2% hours) . The alcohol and excess of ethyl iodide are then removed by distillation from the water-bath, and the residue shaken up with water and extracted with ether. The ethereal extract is washed with a little dilute caustic potash and then with water. It is finally dried over calcium chloride and distilled. After the ether has been removed the phenetole passes over as a colourless oily liquid boiling at 173. In some cases, e.g. the o.- and . -nitre-phenols, the ether is only obtained with great difficulty by the above method. In such cases it is best to prepare the silver salt of the phenol and then treat it in alcoholic sus- pension with the alkyl iodide. The methyl ethers of the phenols are best prepared by means of dimethyl sulphate. The reaction is brought about by dissolving the phenol in excess of cold caustic potash solution (best of 30 to 40 per cent. strength) and then shaking with a slight excess (ij mol.) of dimethyl sulphate : R.ONa + Me 2 SO 4 = R.OMe + NaMeSO 4 . It should be borne in mind that dimethyl sulphate is very poisonous (see p. 183). The yields are usually excellent. 150 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF ANISOLE (C 6 H 5 OCH 3 ). One molecule (9-4 grm.) of phenol is dissolved in 50 c.c. of 10 per cent. caustic soda, and well shaken with 12 c.c. (i mol.) of dimethyl sulphate. The solution becomes warm, and the anisole separates out as an oily layer. The whole is then boiled under a reflux condenser for a short time (to destroy excess of dimethyl sulphate), more caustic being added, if necessary, in order to obtain an alkaline reaction. Finally the anisole is extracted with ether, the extract dried over calcium chloride and then distilled. The anisole passes over at 1 54 and forms a colourless oil. The yield is 90 to 95 per cent. The acetals are to be regarded as the ethers of the unknown gem-dihydric alcohols : /H R.C/ + C 2 H 5 OH = R.CH(OC 2 H 5 ) 2 + H 2 O. x o The ketones form similar compounds, but with greater difficulty. Just as it is only the polyhalide aldehydes, such as chloral, which combine with water to form hydrates, e.g. \ CC1 3 CHO + H 2 O = CC1 3 CH(OH) 2 Chloral Chloral hydrate it is only the polyhalide aldehydes which combine with one molecule of alcohol to form an alcoholate : CC1 3 CHO + C 2 H 5 OH = CC1 3 CH(OH)(OC 2 H 5 ). The acetals are obtained by loss of water between the aldehydes and the alcohols, and the reaction takes place most readily in the presence of alcoholic hydrochloric acid. 1 PREPARATION OF DIETHYL ACETAL (CH 3 .CH(OC 2 H 5 ) 2 ). Eighteen grammes of acetaldehyde are dissolved in 80 grm. of alcohol containing i per cent, of dry hydrogen chloride. After standing for eighteen hours the solution is diluted with its own volume of water, neutralised with potassium carbonate, and extracted with ether. The ethereal extract is twice i B. 30, 3053 ; 31, 545. THE ETHERS AND SULPHIDES 151 washed with a little water, dried over potassium carbonate, and then fractionated. The acetal passes over at 102- 104. The yield is about 50 per cent. The acetals are more readily obtained from ortho- formic ester. 1 In this case the aldehyde or ketone and the orthoformic ester are dissolved in alcohol, a suitable catalyst, such as mineral acid, ferric chloride, ammo- nium chloride, &c., added, and the whole allowed to stand for a long period at the ordinary temperature, or boiled for some time according to circumstances. The yields are often almost quantitative. THE SULPHIDES The sulphides are to be regarded as the ethers of the mer cap tans, and are of but slight interest. They can be obtained by allowing the halogen compounds to react with the mercaptans, and this method has lately become of some importance in the manufacture of the thioindigoid dyes, e.g. : + Cl.CH :CHC1 \/ SH \ I S Thioindigo Red For further details the reader is referred to the original literature. 2 The aliphatic sulphides are best prepared by heating the potassium alkyl sulphates with potassium sulphide in aqueous solution : 2KRS0 4 + K 2 S = R 2 S + 2K 2 SO 4 . 1 B. 40, 3903. 2 Friedlander, "Fortschritte," vol. viii. 469-488 ; vol. ix. 494-646 ; B. 43, 587 ; 44, 3125. 1 52 PREPARATION OF ORGANIC COMPOUNDS The reaction takes place readily, and the yields are usually good. The aromatic sulphides are often obtained by heating the hydrocarbons with sulphur with or without a catalyst (cf. p. 274), or with sulphur dichloride and aluminium chloride. Also aromatic nitro-haloid com- pounds which have a nitro-group in the ortho- or ^ap- position to the halogen atom readily give sulphides on treatment with sulphuretted hydrogen. PREPARATION OF 2.4.2 / 4 / -TETRANITRODIPHENYL SULPHIDE, ( (NO 2 ) 2 C 6 H 3 ) 2 S.i One molecule of 2.4-dinitro-i- chlorobenzene is dissolved in boiling alcohol, rather less than two molecules of strong ammonia added, and sulphuretted hydrogen then passed through the boiling liquid until no more precipitation takes place. The sulphide is then collected, washed with boiling water, and recrystallised from glacial acetic acid. It forms yellow needles which melt at 197. The yield is almost quantitative. It is important that rather less than the calculated amount of ammonia should be used, as otherwise the nitro-groups will be attacked : 2(N0 2 ) 2 C 6 H 3 C1 + H 2 S + 2NH 3 = ((NO 2 ) 2 C 6 H 3 ) 2 S + 2 NH 4 C1. i A. 197, 77. CHAPTER VII THE CARBOXYLIC ACIDS, THEIR ESTERS AND ANHYDRIDES THE CARBOXYLIC ACIDS i. BY THE HYDROLYSIS OF THE NITRILE, ACID CHLORIDE OR ACID AMIDE ON hydrolysis the nitriles pass first into the acid amide and then into the acid : R.C : N R.CO.NH 2 R.CO.OH The first stage is usually lost as the amides are more readily hydrolysed than the nitriles. The amide, however, can be isolated by the alkaline peroxide method described on p. 224. For the complete hydrolysis of the nitrile it is boiled with acids, or, better, with caustic alkali solution. Obstinate cases may require heating under pressure, treatment with mineral acids in glacial acetic acid solution, or treatment with alcoholic alkali. In some cases where the hindering influence of substituent groups is very marked, a fusion with caustic potash is necessary. HYDROLYSIS OF BENZONITRILE (C 6 H 5 CN). Ten grammes of benzonitrile are boiled with 150 c.c. of 20 per cent. caustic potash solution until no more ammonia is evolved. The solution is cooled, somewhat diluted, and then acidified with hydrochloric acid. The benzoic acid is filtered off, washed with cold water, and recrystallised from boiling water. The yield is almost quantitative. Colourless leaflets melting at 120. i 5 4 PREPARATION OF ORGANIC COMPOUNDS HYDROLYSIS OF a-NAPHTHONITRILE (C 10 H 7 CN).i Twelve grammes of a-naphthonitrile, 7-5 grm. of caustic soda, and 55 c.c. of alcohol are heated in a sealed tube to 160 for six hours. After cooling, the contents of the tube are well diluted with water and then acidified with hydrochloric acid. The naphthoic acid is filtered off, washed with water, and re- crystallised from alcohol. Colourless crystals melting at 160. The yield is almost quantitative. The hydrolysis can also be brought about by heating in an op'en vessel with a solution of concentrated sulphuric acid in glacial acetic acid. It is often unnecessary to isolate the pure nitrile, it being in many cases sufficient to hydrolyse the crude substance obtained by the action of potassium cyanide on alkyl halides. If the hydrolysis is carried out with a mixture of alcohol and concentrated sulphuric acid, simultaneous esterification takes place (cf. p. 177). PREPARATION OF DIETHYL MALONATE (CH 2 (CO 2 C 2 H 6 ) 2 ). Fifty grammes of chloracetic acid are dissolved in 100 c.c. of water at 5o-6o, and the solution neutralised in a large basin with sodium carbonate (about 45 grm. of the anhydrous salt) . When no more carbon dioxide is evolved, 40 grm. of potassium cyanide in small lumps are added slowly. When the brisk reaction is over, the solution is evaporated as rapidly as possible in a fume chamber. During the evaporation the whole must be continually stirred. The evaporation is continued until the temperature reaches 135. Without interrupting the stirring the mass is rapidly cooled, coarsely ground, mixed with 20 c.c. of alcohol, and transferred to a flask fitted with a reflux condenser. A well- cooled mixture of 80 c.c. of alcohol and 80 c.c. of concentrated sulphuric acid is then run in during fifteen minutes, and the whole heated on the water-bath for one or two hours. After cooling, 100 c.c. of water are added, and the whole filtered. The residue is washed several times with ether, the filtrate repeatedly extracted with ether, and the ethereal extracts washed with sodium carbonate solution until no longer acid. The ethereal solution is dried with calcium chloride, and the ether then removed by distillation from the water-bath. 1 B. 20, 241. THE CARBOXYLIC ACIDS 155 The residual oil is distilled under reduced pressure. It forms a colourless liquid boiling at 195. Acid chlorides are usually saponified by water. The aromatic acid chlorides, however, are but slowly attacked, and are best heated with dilute (10 per cent.) caustic soda solution. The acid amides are best boiled with 10 per cent. caustic alkali solution until no more ammonia,, is evolved. 2. BY THE OXIDATION OF THE ALCOHOLS, ALDEHYDES, AND KETONES The primary alcohols on oxidation pass first into the corresponding aldehyde (p. 109) and then into an acid containing the same number of carbon atoms as the alcohol : R.CH 2 OH r* R.CHO R.COOH. The secondary alcohols on oxidation first give a ketone, and then an acid with fewer carbon atoms than the alcohol : /CH 3 /CH 3 .OH R.C/H R.C/ R.C/ +C0 2 +HoO. \OH X ^O The tertiary alcohols on oxidation undergo complete decomposition. The oxidation of the aliphatic alcohols is best carried out with chromic acid mixture, whereas in the aromatic series permanganate is the best oxidising agent. In all cases esters and acetals usually appear as side- products. Polyhydric aliphatic alcohols are oxidised with nitric acid, but complete disruption of the molecule often takes place. PREPARATION OF SACCHARIC ACID (COOH(CHOH) 4 COOH). Fifty grammes of glucose are heated on the water- bath with 300 c.c. nitric acid (D = 1-15), and the solution 156 PREPARATION OF ORGANIC COMPOUNDS then concentrated to a syrup. This is dissolved in a little water and again evaporated until a brown coloration makes its appearance. The residue is then taken up in 150 c.c. of water, neutralised with potassium carbonate, and evapo- rated until the volume is about 80 c.c. By frequently scratch- ing the sides of the vessel the acid potassium salt slowly separates out as a crystalline mass. CH 2 OH . (CHOH) 4 . CHO COOH . (CHOH) 4 .COOH. PREPARATION OF OXALIC ACID (COOH) 2 . One hundred and forty grammes of nitric acid (D 1-32) are placed in a large flask together with a trace of vanadium oxide. The whole is warmed on the water -bath to about 50, and then 20 grm. of finely powdered cane-sugar added. As soon as a brisk reaction sets in with a copious evolution of red fumes, the flask is set to stand in cold water for at least twenty- four hours. The oxalic acid is then filtered off and recrystal- lised from a small quantity of boiling water. PREPARATION OF FORMIC ACID (H.COOH).* Fifty grammes of glycerine are dehydrated by cautiously warming in a basin until the temperature reaches 175. It is then transferred to a retort fitted with a condenser, 50 grm. of oxalic acid added, and the whole heated. The reaction sets in at about 90, and the contents of the retort are maintained at io5-uo until the reaction slackens. The whole is then allowed to cool somewhat, another 50 grm. of oxalic acid added, and the whole again heated. This process is repeated until 200 grm. of oxalic acid have been used. The distillate, which consists of aqueous formic acid, is set on one side and the contents of the retort transferred to a large flask and distilled in steam until the distillate is only faintly acid. The united distillates are neutralised with lead carbo- nate, boiled for a few minutes, and then filtered from excess of lead carbonate, the residue being well washed with boiling water. The clear filtrates are then concentrated until crystal- lisation sets in. The lead formate separates on cooling in long colourless needles. These are filtered off, washed with a little cold water, and dried. In order to obtain the free acid, the 1 Formic acid is prepared technically by passing CO over JQ soda-lime at 230 : CO + NaOH = H.C^-ONa. THE CARBOXYLIC ACIDS 157 powdered lead salt is loosely packed into a wide glass tube held in a sloping position and loosely plugged at the lower end with glass-wool or asbestos. The end of the tube is attached to a distilling flask provided with a calcium chloride tube. A fairly slow stream of dry hydrogen sulphide is then passed through the tube, the latter being gently warmed by means of a burner. The lead formate blackens owing to the formation of lead sulphide, and the formic acid collects in the distilling flask. When no more acid can be obtained, the flask is removed, some lead formate added (to remove sulphu- retted hydrogen), and the formic acid distilled off. Colourless liquid with a biting smell. B.P. 100. When a ketone of the type R.CH 2 .CO.CH 2 .R' is oxidised, acids R.COOH and R'CH 2 COOH are ob- tained, where the chain represented by R' is longer than that represented by R. Chromic acid is the best oxidising agent, but the method is of very minor importance. The aldehydes are very readily converted into the corresponding acids by most oxidising agents. Even exposure to the air often brings about the change. Thus benzaldehyde rapidly absorbs oxygen, giving benzoic acid. 3. BY THE OXIDATION OF ALKYL GROUPS This method is limited to the aromatic series. When any aromatic compound containing a side -chain is vigorously oxidised, the whole of the side-chain is burnt to COOH, and a carboxylic acid results, in which the carboxyl group is directly attached to the ring. As oxidising agents chromic acid, permanganate, dilute nitric acid, and potassium ferricyanide are usually chosen. When there are two side-chains present, both are oxidised by potassium permanganate and only one by dilute nitric acid. If the two chains are in the meta- or para- position to each other they are both oxidised by chromic acid, but if in the ortho- position are either unattacked or the ring is completely ruptured. As a 158 PREPARATION OF ORGANIC COMPOUNDS rule, negative groups in the ortho- position hinder oxidation with chromic acid. Potassium ferricyanide only oxidises methyl to car- boxyl when there is a nitro-group in the ortho- position. Oxidation is facilitated by substituting the hydrogen in the side-chain by halogen. If the side-chain is a methyl group and all three hydrogen atoms are replaced by chlorine, it is only necessary to heat the compound with alkalis or with water under pressure : Ph.CCl 3 - [PhC(OH) 3 ] - PhC + H 2 0. \OH This is the technical preparation of benzoic acid. Halogen atoms in the nucleus, however, hinder oxida- tion, and highly halogenated compounds can only be oxidised by the combined action of fuming nitric acid and potassium permanganate. If the side-chains form part of a ring, as e.g. in naphthalene, the or^o-dicarboxylic acid can be ob- tained by heating with sulphuric acid and a trace of mercury sulphate. This is the technical preparation of phthalic acid : 9H 2 SO V COOH + 2CO 2 +ioH 2 O+9SO 2 the sulphur dioxide being reconverted into sulphuric acid by the contact-process. If in addition to the side-chain to be oxidised, the molecule contains amino- or hydroxyl groups, these must first be protected. The amino-group can be acetylated or benzoylated, and the phenolic group treated in the same way, or an ester of sulphuric or phosphoric acid formed. Phenolic groups can also be protected by converting them into methoxy-groups by means of dimethyl sulphate. This method has the disadvantage that the methyl groups are trouble- some to remove when the oxidation has been com- THE CARBOXYLIC ACIDS 159 pleted. The protected amino-compoimds are oxidised with neutral potassium permanganate, i.e. potassium permanganate in the presence of excess of magnesium sulphate : 2KMnO 4 + H 2 O = 2KOH + 2MnO 2 + 30. 2KOH + MgS0 4 = Mg(OH) 2 + K 2 SO 4 . The protected phenols are oxidised with alkaline potassium permanganate. The protecting groups are subsequently removed by hydrolysis. PREPARATION OF BENZOIC ACID (C 6 H 5 COOH). Thirteen grammes of benzyl chloride and n grm. of sodium carbonate are heated under a reflux condenser, and a solution of 22 grm. potassium permanganate in about half a litre of water is slowly run in. The boiling is continued until the colour of the permanganate has completely, or almost completely, vanished. The liquid is then cooled and treated with sulphur dioxide gas until the precipitated manganese hydroxide has redissolved. The benzoic acid is filtered from the cold solution, washed with cold water, and recrystallised from boiling water. Colourless needles melting at 121. The yield is almost theoretical. PREPARATION OF PHTHALIC ACID,i 64 [2 JLAJUJtl. Twenty grammes of naphthalene, 10 grm. of mercuric sulphate, and 300 grm. of concentrated sulphuric acid (monohydrate) are placed in a retort which is clamped with the neck in an upright position. The whole is warmed until the naphthalene has gone into solution. The retort is then lowered to a normal position, an air condenser sealed or luted with plaster of Paris on to the end, and the retort heated strongly. The reaction commences at 2OO-25o and becomes vigorous at 300, a mixture of phthalic acid with some sulphophthalic acid and unchanged naphthalene passing over, together with the carbon dioxide, sulphur dioxide, and water. The distillate is collected in about 250 c.c. of cold water, and the distillation continued until the mass in the retort is nearly dry. The distillate is filtered and the precipitate washed with cold water 1 D.R.P. 91,202. 160 PREPARATION OF ORGANIC COMPOUNDS and then dissolved in caustic soda. Unchanged naphthalene is removed by nitration, and the phthalic acid then repreci- pitated with hydrochloric acid. It is finally purified by re- crystallisation from hot water or aqueous alcohol. It forms colourless plates, and on heating passes into the anhydride, / C0 \ C 6 H 4 <^ /O. This latter sublimes in long needles melting Nxx at 128. The yield is about 70 per cent. PREPARATION OF .-OXYBENZOIC ACID (C 6 H 4 [i]OH [4JCOOH). 1 .-Cresol is converted into potassium-/?. -cresyl sulphate by treating its concentrated solution at 6o-7O with potassium pyrosulphate (ij parts) for eight to ten hours. The potassium salt is then dissolved by warming with an equal weight of potassium hydroxide dissolved in a little water. The solution is heated on the water-bath, and rather more than the calculated quantity (one molecule) of potassium permanganate in 4 per cent, solution slowly added, and the whole heated for some hours. Excess of permanganate is then destroyed by adding a few drops of alcohol and continuing the heating until a filtered sample no longer shows a pink colour. The whole is filtered hot, the filtrate acidified with hydrochloric acid, and then warmed on the water-bath to hydrolyse the sulphuric ester. On cooling, the greater part of the acid crystallises out and the rest is extracted with ether. After recrystallisation from water it melts at 210. The yield is almcst theoretical. PREPARATION OF ANTHRANILIC ACID (C 6 H 4 [i]NH 2 [2JCOOH). 2 Five parts of acet-o.-toluide, 10-3 parts of crystallised magnesium sulphate, and 600 parts of water are heated to 75-8o. At this temperature 14-6 parts of solid potassium permanganate are added, and the whole heated to 85 for i hours. The liquid is filtered hot, and the filtrate on cooling acidified with dilute sulphuric acid, when acet- anthranilic acid is precipitated. M.P. 185. The acetyl group can be split off by boiling with dilute caustic alkali, or better, with dilute hydrochloric acid. Anthranilic acid itself melts at 145. i B. 19, 705. 2 D.R.P. 94,629 THE CARBOXYLIC ACIDS 161 4. FROM THE ALKYL MAGNESIUM COMPOUNDS When an alkyl or aryl halide, preferably the iodide, is treated in absolute ethereal solution with clean magne- sium ribbon, an alkyl or aryl magnesium compound is obtained : R.Hlg + Mg = Mg X Hlg This on treatment with CO 2 forms a carboxylic acid : /O MgHlg R_Mg Hlg + C0 2 - R.C/ ^o ,0. MgHlg ,OH R.C/ +H 2 = R.C^ +Mg(OH)Hlg. The formation of the alkyl or aryl magnesium halide is often facilitated by the addition of a trace of iodine, or by first heating the magnesium in iodine vapour. 1 Tertiary bases, such as dimethyl aniline, also act as catalysts. PREPARATION OF BENZOIC ACID (PhCOOH).2 The ether used in this experiment must be dried by distillation over metallic sodium or phosphorus pentoxide, and all vessels must be scrupulously dry. Forty cubic centimetres of absolute ether, 2-4 grm. of clean magnesium ribbon, 20-4 grm. of iodobenzene, and a trace of iodine are heated under a reflux condenser until the reaction sets in and the liquid remains in ebullition when the water-bath is removed. When the reaction begins to slacken, the water-bath is replaced, and the boiling continued until all the magnesium has dissolved (about half an hour). The solution is then cooled in melting ice, and treated at this temperature with a moderately rapid stream of dry carbon dioxide for three hours. The solution is then decomposed by adding ice, acidified with 15 c.c. of i B. 38, 2759, 2 B. 35 2519. ii 162 PREPARATION OF ORGANIC COMPOUNDS concentrated hydrochloric acid, diluted with its own volume of water, and the benzoic acid shaken out with ether. The ethereal solution is extracted with dilute caustic soda, and the benzoic acid precipitated from the alkaline extract by acidifying with hydrochloric acid. The acid is purified by recrystallisa- tion from water. It melts at 121. The yield is 90 to 95 per cent. Instead of using carbon dioxide, chloroformic ester or a carbonic ester may be used, in both of which cases the ester and not the free acid is obtained : R.Mg.Hlg + Cl.COOEt = R.COOEt + MgHlgCl EtO x /Hlg R.MgHlg + )CO = R.COOEt + Mg/ EtO/ 5. BY THE FRIEDEL-CRAFT'S REACTION Under the influence of aluminium chloride aromatic compounds condense with urea chloride, C1.CO.NH 2 , to give acid amides, with chloroformic ester to give carboxylic esters, and with phosgene to give acid chlorides. In the last case, however, the chief product is usually the ketone (cf. p. 127). The halogen acids, such as chloracetic acid, can also be made to condense. The condensation is usually carried out by dissolving the aromatic compound in about 3 parts of dry carbon bisulphide. The halogen compound (one molecule) is added, and then an equal weight of powdered anhydrous aluminium chloride in small quantities at a time. When the reaction has moderated, the whole is warmed for a short time on the water- bath, the carbon bisulphide poured off, and the pasty residue decomposed with ice. 6. BY KOLBE'S METHOD This method is limited to the preparation of phenolic acids, and consists in treating the dry sodium phenolate with carbon dioxide. The carboxyl group enters the o v ilio- position to the phenolic group, but if the potassium THE CARBOXYLIC ACIDS 163 phenolate is used the carboxyl group often takes the Para- position : C 6 H 5 ONa + CO 2 = C 6 H 5 .O.COONa. C 6 H 5 O.COONa + C 6 H 5 ONa = [i]OH + C 6 H 5 OH. On the manufacturing scale the reaction is carried out under pressure, the whole of the phenolate being converted into the carboxylic acid : C 6 H 5 O.COONa = C 6 H 5 (OH)COONa. The reaction takes place most easily with polyhydric phenols, heating under pressure with aqueous solutions of potassium bicarbonate often being sufficient. 1 PREPARATION OF SALICYLIC ACID, Q^ Thirty grammes of phenol are gradually added to a solution of 12-5 grm. of caustic soda in 20 c.c. of water. The solution is cautiously evaporated in a basin until, on cooling, it can be readily powdered. This powdering should be done as rapidly as possible, and the powdered sodium compound at once transferred to a tubulated retort. The powder is then com- pletely dried by heating in an oil-bath to 140 in a fairly rapid stream of dry hydrogen. When no more moisture condenses in the neck of the retort (about one hour) the temperature is allowed to fall, without interrupting the current of hydrogen. When fairly cool the sodium phenolate is again powdered as rapidly as possible, replaced in the retort, and the temperature raised to 110, a rapid stream of dry carbon dioxide being passed through the apparatus. After an hour the temperature is gradually raised so that in four hours it has reached 190, and at the end of six hours 200. The temperature is main- tained at this point for one hour. During the whole of the above process the retort must be shaken from time to time in order to expose fresh surfaces to the action of the gas. After cooling, the dark-coloured mass is shaken out of the retort without dislodging the phenol which has condensed in the neck, Should any of the sodium salicylate have adhered to the i M. i, 236, 468 ; 2, 448, 458. 2 J- pr. [2] 10, 95. 1 64 PREPARATION OF ORGANIC COMPOUNDS sides of the retort it is dissolved out with warm water. The whole is boiled up with water, filtered if necessary, and the filtrate, after cooling, acidified with hydrochloric acid. The crude, dark-coloured acid is filtered off, washed with cold water, boiled with animal charcoal and water, and filtered. The acid separates from the filtrate on cooling in colourless needles melting at 155. The yield is about 20 per cent., calculated on the first equations given on p. 163. A variation of Kolbe's method consists in heating the potassium phenolate with carbon tetrachloride under pressure with sufficient alcohol to give a clear solution. Cf. p. 120. 7. FROM THE ALDEHYDES AND KETONES BY CONDENSATION REACTIONS (a) PERKIN'S METHOD. This reaction serves for the preparation of aromatic unsaturated carboxylic acids, e.g. cinnamic acid, and is of very general appli- cation. The condensation takes place between aro- matic aldehydes in which the aldehydic group is directly attached to the nucleus, and the sodium salts of ali- phatic acids which contain the group CH 2 COOH, the anhydride of the acid, or acetic anhydride being used as a condensing agent. It is best when possible to use the anhydride of the acid the sodium salt of which is undergoing condensation, as if acetic anhydride is used there is a risk of double decomposition : (CH 3 CO) 2 O + 2CH 3 .CH 2 .CH 2 COONa = 2CH 3 COONa + (CH 3 .CH 2 .CH 2 CO) 2 leading, of course, to a mixture of condensation products. Cf. p. 174. The reaction can be considered to take place in two steps, viz. : (i) An a-hydrogen atom from the fatty acid salt attaches itself to the aldehydic oxygen atom : /K /R Ar,CHO t R,CH ? .COOH = Ar.C^ C^-COONa. \OH\H THE CARBOXYLIC ACIDS 165 (ii) Water is split out with the formation of a double bond : / H / R v/ R Ar.C(- - C^-COONa = Ar.CH : C\ ^ X COONa It should be noticed that it is always the a-carbon atom which becomes attached to the aldehydic group. The reaction takes place best at a temperature of about 180. If the aldehyde contains a phenolic group in the ortho- position to the aldehydic group, a further loss of water takes place with the formation of a lactone : CH 3 C0 2 Na CH f X ,CH =CH C /\ 90 'x '-0-CO X 0(HOHj Salicylic aldehyde Coumaric acid Coumarin PREPARATION OFCINNAMIC ACID (C 6 H 5 CH : CHCOOH) .1 Thirty grammes of freshly distilled acetic anhydride, 20 grm. of freshly distilled benzaldehyde, and 10 grm. of powdered, freshly prepared, anhydrous sodium acetate are heated under a reflux condenser on the oil-bath to 180 for ten to fifteen hours. It is advantageous to provide the top of the condenser with a calcium chloride tube. The product is rendered alkaline with sodium carbonate, and any unchanged benzaldehyde removed by distillation in steam. The liquid is then filtered hot, cooled, and acidified with hydrochloric acid. The cinnamic acid is filtered off, washed with a little cold water, and then recrystallised from boiling water. Colourless prisms melting at 133. The yield is about 15 grm. When sodium succinate is employed in Perkin's condensation, the first step of the reaction takes place with great ease : /H CH 2 .COONa /H /COONa C 6 H 5 CCH . COOH. 1 One atomic proportion of C 2 H 5 \< CHg.CH2.CH2/ sodium is dissolved in 10 to 12 parts of absolute alcohol, and after the solution has cooled, one molecular proportion of acetoacetic ester added. Rather more than one molecule of ethyl iodide is then run in slowly through a reflux condenser. When all the iodide has been added, the whole is heated on the water-bath until it no longer reacts alkaline to moist litmus paper. If this result cannot be reached more ethyl iodide must be added. The solution now contains ethyl acetoacetic ester (see p. 134). Another atomic proportion of sodium dissolved in alcohol is then added, and then rather more than a molecular proportion of n.-propyl iodide is dropped in, and the whole heated as before until neutral. The solution now contains ethyl- w.-propyl acetoacetic ester : CH 3 . CO CCOOEt \CH 2 .CH 2 .CH 3 . The greater part of the alcohol is removed by distillation from the water-bath, and the residue shaken with water until all the solid matter has dissolved. The ester is then extracted i B. 19, 227. THE CARBOXYLIC ACIDS 171 with ether, the ethereal solution dehydrated with anhydrous sodium sulphate, and the ether removed by distillation. The residue is heated until the temperature reaches 145. To bring about its hydrolysis, i part of the ester is heated with a free flame under a reflux condenser for four hours with 2 parts of caustic potash dissolved in J part of water and J part of alcohol. The whole is then diluted with water, ethyl propyl ketone, a by-product due to the ketonic hydrolysis taking place as a side-reaction, and unchanged ester extracted with ether, and the liquid then acidified. The hexane-3- carboxylic acid separates out as an oil and is collected, dried, and distilled. B.P. 209. A synthesis similar to the above can be carried out with malonic ester, and this synthesis has the advantage that the hydrolysis can only go in one direction : .COOEt RR'.C< +3KOH = \COOEt RR'.CHCOOK + K 2 C0 3 + 2 EtOH. Just as in the case of ac$ toacetic ester, only one atom of sodium can be introduced into malonic ester at a time. 1 In this case also only alky I and not aryl halides can be used. The hydrolysis is brought about by concentrated caustic potash, hydrochloric acid, or 50 'per cent. 1 It was pointed out on p. 136 that dialkyl compounds are frequently formed when acetoacetic ester is treated with one molecule of sodium and one molecule of alkyl halide. This also happens in the case of malonic ester : RCH(COOEt) 2 + CHNa ^ RCNa(COOEt) 2 + CH 2 (COOEt) 2 RCNa(COOEt) 2 + RI = R 2 C(COOEt) 2 + Nal. By using only half the calculated quantity of sodium and alkyl halide, the yield of the monoalkyl compound is usually improved. Thus when malonic ester is treated with one molecule of sodium and. one molecule of benzyl chloride, the yield of the benzyl derivative is only 55 per cent., whereas when only half a molecule of sodium and half a molecule of benzyl chloride are used the yield is 85 per cent. B. 44, 1507. 172 PREPARATION OF ORGANIC COMPOUNDS sulphuric acid, or the free malonic acid derivative is heated alone. PREPARATION OF ETHYL MALONIC ESTER (C 2 H 5 CE^COOEty. 1 One-tenth of a gramme- molecule (2-3 grm.) of sodium is dissolved in 25 grm. of absolute alcohol, and 16 grm. of malonic ester added to the cooled solution. Twenty grammes of ethyl iodide are then slowly added through a reflux condenser, and the whole heated on the water-bath until it no longer reacts alkaline to moist litmus (one to two hours). The alcohol is then distilled off, and the residue shaken with water until all the^solid matter has dissolved. The ester is then extracted with ether, the ethereal solution dried with anhydrous sodium sulphate, the ether distilled off, and the residual oil fractionated. B.P. 2o6-2o8. Yield 15 grm. PREPARATION OF BUTYRIC ACID (C 2 H 5 CH 2 COOH).2 Ten grammes of the above ester (ethyl diethyl malonate) are slowly added to a cold solution of 12-5 grm. of caustic potash in 10 c.c. of water. The emulsion thus obtained, when gently warmed under a reflux, suddenly boils up. The boiling is continued until the oily layer has disappeared. The solution is then diluted with twice its volume of water, acidified with concentrated hydrochloric acid (use Congo paper), and extracted with ether, the ethereal solution dried and distilled. The ethyl malonic acid, C 2 H 6 CH(COOH) 2 , is left behind as a crystal- line mass, which melts at 112. Yield 5 grm. On heating to 1 80 for an hour it loses carbon dioxide to form butyric acid, which can then be distilled off. Butyric acid boils at i62-i63, and has a disgusting, rancid odour. By boiling ethyl diethyl malonate for several hours with 50 per cent, sulphuric acid, the hydrolysis of the ester and the loss of carbon dioxide take place simultaneously. ADDENDA The Benzilic Acids. When an aromatic aldehyde is heated with potassium cyanide in alcoholic solution, condensation takes place and a hydroxy-ketone is formed (see p. 131) : zAr.CHO = ArCHOH.CO.Ar. 1 A. 204, 127,134. 