Monographs on Industrial Chemistry 
 
 ORGANIC COMPOUNDS OF 
 
 iNIC AND ANTIMONY 
 
 GILBERT T. MORGAN 
 
ORGANIC COMPOUNDS OF 
 ARSENIC AND ANTIMONY 
 
ORGANIC COMPOUNDS 
 
 OF 
 
 ARSENIC 8f ANTIMONY 
 
 BY 
 
 GILBERT T. MORGAN, 
 
 D.So., F.R.S., F.I.C., M.R.I. A., A.R.C.Sc. 
 
 Professor of Applied Chemistry, City and Guilds Technical 
 College, Fins bury. 
 
 Formerly Professor in the Faculty of Applied Chemistry, 
 Royal College of Science for Ireland; and Assistant Professor 
 
 in the Imperial College of Science and Technology. 
 Corresponding Member of the Royal Dublin Society. 
 
 LONGMANS, GREEN, AND CO. 
 
 39 PATERNOSTER ROW, LONDON 
 NEW YORK, BOMBAY AND CALCUTTA 
 
 1918 
 
 All rights reserved. 
 

V 
 
 PREFACE 
 
 ORGANIC derivatives of arsenic appeal to the scientific public 
 for two widely different reasons. From the historical stand- 
 point these substances are of considerable interest because they 
 have been under investigation throughout a period of time 
 coeval with the birth and development of modern chemistry. Suc- 
 cessive generations of chemists have examined these compounds 
 from points of view which varied with the gradual evolution of 
 chemical science, and the results of their researches have played 
 an important part in the establishment of current theories of the 
 molecular constitution of matter. 
 
 Additional importance is conferred on the subject by the 
 circumstance that very early in the study of organic arsenical 
 compounds it was realised that, in these synthetic products, 
 the physician has at his disposal substances of great physiological 
 potency. It is chiefly this medicinal attribute of organic arsenicals 
 which has evoked the more recent activities in the synthesis of 
 organo-metalloidal compounds. These utilitarian investigations 
 have not been restricted to organic arsenicals, but have extended 
 to the corresponding derivatives of antimony, and accordingly 
 these related products are also discussed in the present mono- 
 graph. 
 
 Both series of organo-metalloidal compounds are already so 
 extensive that a detailed description of every individual member 
 would render this treatise unduly bulky, but a liberal selection has 
 been made comprising those substances having either a practical 
 application or some aspect of theoretical interest. A biblio- 
 graphy of the most important researches and treatises down to 
 the end of 1917 has been included, and these references to original 
 memoirs supply the necessary clue to further information re- 
 garding any known organic arsenical or antimonial which may 
 in the future acquire increased prominence. 
 
 v 
 
 382949 
 
PREFACE 
 
 It is my pleasant duty to express my grateful thanks for 
 assistance received in the compilation of this monograph from 
 the following firms : Les fitablissements Poulenc Freres, 
 Messrs. Burroughs Wellcome & Co., and Messrs. May and Baker. 
 
 I also desire to acknowledge the friendly help received from 
 Dr. W. H. Martindale, from Mr. E. Scholl, formerly of the 
 Farbwerke vormals Meister, Lucius, und Briining; from Mr. 
 F. W. Clifford, Librarian of the Chemical Society ; and from 
 Messrs. E. D. Evens, B.Sc., and W. R. Grist, who have assisted 
 me in reading the proofs and in arranging the index and biblio- 
 graphic data. 
 
 G. T. M. 
 
 CITY AND GUILDS TECHNICAL COLLEGE, FINSBURY, 
 LEONARD STREET, LONDON, E.C.2. 
 
 VI 
 
CONTENTS 
 
 PREFACE 
 
 INTRODUCTION x * 
 
 Chemical xi 
 
 Historical xii 
 
 CHAPTER I. 
 
 CACODYL T 
 
 Earliest Researches on Organic Arsenicals i 
 
 Section I. Cadet's fuming arsenical liquid ...... i 
 
 II. Cacodyl and its derivatives 5 
 
 ,, III. Homologues of cacodyl i? 
 
 CHAPTER II. 
 
