THE SYNTHESIS OF ALIPHATIC ARSENIC COMPOUNDS BY THE MEYER REACTION THE REACTION BETWEEN SECONDARY ARSINES AND ALDEHYDES BY ARMAND JAMES QUICK B. S. University of Wisconsin, 1918 M. S. University of Wisconsin, 1919 THESIS Submitted in Partial Fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY IN CHEMISTRY IN THE GRADUATE SCHOOL OF THE UNIVERSITY OF ILLINOIS 1921 . 5 # ^ ' ij i -i rs- V I if UNIVERSITY OF ILLINOIS THE GRADUATE SCHOOL _ Q ^ 0 0 6 -T y-L > ] Qo J I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY- ArLictn ci Jaiae s ENTITLED T U' E SYIs 0 UaP S . 1.,-p^YE^.W R-RAPTTQu’. T T. THE. RT^IACTIOn LETWEER SECQijjJAIiY AuSIRilj S ARD ALDiihYDES BE ACCEPTED AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF Recommendation concurred in* Committee Final Examination* Required for doctor’s degree but not for master’s table 0 S’ C 0 L T E H T S I THE SYNTHESIS OE ALIPHATIC ARSElilC COiiPOUNDS BY THE Ji^EY^JH REACTION. A. INTRODUCTION 1. The General hethode for Preparing Aliphatic Arsenicals ■‘- 2. The Meyer Reaction. 3* The Statement of the Pro'olem. 6 B. THEORETICAL ^ C. EXPERIJi/jENTAL 1. The Synthesis of Araonic Acids -i-7 2. The Syiithesis of Arsinic Acids. ^5 3* The Syntheses of Arsenic-Substituted Acetic Acj.as aiid Derivatives.* j)l D. ^7 II THE REACTION BETV/EEN SECONDARY ARSINES . AND ALDEHYDES. A. THEORETICAL 49 B. EXPERIiiflENTAL C. SUi^dvoARY * ^4 III MISCELLANESOU REACTIONS A. THEORETICAL 55 B. EXPERIMENTAL 58 1. Di-alky larsine chloride on Soaiiuu it/ialonic ester.* 58 2. Arsines and Cnlor o-arsines on Diazo-acetic Ester. 58 •3» Phenj'’ larsine on the Grignard Reagent. •*•••• 60 C. SUi/uoARY * 6i IV BIBLIOGRAPHY* * 62 V VITA 63 Digitized by the Internet Archive in 2015 https://archive.org/details/synthesisofaliphOOquic "^hls invest ^ati on was undertaken at the susr^estion of Professor Ko^er Adams and carried out un■? A , ;'<■■ 't ' '''i'?“^'‘.',’^‘ » ’ V 'M* 1 I f •'' ‘'1 tj ^ »i( . V ' '^^^"l. /'l: ic — •', »■ 7 /■-: -S' N* »■ '.4 ’ • ■* -i*' ' • i '’ ' ‘ -i Iji t' ;: >r K‘ ',!rf>. . V M 4 \ •« ^ I'iSS , - , ,. . . -. .. , '^ 5 - ./'^’■V - vi^.r-uV'X «r^- , *i- Vi^;^ .‘« • ’ i . '« i .' ) ;.i..';-M.i ■;C)-,«■'■ ,;:'>*\0 s' ■''S-'iJr »au }. . ii .■»<-'*;»■■'■■-'■ . - 4 ^ It' r'* .i ‘ ' ‘ ^ ,'tVo' 4 '^,.' •. ,1 M j?. V C i,: '.i'Hi • i ..{■ 5 ^ i % • ^ * ‘ •* - . •* I ■' * '. 1, /< ' *r’ 0^3*1 *. -k*- -r ■ .' V- ♦ : ■ • • M.; ’ . ,•. . •'W;' v* ,Vl V^j:vu...y •:jt i-- ■’ . ‘ ' ' .'■■•■ 'V.. '■ ■.>. A, .xM 3 P^' .1 <■■■•* >>■, . I 1/ i'^ % • .j.W *- "•'XJ •; .V . , s«,'*.-'..,..iif.v •*'.♦ ■• ♦>; “ ‘-TOT . Iv 'i- - m/ ( , y f -iiS Z .: ,.. <* yA . 4^ ' C|*j • ^ ;w V.'' . . •I' a‘ 'i' j' .^ ’ /”,'• '. fi'/J’ 1 i‘T " "i \ . -i-- ':?. . - -g. ; aMj.: taia*-’-r.i .WW'SI ■ •'[', ' V •■' ■ ^': ‘ ^., .. ' , K';..t'l''^'A ' ' ■ ' 'V^ ■ ' V"- .; *. /'■:,• . . . ' ' . ".•■ . •■ 'a'*- '''■’.:/ fc: " ’• . V v»- : i*' .••.•’•i'{* I' M V . 4 V . ■'' ‘■■‘‘■•^ . " •■ .y^ X '•'' .u ' ■ -4 ' :■',. ivV ,.V- . *pf ■ o ^ '• t w.f _ ‘ ‘ ' 'y'i". ^ ->aw - 5 “ prepare and disagreeable to handle, and the product ootained is difficult to free frora the excess of reagents used. The Grignard reagent is the most important metallic compound used for the synthesis of tertiary arsines (11). It is report- ed -that primary and secondary arsine halides are also formed pro- vided suitable proportions of reagents are used, but the yield is negligible (12) . All the methods so far discussed witn the exception of the reaction with mercury dialk 3^1 lead to the formation of tertiary arsines or to tetra-alkyl arsoniuni halides if an excess of alkyl halide is present. Hevertneless, through the work of Baeyer ( Ij^ ; and later others ( 14 ) a method was evolved for the dealkylation of arsines which depends on the fact that when an alkyl arsenic chloride is distilled, alkyl halide splits off leaving the arsine with one less alkyl group. Thus, by the successive dealkylation a tetra-alkyl arsonium halide can be reduced to arsenic triiml- ide. The following equations serve to illustrate the conversion of an arsonium compound to a secondary’ arsine halide. R4AsX + heat = RsAs + RX RsAs + Xa — RgAsXa RsAsXa + heat = RaAsX + RX While it is thus possible to prepare primary and secondary arsines, it can readily be seen that tne method is much, too cum- bersome for general synthetic work, especially when large quan- taties of luaterials are needed. Another metnod very sirailar to tne foregoing methods is the c ondensat ioii of alkyl halides with an arsenic t-rihalide by means ’i j ‘ ii-i *' ‘ '1 1 ‘ } . . A y , 1 ^ /-.T wrT ' i i .'. 1 ^ / < 1 . .. ; I ' v« y - , . ' - ■ S' - i .. ' .'rt -V. -‘- -i ■ >i- ' 1 ■ . U - . . I • V • S w‘ ». . mV I ; J ^ 'V >' * '» / ‘ V ■ >»»yia» g"a r; * -4- of sodium for the' preparation of primary, secondary, and ter- tiary arsines. Michaelis and Paetow (15) were tne first to employ the method for the preparation of aromatic arsenicals , while Pehn ( l6 ) extended it to the aliphatic series, preparing basic diisoanyl arsine chloride. The method seems fairly satis- factory for preparing secondary arsines, but the yields are less than ^0 per. cent* 2. The Meyer Reaction. A methou which is free from most of the objections of the other methods cited, and which offers the widest application for synthesis in tne aliphatic arseiiical series is the Meyer reac- tion which consists in the interaction of an alkyl halide with sodium arsenite to give an alxyl arsoiiic acid. Although no exact proof of the mechanism of the reaction has been proposed, the follow'ing structural equation is generally accepted: JOlin R ^PWa OWa PaOAs^ + RX NaO-As^ — ^ R-As=0 + NaX ^OKa X ^ORa ONa It can readily be seen that the reaction is analogous to the form-:: ation of aliphatic sulphonic acids from sodium sulphite aiid an alkyl halide. This reaction was first described by G. keyer (17) together with other similar ones which he called anomalous reactions. Klinger and Kreutz ( 18 ) reiiivestigaged the reaction and improved the method so as to obviate the necessity of sealed tubes. The scope of the reaction was considerably broadeneu when Auger (19) found that the alkylation could be carried on further by allow- - 5 “ ing an alkyl iodide to react wiiih the sodium salt of aii alkyl arsenious acid which is prepared hy dissolving axi alkyl-arsen- ious oxide. in a calculated amount of sodiu/a hydroxide. The method was again modified toy Be'hn (10) for the purpose of using it in tone syiithesis of large amounts of ar sonic acids ana x-hen used toy the same author with McGrath (20) for the preparation of two new arsonic acids. Ihe method v/as employed oy Ehrlich and Bertheim (21) for tne synthesis of mixed arsinic acids contain- ing one alkyl aiid one aryl radical. In this case the alxyl halide was allowed to react with sodium phexiylarsenite . Recent- ly Burrows and Turner (22) have utilized the method for the pre- paration of dimethylarsine iodide, and Vaieur aiid JDelatoy (23) have reinvestigated the action of etnyl iodide on potassium ar- senite. The possitoilities of the iaeyer reaction were recognized to some extent in the preparation of toxic gases during the recent war. Large quantities of ethylarsonic acid from which ethyl- arsine dichloride was obtained were prepared in Germany (24) toy the action of ethyl chloride on sodium arsenite under pressure and at an elevated temperature. In this countrj^ met-hylarsnnic acid, t-he source of methylarsine dichloride, was prepared toy the action of dimethyl sulfate on sodium arsenite. ( 23 ). Ija neither case, however, was the arsonic acid isolated. Although the original synthesis has toeen modified at various times, it has, w^i ch the exception of the tvtfo w^ar methods, reiuain- ed fundamentally unchanged, and it has retained its original dis- advantages. In the first place, the use of an alkyl ioaide is - 6 - ob J ect ioiicible sine© it mo-ices tbe isolcitioii oi tiie arsoiiic a-cid exc eedingl3'’ difficult. Unless the iodine is removed before the solution is acidified, the hydriodic acid will reduce the arsen- ic acid immediately. Of course, the iodine can readily be re- moved by means of silver nitrate, but the expense prohibits its use for the preparation of large amouiits of material. The second objection is tne use of alcohol as a solvent, for in the alka- line media it causes the formation of ethers to a considerable extent. Valeur and Delaby (25) have found in their study of the action of ethyl iodide on potassium arsenite, that whexi al- cohol was used as solvent over ^0 per cent of tne ethyl iodide was lost through the formation of ether while when it was omit- ted less than 10 p er cent was lost, although the conversion of the potassium arsenite in the latter case was exceedingly slovtf. Undoubtedly this formation of ether becomes even more iiiarked with the higher alkyl halides. Although the two methods used during the war are free from the oojections cited, they are hard- ly adapted for general use, since one requires the use of an autoclave, while the other is limited to the preparation of methylar sonic acid. 3 . The Statement of the Problem. The brief review of the jleyer reaction clearly points out the fact that it is by far the most important and most promising method for the s 3 mithesis of aliphatic arsenicals. Uot only is it convenient and easy to carry out, but it gives the arsonic acid directlj^ from which the other possible types of arsenicals frtrrr»£B - 7 - ca.il DC prepared* In its present form however it is ill adapted for general synthetic work* The aim in this work is "Do study Xp'ne reaction in order to make it applicable to the preparation of as many t 3 ''pes of alipnatic arsenicals as possible, and to help fill the glaring gaps in t?ie list of this series of compounds. It might be well to mention tha^ up to the present time only four primary and four secondarj^ arsinic acids have been prepared, and that the exact constants for trimethylarsine (26) and cacodyl chloride ( 27 ) were not recorded until last year. In this work trie Meyer reaction is modified as follows J the alkyl bromides are used instead of the iodides, the use of alco- hol as a solvent is abandoned, and in its stead heating and stir- ring is substituted. With these changes attention is first direc- ted to the preparation of simple arsonic acids, then extended to diarsonic acids and to a number of special types such as /^‘-hydroxy ethylenearsonic acid. The second part of the work is concerned with the preparation of arsinic acids, and also a few special types for example, /^-pheno>^ethyl-phenylarsinic acid, are in- cluded. The third part of the investigation centers around the synthesis of arsenic-substituted-acetic acids of the type RAsOa HCHaCOOH, and its derivatives wriich are prepared by the action of cnloroacetic acid and it scderivatives on sodium arylarsenites . The possibility of finding perhaps some compounds of therapeutic value among this series occasioned the preparation of the large number of derivatives. - 8 - B. THEORETICAL In studying the action of an alkyl oroiiiide or chloride on sodium arseiiite it was found that the most important iactors were the reactivity of the halogen in the alkyl halide, the sol- ubility of the alkyl halide, and the temperature of the soaium arsenite solution* The effect of tne first was clearly illus- trated by the great reactivxiess of benzyl chloride, as compared with the inertness of isopropyl bromide. A comparison of the action of ethylene chlorohydrin and ethyl