2 Loc. cit. THE CARBOXYLIC ACIDS 173 This on oxidation (nitric acid) gives the corresponding a-diketone (see p. 123) : Ar.CHOH.CO.Ar + O = ArCO.CO.Ar + H 2 O which on fusion with caustic alkali takes up the ele- ments of water and undergoes a complete rearrangement, a diaryl glycollic acid (benzilic acid) being formed : Ar . CO . CO . Ar + H 2 = Ar 2 COH . COOH. PREPARATION OF BENZILIC ACID (C 6 H 6 ) 2 .COH. COOH. 1 Fifty grammes of caustic potash are dissolved in 100 c.c. of water, and 125 c.c. of alcohol then added. Fifty grammes of benzil are added to the solution thus obtained, and the whole heated on the water-bath under a reflux con- denser. The heating is continued for ten to twelve minutes after ebullition has set in, but longer heating must be carefully avoided. The contents of the flask are poured into a beaker, allowed to stand for several hours, and then filtered. The precipitate is washed with a little alcohol and then removed from the paper and violently shaken with 100 c.c. of cold alcohol. It is filtered, drained at the pump as completely as possible, and then dissolved in cold water (500-1000 c.c.) and filtered. The filtrate is heated to boiling and acidified with boiling dilute sulphuric acid (use Congo paper). The benzilic acid separates out on cooling and is washed with cold water. It forms colourless needles melting at 150. Yield 90 to 95 per cent. This method gives better results than the older method of fusing with caustic potash (5 parts) at 150. The o.-benzoyl benzoic acids are obtained from phthalic anhydride and an aromatic hydrocarbon or a substitution product, in the presence of aluminium chloride. The yields are excellent (go to 95 per cent. as a rule). The reaction has been discussed on p. 129. The sym.-diphenyl methane dicarboxylic acids are obtained by condensing benzoic acid, &c., with formalde- hyde in the presence of mineral acids (Lederer-Manasse synthesis. Cf. p. 97). The condensation takes place in the meta- position. PREPARATION OF DIPHENYL METHANE-s.s'-DICARB- OXYLIC ACID. 2 Twenty-five grammes of benzoic acid are i B. 41, 1644. 2 B. 27, 2324, 3315. 174 PREPARATION OF ORGANIC COMPOUNDS mixed with 125 grm. of concentrated sulphuric acid, and the whole well cooled. Ten cubic centimetres of 40 per cent. formaldehyde solution are then added slowly, and the whole allowed to stand for four days at a temperature of 30. It is then poured into water, and the precipitate collected, washed with cold water and recrystallised from chloroform. It forms colourless tablets which melt with decomposition at 118- 119. THE ACID ANHYDRIDES For convenience the acid anhydrides can be divided into two classes, viz. (i) anhydrides formed by the loss of water between two carboxyl oups in the same molecule ; (2) anhydrides formed by the loss of water between two carboxyl groups in different molecules. The first class of anhydrides is formed only by poly- basic aliphatic acids whose carboxyl groups are sepa- rated by two or three carbon atoms, i.e. acids of the succinic, maleic, and glutaric groups, and by aromatic or^o-dicarboxylic acids, e.g. phthalic acid. This latter rule is not absolute, as terephthalic acid (1-4) forms an anhydride, but only with great difficulty. These anhydrides are, as a rule, very readily formed simply by heating the acid alone or with a dehydrating agent, such as sulphuric acid. The greater number of anhydrides belong to the second class and may be regarded as diacyl derivatives of water. They are formed : i. BY HEATING THE ACID WITH ACETIC ANHYDRIDE PREPARATION OF CINNAMIC ANHYDRIDE (C 6 H 5 CH = CH.CO) 2 O. 1 Fifty grammes of cinnamic acid and 200 grm. of acetic anhydride are boiled under a reflux condenser for six hours. The liquid is then distilled until the temperature reaches 146, and the residue, after cooling, taken up with ether. On evaporating off the ether, the anhydride separates in the crystalline state. It may be recrystallised from alcohol, and forms colourless needles which melt at 136, i B. 34, 186, 2074. THE CARBOXYLIC ACIDS 175 2. BY HEATING THE ACID CHLORIDE WITH THE ANHYDROUS SODIUM SALT CH 3 .CO.O jNa CljCO.CH 3 > (CH 3 CO) 2 O. This reaction usually takes place with great ease. On the manufacturing scale the chloride is not isolated, but the sodium salt is treated with half the quantity of phosphorus oxychloride, &c., requisite for its complete conversion into the acid chloride. In the laboratory, however, it is always best to isolate the chloride. PREPARATION OF ACETIC ANHYDRIDE (CH 3 CO) 2 O. Fifty grammes of well-powdered anhydrous sodium acetate are placed in a retort, and 35 grm. of acetyl chloride slowly dropped in, the retort being well cooled with water and shaken from time to time. When all the chloride has been added, the whole is distilled until no more liquid passes over, the distillate being collected in a receiver provided with a calcium chloride tube to exclude atmospheric moisture. The distillate is then redistilled over a little fresh anhydrous sodium acetate. The anhydride forms a pungent -smelling liquid boiling at 136- 137. Yield about 40 grm. 3. BY TREATING THE ACID CHLORIDE WITH QUINOLINE OR PYRIDINE 1 In this reaction an addition product is first formed, which then reacts with water, hydrochloric acid and the acid anhydride being formed. In other words, diacyl derivatives of water can be obtained by the action of acid chlorides on water under the influence of pyridine or quinoline. PREPARATION OF BENZOIC ANHYDRIDE (C 6 H 5 CO) 2 O.2 Twenty-five grammes of benzoyl chloride are slowly added to 10 c.c. of pyridine and 8 grm. of anhydrous sodium carbonate. After standing for half an hour the whole is poured into water, and the precipitated benzoic anhydride filtered off and 1 B. 34, 2070 ; D.R.P. 117,267. 2 G.22 [2], 215; J.pr. [2], 50, 479. 176 PREPARATION OF ORGANIC COMPOUNDS washed with cold water. By dissolving the dried product (use a vacuum desiccator) in petroleum ether, and then evapo- rating the solution at the ordinary temperature in vacua, the anhydride is obtained as long colourless needles which melt at 42. THE CARBOXYLIC ESTERS In this section only methods for converting the carb- oxylic acid (or the acid chloride or anhydride) into the corresponding ester will be considered. The forma- tion of esters by building up from, or degrading other esters will be found discussed elsewhere. Just as the alcohols may be regarded as analogous to the inorganic alkaline hydroxides, so may the esters be regarded as analogous to the inorganic salts : *O R.COOH + HOR' = R.C^-0 R' + H 2 O. Polybasic acids form neutral and acid esters, analo- gous to the neutral and acid inorganic salts. Poly- hydric alcohols usually form both mono- and poly-acyl derivatives, corresponding to the basic and neutral salts. The alcohols also form esters with inorganic acids, some of which will be found discussed at the end of this chapter. The alcohols must be regarded as very weak bases, and hence, as would be expected, their salts, the esters, are readily hydrolysed by water, just as inorganic salts formed from weak bases, such as Fe(OH) 3 , A1(OH) 3 , are slowly decomposed into their components by water. In other words, the reaction indicated by the equation given above is reversible, and can only be completed by continually removing one of the products,, formed. When the alcohol, acid, and ester all boil at a high temperature, this can be done by heating the reaction mixture in an open vessel so that the water is removed as vapour. As a rule, however, some dehydrating agent is added to the reaction mixture. THE CARBOXYLIC ACIDS 177 i. ESTERIFICATION OF THE FREE ACID BY THE ALCOHOL The alcohol and the acid are. mixed together, and the solution saturated with dry hydrochloric acid gas and then allowed to stand, or sulphuric acid is added and the ester distilled off as it is formed. PREPARATION OF ETHYL ACETATE (CH 3 COOC 2 H 5 ). Fifty cubic centimetres of absolute alcohol are slowly mixed with an equal volume of concentrated sulphuric acid, and the whole distilled from an oil-bath at 140. During the distilla- tion a mixture of 100 c.c. of glacial acetic acid and 100 c.c. of alcohol is dropped into the flask from a tap-funnel at the same rate as liquid collects in the receiver. When the whole of the latter mixture has been added, the distillate is shaken up with strong sodium carbonate solution until the upper layer is no longer acid (use moist litmus paper). The layers are then separated. The upper layer consists of ethyl acetate mixed with some alcohol and ether. The former of these is removed by shaking with concentrated (40 per cent.} calcium chloride solution. The ethyl acetate is then dried with calcium chloride and distilled from the water-bath. The portion which distils below 75 contains ether and is rejected. The portion boiling between 75 and 80 is ethyl acetate, and is fairly pure. .Colourless, pleasant -smelling liquid boiling at 77. Yield about 80 per cent. PREPARATION OF DIETHYL TARTRATE (CHOH) 2 (COOEt) 2 . 1 Finely powdered tartaric acid is shaken with rather more than its own weight of absolute alcohol, and then saturated with dry hydrochloric acid gas, the whole being well cooled with ice. The mixture is allowed to stand for at least twenty-four hours, and then the supernatant liquid poured off from the unchanged acid. The greater part of the hydro- chloric acid is removed from the solution by blowing air through it. The excess of alcohol and water is then removed by distilling in vacua from the water-bath. The residue consists chiefly of the acid ester. It is taken up with the same amount of absolute alcohol as was used previously, and the well-cooled solution again saturated with hydrochloric acid. i B. 13, 1176. 12 1 78 PREPARATION OF ORGANIC COMPOUNDS After standing, it is treated exactly as before, and the residue, which does not distil from the water-bath, then fractionated in vacua. After refractionation the ester forms a colourless viscous liquid which boils at 155 at n mm. and 162 at 19 mm. It solidifies on prolonged standing to a mass of colourless crystals which melt at 48. PREPARATION OF ETHYL BENZOATE (C 6 H 5 COOEt). Twenty-five grammes of benzoic acid are boiled under a reflux condenser with 100 c.c. of 5 per cent, absolute alcoholic hydro- chloric acid solution until on pouring a sample into water, only an oil and no solid matter separates out (about two hours). The excess of alcohol is then distilled off from the water-bath, and the residue poured into water and made slightly alkaline with sodium carbonate. The ester, which separates as an oil, is collected, dried with calcium chloride, and distilled. It forms a colourless liquid which boils at 211. Yield about 80 per cent. 2. BY THE ACTION OF THE ACID CHLORIDE ON THE ALCOHOL This method is especially useful in preparing the aromatic esters. In this case the phenol is dissolved in excess of cold, 10 per cent, caustic soda and the solution shaken with excess of the acid chloride until the latter has disappeared (Schotten-Baumann method). The ester is then collected and purified. Instead of caustic soda, sodium carbonate, chalk, barium carbonate, &c., may be used, and this modi- fication is often useful when working with phenols which are sensitive to alkali. Pyridine also can be used and generally gives excellent results, but in some cases the product is not identical with that obtained when an inorganic base is employed. Thus erythrite when treated with benzoyl chloride in the presence of caustic alkali gives only a tribenzoate, but in the presence of pyridine di-, tri-, and tetra-benzoates are all formed. Esterification in the presence of p}7ridine is usually carried out by dissolving the alcohol or phenol in THE CARBOXYLIC ACIDS 179 5 to 10 parts of pyridine, and then adding the acid chloride, the whole being well cooled. After eight hours the reaction mixture is poured slowly into cold dilute sulphuric acid, and the ester collected and purified. A full discussion of the above methods will be found in Lassar-Cohn's " Arbeitsmethoden." PREPARATION OF PHENYL BENZOATE (C 6 H 6 O. COC 6 H 5 ). Five grammes of phenol are dissolved in 70 c.c. of 10 per cent, caustic soda at 25-3o. Five grammes of benzoyl chloride are then added, and the whole violently shaken until the smell of benzoyl chloride has vanished. The ester is then filtered off, washed with cold water, and re- crystallised from alcohol. It forms colourless crystals melting at 68-69. Instead of phenol, the cresols, naphthols, &c., may be used. With alcohols the reaction takes place even more readily. It is not necessary to isolate the acid chloride in a pure state, but the crude substance prepared from the acid or its sodium salt can be used directly. PREPARATION OF DIMETHYL TEREPHTHALATE, C 6 H 4 TAT - 1 Crude terephthalic acid is warmed with two molecules of phosphorus pentachloride until the mass becomes liquid . Excess of methyl alcohol is then added, and the whole boiled under a reflux condenser for an hour. On cooling, the ester crystallises out. It melts at 140. Yield 90 per cent. PREPARATION OF MANNITOL DIBENZOATE.* Two grammes of mannitol are dissolved in 120 c.c. of pyridine, and 9-3 grm. of benzoyl chloride slowly dropped into the slightly warm solution. After standing some hours, the whole is poured into cold dilute sulphuric acid, the ester collected, washed with cold water, and then recrystallised from alcohol. Colourless needles melting at 178. i A. 245, 140. Cf. also J. pr. [2], 20, 263 ; D.R.P. 38,973, 70,483, 71,446. 2 A. 301, 102. i8o PREPARATION OF ORGANIC COMPOUNDS The above methods can also be employed for pre- paring the esters of sulphonic acids from their chlorides. 3. BY THE ACTION OF THE ACID ANHYDRIDE ON THE ALCOHOL In practice this method is almost confined to the preparation of acetates. The esterification is brought about by boiling the alcohol or phenol with acetic anhydride, alone or in glacial acetic acid solution, with or without the addition of a dehydrating agent such as sulphuric acid, anhydrous sodium acetate, or anhydrous zinc chloride. Other variations of the method are known, for which the reader is referred to larger works. 1 PREPARATION OF MANNITOL HEXA-ACETATE (CH 2 OCOCH3) 2 .(CHOCOCH 3 )4. 2 Ten grammes of mannitol are added to 40 grm. of acetic anhydride, and then a little anhy- drous zinc chloride added. Considerable heat is evolved, and when the reaction has moderated, the whole is heated on the water -bath for a short time, and after cooling poured into cold water. The ester is collected, washed with cold water, and then recrystallised from ether or from a mixture of alcohol and ethyl acetate. It forms colourless rhombic crystals which melt at 119, 4. ESTERIFICATION WITH METHYL SULPHATE This method is, of course, limited to the production of methyl esters. 3 It usually gives excellent results, but great care must be exercised as methyl sulphate is very poisonous. 4 The process is carried out either by shaking the free acid with methyl sulphate and excess of cold dilute caustic soda for half an hour, * See Lassar Cohn, " Arbeitsmethoden, " 4th ed. 1907, p. 15 et seq., and p. 238 et seq. 2 B. 12, 2059. 3 It should be noted that diethyl sulphate is utterly useless for preparing ethyl esters, &c. 4 See p. 183, THE CARBOXYLIC ACIDS 181 and then warming the mixture on the water-bath for half an hour, or the dry potassium salt of the acid is heated with methyl sulphate (if molecules) until no more ester distils over. This method, however, is only used when other methods fail. It, however, affords a convenient method of preparing methyl iodide. (Slowly drop 126 grm. of dimethyl sulphate into a solution of 166 grm. of potassium iodide in 166 c.c. of water heated on the water-bath. The methyl iodide distils over in 90 per cent, yield. D.R.P. 175,209.) 5. FROM THE SILVER SALT OF THE ACID AND THE ALKYL IODIDE This method is only employed when, owing to steric or other causes, the acid cannot be esterified by the usual methods. The iodide or other halide is dissolved in some suitable solvent (benzene, xylol, &c.), and shaken or heated with the silver salt. The silver halide is then filtered off and the filtrate fractionated. THE ESTERS OF INORGANIC ACIDS The esters of the halogen acids (the alkyl and aryl halides) have been fully discussed in Chapter III. Of the esters of nitric acid, glycerine trinitrate (nitroglycerine), and various cellulose nitrates (nitro- cottons, gun-cotton, collodion, pyroxylin, &c.), are prepared by the action of concentrated nitric and sulphuric acids on glycerine and cellulose (cotton waste) respectively. They are used in enormous quantities in the manufacture of explosives, celluloid, photographic films, artificial silk, &c., but cannot be safely prepared in the laboratory. Some of the esters of nitrous acid, especially amyl nitrite (amylium nitrosum) and ethyl nitrite (spiritus setheris nitrosi), are of therapeutic value owing to their dilating the blood-vessels and thus lowering the blood-pressure. Amyl nitrite is also useful for preparing diazo-com- pounds. 1 82 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF AMYL NITRITE (C,H u ONO).i Thirty grammes of fermentation amyl alcohol are cautiously mixed with an equal weight of concentrated sulphuric acid, the mixture well cooled, and then slowly added to a cooled mixture of 26 grm. of potassium nitrite and 15 c.c. of water. The whole is then cautiously distilled . The amyl nitrite passes over below 100, and is well washed with water. It is finally dried over calcium chloride and again distilled. Yellowish liquid, B.P. 96. Great care should be taken not to inhale its vapour as it has a powerful action on the heart . Some of the esters of sulphuric acid are of importance, especially dimethyl sulphate. By the action of con- centrated sulphuric acid on alcohols, alkyl sulphuric acids are formed : R.OH + H 2 S0 4 = R.SO 3 .OH + H 2 O. Excess of sulphuric acid is then removed with lead, calcium, or barium carbonate, and the soluble metal alkyl sulphate either obtained by evaporating the filtrate or, if the free acid is required, exactly the required amount of sulphuric acid is added, and the filtrate then concentrated. PREPARATION OF POTASSIUM ETHYL SULPHATE (C 2 H 5 O.SO 2 .OK). Fifty grammes of absolute alcohol are slowly run into 36 grm. of concentrated sulphuric acid, the whole being well stirred during the operation. Considerable heat is evolved, and the rate at which the alcohol is added is regulated so that the temperature rises to 8o-9o. When all the alcohol has been added, the whole is heated on the water- bath for three hours under a reflux condenser. After cooling, the reaction mixture is poured into about 500 c.c. of cold water and neutralised (use litmus) with a slight excess of chalk or lead carbonate ground to a thin cream with water. The mixture is filtered boiling, and the precipitate washed with boiling water. The clear, boiling filtrate is then treated with con- centrated potassium carbonate solution until no more pre- cipitation takes place (test a filtered sample from time to time), filtered, and the filtrate concentrated until crystallisation 1 J- 1874, 352. THE CARBOXYLIC ACIDS 183 sets in. On cooling, the potassium salt separates out and is filtered off and washed with a little alcohol. The above recipe can also be used for preparing potassium methyl sulphate from methyl alcohol. PREPARATION OF DIMETHYL SULPHATE 1 (CH 3 ) 2 SO 4 . In carrying out this preparation it must be remembered that dimethyl sulphate is very poisonous, and great care must be taken not to inhale any of its vapour. In spite of its high boiling-point the vapours it emits at the ordinary temperature have been known to cause death in several cases. As it is readily absorbed through the skin, care must be taken not to spill any on the hands. Should any be spilt on the clothes these must be changed at once. 2 One hundred grammes of chlorsulphonic acid are placed in a 200 c.c. distilling-flasb provided with a rubber stopper carrying a thermometer, the bulb of which dips into the acid, and a Walter dropping-funnel (see Fig. 3, p. 2). The end of the stem of this latter is drawn out to a fine capillary, and then bent upwards so that the opening is just below the surface of the acid in the flask. Twenty-seven grammes of anhydrous methyl alcohol are placed in the funnel, and before the latter is dipped under the acid, sufficient alcohol to completely fill the capillary is allowed to drop through the tap. The acid must be cooled to - 10 before the reaction is started. The side-tube of the flask is connected with a wash-bottle containing a little concentrated sulphuric acid, and this with a large wash- bottle partly filled with cold water (to absorb HC1 evolved), a safety-tube being provided to prevent the water being sucked back. The alcohol is then slowly dropped in (about an hour and a half is required), the flask being frequently shaken and care being taken to keep the temperature below - 5. When all the alcohol has been added, the contents of the flask are distilled in vacua (20 mm.) from an oil-bath at 140. The dimethyl sulphate which passes over is washed with a little ice-water, and then dried with anhydrous sodium sulphate. It is then pure enough for all practical purposes. It forms a colourless liquid which boils at 188 at atmospheric pressure. 1 A. 327, 105. 2 Archives fur Experim. Pathologic u. Pharmakologie, 47, 115. 127. 184 PREPARATION OF ORGANIC COMPOUNDS The potassium salts of the monoaryl sulphuric esters are prepared by the action of potassium pyro- sulphate on the phenols. As the pyrosulphate of commerce often gives very unsatisfactory results, it is advisable to prepare the salt immediately before use by igniting acid potassium sulphate until it has lost exactly the weight demanded by the equation : 2KHSO 4 = K 2 S 2 Q 7 + H 2 O. CHAPTER VIII THE NITRILES OR CYANIDES THE nitriles or cyanides contain the group CN, and are of considerable importance owing to their ready hydrolysis to the corresponding carboxylic acids (see pp.153, 224). They are obtained by the following methods : i. FROM THE ACID AMIDES This method is common to both the aliphatic and aromatic series, the nitrile being formed by heating the amide with a powerful dehydrating agent : R .C/ =RC ^N + H 2 ^NH,, The dehydrating agent most usually chosen is phosphorus pentoxide, the reaction being carried out by distilling the amide with this reagent. Phosphorus pentachloride and thionyl chloride 1 also give good results. PREPARATION OF ACETONITRILE (CH 3 CN). 2 Fifteen grammes of phosphorus pentoxide are transferred to a distilling flask by pushing the neck of the flask through a hole in the cork of the pentoxide bottle, and then shaking in the required weight. Ten grammes of dry, finely powdered acetamide are added and well mixed by shaking. The whole is then cautiously distilled (the reaction becomes violent if the heating is too rapid) until nothing more passes over. The distillate is treated with about half its volume of water, solid potassium 1 A. 274, 312. 2 A. 64, 332. 185 1 86 PREPARATION OF ORGANIC COMPOUNDS carbonate added until no more dissolves, the layer of nitrile separated from the aqueous solution and finally redistilled over phosphorus pentoxide. It forms a colourless liquid boiling at 82. The yield is about 95 per cent. 2. FROM THE HALOGEN COMPOUNDS This method is confined to compounds containing aliphatic halogen atoms, and consists in treating them with potassium cyanide. Occasionally the re- action is carried out in aqueous solution, but as a rule alcohol is used as a solvent. Although in some cases the exchange takes place at the ordinary temperature, it is usually necessary to boil the mixture under a reflux condenser for some time or, in more obstinate cases, to heat under pressure. PREPARATION OF ETHYLENE CYANIDE (SUCCINO- NITRILE) (CHgCN.CHjsCN). 1 One hundred grammes of ethylene bromide are dissolved in 150 c.c. of alcohol, and the mixture boiled under a reflux condenser. A cold, concentrated, aqueous solution of 670 grm. of potassium cyanide is then run in drop by drop during two hours. After cooling, the liquid is filtered or decanted from the precipitated potassium bromide and evaporated on the water-bath in vacua. The residue is taken up with alcohol, again evaporated in vacuo on the water-bath, and the residue fractionated. The ethylene cyanide forms a colourless liquid which boils at 147 at 10 mm. The yield is 70 to 80 per cent. In all cases where nitriles are being prepared from halogen compounds and potassium cyanide by double decomposition, the potassium halide formed during the reaction tends to form a coating round the potas- sium cyanide, and thus prevent further action. In order to avoid this, the cyanide is added very slowly as a concentrated aqueous solution, or in the form of a very fine powder. In the preparation of malonic ester (p. 154), cyanacetic acid is formed as an inter- mediate product although not isolated. Instead of the halogen compound the sulphate can be used, i Bl. [2] 50, 214. THE NITRILES OR CYANIDES 187 PREPARATION OF ACETONITRILE (CH 3 CN).i One gramme-molecule (65 grm.) of powdered potassium cyanide is dissolved as far as possible in 50 to 60 c.c. of water, and to the cold solution one molecule (126 grm.) of dimethyl sulphate is added in three portions, the whole being vigorously shaken and cooled under the tap after each addition. (N.B. As dimethyl sulphate is very poisonous, great care must be taken to avoid inhaling any of its vapour (see p. 183). The milky liquid thus obtained is then distilled from the water- bath until the temperature reaches 82. The contents of the flask (which must be a large one owing to frothing) are then cooled, another 65 grm. of potassium cyanide added slowly, and the whole very cautiously distilled from the water-bath. A violent reaction sets in, and when this has modified the dis- tillation is continued until the contents of the flask become solid and nothing more passes over. The acetonitrile is purified as described on p. 185. The yield is almost quanti- tative. 3. FROM THE DIAZO-COMPOUNDS This is the method most frequently used in pre- paring aromatic nitriles. The exchange can be brought about in two ways : (a) according to Sandmeyer the diazo-solution is slowly run into hot potassium cuprous cyanide solution, and the whole then heated on the water-bath until no more nitrogen is evolved ; or (b) according to Gattermann 2 the diazo-solution is treated with sulphuric acid and potassium cyanide, and copper powder then added, the details of the method being exactly similar to those given on p. 76 for iodo- benzene and on p. 77 for bromobenzene, with the exception, of course, that the iodide or bromide is replaced by an equivalent amount of cyanide. PREPARATION OF BENZONITRILE (C 6 H 5 CN). 3 A solution of potassium cuprous cyanide, 2CuCN.KCN, is prepared by adding 28 grm. of potassium cyanide to a hot solution of 25 grm. of crystallised copper sulphate in 150 c.c. of water, the whole being heated until the precipitate at first formed has redissolved. (N.B. As cyanogen is evolved, this i B. 40, 3215. 2 B. 23, 1218. 3 B. 17, 2653. 1 88 PREPARATION OF ORGANIC COMPOUNDS reaction must be carried out in an efficient draught chamber.) The solution thus obtained is heated to 90 under a reflux condenser, and a solution obtained by diazotising 9-3 grm. of aniline in the usual way (p. 238), slowly run in, the whole being well shaken at frequent intervals. When all the diazo-chloride has been added, the whole is heated on the water-bath until no more nitrogen is evolved, and then distilled in steam. The distillate is extracted with ether, the ethereal solution washed with dilute caustic soda and dilute sulphuric acid, dried with calcium chloride, and then fractionated. The benzonitrile passes over as a colourless oil boiling at 191, and smelling rather like nitrobenzene. The yield is about 60 per cent. 4. BY THE ADDITION OF HYDROCYANIC ACID TO ALDEHYDES AND KETONES This reaction leads to oxy-nitriles (cyanhydrins) : H H R.C/ + HCN = R.C/-CN X \OH and is best carried out by acting on the bisulphite compounds with potassium cyanide. 1 PREPARATION OF MANDELONITRILE (C 6 H 5 .CHOH.CN) . 2 Fifteen grammes of benzaldehyde are shaken with 50 c.c. of saturated sodium bisulphite solution. After standing for some time the crystalline bisulphite compound is filtered off, washed, first with a little cold water and then with alcohol and ether. The crystals are ground up to a thin meal with water, a cold, concentrated, aqueous solution of potassium cyanide (12 grm.) added, and the whole well shaken. The nitrile separates out as an oil and is collected and washed with water. The yield is almost theoretical. PREPARATION OF ACETONE CYANHYDRIN 3 (Me 2 C (OH) CN). Acetone (one molecule) is shaken with saturated sodium bisulphite solution (one molecule), and, after cooling, a cold saturated solution of potassium cyanide (ij molecules) is slowly added. The crystalline bisulphite compound soon 1 B. 39, 1224 ; D.R.P. 85,230. 2 Loc. cit. 3 B. 39, 1225, 1857; R. 28, 10. THE NITRILES OR CYANIDES 189 passes into solution and is replaced by a fluorescent oil. This is extracted several times with ether, the ethereal extracts shaken with saturated bisulphite solution (to remove acetone) and then washed with saturated salt solution. The ether is evaporated, and the residual oil dried in a vacuum desiccator over concentrated sulphuric acid. Pure acetone cyanhydrin forms a colourless, odourless liquid which boils at 82 at 23 mm. As obtained above it is usually of a yellow colour. The yield is 96 per cent. Strecker 1 showed that aldehyde-ammonias react with hydrocyanic acid to give amino-nitriles : H ^ R.C^-OH + HCN = R.C^CN + H 2 O X NH 2 \NH 2 Tiemann 2 found that the two steps of the synthesis could be carried out in the reverse order : R.C^CN + NH 3 - R.C^-CN \OH \NH Both these methods, however, suffer from the dis- advantage of necessitating the use of concentrated hydrocyanic acid. This can be avoided and both steps carried out in one operation by treating the aldehyde or ketone with ammonium cyanide 3 or an equimolecular mixture of potassium cyanide and ammonium chloride. The condensation is usually carried out in aqueous or aqueous alcoholic solu- tion. A very important modification of this method is due to Bucherer 4 and Kncevenagel. 6 They found 1 A. 75, 27 ; 176, 341 ; 211, 359; B. 37, 1809. 2 B. 13, 381. 3 B. 39, 1722. 4 D,R,P, 157,710, 157,909, 158,090, 158,346; B. 39, 989; 2796, 5 6.37,4059,4073,4087, igo PREPARATION OF ORGANIC COMPOUNDS that secondary amino-nitriles of the general formula /CN RR'C\ , where R is an alkyl or aryl group, X NHAr R' an alkyl or aryl group or a hydrogen atom, and Ar an aryl group, are produced when aldehydes or ketones are acted upon by primary aromatic amines and potas- sium cyanide. The reaction takes place with greater ease if the aldehyde or ketone is first converted into its bisulphite compound by treatment with sodium bisulphite : R .COH + KCN + ArNH 2 = R .C-NHAr + KNaSO 3 +H 2 O. \SO 3 Na X CN PREPARATION OF o.- CARBOXYPHENYL - AMINO - AGETONITRILE, C 6 H 4 ^ ( ^ 2CN . (a)i Seven grammes of finely powdered potassium cyanide and 14 grm. of finely powdered anthranilic acid are suspended in 50 c.c. of ether or benzene in a flask fitted with a reflux condenser. The whole is well cooled with ice or a freezing mixture, and 7-5 c.c. of technical, 40 per cent, formaldehyde added slowly. A brisk reaction sets in and two layers are formed, the lower of which solidifies on cooling to a mass of crystals of the potas- sium salt of the required acid. This is collected, dissolved in water, and acidified with acetic or hydrochloric acid. The free acid separates out and is filtered off, washed with cold water, and recrystallised. It separates from alcohol (3 parts) in glittering leaflets, and from benzene or chloroform in long needles. M.P. i8i-i83. Yield almost quantitative. (fr) 2 Twenty cubic centimetres of technical, 40 per cent. sodium bisulphite solution and 7-5 c.c. of technical, 40 per cent, formaldehyde are mixed, and the mixture warmed to 6o-7o until the smell of formaldehyde has vanished (about 20 minutes). A solution of 14 grm. of anthranilic acid in exactly the equivalent amount of concentrated caustic soda is then added, and the whole heated on the water -bath until no more anthranilic acid is present (about 45 minutes). The * D.R.P. 157,710; B. 39, 989; J-pr. [2] 63, 392. 1 D.R.P. 157,909; B. 39, 2807. THE NITRILES OR CYANIDES 191 reaction is followed by withdrawing a sample from time to time, acidifying it with excess of acetic acid, and adding a few drops of sodium nitrite to the well-cooled mixture. Anthranilic acid, if still present, is thus converted into a diazo-salt, which when poured into an alkaline solution of R-salt gives a red azo-colour. When a sample thus tested gives only a very slight coloration, a solution of 7 grm. of potassium cyanide in 25 c.c. of water is added, and the whole heated to 7O-8o for 20 minutes. After cooling, the whole is made strongly acid with concentrated acetic acid and the nitrile filtered off and purified as before. Yield almost quantitative. /OH ,.,,*,.- r Vr _ r -R [i]NH.CH t .OSO,Na U6l4 [2]COOH "* \ 2 = ^ 8l4 [2]COOH \O.SO 2 Na [i]NH.CH 2 .O.S0 2 Na [i]NH.CH 2 .CN C H4 [2]COOH CeH4 [2]COOH The above synthesis is of considerable importance as the acid obtained is the nitrile of phenylglycine-o.- carboxylic acid, into which it passes on hydrolysis (boiling with hydrochloric acid). Phenylglycine-o.- carboxylic acid, of course, is important as it gives indigo on fusion with alkalis. 5. BY THE ADDITION OF HYDROCYANIC ACID TO THE QUINONES The quinones readily react with two molecules of hydrocyanic acid, but in a different way from the ketones, the product being a 2.3-dinitrilo-hydroquinone : O OH OH /\ 2 + 2HCN \~-CN j CN \/ II I O OH OH A molecule of the quinone is simultaneously reduced to hydroquinone. 