 ALIPHATIC ARSENICALS AND ANTIMONIALS 20 
 
 Syntheses of Alkyl Organo-metalloidal Compounds containing Arsenic 
 
 and Antimony 20 
 
 Section I. General Reactions 21 
 
 II. Aliphatic arsenic compounds 3 2 
 
 III. Aliphatic antimony compounds 53 
 
 CHAPTER , III. 
 
 AROMATIC ARSENICALS 6 4 
 
 Arylarsines and their Immediate Derivatives 64 
 
 Section I . Benzene derivatives with one aromatic nucleus attached 
 
 to one arsenic atom 7 8 
 
 II. Benzene derivatives with two aromatic nuclei attached 
 
 to one arsenic atom 95 
 
 III. Benzene derivatives with three aromatic nuclei attached 
 
 to one arsenic atom .100 
 
 IV. Toluene derivatives with one aromatic nucleus at- 
 tached to one arsenic atom i5 
 
 V. Toluene derivatives with two or three aromatic nuclei 
 
 attached to one arsenic atom . . . . . 108 
 
 VI. Benzyl derivatives TI 4 
 
 vii 
 
CONTENTS 
 
 PAGE 
 
 Section VII. Aromatic arsenicals containing higher aryl groups . 119 
 ,, VIII. Naphthalene derivatives 125 
 
 IX. Benzarsinic acids and their derivatives . . . .128 
 ,, X. Betaines of aromatic arsenicals 138 
 
 XI. Nitro-derivatives of aromatic arsenicals . . . . 142 
 
 CHAPTER IV. 
 
 ATOXYL 153 
 
 The Btchamp Reaction and its Extensions 153 
 
 Section I. ^-Arsanilic acid and its A^-acyl and W-alkyl derivatives 158 
 
 ,, II. Isomerides of />-arsanilic acid 167 
 
 III. Homologues and substitution products of ^-arsanilic 
 
 acid 171 
 
 IV. Homologues and derivatives of o-arsanilic acid . . 178 
 V. Nitroso-, azo-, diazo-, and triazo-phenylarsinic deriv- 
 atives 179 
 
 VI. Organo-mercurial compounds of -arsanilic acid and 
 
 its derivatives 183 
 
 ,, VII. 4 : 4'- Diaminodiarylarsinic acids 185 
 
 VIII. Mixed aromatic-aliphatic ^-amino-arsinic acids . . 187 
 IX. Nitro-derivatives of the arsanilic acids . . . .187 
 
 X. Diaminophenylarsinic acids 195 
 
 XI. Hydroxyphenylarsinic acids 196 
 
 XII. Nitro-derivatives of the hydroxyphenylarsinic acids . 200 
 
 XIII. Arsinic acids of the aminophenols 205 
 
 CHAPTER V. 
 
 SALVARSAN 208 
 
 Aromatic Derivatives containing Tervalent Arsenic. Part I. . . 208 
 Section I. Reduction products of ^-hydroxyphenylarsinic acid 
 
 and its derivatives 212 
 
 II. Aminoaryl derivatives containing tervalent arsenic . 217 
 
 III. Salvarsan 224 
 
 IV. Isomerides of Salvarsan 232 
 
 V. Derivatives and homologues of Salvarsan . . . 234 
 
 ,, VI. Tetraminoarsenobenzenes 243 
 
 VII. Diaminotetrahydroxyarsenobenzene and its derivatives 245 
 
 VIII. Hexaminoarsenobenzene and its derivatives . . 247 
 
 CHAPTER VI. 
 
 NEOSALVARSAN 251 
 
 Aromatic Derivatives containing Tervalent Arsenic. Part II. . . 251 
 
 Section I. Neosalvarsan 251 
 
 II. Galyl and Ludyl . 255 
 
 III. Arsenoarylglycines 257 
 
 IV. Arsenohippuric acid 260 
 
 viii 
 
CONTENTS 
 CHAPTER VII. 
 
 PAGE 
 
 AROMATIC PRIMARY ARSINES 262 
 
 Synthesis of Dissymmetric Arsenobenzene Derivatives .... 262 
 
 Section I. Substituted primary arylarsines 263 
 
 II. Dissymmetrically substituted arsenobenzenes . . . 265 
 
 III. Polyarsenical compounds containing aromatic groups . 270 
 
 CHAPTER VIII. 
 