bromide indicate the effect of solubility, the former react iiig 10 times as fast as the latter. The best estiiaate of the method, however, can be obtaiii- ed by a study of the synthesis of a series of arsonic acids. The first compound to be prepared was the sodium salt of methylars Ohio acid. No improvement over the existing method could be fouiid, for, in the first place, the formation of ether due to alcoholic potash is slight, and in second place, the iso- lation of the acid in the form of its sodium salt is exceedingly easy, since the latter is iiisoh-ible in ^0 per cent alcohol. The reaction does take place in the absence of alcohol, but the yields are somewhat lower, and, eventually, alcohol must be added to precipitate the product. The advaiitages of the modified Meyer synthesis become appar- ent in the preparation of ethylarsoiiic acid. While the formation of ether is over per cent v/hen alcohol is used, no appreciaole amount of ether was formed with the new modification. V/nile ethyl arsonic acid was never isolated directly as the free acid in the - 9 - old method by either Dehii ( l6 ) or Valeur ( 25 ), no difricul&y was experienced in doing that. Although Dehii obtained farily satisfactory results in the preparation of propylarsonic acid ’03'' the old method, ihe modi- fied s3rnthesis again proved superior. The 3’’ields v/ere decidedly higher, and the acid was readily obtained oy simply acidifying the reaction mixture after it had been concentrated to a small volume. Although xi-propyl bromide reacted readily with sodium arsen- ite, isopropyl bromide did not react, consequently, the arsenic acid could not be prepared. ]^o doubt the low boiling point of the alkyl halide and the stabilit3" of the irialogen atom are the , main reasons for the negative results. n-Eutyl bromide acted somewnat slower than n-propyl oromide, but no difficulties were met in trie preparation of large quanti- ties of the arsonic acid. Due to its relative insolubility in water its isolation is exc eedingl3'' simple. Although no primtiry or secondan^ allyl compound of arsenic has previously been prepared, the preparation of allylarsonic acid is surprisingly easy. Whereas the preparation of simple saturated aJ-iphatic arsomic acid took about 24 hours, this syn- thesis was complete in 4 hours. No trouble was experienced in isolating the free acid. Ethylene chlorohydrine reacted very readil3'' with sodium ar- senite, but attempts to isolate the product failed. A syrupy liquid vi/hich apparently was the impure compound since it showed the properties of an arsonic acid, was obtained. ■i.'i - - ■ , I , , ^ - V. i ■ . . • ' vi. i . ( 1 L . V. - .. . - . I -k ' >••’ • >- • ■ jl s‘' t . ... »k *i 'J • .J ' ji. .'it. ■• . . . ^,. ■ s » ' - # A ' » ti ■ - • -■ c . .1 . . ■ } :>< r, , . - 10 - For unexplainable reasons no appreciable reactioii took place vvhen sodiim arsenite was treated v-/ith such compounds as phenr* ethyl bromide, and /phenoxypropyl bromide. Negative re- sults were also obtained with et'i'Xjrlene dibromide, ana trimefnyl- ene bromide. Although the latter reacted, it was not possiole to isolate tne product. The arsonic acids are the starting materials for the other types of compouiids, as the arsines, the alkylarsiiie chlorides, and aikylarsines oxides. In this work etriyl and n-butylarsine dichloride were prepared. The arsonic acid was dissolved iii concentrated hydrochloric acid t o which a few crystals of potas- sium iodide hau been added, and the solution saturated w/ith sulphur dioxide. The desired product was obtained as an oil which could be purified by distillation. This method failed with allyl arsonic acid. An oil was obtained on extracting the solution with ether, but on atteiripring to distil it^ a tarry mass resulted, apparently polymerization having taken place due to the unsaturated linkage. Secondary Arsinic Acids. No really satisfactory” method is described in the litera- ture for the preparatioii of secondary arsinic acids. Cadet’s reaction is limited to the preparation of cacodylic acid, and, furthermore, it is beset with experimental difficulties. One of the most satisfactory meohods descrioed is -Dne condensation of an alkyl halide with arsenious chloride 'oy means of sodium using molecular proportions, nichaelis and Paetow (15) usiiig benzyl chloride found chat the secondary arsine chloride pr ed ominaxea . - 11 “ Dehn ( l6 ) used the reaction for the preparation of di-isoaiuyl- arsine dichloride which he converted into the corresponding ar— sinic acid by the action of bromine on the alkyl- arsine chloride in aqueous solution. In attempting to apply this syiithesis to the preparation of di-n-butylars iiiic acid results wnich were not altogether satisfactox^^ were obtained. The yield of oasic di- n-butyl arsine chloride was never more thaxi ^0 per cent, axia its conversion to the arsinic acid w'as far from quantitative, es-pec— ially when the directions of behti were followed, ixi which the bromination was carriea out in a warm solutioii. The oest results were obtained when the oromine was slowly addea to a well stirred and cooled solution, although even thexi the yield was only ^0 per cent. Follov/ing the usual procedure for making arsonic acids, the Meyer reaction was applied to the syaithesis of dialky lar sinic acids with satisfactory results. A sodium alkylarsenite was pre- pared by dissolving axi alkylarsixie dichloride in a calculated amount of 10 il. sodium hydroxide. The reactions involved in the synthesis were: RAsCla + 4NaOH -> RAs( OHa )a + 2RaCl RAs(0Na)a + RCl RaAsOaWa + RaCl The synthesis of the secondary arsinic acids proceed. s much faster than that of the arsonic acids. Whereas it required about 24 hours of heatiiig and stirriiig to prepare the arsonic acid, only 4 hours were required to prepare aixy of trie arsinic acids. In this work diethyl, di-n-but^^l, ana propyloutylars inic acids were prepared. Due to the great solubility of diethylarsinic i.J L [ di ) £U»0C ..iiVwi , . . ... . L» / r !•*. uJ: ii L : ' X *' * * * * f * A. ^ . .. . . , i ;. -Ot^ i.u , . o : :*V .1- - ‘•-• \ ,, ♦, . X- Ov •‘ '^ 6 '^ k ' .i. . > V ._ *'.’• 1 . . . .V ■ ! • ‘ ..V. . ^ ni . . >Jt . i - 12 - acid, li was difficult to get it entirely free from traces of sodium chloride. lii tne case of diDutyl arsinic acid, a yield of 96 per cent was obtained. The great tendency of tne arsinic acids to remain oils if impure, caused a considerable aiiiount of diffi- culty. Although butyl bromide reacted with sodium pheiiylarsenite to the extent of 90 per cent, no crystalline product ooula be ob- tained. On acidifying the reaction mixture, an oil separated which could not be purified. Ehrlich and Bertheim (21) prepared a number of these alipha- tic-aromatic arsinic acids by tne action of an alkyl iodide on an alcoholic potassium arsenite solution. After a cedious and ex- pensive procedure, which involved the removal of the iodine by means of silver nitrate, and the isolation of tne acias tnrough the silver salts, they were obtainea in the form of crystalline solids. Ill trying to prepare phenyletn^/'iarsinic acid, Oiie of the acids prepared by Bertheim ana Ehrlich, by- tne new metnod an oil was also obtained. The oil possessed the chemical properties of a secondary arsinic acid , especially in regard to soluoility in ammonia and alkalies. If means were found to purify the product, it would undoubtedly be obtained in crystalline form witn yields that would surpass those obtaiiied by uhe older method. In order to get an estimate of the scope of the neyer reac- tion a few special types or arsinic acids were prepared. /^Pheny- oxyet hy 1-phenylarsinic acid was prepared witn somewhat poor yields by the action of phenoxyethyl bromide on sodium pherylarsenite. An interesting di-arsinic acid was prepared having the formula I ) I \ I yj ♦ t. » • • J • i I k*#«^ . J. I ,\ 4 :: I r V" U' i,.. ii ■ap - 13 “ CeHBAsOaHCHaCHaAsOaHCfs^ In trying to make the corresponding t r imet tiylene diarsinic acid an oil was also obtained for which no means of purification were found. Waile amino acids occupy an important position in organic chemistry, only one arsenic-substituted aliphatic acid is known. This compound, which is p-amino-phenylarsinic-acetic acid^was prepared by Ehrlich and Bertheim (28) by the action of chloro- acetic acid on sodium p-amino-phenylarsenite . This new exten- sion of the Meyer reaction v^as , however, noD developed further. The derivatives of p-amino-phenylarsinic-acetic acid as well as those of the simplier, phenyl-- arsinic- acetic acid are interestiiig oecause they represent a new type of arsenic com- pound which has not oeen investigated in regara to its physio- logical properties. Bixice a most thorough study has been made of arsenicals in which botn the arsenic o,xia the xiitrogen are at- tached airectly to the aromatic nucleus, it seems advisaole to direct attentioxi to compounds in whicn these tvxo elemexits are linked to aliphatic side chaixis as is the case in the aromatic- substituted amides of these two acids. These substances 'possess properties wnicn make them adapta- ble for therapeutic study. Thej'' dissolve readily ixi sodium bi- carboiiate to form neutral solutions. The arsexiic is in the sta- ble pentavelent state wnich is desirable for preliminary' biolog- ical study. Due to the simplicity of synthesisixig one deriva- . tives, the parent substance can be modified almost at will. The extent to which the modif icatioxis can be carried out is illus- trated by the compouxid f'ormed by condexisixxg p-amixio-pnexiylarsen- -’1 , . _ . ^ V , i'l j . s * - .V • . ^ . i. . / i . > '• . . ; , I . , . . V, . ,.1 ■ ■ J. . tj .■ i V 1- - i ^ J. '*iX • .. J ........... 'i. . ..i j j ■i i .. . ■ ^ ..... ' ^ • .i-. - - - - • ■ ' • > ■ • - - r. -V ^ *j . . .‘is V ^ X..' i. '*r*' i u. .' — V* ^ V ■ i , t cj i, 1 it* v«i ■X- < ^ J J. > I > }j . . f \ : o Lo .1 r 'i ; f V I 4 W . ^ J t % i i , t >1 ' j ■- . •' V* ■ - 14 - ious acid with chloroacetyl arsanilic acid. It still retains an active amino group on one end of tne molecule and tne arsonic acid radicle on the other, while the two aromatic nuclei are connected hy an ars inic-acetyl-amide chain* Phenyl-arsinic-acetic acid was prepared oy the action of chloroacetic acid on sodium phenylarsenio e wnicn was rnaae oy merely dissolving pnenylarsine dichloride in the calculated amount of sodium hydroxide. By reducing the compouiid formed with sulphur dioxide in concentrated hydrochloric acid solution, pheijyl-bromoarsine-acetic acid was formed, snowing that pheiiyl- arsiiiic-acet ic acid reacts as a secondary arsinic acid. In order to prepare derivatives of this acid, it was desirable to make the acid-chloride, but it was soon found that the reagents nec- essarj-" to make the latter c orapound^ split the arsenic radical from the acetic acid group no matter how carefully the conditioxis of the reaction were governed. Since the acid ciiloride could not be prepared, it was xiec- essary to fixid some other way to make these acetyl derivatives. It was found thax Ciiloroacetyl derivatives, especially? lihe aroma- tic substituted amides would react equally as well as tne free acid, giving directly^ tne desired phexiylarsinic acetyl derivative as illustrated oy tne follov>?ing equatioxi: CeHBAs(0Pa)3 + ClCE3C0Kim-> CeHeAsOalmCHa COhHR + RaCl The procedure was surprisingly simple. A calculated amount of dhe chloroacetyl derivative was added to a solution of sodium phenylarsexiit e prepared in the usual way. The desired reaction took place without heatixig or stirring, and was generally com- t' u - . - I i fN ’fi ... ^ . .c *>.L - ' " ■’ J J I'*.".. . . ..:j . .1 I ..; ^ I . _ i. i i - •• '■*- ‘ .j <. * u. . . ' - . . . ■ V i 4 ^ ., Cy ‘ .» f .» C j : ; - io .