192 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF DICYANO-HYDROQUINONE (HO) 2 C 6 H 2 (CN) 2 . 1 Twenty grammes of />.-benzoquinone are dissolved in 60 c.c. of alcohol, and a cold mixture of 25 c.c. of concentrated sulphuric acid and 50 c.c. of alcohol added. The mixture is well cooled, and a concentrated solution of potassium cyanide slowly run in until a green fluorescence appears and the liquid reacts alkaline. The whole is then acidified with sulphuric acid and the alcohol removed by distillation in vacuo from the water-bath. The residue is washed with water, and then recrystallised from hot water with the addition of animal charcoal. It crystallises in pale yellow leaflets which contain two molecules of water. On heating, it decolorises at about 230. Its neutral solution fluoresces blue, its acid solution violet, and its alkaline solution green. 1 B. 33, 675; D.R.P. 117,005. CHAPTER IX THE NITROSO- (AND *so-NITROSO-) AND NITRO-COMPOUNDS THE NITROSO-COMPOUNDS THE nitroso-compounds are obtained : i. BY THE OXIDATION OF THE ALIPHATIC AMINES (R 3 C.NH 2 ) OR OF THE AROMATIC AMINES (ArNH 2 ). The oxidising agent chiefly used is monopersulphuric acid (Caro's acid). This is prepared from potassium or ammonium persulphate and sulphuric acid as follows : Eighteen parts of finely powdered potassium per- sulphate, or an equivalent amount of the ammonium salt, are slowly added (during an hour) to 20 parts of cold concentrated sulphuric acid, the whole being well stirred, and the stirring continued for half an hour after the whole of the persulphate has been added. Care must be taken not to allow any rise in temperature. The whole is then slowly poured into 80 to 100 parts of ice-water and either directly used or it is first neutralised with anhydrous sodium carbonate. The solution must not react alkaline. If it is desired to preserve the reagent, the concentrated acid is not poured into water, but is rubbed up to a dry powder with 60 grm. of potassium sulphate and then kept in well-stoppered bottles. It is, however, best to prepare the reagent directly before use. The active oxygen in the solution is estimated either by adding a known excess of ferrous sulphate and then titrating the excess of ferrous salt with permanganate, or excess of 193 13 194 PREPARATION OF ORGANIC COMPOUNDS oxalic acid is added and the excess titrated in the presence of silver sulphate : * K 2 S 2 8 + H 2 S0 4 + H 2 = K 2 S0 4 + H 2 SO 4 + H 2 SO 5 . PREPARATION OF NITROSOBENZENE (C 6 H 6 NO). 2 Three grammes of aniline dissolved in 150 c.c. of water are added to the calculated volume of a neutral solution of Caro's acid, prepared as described above. The nitrosobenzene separates out, and is collected, washed with a little water, and then steam-distilled. Colourless or yellow crystals melting at 68. It is green when fused or dissolved. PREPARATION OF w.-NITRO-NITROSOBENZENE (C 6 H 4 (NO)NO 2 ) . 3 Twenty grammes of finely powdered m.-nitraniline are suspended in 1500 c.c. cold water. A neutralised solution of Caro's acid, prepared as above and containing 4-7 grm. of active oxygen (about 90 grm. of persulphate will be required), is then added and the whole well stirred for half an hour. The precipitate is then collected, washed, and steam-distilled in small portions (not more than 3 grm. at a time as otherwise decomposition will take place). It forms colourless needles melting at 90. The yield is about 80 per cent. 2. BY THE OXIDATION OF THE HYDROXYL- AMINES. The aliphatic hydroxylamines are best oxidised with potassium bichromate and sulphuric acid, whereas in the aromatic series ferric chloride is the best oxidising agent. PREPARATION OF m.-DINITROSOBENZENE (C 6 H 4 (NO) 2 ). 4 Five grammes of ra.-dinitrobenzene are dissolved in 50 c.c. of alcohol containing 6 c.c. of glacial acetic acid. Two grammes of zinc dust are then slowly added, the tempera- ture being kept below o by means of a freezing mixture. When the greater part of the zinc has gone into solution, too c.c. of water and then 200 c.c. of a 10 per cent, ferric 1 B. 38, 3965- 2 D.R.P. 105,875, 110,249, 110,575, 110,578. 3 B. 36, 3800. " 4 B. 38, 1899. THE NITROSO- AND NITRO-COMPOUNDS 195 chloride solution are added, and the whole at once steam distilled. The first 20 c.c. of distillate are collected, and on standing soon precipitate a yellow powder, melting at 146 to a green liquid. C 6 H 4 (N0 2 ) 2 + 8H = C 6 H 4 (NHOH) 2 + 2 H 2 O. C 6 H 4 (NHOH) 2 + 20 = C 6 H 4 (NO) 2 + 2H 2 O. 3. BY THE ADDITION OF N 2 O 3 OR NOC1. Nitrosyl chloride and nitrogen trioxide both add on to double bonds, the former giving a chloronitroso- compound and the latter a nitrosite, e.g. Me 2 C(ONO) . CMeHNO. PREPARATION OF TRIMETHYLETHYLENE NITROSITE (Me 3 C(ONO) CMeHNO). 1 Twenty grammes of trimethyl- ethylene (so-amylene) are dissolved in 60 c.c. of ether, and the whole cooled to o. A stream of moist nitrogen trioxide (obtained by the action of 80 c.c. of nitric acid of density 1-43 on 1 20 grm. of arsenious acid) is then led into the solution. The gas is absorbed with considerable evolution of heat, and care must be taken that the temperature does not rise above 10. When no more gas is absorbed and the smell of trimethyl- ethylene has practically vanished, the reaction is stopped, and excess of nitrous acid removed from the ethereal solution by washing ten or twelve times with water. The ethereal solution, which should now have a pure blue and not a greenish blue colour, is dried with sodium sulphate, and the ether removed by distillation from as cool a water -bath as possible, the flask being continually shaken during the distillation. A blue liquid remains which is freed from traces of ether and trimethylethylene by placing in a vacuum desiccator over solid potash and sulphuric acid. The yield is 35 grm., but the substance is not quite pure. It is purified by allowing it to stand at the room temperature for a day or two, when it changes into a crystalline polymer (colourless needles). This is washed with ether and then depolymerised by heating for a short time to 75. 4. THE NITROSO-PHENOLS (which are identical with the quinone monoximes) and the AROMATIC i B. 35, 2327, 2978, 4120 ; 36, 1765. 196 PREPARATION OF ORGANIC COMPOUNDS NITROSO-TERTIARY AMINES are obtained by the action of nitrous acid on the phenols or on the tertiary bases. The nitroso-group takes the para- position in both cases. Monohydric phenols only give mono- nitroso-compounds, but dihydric phenols give dinitroso- compounds. The action of nitrous acid on a-naphthol leads to a mixture of a- and /5-nitroso-a-naphthols, the nitroso-group entering the o.- and p.- positions. /3-Naphthol gives only i-nitroso-2-naphthol. The nitroso-phenols can also be obtained by heating the nitroso-tertiary bases with alkali. PREPARATION OF .-NITROSOPHENOL (NOC 6 H 4 OH). (a) 1 Ten grammes of phenol and 40 grin, of potassium nitrite are dissolved in two litres of ice- water, and then 25 grm. of glacial acetic acid diluted with ten volumes of water slowly added with continual stirring. The whole is allowed to stand over-night, and then filtered and extracted with ether. On shaking the ethereal extract with concentrated caustic soda solution brown needles of sodium nitrosophenate separate. These are collected and spread on a porous plate until the whole of the adhering liquid has been absorbed. They are then dissolved in a little water and decomposed with dilute sulphuric acid. The precipitated nitroso-phenol is collected, washed, dissolved as rapidly as possible in a little boiling water, the solution filtered hot, cooled, and finally extracted with ether. On removing the ether by distillation, nitroso- phenol is left in a pure state. Rhombic crystals melting at 125. The yield is almost quantitative. (b) 2 One hundred grammes of 3 per cent, caustic soda solution are boiled under a reflux condenser, and 2 grm. of ^.-nitrosodimethylaniline hydrochloride added little by little, time being allowed after each addition for practically all the oil which separates to disappear. After all the p.- nitrosodimethylaniline has been added, the boiling is continued until the solution becomes reddish yellow in colour. It is then cooled in ice, made faintly acid with dilute sulphuric acid and extracted with ether. On evapo- rating the ether the nitrosophenol remains as a mass of crystals. The nitrosophenol obtained by these two methods is identical i B. 7, 967 ; A. 277, 85. 2 B. 7, 809. THE NITROSO- AND NITRO-COMPOUNDS 197 with the quinone monoxime obtained by boiling quinone with one molecule of hydroxylamine hydrochloride. PREPARATION OF 2.4-DINITROSORESORCINOL (Fast Green O). 1 Ten grammes of resorcinol are dissolved in 250 c.c. of water containing n grm. of concentrated sulphuric acid. Ice is then added until the temperature has fallen to o. A solution of 13 grm. of sodium nitrite in 100 c.c. of water is then slowly added with continual stirring, more ice being added from time to time so as to keep the temperature below 8. The solution, which should be faintly acid in reaction, is allowed to stand for an hour and then filtered. The precipitate is washed with ice-water and then dried on a porous plate. Greyish brown powder. Yield 18 grm. It dyes cotton or wool green on an iron mordant. OH or NO N.OH PREPARATION OF .-NITROSO-DIMETHYLANILINE HYDROCHLORIDE (NO . C 6 H 4 NMe 2 HCl) . 2 One hundred grammes of dimethylaniline are dissolved in 350 c.c. of con- centrated hydrochloric acid, and ice added to the solution until the temperature falls below o. A cold concentrated solution of 60 grm. of sodium nitrite is then slowly run in with continual stirring, the temperature being kept below 8. When all the nitrite has been added, the whole is allowed to stand for an hour and then filtered, and the precipitate washed with dilute hydrochloric acid and dried. Yellow needles melting at 177. Yield about 90 per cent. 5. THE NITROSAMINES. The nitrosamines con- tain the group R 2 N.NO, and are obtained by the action of nitrous acid on the secondary amines. 1 Schultz, " Chemie des Steinkoklenteers " (1901), II. 242. 2 B. 12, 523. 198 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF DIPHENYL -NITROSAMINE (C a H 5 ) 2 N.NO. 1 Thirty-four grammes of diphenylamine are dissolved in 150 c.c. of warm alcohol, and the solution then cooled to the ordinary temperature. Sixteen cubic centi- metres of pure concentrated hydrochloric acid are added, and then a solution of 14 grm. of sodium nitrite in 250 c.c. of water is slowly run in, the whole being well stirred and cooled in ice or a freezing mixture. After the whole of the nitrite has been added the solution is allowed to stand for one hour in a freezing mixture and then filtered, and the precipitate washed with a large quantity of cold water. It is finally recrystallised from alcohol or petroleum ether and dried between filter-paper. Pale yellow leaflets melting at 165. Yield 75 per cent. 6. THE wo-NITROSO - COMPOUNDS. The iso- nitroso compounds are the monoximes of the a-diketones and are obtained by the action of nitrous acid on those ke tones which contain the group CH 2 CO . PREPARATION OF iso - NITROSOCAMPHOR, 2 ,CO One hundred and two grammes of cam- = NOH. phor are dissolved in 500 c.c. of dry ether, and 15 grm. of sodium wire added. The flask, which should be a large one, is well cooled in ice-water or a freezing mixture. A small quantity of amyl nitrite is then added, when the solution becomes yellow and some frothing takes place. Once the reaction has started, the amyl nitrite (78 grm. in all are required) can be added more rapidly, but the flask must be kept well cooled and must be vigorously shaken after each addition of the nitrite. When all the nitrite has been added, the whole is allowed to stand for an hour, when part of the sodium iso-nitrosocamphor will separate out. At the end of this time the whole contents of the flask are slowly poured into ice-water (take care that there is no unchanged sodium left !) and the ethereal layer removed. The reddish yellow aqueous solution is extracted several times with ether in order to remove borneol and unchanged camphor, and is then freed from dissolved ether by blowing air through it for a short time. The iso- * B. 33, 1026. 2 A. 274, 73. THE NITROSO- AND NITRO-COMPOUNDS 199 nitrosocamphor is finally thrown down by adding dilute acetic acid until no more precipitation takes place. The yield is about 40 grm., and the compound is usually sufficiently pure for the preparation of camphor quinone (p. 130). It may be further purified by recrystallising several times from petroleum ether and benzene, or from dilute methyl alcohol. The pure compound melts at 152-! 54. THE NITRO-COMPOUNDS THE ALIPHATIC NITRO-COMPOUNDS (a) DIRECT NITRATION. Concentrated nitric acid usually either does not attack or completely destroys fatty hydrocarbons, but the higher paraffins and naphthenes can be nitrated by prolonged heating with a 20 per cent, acid under pressure. The yields, however, are poor, owing to oxidation. Dilute nitric acid also nitrates the benzene hydrocarbons in the side- chain, the nucleus being unattacked. According to a recent patent, 1 nitrophenyl-nitromethane and its derivatives are readily obtained by heating nitro- toluene, &c., with 40 to 90 per cent, nitric acid in open vessels. PREPARATION OF PHENYLNITROMETHANE (o>- NITROTOLUENE) (C 6 H 5 CH 2 NO 2 ) . 2 Twenty grammes of toluene and 120 c.c. of 13 per cent, nitric acid are heated for five hours in a sealed tube to io5-io8. The product is made alkaline with caustic potash, and unchanged toluene removed by extraction with ether. The alkaline solution of sodium phenylnitromethane (Ph . CH = NO 2 Na) is then decom- posed by saturating with carbon dioxide. The liberated nitro-compound is extracted with ether, the ethereal solution dried with calcium chloride, and the ether distilled off from the water-bath. The residual yellow oil is fractionated under reduced pressure. The phenyl nitromethane passes over as a colourless liquid boiling at 141 at 35 mm. (b) BY THE REPLACEMENT OF HALOGEN. Methyl iodide when treated with silver nitrite gives i E. P. 6076 11 . a B. 28, 1861. 200 PREPARATION OF ORGANIC COMPOUNDS nitrome thane, but the higher alkyl halides give a mixture of the nitro -hydrocarbon and nitrous ester, the latter in increasing quantity as the molecular weight of the alkyl radical increases. When sodium nitrite acts on the alkyl halides, only nitrous esters, R.ONO, are obtained, but with halogen fatty acids the nitro - acid is produced, and this readily loses carbon dioxide to form the nitro -hydrocarbon, e.g. : NaNO 2 H 2 O CH 2 ClCOONa -* CH 2 NO 2 . COONa NaHCO 3 + CH 3 NO 2 . PREPARATION OF NITROMETHANE (CH 3 NO 2 ).i Five hundred grammes of chloracetic acid are dissolved in i litre of water, carefully neutralised with solid sodium carbonate, and 300 grm. of sodium nitrite in 500 c.c. of water added. About 300 c.c. of the solution thus obtained are placed in a 2-litre flask provided with a condenser, and heated to boiling. The rest of the solution is then slowly run in from a tap funnel at such a rate that oily drops are always seen in the condenser (about 2 J- hours will be required) . The liquid in the flask assumes a dark red colour, and a colourless oil collects in the receiver, which should consist of an apparatus as described on p. 25 (if this is not used the receiver must be changed frequently), and the oil separated from the aqueous part of the distillate. The distillation should be continued until 250 c.c. of liquid have been collected after no more oily drops are visible in the condenser. The aqueous part of the distillate is then redistilled with the addition of common salt (35 grm. to every 100 c.c.). The distillation is carried on until two-thirds of the liquid have passed over, the oil being continually separated as before. The aqueous part of the distillate is then again distilled with salt, and this process continued until no more oil can be obtained. Finally all the yields of oil are united, dehydrated with calcium chloride, and distilled. Practically the whole passes over at 101. Yield about 25 per cent. THE AROMATIC NITRO-COMPOUNDS The only method of any practical importance for the preparation of aromatic nitro-compounds is direct nitration with nitric acid. Amino-compounds, phenols, i B. 42, 3438. THE NITROSO- AND NITRO-COMPOUNDS 201 &c., which are very sensitive to oxidation, must first be protected by replacing one of the amino- or phenolic hydrogen atoms. This is best done by preparing an ester (of the phenol) or an anilide (see p. 228). The amino-compounds can also be converted into the benzylidene derivative by means of benzaldehyde (see pp. 115, 233). NITRIC ACID ALONE. Concentrated nitric acid often contains nitrous fumes which sometimes have a deleterious action. They can be destroyed by heating the acid with a little urea : CO(NH 2 ) 2 + 2HN0 2 = CO 2 + 3H 2 O + 2N 2 . This treatment, however, is not usually necessary. PREPARATION OF o.- AND /.-NITROPHENOL (C 6 H 4 (OH)NO 2 ). Fifty grammes of phenol are slowly added to 275 c.c. of nitric acid (D = i-n),the whole being well cooled with water. After each addition of phenol the flask must be well shaken. The solution becomes very dark in colour and an oily mass separates out. After all the phenol has been added the whole is allowed to stand for twelve hours. The supernatant acid is then poured off, the residue washed several times by decantation and then steam- distilled. o.-Nitrophenol passes over in the pure state and solidifies in the receiver to yellow needles melting at 45. Yield 15 to 20 grm. The residue in the flask is boiled with dilute caustic soda, filtered, the filtrate boiled for a short time with animal charcoal, refiltered, and then concentrated to a small volume. After cooling, concentrated caustic soda solution is added, which causes the sodium salt of p.-mtro- phenol to separate as yellow crystals. These are filtered off (use glass-wool), dissolved in cold water, the solution filtered, acidified with concentrated hydrochloric acid, and the pre- cipitated p.-nitrophenol recrystallised from boiling water to which a few drops of concentrated hydrochloric acid have been added. Colourless needles melting at 114. Yield about 15 NITRIC ACID AND AN ORGANIC SOLVENT. The solvents used may be divided into two classes, viz. : (a) solvents immiscible with nitric acid ; (b) solvents 202 PREPARATION OF ORGANIC COMPOUNDS miscible with nitric acid. Examples of the former are carbon tetrachloride, paraffins, and with dilute nitric acid, benzene. During the nitration the solu- tion must be kept violently agitated, and the nitric acid is always added to the solution of the substance to be nitrated. The method is seldom employed, but is sometimes useful with substances which are readily oxidised, as the solvent to some extent protects the nitrated compound from further action of the acid. As solvents of the second class glacial acetic acid and sulphuric acid are by far the most common. The latter is dealt with in the next section under "mixed acids." PREPARATION OF s.s'-DINITROCARBAZOLE. 1 Twenty grammes of carbazole are dissolved in 100 c.c. of glacial acetic acid, and the solution then heated to 80. At this temperature 26 grm. of nitric acid (D = 1-38) are slowly added, the whole being well stirred. When all the acid has been added the solution is heated to 100 for about half an hour and then allowed to cool. The dinitro carbazole separates out and is collected. NO, N0 2 MIXED ACIDS. A mixture of nitric and concen- trated sulphuric acids is the most commonly employed nitrating agent. The proportions in which the acids are used vary to a considerable extent, but i part of nitric acid (D = 1-4) to about i parts of concen- trated sulphuric acid is an average proportion. Excel- lent results are sometimes obtained by adding the nitric acid in the form of one of its salts, usually as potassium nitrate. Considerable heat is evolved when nitric acid is added to concentrated sulphuric acid, and the former must, therefore, be added slowly to the latter. 1 D.R.P. 46,438, 128,853. THE NITROSO- AND NITRO-COMPOUNDS 203 PREPARATION OF NITROBENZENE (C 6 H 5 NO 2 ). Sixty- three grammes of nitric acid (D = 1-4) are slowly added to 50 c.c. of concentrated sulphuric acid, and the mixture, after cooling, slowly run into 50 grm. of benzene. During this addition the flask must be well shaken and the temperature must not exceed 25. When all the acid has been added and no further rise in temperature takes place, the whole is heated on the water-bath to 60 for one hour under a reflux condenser. After cooling, the upper layer of nitrobenzene is separated, well washed, first with water, then with dilute sodium carbonate, and finally again with water. It is then dehydrated over calcium chloride and distilled. A little unchanged benzene passes over first, but the greater part of the liquid passes over at 2o6-2O7. It forms a pale yellow oil with a smell of bitter almonds. PREPARATION OF m.-DINITROBENZENE (C 6 H 4 (NO 2 ) 2 ). Twenty grammes of nitrobenzene are slowly added to a mixture of 20 c.c. of fuming nitric acid (D = 1-5) and 20 c.c. of con- centrated sulphuric acid. The whole is then heated on the water-bath until a completely hard and solid yellow precipi- tate is obtained on adding a few drops to a test-tube of cold water. Without cooling, the whole is then poured into a large volume of cold water, the precipitate filtered off, washed, and recrystallised from alcohol. Long colourless needles melting at 90. Yield almost quantitative. PREPARATION OF a -NITRON APHTHALENE (C 10 H 7 NO 2 ). Fifty grammes of finely powdered naphthalene are slowly added to a mixture of 30 c.c. of nitric acid (D = 1-4) and 30 c.c. of concentrated sulphuric acid, the temperature being kept at 40-5o. When all the naphthalene has been added, the whole is heated to 60 and then poured into cold water. The precipitated nitronaphthalene is collected, boiled up with water, and the water poured off from the molten substance. It is then steam-distilled until no more unchanged naphthalene passes over. The residue while still hot is poured on to crushed ice or into a large bulk of cold water. The nitro- naphthalene is filtered off and recrystallised from spirit. Long yellow needles. M.P. 61. Yield about 90 per cent. PREPARATION OF 2-NITROBENZIDINE (NH 2 [ 4 ]C 6 H 4 [i][i']C 6 H 4 [2']NO 2 [4']NH 2 ).i Twenty-eight grammes of pure 1 B. 23, 796. 204 PREPARATION OF ORGANIC COMPOUNDS benzidine sulphate are added to 300 grm. of pure concentrated sulphuric acid and the whole well stirred. If necessary, solution is completed by warming to 5o-6o. The solution is then cooled to io-2O (the temperature must not fall below 10). At this temperature 10 grm. of potassium nitrate are slowly added, and the stirring continued for some hours. The solution is poured into a litre of cold water, and the precipitated nitrobenzidine sulphate filtered off and re- crystallised from boiling water in the presence of animal char- coal. By using double the amount of potassium nitrate 2-2'- dinitrobenzidine is obtained. PREPARATION OF m.-NITROBENZOIC ACID (C 6 H 4 [i] COOH[3]NO 2 ). Fifty grammes of benzoic acid, which have been dehydrated by fusing, are intimately mixed with 100 grm. of potassium nitrate. The mixture is then slowly added to 150 grm. of concentrated sulphuric acid, the whole being well stirred. When all has been added, the mixture is gently warmed until the nitrated acid separates out as an oily layer. This solidifies on cooling and is removed and roughly purified by twice melting it with water. It is then steam-dis- tilled to remove unchanged benzoic acid, and the residue dissolved in about twenty times its weight of boiling water. The solution is made slightly alkaline with hot concentrated baryta water and then cooled. The barium salt of the meta- nitro-acid separates out, the ortho- and para- acids remaining in solution. It is collected, washed, and decomposed with hydrochloric acid. The precipitated m.-nitrobenzoic acid is filtered off, washed, and dissolved in sodium carbonate solution. The solution is freed from suspended barium sulphate by filtration, the w.-nitrobenzoic acid precipitated by hydro- chloric acid, and recrystallised from water. It melts at 141. Yield 45 per cent. PREPARATION OF I-CHLOR-2.4-DINITROBENZENE. Chlorobenzene is boiled with excess of concentrated nitric acid (D = i -5) or is heated with mixed acids until a sample gives a completely solid precipitated with water. The whole is then poured into water or crushed ice, and the solid collected, washed, and recrystallised from alcohol. It melts at 38. PREPARATION OF /.-NITRANILINE (C 6 H 4 [i]NH 2 1 One hundred grammes of acetanilide are dissolved 1 B. 17, 262. THE NITROSO- AND NITRO-COMPOUNDS 205 in 100 grm. of hot glacial acetic acid, and the solution, after cooling, mixed with 400 grm. of concentrated sulphuric acid. The whole is well cooled in a freezing mixture, and a cold mixture of 59 grm. of nitric acid (D = 1-48) and 120 grm. of concentrated sulphuric acid slowly run in with stirring. After standing for a time the whole is poured on to crushed ice, the precipitated p.-nitroacetanilide filtered off, washed, and recrystallised from water or dilute alcohol. Yield 95 per cent. M.P. 207. To convert this into ^.-nitraniline, it is boiled under a reflux condenser with 2^- parts of concentrated hydrochloric acid or 25 per cent, sulphuric acid until the whole dissolves. The solution is then made alkaline with caustic soda or ammonia, and on cooling, the nitraniline crystallises out. It is filtered off, washed, and recrystallised from boiling water. Yellow needles. M.P. 147. Yield about 90 per cent. PREPARATION OF NAPHTHOL YELLOW S. 1 One hundred grammes of a-naphthol are finely powdered and slowly added to 225 c.c. of concentrated sulphuric acid at 100 C. The temperature is then raised to 120, and kept at that point for three to four hours. The mixture is poured into 600 c.c. of water and stirred until the temperature has reached 30. At this point 145 c.c. of concentrated nitric acid are slowly run in, care being taken that the temperature does not rise above 45. After standing for a time the free acid separates out and is washed with saturated salt solution until free from acid. It is then mixed with boiling water, and potassium car- bonate added until a permanent alkaline reaction is obtained. The potassium salt separates out on cooling and is filtered off. It forms an orange-yellow powder which dyes wool or silk from an acid bath. OK K0 3 S N0 2 Naphthol Yellow S When sulphonic acids are nitrated it often happens that the sulphonic acid group is replaced by the nitro- group. 1 Cain and Thorpe, " Synthetic Dyestuffs," p. 226. 206 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF PICRIC ACID (2.4.6-TRINITRO- PHENOL) . Fifty grammes of phenol are heated with an equal weight of concentrated sulphuric acid until a clear solution of phenol sulphonic acid is obtained. After cooling, the solution is poured into half its volume of water, well cooled, and then slowly run into 140 c.c. of concentrated nitric acid. During this operation, which should be carried out in a large flask, the whole must be well cooled and shaken. Oxides of nitrogen and considerable heat are evolved. When all the phenol sulphonic acid has been run in, 53 c.c. of fuming nitric acid (D = 1-5) are added, and the whole heated on the water-bath for two hours. On cooling, the picric acid separates out and, after dilution, is filtered off, washed with cold water, and recrystallised from boiling water. It forms long, pale yellow needles which melt at 122, and explode violently if suddenly heated. It is a strong acid, about as strong as hydrochloric acid, and readily forms metallic salts. As these are exceedingly explosive, especially the salts of the heavy metals, care should be taken not to allow picric acid to remain in contact with metallic substances. ADDENDA THE PICRATES. Some aromatic organic com- pounds, such as the hydrocarbons and naphthols, readily form beautifully crystalline double compounds with picric acid. These are obtained by digesting the hydrocarbon on the water-bath with an aqueous solution of picric acid saturated at the ordinary tem- perature, or by mixing with picric acid in some suitable organic solvent, such as alcohol. They often form a ready means of separating and purifying aromatic hydrocarbons, and have also been used for their estimation. Thus benzene, naphthalene, &c., when digested with concentrated aqueous picric acid which has previously been titrated (baryta water and phenol- phthalem or lacmoid), are quantitatively converted into the picrate. This is then filtered off, and the filtrate re titrated. This is the quantitative estimation of naphthalene in coal gas. The picrates are also very well adapted for recognising compounds which form them, as they crystallise well, have sharp melting- THE NITROSO- AND NITRO-COMPOUNDS 207 points, and the picric acid present can be determined by titration. They are often highly coloured. NITRODIPHENYL METHANES. These can be ob- tained by condensing two molecules of an aromatic nitro-hydrocarbon, nitrophenol, &c., with one molecule of formaldehyde. In the absence of other groups, the condensation takes place in the meta- position to the nitro-group. The condensation is best brought about with concentrated sulphuric acid, and takes place at the ordinary temperature or on gently warming. The reaction is merely an extension of the Lederer-Manasse synthesis discussed on p. 97 : N0 2 N0 2 N0 2 N0 2 /\ H.CHO When preparing a symmetrically constituted body the synthesis is carried out in one step, but unsym- metrical compounds can be obtained by condensing benzyl alcohol or nitrobenzyl alcohol with nitrobenzene, benzene, &c. PREPARATION OF 3.3'-DINITRODIPHENYL METHANE (C 6 H 4 NO 2 ) 2 CH 2 . 1 Twenty-four grammes of nitrobenzene, 120 grm. of concentrated sulphuric acid, and 9 c.c. of 40 per cent, formaldehyde are heated for eight days to 4O-5O. Excess of nitrobenzene is then removed by distillation in steam, and the solid residue collected, washed, and recrystallised from glacial acetic acid. M.P. 174. 1 B. 27, 2322 ; D.R.P. 67,001. CHAPTER X THE AMINO-COMPOUNDS THE amino-compounds may be divided into two groups, viz. the AMINES, R 3 C.NR 2 , and the AMIDES, RCO.NR 2 , where R may be hydrogen, alkyl, aryl, or halogen. Further, the amines may be divided into four groups, viz. primary amines, RNH 2 , secondary amines, NR 2 H, tertiary amines, NR 3 , and quater- nary ammonium bases or their salts, NR 4 OH, these last containing pentavalent nitrogen. The amides form secondary and tertiary compounds, but not ammonium bases. For convenience, the amino-com- pounds will be discussed in the following as primary compounds, secondary compounds, &c. THE PRIMARY COMPOUNDS i. BY THE REDUCTION OF THE NITRO- COMPOUNDS This is by far the most important method of obtaining aromatic primary amines. It does not serve for the preparation of amides, and is of no practical importance in the aliphatic series. A large number of reducing agents may be employed, of which the following are the most important : METAL AND ACID. The metal is usually zinc (dust or granulated), tin, or iron, and the acid, dilute sul- phuric, hydrochloric, or acetic, but hydrochloric acid is most used. In the case of tin, 1 the stannous salt 1 Pure tin is only attacked slowly by hydrochloric acid. This can be remedied by adding a crystal of copper sulphate. 208 THE AMINO-COMPOUNDS 209 is first formed, but this is further acted on, stannic chloride being the final product : Sn + 2HC1 = SnCl 2 + H 2 . SnCl 2 + 2HC1 = SnCl 4 + H 2 . Instead of tin and hydrochloric acid a solution of stannous chloride in hydrochloric acid or in caustic alkali (stannite) is often used, the former being employed in the quantitative estimation of nitro-groups. 1 Tin reducing agents have the disadvantage that the amino- compound often forms a tin chloride double salt which requires further treatment before the free base can be obtained. Iron and hydrochloric acid is the reducing agent used on the large scale, and also gives excellent results in the laboratory. The iron should be used as powder, or as filings which have been sifted to re- move the larger pieces. Theoretically only a very small quantity of hydrochloric acid is required as its action is catalytic, e.g. : + 48HC1 + 8C 6 H 5 NO 2 = 24FeCl 2 + 8C 6 H 5 NH 2 + i6H 2 O. 24FeCl 2 + 4 C 6 H 5 N0 2 + 4H 2 O - i 2 Fe 2 Cl 4 O + 4 C 6 H 5 NH 2 . i2Fe 2 C! 4 O + 9Fe = 3Fe 3 O 4 9 Fe + 4 H 2 + 4C 6 H 5 N0 2 - 4 C 6 H 5 NH 2 + 3Fe 3 O 4 . On the large scale about one-fortieth of that required by the first equation is used, but in the laboratory it is best to employ about one-twentieth, unless it is desired to have all the iron in solution at the end, in which case an excess of acid must be used. PREPARATION OF ANILINE (C 6 H 5 NH 2 ). (a) Fifty grammes of nitrobenzene and 90 grm. of granulated tin are heated on a water-bath in a large flask provided with an inverted air-condenser, and 200 c.c. of technical concentrated hydro- chloric acid added slowly, with continual shaking. Much heat is evolved and the liquid boils. If the reaction becomes too 1 This method is being superseded by Knecht's titanous chloride method- 210 PREPARATION OF ORGANIC COMPOUNDS violent it should be moderated by cooling the flask with water. When all the acid has been added (about half an hour) the whole is heated on the water-bath until the smell of nitro- benzene is no longer noticeable. The contents of the flask are then allowed to cool until the stannic chloride double salt begins to crystallise. Concentrated caustic soda solution is then slowly added until almost all the stannic oxide which is first precipitated is redissolved. The liquid is then steam- distilled until the distillate comes over clear. The lower layer of the distillate is drawn off, and the upper aqueous layer, which contains about 3 per cent, of aniline, saturated with common salt. /On standing, the aniline rises to the surface, and is separated from the brine and added to the first portion of oil. The whole is then distilled. A little water which passes over first is rejected, the aniline itself passing over at 182. Instead of saturating with salt as above the aniline may be extracted with carbon tetrachloride, chloroform, or ether, in which case the solution is dried with anhydrous potassium carbonate and the solvent removed on the water-bath before adding the main portion of the oil. Almost colourless liquid which soon becomes red. Yield about 90 per cent. (b) Sixty grammes of iron powder are shaken with 80 c.c. of hot water and a few drops of nitrobenzene. Five cubic centimetres of concentrated hydrochloric acid are added and then, little by little, 50 grm. of nitrobenzene. After each addition of nitrobenzene the flask is well shaken and cooled with water so that the temperature keeps between 80 and 90. When all the nitrobenzene has been added and no more heat is evolved, the whole is steam-distilled and the aniline collected as above. Owing to the small quantity of acid used there is no need to make the contents of the flask alkaline before steam-distilling off the aniline. Yield about 90 per cent. PREPARATION OF .