 LUARGOL 277 
 
 Co-ordination Compounds of Aromatic Arsenicals 277 
 
 Section I. Co-ordination compounds of arsenobenzene and its 
 
 derivatives 281 
 
 II. Luargol 285 
 
 III. Co-ordination compounds of aromatic polyarsenides . 286 
 
 CHAPTER IX. 
 
 AROMATIC ANTIMONIALS 293 
 
 Part I. Aromatic Stibines and their Immediate Derivatives . . . 293 
 Section I. Aryl derivatives containing one aromatic group attached 
 
 to one antimony atom 298 
 
 II. Diaryl antimony derivatives 301 
 
 III. Triaryl antimony derivatives 304 
 
 Part II. The Diazo-synthesis of Aryl Antimony Derivatives . . . 313 
 
 Section IV. Aromatic stibinic acids - . 3 I 3 
 
 V. Mono-aryl derivatives containing tervalent antimony . 322 
 
 CHAPTER X. 
 
 MISCELLANEOUS ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 327 
 
 Section I. Hydroaromatic derivatives of arsenic and antimony . 327 
 
 II. Heterocyclic rings containing arsenic and antimony . 330 
 
 III. Arsenical derivatives containing Heterocyclic Nuclei . 333 
 
 IV. Arsenical Esters and Arsenical Lipoid and Protein 
 
 Combinations 337 
 
 APPENDIX 344 
 
 BIBLIOGRAPHY 351 
 
 INDEX OF AUTHORS' NAMES 361 
 
 INDEX OF SUBJECTS 364 
 
 IX 
 
INTRODUCTION 
 
 I. Chemical. 
 
 ARSENIC and antimony belong to the nitrogen group of 
 chemical elements, one of a pair of related families constituting 
 the fifth series of elements in the periodic system of classification. 
 The relative positions of the members of these two natural 
 families of elements are shown in the following table. 
 
 Inasmuch as the physical and chemical properties of arsenic 
 and antimony bridge over the differences between the non- 
 metals nitrogen and phosphorus and the metal bismuth, 
 these two intervening elements are frequently termed metalloids, 
 this expression signifying that certain of their attributes are 
 metallic, whereas others are non-metallic. 
 
 Periodic Classification : Fifth Vertical Series. 
 Typical oxide, R 2 O 5 . Typical fluoride, RF 5 . 
 
 Family A : Nitrogen group. 
 Typical hydride, RH 3 . 
 Typical alkyl derivative, R(CH 3 ) 3 . 
 Element. At. Wt. 
 
 I nitrogen . . 14 
 (phosphorus . 31 
 (ARSENIC . . 75 
 \ANTIMONY . 120 
 metal bismuth 208 
 
 non-metals 
 metalloids 
 
 Family B :< Vanadium group. 
 Hydrides and organic deriv- 
 ati ves' unknown . 
 Element. 
 
 metals 
 
 ( vanadium 
 \ columbium 
 (tantalum 
 
 At. Wt. 
 
 93*5 
 181 
 
 The members of the two families A and B show occasional 
 points of resemblance. Phosphorus, vanadium, and arsenic 
 form an isomorphous series as illustrated by the following 
 mineral species : 
 
 Pyromorphite 3Pb 3 (PO 4 ) 2 ,PbCl a . 
 
 Vanadinite 3Pb 3 (VO 4 ) 2 ,PbCl a . 
 
 Mimetite 3Pb 8 (As0 4 ) a ,PbCl 8 . 
 
 Antimony, columbium, and tantalum show a certain similarity 
 in their oxy-salts, as, for example, in the series 
 
 KSbO 3 , KCbO 3 , and KTaO 3 . 
 
 XI 
 
INTRODUCTION 
 
 These points of resemblance between the two families are, 
 however, much less conspicuous than their dissimilarities. Two 
 of the most striking differences are in regard to the respective 
 affinities of the members of the two families for organic radicals 
 and for hydrogen. 
 
 The members of the nitrogen family without exception furnish 
 organic derivatives, but on the contrary vanadium and the other 
 two metals of its family have not so far been induced to combine 
 directly with hydrocarbon radicals. 1 
 
 The organic compounds of arsenic and antimony are not 
 found in nature ; they are invariably obtained as products of 
 chemical synthesis. 
 