* U /• .f ; ts • w - - ^'• ■y ^ ' ‘J ^• 4 . .. . - r‘ • X - ^ ^ ; l"*'' *• ^ i'; - .^-,-vAty • i . j"r , . C .. .ii •.:{ . 4 -jC V i 4 , 4 . I . i >^4- -4 -*. 4- '-0 < • I t-V L;;i 4 . .f:y ; ^ . • • V. ...lU , .1 - .i, ut-.T .eCri^L.'oilll* -.'1..I -iitir! a .>•. f- I'? uit4 OJ :• i. j-iJi.W .. '.t : .4 0 i itjw .,r, jjijo'ivi &fi!a »b*i . ,4 .V^ '■ b&^TnV I . . .vft»o i9ii 0 ^ tit4 , O' • .ii4 .j L‘. . inr^iOtx-t- v-'iX^*o l«q & Ul 4 !' M w i.. '''^ i. C i I t.. U Xi»5 .itSf^A’ .* 4 . t 7 p i,..i> 4 wa 1 '.. -,. . , 4 , I .•* .e>^ ..oijiSujL iXnwq' V' ..o«.. v>w' 1 t4 L>i'\ jOqm' ' t J.,u , Jj,. ;. . *4... j4. -. '.444j4^.‘*^ia ’iO j.OrfiX':'X^i r .i .. -%. 4 .i . .nojJL'Of/ '•;i '.^vi-4* 4 --. iU.n .14 4' i ttuo«f \ 4 , . 4 »j. i.’i-l. ^K'J< iLU L^ti ,.* tulv i.iyjJ .C -.. ..i.i.Orc4eUH &£f5‘ ,. j ^'0 •■ J I- c-iJXix :;i eixiM'aqaioo . ■ ■•i' r.. , ■ .,' .n.^ ‘‘•i ti 0*lUvT OvJ .0 . .. i.: . l -l r .i; -.pi1r,Wo - 16 - Because of the therapeutic value of arsauiiic acia, the pre^ paration of a numtoer of derivatives of p-amino-phenylarsixiic- acetic acid seemed advisable. These c ompounas were prepared in the same way as those in fhe precediijg series. The cnloroacetyl derivatives were allowed i^o react witn tne sodium salt of p— aiuino phenylarsenious acid prepared by dissolviiig 1 mol- of the Hydro- chloride of p-amino-phenylarsine dicnloride in mols, of sodium hydroxide. To iMike the latter substance, arsaiiidic acid dis- solved ixi concentrated iij’'drochloric acid was reduced by means of sulphur dioxide. The reaction was em:irel3'- similar to the pre- cediiig oiie, and the products resembled the correspond iiig phenyl- arsinic-acetyl derivatives in their general physical and chem- ical properties. The presexice of a free aimlno group rendered the compounds soluble in concexit rat ed hydrochloric acid, and made the prepar- ation of N-gylcyl, and y-acetyl derivatives possible. While the syntheses of aromatic-substituted amides proceed- ed smoothly in all cases, the preparatioxi of aliphatic acetyl derivatives was attexided witri little success. The only compouxid prepared was one calcium salt of p-amino-pnexicy^larsinic -( acid ) acetyl urea. Tnese negative results are uxiuouotedly explaiiied by the fact that the speed of the hydrolysis of tne aiipnatic acetyl derivative exceeds that of the expected react! oxi. mm - 17 “ C. EXPERIMEirrAL 1. The Synthesis of Arsonic Acids. jt Di-Sodiuia methvlars onate . 94 g. of methyl iodide_ were add- ed to a well stirred solution of 60 g. of arsenious oxide in 600 cc. of 2*5 tl sodium nydroxide maintained at a temperature 0 ^ - a. , - of 43-50 • At the end of 30 minutes an equal volume ol alconoi was added to precipitate tiie sodium salt of metnylarsonic acid. After allowing tne solution 10 stanu several xiours, the product was filtered off, v^asded witn alcohol, and finally dried for one ^ 0 hour at oO in vacuo. The yiela was 100 g. To remove traces of insoluble impurities, tne product was redissolved in a small volume of water, filtered and reprecipitated with an almost quan- titative yield by the addition of alcohol. following the directions of Klinger ana Kreutz, ( iS ) prac- ticall 3 r quantitative yields were obtained. St hvlar sonic aci d . The acid was prepared oy the action of ethyl bromide on sodium arsenite. To the sodium arsenite pre- pared by dissolving 19S g arsenious oxide in 300 cc. of 10 N sodium hydroxide, 110 g, the theoretical amount of ethyl bromide^ were added, but to compensate for the loss due to its volatility 50“73 §• more were added in the course of the reaction, ihe reaction v ana Dehn (10), 99»5°» In another experiment ethylarsine dichloride, itistead of the acid, was isolated. The reactiati mixtuir-e was concentrated and acidified as before, but after the solution had been reduced to a small volume ^ volumes of concentraced Hydrochloric acid were added and the precipitated sodium chloride filtered off. After the addition of a small amount of potassium iodide the solution was saturated with sulphur . dioxide when the desired product sep- arated as a dark colored oil which distilled between 190-I69. from 100 g arsenious oxide, 10^? g of produce were obtained. Ex- traction of the aqueous layer with ether undoubtedly would nave increased the yield. The reaction could readily be followed since it ixivolved the conversion of tne arsenic from the trivalexit to the pentavalexit state. At regular intervals, a ^ cc, sample was removed from the reaction mixture and diluted to 100 cc . A 9 cc. portion of this solution was diluted with water, sxightl^/" acidified, then treated v;ith an excess sodium bicarboijate , and titrated with a -19- standard iodine solution. n-Proovlarsonic acid . Tne direction outlined for the prepar- ation of the preceding arsonic acid were followed. To sodium arsenite ( 9S g of arsenious oxide dissolved in '■^00 cc. of 10 N sodium hydroxide), I 23 g of n-propyl ‘bromide were added. At t'ne end of 24 hours 65 por cent of fne sodium arsenite had reacted. The reaction mixture was neutralized to phenolphthalein, concen- trated to approxin:aDely one-half its original volume, and filter- ed. The filtrate was rendered acid to Congo red, heated to coiling, and filtered. On cooling t‘he desired product separated in the form of platelets together with some arsenious oxide and sodium chloride which could readily be removed cy one or two recrystaliizat ioiis from hoo water. A j'-ield of 100 g. was ob- 0 tained. The melt hig poiiit oi’ a purified sample was 123-7 wriich agrees wifn the one recorded in the literature (l6). Isopropvlarsonic acid . Althoitgh tne same directions as fhose used to prepare the n-proplyarsonic acid were followed, no reaction 'had taken place after 24 hours oi' ‘rieating and stirring. n-ButvlarsQ 2 iic acid , following the general met'nod already outlined for the preparation of arsonic acids, little difficulty was experienced in the preparation of large quantities of butyl- arsonic acid. Approximately 3 hg. of the acid were made. A typical run was as follows: 273 g* of n-butyl bromide were added to the sodium arsenite prepared oy dissolving 196 g. arsenious oxide dissolved iii 600 cc. of 10 M sodium nydroxide. ine mixture v;as heated on a water bath and stirred. Approxiii:ately 30 per cent of tne sodium arsenite ‘j:iad reacted at tne ena of 24 nours - 20 - G-iid 70 psr C 62 it cit "ti'ie end of ^6 nours. After steoju distilxiiig off the excess butyl bromide and the butyl alcohol formed oy the hj^droiysis of the alkyl halide by the free alkali/tne solution was neutralized to phenolphtnalein, concentrated until a cmisid- erable amount of salt had separated out, and filtered. Oil acid- ifj'-ing, the arsonic acid separated in the form of a thick crys- talline paste in almost quantitative yields '^00 g- of crude mat- erial containing about 14 per cent arsenious oxide, and some sodium chloride was obtaiiied. The butj"! alcohol ootained ac- counts for the butyl bromide lost in the reactioti. The product can readily be purified by recrj^'etall ization from hot vmter in which media it is fairly soluble, although alcohol is more effective in removing -che last traces of arsenious oxide. A number of experiments were carried out to determine the best conditions for tne reaction. It was found that when sodium carbonate was used instead of sodium hydroxide to dissolve tne arsenious oxide, no reaction took place. It was further found that the best results were ootained when tne arsenious oxide and sodiimi h 3 ^droxide were used in ohe proper proportions to make normal sodium arsenite. Practically no reaction took place when either more or less sodium hydroxide was used. The effect of alcohol as solvent was also investigated. The usual procedure was followed except in that potassium arsenite vi/as used, and that 1 part of alcohol was added to 3 parts of the alkali solu- tion. The reaction proceeded until about 20 per cent of i,he potassium arsCLnite had reacted axia thexi stopped completely. n-Butylarsonic acid on recrystallization is obtained as - 21 - a flak 3 '- crj' stallixie solid. In its general oehavior and physical properties ii, resmebles the o^her arsonic acids. Oil boiling v;ib h magnesia mixture it precipitates a,s the magnesium salt. Subs., 0.2 g, 0.2 g: 21.1, 21.1 cc. O.IO 38 M I. Calc, for C4 EiiAs03* As, 41,18 0/0 found: As, 41.2^ 0/0 Jt 41.23 0/0 E utylarsine dicriloride . C 4 HsAsCl 3 «- 130 g of crude n-Out-j’i- arsonic acid were dissolved in 3 OO cc. of conceiiorated ri;y'dro- chloric acid to w/iich a few crj^'etals of potassium iodide wnich acted as a catalyst nad been added. On saturating the solution with sulphur dioxide, 100 g. of crude butj’-larsine dichloride was obtained. It v;as fractionated twice under reduced pressure and once under ordiiiarj' pressure. In this way a colorless highly o refractive oil boiling at 192—4 was obtained. It is fairly stable in water but dissolves readily’- in concentrated alkali. In physiological properties it corresponds to the other primary arsine chloride, although somewhat less inarkedlj'' so. Subs. 0.5033 g: 0.1756 g. Cl Calc, for C4E9ASCI3 : Cl, ^ 4 *^ 4 * founded, ^ 4*88 1 a-r s Q a_ci d . CsHsAsOaHa .-Triis acid was prepared like the precediiig ones. 23O g of allyl bromide were added to the calculated amount of sodium arseiiite (196 g arsenious oxide dis- solved in 600 cc. 10 N sodium nj-droxiae ). The reaction was 66 per cent complete iii Oiie hour anu 90 par cent iii 2 rioui’s. The reaction mixture was neutralized to phenolpnthalein, concentrat- • ^ All analyses for arsenic were made 03 " trie Hooertson's method.f 20 I \ } 1 4 - ^ i: i t* I I , . . : i.ii ^ } .1 * \ - 22 - ed to approximately one-half its original volume and filtered. On acidifying, the acia precipitated in needle-like crystals to- gether V(/ith some sodium cjiloride. Without separating from the mother liquor^ it was redissolved heating and filtered, thus re- moving the greater part of the salt. On cooling, the product was obtained as colorless crystals. To remove the last trace of sodium chloride an additional recrystallization from hot water was necessary. The yiela of crude material was 27O g. In general appearance and solubility it resembles the otner arsonic acids. It decolorizes bromine rapidlj^ in aqueous solu- tion, but only slowly when dissolved in not glacial acetic acid or suspended in carbon tetrachloride# An attempt to convert tne acid to the chloroarsine failed^ for altnougn an oil was obtained on extracting with etner the solution saturated with sulpnur di- oxide,, no definite compound could be obtained by f ract ioiiati on. Most of the oil poljnterized to a guKjmy i;iass on heatiiig. Subs. 0.2 g. : 26.4 cc. 0.09205 N I, Calc, for C3H7ASO3 : As 4^.16 0/0 Found: As, 45.40 0/0 it Benzvlarsouic acid . 126 g. of benzyl chloride was added to the theoretical amount of sodium arsenite (99 g» 01 arsenious oxide dissolved in ^00 cc. 10 N sodium hydroxide ). The solution was first heated on a steam bath and stirred, and later vigorous- ly boiled for one hour. The oily layer was removed axid tne solu- tion carefully neutralized. A small amount of flocculent mater- ial which had separated was filtered off, and the filtrate acidi- fied. The acid w'nich precipitated as a vTnite curd v»(as filtered 0 Qffj wasned_v?ith water ,_a.nd_dried_ at 90 iii vacuo. The yielas * Unpublis’hed~w6rk, “Adai/Is “and “JOTniTscmr - -- -- -- -- -- -- 1 I i j ) ■j 1 . ^ L i ^ J ■ ' V L# * *^ ^ i. i. *T*I ' w i i». > e OWi I I '^.7 » 1 . 