-PHENYLENEDIAMINE HYDRO- CHLORIDE (NH 2 ) 2 C 6 H 4 2HC1. Seventy grammes of .-nitro- acetanilide and 150 grm. of sifted iron filings are mixed with sufficient water in a large flask to form a thin cream. Twenty cubic centimetres of technical hydrochloric acid are then added, and the whole heated on the water-bath until the reaction sets in (about 90) . The flask is then at once removed from the water-bath and continually shaken until its contents THE AMINO-COMPOUNDS 211 no longer boil. They are then filtered while still hot into a litre of concentrated hydrochloric acid and the iron residue washed once or twice with a little boiling water. The p.- phenylenediamine hydrochloride, which is insoluble in con- centrated hydrochloric acid, separates out from the filtrate, and, after cooling, is collected, washed with concentrated hydro- chloric acid, and dried in the oven. It usually has a pink colour, due to the oxidation of the free base during filtration. This can be avoided by first adding a few cubic centimetres of sodium bisulphite solution. The yield is about 75 per cent. PREPARATION OF a-NAPHTHYLAMINE (C 10 H 7 NH 2 ). Equal weights (about 50 grm.) of o-nitronaphthalene, iron powder, and water are mixed together and warmed, and a little concentrated hydrochloric acid (about 5 c.c.) added. The flask must be well shaken and the temperature kept at about 80. When no more heat is evolved the mixture is made alkaline with milk of lime, cooled, and filtered. The iron residue is dried in the air, and the naphthylamine either extracted with ether, or the residue is carefully distilled in vacua and the crude naphthylamine which passes over redis- tilled under reduced pressure. Yield 50 to 60 per cent. It may be recrystallised from dilute alcohol, and melts at 50. Care should be taken to prevent its coming in contact with the fingers or clothing as it has a disgusting, though not very strong, odour. ALKALI SULPHIDES. The alkali sulphides used are the sulphide, M 2 S, the sulphhydrate, MSH (obtained by saturating a solution of the sulphide with H 2 S, and then removing excess of the latter by blowing a current of hydrogen through the liquid), and the disul- phide, M 2 S 2 (obtained by boiling an aqueous solution of the sulphide with one equivalent of sulphur, e.g. 240 grm. of the crystallised sulphide, 200 c.c. of water, and 32 grm. of sulphur are boiled under a reflux condenser until complete solution takes place, and the solution then diluted to half a litre). The sulphides are especially useful for the reduction of nitrophenols, but reduction only takes place when the nitro-group is not in the ortho- position to a halogen atom, another nitro-group, or other negative radical. 212 PREPARATION OF ORGANIC COMPOUNDS When such or^o-substituents are present one of the groups is split out and replaced by S.Ar or SH (cf. pp. 106, 152). The following equations may be used in calculating the amount of reducing agent required, but it is usually advisable to employ an excess : R.NO 2 + Na 2 S + H 2 O = RNH 2 + Na 2 S(V 4RN0 2 -f 6NaSH + H 2 O = 4RNH 2 + 3Na 2 S 2 O 3 . RNO 2 + Na 2 S 2 + H 2 O = RNH 2 + Na 2 S 2 O 3 . The sulphides are also useful for reducing polynitro- compounds, as with their aid it is often possible to reduce one nitro-group without affecting the others. PREPARATION OF m.-NITRANILINE (C 6 H 5 NO 2 NH 2 ).2 (a) Twenty grammes of w.-dinitrobenzene are dissolved in 60 c.c. of alcohol, and 16 grm. of concentrated aqueous ammonia added. Sulphuretted hydrogen gas is then passed into the solution, which should be warmed from time to time, until an increase in weight of 12 grm. has taken place. The nitraniline is then precipitated with water, and filtered off together with the sulphur which separates during the reaction. The precipitate is washed with a little cold water, and then extracted several times with concentrated hydrochloric acid. The acid extracts are concentrated somewhat, cooled, and then made alkaline with strong ammonia. The precipitated nitraniline is col- lected, washed with cold water, and then recrystallised from boiling water. It forms yellow needles melting at 114. (6) Seventeen grammes of w.-dinitrobenzene are dissolved in 170 c.c. alcohol and the whole heated to boiling under a reflux condenser. A concentrated aqueous solution of sodium sulphhydrate, obtained from 36 grm. of crystallised sodium sulphide (see p. 211), is then slowly added. The alcohol is then distilled off, the residue diluted somewhat with cold water, filtered, and the precipitate recrystallised from boiling water. 1 This equation is very unreliable as the reaction often takes place according to the following : ArN0 2 + 3H 2 S = ArNH 2 + 38. 2 A. 176, 44. THE AMINO-COMPOUNDS 213 HYDROSULPHITE. Sodium hydrosulphite, Na 2 S 2 O 4 , is one of the best reducing agents known : H 2 O + Na 2 S 2 O 4 + O = 2NaHSO 3 . The reagent can be applied in several forms, viz. : (a) As the dry, powdered sodium salt, usually in the presence of caustic alkali. The most satisfactory form of the salt is the concentrated powder put on the market by the Badische Company, (b) As the formaldehyde condensation product, known commercially as " sulph- oxylate." (c) In the nascent state, as sodium bisulphite and sodium formate or hypophosphorous acid, or as zinc dust and sodium bisulphite. Nitro- benzene itself is not readily attacked by hydro- sulphite, but nitrophenols are instantly reduced. PREPARATION OF o.- AND p.- AMINOPHENOLS (C 6 H 4 (NH 2 )OH). The nitrophenol is dissolved in rather more than one equivalent of dilute caustic soda (about 10 per cent.} and the solution heated to boiling. Dry sodium hydrosulphite powder is then added little by little until the red colour of the solution disappears. On cooling, the ammo- phenol separates out as a mass of colourless crystals, which are filtered off and washed with cold water. The ortho- compound melts at 170, the para- at 184. PREPARATION OF 2.4 - DIAMINO - i - NAPHTHOL - 7 - SULPHONIC ACID HYDROCHLORIDE. 1 Sixty grammes of sifted zinc dust are added to 500 c.c. of technical, 40 per cent. bisulphite solution, and the whole shaken until a rise of temperature is felt. Naphthol Yellow S is then added little by little to the mixture, the whole being well shaken after each addition. The rate of addition of the dyestuff should be regulated so that the liquid is kept boiling by the heat of the reaction. When a permanent red coloration is obtained (about 80 grm. of Naphthol Yellow S will be required) the addition of the dye is interrupted, and a mixture of zinc dust and bisulphite solution, which has been allowed to get warm, is added until the colour disappears. The solution is filtered while still hot into 1500 c.c. of technical concentrated hydro- 1 B. 14, 2029; 32, 232. 2i 4 PREPARATION OF ORGANIC COMPOUNDS chloric acid, and the residue washed with boiling water. The strongly acid liquors are allowed to stand over -night, and then the colourless or pink amino-compound filtered off. Yield 67 per cent. OK OH NHo.HCl SO.H? NO 2 NH 2 Naphthol Yellow S 2. BY THE REDUCTION OF THE AZO- COMPOUNDS The azo-compounds are very readily obtained by the action of the diazo-salts on the phenols in alkaline solution, or on the amines in acetic acid solution. The azo-group enters the para- position to the hydroxyl or amino-group if this position is unoccupied, or the ortho- position if the para- is not available. A further discussion will be found on p. 247. The azo-compounds on reduction undergo rupture at the double bond, two primary amines being produced : R.N :N.R' + 2H 2 = RNH 2 + R'NH 2 . This method of preparing amines often proves exceedingly useful. This may be illustrated by the commercial synthesis of phenacetin (acetyl />.-pheneti- dine), which is carried out as follows. One molecule of ^.-phenetidine is diazotised and coupled with one molecule of phenol : EtO[i]C 6 H 4 [4]N EtO[i]C 6 H 4 [ 4 ]NH 2 -* || EtO[i]C 6 H 4 [ 4 ]N The hydroxyl group of the resulting azo-colour is then ethylated, and . 2 -diethoxyazobenzene reduced, thus yielding two molecules of ^.-phenetidine : EtO[i]C 6 H 4 [4]N :N[4']C 6 H 4 [i'] + 2H 2 = 2EtO[i]C 6 H 4 [4]NH 2 . The process is then repeated until sufficient />.-pheneti- THE AMINO-COMPOUNDS 215 dine has been prepared, which is then converted into phenacetin by acetylation. As reducing agents for azo-compounds may be men- tioned, metal and acid, stannous chloride, zinc dust and water or ammonia, or hydrosulphite in alkaline solution. The last is the most satisfactory. The re- action is carried out by dissolving or suspending the azo-colour in water containing a little caustic soda, and then adding hydrosulphite powder to the boiling liquid until the colour is discharged. PREPARATION OF .-NAPHTHYLENEDI AMINE (C 10 H 6 [i.4](NH 2 ) 2 ).i Aniline (18-6 grm.) is dissolved in 500 c.c. of water and 65 c.c. of technical hydrochloric acid. Ice is then added until the temperature falls below o, and the whole diazotised in the usual way with a solution of 14.5 grm. of sodium nitrite (see p. 238). a-Naphthylamine (28-4 grm.) is dissolved in cold dilute hydrochloric acid (about 400 c.c. water and 100 c.c. 2N acid) , and the solution cooled by the addition of ice. The diazo-benzene chloride solution prepared as above is then added and the whole mechanically stirred. Crystallised sodium acetate is then added until no more free hydrochloric acid is present (test with Congo paper) . The separation of the azo-colour commences almost at once and is complete in about two hours, during which time the solution must be well stirred and the temperature kept below 5 by the addition of ice. The precipitate is filtered off, well washed with water, and dried in the steam-oven. i-Aminonaphthylene-4-azo-benzene forms red needles with a green reflex. The yield is quantitative. To reduce it to the diamine, it is suspended in 500 c.c. of water and sifted zinc dust slowly added to the boiling suspension until the colour is discharged. The whole is then filtered hot into 500 c.c. of 50 per cent, sulphuric acid. On cooling, the^.-naph- thylenediamine separates out as colourless needles, the aniline remaining in solution as the sulphate. NH 2 NH 2 /\/\ + C 6 H NH 2 N = N.C 6 H 5 NH 2 i -Aminonaphthylene-4-azo-benzene .-Naphthylenediamine 1 B. 22, 1381. 216 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF I.4-AMINONAPHTHOL (C 10 H 6 [i] OH[4]NH 2 ). 1 One hundred grammes of technical Orange I are dissolved in 500 c.c. of boiling water, and the solution thus obtained poured into a warm solution of 120 grin. of stannous chloride in half a litre of pure, concentrated hydrochloric acid. Decolorisation takes place almost at once (if not, more stannous chloride must be added), and then another 200 c.c. of cold, concentrated acid are added, and the whole well stirred. The aminonaphthol separates as the hydro- chloride, and is filtered off when the temperature has fallen to about 45. It is washed with dilute hydrochloric acid. The yield is about 36 grm. ONa OH NH 9 2H 2 = Orange I NH 2 i .4- Amino- naphthol S0 3 H Sulphanilic acid PREPARATION OF a-AMINO-/3-NAPHTHOL. 2 A warm solution of 130 grm. of tin in 750 c.c. of technical hydro- chloric acid is added to 100 grm. of Orange II (Mandarin) in i litre of boiling water. After decolorisation has taken place the solution is filtered as rapidly as possible. On cooling, the aminonaphthol separates from the filtrate as the hydrochloride (colourless crystals). NH, OH Orange II (Mandarin) a-Amino- /3-naphthol S0 3 H Sulphanilic acid Both the above aminonaphthols can also be prepared by treating boiling alkaline solutions of Orange I B. 25, 423- 2 B. 25, 980. THE AMINO-COMPOUNDS 217 or II with hydrosulphite until decolorisation takes place. On cooling, the aminonaphthol separates out. 3. THE BENZIDINE AND SEMIDINE CHANGE Aromatic hydrazo-compounds when treated with acids undergo an intramolecular rearrangement whereby a diphenyl derivative is formed, e.g. : C 6 H 5 .NH.NH.C 6 Hydrazobenzene NH 2 .C 6 H 4 .C 6 H 4 .NH Benzidine When both para- positions are unoccupied, as in the above example, a ^>. 2 -diaminodiphenyl is formed (" para- benzidine change"). When one or both of the para- positions are occupied, either an o. 2 -diaminodiphenyl (" or^o-benzidine change ") or an ortho- or para- semidine is formed, e.g. : CH 3 /\ NH NH /' \/ CH 3 CH, NH NH, CH, An o^/zo-semidine For a discussion on the benzidine and semidine change the reader is referred to Stewart's " Stereo- chemistry," p. 396. The change is brought about by the action of acids. PREPARATION OF BENZIDINE (NH 2 [ 4 ]C 6 H 4 .C 6 H 4 [4/]NH 2 ). (a) From hydrazobenzenel Five grammes of 1 J- pr. [i] 36, 93- 2i8 PREPARATION OF ORGANIC COMPOUNDS powdered hydrazobenzene are shaken with 125 c.c. of 3 per cent, hydrochloric acid at a temperature of 2O-3O until dissolved. The solution is then warmed to 50, and any benzidine hydrochloride which separates redissolved by the addition of water. The solution is filtered while still warm. Excess of cold caustic soda is added to the nitrate, and the precipitated benzidine collected, washed with cold water, and recrystallised from boiling water or dilute alcohol. Colourless plates melting at 127. (b) From azobenzene* Ten grammes of azobenzene are dissolved in alcohol, and the solution warmed with a solution of 3-5 grm. of tin in 10 c.c. concentrated hydrochloric acid. When decolorisation has taken place the alcohol is removed by distillation, the residue dissolved in water, and the benzidine precipitated as the insoluble sulphate by dilute sulphuric acid. The precipitate is washed free from tin, first with dilute hydro- chloric acid and then with water, and finally decomposed with ammonia. The free base thus obtained is filtered off and recrystallised as above. Some aniline is also formed in the above reaction (see p. 214). 4. BY THE REPLACEMENT OF HALOGEN ATOMS Halogen atoms can be replaced by the amino- group by heating the halogen compound with ammonia or ammonium carbonate, or with potassium phthali- mide, and then hydrolysing the resulting phthalimide derivative (Gabriel's method) : )N.K + R.C1 CO- \ NR + KC1 CO- j CO, /NCOOH >NR + 2H 2 = + RNH 2 I OX I I COOH The method is of very little value with aromatic halogen compounds unless nitro- or other negative 1 Schultz, " Chemie des Steinkohlenteers " [1886], s. 359. THE AMINO-COMPOUNDS 219 groups are present in the ortho- or para- position to the halogen atom, but it is very useful for preparing aliphatic amines, and Gabriel's modification of the method has proved of considerable value in the study of the amino-acids. For preparing acid amides, the action of the acid chloride on ammonia is the most frequently used method, the reaction in nearly all cases taking place readily at the ordinary temperature. For this purpose it is not necessary to isolate the chloride in the pure state, but merely to use the impure product prepared as described on p. 68. PREPARATION OF GLYCOCOLL (GLYCINE) (NH 2 .CH 2 . COOH) (a) One hundred grammes of chloracetic acid are dissolved in an equal weight of water, and the solution thus obtained slowly run into 1200 c.c. of 25 per cent, ammonia, the whole being well stirred. After all the acid has been added the solution is allowed to stand for twenty-four hours, and then boiled in a basin until it no longer smells of ammonia. (It is important to get rid of all the ammonia.) It is then neutralised while hot with a slight excess of copper carbonate, filtered, and the filtrate evaporated until crystallisation sets in. On cooling, the copper salt of glycocoll separates out (blue needles) and is filtered off and washed, first with dilute, and then with stronger alcohol. It is dissolved in water, and the copper precipitated from the boiling solution by hydrogen sul- phide. The copper sulphide is filtered off and well washed, and the filtrate concentrated to a small bulk. On cooling, the glycocoll separates out as monoclinic crystals which melt with decomposition rather indefinitely at 2^2-2^6. It is soluble in 4 parts of cold water, but almost insoluble in alcohol and ether. (b) * One hundred grammes of potassium phthalimide and 65 grm. of chloracetic ester are heated for an hour and a half to 140-! 50, and the resulting liquid, while still hot, poured into a basin. After cooling, the solid mass is ground up and dissolved in 50 per cent, boiling alcohol. On cooling, the phthalimide / C \ compound, C 6 H 4 <^ ^N.CH 2 CO 2 Et, separates out and is >CCK 1 B. 22, 426. 220 PREPARATION OF ORGANIC COMPOUNDS washed free from potassium chloride with dilute alcohol. The yield is 95 per cent. The hydrolysis is best effected in two steps. One molecule of the above compound is boiled for a short time with two molecules of 10 per cent, caustic potash, and the solution then allowed to cool completely. Two molecules of concentrated hydrochloric acid are then added, the whole cooled to o, and the o.-carboxylbenzoyl glycocoll, COOH[i]C 6 H 4 [2]CONH.CH 2 COOH, which separates out fil- tered off, and washed with ice-water until free from chloride. It forms colourless leaflets which sinter at 100, and melt at iO5-io6. The yield is 85 per cent. To bring about the second stage of the hydrolysis, the above compound is refluxed for two hours with twice its weight of 20 per cent, hydrochloric acid, the flask being well shaken from time to time. A clear solution is at first obtained, but phthalic acid soon begins to separate. After cooling, the liquid is filtered, and evaporated on the water-bath to dryness. The residue is extracted with not too much ice-cold water, filtered from the undissolved phthalic acid, and the filtrate concentrated. The glycocoll which separates on cooling is washed with ice-cold alcohol. PREPARATION OF OLEAMIDE (CH 3 (CH 2 ) ? CH ; CH. (CH 2 ) 7 .CONH 2 ). 1 Twenty grammes of pure oleic acid are well mixed with 4 grm. of phosphorus trichloride, and the whole after standing for a short time gently warmed. The solution thus obtained is slowly dropped into 300 c.c. of con- centrated ammonia. The precipitate is filtered off, ground up with 2 per cent, caustic soda solution, well washed with water, and then recrystallised from dilute alcohol. Colourless scales melting at 75-76. Yield 80 per cent. Other acid amides can be obtained in exactly the same way, but the amides of the lower fatty acids are soluble in water, and as they are also steam-volatile they must be isolated by evaporating the ammo- niacal liquors at the ordinary temperature. 5. BY THE REPLACEMENT OF HYDROXYL GROUPS When phenol is heated with ammonia under pressure but little aniline is formed. Amino-compounds, however, are readily formed when polyhydric phenols 1 B. 31, 2349. THE AMINO-COMPOUNDS 221 or naphthols are heated with ammonia, and this method is used on the large scale. The ammonia is applied either as a concentrated aqueous solution, or as its addition compound with zinc or calcium chloride, MC1 2 . 2NH 3 . The zinc chloride compound, ZnCl 2 2NH 3 , is obtained by passing dry ammonia over powdered anhydrous zinc chloride as long as any gas is absorbed ; or ammonia gas can be passed into the molten chloride. In either case the reaction takes place with considerable evolution of heat, and a hard mass is obtained which must be preserved in well-stoppered bottles. PREPARATION OF w.- AMINOPHENOL (C 6 H 4 [i]NH 2 [3JOH). 1 Ten grammes of resorcinol, 6 grm. of ammonium chloride, and 20 grm. of 10 per cent, ammonia are heated in a sealed tube to 200 for ten hours. After cooling, the reaction mixture is made strongly acid with hydrochloric acid (a large excess of acid must be used) and then unchanged resor- cinol extracted with ether. On neutralising the residue with caustic soda, part of the aminophenol separates and is filtered off. The rest is extracted with ether and the ether removed by distillation. The aminophenol is finally purified by re- crystallisation from toluene. It melts at 122. PREPARATION OF /3-NAPHTHYLAMINE (C 10 H 7 NH 2 ).a Sixty grammes of /3-naphthol and 240 grm. of powdered zinc ammonia chloride are well mixed and heated on an oil- bath under a reflux condenser for two hours to 200. After cooling, 25 per cent, caustic soda solution is added until the zinc oxide at first precipitated is redissolved, and the solution then boiled for a few minutes. After cooling, the naphthyl- amine is extracted with ether, the ether removed by distillation, and the naphthylamine purified by recrystallisation from water or dilute alcohol. It forms colourless plates melting at 112. Instead of extracting with ether, the base can be isolated by distillation with superheated steam. The distillate is concentrated and the naphthylamine which separates collected and recrystallised. 1 Am. 15, 40. 2 B. 13, 1300. Cf. Cain and Thorpe, " Synthetic Dyestuffs," p. 221. 222 PREPARATION OF ORGANIC COMPOUNDS The sulphurous esters of the phenols react with ammonia much more readily than the phenols them- selves, and are thus well adapted for the preparation of primary amines. In carrying out the reaction the ester is not isolated, but a mixture of the phenol, ammonium sulphite, and ammonia is heated under pressure. This method gives almost quantitative yields of /3-naphthylamine from /3-naphthol. For further details the reader is referred to the original literature. 1 Salts of organic acids as a rule are not very readily attacked by ammonia (see p. 266), but acid amides can often be obtained by the action of concentrated ammonia on the esters. PREPARATION OF OXAMIDE (CONH 2 ) 2 . Five grammes of diethyl oxalate are slowly added to 50 c.c. of concentrated ammonia (D = 0-88). After dilution the white crystalline precipitate is filtered off and well washed. On heating, it decomposes with partial sublimation. A standard method for preparing acid amides consists in heating the ammonium salts of the acids. PREPARATION OF ACET AMIDE (CH 3 CO.NH 2 ). Fifty grammes of ammonium acetate are melted and poured into a bomb tube which has been previously warmed. The tube is then sealed, and heated to 200 for six hours. The resulting liquid is distilled and the portion boiling above 180 collected. This on standing solidifies, and is freed from mother-liquor by pressing between filter-paper. The solid mass thus obtained is redistilled (B.P. 222), and the distillate, which has a strong smell of mice, recrystallised from benzene. Colourless, almost odourless crystals melting at 82 and boiling at 222. Yield about 50 per cent. i D.R.P. 117,471, 121,683; J. pr. [2] 69, 49, ; 70, 345; 7 J > 433 ; 75, 249 ; 77, 403 ; 79, 369 ; 80, 201. THE AMINO-COMPOUNDS 223 6. BY THE DISRUPTION OF THE ACID AMIDES (HOFMANN'S REACTION) This reaction provides a ready means of preparing amino-compounds from acid amides, and is employed technically for the preparation of anthranilic acid from phthalimide, anthranilic acid being an inter- mediate compound in the manufacture of indigo. The reaction is brought about by the action of hypo- bromite (on the large scale hypochlorite is used) and caustic soda, and probably takes place in the following steps : R.CONH 2 55 R.CO.NHBr NaOH R C ONa Tautomeric || change Br N H-l- OH Br-l-C ONa 9. i 11 RNH 2 +Na 2 C0 3 +NaBr ^oH Tl II H 2 R.N The third step, it will be observed, is analogous to the Beckmann rearrangement of the oximes (see p. 232). PREPARATION OF METHYLAMINE HYDROCHLORIDE (CH 3 NH 2 . HC1) . Thirty grammes of dry acetamide are mixed with 80 grm. of bromine, and the mixture well cooled with cold water. A 10 per cent, solution of caustic potash is then added until the colour of the liquid passes from red to yellow. The solution thus obtained is added slowly to a solution of 75 grm. of caustic potash in 150 c.c. of water. Considerable heat is evolved, and care must be taken not to allow the tem- perature to exceed 75. When all the solution has been added, the whole is maintained at this temperature for half an hour and then distilled, and the distillate absorbed in dilute hydrochloric acid. During the distillation the liquid is apt to bump violently, but this can be remedied to a large extent by adding porous pot, or by blowing a fine stream of air through the liquid (see p. 23). When the distillate no longer comes over alkaline, the hydrochloric acid is evaporated to 224 PREPARATION OF ORGANIC COMPOUNDS dryness, and the residual mixture of methylamine hydrochloride and ammonium chloride repeatedly extracted with small quantities of boiling absolute alcohol, in which the ammonium salt is insoluble. On cooling the alcoholic extracts, the methylamine hydrochloride separates as colourless, deliquescent leaflets which melt at 227. The yield is about 85 per cent. PREPARATION OF ANTHRANILIC ACID (C 6 H 4 [i]NH 2 [2JCOOH). 1 Fifty grammes of finely powdered phthalimide and 100 grm. of caustic soda are dissolved simultaneously in 350 c.c. of water. Half a litre of a 5 per cent, solution of sodium hypochlorite is then slowly run in, the liquid being well shaken during the operation. When all the hypochlorite has been added, the whole is warmed for a few minutes to 80, cooled, and accurately neutralised with hydrochloric acid. An excess of strong acetic acid is then added, when the greater part of the anthranilic acid separates as a crystalline precipi- tate, and is filtered off, and washed with cold water. The liquors are treated with copper acetate solution as long as any precipitation takes place, the copper anthranilate filtered off, washed, and then decomposed by suspending in a little boiling water and passing sulphuretted hydrogen through the liquid. The precipitated copper sulphide is removed by filtration, and the filtrate allowed to cool. The anthranilic acid crystallises out and is filtered off. A further quantity may be obtained by evaporating the filtrate. The acid is finally purified by recrystallisation from water. It forms colourless or slightly yellow leaflets which melt at 144- 145. 7. FROM THE NITRILES In the saponification of the nitriles the acid amide is the first product. When the saponification is brought about by boiling with alkalis or acids, the amide cannot be readily isolated as it undergoes further decomposition : R.C = N -> R.CO.NH 2 -> R.COOH+NH 3 . When, however, the hydrolysis is brought about by hydrogen peroxide in the presence of dilute caustic soda, the reaction does not proceed beyond the first stage, and the amide can often be obtained in almost i D.R.P. 55,988, THE AMINO-COMPOUNDS 225 theoretical yield. The reaction is brought about by shaking the nitrile with 10 or 20 volume hydrogen peroxide containing some caustic soda. The reaction goes best at a temperature of about 40. PREPARATION OF BENZ AMIDE (CgH^ONH,,). 1 Ten grammes of benzonitrile are added to 150 c.c. of 10 volume (3 per cent.} aqueous hydrogen peroxide to which 2 or 3 c.c. of 10 per cent, caustic soda solution have been added. The whole is warmed to 40, and then violently shaken until the oil has completely given place to a white precipitate. This is filtered off, and recrystallised from alcohol. M.P. 163. During the shaking an opening must be left for the oxygen evolved to escape : C 6 H 5 CN + H 2 2 = C 6 H 5 CO.NH 2 + O. The yield is quantitative. Primary amines, R.CH 2 NH 2 , can also be obtained by reducing the nitriles. 2 The reduction is carried out with zinc and sulphuric or hydrochloric acid, usually in alcoholic solution, or with sodium and alcohol. In the latter case the nitrile is dissolved in 10-15 parts of alcohol, and about four times the calculated amount of sodium rapidly added to the boiling solution. Under these conditions aromatic nuclei, if present, are simul- taneously reduced. The yields are usually rather poor, as part of the nitrile is hydrolysed to the acid and part completely reduced : RCN + H 2 = RH + HCN. THE SECONDARY AND TERTIARY COMPOUNDS i. FROM THE HALOGEN COMPOUNDS Just as primary amines are obtained from the halogen compound and ammonia, so also are the secondary and tertiary amines obtained respectively from the primary and secondary bases : RNH 2 + RC1 = R 2 NH + HC1. R 2 NH + RC1 = R 3 N + HC1. 1 B. 18,355. 2 B. 18,2957; 19, 782; 20, 1709; 24, 3355. 226 PREPARATION OF ORGANIC COMPOUNDS When an aliphatic halogen compound is treated with ammonia, primary, secondary, tertiary, and quaternary compounds are all formed : RCl RCl RCl RC1 + NH 3 RNH 2 -> R 2 NH -* R 3 N R 4 N.C1. In the aromatic series the formation of secondary and tertiary bases proceeds much less readily, and to obtain satisfactory yields it is necessary to employ a catalyst. It has been found that the presence of cuprous chloride or finely divided copper greatly accelerates the splitting out of halogen acid between a molecule of an aliphatic or aromatic halogen compound and a primary or secon- dary base, phenol or mercaptan. It is only necessary to use a trace of copper powder. The copper powder can be made by sifting zinc dust into a cold, saturated solution of copper sulphate, as described on p. 75. Copper powder can also be bought under the name of " copper bronze " or " Naturkupfer C." These contain a trace of oil, and before use must be well washed with ether or petroleum spirit. The copper-powder method has been very largely employed in the aromatic series, and the following rules are fairly general : Primary aromatic base + aliphatic halogen com- pound. Both secondary and tertiary bases are obtained with ease. Primary aromatic base + aromatic halogen com- pound. The secondary base only is formed, but, as a rule, tertiary bases can be obtained by using the aromatic iodide. Secondary mixed base + aromatic halide. The tertiary base is formed, although it is often necessary to employ the bromide or iodide. In carrying out the reaction it is usual to add some substance, such as anhydrous sodium acetate or sodium carbonate, to absorb the halogen acid liberated. Any neutral solvent, such as nitrobenzene, benzene, naphthalene, amyl alcohol, &c., can be used, or, with liquid or easily fusible bases, a,n excess of the base THE AMINO-COMPOUNDS 227 can be used without a solvent. If it is desired to prepare a secondary base it is best to use a large excess of the primary amine, especially if condensation is taking place with an aliphatic halogen compound. When preparing tertiary bases an excess of the halogen compound is used. PREPARATION OF PHENYLGLYCINE-o.-CARBOXYLIC ACID (COOH[2]C 6 H 4 [i]NH.CH 2 COOH).i Twenty grammes of potassium-o.-chlorbenzoate or an equivalent amount of the free acid, 5-6 grm. of caustic potash, 7 grm. of potassium carbonate, 7-5 grm. of glycocoll, 15 c.c. of water, and about o-i grm. of copper powder are heated to boiling under a reflux condenser on the oil-bath for one hour. The liquid becomes at first blue, then green, and finally yellow. Boiling water is then added until the crystals which have separated pass into solution, and the whole filtered into excess of hydro- chloric acid. The phenylglycine-o.-carboxylic acid separates out in almost quantitative yield, and is purified by recrystallisa- tion from water. It melts with decomposition at 207. PREPARATION OF N.-METHYL ANTHRANILIC ACID, 2 C 6 H 4 iT Anthranilic acid (13-7 grm.) is dissolved in 140 c.c. of water and accurately neutralised with caustic potash. Methyl iodide (14-5 grm.) is then added, and the whole boiled under a reflux condenser for several hours until the methyl iodide has disappeared. After cooling, the methyl anthranilic acid is filtered off, washed, and recrystallised from alcohol. M.P. 179. PREPARATION OF N.-PHENYL ANTHRANILIC ACID (C 6 H 4 [i]NHC 6 H 5 [2]COOH). (a) 3 Twenty grammes of an- thranilic acid, 32 grm. of bromobenzene, 20 grm. of anhydrous sodium carbonate, and about i grm. of Naturkupfer C are boiled under a reflux condenser with 120 grm. of nitrobenzene for three hours. The nitrobenzene is then removed by distillation with steam, and the aqueous residue filtered, cooled, and acidified with hydrochloric acid. The greenish crystals which separate are washed, dried, and then recrystal- lised from benzene. M.P. 186 (cor.). Yield 95 per cent. 1 D.R.P. 142,507 ; cf. also 142,506. 2 M. 21, 930. 3 B. 39, 1691. 228 PREPARATION OF ORGANIC COMPOUNDS (b) * Twenty grammes potassium-o.-chlorbenzoate, 10 grm. of aniline and 0*2 grm. of copper powder are boiled for thirty hours with 100 c.c. of water. After cooling, the crystals which separate are filtered off, washed free of aniline with dilute hydrochloric acid, and then recrystallised from alcohol. Yield 80 per cent. The acyl amino-compounds, R.NH.CO.R, are ob- tained (a) by heating the primary amine with the acid ; (b) by heating the amine with the acid anhydride with or without a condensing agent, such as the anhy- drous sodium salt, sulphuric acid, &c. ; (c) by treating the amine with the acid chloride, either alone or, in the case of stable chlorides such as benzoyl chloride, in the presence of 10 per cent, aqueous caustic soda (Schotten-Baumann method), sodium carbonate, lime, chalk, &c. For a full description of these and other methods the reader is referred to Chapter I of Lassar- Cohn's " Arbeit smethoden." The secondary amines are only acylated with diffi- culty, and usually require prolonged heating with the acid anhydride and a condensing agent. With aromatic acid chlorides the Schotten-Baumann method usually gives excellent results. The primary amine is suspended in 10 per cent, aqueous caustic soda, and an excess of the acid chloride added little by little, the solution being shaken after each addition until all the chloride has disappeared. Good results are also obtained by heating the amine with the acid, acid anhydride or acid chloride, in nitrobenzene or naphthalene solution. PREPARATION OF ACETANILIDE (C 6 H 5 NH . COCH 3 ) . (a) Twenty grammes of aniline and 15 grm. of glacial acetic acid are boiled under a reflux condenser for twelve hours. The condenser should be simply a wide glass tube, long enough to condense the acid and aniline, but not the water evolved during the reaction. The product is poured into hot water containing a little hydrochloric acid, cooled, filtered, and the precipitate recrystallised from boiling water or dilute alcohol, Colourless leaflets. M.P. 115. i D.R.P. 145,189 ; B. 36, 2382, THE AMINO-COMPOUNDS 229 (b) Aniline is slowly added to its own weight of acetic anhydride, contained in a flask fitted with a reflux condenser. Much heat is evolved, and after all the aniline has been added the whole is gently boiled for a few minutes. It is worked up exactly as above. (c) Aniline is slowly added to its own weight of acetyl chloride, the whole warmed on the water-bath and poured into water. PREPARATION OF BENZANILIDE (C 6 H 5 NH . COC 6 H 5 ) . Eight grammes of aniline are shaken up with about 150 c.c. of cold 10 per cent, caustic soda. Fourteen grammes of benzoyl chloride are added in four portions, and after each addition the solution is vigorously shaken until the smell of benzoyl chloride disappears. Care must be taken to avoid . rise in temperature. When all the benzoyl chloride has been used, the benzanilide is filtered off, washed with cold water, and recrystallised from dilute alcohol. M.P. 165. PREPARATION OF BENZOYL - a - AMINOANTHRA - QUINONE (C 14 H 7 O 2 NHCOC6H 5 ).i Ten grammes of a-amino- anthraquinone, 100 grm. of nitrobenzene, and 20 grm. of benzoyl chloride are boiled under a reflux condenser for half an hour. On cooling, the benzoyl compound separates out, and is collected and washed with alcohol or ether. It forms a yellow crystalline powder which dyes cotton bright yellow from an alkaline hydrosulphite vat. It is the Algol yellow W.G. of commerce. By the above methods acid anilides are readily obtained from almost all primary aromatic amines, such as the toluidines, naphthylamines, &c. PREPARATION OF HIPPURIC ACID (C 6 H 5 CO.NH. CH 2 .COOH). 2 Fifteen grammes of finely powdered glycocoll are slowly added to 100 grm. of molten benzoic anhydride, and the whole warmed on the oil-bath until a red coloration appears. The melt is then dissolved in water, neutralised with alkali, and acidified. After standing for a few days the precipitate is collected, boiled with water and animal charcoal, and the filtrate concentrated on the water-bath until crystallisation sets in. i D.R.P. 225,232. 2 B. 17 1663. 230 PREPARATION OF ORGANIC COMPOUNDS Instead of using methyl iodide, primary and secon- dary amines are usually readily methylated by dimethyl sulphate. The reaction is brought about by heating the amine with dimethyl sulphate alone, or more usually in the presence of an inert solvent, such as nitrobenzene, and it is important to avoid all traces of moisture. This is best achieved by boiling the amine alone or in nitrobenzene, &c., solution for a few minutes without a condenser before adding the sulphate. It must be borne in mind that dimethyl sulphate is very poisonous, and all work with it must be carried out in a fume-chamber, and every care taken to avoid inhaling any of its vapour. In spite of its high boiling-point a small quantity of it spilled on the clothing has been known to cause death. 1 No remedy is known. PREPARATION OF w.-NITRO-MONOMETHYL ANILINE (C 6 H 4 [i ]NHCH 3 [3]NO 2 ). 2 Ten grammes of dimethyl sulphate are heated to 140, and 7 grm. of w.-nitraniline added little by little, the whole being well shaken after each addition, and the temperature maintained at I4O-I5O. (Take care! See warning above.) After cooling, the orange-coloured mass is diluted with ice-water, and then 10 c.c. of concentrated hydrochloric acid and 36 c.c. of 10 per cent, sodium nitrite added. The nitrosamine, C 6 H 4 NO 2 N(NO)CH 3 (M.P. 67), separates out, and is collected and reduced to the secon- dary base. In this case it is impossible to use a powerful reducing agent, such as zinc dust and acids, as this would also reduce the nitro-group. It has been found, 3 however, that hydrochloric acid alone is capable of reducing nitrosamines, and this is the best method when there is danger of more powerful reagents attacking other groups in the molecule. The reduction is carried out simply by boiling the nitrosamine with concentrated hydrochloric acid. The nitromethylaniline is finally purified by recrystallisation from alcohol or aqueous alcohol. It forms reddish yellow needles melting at 66. 1 Archiv. f. Esperimentelle Pathologic und Pharmakologie, 47, 115 ; 127. C. 1901, i, 364. 2 A. 327, 112. 3 A. 128, 151 ; B. 31, 2527. THE AMINO-COMPOUNDS 231 PREPARATION OF DIMETHYLANILINE (C 6 H 5 N(CH 3 ) 2 ). Seventy-five grammes of aniline, 25 grm. of aniline hydro- chloride, and 75 grm. of methyl alcohol are heated in an auto- clave or in sealed tubes for eight hours to 240. The product is made alkaline with caustic soda and then steam-distilled. The oil is separated from the aqueous portion of the distillate, dried over solid caustic potash, and then fractionated. The dimethylaniline passes over between 190 and 200. It is a colourless liquid which rapidly darkens. B.P. 192. Its formation in the above preparation is probably due to the intermediate formation of methyl chloride. 2. BY HEATING THE PRIMARY BASE WITH ITS HYDROCHLORIDE This method is confined to the preparation of secon- dary aromatic bases, and is that used technically for the preparation of diphenylamine. PREPARATION OF DIPHENYLAMINE, 1 (C 6 H 5 ) 2 NH. One molecule (93 grm.) of aniline and i molecules (195 grm.) of aniline hydrochloride are heated in a closed vessel for thirty-six hours to 230. The product is extracted with boiling dilute hydrochloric acid and then with water. The insoluble portion is further purified, first by distillation, and then by recrystallisation from ligroin. Colourless leaflets melting at 54, and boiling at 310. 3. BY HEATING THE AMINES WITH IODINE A very general method for preparing diarylamines in excellent yield has been the subject of a recent patent. 2 It consists in heating the primary base, or a mixture of two primary bases, or a mixture of a primary base and a phenol, with a trace of iodine. The action of the iodine is catalytic and only 0-5 per cent, of the weight of the reaction mass is required. PREPARATION OF /3/3-DINAPHTHYLAMINE, (C 10 H 7 ) 2 NH. One hundred grammes of /3-naphthylamine and 0-5 grm. of iodine are heated for four hours to 230. After cooling, the 1 Z. 1886, 438. 2 D.R.P. 241,853. 232 PREPARATION OF ORGANIC COMPOUNDS melt is recrystallised from benzene. M.P. 170 -171. The yield is almost quantitative. PREPARATION OF PHENYL-/3-NAPHTHYLAMINE (C 10 H 7 NH.C 6 H 6 ). Seventy-two grammes of /3-naphthol and 90 grm. of aniline are heated with I grm. of iodine for seven hours to ioo-i90. The melt is boiled out, first with dilute hydrochloric acid and then with dilute caustic soda. The residue is dried and then distilled in vacua. The phenyl naphthylamine passes over in almost theoretical yield at 237 (15 mm.). It melts at 108. 4. BY THE REARRANGEMENT OF THE OXIMES (Beckmann Change) The oximes on treatment with acids, acid chlorides (especially phosphorus pentachloride) , or acid anhy- drides undergo a remarkable change and become acid amides : R.C R' R C OH Tautomeric R C = O II. II | N OH N R' change NHR' REARRANGEMENT OF BENZOPHENONE OXIME. One molecular portion of phosphorus pentachloride is dissolved in twice its weight of phosphorus oxychloride, and then slowly added to one molecular proportion of benzophenone oxime, the whole being well cooled with ice. When all the chloride has been added, the whole is allowed to stand until a pale yellow preci- pitate has settled out from a clear yellow liquid. When this has taken place the phosphorus oxychloride is removed by distillation in vacua from the water-bath. When no more phosphorus chloride passes over, a few cubic centimetres of petroleum ether, which has been dried over sodium, are added, and the whole again distilled in vacuo. This process is repeated until phosphorus compounds can no longer be detected in the distillate. Without allowing the residue to cool, it is mixed with 8 parts of dry petroleum ether, and shaken until a semi-solid precipitate separates out. The solution is then carefully poured off, and evaporated by distillation under reduced pressure. Benzophenone- imide chloride, (C 6 H 5 ) 2 C : NCI, is left as a crystalline mass melting at 41. It is shaken up with 90 per cent, alcohol, made alkaline with caustic soda, THE AMINO-COMPOUNDS 233 and the solution then diluted with water. The benzanilide which separates is recrystallised from absolute or aqueous alcohol. M.P. 163. ADDENDA A class of tertiary amines is obtained by the action of aldehydes on primary amines : R.CHO + H 2 NR = RCH : NR' + H 2 O. These are very readily decomposed into the amine and aldehyde, and are useful for isolating aldehydes (p. 108). Their formation also forms a ready means of " protecting " the amino-group during nitration, for which purpose the compounds obtained from benzal- dehyde (the benzylidine derivatives) are usually chosen. PREPARATION OF SODIUM BENZYLIDENE NAPH- THIONATE (SO 3 Na[i]C 10 H 6 [4]N : CHC 6 H 5 ).i Twelve grammes of sodium naphthionate are dissolved in 60 c.c. of warm water, and 3 grm. of benzaldehyde dissolved in 3 c.c. of alcohol added. The whole is well shaken, and on cooling yellow leaflets separate (6|- grm.). These are collected, and by adding more benzaldehyde to the nitrate a further quantity can be obtained. The crystals contain one molecule of water, which they lose at i4o-i5O. UREA. Urea is the amide of carbonic acid, and is most readily obtained by the intramolecular rearrange- ment of ammonium cyanate : NH 4 CNO CO(NH 2 ) 2 . The rearrangement takes place very readily on merely evaporating the aqueous solution of the salt, and is reversible at a higher temperature. PREPARATION OF UREA (CARBAMIDE) (CO(NH 2 ) 2 ). Twenty grammes of potassium cyanide are dissolved in 300 c.c. of water, and a solution of 33 grm. of potassium permanganate in i litre of water slowly run in during an 1 A. 247, 325 : B. 20, 2002. 234 PREPARATION OF ORGANIC COMPOUNDS hour. During the process the temperature must be kept.. at about 5, and the whole must be well agitated. This is best done by blowing or sucking air through the solution, the oxygen assisting the oxidation. Manganese dioxide is then removed by nitration, and any excess of permanganate destroyed by adding a little sulphurous acid. The solution is again filtered, 35 grm. of ammonium sulphate added to the filtrate, and the whole taken to dryness on the water- bath. The residue, which consists chiefly of urea and potassium sulphate, is repeatedly extracted with small quantities of boiling alcohol until a sample of the extract leaves very little residue when evaporated to dryness. On concentrating the alcoholic extracts, the urea separates out as colourless prisms which melt at 132. 3 KCN + H 2 + 2KMn0 4 - 2KOH + 2MnO 2 + 3KCNO. 2KCNO + (NH 4 ) 2 SO 4 = K 2 SO 4 + 2NH 4 CNO. NH 4 CNO = CO(NH 2 ) 2 . The syw-disubstituted ureas are obtained by the action of carbonyl chloride on the primary amines. Those obtained from ^.-phenylenediamine and from the amino-naphthol sulphonic acids, especially J-acid (NH 2 .OH.SO 3 H.i.5.7), are of considerable technical value as they form azo-colours which are substantive to cotton, i.e. dye cotton without a mordant. The simplest of these is Cotton Yellow G : The Benzo Fast Scarlets, however, are of greater im- portance. They are obtained by coupling the urea derived from J-acid with diazo-compounds. THE THIOAMIDES AND THIOANILIDES. With the exception of the thioureas, the thioamides and thioanilides are fairly readily obtained by heating the corresponding oxygen compounds with phosphorus pentasulphide. In preparing the thioamides it is THE AMINOCOMPOUNDS 235 necessary to use a large volume of some inert solvent, such as benzene, as otherwise the phosphoric oxide formed during the reaction will react with the amide to form a nitrile : R.CO.NH 2 R.CN-f-H 2 O. PREPARATION OF THIOUREA (THIOCARB AMIDE). One hundred grammes of ammonium thiocyanate are heated to 145 for six hours. The melt is ground up and unchanged thiocyanate extracted with about 50 c.c. of cold water. The residue is then recrystallised from hot water. It forms colourless prisms or needles melting at 172. Yield about 15 grm. /NH 2 /NH N=C S NH 4 -* NH = C/ or S = C/ The rearrangement is exactly analogous to that undergone by ammonium cyanate, and is also reversible. PREPARATION OF sym - DIPHENYLTHIOURE A (THIOCARBANILIDE) (CS(NHC 6 H 5 ) 2 ).i Fifty grammes of aniline, 50 grm. of alcohol, 50 grm. of carbon bisulphide, and 0-25 grm. of crystallised sulphur are boiled on the water-bath for six hours under a reflux condenser. 2 The carbon bisulphide is then removed by distillation, the residue washed free of aniline by dilute hydrochloric acid, and then recrystallised from dilute alcohol. Colourless plates. M.P. 151. Yield almost theo- retical. /NH.C 6 H 5 CS 2 + 2C 6 H 5 NH 2 = q=S + H 2 S. \NH.C 6 H 6 The above method is of very general application for 1 Fischer, "Anleitung zur Darst. organ. Prep." (1905), p. 7. 2 Carbon bisulphide is very highly inflammable, and care must be taken not to bring, a light near it. In the above experiment steam, if available, is the best source of heat. If steam is not available, a large bucket of hot water, which is renewed from time to time, can be used. It is not safe to heat the water-bath directly by a flame. 236 PREPARATION OF ORGANIC COMPOUNDS the preparation of sym-diaryl thioureas from primary aromatic amines with the exception of the amino- anth/aquinones. The sulphur acts as a catalyst and greatly facilitates the reaction. Like the corresponding ureas, the syw-diaryl thio- ureas give direct cotton azo-colours. Thus the thio- urea derived from ^.-phenylenediamine when diazo- tised and coupled with sodium naphthionate gives Salmon-red. Some of the Benzo Fast Scarlets are azo- dyes obtained by coupling diazo-compounds with the thiourea derived from J-acid. PREPARATION OF THIOACET AMIDE (CH 3 .C^NH 2 ).i Five molecules of acetamide and one molecule of finely powdered phosphorus pentasulphide are boiled under a reflux condenser with a large excess (about 50 parts) of benzene for twenty minutes. The solution is then filtered, and concentrated until the thioamide crystallises out. Yellow prisms (from ether) melting at iO7-io8. The thioamides can also be conveniently prepared by treating the alcoholic solution of the nitrile with hydrogen sulphide in the presence of ammonia, e.g. : C 6 H 5 CN + H 2 S = C 6 H 5 CSNH 2 . PREPARATION OF THIOBENZANILIDE (C 6 H 5 NH. CS.C 6 H 5 ). 2 Twenty grammes of benzanilide are intimately mixed with 10 grm. of finely powdered phosphorus penta- sulphide and 10 grm. of finely powdered phosphorus trisulphide. The whole is then cautiously heated over a naked flame with continual shaking until fusion takes place, and the melt takes a yellow colour. After cooling, the whole is extracted several times by boiling with alcohol or acetone, the united extracts made strongly alkaline with caustic soda, and then poured into a large bulk of water. The dark coloured solution obtained on filtration is then saturated with carbon dioxide, when the thiobenzanilide separates as a yellow crystalline precipitate which does not require further purification. It melts at 97-98. The yield is about 90 per cent. 1 A. 250, 264. 2 Proc. 27, 8. CHAPTER XI THE DIAZO-, DIAZOAMINO-, DIAZOIMINO,- AZO-, AZOXY-, AND HYDRAZO-COMPOUNDS I. THE DIAZO-COMPOUNDS THE true diazo-compounds contain the group, Ar.N = NAc, where Ac is an inorganic or organic acyl group, or a halogen atom, and Ar is an aromatic group. The N\ / fatty diazo-compounds contain the structure || )C\ N/ and are of very minor importance. The aromatic diazo-compounds are, as a rule, dangerously explosive in the dry state, diazo- benzene nitrate exploding with even greater violence than mercury fulminate. Hence, in preparing derivatives, such as the azo-dyes, it is usual merely to work with the aqueous solution or suspension of one of the salts, usually the chloride. Some of the diazo-compounds, however, are quite stable. Thus the diazo-salts derived from i-naphthol-2-amino-4- sulphonic acid can be nitrated and sulphonated, and the diazo-sulphate of ^.-nitraniline is an article of commerce, being used in conjunction with /3-naphthol in the preparation of Para-red, an insoluble dyestuff produced directly on the fibre. The only practical method of preparing diazo- compounds is the action of nitrous acid on the primary aromatic amines : Ar .NH 2 + HO .NO + HC1 = ArN : N .Cl + 2H 2 O. If it is desired to isolate a water-soluble diazo-salt, 237 238 PREPARATION OF ORGANIC COMPOUNDS the primary amine is dissolved in alcohol, acid added, and then the calculated quantity of amyl nitrite slowly run in, the temperature being kept at about 5. The diazo-compound is then precipitated with ether. Thus when 50 grm. of aniline hydrochloride are dissolved in 150 c.c. of alcohol and treated with 65 grm. of amyl nitrite at a temperature below 10, 53 grm. of diazo- benzene chloride can be obtained by precipitating the reaction mixture with ether. In almost all cases, however, the diazotisation is carried on in aqueous solution with nitrous acid. For this purpose one molecule of the amine is dissolved or suspended in 10 to 20 parts of cold water con- taining 2% ^0 3 molecules of mineral acid (usually hydrochloric acid), the solution cooled to 5 by the direct addition of ice, and an aqueous solution of one molecule of sodium nitrite * run in slowly with continual stirring, rise in temperature being prevented by adding more ice from time to time. After all the nitrite has been added the stirring is continued for ten minutes, after which time the solution should give a faint reaction with starch-iodide paper. If no reaction is obtained, a little more nitrite must be added ; if a strong reaction is obtained, a little more of the base. Under these conditions the base is usually quanti- tatively converted into its diazo-salt, which in most cases remains in solution, and, if desired, can often be precipitated by the addition of a suitable salt, such as sodium picrate or sodium dichromate, 2 the diazo- 1 Commercial sodium nitrite contains about 98 per cent, of NaNO 2 and is slightly deliquescent. It can be conveniently replaced by barium nitrite, which, although exceedingly soluble in water, is not in the least hygroscopic, and can, therefore, be weighed out accurately. The use of barium nitrite has the advantage that all inorganic matter can be removed from the solution by adding the calculated quantity of sulphuric acid, or a slight excess of sulphuric acid and then barium carbonate. This is a great advantage when it is desired to isolate the diazo-salt by precipitation with alcohol and ether. 2 Bl. j>] 7, 270 ; P.P. 73,286. THE DIAZO-, ETC., COMPOUNDS 239 picrate or chr ornate separating out. In some cases, e.g. diazotised ^.-aminobenzanilide, even the carbonate can be obtained by this method. * Some diazo-chlorides, however, notably those of sulphanilic and naphthionic acids, are insoluble in water and separate out. These can, if desired, be filtered off, but must on no account be allowed to dry, as they are very explosive. If the amine to be diazotised is difficultly soluble in cold dilute acids, it should be dissolved boiling, and the solution then cooled as rapidly as possible, with violent agitation, in order that the base may separate out in a finely divided state. Amino-sulphonic or carboxylic acids are best dissolved in alkali, and then reprecipitated by acids. Bases which are only attacked by nitrous acid with difficulty can often be successfully diazotised by dissolving in concentrated sulphuric acid, and a concentrated solution of sodium nitrite then run in very slowly at a temperature of 15 ; or solid sodium nitrite or its solution in concentrated sulphuric acid (nitrosyl sulphuric acid) can be used. It will be noticed in the above directions that a large excess of acid is always employed. This is necessary in order to prevent the formation of diazo- amino compounds : Ar.N 2 .Cl + HNHAr = ArN 2 .NH.Ar. If an organic acid, such as acetic acid, is used in place of mineral acid, a very large excess is required. Thus a i per cent, solution of aniline diazotised in the presence of 2-J- molecules of acetic acid gave only 19-20 per cent, of diazobenzene acetate, and quan- titative yields could only be obtained when 36 molecules of acetic acid were used. The tendency to form diazoamino-compounds differs considerably with the different amines, and in cases where the tendency is great, as, for example, with />.-nitraniline, the whole of the nitrite must be added at once. DIAZOTISATION OF .-NITRANILINE. Seven grammes of /?.-nitraniline are dissolved by boiling with 20 c.c. of concen- 1 Soc. 87, 921. 2 4 o PREPARATION OF ORGANIC COMPOUNDS trated hydrochloric acid and 20 c.c. of water. After cooling, the whole is poured into 200 c.c. of water and ice then added until the temperature falls to 10. A concentrated solution of 3 -6 grm. sodium nitrite is then added all at once, the whole being vigorously stirred. No precipitation of the diazoamino-compound should take place. Although the directions given above are of very general application, there are cases to which they are not applicable. Thus w.-phenylenediamine when diazotised in the ordinary way gives Bismarck brown, one molecule being tetrazotised and then coupling with two molecules of the unchanged base : C 6 H 4 (N 2 C1) 2 +2C 6 H 4 (NH 2 ) 2 -, C 6 H 4 The base, however, can be tetrazotised by a special procedure. TETRAZOTISATION OF m.-PHENYLENEDIAMINE.i Eighty cubic centimetres of concentrated hydrochloric acid are diluted with 320 grm. of ice, and the whole well cooled in a freezing mixture. A strong aqueous solution of 15 grm. of sodium nitrite is added and then, as rapidly as possible, a cold aqueous solution of 9 grm. w.-phenylenediamine hydrochloride to which i c.c. of concentrated hydrochloric acid has been added. During the addition of the diamine the solution must be well stirred. o.-Phenylenediamine cannot be diazotised, as it forms an azoimino-derivative : 2 /N C 6 H / [ >NH \ N / ^.-Phenylenediamine gives a mixture of the diazo- and tetrazo-derivatives, and, therefore, its technically important diazo-derivatives must be prepared in two steps. For this purpose either ^.-nitraniline is 1 B. 30, 93, 2203, 2899 ; D.R,P, 103,660. 2 B. 9, 221. THE DTAZO-, ETC., COMPOUNDS 241 diazotised (p. 239), and then coupled with a phenol, the nitro-group reduced with ammonium sulphide, and the resulting aminoazo-compound again diazotised and coupled : N0 2 C 6 H 4 .NH 2 N0 2 .C 6 H 4 .N 2 C1 NO 2 . C 6 H 4 N 2 . Ar ArN 2 .C 6 H 4 .N 2 Ar *- N 2 C1 . C 6 H 4 N 2 Ar NH 2 .C 6 H 4 N 2 Ar (see p. 253) ; or monoacetyl-/>.-phenylenediamine is diazotised and coupled, the acetyl group split off, and the primary amine thus obtained again diazotised and coupled. Nitro-groups in the ortho- or para- position often protect amino-groups from the action of nitrous acid. Thus when mononitro-^.-phenylenediamine : NH, is treated with nitrous acid, only the amino-group at 4 is attacked. If, however, the diazo - compound thus obtained is coupled, the resulting aminoazo- compound is readily diazotised. The amino-group at i is also readily diazotised if the group at 4 is first acetylated. The sulphonic group exerts an influence similar to that of the nitro-group. Benzidine, &c., cannot be diazotised, but is readily tetrazotised. In order to obtain the diazo-compound one amino-group must first be protected by acetylation, or a molecular mixture of tetrazotised benzidine and benzidine is allowed to stand for three days : C1N 2 C 6 H 4 .C 6 H 4 .N 2 C1 + H 2 N.C 6 H 4 .C 6 H 4 .NH 2 - 2NH 2 .C 6 H 4 .C 6 H 4 .N 2 C1. The amino-naphthols, in which the amino- and hydroxy -groups are in the ortho- (1.2) positions to each other, are oxidised by nitrous acid to the correspond- 16 242 PREPARATION OF ORGANIC COMPOUNDS ing /S.-naphthoquinones. This oxidation, however, can be prevented by carrying out the diazotisation in the presence of copper, 1 mercury, zinc, iron, or nickel salts. When this procedure is adopted only one equivalent of mineral acid is used. When an amino- naphthol sulphonic acid is to be diazotised, no acid is added, the sulphonic group liberating the nitrous acid. The amino-naphthols can also be diazotised by replacing the mineral acid by acetic, oxalic, tartaric, or phthalic acid. DIAZOTISATION OF I-AMINO-2-NAPHTHOL-4-SUL- PHONIC ACID. (a) 2 Twenty-four grammes of the acid are dissolved in about 500 c.c. of water containing one equivalent of sodium acetate or carbonate. Two hundred grammes of 30 per cent, acetic acid are then added, and the whole cooled to io-is. Sodium nitrite solution is then added very slowly (several hours will be required) to the well-stirred solution until a permanent reaction is obtained with starch- iodide paper. (b) 3 Twelve grammes of the acid are made into a paste with 50 c.c. of water containing i grm. of crystallised copper sul- phate. A concentrated aqueous solution of 3-5 grm. of sodium nitrite is then added very slowly to the well-stirred liquid, the temperature being maintained, at io-i5. DIAZOTISATION OF a-AMINO-/3-NAPHTHOL. 4 Twenty grammes of the hydrochloride are dissolved in 1500 parts of water, containing 5 parts of copper sulphate, and the diazo- tisation brought about by the very slow addition of 8 grm. of sodium nitrite in 500 c.c. of water. During the diazotisation the temperature should not exceed 8. II. THE DIAZOAMINO-COMPOUNDS The diazoamino - compounds contain the group Ar.N:N.NHR, and, as was pointed out on p. 239, are formed by the union of one molecule of a diazo- salt with one molecule of a base. Since diazobenzene chloride and ^.-toluidine, and diazo-^.-toluene chloride 1 D.R.P. 155,083, 171,024, 172,446, 175,593, 176,618-19-20. 2 D.R.P. 155,083. 3 D.R.P. 171,024. 4 D.R.P. 172,446. THE DIAZO-, ETC., COMPOUNDS 243 and aniline give the same compound, it is probable that an addition compound is first formed, which then loses hydrochloric acid : |H Cii H C 6 H 5 N : N.C1 + C 7 H 7 NH 2 - C 6 H 5 N N N C 7 H 7 I C 6 H 5 N = N NH . C 7 H 7 The combination of the diazo-salt with the base takes place in neutral or faintly acid solution, and is in many cases accompanied by the simultaneous formation of an aminoazo-compound. Thus the benzene mon- amines usually give almost quantitative yields of diazoamino-compounds, but diazotised sulphanilic acid and monomethyl aniline give a mixture of diazo- amino-compound and azo-dye. The diphenylamines and naphthylamines, on the other hand, give only the azo-compound, the diazoamino-compound only being obtained by splitting out water between a molecule of the nitrosamine and a molecule of a primary base : Ar . NH . N : p H^N Ar Ar . NH . N : N Ar or by the action of Grignard's reagent on the diazo- imides. 1 In order to prepare a diazoamino-compound by the interaction of a diazo-salt on a base, several procedures can be adopted. Thus one molecule of the base can be diazotised in the ordinary way and then mixed with a molecule of the same or other suitable base, and sodium acetate then added until no more mineral acid is present (test with Congo paper) . Under these conditions the diazoamino-compound separates out, and after standing for a time is filtered off. Or two molecules of the hydrochloride of the base are diazotised with one molecule of sodium nitrite in the absence of free mineral acid, the diazoamino- compound being continually formed during the process. A third variation, not often adopted, is to pass gaseous nitrous acid into an alcoholic solution of the base. 1 B. 36, 909 ; 38, 670 ; 40, 2390. 244 PREPARATION OF ORGANIC COMPOUNDS Mixed diazoamino-compounds can be obtained by allowing a diazo-solution to act on an aliphatic amine according to the first of the above methods. Under these circumstances, however, only benzylamine reacts smoothly, there being a great tendency to form disdiazoamino-compounds, (ArN 2 ) 2 NR, in the case of methylamine, ethylamine, &c. This can be avoided by accurately neutralising the diazo-solution with sodium carbonate, and then adding it to the aqueous solution of the base mixed with ice and sodium car- bonate and covered with ether. The ether takes up the diazoamino-compound as soon as it is formed, and thus protects it from being further attacked by the diazo-solution. PREPARATION OF DIAZOAMINOBENZENE (C 6 H 5 N : N . NH . C 6 H 5 ) .* Ten grammes of aniline are dissolved in 100 c.c. of cold water and 30 c.c. of concentrated hydrochloric acid, the solution cooled to 2 by adding ice, and then diazotised by running in slowly a solution of 8 grm. of sodium nitrite in 50 c.c. of water. During the diazotisation the solution should be well stirred, and rise in temperature prevented by adding more ice from time to time. An ice-cold solution of 14 grm. of aniline hydrochloride, or of 10 grm. of aniline and the calculated quantity of hydrochloric acid, in 50 c.c. of water is then added to the diazo-solution, and finally a concentrated, ice-cold solution of 50 grm. of sodium acetate. After stirring for half an hour the diazoamino-benzene is filtered off, washed with water, dried between filter-paper, and recrystallised from petroleum ether or alcohol. It forms yellow plates which melt at 98 and explode at higher temperatures. The yield is quantitative. PREPARATION OFN.-METHYL DIAZOAMINOBENZENE- />.-SULPHONIC ACID (C^N . (CH 3 )N 2 . C 6 H 4 SO 3 H) .2 Seventy- seven grammes of the sodium salt of sulphanilic acid are dis- solved in 3500 c.c. of water containing 36 grm. of sulphuric acid. The solution is cooled to 5 by adding ice, and then diazotised by the slow addition of 24 grm. of sodium nitrite in 750 c.c. of water. The diazo-solution thus obtained is run 1 Gattermann, " Praxis der organ. Chemikers " (1909), p. 246. 2 B. 20, 925. THE DIAZO-, ETC., COMPOUNDS 245 slowly into a well-cooled solution of 40 grm. of monomethyl aniline in 2500 c.c. of water and 40 c.c. of concentrated hydro- chloric acid, sodium acetate or caustic soda being added simultaneously so as to keep the reaction mixture as nearly neutral (litmus) as possible. This is important, and the solu- tion must not be allowed to become alkaline. When the whole of the diazo-solution has been added, the azo-dye and the diazoamino-compound are salted out as their sodium salts by saturating the solution with common salt. The precipitate is filtered off and washed with brine. In order to get rid of the azo-dye, the whole is dissolved in concentrated ammonium sulphide solution by warming on the water -bath, and the warming continued for some time. After cooling, the brown-coloured solution is allowed to stand for a day or two, when it deposits grey leaflets. These are collected, washed, and recrystallised from hot water, when they should separate colourless. The action of the ammonium sulphide is to split the azo- linkage in the aminoazo - compound formed by a side- reaction : NHMe.C 6 H 4 .N 2 .C 6 H 4 SO 3 Na + 4H = ,NMeH yNH 2 CeH 4 v + C 6 H 4 . \NH 2 \S0 3 Na The aromatic disdiazoamino - compounds, (ArN 2 ),j NAr, are best prepared by combining two molecules of the diazo-chloride with one molecule of the primary base in alkaline alcoholic solution. 1 III. THE DIAZOIMIDES /^ The diazoimides contain the group R.NC || and are often known as triazo-compounds. They may be regarded as organic derivatives of hydr azoic acid, and can be obtained by the action of sodium azide on the corresponding diazo-salt or halogen compound. 2 As a rule, however, they are prepared (a) by the action 1 B. 27, 705. 2 Soc. 91, 1942, &c. ; B. 26, 86. 