4 - ' iX o '.A f' * 1 ^ 4 % 1 . 1 *■ J- * > « ~ . j \ • i ,. I V i V o H \ i •I V . ^ j. O ; ^r V '. I r ! k* vCi ‘.il* , V , W ;. ' . A. ••■ L i i f' i' ' - : 1 ^ 4 ^ Ut |i I .. t •• T\ -23- averaged froui 130—5 v/iiicJi is 6O—63 0/0 of theory • ihe recovered oil which was maiiily benzyl alcojiol accouiits lor most ol the oeii— zyl chloride 2iot converted ixito the arsonic acid. The product o obtained after oxie crystallization melted at l67“S . Attempt DO prepare n7drox\ -ethylenearsoxiic ac_id_ . CHaOHCHaAsOsHa .-On addiiig 32 g. of ethylene chlorhydrixie to 4o g of arsenious oxide dissolved in 120 cc . 10 N sodium nydroxide an immediate reaction took place. In ten minutes over 70 per cexit of the reaction was complete. Since the acid did xiot precipi- tate on acidifying the solution evexi after it nad been concexi- trated to a small volume, it was evaporated to dryness atid the residue extracted with absolute alcohol. After evaporatixig the alcohol a syrupy liquid remained which presumably was the desir- ed compound. It reacted v.ith acetic aiihydride although no defin- ite product could be isolated. Benzoyl chloride did not give a satisfactory result. On addixig mgnesia mixture to an ammonia- cal solution of the crude product, a gelatixious precipitate was obtained on nefxting. Attempt to prepare Phenoxv-etnylarsoxiic acid . CeHeOCHaCHsAsOsHa . 60 g. of pheno^iy-ethylbroi.aide were adaed to a solution of sodium arsenite prepared by dissolviiig 60 g. arsen- j ous oxide ixi I80 cc. 10 N sodium hydroxide. Titration of sam- ples of the mix-cure indicated tnat a slight reaction took place during the first 6 hours, and tnexi stopped completely even tnough an additional amount of the alkyl nalide was added. Even if a small amount of product may have been formed, it was impossible to isolate it on account of tJie large amount of arseixious oxide present. -24- At tempt t Q prepare Y PhenQx\^-prop\ lars oni c a.Qia « CeHsOCliaCHaCHaAsOsH. i'oliowitig the same direction outlined for the preceding experiment, there was onl}^ a very slight reaction I which stopped aoruptly. Even refluxing the solutioii over a. free- flame did not produce any effect. Attempt to prepare Etnvlexie di-ArsOxiic a cid . C2K4( AsOsHa )a .- following the directi otis given for tne preceding experimeiit o , no appreciable reaction was obtained when ethylene dioromide was heated and stirred witn sodium arsenite. Attempt to prepare Irimetfn'^lene di-Ars onic a c ia « CsHc ( AsOsHs )a •~40 g. of trimeth 3 i^lene dibromide was added to 80 g, arsenious oxide in 240 cc. 10 a sodium hydroxide. I’he mixture was heated on a steam ^atn and stirred. At tne exid of 25 nours 70 per cent of the arsenious acid nad reached aitnougn it was necessar 3 ^ to add 40 g. more of trimethylene dibromide. Six.ce the product could not be precipitated by acia, the solution was evaporated to dryness, and extracted witn alconol. After evapor- ating the alconol a gumuiy mass was obtained which was dissolved in hot water, treated witn animal criarcoal, ana filtered. On cooling a wnite precipitate separated out whicn oxi analysis w^as fouiid to contain over 70 per cent arsenic whicn ixiaicaoes tnat instead of oeing the desired proauct it was mainly arsexxious oxide - 25 “ 2. The Syntiieeis of Areinic Acids. Dibutvlars iiiic acid . TJiis compound was prepared by t-vi/o dif- ferent met-hods, namely, by tne Meyer metnod, and by the condensa- tion of butyl bromide and arsenious cnloride througn sodium. The former method, however, is in all respects far superior. i’irst Method. -The preparation of the secondary acid depended on the action of outvl bromide on sodium butylarsenit e wnich was readily prepared by dissolving butylarsine dicnloriae in an equi- valent quantity of sodiui.i hydroxide soluoion. The exaci: details of the experiment are as follows. 6l g. of butyl bromide were added to a solution of 90 g. of but 3 ''lars ine dicnloride in l80 cc. of 10 N sodium hydroxide. Afuer stirring the mixture for tnree hours on the water bath, over 95 Per cent of the arsenious acid had reacted. The solution v;as neutralized to phenolphtnaieixi, axid concentrated to about two-tnirds oi‘ its origixial vo±a-.e, fil- tered, axid tne filtrate carefully acidified. Tne mass of crys tab- line product vmicn separated out was filtered off, wasned, and u**Ted. The yield of crude product was 85 g. whic/^ is ^4 per cent of the theory. It was pure after one recrystallizatioxi from o water as ixidicated oy a coxistant melting poixit, 137 -o • la pre- cipitatixig tne acid it is xiecessary to avoid axi excess sixice this causes the product to chaxige to an oil. Tne pure compouxid con- sists of flaky unctuous plates which readily dissolve ixi either hot water or alcohol. It dissolves readily in ammoiiium hydroxide but on prolonged ooilixig the ammoxiia is coiled off axia tne acids agaixi separates ixidicatixig that tne ammonium salt is readily dis- sociated. I ll ( II 1 I }\ I . J • . L - 1 I . . / J. :X . ■ . ■ '-i V i , • ... 1 vJ w r.o tl 1 ! ,V- ► 4. ‘ % vj a .1 ■»s*PSEE.i: - 26 - Second Metjiqd. To a well-stirred mixture containing 50 g. of one basic di-n-'bu&ylarsine chloride, descrioea oelow, 700 cc. of water, and 150 g. of ice, a calculated amount (57 g* ) bromine was added dropwise. A neavy oil colored saightly oy the excess of brorniiie collected on trie oottom of tne fiask. On reiidering the solution alkaline witn aimaonia all want into sol- ution. On adding magnesia mixture to the boiling solutioxi, there was xio appreciable precipitation inaicating the aosexice of but 3 ’’i- ar sonic acid. After filtering, the solutioxx was coxi-' cexit rated to oxie-third its original volume wnereupoxx axi oil sep- arated which on cooling solidified and wnich was identified as di-n-butyl-arsixiic acid. Repetition of process brought the yield up to 20 g. finally, further coxic entrati on yielded an oil which showed little texidexicy to ciys ballize . Subs. 0.2 g : 58.8 cc. 0 . 105 S H I. Calc, f or : CsHioAsOa As 55»7S 0/0 Found 55*S4 0/0 Subs. 0.5 e* • 15‘55 02 . 0.147 NaOH Found I 5 .O cc. Basic d i-bu tv lar s ixxe chloride. This suostance is the in- termediary compound from wnich dibutyl arsixiic acid was prepared. A mixture of 152 g. of arsenious chloride axid 200 g. of butyl bromide were addea to 67 6 * of pulverized sodium covered with 500 cc. of dry oenzene at sucn a rate as to ixiaintaixi a vigorous reaction. In the course of three hours it was complete. Txie solid material coxisisting of sodium chj.oride axid a red amorphous substaxice similar to B'dnsen's "Ery thrarsixi” (51) was filtered off, axid the amber colored filtrate fractioxiated. The first fraction was almost exitirely benzene, wnile the second fraction !l I I I • i . j. j. ■! . } ' ! I I I i ■■ i'. ; . ! I I I 1 I I <.* . 1 X- -^^5^ - 27 - 0 collected between 100-140 consisted of a mixture of arsenious chloride, butyl bromide, and benzene. ine third fraction boiled 0 between 237—^1 • I’he yield was 70 g. or ^0 per cent of t-ne theory,. On the second f ract i ctnation it boiled at 237-S (unc. ), and was obtaiiied as a heavy colorless oil containing a smll amount bY a white solid which readily settled. Analysis indicates that it is a basic di-buty larsine chloride. Subs. 0.2940 g. : Cl 0.0338 Calc, for [[c^Eg ) 3 AsC^ 6 ' [( C 4 He )aA_^aj0 : Cl 12.22 0/0 found Cl, 12 . 18 0 / 0 ji^em.vlarsinic ac i d ( 3^ )»-follo*iiig ohe directions outlined for di-n-butyl arsinic acid, 53 g» ethyl bromide were added to 90 «. of ethy larsine dichloride dissolved in 210 cc . ol' 10 E sodium hydroxide. After stirrixig trie mixture which was warmed on the steam bath for 4 nours, the reaction was 90 per cent complete. It was necessary however to add 20 g. more of ethyl bromide to replace the loss due to volatilization. After boiling off the excess of ethyl bfomide, the solution was neutralized to phenol- phthalein, concentrated to a small volume, ana filtered. Since the addition of acid did not cause the separation of the product, it was necessary to concentrate further. It finally began to separate out as crystalline platelets, together with a sruall amount of sodium chloride. The acid can also be obtained by ex- tracting the dry residue with alcohol. On adaing etner to onis solution, the acid separates in the form of iridescent platelets. The preparation of the substance entirel 3 ^ free from sodium cnlor- -28- ide is difficult, and is, for purposes, uiinecessary . n-Propvl . n-ButvIar sinic acid .-This mixed aliphatic second- ary arsinic acid was readily prepared by the action of propyl bromide on sodium butylarsenite . The proportions used were 12. 5 g. of propyl bromide to 20 g. of n-butylarsine dichloride dis- solved in 40 cc. 10 U sodium hydroxide. After four hours neat- irig and stirring, the reaction was over 80 per cent complete. The reaction mixture was boiled to remove any excess of propyl bromide, then acidified, treated witn bromine water to oxidize the unchanged arsenious acid to the c orrespondixig ar sonic acid which was removed oy means of rngxiesia mixture after the solu- tion had beexi rendered alkalixie with amuaonia. Oxi concentrating the filtrate axi oil separated wnich oxi coolixig solidified to a cr3rstalliiie mass. It was pure after one cry stalrization from hot water. The acid resembles di-n-but3''lar sinic acid in both physical and chemical properties, but it is appreciabl3^ more sol- o uble in water. It melts at 127-8 4 . Subs. 0,2 g. 0.2 g. : 21.1, 21.0 cc . 0.09205 N I Calc, for C7H17ASO3 : As 5^.01 0/0 Pouxid: As 5^*24 0/0 56.12 0/0 Atte mpt tp_ prepare n-butylphenvlar sixiic acid. -Poll owing the directions given for the preparation of the other secondaxr^- ar- sinic acids, ii-butyl bromide was added to sodium phexi3’‘larseiiite prepared by dissolving phexiylar sine di chloride in a calculated amount of 10 14 sodium jivaroxide. After heatixig axid stirrixig for one hour the reaction was over 90 per cent complete. After boil- ing off the excess of butyl bromide, the free alkali v/as iieutral- . f. ' . -w , . */ i. ► * * ■ ■ I k. i-* . , i i . - T •. . ,;. •’/ sJ l - - i » U . , ' * . u ■ » . jL .i- * - •• .,,..-1 . .. *J . X . : i;r.'j: . . , 1 V C'.l I « ■ . ', ' J. ■ J '' i V.fVj « -V ,t.< i ;i- }, i! K w' ' • V. U > . • 1 V . • n.^- i — ' -2 9“ ized, and the solution treated v^^ith aniiiial charcoal and filter- ed. On acidifying the filtrate an oil separated which could xiot oe riiade to crystallize. It dissolved coiupletely in aitrrionia out on prolonged boiling, the oil separated out agaiii. The presence of a disagreeaole odor indicates the presence of an impurity which may be responsible for keeping the substance an oil. Attempt to prepare ethvl ohenvlarsinic acid. SuDstituting ethyl bromide for n-butyl bromide in the process described above similar results were obtained. Although the pure product is described as a crj’-stalline solid^ no means were fouiid to crystal- lize the oil which was ootainea. f PnenvlQxv-etrivl-iJhenv larsinic acid. CeH60CH2CH3( Ceh5 ) AsOgH - .