246 PREPARATION OF ORGANIC COMPOUNDS of nitrous acid on the hydrazines, the nitroso-compound first formed readily losing water on gently warming : HNO 2 H 2 O Ar.NH.NH 2 Ar.N NH 2 Ar.N N I \/ NO N or (b) by the action of the diazo-salt on hydroxyl- amine : 1 R.N:N.HSO 4 + NH 2 OH > R.N N.HSO 4 R.N N I I \/ NH 2 OH N If negative groups are present it is best to replace the hydroxylamine by potassium hydroxylamine mono- or disulphonate. Thus ^.-nitrobenzene diazo- chloride, treated in the cold with 2^ molecules of potas- sium hydroxylamine sulphonate, gives an almost quantitative yield of ^.-nitro-diazobenzeneimide. 2 The diazoimides can also be obtained by the action of the diazo-salt on the hydrazines. 3 PREPARATION OF DI AZOBENZENEIMIDE, /N C 6 H 5 .N^ || Thirty grammes of phenylhydrazine are mixed \N with 400 c.c. of water containing 45 c.c. of concentrated hydrochloric acid. The mixture is then cooled by the addition of ice, and a solution of sodium nitrite slowly run in with continual stirring until a permanent reaction is obtained with starch-iodide paper (about 24 grm. of nitrite will be required). The diazoimide separates out as an oil. The greater portion of the water is then siphoned off, the oil extracted from the residue with ether, the ether removed by distillation from the water-bath, and the residue steam-distilled. The oil is extracted from the distillate with ether, the solution dried with anhy- drous sodium sulphate, and the ether removed by distillation. The yield is about 70 per cent. Diazobenzeneimide forms a yellow oil with a stupefying odour. It boils at 59 at 12 mm. If heated at the ordinary pressure it explodes. 1 B. 25, 372 ; 26, 1271. 2 B. 33, 3408. 3 B. 20, 1528 ; 26, 1263 ; 33, 2746; J. pr. [2], 66, 336. THE DIAZO-, ETC., COMPOUNDS 247 IV. THE AZO-COMPOUNDS The azo-compounds contain the group Ar .N = N . R, and are of the greatest importance as forming the valuable azo-dyes. As the methods used in preparing the compounds differ according to whether a hydroxyl or an amino-group is present or not, they will be considered in two groups. A. Amino- and Hydroxyl Groups are Absent. (i) By the Reduction of the Azoxy-Compounds. This is the standard method of preparing the azo-hydro- carbons, the reduction being effected by distillation over iron filings. PREPARATION OF AZOBENZENE (C 6 H 5 .N = N.C 6 H 5 ) * Twenty grammes of azoxy benzene and 60 grm. of iron filings, both of which have been carefully dried on the water-bath, are well mixed by grinding, and are then carefully distilled from a very small retort, conveniently made by blowing a bulb on a piece of wide glass tubing, until nothing more distils over. The distillate, which contains traces of aniline, is washed with a little dilute hydrochloric acid, and well pressed between filter-paper. It is finally purified by recrys- tallisation from ligroin, in which it is very soluble. It forms red plates melting at 68. The yield is 70 per cent. (ii) By the Reduction of the Nitro-Compounds. The nitro-compounds can be reduced to azo-compounds by the action of zinc dust and alkali, by alkaline stannite solution, or by prolonged heating with concen- trated caustic soda and carbon (coal). 2 The best yields, however, are obtained by carrying out the reduction electrolytically, 3 the nitro-compound being dissolved in 70 per cent, alcohol containing sodium acetate. By this method azobenzene is obtained from nitrobenzene in 90 per cent, yield. (iii) By the Oxidation of the Primary Amines. This method is not much employed, but is useful when several side-chains are present. The oxidation is 1 A. 207, 329. 2 D.R.P. 210,806. 3 B. 33, 2331. See also Elb's " Electrolytic Preparations," p. 78. 248 PREPARATION OF ORGANIC COMPOUNDS carried out with alkaline permanganate or potassium ferricyanide. 1 The hydrazo-compounds can also be oxidised to the azo-compounds (mercuric oxide and ether), and this method is useful for preparing mixed azo-compounds and fatty azo-compounds. (iv) Mixed Azo-Compounds are obtained when a diazo-salt reacts with a fatty compound containing a reactive hydrogen atom, such as acetoacetic ester, 2 malonic ester, nitromethane, 3 &c. (v) Nitroso-Compounds condense with primary amines with the loss of water to form azo-compounds : 4 R.Nj6T'HiNR' = R.N = N.R' + H 2 O. B. Amino- or Hydroxyl Groups are Present. The amino-azo and oxyazo-compounds are of in- finitely greater importance than the above-mentioned azo-compounds, and although most of the above methods are applicable to their preparation, they are usually prepared by coupling a diazo-salt with a phenol, phenolic ether, or an aromatic amine. Ar.N:N.Cl + C 6 H 5 OH = ArN :N.C 6 H 4 .OH+HC1. In the case of benzene derivatives the azo-group enters the para- position to the amino- or oxy-group if this is free. If the para- position is occupied the azo- group takes the ortho- position. In the naphthalene series, if the amino- or hydroxy- group is in the a- position, the azo-group takes the para- position with respect to it unless there is a sul- phonic acid group at 3, 4, or 5, in which case the ortho- position is taken. If the amino- or hydr oxy-group is in the /3- (2) position the azo-group takes the a- (i) position. If this position is occupied no azo-compound is formed. Under ordinary circumstances, dioxy- and diamino-benzenes only couple when the hydroxy- and amino-groups are in the meta- position to one another (" Chrysoidine law"), but the ortho- and para-com- pounds will couple under special conditions. 1 A. 142, 364 ; B. 17, 476. 2 B. 9, 384 ; II, 1417 ; 17, 1926 ; 25, 746 ; 32, 197. 3 B. 27, 155 ; 33, 2043, 4 B. 7, 1638. THE DIAZO-, ETC., COMPOUNDS 249 As a rule, only one azo-group enters the molecule, but a-naphthol gives an azo- and a disazo-compound, and resorcinol gives an azo-, a disazo-, and a trisazo- compound. Some heterocyclic compounds, e.g. i-phenyl-3-methyl-5-pyrazalone, also couple with diazo- compounds. 1 The oxyazo-compounds are formed in the presence of alkali, and are obtained by slowly adding the diazo- solution to a solution or suspension of the phenol in caustic alkali or alkali carbonate, care being taken that excess alkali is always present. Under these circum- stances, if no sulphonic or carboxylic acid groups are present in either component, the azo-compound sepa- rates out and only requires to be filtered off, washed, and recrystallised. Such products are, however, useless as dyestuffs, owing to their insolubility in water. 2 If either or both the components contain the sulphonic acid group, most or all of the azo-colour remains in solution. It is usually isolated by heating the solution to 80, and then adding sodium chloride slowly until the liquid is almost saturated. Under these conditions the dyestuff separates out more or less completely as its sodium salt, and is filtered off hot. Such products are usually contaminated with considerable quantities of salt, but in many cases the dyestuff can be dissolved out and recrystallised by extraction with alcohol. In place of sodium chloride it is sometimes advantageous to use potassium chloride (" waste salt ") or calcium chloride. Dyestuffs which are very soluble and do not salt-out well are sometimes better precipitated as the free acid by adding excess of hydrochloric acid. Whether this method or the usual salting-out method is adopted, the dyestuff should not be made to separate too rapidly, as if this is done it will probably form a colloidal mass which is very difficult to filter. 1 A. 238, 183. 2 A few of them, however, such as Para Red, are produced directly on the fibre (" ice colours "). The fabric is first soaked in a solution of the diazotised amine (e.g. ^.-nitraniline) and then passed into an alkaline solution of a phenol, usually /3-naphthol. 2 5 o PREPARATION OF ORGANIC COMPOUNDS In order to avoid using an unnecessarily large quantity of salt and thus getting an impure product, the process of salting-out should be followed by "spotting" the solu- tion on filter-paper from time to time. The appearance of the spot will show how far the salting-out has gone. The aminoazo-compounds are formed in neutral or weakly acid solution, or in the presence of acetic acid, but in the case of the aminoazo-benzenes the isomeric diazoamino - compound is usually formed (cf. p. 239). With the naphthylamines, however, the aminoazo-compound is the sole product. The coupling is usually brought about by adding the diazo-solution to a solution of the base in hydrochloric acid, and then adding sodium acetate until no more mineral acid is present (Congo paper). The formation of the azo-compound is usually complete in the course of an hour, during which time the solution must be kept ice-cold in order to prevent the decomposition of the diazo-compound. If insoluble it can be filtered off directly, but if soluble must be precipitated as in the case of the oxyazo-compounds (vide supra) . Experimental details for the preparation of a number of representative azo-colours will be found in " The Synthetic Dyestuffs," by Cain and Thorpe. The method will be illustrated here by three examples. PREPARATION OF ORANGE II. Sulphanilic acid ( I 7'3 rm -) i s dissolved in 300 c.c. of water containing 4^-5 grm. of caustic soda, and ice added until the temperature falls below 5. The solution is then neutralised with hydrochloric acid, another 30 c.c. of concentrated hydrochloric acid added, and the solution diazotised with 7-2 grm. of sodium nitrite in about 50 c.c. of water. The nitrite must be added slowly, and the temperature kept below 5. When all the nitrite has been run in, the solution should show a faint reaction to starch iodide paper. If this is not the case a little more nitrite should be added. The diazo- chloride separates out in fine needles, but must on no account be filtered off or allowed to dry, as it is very explosive. /3-Naphthol (14-4 grm.) is dissolved by heating with 4-5 grm. of caustic soda and 15 c.c. of water and then pouring the solution into 1 50 c.c. of cold water. The solution thus obtained THE DIAZO-, ETC., COMPOUNDS 251 is cooled to 15, and the suspension of the diazo-salt obtained as above run in slowly with continual stirring. The whole should be tested from time to time to make certain that sufficient alkali is present. After standing for an hour most of the dye will have separated from the solution. The rest is precipitated by the addition of salt, and the whole filtered off and dried. The yield is 34 grm. HO NaS0 3 PREPARATION OF BENZOPURPURIN 48.1 Tolidine (2 1 '2 grm.) is dissolved in 300 c.c. of hot water and 20 c.c. of concentrated hydrochloric acid, the solution cooled to 5, another 30 c.c. of concentrated hydrochloric acid added, and the whole diazotised as usual with a solution of 14.4 grm. of sodium nitrite. The solution thus obtained is poured into a suspension of 54 grm. of finely ground sodium naphthionate in i oo c.c. of cold water, and the whole well stirred. At the end of half an hour the addition of a solution of 3 5 grm. of anhydrous sodium carbonate is commenced, but the addition is made so slowly that the whole of the carbonate has not been run in until twenty-four to thirty-six hours have elapsed. The solution is then heated to 80, and the dyestuff salted-out. It forms a brown powder which dyes cotton red from an alkaline bath. S0 3 Na ,CH NH 2 NH 2 CH 3 \/\/ SO 3 Na Benzopurpurin 46 1 Cain and Thorpe, " Synthetic Dyes tuffs " (1905), p. 231 252 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF I-PHENYL-3-METHYL-4-PHENYL- MeC CHN : NPh AZO-5-PYRAZALONE, * NcO Phenyl-methyl- N NPh pyrazalone (17-4 grm.) is dissolved in glacial acetic acid, the solution cooled with ice, and then treated slowly with diazo- benzene chloride solution obtained from 9-3 grm. of aniline. The azo-compound is collected, washed with water, and re- crystallised from glacial acetic acid. It forms orange-red needles with a blue reflex, which melt at 155. Aminoazo-compounds can also be obtained by the intramolecular rearrangement of the diazoamino- compounds. The rearrangement is brought about by heating with the primary base and its hydrochloride : C 6 H 5 N=N.NH.C 6 H 5 -* C 6 H 5 N-N.C 6 H 4 NH 2 and this method is of value for preparing aminoazo- compounds which cannot be obtained by coupling, owing to the formation of diazoamino-compounds. The amino-group takes the para- position to the azo- group if this is free. If the para- position is occupied, the ortho- position is taken, but the reaction does not usually proceed smoothly. PREPARATION OF .-AMINOAZOBENZENE (ANILINE YELLOW) (NH 2 C 6 H 4 N 2 C 6 H 6 ). 2 Ten grammes of finely ground diazoamino-benzene and 5 grm. of aniline hydrochloride are well mixed with 25 grm. of aniline, and the whole heated on the water-bath to 45 for one hour with frequent shaking. After standing over-night the whole is mixed with a little water, and then fairly strong hydrochloric or acetic acid added until all the aniline has gone into solution, care being taken to prevent any considerable rise in temperature. After cooling, the precipitate is collected by filtration and washed with a little cold, very dilute hydrochloric acid. The hydrochloride which remains on the filter can, if desired, be recrystallised from hot, very dilute hydrochloric acid. In order to obtain the free base, the hydrochloride is warmed with a little dilute ammonia, filtered, and then recrystallised from aqueous 1 A. 238, 183. 2 B. 10 1309 ; 20, 372, 904 ; Soc. 47, 923. THE DIAZO-, ETC., COMPOUNDS 253 alcohol containing a little ammonia. It forms orange-red prisms which melt at 127. The yield is about 70 per cent. The oxyazo-compounds can be obtained in a similar way by warming the diazoamino-compounds with phenols : Ar . NH . N : NAr + ArOH = ArN : N . ArOH + ArNH 2 . The azoxy-compounds are also rearranged to oxy- azo-compounds by warming with concentrated sulphuric acid. 1 From a theoretical point of view the formation of oxyazo-compounds by the action of hydrazines on quinones is of interest as pointing to the quinonoid structure : 0-C 10 H 7 = ;OH2J 1 0=C 10 H 7 =N NHC 6 H 5 . With benzoquinones the reaction only takes place when the hydrazine contains negative groups in the ortho- or para- position. Thus phenylhydrazine does not give an azo-compound with benzoquinone, but azo-compounds are obtained when [2] or [4] mononitro- or [2.4] dinitro-phenylhydrazine is employed. It is curious that [2.4.6] trinitro-phenylhydrazine will not give an azo-compound. For further information on this subject the reader is referred to the literature. 2 Finally, it may be pointed out that nitroazo-com- pounds can be reduced to aminoazo - compounds by treatment with ammonium sulphide, the azo- group not being attacked when the reduction is carried out under suitable conditions. This method is useful for preparing the disazo - colours derived from ^.-phenylenediamine (see p. 241). 1 B. 13, 525 ; A. 215, 218. 2 A. 340, 85 ; 357, 171 ; 360, n ; B. 17, 3026 ; 28, 2415. 254 PREPARATION OF ORGANIC COMPOUNDS V. THE AZOXY-COMPOUNDS The azoxy-compounds contain the group /\ R N N R and may be regarded as the first oxidation products of the azo-compounds. They are invariably obtained by the alkaline reduction of the corresponding nitro- or nitroso-compounds, the reduction being effected by means of alcoholic soda or potash, sodium amalgam and alcohol, zinc dust and alcoholic ammonia, or by alkaline potassium arsenite. The reduction can also be carried out by the electrolysis of the nitro-compound in dilute caustic soda. 1 n / \ PREPARATION OF AZOXYBENZENE (C 6 H 5 N = N.C 6 H 6 ). (a) 2 Twenty grammes of sodium are slowly added to 200 grm. of methyl alcohol, contained in a flask fitted with a reflux condenser. When the sodium has dissolved, 30 grm. of nitro- benzene are added, and the whole boiled on the water-bath for five hours. The alcohol is then distilled off, and the residue poured into cold water and thoroughly stirred. After the oil has solidified it is well washed with water, dried by pressing between filter-paper, and then recrystallised from ligroin, in which it is easily soluble. It forms yellow needles which melt at 36. The yield is about 90 per cent. (b) 3 Twenty-five grammes of nitrobenzene are boiled under a reflux condenser for eight hours with 30 grm. of arsenic trioxide, 40 grm. of caustic soda, and 400 c.c. of water. After cooling, the oil is collected, washed several times with water, made slightly acid with dilute sulphuric or hydrochloric acid, and then distilled in steam. A little unchanged nitrobenzene passes over first, and then pure azoxy benzene. The yield is 60-70 per cent. 1 B. 33, 2332. 2 J- pr. [i] 36, 98 ; B. 15, 865. 3 J- pr. [2] 50, 564 ; D.R.P. 77,563- THE DIAZO-, ETC., COMPOUNDS 255 VI. THE HYDRAZO-COMPOUNDS The hydrazo - compounds contain the group R.NH.NH.R, and are invariably obtained by the moderated reduction of the nitro-, nitroso-, or azo- compounds. In order to avoid the intramolecular rearrangement of the hydrazo-compound to a benzidine derivative (see p. 217), the reduction must be carried out in neutral or alkaline solution. The nitro-compounds are best reduced with zinc dust and caustic soda in aqueous alcoholic solution. Instead of zinc dust, the cheaper lead powder x can be used. The 'electrolytic method also gives satisfactory yields. 2 The azo-compounds are best reduced with zinc dust and alcohol, alcoholic ammonium sulphide, iron powder and caustic soda, and sodium or aluminium amalgam and alcohol. PREPARATION OF HYDRAZOBENZENE (C 6 H 5 NH. NHC 6 H 5 ). (a) 3 Fifty grammes of nitrobenzene and 25 grm. of alcohol are heated to boiling under a reflux condenser, and 80 grm. of zinc dust added. To the gently boiling mixture a solution of 3 grm. of caustic soda in 50 c.c. of 90 per cent. alcohol is slowly added during two to three hours. After boiling for a short time the product should be of a clear grey colour. Should this not be the case, a little water and a little more zinc dust must be added, and the boiling continued. When the reduction is complete the whole is diluted with water, the alcohol driven off in a current of steam, and the solid residue well washed on a sieve. If a sieve of suitable mesh is used, the excess of zinc dust, &c., is readily washed away from the crystalline hydrazobenzene, the latter remaining in an almost pure condition. The crude product can also be extracted with alcohol in a Soxhlet apparatus, or it can be suspended in a large volume of ice-water, and then treated very carefully with hydrochloric acid. The latter method, however, is very apt to bring about the benzidine rearrangement (p. 217). It forms colourless plates which melt at 125. The yield is about 90 per cent. i D.R.P. 81,129. 2 Z- El. Ch. 5, 108. 3 Schultz, " Chemie des Steinkohlenteers " (1901), vol. i, 94. 256 PREPARATION OF ORGANIC COMPOUNDS (b) l Azobenzene is dissolved in 6 parts of alcohol, a little water added, and the whole warmed on the water-bath with aluminium amalgam until colourless. It is then filtered hot, and the residue extracted with alcohol in an extraction apparatus. The aluminium amalgam is prepared as follows. Aluminium foil is treated with cold 10 per cent, caustic soda until a brisk evolution of hydrogen sets in. The caustic soda solution is then poured off, the foil washed three times with cold water, covered with water, and a little i per cent, mercuric chloride solution added. After a few seconds the solution is poured off, the foil well washed, and the whole process repeated . VII. THE HYDRAZINES The hydrazo-compounds considered above are to be regarded as the symmetrical di-substituted derivatives of hydrazine. The hydrazines are the mono-substituted and unsym- metrical di-substituted derivatives, and have the general formula RR'N.NH 2 , where R is alkyl or aryl and R/ alkyl, aryl, or hydrogen. Only the mono- substituted products, R.NH.NH 2 , will be con- sidered. The aliphatic members, with the exception of semi- carbazide, NH 2 .CO.NH.NH 2 (obtained by heating urea with hydrazine hydrate to ioo), 2 are of no importance. They are readily obtained by acting on the alkylene oxides with hydrazine hydrate, ethylene oxide giving two compounds : CH 2X CH 2 .NH.NH 2 CH 2 .NH.NH 2 No i -> i CH 9 CH 2 OH CH 2 .NH.NH 2 Both these are viscous oils, but form crystalline con- densation products with formaldehyde, e.g. CH 2 OH. CH 2 NHN : CH 2 . The aromatic derivatives are of considerable import- ance and are universally obtained by the reduction of the diazo-compounds. A large number of methods 1 J. pr. [2] 52, 141- 2 J- pr. [2] 52, 465. THE DIAZO-, ETC., COMPOUNDS 257 have been proposed for effecting the reduction, of which the following may be mentioned : Sulphurous acid (sulphites and bisulphites), zinc dust and alkali, zinc dust and acetic or hydrochloric acid, sodium amalgam, sodium stannite, and stannous chloride and hydro- chloric acid. Of these sulphurous acid, stannous chloride, and zinc dust and acetic acid are the ones most frequently used. PREPARATION OF PHENYLHYDRAZINE (C 6 H 5 NHNH 2 ) .1 Twenty grammes of aniline are dissolved in about 180 c.c. of concentrated hydrochloric acid, the solution cooled below o in a freezing mixture, and then diazotised in the usual way until a permanent reaction is obtained with starch -iodide paper (20 grm. sodium nitrite). Without removing the solution from the freezing mixture a cold solution of 120 grm. of stannous chloride in about 100 c.c. of concentrated hydro- chloric acid is added. After standing for an hour the phenyl- hydrazine hydrochloride is filtered off. In order to obtain the free base it is well shaken or ground up with excess of caustic soda solution, the oil which separates extracted with ether, and the ethereal solution dried with potassium carbonate. The ether is then distilled off and the residual oil fractionated in vacuo. It forms an almost colourless oil which soon assumes a red colour. B.P. 241 at 760 mm., with slight decom- position, and at 120 at 12 mm. without decomposition. M.P. 23. As phenylhydrazine is poisonous care should be taken not to inhale its vapour or to allow the liquid to come in contact with the skin. * B. 16, 2976 ; 17, 572. CHAPTER XII SULPHINIC AND SULPHONIC ACIDS SULPHINIC ACIDS, R.S0 2 H THE sulphinic acids are of but little importance, and only require mention as the members of the aromatic series are often readily obtained from the corresponding diazo-compounds by the action of sulphurous acid and copper powder, and sometimes form a convenient source of sulphonic acids, into which they readily pass by oxidation with permanganate. In replacing the diazo-group by the sulphinic acid group very careful cooling is necessary. The amine is diazotised in the usual way with sulphuric acid and sodium nitrite, and the solution then saturated with sulphur dioxide x until every 100 c.c. of liquid has taken up at least 15 grm. of the gas. The solution should remain clear. Without interrupting the stream of gas, and with continual careful cooling, copper powder (see p. 75) is added little by little until on interrupt- ing the stream of SO 2 for a minute it sinks to the bottom of the vessel. If the sulphinic acid is insoluble in water it is filtered off, dissolved in carbonate solution, filtered free from copper, and then reprecipitated with acid. Otherwise the solution must be extracted with ether, chloroform, or other solvent, the extract shaken up with sodium carbonate solution, the aqueous layer separated and acidified, and then re-extracted with a 1 Liquid sulphur dioxide can be bought in glass siphons, and these form the most convenient source of the gas. Other- wise it can be evolved by dropping concentrated sulphuric acid into technical, 40 per cent, bisulphite solution. 258 SULPHINIC AND SULPHONIC ACIDS 259 suitable solvent. On removing the solvent the sulphinic acid is left behind. As some sulphinic acids are very sensitive to heat it is best either to let the solvent evaporate spontaneously at the ordinary temperature, or to distil off under reduced pressure from as cool a water-bath as possible. The acids can also be quantitatively precipitated as their ferric salts by adding ferric chloride to the strongly acid solution. 1 Instead of copper powder, cuprous oxide may be used 2 or excess of sodium bisulphite may be added, then an alcoholic solution of sulphurous acid, and finally a small quantity of copper sulphate. 3 PREPARATION OF NAPHTHALENE- I.4-SULPHOSUL- PHINIC ACID. 4 Sixty grammes of sodium naphthionate (sodium naphthylamine sulphonate [1.4]) are diazotised in the usual way (see p. 238) with 250 c.c. of 13 per cent, hydrochloric acid and 200 c.c. of 6 per cent, sodium nitrite solution. The diazo-salt is insoluble and separates out, but must on no account be filtered off as it is extremely explosive. The liquid is then saturated with sulphur dioxide (at least 50 grm. of the gas must be taken up), the temperature being kept below o. Copper powder (see p. 75) is then added little by little until no more nitrogen is evolved, a slow stream of sulphur dioxide being passed through the liquid the whole time. After filtration the liquid is saturated with common salt, when the acid sodium salt of the sulphosulphinic acid is precipitated in almost quantitative yield. After recrystallisation from water it forms colourless leaflets. On dissolving the sodium salt in water and then saturating the solution with gaseous hydrochloric acid, the free acid is precipitated in glittering needles. For details of the preparation of other sulphinic acids by this method the reader is referred to Gattermann's original paper. 5 i Soc. 95, 342. 2 D.R.P. 100,702. 3 D.R.P. 130,119. 4 B. 32, 1146. 5 B. 32, 1136 et seq. ; Soc. 95, 342. 260 PREPARATION OF ORGANIC COMPOUNDS SULPHONIC ACIDS, RS0 3 H AROMATIC SERIES. As the aromatic sulphonic acids are infinitely more important than the aliphatic, they alone will be discussed. The methods for introduc- ing the sulphonic acid group are two in number, viz. : (i) DIRECT SULPHONATION. This is by far the most important method and consists in heating the aromatic compound with sulphuric acid. Either ordinary vitriol is used, in which case phosphoric anhydride or anhydrous potassium sulphate may be added to remove the water formed during the reaction : RH + H 2 S0 4 = R.S0 3 H + H 2 or the fuming acid (oleum) is employed. Oleums of certain concentrations are apt to go solid when standing in the laboratory, and in this case must be melted before use. To do this the stopper is removed, and the mouth of the bottle closed by laying a watch-glass over it. The bottle is then placed on a layer of dry sand about 3 in. deep in a bucket, and about half buried in the same substance. The bucket is then heated with a small flame until the acid is melted. Under no circumstances should the bottle be heated in a water-bath, as, should the bottle crack, the acid coming in contact with the hot water may give rise to a serious accident. Sulphonation is also sometimes brought about by means of chlorsulphonic acid (cf. p. 73). In order to isolate the sulphonic acid from the sul- phonation mixture the latter is poured into water, and the sulphonic acid either salted out by saturating the solution with common salt or potassium chloride, 1 or the solution is neutralised with chalk, or barium or lead carbonate. The precipitated sulphate is then removed by nitration while hot and well washed with 1 The acid comes out as the sodium or potassium salt, usually contaminated with sodium or potassium chloride. It can often be purified by alcohol, in which NaCl and KC1 are insoluble. SULPHINIC AND SULPHONIC ACIDS 261 boiling water. The filtrate, which contains the calcium, barium, or lead salt of the sulphonic acid, is then concentrated until crystallisation takes place. To obtain the sodium salt the boiling solution of the calcium, &c., salt is treated with sodium carbonate until no more precipitation takes place. The precipi- tated carbonate is then removed by filtration, and the filtrate concentrated. To obtain the free acid either the calcium, barium, or lead salt is treated with exactly one equivalent of sulphuric acid and the filtrate concentrated, or, what is better, the lead salt is decomposed by sulphuretted hydrogen and the precipitated lead sulphide removed by filtration. The temperature at which the sulphonation is carried out sometimes affects the position of the entering group. Thus naphthalene sulphonated below 80 gives the a-sulphonic acid, whereas above 80 the /3-acid is exclusively formed. A similar directing influence is exerted by traces of mercury salts during the sulphonation of anthraquinone. Thus under ordinary conditions the sulphonic group enters the /3- position, but in the presence of mercuric sulphate (o-i per cent.) the a-acid is exclusively formed. According to D.R.P. 214,516, small quantities of vanadium salts have a beneficial effect on the course of the reaction. A similar influence is exerted by infusorial earth. A variation of the above method of sulphonation, often used technically for preparing amino-sulphonic acids, consists in roasting the sulphate of the base. The sulphonic group then enters the p.- position to the amino-group. NH 2 H 2 SO 4 NH 2 S0 3 H Naphthionic acid 262 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF CALCIUM BENZENE SULPHONATE (PhSO 3 ) 2 Ca. 1 Fifty grammes of benzene are added to 300 grm . of concentrated sulphuric acid (66 Be.) Ignited infusorial earth (Kieselguhr) is then added until the whole forms a stiff meal. The mixture is allowed to stand for twenty-four hours at the ordinary temperature, after which it is mixed with 2000 c.c. of water. The boiling solution is then neutralised with chalk, filtered from calcium sulphate, and the precipitate well washed with boiling water. The united filtrates are then concentrated until crystallisation sets in. On cooling, the calcium salt separates out and may be further purified by recrystallisation from a little boiling water with addition of animal charcoal. If a good quality of guhr is used, the benzene is completely converted into its monosulphonic acid. PREPARATION OF SODIUM a-NAPHTHALENE SUL- SO,Na PHONATE,2 Forty grammes of finely pow- \/\/ dered naphthalene are added to 30 grm, of concentrated sulphuric acid (monohydrate is best) and the whole heated for eight to ten hours to a temperature of 75-8o. This latter temperature must on no account be exceeded (see p. 261). The mixture is then poured into 350 c.c. of hot water, and, after cooling, excess of naphthalene removed by filtration. The filtrate is then heated to boiling and neutralised with lead carbonate. The precipitated lead sulphate is filtered off, washed with boiling water, and the filtrate concentrated until crystals begin to form. The first crystals that separate are contaminated with the lead salt of the /3-acid and are therefore removed by filtering the hot liquid, and are rejected. On further concentrating the filtrate and then cooling, the more soluble a-salt is obtained mixed with a little of the /3-salt, and some lead sulphate. It is therefore dissolved in 10-12 parts of boiling alcohol and filtered from the insoluble /3-salt and lead sulphate. On cooling, the pure salt separates out in colourless leaflets containing three molecules of water. To convert it into the sodium salt it is dissolved in boiling water and sodium carbonate solution added until no further precipitation takes place. The lead carbonate is then removed i D.R.P. 71,556. 2 B. 3, 196. SULPHINIC AND SULPHONIC ACIDS 263 by filtration and the filtrate concentrated until crystallisation sets in. PREPARATION OF SODIUM /3-NAPHTHALENE SUL- SO 3 Na PHONATE, 1 Fifty grammes of naphthalene and \/\/ 40 grm. of concentrated sulphuric acid are heated to 1 60 for eight hours. The resulting mixture is poured into about 400 c.c. of water, and after cooling filtered from un- changed naphthalene. The filtrate is heated to boiling, neutralised with chalk, and the filtrate and washings from the calcium sulphate concentrated until crystallisation sets in. The calcium salt thus obtained is dissolved in boiling water and treated with sodium carbonate until no more preci- pitation takes place. The nitrate is then concentrated until the sodium salt crystallises out. This is finally purified by recrystallisation from a little boiling water containing animal charcoal. PREPARATION OF POTASSIUM ANTHRAQUINONE S0 3 K CO a-SULPHONATE,2 Fifty grammes of anthraquinone are carefully ground up with 0-5 grm. mercuric sulphate, and the whole added to 60 grm. of 20 per cent, oleum contained in a flask or cast-iron or lead pot. The whole is then heated in an oil-bath for three-quarters of an hour to a temperature of 150, and must be mechanically stirred the whole time. The melt is poured into 500 c.c. of boiling water, the whole boiled and then filtered while hot from unchanged anthraquinone. The precipitate is well washed with boiling water, and the united filtrates heated to 90, at which tempera- ture 50 c.c. of a cold saturated solution of potassium chloride are added. The slightly soluble potassium salt begins to separate almost at once as pale yellow glittering leaflets, which after standing over-night at the ordinary temperature are filtered off from the dark-coloured liquid and washed with cold 1 B. 3, 196. 2 D.R.P. 149,801 ; B. 36, 4197 ; 37, 67. 264 PREPARATION OF ORGANIC COMPOUNDS water. Yield about 75 per cent., allowing for the anthra- quinone recovered unchanged. On sulphonating anthraquinone without the addition of mercury salts, the /3-acid is exclusively formed. PREPARATION OF SULPHANILIC ACID, Acid aniline sulphate, C 6 H 5 NH 2 . H 2 SO 4 , is first prepared by stirring 100 grm. of aniline into 60 c.c. of concentrated sulphuric acid in a shallow basin. The whole is then heated in an oven so that at the end of four hours the tempera- ture has reached 205. This temperature is maintained for another six hours, and the melt is then broken up and dis- solved in hot water, sufficient caustic soda being added to give an alkaline reaction (about 40 grm.). The solution is then boiled for a few minutes with animal charcoal and filtered hot. On treating the filtrate with hydrochloric acid until acid to Congo paper, the sulphanilic acid crystallises out, and, after standing over-night, is filtered off and dried at 100. It forms large colourless plates. Yield about 150 grm. Treatment with sulphites or bisulphites often causes the entrance of the sulphonic acid group, especially in compounds of a quinonoid character. Nitro-groups, if present, are often simultaneously reduced to amino- groups, or may themselves he replaced l by the sul- phonic group. PREPARATION OF w.-NITRANILINE SULPHONIC ACID (C 6 H 3 [ i ]NH 2 [3 ]NO 2 [4]SO 3 H) . 2 Thirty-three grammes of m.-dinitrobenzene are added in small quantities to 100 grm. of neutral sodium sulphite dissolved in 400-500 c.c. of warm water, the whole being vigorously stirred. As soon as the dinitrobenzene melts, a vigorous reaction sets in, and after a short time a clear solution is obtained. The nitraniline sulphonic acid is precipitated as yellow needles by adding about 50 c.c. of concentrated hydrochloric acid. PREPARATION OF p.-PHENYLENEDIAMINE SUL- PHONIC ACID (C 6 H 3 [i. 4 ](NH 2 ) 2 [2]S0 3 H). 3 Thirty-two 1 B. 15, 597. 2 D.R.P. 86,097 J B. 29, 2448. 3 D.R.P. 64,908. SULPHINIC AND SULPHONIC ACIDS 265 grammes of quinone dichlorimide are mixed to a paste with a little water and then added to 200 c.c. of a 50 per cent. solution of sodium bisulphite. After standing for a short time at the ordinary temperature the reaction sets in with evolution of sulphur dioxide, but it must be rendered complete by warm- ing on the water -bath for a short time. After cooling, the white precipitate is collected and recrystallised from hot water. The acid forms colourless needles containing two molecules of . water of crystallisation. Instead of starting with the ready prepared dichlorimide, C1N : C 6 H 4 : NCI, the di-imide, NH : C 6 H 4 : NH, can be pre- pared by the oxidation of ^.-phenylenediamine, and the solution thus obtained treated directly (without isolating the di-imide) with sodium sulphite. To carry out the pre- paration by this method 30 grm. of ^.-phenylenediamine hydrochloride are added to 240 c.c. of water and 120 c.c. of acetic acid of about 40 per cent, strength. The mixture is cooled with ice, and then i6 grm. of sodium or potassium bichromate dissolved in 180 c.c. of water added. To the green solution thus obtained, 70 grm. of crystallised sodium sulphite dissolved in 180 c.c. of water are added, whereupon the solution becomes colourless and the phenylenediamine sulphonic acid is precipitated as a crystalline mass. This is recrystallised as before. As the di-imide is a very unstable substance it is better to add the sulphite before adding the bichromate. Yield about 50 per cent. NH 2 NH /\ -S0 3 H H 2 S0 3 = NH NH 2 266 PREPARATION OF ORGANIC COMPOUNDS (ii) OXIDATION OF SULPHINIC ACIDS. As the sulphinic acids are readily obtained from the corre- sponding amines by means of Gattermann's diazo- reaction, this method affords a ready means of obtaining sulphonic acids, such as naphthalene-i.4-disulphonic acid, which cannot be obtained by direct sulphonation. The oxidation is brought about either by potassium permanganate in alkaline solution, 1 or the ferric salt of the sulphinic acid is treated with ammonia and sodium hypochlorite, 2 and the resulting sulphonamide, R.S0 2 NH 2 , decomposed by boiling with dilute alkali. PREPARATION OF NAPHTHALENE- M-DISULPHONIC ACID. 3 Thirty grammes of the acid sodium salt of naphthalene sulphosulphinic acid described on p. 259 are dissolved in a little hot water (about 200 c.c.) containing 14 grm. of caustic potash. Thirty-three grammes of potassium permanganate are then added, and the whole heated on the water-bath for an hour. Excess of permanganate is then removed by adding a small quantity of alcohol, and the precipitated manganese dioxide removed by filtering the hot liquid. On saturating the filtrate with common salt, the sodium salt of the disulphonic acid is precipitated in excellent yield. PREPARATION OF BENZENE SULPHINIC AND SUL- PHONIC ACIDS. 4 Aniline is dissolved in dilute sulphuric acid (about six molecules) and diazotised in the usual way. The diazo-solution is then almost saturated with sulphur dioxide, the temperature being kept below o, and, without interrupting the stream of the gas, copper powder is slowly added until no more nitrogen is evolved. The whole is then filtered and the copper well washed with cold dilute ammonia. The united filtrates, which must still contain an excess of free sulphuric acid, are treated with concentrated ferric chloride solution until no more precipitation takes place. Ferric benzene sulphinate separates in quantitative yield, and is best converted into the free acid by shaking with a slight excess of dilute aqueous ammonia. On adding cold concentrated hydrochloric acid to the filtrate, the free acid separates out. M.P. 85. i B. 32, 1156. 2 Soc. 95, 342. 3 B. 32, 1156. 4 Soc. 95, 342. SULPHINIC AND SULPHONIC ACIDS 267 In order to obtain the sulphonic acid, 18 grm. of iron salt are shaken up with 25 c.c. of concentrated ammonia and 2 -5 grm. of ammonium chloride. A slight excess of sodium hypochlorite is added, and the whole allowed to stand for one hour. It is then made acid with hydrochloric acid (use Congo paper), when the ferric hydroxide passes into solution, leaving a residue of benzene sulphonamide, C 6 H 5 SO 2 NH 2 . This can be converted into the acid by boiling with a slight excess dilute caustic soda until no more ammonia is evolved. The sodium salt is then isolated by concentrating the solution. CHAPTER XIII MISCELLANEOUS TYPES THE PYRAZOLONES THE most important pyrazolones are the 5-pyrazolones which contain the group 4 3 C CO 5 II I N N 2 I and are obtained by the action of hydrazines on /3-diketonic compounds. The most important member of the series is i-phenyl-3-methyl-5-pyrazolonc. * PREPARATION OF i - PHENYL - 3 - METHYL - 5 - PYRA- ZOLONE. 1 Ten grammes of phenyl hydrazine are added to 1 2 -5 grin, of acetoacetic ester, and the whole well shaken. Considerable heat is evolved, and when the reaction is over, the oily product is separated from the water formed during the reaction, and heated on the water-bath until a sample poured into ether becomes quite solid (about two hours). The whole is then poured while still hot into ether, the white precipitate collected, well washed with ether, and then dried. If desired it may be crystallised from hot methyl alcohol. Colourless prisms melting at 127. The yield is almost quantitative. The preparation can also be carried out by heating the above quantities of phenyl hydrazine and acetoacetic ester on the water-bath with 20 grm. of glacial acetic acid until a sample when poured into its own volume of ether gives a hard crystal- 1 A. 238, 147 ; B. 16, 2597 ; D.R.P. 26,429. 268 MISCELLANEOUS TYPES 269 line precipitate (about two hours). The whole is then poured into 100 c.c. of ether and the pyrazolone collected. CH 3 . C . CH 2 . CO . OC 2 H 5 / \ || CH 3 .C COiOEt! foi - || 11: 1 ! H 2 |N.NH.C 6 H 5 ft NC 6 H 5 CH 3 .C CO II I N NC 6 H 5 The above compound is of technical importance, as on methylation with methyl iodide in alcoholic solution it gives antipyrine : / CH \ CH 3 C CO I I CH 3 N- NC 6 H 6 used in medicine as an antipyretic, and is also the mother-substance of some azo-dyes. ,/ NH \/\ THE ACRIDONES The acridones have the structure and are obtained from the N-phenyl anthranilic acids (p. 227) by heating with dehydrating agents, such as concentrated sulphuric acid (at 9O-ioo) or anhydrous zinc chloride. PREPARATION OF ACRIDONE. 1 Ten grammes of phenyl anthranilic acid are dissolved in 70-100 c.c. of concentrated i B. 25, 1734. 270 PREPARATION OF ORGANIC COMPOUNDS sulphuric acid, and the whole heated on the water-bath for from two to three hours. After cooling, the melt is poured on to crushed ice and the precipitate collected, well washed with caustic soda and then with water, and finally recrystallised from boiling alcohol. It forms colourless microscopic needles which exhibit an intense violet fluorescence and melt at about 350. THE XANTHONES The structure -\/\/\ \/\co/\/ is characteristic of the xanthones. They can be obtained by loss of water (cone. H 2 SO 4 at 100 or fused ZnCl 2 ) from the O.-phenyl salicylic acids (diphenyl ether ortho-ca.rbox.ylic acids) in a manner exactly similar to that employed in the case of acridone. THE THIOXANTHONES /\/ S i These contain the structure \/\ and can be obtained from the phenylated thiosalicylic acids, 1 just as the xanthones are obtained from pheny- lated salicylic acid. A more convenient method, however, has recently been published by Smiles and his co-workers. 2 This consists in condensing thio- salicylic acid with an aromatic compound in the presence of concentrated sulphuric acid. Apparently the first reaction is the formation of a sulphoxylic acid, which then condenses with the second component with loss of water, an aryl thiosalicylic acid being formed. 1 B. 43, 584; 44, 3125. 2 Soc. 97, 1290 ; 99, 640. MISCELLANEOUS TYPES 271 This in turn loses another molecule of water to form the thioxanthone : SH - I UCOOH COJOH In some cases fo's-thioxanthones are formed. The disulphides x react in an exactly similar way. THE PHENOXAZINES These compounds contain the structure \/\ NH- and can be obtained by heating the o^o-amino-phenols with the pyrocatechols. PREPARATION OF PHENOXAZINES Equal parts of o.-aminophenol and pyrocatechol are heated for forty hours to 26o-28o. The cooled melt is extracted several times with water and then with boiling dilute caustic soda. The dried residue is extracted with ether in a Soxhlet apparatus, the ethereal extract washed with dilute caustic soda, boiled with animal charcoal, and the ether removed by distillation from Soc. 97, 1290; 99, 641. 2 B. 20, 943. 272 PREPARATION OF ORGANIC COMPOUNDS the water-bath. The residue is then recrystallised several times from dilute alcohol. Colourless leaflets melting at 148. The technically important oxazine dyes are quinonoid in character and have the structure : O Cl .O, R 2 N or and \/\/ \/\ N /\/ O N They are prepared by condensing quinone dichlorimides, nitroso-phenols, or salts of nitroso-diarylamines with phenols or tertiary ammo-phenols. The reaction usually takes place simply by heating p.-mtroso- dimethylaniline hydrochloride (three molecules) with the phenol (two molecules) in the presence of some suitable solvent, such as alcohol or glacial acetic acid. One molecule of the nitroso-amine is reduced during the reaction to the ^.-diamine. PREPARATION OF GALLOCYANINE. 1 Ten grammes of gallic acid and 17 grm. of .-nitroso-dimethylaniline hydro- chloride are boiled under a reflux condenser with 200 c.c. of alcohol until a drop of the liquid placed on filter-paper gives a dark blue spot with no yellow rim, and after continuing the heating for a time an exactly similar spot is obtained. The alcohol is then distilled off from the water-bath, the residue evaporated to dry ness and then boiled with 200 c.c. of water. The dyestuff is filtered off and dried in a vacuum desiccator. It forms a bronze-coloured powder which dyes wool bluish violet on a chrome mordant. 1 Cain and Thorpe, "Synthetic Dyestuffs " (1905), p. 258. HO OH x\ MISCELLANEOUS TYPES OH 273 OH NMe 2 HCl HOr O HO HO O = 2 or N(CH 3 ) 2 co- NH \/\l 3 HC1 + 3 H 2 CO / NMe 2 PREPARATION OF MELDOLA'S BLUE. 1 Twenty-one grammes of /3-naphthol and 53 grm. of ^.-nitroso-dimethyl aniline hydrochloride are boiled on the water-bath in alcoholic solution for eight to ten hours. The dyestuff is then precipi- tated as its zinc chloride double salt by adding zinc chloride solution until no more precipitation takes place. It is collected and dried in a vacuum desiccator. It forms a dark violet powder which dyes cotton blue on a tannin and tartar emetic mordant. It has the structure : Cl ClMe 2 N Me 2 N \/ or 1 Cain and Thorpe, " Synthetic Dyestuffs " (1905), p. 257. 18 274 PREPARATION OF ORGANIC COMPOUNDS THE THIAZINES The thiazines or thiodiphenylamines are the sul- phur analogues of the phenoxazines and contain the /\/ NH \/\ structure \/\ s They are readily obtained in excellent yield by heating the diphenylamines with sulphur in the presence of anhydrous aluminium chloride, iodine, or other contact- substances. The reaction is carried out with or without a solvent. PREPARATION OF THIODIPHENYLAMINE. 1 Seventeen grammes of diphenylamine, 6-5 grm. of sulphur, and 2-5 grm. of anhydrous aluminium chloride are melted together. The reaction sets in with brisk evolution of sulphuretted hydrogen at I40-I50, and is moderated by lowering the temperature a few degrees. When the reaction has slackened, the tempera- ture is raised to 160 for a time. The cooled melt is ground up, and extracted, first with water and then with dilute alcohol. The residue consists of almost pure thiodiphenyl- amine. It may be recrystallised from alcohol. Yellowish eaflets melting at 180. The yield is 93 per cent. When an amine, or a mixture of two amines or a mixture of an amine and a phenol is heated with a suitable catalyst (I, A1C1 3 , &c., see p. 231), a diaryl- amine is formed. If sulphur is also present a thio- diarylamine results. The yields are excellent. 2 When thiodiphenylamine is nitrated, a dinitro- /\/ NH \/\ sulphoxide is obtained, 3 and when this is reduced it yields a diamino-thiazine : 1 Pat. Anm. Kl. 12 q. 17,228, 17,440, 17,995. 2 Pat. Anm. Kl. 12. O. K. 44,367. 3 A. 230, 73. MISCELLANEOUS TYPES 275 NH 9 NH, This is leuco-ihiomne (Laut's violet), the dyestuff itself being the chloride of the oxidised product, and having the formula : \/\ C1NH 2 or NH 2 NH 2 (The oxidation of the leuco-compound takes place with great ease when its solutions are exposed to the air.) These thiazine dyes are also obtained when />.-diamines are oxidised by ferric chloride in the presence of sulphuretted hydrogen (test for />.-diamines), and when a ^.-diamine and a monamine are oxidised in the presence of sodium thiosulphate and zinc chloride. PREPARATION OF METHYLENE BLUE.* Fifteen grammes of .-nitroso-dimethylaniline or a corresponding quantity of the hydrochloride are dissolved in 55 grm. of con- centrated hydrochloric acid and 40 c.c. of water, and then reduced in the cold to the corresponding diamine by means of zinc dust. Sufficient zinc dust must be used to neutralise the whole of the hydrochloric acid. The reduced solution is filtered from excess of zinc dust, diluted to 500 c.c., and then 1 6 grm. of dimethylaniline dissolved in exactly one equivalent of hydrochloric acid added. Fifty grammes of sodium thiosulphate, and then 25 grm. of sodium or potassium bichromate (both in concentrated solution), are next added and the whole boiled for two hours. After cooling somewhat, 150 grm. of 30 per cent, sulphuric acid are added and the whole boiled until all the sulphur dioxide has been expelled. The i D.R.P. 38,573- 276 PREPARATION OF ORGANIC COMPOUNDS solution now contains leuco-methyleue blue. This is oxidised to the dyestuff by adding a concentrated solution of 8 grm. of neutral sodium chromate, and the colour then precipitated by adding salt. It is collected, dissolved in a little boiling water containing hydrochloric acid, and again salted out. It forms a dark-coloured powder with a strong metallic lustre. It dyes cotton blue on a tannin mordant. The mechanism of the above preparation is indicated by the following equations : Me N NH 2 H 2 S 2 8 +0 NH 2 H Me 2 N \/\ S-S0 3 H \/ NMe 2 J +20 N S0 3 HC1 + O N Methylene blue THE AZINES The azines or quinoxalines have the structure : ***. s /\ /N^ or \/\N/\ and can be obtained from the o.-diamines by con- densing with a-diketones, such as benzil, &c., glyoxal, MISCELLANEOUS TYPES 277 a-aldehydic or ketonic acids, e.g. glyoxylic acid, pyruvic acid, or with oxalic acid. The reactions, as a rule, take place with great ease merely by boiling the diamine with the second component in some suitable solvent, such as glacial acetic acid. The compounds above cited all give rise to quinoxalines, ,N< e.g. compounds of the type The true azines, the phenazines are of \/\ N /\/ greater importance, and are obtained by condensing the o.-diamines with o^Ao-quinones, such as phen- anthraquinone, /3-naphthoquinone, &c. The reaction takes place with great ease, and as the azines are well-defined crystalline compounds, which often show characteristic colour reactions with acids, their forma- tion provides a ready means of identifying the ortho- diamines which are frequently formed when an azo- dye is reduced. The condensation takes place either on boiling the diamine and the quinone (usually phenanthra- quinone) in glacial acetic acid solution for a short time, or if, as is often the case, the diamine cannot be readily isolated, the phenanthraquinone is dissolved in sodium bisulphite, excess of sodium acetate added, and the solu- tion thus obtained added to the boiling aqueous solution of the diamine rendered slightly acid with acetic acid. ISOLATION OF AN AZINE FROM CONGO RED.i Seven grammes of Congo Red are dissolved in a little boiling water and the solution made strongly alkaline with ammonia. Zinc dust is then sifted in until the red colour vanishes. After cooling, the benzidine (see below) and unchanged zinc dust are filtered off, the filtrate acidified with acetic acid, heated to boiling, and then treated rapidly with a warm solution 1 B. 19, 1721. 278 PREPARATION OF ORGANIC COMPOUNDS of 4 grm. of phenanthraquinone in aqueous sodium bisulphite to which excess of sodium acetate has been added. The azine begins to separate almost at once. When the separation is complete the precipitate is collected, washed with cold water, dissolved in hot water, an equal volume of alcohol added and then a drop of caustic soda solution. On cooling, the sodium salt separates out as silky yellow needles which give a violet solution in concentrated sulphuric acid, changing orange - yellow on dilution. The formation of the azine takes place as follows : NH 2 N!H 2 O = 1C 1 \/\ Congo red /\/\N/\/ \ \/ The important dyestuffs, the eurhodines, apo- safranines, safranines, indulines, and nigrosines are all azines. For the methods whereby they are prepared the reader is referred to works on tinctorial chemistry. 1 1 Cain and Thorpe, " Synthetic Dyestuffs " (1905) ; Schultz, " Chemie des Steinkohlenteers " (1901); Mohlau u. Bucherer, " Farbenchemisches Praktikum" (1908). MISCELLANEOUS TYPES 279 THE QUINOLINES AND ISOQUINOLINES The quinolines and isoquinolines respectively contain the groups and N The latter compounds are somewhat difficult to prepare, and will not be further mentioned. The quinolines themselves are readily obtained by several methods, viz. : (i) SKRAUP'S SYNTHESIS. This is the most gene- rally employed method, and is of universal applica- tion to all primary aromatic amines which have one carbon atom in the ortho- position to the amino-group free. The synthesis is carried out by heating the amine with glycerine in the presence of concentrated sulphuric acid and an oxidising agent. The reaction takes place in the following stages : CH 2 OH . CHOH . CH 2 OH 2H 2 O CH I CH JO H 2 iN CH CH 2 o CH N \/\/ N CH CJH As an oxidising agent it is usual to employ the nitro- compound corresponding to the amine. Thus if the base is aniline, the oxidising agent is nitrobenzene; if toluidine, the corresponding nitrotoluene is used, &c. Better results, however, are generally obtained by using arsenic acid as an oxidising agent. 280 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF QUINOLINE (C 9 H 7 N).* Twenty-four grammes of nitrobenzene, 38 grm. of aniline, 120 grm. of glycerine, and 100 grm. of concentrated sulphuric acid are well shaken together and then cautiously heated under a reflux air-condenser on the sand-bath until a reaction sets in with evolution of white fumes. The flask is at once removed from the sand-bath and the reaction allowed to proceed without external heating. When the reaction has subsided, the whole is heated to gentle boiling for two hours, cooled, and diluted with water. Excess of nitrobenzene is distilled off in steam, the residue made alkaline with caustic soda and again distilled in steam, when a mixture of quinoline and aniline passes over. In order to separate these the distillate is cooled to 5 by the addition of ice, made acid with sulphuric acid, and then treated slowly with a concentrated solution of sodium nitrite until the liquid gives a blue coloration to starch-iodide paper after standing for ten minutes. The solution is then boiled for a quarter of an hour in order to convert the diazo- benzene chloride into phenol, made strongly alkaline, and again distilled in steam. The distillate is extracted with ether, the ethereal solution dried with solid caustic potash, and the ether removed on the water-bath. The residue is then fractionated. Colourless or pale yellow liquid boiling at 237. The yield is 60 per cent. PREPARATION OF o -NITROQUINOLINE (C 9 H 6 O 2 N 2 ).2 One hundred grammes of concentrated sulphuric acid, 5 1*5 grm. of arsenic acid, 1 10 grm. of glycerine, and 50 grm. of o.-nitrani- line are well shaken together and cautiously heated under a reflux condenser until a reaction sets in. The flask is removed from the sand-bath until the reaction has moderated, and the whole then boiled gently for three hours. After cooling, the product is diluted with a large volume of water, allowed to stand over-night, and then filtered. The filtrate is treated cautiously with caustic soda until a brown precipitate makes its appearance. The first portion of this precipitate is removed by filtration and discarded, and the precipitation then completed by adding caustic soda to the filtrate until alkaline. The crude nitro quinoline thus obtained is collected, washed with water, dissolved in alcohol, and boiled with animal charcoal. On slowly adding water to the alcoholic solution 0. -nitro - 1 M. i, 316 ; 2, 139 ; B. 14, 1002. 2 B. 29, 705. MISCELLANEOUS TYPES 281 quinoline separates out in the crystalline form. It forms monoclinic needles which melt at 88-89. The yield is 56 per cent. A variation of the above synthesis is due to Doebner and Miller. They showed that quinolines can be obtained when anilines (one molecule) are condensed with two molecules of acetaldehyde or of an aldehyde of the general formula, CHO.CH 2 R, where R represents an alkyl or aryl group. The condensation takes place in the presence of sulphuric or hydrochloric acid. Instead of using two molecules of the same aldehyde, a mixture of two aldehydes or of an aldehyde and a ketone can be used, or the benzylidene derivative can be isolated from the aldehyde and the base, and this then condensed with another aldehyde or ketone by means of zinc chloride. The reaction takes place especially easily when naphthylamine is condensed with pyruvic acid and an aldehyde, and the production of a-alkyl cinchoninic acids can be used as a test for aldehydes. The reaction takes place as follows : where R is an alkyl or aryl group, and R' and R" an alkyl or aryl group or a hydrogen atom. In the case of the above-mentioned reaction with naphthylamine, pyruvic 282 PREPARATION OF ORGANIC COMPOUNDS acid, and an aldehyde, a naphthocinchoninic acid of the COOH formula is produced. The hydrogen evolved during this synthesis often partially reduces the quinoline to a tetrahydroquinoline. PREPARATIONOFa-METHYLQUINOLINE(QUINALDINE), Thirty grammes of aniline, 60 grm. of N = C.CH 3 technical concentrated hydrochloric acid, and 20 grm. of zinc chloride are heated on the water-bath under a reflux condenser, and 25 grm. of acetaldehyde slowly dropped in during about two hours. When all the aldehyde has been added, the whole is boiled on the sand-bath for an hour and a half, made alkaline with caustic soda, and distilled in steam. The crude quinaldine is collected and fractionally distilled. Colourless liquid boiling at 247. PREPARATION OF a-PHENYL-a-NAPHTHOCINCHONINIC ACID. 2 Twelve grammes of pyruvic acid and 15 grm. of benzaldehyde are dissolved in alcohol, and an alcoholic solution of 20 grm. of a-naphthylamine added through a reflux con- denser in the course of a few minutes. A vigorous reaction sets in, and when this has subsided the whole is boiled on the water-bath for five hours. After cooling, the contents of the flask are filtered, the precipitate washed with alcohol, and then dissolved in hot dilute caustic soda. When the solution has cooled to 50 it is filtered, the precipitate rejected, and the filtrate allowed to cool. The sodium salt of the acid separates in colourless needles, and is recrystallised several times from boiling water. The free acid can be obtained by treating the sodium salt 1 B. 16, 2465 ; D.R.P. 28,217. 2 A. 249, no; 281, i. MISCELLANEOUS TYPES 283 with hydrochloric acid, and then recrystallising the precipi- tate from a mixture of alcohol and acetone. It forms lemon- yellow needles which melt with decomposition at about 300. The yield is 30 per cent. COOH OCHPh COOH /Y NCH I .CPh + H 2 + H 2 N/ \K[S V The hydrogen reduces part of the quinoline to a tetrahydro- compound. The corresponding a-phenyl-/3-naphthocinchoninic acid is obtained from /3-naphthylamine in exactly the same way. The reaction, however, is more violent, and hence the solution should not be too concentrated. It is best purified through its ammonium salt. It crystallises in lemon-yellow needles from alcohol containing a little hydrochloric acid, and from mixtures of amyl alcohol and glacial acetic acid in colourless needles. It melts with decomposition at 296. Both of the above compounds can also be prepared by allowing an ethereal solution of a molecular mixture of the three components to stand for twenty-four hours at the ordinary temperature. (ii) BAEYER'S SYNTHESIS. The second important synthesis of quinoline compounds starts out from primary aromatic amines containing a side-chain in the 284 PREPARATION OF ORGANIC COMPOUNDS ortho- position, consisting of three carbon atoms, the last of which carries an oxygen atom, e.g. o.-amino- cinnamic acid, o.-aminocinnamic aldehyde, &c. The condensation usually takes place very readily by merely heating in some suitable solvent. The reaction can often be carried out by starting with the corresponding nitro-compound and heating it with alcoholic ammo- nium sulphide. PREPARATION OF CARBOSTYRIL. 1 o.-Nitrocinnamic ester in portions of 30-40 grm. is heated with an excess of saturated alcoholic ammonium sulphide for some hours on the water-bath in closed vessels (soda-water bottles can be used conveniently). After cooling, some of the ammonium salt of carbostyril will have separated out and is collected. The alcoholic filtrates are acidified, evaporated to dryness, and the residue extracted with hot, very dilute caustic soda. After filtering, the alkaline liquors are saturated with carbon dioxide, which causes the carbostyril to be precipitated. It melts at 199. CH \ /\/ CH \ CH CH C = C = or Lactam form Carbostyril C = I NHJHOEtj CH^ CH C.OH N * Lactime form There are two important variations of this synthesis, viz. (a) the o.-amino-benzaldehydes or o.-amino-benzo- ketones are condensed with compounds containing the group CH 2 CO , viz. aldehydes, ketones, aceto- 1 B. 14, 1916. MISCELLANEOUS TYPES 285 acetic ester, &c. ; and (b) o.-toluidine is condensed with glyoxal or pyruvic acid : H ,CiH 2 Oi=C.CH C.CHg C.OH Pyruvic acid CH CH N* CH, N' CH Glyoxal Of these variations, the first is the more important. The condensation takes place very readily at the ordi- nary temperature or on gently warming the reacting substances in alcoholic solution in the presence of a trace of caustic soda. PREPARATION OF QUINALDINE. 1 One molecule of o.-amino-benzaldehyde and rather more than one molecule of pure acetone are dissolved in alcohol, and a few drops of alco- holic caustic soda added. The condensation takes place at the ordinary temperature. The quinaldine is collected by steam distillation and washed with water until free from acetone. B.P. 247. ,H / N|H 2 Of C.CH 3 1 B. 16, 1834. CH C.CH 3 N 286 PREPARATION OF ORGANIC COMPOUNDS PREPARATION OF a-PHENYL QUINOLINE. 1 o.-Amino- benzaldehyde and acetophenone (i molecules) are dissolved in aqueous alcohol, a few drops of caustic soda added, and the whole warmed for a short time. It is then acidified with hydrochloric acid, excess of acetophenone removed by steam- distillation, and the residue made alkaline with caustic soda. The precipitate is recrystallised from dilute alcohol. Colourless needles melting at 84. PREPARATION OF QUINALDINE-/3-CARBOXYLIC ESTER. 2 An aqueous solution of o.-aminobenzaldehyde ( one molecule) and an alcoholic solution of acetoacetic ester ( one molecule) are mixed and allowed to stand at the ordinary temperature. The separation of the condensation product starts almost at once. When nothing more separates, the long white needles are collected and recrystallised from dilute alcohol. They melt at 71. CHIO N|H 2 HgjC.COOEt ; ; C.CH 3 CH, N C.C0 2 Et C.CH When o.-amino-benzaldehyde and acetoacetic ester are heated together without a solvent to 160 the reaction takes a different course. HgC.CO.CHa -CO CEL >C.CO.CH 3 ,CH or ,CO Lactam form 1 Loc. cit. *C.CO.CH 3 X.OH /S-Acetyl carbostyril N ' Lactime form 2 B. 16, 1835. MISCELLANEOUS TYPES 287 The solid product is washed with ether to remove excess of acetoacetic ester, and then recrystallised from glacial acetic acid. Colourless needles melting at 232. (iii) NIEMENTOWSKI'S SYNTHESIS. An interest- ing synthesis of the a-aryl-y-oxyquinolines consists in condensing anthranilic acid with acetophenones. The condensation takes place on prolonged heating (two to five days) at I2O-I5O. It is really a variation of the above. PREPARATION OF a-PHENYL-y-OXYQUINOLINE.* A mixture of equal parts of anthranilic acid and acetophenone is heated to I2o-i3o for two to three days. The cooled melt is made alkaline with dilute caustic soda, extracted with ether, the aqueous portion acidified with acetic acid, and again extracted with ether. The ethereal extracts are discarded and the aqueous portion of the liquid filtered. The precipitate is well washed with water, dissolved in dilute caustic soda, and the solution saturated with carbon dioxide. The quinoline derivative separates out and is recrystallised from alcohol. It melts at about 250. COiOH X/SL H!CH 2 OiC.Ph CH, Ph OH C, or CH CPh Ketonic form Enolic form a-Phenyl-7-oxyquinoline B. 27, 1396. 288 PREPARATION OF ORGANIC COMPOUNDS THE TRIPHENYL METHANE GROUP The triphenyl methane hydrocarbons are best obtained by condensing three molecules of an aromatic hydrocarbon with chloroform in the presence of alu- minium chloride, as described on p. 43. An inte- resting synthesis also consists in heating k the benz- hydrols with benzene and phosphorus pentoxide 1 to 140. Triphenylmethane The most important members of the group are the triphenyl methane dyes. These may be divided into five classes, viz. : (i) The malachite green group, derived from ^. 2 -diamino-triphenyl methane. (2) The rosaniline group, derived from /). 3 -triamino-triphenyl methane. (3) The benzeins, derived from ^. 2 -dioxy- triphenyl methane. (4) The aurines or rosolic acids, derived from ^>. 3 -trioxy-triphenyl methane. (5) Phthalems, rhod- amines, and pyronines, derived from dioxy- or diamino- triphenyl methane carboxylic acids. It is impossible to give more than a rough outline of the methods employed in preparing these colours. For a fuller discussion the reader is referred to works dealing with tinctorial chemistry. 2 THE MALACHITE-GREEN DYES. The di-.-amino- triphenyl methanes are the leuco-compounds of this group of colouring-matters. On oxidation they pass into the carbinols (colourless), which in the presence 1 B. 7, 1204. 2 Such as Cain and Thorpe, "Synthetic Dyestuffs " ; Schultz, "Chemie des Steinkohlenteers," vol. ii; Mohlau u. Bucherer, " Farbenchemisches Praktikum." MISCELLANEOUS TYPES 289 of acids lose a molecule of water and pass into the dyestuffs proper : NH 2 C1 NH 2 NH 2 || /\ /\ \/ O HC1 II C 6 H 5 . C . H _ C 6 H 6 . C . OH > C 6 H 5 C + H 2 O A A \/ \/ \/ NH 2 NH 2 NH 2 The free bases are unstable. Thus on adding one equivalent of an alkali to malachite green, a coloured solution of the ammonium base is obtained, having high electrical conductivity. On standing, however, the solution becomes colourless, and the conductivity simultaneously falls, owing to the formation of the non-ionised carbinol. 1 The change may be represented thus : /C 6 H 4 NMe 2 Ph.C -~ Ph.C/ - X C 6 H 4 = NMe 2 Cl ^C 6 H 4 = NMe 2 OH Malachite green Ammonium base /C 6 H 4 NMe 2 Ph.C^-OH \C 6 H 4 NMe 2 Carbinol The dyes of this series are obtained by condensing benzaldehyde, benzhydrol, or benzotrichloride with the hydrochloride of an amine by means of phosphorus 1 B. 33, 303- 19 2QO PREPARATION OF ORGANIC COMPOUNDS pentoxide or zinc chloride. The resulting dianuno- triphenyl methane is then oxidised, usually by means of lead oxide, to the carbinol, which in the presence of acids at once loses water to form the dyestuff (see above). The dyes are usually isolated as the zinc chloride double salt. The amine always condenses in the para- position to the amino-group. PREPARATION OF MALACHITE GREEN.