-A mixture containing 49 g» of fpnei^y oxyetnylbromiue and 49 g. of phenylarsine dichloride dissolved in 80 cc. of 10 ii sodium hydroxide was neated on tne steam bath aiid stirred. At the end of 4 hours over 70 per cent of the arsenious acid nad reacted. After removing the small excess of the unchanged nal- ide, the excess alkali was neutralized wnereupon the unchanged phenylarsine oxide together with a small amount of soapy mater- ial separated. This was filtered off, aiid the solution acidi- fied, whereupon an oil separated vi/hich immediately crystallized. On recrystallization from a large volume of water it was pure, o melting at 122-9 • The product is appreciably more solu.ble in chloroform, beiizene, ether, aiid similar solvents thaix tne ordi- nary arsinic acids. A yield of 20 g. of pure product was obtaiii- ed. ...I i .1 r . J. r.v. 1' . i'j j I I I ' J 'j ■*» Subs. 0.2 g. : 14 cc . 0.09205 W I. Calc, for C 14 H 1 BASO 3 : As, 24.50 0/0 ij'ound: As 24.60 0 / 0 , iiJthvleiie-diPhenYl~di-arsinic acid . CaH4( CeHeAsOaH )a .- 52 g. of phexi 3 "larsine dichloride dissolved in 120 cc. of 10 ]ii sodium h 3 '‘droxide were treax-ed with 60 g. 01 ethj''lexie didromide. After four hours heatixig 50 per cent of trie phenylarsexiious acid nad reacted. After removing the ui.changed phenyiarsine oxide in the usual way, the solutioii was acidified. An oil wnicn snowea little tendency to crystallize separated. It was redissolved in dilute ammonium hydroxide, filtered, and agaixi precipitated by carefully" acidification. Again the product came out as an oil, but on standing solidified. A ver 3 ' poor yield was obtained. Tne product is somewhat soluble in hot water or in alconol. m. p. 209-11. Subs. 0.2 g. : 21.7 cc. 0.09205 i-'i I Calc, for Ci4Hi.eAs204 : As 57*66 0/0 i’ound ; As 57*55 o/d Subs. 0.2 g. require sJf 8.8 cc. 1.55 1'^ I'laOH Found: 8.4 cc. Attempt to prepare Tr imethvlene - diphenvl-drAr s inic ac^id. Triirietnylene bromide reacted readily with sodium phenylarsenite , but on attemptixig to isolate the product an oil was obtaixied which could xiot be crystallized. - i - 31 - 3. The Syntheses of Arsenic-Sub stitu^ed Acetic Acids and Derivatives. Phenvlarsonic acid . The acid was prepared by the Eart re- action followiiijc: the German factor 3 " method employed during the war (24). Since the method requires close attention to details ill order to obtain satisfactory results, the directions follow- ed in the laboratory are given. To prepare the benzene diazonium cnloride, 74-0 cc. of ani- line were dissolved in 2000 cc. of concentrated ny dr ocriloric acid, and 4000 cc. of waxer with enough ice -co iixaintain a tem- 0 perature of 0- 10 . To this solution ^60 g. of sodium nitrite dissolved in 800 cc. of water were graduall^^ added with coxistaiit shaking, for conveiiience, the solutions Vi/ere made up in four parts so that wnile one was run into the sodium arseiiite solu- tion, another could be diazotized. Tne sodium arseiiite solution was prepared oy mixing toge- ther 960 g. of arsenious oxide, 1600 g. of sodium carbonate, 450 g. of cupric sulphate, and 4000 cc. of water. After stir- ring this solution for 30 minutes, tne benzene diazoxiium chlor- ide was slQwljr added during the course of 2 f/2 to 5 hours. To prevent foaming a little benzene was frequentlj?- added. The stir- ring- was continued ^0 minutes after all the solution had oeen run in. After allowing the reaction mixture to settle over night, the clear amoer liquid was siphoned from the tarry laater- ial, concentrated until the separation ol' salt prevented further evaiyorat i on, anu filterea not. On aciaifying with concentrated hydrochloric acid, the phenyl-arsonic acid separated as a tnick ! ’I I V I - 32 - crystalline mss A^hicri was filtered off and dried. I'rie yields were 30~33 ceiit. Phenylarsine dicnjoride . To prepare tnis compound, a slow stream of sulphur dioxide was passed through a solution coxitaiix- ing 1 part of phenylar sonic and 3 parts of concentrated iiydro- chloric acid to which a few crj^stals of potassiuia iouide nad oeen added. The dark brown oil which appeared was separated from the aqueous layer, and distilled. The pheiiylarsine dicnlor- ide was thus obtained as a lighix, amber colored oil in 7O-85 per ceiit yields dependiiig' upon the purity of the ar sonic acid used. Ij^'-d r.o chloride p-araino-phenvlarsine di chloride « On passing a stream of sulfur dioxide through a solution of 1 part of arsanilic acid in 3 parts of eonceiitrated hydrocnloric acid, the hydrochloride of p— amino— phenj^^lar sine dichloride separated as a crystalline mass in practically quaiititative yields. tanilide » Tnis compound was prepared accordiiig to the method developed oy Jacobs aiid B^eideloerger ( 33 )» 1.3 parts of chloroacetyl chloride w^ere slowly added to a well stirred aiid cooled solution ol i part of aniline in 3 parts of glacial ace- tic acid and 3 parts of saturated sodium acetate solutioii. The product separated immediately. A yield of 83 per cent calculat- ed on the amount of aniline used was obtaiiied. Cnloroacety l phenetidine . The compound m-as prepared iii tne same way as the preceding one with 77 per cent yields. 6 ty l ~^ r sani ^ li j: acid . The method of Jacobs and Heideloerger was followed ( 34 ). A mixture of 50 g. of arsanilic acid and 130 g. of cnloroacetic acid were heated on a boiliiig: - 33 - v/ater bath for 2 hours. The melt was poured into a cold satur- ated solution of sodium chloride, and the precipitated cnloro— a.cetj^'l derivative was filtered , off , washed, and dried. A yield of 55 per cent was obtained . It was used without further puri- f ication. C hloroacetvl-P-amino-benzoic acid . To 10 g. of p-amixio- bensoic acid suspended in a mixture coxisistixig of 50 cc. of glacial acetic acid axid 50 cc. of saturated sodium acetate sol- ution, chloroacetyl cxiloride was slowly added witn vigorous stirring. The white amorphous solid 'was i'iltered off, wasnea with water, and dried. 15 g. of the crude maberial were ootaixi- ed. It was used without further purification, out a sample for analysis was recr 3 ^stallized from alcohol. Subs. 0.2 g. : 0.0329 g Cl. Calc, for CsHfiOs WCl : Cl, l 6.62 0/0 I'ound: Cl, 16.45 0/0 Chloroacetvl-o-amixio-oenzoic acid .( 35 ). This compound was prepared from chloroacetyl chloride axid o-amixio-oenzoic acid in the same wajr as the precedixig oxxe with similar yields. Chloroacetyl -u rea ( 36 ). Oxi mixing 150 g. of chloroacetj^'l chloride and 60 g. of urea a vigorous reaction exisued. Al’ter the reaction died dowxi, the mixture was heated on the water bath for axi hour. The white chalkj'- solid was filtered off, wash- ed with water, and dried. 65 g. of material were obtained. -34- Pheuvl- arsinic -( acid )* L.cetic acid and derivatives » Phenyl-arsinic ~( acid )- acetic acid » CeKeAsOaHCHaCOOH. -This compound v/as made oy the modified Meyer synthesis. 121 g, of sodium chloroacetate dissolved in 150 cc. of water was added to a solution of sodium phenyl-arsenite prepared by slov/ly adding 180 g, of phei:y 1-arsine dichloride to a cooled solution of 146 g. of sodium I'lydr oxide iii 450 cc. of water. There was an imme- diate reaction writh the separation of a vmite solid. Altriough the reaction was .90 per cent complete in 30 miiiutes, t?ie solu- tion was allowed to stand several hours. On adding acid until the solution was neutral to ijhenolpnthaleiii, the white solid w'ent into solution, and a little tarry material consisting main- 13’' phenyl— arsine oxide separated out. The solutioxi was I’ll— tered, axid then made acid to Coxigo red wnereupon the desired compound separated as a crj^stallixie itass axia i'illea the coxitaiXi— er . A yield of 120 g. w'nich is 96 per cent of the theory'' was o'bt.aiiied. A portion recrj'^stallized from not vi/ater melted sharp- 0 ly with iitmediate dec omposi ui 0 x 1 at 141—2 • Tne compouxid is very soluble ixi not water, less in hot alcohol and very slightly ixi most of the other conmion solvents. Subs. 0.2 g. : 17.8 cc. 0.09205 H I. Calc, for CaHe04As : As, 30.72 0/0 Pound: 30. 6l Hien3".l ~chl o r 0 -ar s ixie -a c e t i c acid. CeHBAsClCKaCOOH.-To prepare this substance, a slow stream of sulphur dioxide was passed through a solution of 60 g. of phenyl-arsinic-acetic acid dissolved in l3o cc. of coxicentrat ed hydrochloric acid to vxhich - 35 - a few cr 7 /stals of potassium iodide had been added. The phenyl- chloroarsine acetic acid separated iii the forra of plates whicn were filtered off and dried. The yield was 95 cent. The compound is very soluble in ether, benzene, or similar solvents, but it is best recry staliized from cnloroform. It melts snarply 0 at 102-3 . Subs. 0.5 s* • 0.0716 g. Cl Subs. 0.2 g. : 15 «S cc. 0.09205 y I Calc, for CaHeOaAsCl : Cl 14.59 0/0 As, d0.41 0/0 Found : Cl 14.52 0/0 As, 50*75 0 / • PhenYl-br omo-a r s ine~ac et i c ac id . CeHsAsBrCHc COOH. -The oromo compound was prepared in the same v;ay as the precedixi^, one. It resembles the chloro-compo-und ixi chemical and physical properties but it has a lower solubility which makes purification through o recrj’-stallizatioii rauch easier. It melts at 115-4 . Subs. 0.5 g'» • 0.1356 g. Br. Calc, for CaHaOaAsBr : Br 27.46 0/0 Found: Br, 27.12. Attempts to prepare Phenvl-Chloro-arsine-ac e tvl Cnloride . CeHaAsClCHaCOCl . -The preparation of the acid chloride was tried iii several ways. For the first attempt, 19 S* phosphorous pentachloride was added to a cooleu soxutioxi 01 20 g. 01 phenyl- chloro-arsixie-acetic acid in 75 co. 01 chloroform. After the reactioii had subsided, the solutioxi was heated on a water oath for an nour, then the solvent axid the phosphorous oxychloride boiled offhand the residue distilled under diminished pressure. 17 g* of a slightlAT^ reddish oil which oii subsequeiit f ractiunacioxi 0 boiled at 114-6 at 10 ram. was obtaixied. Tne boiling point ixidi- -56- cated that the product was phenyl-arsiiie-diciiloride^ and this was subs taiit iated by treating a little of the oil 'with oromiho wnen crystals of phenvlar sonic acid were obtained* Thionyl chloride was tried next* On addiiig 20 g. of phenyl- cln.oroars ine-acet ic acid to 50 cc * of thioiiyl chloriue coolea in ice a moderate react io 2 i set in which was complete in about 0 two hours* The temperature was kept oelow 20 . After removixig the excess thioiij^l chloride uiider diminished pressure, l6 r,* of material remained* In order to test wnether it contaiiied any of the desired substituted acetyl chloride, it was dissolved i 2 i 20 cc * of oeiizene and treated witn 5 of anirine dissolvea in 20 cc . of the same solveiit. A greexiish crystallixie precipi- tate separated which 021 recrystallization from alcohol was oo- tained in trie I'orm 01 long needles which proved to oe phenyl cnloroarsine aniline Ceh-sAsCl AliCeKs, (57) for oii treatment with water it decomposed giving phenyl-arsine oxide whicn reitained as a gummy mass and anilixie hydrochroride which went into solu- tion from vfnich the aniline was obtained by the addrtio**. of ao-kali. There w^as no indication, whatsoever, of the foririation of an anilide* Y/ith phospnOi>.rous trichloride similar results were obtained* Attempt to prepare Pnenvlarsinic ( acid ) a<;^Qtamide , CeHeAsOaHCHa CONE 3 •-I’ollowing the usual procedure, 9*5 g* of chloroacetamide was added to a solution of 22 g. of pheiiylarsine dichloride dissolved in 40 cc. of 10 E sodium hydroxide* Altnoug! there was some decrease in the amount of the arsenious acid, hydrolysis of the amide went on much faster as was shown oy the - 57 “ copious evolution of ammonia. After removing the excess of phenylarsine oxide, t?ie solution was acidified. Ho product, however, separated nor could one be isolated.. Attempt to pr eoare ethyl-pheiivlarsinic acetate . CeK5As02HCH3C00C3B'.5 . -Ethyl chloroacetat e was allowed to react with sodium phenylarsenite made in the usual manner. A vigor- ous reaction ensued followed by the separation of a gummy mass which consisted partly of pherylarsine oxide and presuni- ahiy partly of the desired product. It wa.s found difficult to isolate the product so the work was abandoned. Pheuvlarsinic ( soicO acetanilide . CeKeAsOaHCEs CONHCeHf? .