* Twenty grammes of benzaldehyde, 50 grin, of dimethyl aniline, and 20 grm. of powdered anhydrous zinc chloride are heated on the water-bath in a basin for four hours, the whole being well stirred at frequent intervals. The melt is liquefied by the addition of boiling water, transferred to a flask and distilled in steam until no more unchanged dimethylaniline passes over. On cooling, the leuco-ba.se adheres to the flask, and the aqueous zinc chloride solution is decanted. The base is washed several times with cold water by decantation, and then recrys- tallised from boiling alcohol. As it separates rather slowly it is advisable to allow the alcoholic solution to stand over- night before collecting the crystals. If the substance separates as an oil it is a sign that the solution has been too concen- trated, and the base must, therefore, be again dissolved with the addition of more alcohol. The leuco-ba.se separates as colourless needles, a further quantity of which may be obtained by concentrating the alcoholic mother-liquors. The yield is almost quantitative. It is oxidised to the dye as follows : Ten grammes are dissolved in dilute hydrochloric acid contain- ing 2.7 grm. of hydrogen chloride (this must be exact), the solution diluted to 800 c.c. and then well cooled by the addition of ice. A thin paste of exactly 7.4 grm. of pure lead peroxide is added little by little during five minutes, and the whole shaken for another five minutes. (The lead peroxide should be freshly prepared.) The lead is then precipitated by sodium sulphate (about 10 grm. of the salt in 50 c.c. of water), the lead sulphate removed by filtration, and a concentrated solution of 8 grm. of zinc chloride added to the filtrate. On adding saturated salt solution the dye is precipitated as its zinc chloride double salt. This is collected, dissolved in water, and again salted out. It forms yellowish green crystals. The yield is about 80 per cent. 1 A. 206, 122. MISCELLANEOUS TYPES 291 ^CeH* [ 4 ]NMe 2 // C 6 H 4 NMe 2 Ph.CHO PhCH Ph.C.OH \C 6 H 4 [ 4 ]NMe 2 \C 6 H 4 NMe 2 Leuco base /C 6 H 4 [ 4 ]NMe 2 Ph.C/ ^C 6 H 4 [ 4 ]NMe 2 Cl The zinc chloride salt has the formula : C 6 H 4 NMe 2 f x642 v (C 6 H 6 .C/ . ^ / 2ZnCl 2 .H 2 THE ROSANILINE DYES. Just as the 2 .-diamino- triphenyl methanes are the /^wco-compounds of the malachite-green dyes, so are the /> 3 -triamino-triphenyl methanes the /^co-compounds of the rosaniline colours, into which they pass by oxidation and subse- quent loss of water in the presence of acids. The rosanilines are obtained by methods analogous to those employed in the preparation of the malachite greens, viz. : (i) By condensing the ^.-amino-benzaldehydes with amino-compounds. It is usual not to isolate the amino- aldehyde, but to condense the amino-hydrocarbon with a ^.-toluidine in the presence of an oxidising agent, e.g. : i HJ/" ^-NH, T (NHaCjHtk.CH Lento-compound 1 TT/"*1 :C(C 6 H 4 NH 2 ) 2 ~ (NH 2 .C 6 H 4 ) 3 .COH Dyestuff Carbinol base 292 PREPARATION OF ORGANIC COMPOUNDS Instead of two molecules of the same amine, molecules of, two different amines can be condensed with the aldehyde, provided that the far a- position to the ammo- group is unoccupied. Thus magenta is obtained by oxidising a mixture of aniline and o.- and ^.-toluidine ("aniline oil for red"). It should be noted that in order to obtain a rosaniline by this method, there must be present one molecule of a ^.-toluidirie together with two molecules of an aniline or an o.-toluidine, or one molecule of an aniline and one molecule of an o.-tolui- dine. Although rosanilines derived from m.-toluidines are known, they cannot be prepared by this method. A variety of substances has been proposed as oxi- dising agents, viz. mercuric chloride, mercurous and mercuric nitrates, stannic chloride, arsenic acid, and nitrobenzene in the presence of ammonium vanadate or ferrous chloride. Of these, arsenic acid and nitro- benzene are of by far the greatest importance, but the arsenic acid method has the great disadvantage that it is very difficult to free the product from traces of arsenical impurities. For this reason the nitro- benzene procedure is the one almost invariably used on the large scale. PREPARATION OF MAGENTA (FUCHSIN). " Aniline oil for red " consists of a mixture of 20 parts by weight of aniline and 80 parts of commercial toluidine, this latter containing 64 per cent, of o. -toluidine and 36 per cent, of . -toluidine. One hundred grammes of this mixture, 67 grm. of concentrated hydrochloric acid, and 55 grm. of nitrobenzene are mixed together and heated on an oil-bath to 100 under a reflux air condenser. A solution of 3 grm. of iron powder in the minimum amount (two molecules) of hydrochloric acid is slowly added, and the temperature then raised to 180 and maintained at this point until a sample drawn out on a glass rod solidifies on cooling (four to eight hours) . The whole is then distilled in stearn until nothing more passes over, the residue poured into 500 c.c. of boiling water and well stirred, concentrated hydrochloric acid being slowly added until an acid reaction is obtained (about 12 Ire. will be required) . Twenty-five grammes of salt are then added and the whole MISCELLANEOUS TYPES 293 boiled for a few minutes. The aqueous solution is poured away and the residue allowed to cool and solidify. It forms a tjrjttle green mass, which is weighed, ground up, and extracted 1500 c.c. of boiling water to which 12 c.c. of concentrated hydrochloric acid have been added. The nitrate is cooled to 60, filtered, and the precipitate discarded. Salt, equal in weight to that of the crude melt obtained after the steam distillation, &c., is added to the filtrate, and the whole set aside for some time. The magenta is then filtered off and recrystallised from water containing hydrochloric acid. It forms dark-coloured crystals with a green reflex, which dye silk and wool bluish red. It also dyes cotton on a tannic acid and tartar emetic mordant. The oxidation with arsenic acid is carried out in exactly the same way, i-2 parts of syrupy arsenic acid (D = 1-8-2-3) being used to every part of red-oil. The oxidation is carried out at i8o-i90 and requires about eight hours. The dyestuff is isolated as described above. NH a ^- CHa Magenta = NH 2 C1 (ii) The Phosgene Process. A tertiary aromatic base is treated with phosgene in order to convert it into the corresponding ^> 2 -~diamino-benzophenone. This is then either directly combined with another molecule of a base under the influence of dehydrating agents, such as zinc chloride, or it is first converted into its dichloride by means of phosphorus oxychloride. These p 2 .-dia- mino-benzophenone dichlorides are blue in colour, and probably have the structure : C1R 2 N - C 6 H 4 = C C 6 H 4 NR 2 Cl PREPARATION OF CRYSTAL VIOLET. 1 Phosgene is passed into 100 grm. dimethylaniline at 20 until an increase i D.R.P. 29,943 ; cf. D.R.P. 27,789. 294 PREPARATION OF ORGANIC COMPOUNDS in weight of 18-20 grm. has taken place. After standing for twenty-four hours, 50 grm. of dimethylaniline and 30 grm. of powdered anhydrous zinc chloride are added, the whole heated to 40-5o, and then treated, with continual stirring, with phosgene until 20 grm. of the gas have been taken up. The reaction is completed by heating for six hours to 50. The whole is then made alkaline with excess of caustic soda, and unchanged dimethylaniline removed by distillation in steam The residue is filtered, the precipitate washed with water, and then repeatedly extracted with boiling, very dilute hydro- chloric acid until the extracts are almost colourless. The dyestuff is then precipitated from the extracts by slowly adding salt. It can be recrystallised from a little water. It forms glittering bronze-coloured needles. Me 2 N . C 6 H 5 S Me 2 N . C 8 H 4 . C . O H.C 6 H 4 NMe 2 HC1 (Me 2 N . C 6 H 4 ) 3 . C Me 2 N - < \NMe 2 OH (iii) New Fuchsin Process. Formaldehyde is con- densed with an aniline to form anhydro-formaldehyde aniline. This on heating with a mixture of aniline and aniline hydrochloride undergoes a molecular rearrange- ment and takes up a molecule of aniline to form a di- ^>.-amino-diphenyl methane. This when oxidised in the presence of aniline hydrochloride gives the dyestuff : CHap H 2 !NC 6 H 6 CH 2 =NC 6 H 5 j CH 2 (C 6 H 4 [ 4 ]NH 2 ) 2 C 6 H 5 NH 2 .HC1 C 6 H 5 NH 2 HC1 +0 C1H 2 N = C 6 H 4 = C (C 6 H 4 NH 2 ) 2 MISCELLANEOUS TYPES 295 The second stage of the synthesis takes place by heating the mixture for twelve hours on the water-bath. On steam -distilling from alkaline solution the excess of aniline is removed, and ^>. 2 -diamino-diphenyl methane remains as an oil which solidifies on cooling, and can be recrystallised from benzene. It melts at 85. The final stage is carried out by oxidation with nitrobenzene in the presence of ferrous chloride at 170. The excess of aniline is then removed and the dyestuff salted out. 1 Instead of aniline a large variety of primary bases can be employed. The last two steps in the synthesis can be conve- niently carried out in one operation. The methylated rosanilines are violet dyes, e.g. Crystal Violet (see p. 293). In addition to methods consisting in the condensation of methylated amines, they can be obtained by methylating magenta by the usual methods. The technical preparation of Methyl Violet B is of interest. It is obtained by oxidising dimethylaniline with copper salts in the presence of common salt and phenol : 2 C 6 H 6 N(CH 3 ) 2 -2. CH 2 + NHCH 3 .C 6 H 5 2C 6 H 5 N(CH 3 ) 2 J + 20 NHCH 3 C 6 H 4 . C(C 6 H 4 N(CH 3 ) 2 ) 2 J HC1 NHCH 3 < Methyl Violet B The phenylated rosanilines are blue dyes and are obtained by heating rosaniline bases with aniline, &c., 1 D.R.P. 61,146. 2 B. 12, 1610 ; 13, 212, 2100 ; 14, 1952 ; 16, 2005 ; D.R.P, 8251, n,8n. /\ \-N(CH 3 ) 2 c \ \=N(CH 3 ) 2 C1 296 PREPARATION OF ORGANIC COMPOUNDS just as diphenylamine is obtained by heating aniline with aniline hydrochloride. The reaction would prob- ably be facilitated by the presence of small quantities of iodine (see p. 231), but no experiments seem to have been made in this direction. The reaction is usually carried out by heating rosaniline base with a large excess (about 10 parts) of aniline to 180 for three hours in the presence of small quantities of benzoic acid. THE ROSOLIC ACID DYES. The 3 .-trioxy- triphenyl methanes are the leuco-compounds of the aurines or rosolic acids. They differ from the rosani- lines in that the carbinols are, as a rule, incapable of existence, and pass at the moment of their formation into the dyestuffs. (HOC 6 H 4 ) 2 . CHC 6 H 4 OH -* (HO . C 6 H 4 ) 2 C C 6 H 4 OH OH 1 (HOC 6 H 4 ) 2 .C = C 6 H 4 Aurine They are usually prepared by the action of concen- trated sulphuric acid on a mixture of the phenol and oxalic acid at I2O-I3O. The reaction requires about six hours : ,0 2C 6 H 5 OH (C0 2 H) 2 C( + CO * C(C 6 H 4 OH) 2 II O C 6 H 5 OH C(C 6 H 4 OH) 3 I OH [H 2 (HOC 6 H 4 ) 2 C = They can also be prepared by the action of formalde- hyde on phenol by a synthesis analogous to the new fuchsin process (p. 294) : MISCELLANEOUS TYPES CH 2 (C 6 H 4 OH) 2 297 C 6 H 5 OH +0 H.iC 6 H 4 .OH C(C 6 H 4 OH) 2 C 6 H 4 = THE PHTHALEINS AND PYRONINES. These are hydroxy-derivatives of triphenyl methane-o.-carboxylic acid, the pyronines differing from the phthaleins by containing an oxygen bridge : HO ,OH HOr OH '\ O \/ Pheno Iphthalein Fluorescei'n Both classes of compounds are obtained by heating phthalic anhydride with phenols and a dehydrating agent, the pyronines being formed from w.-dihydric phenols, such as resorcinol. The dehydrating agents used are sulphuric acid or zinc chloride. PREPARATION OF PHENOLPHTHALEIN. Twenty grammes of phthalic anhydride, 40 grin, of phenol, and 16 grm. of concentrated sulphuric acid are heated to 115- 120 for eight hours. The deep red melt is poured while still hot into a litre of cold water, and the whole then boiled until the smell of phenol has disappeared, the water being renewed from time to time as it evaporates. The precipitate is then collected, washed with cold water, and extracted with dilute caustic soda. The deep red solution is acidified with acetic acid or a little hydrochloric acid, allowed to stand for some time, and 298 PREPARATION OF ORGANIC COMPOUNDS then filtered. The precipitate is dried, boiled under a reflux condenser for an hour with 6 parts of absolute alcohol and some animal charcoal, filtered, and the charcoal well washed with alcohol. The alcoholic filtrate is then poured into eight volumes of cold water and the whole filtered through a moist paper. The filtrate is freed from alcohol by evaporating on the water-bath, when the phenolphthalem separates out as a colourless crystalline powder melting at 25O-253. It dissolves in caustic alkalies with a deep red colour. PREPARATION OF FLUORESCEIN. Ten grammes of phthalic anhydride and 15 grin, of resorcinol are heated to 1 80 in a metal dish or crucible in an oil-bath. Seven grammes of powdered anhydrous zinc chloride are then stirred in, and the temperature raised to 210 and maintained at this point until the melt has become quite hard (one to two hours) . After cooling, the mass is chipped out of the dish, ground up, and then boiled for a few minutes with 150 c.c. of water and 10 c.c. of concentrated hydrochloric acid. The liquid is filtered hot and the residual fluorescein well washed with water. The yield is almost quantitative. It forms a deep red powder, which dissolves in alkalies to a red solution with a green fluorescence. INDIGO When phenylglycine or phenylglycine-o.-carboxylic acid is fused with a mixture of caustic potash and caustic soda indoxyl is formed. This on oxidation in alkaline solution with atmospheric oxygen gives indigo : v CO a HCH 2 NHr - >CO ~- COOH I J CH/ 1 / \ NH \ CP ,NH / \ \ y CO / V^ Vo- \ / \/ Indigo \/ MISCELLANEOUS TYPES 299 The yields, however, are very poor from phenyl- glycine about 8-10 per cent., from phenylglycine-o.- carboxylic acid about 25-30 per cent., and a large number of methods for improving them have been proposed. Thus it is stated that when the fusion is carried out in vacuo yields of 90 per cent, can be obtained. 1 The addition of certain substances, such as barium oxide, 2 lime, 3 sodium ethylate, 4 metallic hydrides, carbides or nitrides, metallic sodium, soda- mide, 5 &c., also has a beneficial effect on the course of the reaction, and although the composition of the alkali-melt and the method of recovering the alkali are preserved as trade secrets, the sodamide method is probably the one used on the large scale. The method given below is the one most suitable for carrying out in the laboratory. The phenyl- glycine-o.-carboxylic acid can be obtained by condens- ing anthranilic acid with chloracetic acid, or by con- densing o.-chlorbenzoic acid with glycocoll. It is also readily obtained by saponifying the nitrile described on page 190. Which of these methods is actually used on the large scale is not known. PREPARATION OF INDIGO. 6 Ten parts of the sodium or potassium salt of phenylglycine-o.-carboxylic acid are dis- solved in a solution of 10-12 parts of pure caustic potash in 4-6 parts of water. The solution is rapidly evaporated to dryness on the water-bath with continual stirring, and the dry mass finely powdered and then added to 8-14 parts of molten paraffin (M.P. 60) at 25O-27o in a nickel crucible. Steam is evolved and much frothing takes place. The tempera- ture is maintained at 26o-28o, and the whole continually stirred until it assumes a yellow colour. After cooling, the paraffin is removed either by extraction with carbon tetra- chloride or chloroform, or by boiling the melt with water containing a little sodium bisulphite (to prevent oxidation), and filtering through a wet paper. Air is then blown through the clear boiling alkaline solution of sodium indoxyl until i B. 23, 3437. 2 D.R.P. 179,933- 3 Ibid., 63,331. 4 Ibid., 138,903. 5 Ibid., 137.955- * Ch. Z. 1911, 397. 300 PREPARATION OF ORGANIC COMPOUNDS nothing more separates out. The indigo is then filtered off, washed and dried. If desired it can be recrystallised from aniline or nitrobenzene. Yield about 90 per cent. THE INDAMINES AND INDOPHENOLS These can be obtained by condensing a ^.-nitroso- phenol or a ^.-nitroso-tertiary-amine with phenols or with primary or secondary amines in which the para- position is unsubstituted. They are more conveniently obtained, however, by oxidising a ^.-aminophenol or a ^>.-diamine containing at least one primary amino- group, in the presence of a primary or secondary amine or phenol in which the para- position is unsubstituted : Me 2 N.C 6 H 4 .NO + C 6 H 5 OH - Me 2 N.C 6 H 4 .N = C 6 H 4 = O An indophenol Me 2 N.C 6 H 4 .NO + C 6 H 5 NH 2 -+ Me 2 N.C 6 H 4 .N = C 6 H 4 = NH An indamine Me 2 N.C 6 H 4 .NH 2 + C 6 H 5 OH -* Me 2 N.C 6 H 4 .N = C 6 H 4 = O An indophenol Me 2 N.C 6 H 4 .NH 2 + C 6 H 5 NH 2 ->Me 2 N.C 6 H 4 .N = C 6 H 4 = NH An indamine It will be seen that the indophenols are derivatives of quinone-imide and the indamines derivatives of the quinone-di-imides. Although the indophenols and indamines are highly coloured and are capable of dyeing fabrics from a hydrosulphite vat (like indigo), they are of very little value as dyestuffs owing to their being loose to light and acids. They are, however, of some importance as intermediate products, a number of them being used for the production of sulphide colours. Thus extremely valuable blue dyes have lately been obtained by fusing the indophenols derived from carbazole with sulphur and sodium sulphide. These are peculiar as they dye from an alkaline hydro- sulphide vat, and not from a solution of sodium sulphide, as is the case with other sulphide dyes. As both indophenols and indamines are decomposed MISCELLANEOUS TYPES 301 by mineral acids into a molecule of ^.-diamine or p.- aminophenol and a molecule of quinone or quinone- imide : Me 2 N.C 6 H 4 .N=C 6 H 4 = O -* Me 2 N.C 6 H 4 .NH 2 +O = C 6 H 4 = O HO.C 6 H 4 .N = C 6 H 4 = NH -> HO.C 6 H 4 NH 2 +O = C 6 H 4 =NH their preparation by the second method mentioned above must be carried out in neutral or acetic acid solution, in which case bichromate is usually employed as an oxidising agent, or in alkaline solution, in which case sodium hypochlorite or potassium ferricyanide is used. PREPARATION OF a-NAPHTHOL BLUE. 1 Ten grammes of ^.-nitroso-dimethyl aniline hydrochloride are dissolved in i litre of water. The whole is heated to 45-5O, and at that temperature reduced to the ^.-diamine by adding 15 grm. of sifted zinc dust, and then stirring the whole until colourless. Excess of zinc dust is then removed by filtration, and a solution of 12 grm. of a-naphthol in about 35 c.c. of 10 per cent, caustic soda added to the clear nitrate. A solution of 10 grm. of sodium or potassium bichromate in 200 c.c. of water is next added, and technical 30 per cent, acetic acid then slowly run into the well-stirred liquid until it reacts acid to litmus. The indophenol separates and is filtered off, well washed, and dried. It forms a deep blue powder which sublimes when carefully heated. The yield is almost quantitative. i D.R.P. 15,915. INDEX Figures printed in heavy type indicate that full experimental details are given for the preparation of the substance referred to ACETALDEHYDE, 96, IOQ Acetals, 147, 150 Acetamide, 222 Acetanilide, 228, 229 Acetchloranilide, 61 Acetic anhydride, 168, 174, 175 Acetoacetic ester. See Ethyl- aceto acetate Acetone, 122 cyanhydrin, 188 Acetonitrile, 185, 187 Acetophenone, 127 Acetsalicylic acid, 127 Acetyl acetaldehyde, 119 acetone, 133 acetophenone, 133 carbostyril, 286 chloride, 68 phenetidine, 214 Acid amides, 218, 223 anhydrides, 174 chlorides, 52, 57, 64, 80 Acids. See Carboxylic, &c. Acridone, 269 Acrolein, 40 Acylamino compounds, 228 Agitators, 5 Alcohol (ethyl), 18 Alcoholates, 147, 150 Alcohols, 82 dehydration, 39 oxidation, 109, 122, 155 reduction, 41, 91 Aldehydeammonia, no Aldehydes, 108 condensations, 97, 117, 131, 143, 109, 122, 155, 164, 173, 188, 207, 233, 277, 281, 284, 286, 291, 294, 296 oxidation, 155 reduction, 41, 95 Aldol, 117 condensation, 97, 117 Algol Yellow W.G., 229 Alizarine, 102 Aluminium amalgam, 41, 93, 255 chloride, 31, 42, 43, 49, 121, 127, 129, 152, 162, 173, 274 iodide, 80 Amides, 218, 223 hydrolysis, 153 Amino azobenzene, 252 cinnamic acid, 284 aldehyde, 284 compounds, 208 acylation, 115, 138, i39> tS*' 193. 241 group, replacement by hy- droxyl, 89 guanidine, 145 naphthalene - azo - benzene, 215 naphthol, 216 diazotisation, 241, 242 sulphonic acid, 242 naphthoquinoneimide sul- phonic acid, 141 phenol, 213, 221 Ammonia, 31, 36, 108, 143, 167, 1 68 Ammonium sulphide, 241, 245, 253, 255, 284 sulphite, 222 Amyl nitrite, 182, 238 303 304 INDEX Amylene nitrosite, 195 Anhydro -formaldehyde aniline, 294 Anilides, 228 Aniline, 28, 209 Yellow, 252 Anils, 115 Anisole, 1 50 Anthranilic acid, 160, 224 Anthranol, 94 Anthraquinone, 126, 130 sulphonic acid, 261, 263 Anthraquinonoid dyes, 93 Antimony chloride, 49, 59, 79 Antipyrine, 269 Aposafranines, 278 Arsenic acid, 279, 292 Arsenious acid, 254 Aurines, 288 Autoclaves, 12 Azines, 276 Azo benzene, 247 compounds, 247 reduction, 214, 245, 277 Azoxybenzene, 254 compounds, 254 reduction, 247 BAEYER'S synthesis, 283 Barium oxide, 299 Basins, 2 Baths, 6 Beakers, 2 Beckmann change, 232 Benzaldehyde, 113, 114 Benzalmalonic acid, 166, 168 Benzamide, 225 Benzanilide, 229 Benzeins, 288 Benzene sulphinic acid, 266 sulphochloride, 74 sulphonic acid, 262, 266 Benzhydrol, 93, 288 Benzidine, 217, 241 diazotisation, 241 rearrangement, 217 Benzil, 123, 173, 276 Benzilic acid, 173 Benzo Fast Scarlet, 234, 236 Benzoic acid, 153, 159, 161 anhydride, 175 Benzoin, 131 condensation, 97, 131 Benzonitrile, 153, 187 Benzophenone chloride, 66 imide chloride, 232 oxime, 144, 232 Benzopurpurin 46, 251 Benzoquinone, 138, 142 chlorimide, 140 dichlorimide, 141 monoxime, 144, 196 Benzoyl acetoacetic ester, 135 aminoanthraquinone, 229 beazuic-acid, 129, 173 chloride, 52, 65, 98 Benzpinacone, 93 Benzyl acetoacetic ester, 136 alcohol, 83, 98 aniline derivatives, 115 chloride, 52 Benzylidene derivatives, 115, 233 naphthionic acid, 233 Bismark Brown, 240 Bleaching powder, 61 Boric acid, 102, 116 Boron bromide, 79 iodide, 80 Brilliant Yellow paper, 34 Brom acet-toluide, 53 benzene, 51, 77 benzoic acid, 77 naphthalene, 55, 58 succinic acid, 57 toluidine, 53 Boiling-points, 29 Bomb-tubes, 12 Bucherer's synthesis, 189 Butyric acid, 172 CALCIUM iodide, 80 Camphene, 41 Camphor, 124 aldehyde, 119 quinone, 130 semicarbazone, 145 Carbamide, 233 Carbon monoxide, 121, 296 Carbonic ester, 162 Carbonyl chloride, 74, 80 Carbostyril, 284 Carboxybenzoyl glycocoll, 220 phenylamino acetonitrile, 190 Carboxylic acids, 153 esterification, 177 reduction, 46, 116, 122 INDEX 305 Caro's acid, 96, 193 Caustic potash. See Caustic soda soda, 31, 85, 120, 134, 173, 285, 299 Cerium dioxide, 113 Chloral, no Chloranil, 59, 78, 139 Chloracetic acid, 50, 60 benzene, 76 dinitrobenzene, 204 formic ester, 162 Chlorine, 50 Chlor malonic acid, 60 Chloroform, 78 Chloropicrin, 78 Chlor oxybenzyl alcohol, no chloride, 109 sulphonic acid, 73 toluene, 77 Chromic acid, 109, 122, 126, 138, 142, 155, 157, 194, 301 Chromyl chloride, 112 Chrysoidine law, 248 Cinchoninic acids, 281 Cinnamic acid, 165, 167 dibromide, 62 dichloride, 62 anhydride, 174 Claisen's reaction, 131, 167 Column apparatus, 26 Condensers, 3 Congo paper, 33 Congo Red, 277 Conjugated double bonds, 62 Copper bromide, 79 powder, 37, 45, 75, 106, 109, 187, 226, 258 sulphate, 106, 242, 295 Cotton Yellow G, 234 Coumarin, 165 carboxylic ester, 169 Cresol, 91 dimethylol, 98 Crystal Violet, 293, 295 Crystallisation, i 5 Cuprous bromide, 32 chloride, 31, 45, 121, 226 Cyanhydrins, 147, 188 Cyanides. See Nitriles DESICCATORS, 19 Diacetyl oxyanthranol, 94 Diaminonaphthol sulphonic acid, 213 Diazo aminobenzene, 244 compounds, 242 benzene chloride, 238 imide, 246 compounds, 237 reduction, 44, 45, 256 group, replacement by halo- gen, 74 hydrogen, 44 mercaptan group, 1 06 nitrile group, 187 polysulphide group, 107 sulphinic group, 258 thiocyanic group, 1 06 imides, 245 Dibenzyl, 47 Dibromsulphanilic acid, 55 Dichloracetone, 123 benzoic acid, 59 malonic acid, 60 nitraniline, 55 quinone, 59 uric acid, 67 Dicyanohydroquinone, 192 Diethyl acetal, 150 acetoacetic ester, 134 amine, 168 malonate, 154, 166, 168, 169, 248 tartrate, 177 Dimethyl aminobenzhydrol, 101 aniline, 38, 231 benzophenone, 128 sulphate, 149, 180, 183, 230 terephthalate, 179 Dinaphthylamine, 231 Dinitrobenzaldehyde, 115 benzene, 203 benzidine, 204 carbazole, 202 diphenyl, 37, 46 methane, 207 phenol, 85 Dinitroso benzene, 194 resorcinol, 197 Dioxydiphenyl, 90 Dipentene, 39 Diphenyl, 37, 45, 46 amine, 23 1 chloracetic acid, 67 20 INDEX Diphenyl ethane, 36 methane, 41, 44 dicarboxylic acid, 173 nitrosamine, 198 thiourea, 235 Diphenylene glycollic acid, 104 Disdiazoamino compounds, 245 Distillation, 23 Doebner and Miller's synthesis, 281 Drying liquids, 20 solids, 20 ESTERS, 176 condensations, 119, 131, 132, 151, 162 hydrolysis, 82 Etard's reaction, 112 Ethane, 46 Ether (ethyl), 18, 148 Ethers, 148 Ethyl acetate, 177 acetoacetate, 132, 168, 169, 248, 284, 286 acetoacetic ester, 134, 168 benzene, 36 benzoate, 18, 178 bromide, 68, 71 chloride, 71 cinnamate, 168 formate, 119 iodide, 69 malonic ester, 172 Ethylene, 40, 46 dibromide, 68, 71 dicyanide, 186 Eurhodines, 278 Extraction apparatus, 2 1 FAST Green O, 197 Fenton's reagent, in, 122 Ferric chloride, 43, 127, 142, 151, 194 Ferrous chloride, 292, 295 Filtration, 8 media, 10, n Fittig's synthesis, 35 Flasks, i Fluorenone, 126 Fluorescein, 297, 298 Formaldehyde, 97, 109, 173, 207, 294 Formic acid, 156 Formyl chloride, 121 Fractionating column, 26 Freezing mixtures, 8 Friedel-Craft's reaction, 42, 127, 162 Funnels, Buchner, 9 dropping, 3, 22 Hirsch, 9 hot water, 9 separating, 22 GABRIEL'S synthesis, 218 Gallocyanine, 272 Gattermann's reaction, 75, 187, 258, 266 Glucosazone, 125 Glycerine, 279 Glycine, 219 Glycocoll, 219 Glycollic acid, 84 Glyoxal, 276, 285 Glyoxylic acid, 117, 277 Griess' reaction, 74 Grignard's reaction, 87, 161,243 HALOGEN atoms, replacement by amino - groups, 218, 225 by nitro-groups, 199 compounds, 49 Hippuric acid, 229 Hydrazines, 256 Hydrazo benzene, 255, 256 compounds, 255 oxidation, 248 Hydrocarbons, 35 oxidation, 47, 101, 112, 126, 137. 157 Hydroxyl group, replacement by amino-group, 220 INDAMINES, 300 Indigo, 298, 299 Indigoid dyes, 93, 153 Indophenols, 300 Indoxyl, 298, 299 Indulines, 278 Iodine, 49, 231, 274, 296 chloride, 60, 79 lodoacetic acid, 80 benzene, 75 dichloride, 78 nitraniline, 61 xylene, 58 INDEX 307 lodosobenzene, 79 lodoxy benzene, 79 Iron, 45, 49, 208, 247, 255 Isophthaldehyde, 112 Jsoquinolines, 279 KETONES, 122 condensations, 117, 119, 132, 143, 164, 188, 268, 277, 281, 284, 287 oxidation, 155 reduction, 41, 91, 93 KncevenagePs synthesis, 162 Kolbe's synthesis, 162 LAUT'S Violet, 275 Lead, 255 oxide, 122, 142 Lederer-Manasse condensation, 97, 173, 207 Lewco-Malachite Green, 101, 288, 290 Leuco-ihiomne, 275 Lime, 299 Limonene, 39 hydrochloride, 64 Litmus paper, 33 MAGENTA, 292 Magnesium, 87 Malachite Green, 101, 288, 290 Malonic ester. See Diethyl malo- nate Mandarin, 216, 250 Mandelonitrile, 188 Manganese alum, 114 dioxide, 114 persulphate, 1 14 Mannitol dibenzoate, 179 hexacetate, 180 Mannose phenylhydrazone, in Manometers, 1 1 MarkownikofFs rule, 63 Meldola's Blue, 275 Melting-points, 28 Menthene, 38, 41 Menthone, 123 Mercaptans, 104 Mercuric chloride, 79, 292 fulminate, 121 nitrate, 292 oxide, 248 sulphate, i 58, 261 Methylene Blue, 275 Methylene bromide, 79 group, oxidation, 126 Methyl amine, 223 tso-amyl ketone, 136 anthranilic acid, 227 diazoaminobenzene sul- phonic acid, 244 iodide, 181 propyl ketone, 136 quinoline, 282, 285 carboxylic acid, 286 Violet B, 295 NAPHTHALENE, 18 disulphonic acid, 266 sulphonic acid, 261, 262, 263 sulphochloride, 65 sulphosulphinic acid, 259 Naphthionic acid, 261 Naphthocinchoninic acid, 283 Naphthoic acid, 154 Naphthol, 87 Blue, 301 sulphonic acid, 89 Yellow S, 205 Naphthonitrile, 1 54 Naphthoquinone, 138, 140, 277 sulphonic acid, 140 Naphthylamine, 211, 221, 281 Naphthylene diamine, 215 Neville and Winther's acid, 89 New fuchsin process, 294 Nickel, 41, 42 Niementowski's synthesis, 287 Nigrosines, 278 Nitraniline, 204, 212 diazotisation, 239 sulphonic acid, 264 Nitric acid, 17, 19, 30, m, 140, iSS. 157. 199 Nitriles, 185 hydrolysis, 152, 154 reduction, 225 Nitrobenzaldehyde, 115 benzene, 203 benzidine, 203 benzoic acid, 204 compounds, 199 reduction, 208, 247, 254, 255, 264, 301 cresol, 91 dimethylaminobenzhydrol, TOO diphenylmcthanes, 207 308 INDEX Nitromethane, 220, 248 methylaniline, 230 naphthalene, 203 nitrosobenzene, 194 oxybenzyl alcohol, 99 phenol, 201 phenyl acetylene, 47 nitromethane, 199 phenylenediamine, 241 quinoline, 280 w-Nitrotoluene, 199 Nitrosamines, 197 Nitrosites, 195 Nitroso benzene, 194 j'so-Nitroso camphor, 198 Nitroso compounds, 193 tso-Nitroso compounds, 198 hydrolysis, 130 Nitroso compounds, reduction, 254, 255 dimethylaniline, 197 phenol, 195, 196 tertiary amines, 196 Nitrosyl chloride, 195 sulphuric acid, 102, 239 Nitrous acid, 122, 140, 194, 241 OLEAMIDE, 220 Oleum. See Sulphuric acid Orange I, 216 Orange II. 216, 250 Osazones, 122, 146 Osones, 122, 146 Ovens (Victor Meyer), 19 Oxalic acid, 156, 277, 296 Oxamide, 222 Oximes, 143 Oxybenzaldehyde, 116, 120 Oxybenzoic acid, 160, 163 Oxybenzyl alcohol, 98 Oxygen atoms, replacement by halogen, 64 Oxymethylene camphor, 119 Oxyquinoline (carbostyril), 284 Ozone, 114 PALLADIUM, 42 Palmitic acid, 59 Para Red, 237, 249 Paraconic acid, 166 Perkin's reaction, 164 Phenacetin, 214 Phenanthraquinone, 277 Phenazines, 277 Phenetole, 149 Phenol, 87 Phenols, 82 oxidation, 139, 142, 158 Phenoxazine, 271 Phenyl anthranilic acid, 227, 269 benzoate, 179 brompropionic acid, 63 Phenylenediamine, 210 tetrazotisation, 240 sulphonic acid, 264 Phenyl j'so-crotonic acid, i65 glyceric acid, 97 glycine, 298 carboxylic acid, 191, 227, 298 hydrazine, 95, 109, 122, 146, 257 methyl carbinol, 88, 92 phenyl- azo-pyrazolone, 252 pyrazolone, 268 naphthocinchoninic acid, 282, 283 naphthylamine, 232 nitromethane, 199 oxyquinoline, 287 paraconic acid, 166 quinoline, 286 Phenoquinone, 102, 103 Phosgene, 74, 80, 293 Phosphoric acid, 40 Phosphorus bromide, 56, 65, 68 iodide, 68 oxychloride, 66, 293 pentachloride,49, 56,64,232 pentoxide, 185, 266, 290 trichloride, 68 Phthaleins, 288, 297 Phthalic acid, 158, 159 anhydride, 129 Phenolphthalei'n, 297 Picrates, 145, 206 Picric acid, 85, 206 Pinacones, 92 Piperidine, 168 Platinum, 42, 96 Potassium bisulphate, 39, 125 cyanide, 117, 131 ethyl sulphate, 182 ferricyanide, 47, 157, 248, 301 iodide, 80 methyl sulphate, 183 INDEX 309 Potassium permanganate, 96, 1 55 l $7> 248, 266 persulphate, 47, 193 Pumps, 1 1 Pyrazolones, 268 Pyrenequinone, 137 Pyridine, 18, 51, 175, 178 Pyrocatechol, 90 Pyrogallein, 103 Pyrogallolquinone, 103 Pyronines, 288, 297 Pyruvic acid, 39, 125, 277, 281, 285 QUINALDINE, 282, 285 carboxylic ester, 286 Quinhydrone, 102, 103, 142 Quinoline, 18, 38, 168, 175, 280 Quinolines, 280 Quinone, 138, 142 di-imides, 137, 300 imides, 137, 300 monoxime, 144, 195, 198 Quinones, 137, 301 addition reactions, 102, 191, 253. 264 reduction, 42, 95 Quinoxalines, 276 REIMER'S reaction, 120 Resorcinquinone, 103 Rhodamines, 288 Rosanilines, 288, 291 Rosolic acids, 288 SACCHARIC acid, 155 Safranines, 278 Salicylaldehyde, 116, 120 Salicylic acid, 163 Saligenic acid, 100 Saligenin, 98 Salmon Red, 236 Sandmeyer's reaction, 45, 75, 187 Schotten-Baumann method, 178, 228 Semicarbazide, 144, 256 Semidine change, 217 Silver chloride, 78 oxide, 142 Skraup's synthesis, 278 Sodamide, 132, 299 Sodium, 32, 35, 41, 42, 92, 132, 168, 225, 299 Sodium acetate, 117, 180, 226 amalgam, 42, 91, 116, 254, 255 bisulphite, 89, 108, 213, 259, 264, 277 bromide, 57, 58 carbonate, 117 chloride, 57, 58 disulphide, 211 ethoxide, 33, 119, 132, 299 granulated, 33 hydrosulphite, 94, 213, 215 hypobromite, 92, 233 hypochlorite, 233, 266, 301 iodide, 80 nitrite, 139, 140, 238 powder, 33 press, 32 sulphide, 211 sulphite, 117 sulphydrate, 211 Solvents, i 5 Soxhlet apparatus, 21 Starch-iodide paper, 34 Still-heads, 26 Stirring, 5 Strecker's reaction, 189 Sublimation, 27 Succinonitrile, 186 Succinosuccinic ester, 132 Sulphanilic acid, 264 Sulphides, 151 Sulphinic acids, 258 oxidation, 266 Sulphonic acids, 260 conversion into phe- nols, 85 reduction, 104 Sulphur, 49, 50, 152, 236, 274 bromide, 57, 58 chloride, 57, 58, 152 dioxide, 95 iodide, 57, 58 Sulphuric acid, 17, 30, 40, 158, 260, 269, 270, 279, 281, 296, 297 Sulphuryl chloride, 59, 60, 73 TETRABROMDIPHENYLAMINE, 54 Tetranitrodiphenyl, 37 sulphide, 152 Thiazines, 274 Thio amides, 234 carbamide, 235 3 io INDEX Thio carbanilide, 235 UNSATURATED compounds, addi- cyanic esters, 106 tion of halogen, 61 diphenylamine, 274 addition of halogen glycollic acid, 105 acid, 63 indigo, 151 oxidation, 47, 96 Thionine, 275 reduction, 42 Thionyl chloride, 71 Urea, 233 Thiosalicylic acid, 106, 107, 270 semicarbazones, 145 VANADIUM salts, 261, 292 urea 235 Vanillin, 114 xanthones, 270 Tiemann's reaction, 189 Tin (and tin salts), 45, 208, 215, WURTZ'S synthesis, 35 247. 292 Tribromphenol 53 XANTHIC esters, 106 Trimethylethylene mtrosite, 195 Xanthones, 270 Tnphenyl benzene, 118 methane, 43 group, 288 ZINC, 41, 42, 45, 91, 208, 215, methyl carbinol, 101 221, 225, 247, 254, 255 chloride, 82 chloride, 40, 70, 180, 269, Turbines, 5 270, 281, 290, 293, 297 BALLANTYNE & COMPANY LTD TAVISTOCK STKEKT COVENT GARDEN LONDON UNIVERSITY OF CALIFORNIA LIBRARY BERKELEY Return to desk from which borrowed. This book is DUE on the last date stamped below. MAS 31 Z2Mar'56VLg ~ 8 1956 LD 21-100m-9,'47(A5702sl6)476 , *'. UNIVERSITY OF CALIFORNIA LIBRARY