- The Meyer reaction was employed for the synthesis for this compound. 53 g. of phenylarsine di- chloride were dissolved in 63 cc. of 10 H. sodium hydroxide (a 3 per cent excess over that required by theory). To tnis solution 27 g. of chloroacetaniride Mere added with stirring to obtain a homogeneous mixture. As the reaction proceeded, a consiaerable amount of heat was evolved, and the chloro- acetanilide disappeared. After three hours the reaction was complete. The solution w^as then diluted witn. axi equal voluiae of water, and enough hydr oc/iloric acid added to make it neutral to phenolphthalein when the unchanged pheny- larsine oxide precipitated as a gumray mss. This, together with small traces of unchanged chloroacetanilide , was filter- ed off, and the clear filtrate acidified until acid to Congo red, whereupon the desired product was completely precipi- - 58 - itated. It was filtered off, washed witJi a large volume of not water, and dried. 50 of material were obtained which corres- ponds to a 90 per cent yield. It can toe furtne r purified b3!^ re- crystallization from hot water in which it is very sparixigly soluble. A sample tnus prepared consistea of tiny clusters of needle crystals melting at lS 2 - 5 ^ witii evolution of gas. Tne compound is insoluble in oerizene, chloroform, caroon tetracnlor- ide, acetone, ether, or similar solvents, tout it is appreciaoly soluble in glacial acetic acia ana somewnat ixi etnyl and metnyl alcohols. It is a fairly stroiig acid liberating cartooxi dioxide from carbonates. Subs. 0.2 g. : 12.2 cc. O.IO 59 K I Calc, for Cl 4H14 OsHAs : As, 23»50 0/0 Jound: As, 25 « 75 ‘ Phenvl-bromoarsine-acetanilide . CeHoAsBrCHa CONKCelie .-A slow stream of sulphur dioxide was passed through a cooled solution of 20 g. of phenylarsinic-acet ic acid in a mixture of 10 cc. of glacial acetic acid, 20 cc. of concentrated h3''drooromic acid, and 50 cc. of water in which a few crystals of potassium iodide ?’ad been dissolved. An oil, which in the course of the reaction hardened to a semi-solid substance together with a mass of crystals separated. The 3''ield of dr3r product was 17 g. On re- crystallization from methyl alcohol a wnite crys&alline product melting at loS-110 was obtained. Subs. 0.2 g, : 11.7 cc. 0.09205 H I. Sues. 0.4 g. : 0 . 0894 g Br . Calc, for Ci 4 Hi 3 As 0 i\IBr : As, 20.47 0/0 Br, 21.85 0/0 Bound: As, 2O.15 0/0 Br, 22.56 0/0. -> 9 - Pheiiylarsinic-acetyl-phenetidine . CeHsAsOsHCHaCONHCeHsOCahe •V'J This compound v\?as prepared in the same way as the correspoiiding aniline derivative encu^i- i.hat an equal volume of alcohol was added to the reaction mixture. l 8 g. of the chloro-acetj'^l-phene- tidine was added to 19 g- of phenylarsine dichloride dissolved in 59 cc. of 10 N sodium hydroxide. Only 9 g* of product were obtained, but subsequent work shows that much better yields could be obtained by the omissioxi of the alcohol. The compcuiid is appreciably more soluble in hot water and alcohol than the corresponding anilide. It is best recrystallized from alcoriol from which it can be ootaiiied as needle crj^stals whicri melt at 0 175 with decomposition. Suos. 0.2, 0.2 : 10. 7 > 10.75 oc. 0.1058 iJ I. Calc, for Ci 4 Hi 804 kAs : As, 20.65 0/0 Pound : as, 20. Si 0/0 20.91 0/0 P henYlarsinic--acetYl-arsanii.ic acid . CeHsAsOaKCHaCOllHCeHeAsOsHs (p). 51 S* of the sodium salt of c'hloroacetyl-arsanilic acid dissolved in 50 cc. of water was added to the theoretical amouiit of sodium phenyl-ars enite (22 g. of phenyl arsine dichloride and 50 cc. 8 iJ sodium hydroxide). The reaction was complete in 2 hours. After the addition of acid until the solution was neutral to phenolphtnalein, the un- changed phenyl-o.rsine oxide was filtered off, and the product precipitated by acidification. Trie chalky precipitate was fil- tered off, extracted first with a large aiaount of hot water, then o with hot alcohol, and finally afied at 110 . It is insoluble in r!, , • , ♦ * >> J . L - * w Eg 111 . ■ . . .' i,jOS U / ** r- ‘ • ** i, . . . ‘ \ ^ ' it • ^ -I I : : • r . f ^ ». * V •-■-' ; ^ *.c .•ti i'C *v. r \ -40- all thp common solvents, wjiich prevents its purification through recr 3 ’ stallization. It can however be converted into its soluble sodium salt aiid reprecipitated by acidification. Ine product even without recrystallization is pure as indicated by tne ana- lysis. The yield was around 70 per ceiit. Subs. 0.2, 0.2 : 17.4, 17.4 cc. O.IO^^S a Calc, for Ci 4 Hi 60 el>iAs 3 : As, 3^.84 o/o found: As, 33.84 o/o 33»h4 o/o Pnenvlarsinic-acetyl-o-axiiino-benzoic . CeH 6 As 02 HCH 3 C 0 NHCeH 5 C 00 K (h) The saj:ae procedure as for preceding preparation was used. 22.5 g. of sodium cnloroacetyl-o-a.-ino- benzoate in 50 cc. of water was added to the calculated amount of sodium pheiii^l-arsenite solution (22 g. of phanylarsine di- chloride in 40 cc. of 10 N sodium ?iy droxide ) . The precipitation was conducted as before. Since tne product was too insoluble to be purified by recrystallization, it was dissolved in dilute sodium carbonate solutioii, boiled with animal charcoal, filtered, aiid reprecipitated by means of hydrochloric acid. It is a white 0 chalk^v powder which melts with decomposition at 198-200 C. Subs. 0.2 g. : 11.9 cc. 0.09205 W I Calc, for Ci5Hi40Bh’As : As 20.65 0/0 found: As, 20.47 0/0 - 41 - Derivat ives of P amino ohenvl arsinic ( acid ) acetic acid . P- Aiiiino-nhenvlars Inic-acetanilide « ( p )H3NCeH4AsO2HCKaCOKHC0iij^ This compound was prepared oy adding 34 g of chloroaceianilide to a solution of sodium p-amino-phenylarseni^e prepared by dissolv” iiig 38- g of the hydrochloride of p-amino-phenylars ine dichloride iii 100 cc. of 10 li sodium hydroxide. A reaction set in iinmediate- ly and was complete in one hour. After standing for several hours the solutioiiwas rendered neutral to phenolphthalein, the small amount of unchang'ed p-amino-phenylarsine oxide together with traces of unchanged chlor oacetanilide filtered off, and tne solu- tion treated with concentrated hydrochloric acid until just acia to Congo red. Excess aciaity v;ae avoided to prevent part of the product beixig redissolved on account of trie presexice of the amino group. A 3^ield of 42 g, which is 64 per cexit of theory was oo- tained. It could readily be purified eitrier from alcohol or hot water. It is oxilj^ slightl3^ soluble in methyl alcohol, axid acetoxi.e axid iiisoluble in benzexie, ethyl acetate, etner^ or similar sol- vents. The pure product melts at l 8 l- 2 ^ w/ith evolution of gas. Subs. 0.2 : 13 cc. 0.09203 N I Calc, for Ci-iEisOaNaAs : As, 22 .44 Fouxid : As, 22.36. E-Ace tv l-P-aiaino -O henvlarsixiic-acetaxiixide . CHsCONKCeRsAsOsHCHsCOHHCeHE .-This acet3' l derivative wasrreadily prepared by warming a mixture of 10 g. of the axiilide axid 13 cc. of acetic anhydride. As soon as the reactioxi started, the flask was wrapped ixi a tov a»>' , > • ’. ' ‘•V. t\ f - »K V / * > J. X , ■*' 1, .0 V * %j ^ .1. ji ■ ■•- -J , , • i i A. i- • ' V H i } (Jil ..t ; - t' -. \ i . 1 L.* f I -42“ bath for 15 iniiiuteG, then diluted with five parts of water whereupon tne desired substance prec ipitatea . It was I’iltered off, extracted with dilute hydrochloric acid to remove aiiy of the free amino compound, thoroughly washed with v^ater, ana dried. Almost quantitative yields were obtained. It was recrys- tallized from hot water. It consists of elongated platelets 0 which melt at 205-6 with decomposition. Subs. 0.2 g, 0.2 g. : 11.65, 11«65 cc. O.O9205 cc . N I Calc, for CieHi704N3As : As, 19»94 0/0 ]?ound: As, 20.04 0/0 20.04 0/0 H-g Ivcvl-D-aruino-DhenYlars ini c -acetanilide . HOOCCHsNHCeK^AsOaHCHaCONHCeHB .-The glycyl derivative was prepar- ed from p-amino-phenyl-arsinic acetanilide by heating 10 g. of it dissolved iii 50 cc. of 4 per cent sodium h3^droxide solution containing 7 of chloroacetic acid. After refluxing for ^^4 hours the solution cleared with the separation of a small amount of oil. The refluxing was continued about 4 hours during which period a granular solid separated out. In some ruixs the Ablu- tion reKiained clear until cooled when an oil separated which on standing turned crystalline. The product could be recrystalliz- ed from methyl alcohol, but simple extract! Oii with hot water or a small amount of hot alcohol seemed to remove all impurities leaving a white product meltirig at 199^^ with decomposition. The yield of crude product was 6 g. Subs. 0.2 g. 0.2 g. : 11.15, 11«2 cc. 0.09205 li 1 Calc, for CieHiaOBHaAs : As, 19*12 0/0 Found: As, 19 *lS 0/0 19.26 0/0 t - > jL lx. i. I . A > - 43 - p-Ajiiin o phenvlarsinic-acetvl-o'rienetidine » HsNCeKfAsOaKCHsCONHCeH^OCsHsCp ) 21 g. of chloro-acetyl phene- tidine were added to t?ie calculated aiaount of sodium p-amino- phenylarsenite (29 g* of the hydrochloride of p-amino- phenyl arsine dichloride in ^0 cc. of 10 if. sodium hydroxide). The re- action was complete in three hours. After precipitat iiig- the un- changed p-amino-phenylarsine oxide by reiidering the solution neuiiral to phenolpntnalein, and filtering, i-he product was ob- tained by further additioii of acid. li is suff iciexit-lj^ soluble for recrystallization from either hot wafer or alcohol, but is best purified by means of the latter solvent. In its chemical and physical properties, especiallj^ soluoility, it resembles 0 the correspondizig anilide, d* p. 201 . 5 - 202. 9 . Subs. 0.2, 0.2 : 11,5 cc. 11.5 cc. 0.09205 N I Calc, for CieHi0O4N3As : As, 19*83 0/0 PoundlAs, 19*78 0/0 19*78 0/0 K Acetyl-p-amino-phenvlarsinic-acety 1-phenet idine . CHsCONHCeHfS^AsOaHCHaCONHCeK^OCaHsC p )*-The acetyl derivafive was prepared in the same manner as the corresponding aniline deriva- tive already described, from 10 g. of the free amino -compouxid -created with I 5 cc . of acetic anhydride, 12 g. of unpurified product were obtaixied. After recrystallization from alcohol, a 0 crystalline soo.id, melting at 214-5 with tne evolution of gas was obtaixied. Suds. 0.2, 0.2 g. : 10. 3, 10. 3 cc. O.O 9205 i'j I Calc. CisEsiOeiiaAs J As, 17.84 0/0 found: As, 17*>72 0/0 17.72 0/0 V-i I I ' \ , . i. J 'zrr */■ I T“P“< -44- i.-C7lvcvl-P-aa;iijiQ-T)heiivlarsinic-acetvl-phenet_idj4M » HOOCCHartHCeHifAsOaHCHaCOIIHCeH^OCaHe (p). Although the same methoc which was used for the correspoiiding aniline compound was fol- lowed the j^ields were very poor. 10 g. of the amino compound were dissolved in 20 cc . of 4 per cent sodium hydroxide solution and refluxed with 6 g. of chloroacetic acid f or 8 hours. Only 3 g. of product was obtained. It was exceedingly difficult to purify the crude material, the purest product being obtained by merely extracting the material with boiliiig water which re- moved the more soluble impurities. A sample thus prepared melt- ed at 197^ with ii^imediate decomposition. Suds. 0.2, 0.2 : 10.1, 10.1 cc. 0.09203 h I Calc, ior Ci sHaaOePaAs : As, 17»19 o/o xO.iiid: As, x9»37o/o 19.370/0 Q-Ataino-phenvlarsinic-acetYl-arsanilic acid . Hai.CeHfAsOiiHCHaCOj'jIiCeHf AsOsHa •-I’he comp ouiid was prepared by add- ing 29 g. of chloro-acetyl-arsanilic acid dissolved in 40 cc. 3 N. sodium hydroxide to the theoretical amount of sodium p-aiiiino- phenyl arsenite prepared by dissolving 29 g. of che hydrochloride of p-amino-phenyl-arsine dichloride in 30 00 » 10 N soaium 1 hydroxide. A considerable amount of heat was. evolved in the reaction. After three hours the solution was rendered iKsutral to phenolphtnalein, boiled with animal charcoal, and filtered. The filtrate wa.s carefull 3 ^ acidified, avoiding an excess of min- eral acid which would redissolve the product^ and the white chalky solid which separated was filtered off, extracted with hot wax,ei , and dried. The product was f ou 2 id suff icioiitly pure 1-ts' \ ; ■ 7^%i i ' ‘ '“" ' '' ■' ■ *"* I , w . •.. ^ ... . ,1 i • I- , '* ” ' / 'Vj'J , ^ - , .... {j I- w, O'J J»f ' J. . '* .i;.: 4 • • ' . '•? ' • ‘ ■ yj. X ';; - ( r : V. t.; . "■ L L-v*’v .1 ..X !? ••• • ^ • . \ . .. ... t .. v; ^ . . r L*: ' ii .. J i. 1- • , L . . : ’1 . V T . . S “*■• • O : . >-■ ■ * ii . ; k i • . • V •• C- • ' >•' *■ ^ / ' V i ^ ^ V. ^ ^ i .44^ is _ - r 'f i j, . .. ■'.:L. i-'J-i J .- s. .. v..^. \\, S; i* ...‘ - 1 j • » * • .4- *. Jw ^ » 4 4 '■ • V4. - » ^ ‘ i' • j. ‘ - , ( .., CO.v^‘ ’ 4 * ^ ' « • • •>* V.. : :,:yi. : 1 . .-.■■■> v - • , ..t. I , J. ■ , . ••v~V' ■; ^ * '• ' - 45 - for the purpose at hand, but a sample for analj^sis was recrys- tallized from hot water in wnich it is very sparingly soluble. A yield of 25 g, or 53 cent was obtained. In some runs a 0 product which turned yellow especially when dried at aoout 100 was obtained. This trouble was avoided however oy coiling the reaction mixture with aiximaj. charcoal cefore precipitating cn.e acid, and by extracting the product thoroughly with hot water. 0 The compound does not melt but turns dark at 25O-6O . Subs. 0 . 2 , 0.2 : 18. S, 18.9 oc. 0.02205 H I- Calc, for Ci 4 Hie 0 eN 2 As 3 : As, 32«73 0/0 l?ou**a: As, 32.51 0/0 N-Acetyl-o-amino-ohenylarsinic-acetyl-arsanilic acid . CHsCONHCeHi^AsOaHCHaCOi'raCeHifAsOsHa*^.''- 10 g. of the free amino compound were treated with 15 cc. of acetic anhydride and heated until the reaction set in. The product was throwii out of solu- tion by diluting the solution with 4 parts of water. The yield was poor. Hie sample for analysis was prepared by recrystalli- zation from hot v^rater. Sues. 0 . 2 , 0.2 g. : 17.3, 17*35 *20* 0.09205 h I. Calc, for Cl 6H18O7N3AS2 : As, 29. 9 S 0/0 i'ound: As, 29*75 o/< 29 *S 9 0/0 p -/umihO-pnenylar s inic -ac e tv 1-P-atii.ino beiizoic acid . H 24 CeH^As 03 llCH. 2 C 0 EHCeHi$«c 00 H (p).-The usual procedure was follow- ed for the preparation of tnis cojnpound. 42 g. oi’ chloroacetyl- p-amino-benzoic acid dissolved in 10 cc. 10 W sodiuxt hydroxide was added to the calculated aiaount of sodium p-amino-pheny lar- senite (58 g. of the hydrochlorid e of p-amino phenyl arsine di- I < f I ! . I I l< k' f t « • j ir- f. I I . J r*; •44 -46- chj.oride in 100 cc. 10 N sodium ii^'-droxide ). A ^0 per ceiio yield was obtained. To purify the product it was found oest to re- crystallize from a small volume of hot water usiniu the filtrate again as solvent since an appreciable amount of suDstaiice reiaains in solution. The purified compound consists of needle crystals 0 melting at 217 with decomposition. Subs. 0.2 g, : 11.4 cc. 0.09205 N I Calc, for Cl 4H1 sOfsKaAs : As, 19*83 0/0 Pound: As, 19*60 c/o p-Aniino-'Phenvl arsinic-acetvl urea .HallCeH^AsOaKCHa COilHCOiiHa • Xue Caiciuiri salt . On mixing 8 g. of chlor oacetyl-urea wit'h a solution of 15 g. of the hydrochloride of p-amino-phei]5"larsi.*e dichloride in 25 cc . 10 h sodium hydroxide, the arsenious io^ disappeared to the extent of 90 per cent in 1 hour. After remov- ing the excess of phenylarsine oxide in the usual manner, the solution was rendered alkaline with a.mmonia and treated vi^ith a solution of calcium chloride w'nereupon a sandy-like substance separated out. It was amlyzed without further purification. 0 Subs. 0.5 g. : 0.0726 g. HaO loss( heating;' at 110 for 1 hour Subs. 0.2 g. : 12 cc. 0.09205 b I Care, for CisHsaAsOsNe Ca . 6 H 2 O : H 3 O, 14.52 0/0 As, 20.05oyO Pound: H3O, 14.44 0/0 As, 20.64 0/0 1 rl |1 K' <■ (I - 47 - SUidiuAHY The keyer Reactioxi was modified by substituting eitner an alhyl bromide or chloride for a«« alhyi iodide, by omitting alco- nol as a solvent, and by heating and stirriiig the reaction mix- ture . Methyl, ethyl, n-propyl, n-butyl, and allyl ar sonic acids, the last two of which are new, were prepared by tne modified Meyer reaction. The method failed for the preparation of iso- pro pylarsonic acid, ethylene di-arsonic acid, tri-methylene-di- arsonic acid, f phenoxy-ethy^lar sonic acid, and y pnenoxypropyl- arsonic acid . n-Butyl and ethylarsine dichloride v/ere prepared by reduc- ing the correspondiir’’ arsoiiic acids dissolved in concentrated .hydrochloric acid with sulfur dioxide. A number of dialhylarsinic acids, includiiig dietnylarsinic acid di-n-but3^1arsinic acid, and n-outyl-i.-propylarsinic acid of wnich fhe last two are new, were readily prepared by the li.odifi- ed method. A few special types of compounds such as f phenos^- ethyl-pheiiylarsinic acid were also made. An attempt to prepare aromatic -aliphatic arsinic acids fail ed since the product which was obtained as an oil could *.ot ^e crystallized. Phenylarsi2iic-acet ic aciu was prepared by the actioxi of cnloroacetic acid on sodium phenylarsenitw-. It was reduced to pnei.yl-chloroarsine-aceti c acid bj^ means of sulfur dioxide. On attempt to convert the latter compound to the acetyl cnloride ^ rm i >J 1. ii.l. *‘ ■ •V L y- \ ,.v‘ vl... , . ii J W Ai- i. ^1 I - f . / . , , . ;...•,*. 4 . . .;. i. ‘ . i ’ >' * .1 , V ' ‘ y. ♦ I I I I - 48 - derivative failed since the necessary reagents split the arsine radical from the acetic acid group. A number oi' aromatic substituted amides of phenylarsinic- acetic acid were prepared by the actioii of the correspondiiig chloroacetyl derivative on sodium phenyl-arsenit e« A similar series of derivatives of p-amino-phenylarsinic-acetic acid were also prepared 4TVjh)L^i|MBK '- I* ^ ’ T ' . • I V "i itr. n!i •\ ■' ■" 'V-W'Prs ^ V \. .. i -A % >■ b ' " ; j' ’••’*>•' „ -.,;>• • , ■.'>>■ ji '.’A*’*' ' ' "? * '* ' ' ’aT ' -’ ^ ,'^A Z'yU^y :ng^i7T«ui 0iti: ; (■■;. ' I ' ■*,■>■ ' ■"■• ' '■• ■:■ -Fvfi '^w ,' ■:*; ■ te. -T-i',*-, V ’ • ..■'H'.i ..V< ■f - .( •> iy .■■ '■ f V.. . • ■ • L ■,*.'• L 'LiiXt’. t rt{ -■ t’Ww .■ / i ‘ \ < ti'f ,■ '<». -■ ^ ^ It ■ j^' Au%j. 1 jUPlx“ . I' '-MW-', ■ ■»;■.■»..' .'.'■t's;®fc '5« 'fc'v.. . . .VfsilPS . 'a '■ V*— 'k i'' V; 7 liliV, \' : ■• •''“i .. ■ • m Aiil ' “ ‘T' '.«' ' V;L. , I . . , . ' vv; W" , . 5. .'tt.,*. ^‘S ,Mf*- •* . ^ , A. ^ ^ ‘ • •' ' » ,*S..J , ,.v. ^ .*' ' f-f . 4 r LSI* -A^>i PART TI The Action between Secoiidary Arsines and Alde’riydes* - 49 - THEORETICAL Recently Adams and Palmer (58) found that primary arsines reacted with aldehydes to ;^ive an addition produce to v/hich they assigned the structure: ( RCHOH )3As.R. In order to find v;hether this reaction can oe extended to the secondary arsines, this work was undertaken. Dipneny''larsine was chosen as a representative secondary arsine, while benzaldehyde and butyr-aldehyde as aromatic and aliphatic aldeh3^des respectively. The arsine reacted with both aldehydes, but in Doth cases tne additioii product was too unstaole and too sensitive to oxidation to permit its isoiatiox*. The reaction v;as not an oxidation of the arsine by the alde- hyde, for in the first place, no reduction products of the aldehyde could be detected, aiia, ix* the secoiid place tne reac- tion mixture before beii]^: exposed t 0 air uissoived completely in ether, whereas, the oxidatioii products of diphenylarsine, especially diphery’-larsinic acid, are out siightly soluble in t'hat solvent. It was further found that a luucn larger part of the arsine aiid alde'h3'’de than could be accounted for as unchang- ed material, Judging from the intensity of the reaction, could be recovered by fractional distillation under diminisned pres- sure . The experimental evidence, especiall3^ in the case of ben- zaideh3'-de, pointed to the formation of an additioii product which vvhen exposed to air immediately underwent oxidation wicn suose- quent cleavage giving benzaldehyde again and the oxidation pro- ducts of phenylarsine . The y§P^F.f^ipn of a solid to the extent -50 that the vmole solution solidified indicated tnat a large amount of a solid product was formed. This was not aipheiiyi- arsinic aoia or pheiiiylcacod:^' 1 since ootn are spariiigly soluble in ether, wnereas the reaction mixture dissolvea corapietely in that solveiit. li’urthermore, it seemed improbable tnat it was mainly phenyl-arsine oxide since this suostance was never found present in large amount. A possible explanatioii of rhe reaction is as follows:- (CeH5)2AsH + RCHO —> ( CeHe ^aAs - CHOHR ■■ ii ( CeHe )2 AsCH 0HK — > ( Ceils ) 2 As ^ — R~:^( CeHs }3As + KCiiO 0/ rf 0 I :. , V: " ; r^'i ■'■''«r 3 '''’^''v-' V'i'rw , .:>'■? , : . ,:, ... . _ . .•'... ■'■ I'.' VCIY' '•' v\«- 'K-''i ’.TT5 •• If * l" ' ' ' vl ' ■ ■** Jfcf ■ li ,,\ i ■ i. . . ■• U »»4J ' «tV( I I • I • r- .S >. >J ' i 4 ' •- . w ‘‘tt j” )i$i4v,^T-i* ^ * ' .1 ;.' • » iw* .;/ 1 . !• . . u i^,> L - ; ^ . uo; : = :., , ^ i ?. *'• '.'*w,J> li-vj » \!' ' ,• A. I r ’ .A ^ \ ^ it r ■ Mf * '* * U ■ . *= •» ^ ■'V.*' ‘r ;''«ai»W •-> f. ) . •*■ ■:. IK' .•>;' ■y-i.. '■ r ,fV .7 1 , ■ ■• ,. ■,' 7 i£«>d’ , a; ■. \ '"i 'i ■* ■ " ' . *, ^ '-^vl ^ ■7 ■■■ ■' >>< r ,\ 'i ■ ■K •' V, fV ' * ' j V '■!,! '» kLft ^ ,vHUiaOT^ fractional distillation under diminished pressure, 9 g» of the aldehy^de ana 25 grams 01 the arsine were recovered. A siuall amount of a heavy red oil remained wnicn could xiot be distilled without decomposition. By extracring tnis oil witn Eodi'i^rii carboziate, and subseciuenu acidif icax-ioxi ol i/he extract, a considerable amount of dipheuylarsinic acid was oo— taiiied showing that this substance was the maiii constituexit of the oil. No condensation products could be isolated. - 54 - SUMkARY The reaction oe tween diphenylarsixie axid two axdenyuee, GUtyl and Derisaldehyde, was stuaied. In ooth cases a reaction took place, presumably wizh the formation of an addition pro- duct, v/hich was too unstable and too sensitive to oxidation to allow its isolation. Ainong t?ie products isolated after ex- posing the reaction mixture to the air were the aldeh3''de, di- phenj^larsine oxide, and diphenylarsinic acid. I ( / / 1 ^ I I',' y *'£ ’ yK ‘ J.; V ■’ PART III Miscellaneous React-ions. - 55 - TKEORKTICAL 111 order to prepare areenic-euGs-citut ed aliphatic acids various iiiethods of synthesis were attempted before it was fouxid cnat the keyer reaction waa applicaole for tnat synthesis. Tne malonic ester sj^nthesis was the first to be considered. It was hoped that an alJQ'-larsine group could be introduced i/ito the malonic ester by means of aikyl chloroarsine in the same way as an alkyl group b}^ an alkyl halide. The expected reac- tion; COOC3H6 COOC2HB COOH CHs + Na( C4 Hp )3AsC 1 — >CHAs( C4H9 )s — ^CHAs( C4H9 > COOCaHn COOCsHb COOH ( C4H9 ) 2 AsCH 3 C 00 H did not materialize. Instead of actiiig like an alkyl halide, the di butylarsine chloride was simply hydrolj-zed to tne corres- ponding arsine oxide which on long exposure to air oxialzed to dibutylarsinic acid. The possibility of utilizing diazoacetic ester v^as next in- vestigated. Judging from analogous reactions of diazoacetic ester, the follovving reactioii seemed probable: CH3ASCI3 + H3CHCOOC3H5 CH3As( CHCICOOC2H6 )3 + R3 The results, however, were negative. Although a reaction occur- red as indicated by the evolution of nitrogen, onl.y gummy pro- ducts, for which no method of purification could be found, v/ere obtained. Ko reaction occurred when secondary chloroarsizies were used. Since the chloroarsiiies gave unsatisfact ory results it v;as f , . , I .y n : H . 'JM • « 'V ,* -irsf'. i J.- . 1 • "■ . \ '• '■ .-• },'i • ; ' ' k / 4 - ’ ; ... V JQ\: - 56 - thought that perhaps tne arsines themselves might react ?>^ith the diazoacetic ester to give the desired arsenic -su'ostituted acetic acid as indicated by the following equations: CeHsAsHa + i^aCHCOOCaHs CeH6As( CHa COOCaHs )a + ha (CeHB)aAsE + haCHCOOCaHB ( CeHs )aAsCH3C00H + ha A reaction occurred wii-h both pri/i;ary and v/ith secondary arsine as iiidicated by tne brisk evolutioxi of nitrogen, out the difficulty arose in tne isolation of tne products. In the case of diphexiylarsiiie , the resulting product was unstable axid imme- diatel5'' oxidized giving diphei]5’’larsiiiic acid instead of the de- sired product. With pheiiylarsine an oil was obtained v/hicn could. .not be distilled evexi under reduced pressure vtfithout de- composition. Saponification of the ester, instead of giviiig the desired acid, gave pheii3'’larsine oxide, indicating that the alka- li used hydrolyzed the compouiid betweexi che arsinic and acetic acid groups. In view of the fact bhc^t this prelimixiary work did not look promising, and that the starting materials were diffi- cult to prepare in large amounts, the work was abandoned at this point. Another possible rnetiiod for s3^nthesising an arsinic-acetic acid derivative was seexi in the condexisatioxi of ethyl chloro- acetate with a chloro-arsine by means of a metal sucn as sodium or magnesium. It was sooxi found that the latter did xiot cause an.y condensation, while the former produced a mixture of guimgy products. A reactioxi whicn appeared to be the most promising was tnat - 57 - between the Grignard reagent and pheiiylarsine . The equation is as follov/s: CHsMgl + CsHbAsHs > CH 4 + CeHeAsC iiigl )a This reaction went very sniooth;ly, and it seems quite feasible that the product formed could be converted to an acetic acid derivative by treatment with ethyl chloroacetat e as indicated by the equation: CeH 6 As(MgI )3 + CICH3COOC3K6 CrHbAsC CH3COOC3E6 )3+kgClI Since the desired type of compound could be readily synthesized by the Meyer reaction, further work was discontinued, Neverthe- less, this latter reaction of the arsines is not only interest- ing, but may be useful in the synthesis of certain types of compounds » **■■■ ‘ '•J.w j S»- . d ■ ■ :(. .(’I 1 1. ^ . . i. . f* •‘i;; ^ >. o .va ■ - V. 1 ■ - £ '. ' ' * ' ' *• .' L j f XI • El* . r IV . / . ^‘h ' ' ; '■ -■ ■ • ‘i’ ■' ': '»i|J -J c ...1 . ,'• ■■ '■ 'ir-.-'n- ... ".■.;',’"'"’W- ,- -•' . ,v V p- s »!,( •’’An'3 '''?S I rt' V7;.. -A‘ ' £’^'' Vj'i V H XW V- V-. ■', nc^., »^SiA^;:. 1t^ i • ' / A ‘ - f j! *V • ^ ■'.tt4,A. ; .,±,^ .'■ nH'li! s? .*^iA i.t l ,.~- ■ t W L ftMilM ■! < ■ -►*••' ^ 8 - E^PEHIi/lSlTTAL Alkviarsine cnlor ide on sodium-malonic ester* The ordinary procedure for a njaionic ester synthesis was followed. 1.5 g. of sliced sodium was added gradually to I 3 cc. of absolute alcohol. When all had gone iiibo solution, 10. 7 g. oi‘ freshly distilled ethyl malonate was alowly added, and this followed by 15 g. of basic di'outylarsine chloride . The mixture was refluxed for five hours, the greater amount of the alcohol distilled off, the residue poured into ice water, and then ex- tracted with ether. The ether was allowed to evaporate spontan- eously, and at the end of tv;o weeks a crystalline mass mixed with a very tarry riiateriax remairied. The crystals were filtered off, and the adiiering tar carefull 3 '- washed off with ether. The product thus obtained melted correctly for dibutylarsinic acid. A yield of 7 8 ^* of the same were obtained. There was no indica- tion of the presence of the desired dibuty larsinic-malonic ester. piazQ-acet ic ester on Ars i^ies . Ethyl diazQ acetat e . This compound was prepared from glyco- coll ester hyaro chloride ' 03 ?^ Silberrad's modification of the Curtius method with satisfactory results. (-40} Diazo - acetic ester and Me thvlars ine dichloride . To a solu- tion of 24 g. of diazo-acetic ester in 25 cc. of petroleum ether, 9 cc. of methylarsine dichloride were gradually added. A brisk reaction set in immediately as indicated by the evolution of nitrogen. A white precipitate soon began to separate out, but in the course of an hour it became gummy and finally turned to ; j. Iv •J ¥- . i j . I J I • . ‘ ^ 1,4 ‘ "'lai . ■■ .;..,/2 L w 4 « A k ? I*"- t. .a '■ A ■ J ,. •. . ir -”'^v | i ' \ 'u ‘t|‘ (■;u !• !■ ■ 1 ■ : ( . ) i . - 59 - an oil insoluble in the solvent used* ITie reaction was complete in about 3 hours. Al’ter removing the petroleum ether, 13 B* of a dark pitch-like substance remained vniich could noo oe distill- ed even under diminished pressure wiuhoui. decomposition. It was saponified by refluxing with ^0 cc. of 10 per cent sodium nydroxide solution. On acidification, there was no precipitate, however, and no acid could be isolated. Diazo-acet ic ester with Diphenv lar s ine . The reaction was carried out in a small flask fitted with a reflux condenser and a dropping funnel. A slow stream of dry carbon dioxide was passed through the apparatus while 14. S cc. of ethyl-diazo- acetate were added dropwise to 32 g. of aiphenj^'l-a-rsine . On slight warmirig a steady evolution of nitrogen set iii, ana in the course of a naif hour, the reaction was over. As soon as the reaction mixture was exposed to the air, oxidation took place as shown by the evolution of heat. In a short time di- phenylarsinic acid began to separate out and v/as the main pro- duct. No other compound appeared to be present in any apprecia- ble amount s . Diaz o-acetic ester with Phenvlarsin e. Tne reaction was carried out in the same manner as in the preceding experiment. 28 g. of diazo-acetic ester were slowly added to 23 g. of phenyl- arsine. An immediate but moderate reaction set in wriich continu- ed about four hours. V/]ien tne reaction was completed on the water bath a brisk evolution of nitrogen occurred. At the end of 13 minutes iieither ethyl aiazo-acetate , nor free phexiylar- 1 X- \ V JK i j ',Vi \ • V ■ ■ ' K . ■' I 1 ' '\ 4 '' •wer^ - 60 - sine remained. About 30 g* of oil wab obtained whic]^ since it could not be distilled v,/ithout dec omposi bi oii^ was saponified oy means of a 10 per cent sodium hydroxide solution. After reflux- ing for 3 hours all went into solution. On rendering tne solu- tion acid, a gummj'' substance separated whic'n on standing? hard- ened to a granular macs. About 10 g. of material were obtained. After recrystallization from chloroform, the product vi^as iden- tified as phei]ylarsine oxide. There was no iiidication of the desired acetic acid derivative. Grignard Reagent on Arsines . Gr jgnard Reagent on Pnenvlarsine . Tne Grignard reagent was prepared in the usual manner by adding: 20 g. of methyl iodide to 3*3 of finely’" divided magnesium covered with 100 cc. of drj^ ebher. The main reaction was carried out in a liter flask fitted with a small dropping funnel ana a reflux condenser to which a delivery tube extending into a basin of water w-as at- tached. The liberated methane was collected over water in a graduated flask. 0 Subs. 3 S* phenylarsine 1042 cc. metnane at 24 743 mm. 0 Calc. vol. for methane at 0 760 rmn. : 93S cc. Found: 906cc n -r- ^ti rarsm -6i- SUMviARY An attempt to introduce aii alkyiarsine group into maloiiic eJBter in the same way that alkyl groups are iiitroduced , Tailed, the alkyl-arsine chloride merel3^ Deiiig hydrolysing to the cor- responding oxide. An attempt to prepare arsenic-suosti wUt ed acetic acid cy cue action of diazoacetic ester On jaeth3''ldichlor oarsine result- ed ii* tarr3?- products which could not oe purified. A siiiiilar attempt using diazoacetic ester on phen 3 ^ 1 arsine failed. Although a reaction took place, the desirea product could xiot be isolated. Unsatisf actory resulus were also obtained w'hen dizao- acetic ester reacted with diphen3a- arsine. The product formed was too sensitive to oxidation to allow its isolawion. Phenylarsine reacts v/ith the Grignard reagent analogously to aniline giving off a, h 3 ^drocarbon in the theoretical amount. - 62 - BIBLIOaHAPHY. 1. Becharap, Compt.rend* , 870 , 356 fl86o) 56, 1172 ( 1863) 2. Bart, B.R.P. 2502i64 3. Cadet, Memoirs de Mathematiqne et de Physique, 3, 623 (1760) 4. Landolt , Annalen, 8S , 321 (1854) 5. Gahours , Annalen , IFF , 198 (1862) 6. Mannheim, Annalen, 341 ,196 (1905) 7. Partheil, Arch-.Pharm. , 237 , 134 (1899) 8. Hoffmann, Annalen, 103 , 356 (1857) 9. La Coste , Annalen, 208 . 33 (1881) 10. Pehn and Mleox, Am.Chem.J., 33, 129 (1905) 11. Eihbert, Ber. , 3^, 160 (190"^ 12. Auger and Billy, Gompt.rend., 139 , 597 (1904) 15. Baeyer, Annalen, 107 , 282 (1856) 14. Gahours, Gompt.rend., 1023 (i860) 15. Michaelis and Paetow, Annalen, 253 . 60 (1886) 16. Pehn and lYilcox, Am.Chera. J. , 48 (1906) 17. Meyer ,G., Ber. 16,1440 (1883) 18. Klinger and Kreutz , Annalen, 249 . 147 (1905) 19. Auger, Gompt.rend., 137 . 925 (1903) 20. Pehn and Me G-rath , J.Am .Chem .Soc . , 347 (1906) 21. Ehrlich and Bertheim, Ber., ^,350 (1915) 22. Burrows and Turner, J. Chem. Soc., 119 . 326 (19 21) 23. Yaleur and Pelahy, Bull. Soc .chim. , 27., 370 (1920) 24. Porris, J .Ind. Eng. Chem. , 11, 817 (1919) 25. Uhlinger and Cook, J.Tnd.Eng.Chem. , IX, 105 (1919) 26. Henshaw and Holm, J .Am. Chem .Soc . , ^2, 1468 (1920) 27. Steinkopf and Mieg, Ber., 1013 (1920) 28. Ehrlich and Bertheim, Ber., 917 (1910) 29. La Coste, Annalen, 208 . 34 (1881) 30. Robertson, J. Am, Chem. Soc . , 42.. 182 (1921) 31. Bunsen, Annalen, 4£, 4l (1842) 32. Landolt, J.pr.Chem. , 283 (1854) Annalen, 8.2, 365 (1854) 33. Jacobs and Heidelberger , J .Am .Chem. Soc . , 39., 1439 (1917) 34. Jacobs and Heidelberger, J .Am .Chem .Soc . , 41. 1810 (1919) 35. Pawlewski, Ber., 2ii, 1684 (1905) 36. Toramasi, Gompt.rend., 840 (1873) 37. Schulte ,, Ber . , 42. 1955 (1855) 38. Adams and Palmer, J.Am .Chem. Soc . , 42, 2375 (1920) 39. Michaelis, Annalen, 321 . 151 (190^7 40. Silberrad, J. Chem. Soc. , 81, 600 (1902) -63- YITA The ’;7riter was horn at Theresa, ’Wisconsin, July 18, 1894. He completed his elementary school course in that village, and was graduated from the liadison (’Yisconsin) High School in 1914. The following fall he entered the Univeisitj; of 'Yisconsin Irom which institution he received the degree of Bacheloi of Science in Ghemistrj', June 1918, and the degree of Haster of Science, June 1919. After teaching at Vanderbilt University for one year, he entered the University of Illinois in the summer of 19 2C, holding a fellowship for the year 192C-E1. Appointments : Assistant University of Wisconsin 1918-19 Instructor Vanderbilt University 1919-20 Fellow University of Illinois. 1920-21 Publications ; The Preparation of p-Phenylenediamine and Aniline from Their Corresponding Chlorobenzenes. By Armand J. Quick. J .Am.Chera.Soc. , 42, 1033 (1920) The Properties of Subsidiary Valence Croups. I. The vlole- cular Volum.e Pielat ionships of the Hydrates and Ammines of Some Cobalt Compounds. II. Subsidiary Croup Mobility as Studied by the Heat Decomposition of Some Cobalt- amraines. By George L, Clark, A.J. Quick, and 7/illiam D. Harkins. J . Am .Chem.E oc . , 42, 2483 (1920)