 Arsenic and antimony usually occur in the mineral kingdom 
 in combination with sulphur, forming either simple or complex 
 sulphides. Arsenic furnishes two simple sulphides, realgar > 
 As 2 S 2 , and orpiment, As 2 S 3 , whilst antimony is commonly 
 obtained from the crystalline stibnite, Sb 2 Ss. 
 
 In combination with cobalt, arsenic gives rise to the mineral 
 smaltite, and with sulphur and cobalt it occurs as cobaltite. 
 These two mineral species were often confounded by the earlier 
 French mineralogists and chemists, who applied the name 
 " Cobolt " to these two naturally occurring arsenical cobalt 
 compounds. 
 
 II. Historical. 
 
 In the earlier half of the eighteenth century the French 
 chemist Hellot obtained private information from a German 
 artist that the mineral cobolt from Schneeberg when extracted 
 with aquafortis yielded a solution which could be employed in 
 the preparation of sympathetic inks. He was thus led to ex- 
 amine specimens of cobolt from various sources with the object 
 of testing their suitability for the production of inks to be used 
 in writing secret despatches. His results, which were published 
 in the form of two memoirs to the Academic Royale des Sciences 
 in 1737, described the action of mineral acids and especially of 
 aquafortis on the cobolt from Schneeberg, Anneberg, and other 
 German sources and also on French specimens from Sainte- 
 Marie-aux-Mines (Vosges) and the Dauphine". Judging from 
 the origin of these specimens it seems likely that they were 
 
 1 This difference between the combining powers of the two families 
 of this series towards hydrocarbon radicals is noticeable in other vertical 
 series of the periodic arrangement. (Morgan, Science Progress, 1914, 8, 
 6950 
 
 xii 
 
INTRODUCTION 
 
 samples of smaltite, this mineral species being known to occur 
 in the foregoing localities. Hellot refers to the fact that the 
 blue ceramic pigment, smalt, is made from cobolt and that this 
 mineral is a source of white arsenic. 1 These experiments on the 
 production of sympathetic ink containing cobalt salts were 
 resumed about twenty years later by Louis Claude Cadet de 
 Gassicourt, a military apothecary stationed in Paris. 2 His 
 memoir published in 1760 is chiefly concerned with the extraction 
 of cobalt solutions suitable for the production of sympathetic 
 inks by the action of various acids including organic acids on 
 the mineral " cobolt." As a side issue he refers to experiments 
 made on the white arsenic also derived from cobolt. This 
 investigation, described in his own words in the opening chapter 
 of this monograph, led in a singularly fortuitous manner to the 
 production of the earliest known organo-arsenical compounds. 
 The product, a liquid with an intolerable stench, had the 
 remarkable property of taking fire on exposure to the atmosphere. 
 On this account it was known for many years as " Cadet's fuming 
 arsenical liquid." A few years later this liquid was again pre- 
 pared by Guyton de Morveau, Hugues Maret, and Jean Frangois 
 Durande, three French chemists working in Dijon, who 
 placed on record the disagreeable odour of the product and 
 its spontaneous inflammability in air at the ordinary tempera- 
 ture. 8 
 
 For a third time this uninviting material was examined by a 
 French chemist, Louis Jacques Thenard, who made repeated 
 distillations of the mixture of white arsenic and potassium 
 acetate by means of which Cadet had obtained his original 
 result. A more detailed study led Thenard to the conclusion 
 that the liquid was a complex acetate containing arsenic. 
 He also investigated its chemical reactions and identified some of 
 the volatile by-products set free during its preparation. 
 
 The next investigator to undertake the difficult and dis- 
 agreeable task of elucidating the chemical nature of this re- 
 
 1 " Sur une nouvelle encre sympathique." Histoire de I'Academie 
 Royale des Sciences, 1737, 1, 101 and 228. 
 
 2 " Suite d'Exp&riences nouvelles sur 1'encre sympathique de M. Hellot 
 qui peuvent servir a 1'analyse du cobolt ; et Histoire d'une liqueur fumante 
 tiree de 1'arsenic." Par M. Cadet, apothicaire-major de 1'Hotel Royal 
 des Invalides. Memoires de Mathematique et de Physique. Presentes 
 a 1' Academic Royale des Sciences par divers Savans et lus dans ses 
 Assemblies, 1760, 3, 623. 
 
 3 Elemens de chimie theorique et pratique, 1778, 3, 39- 
 
 xiii 
 
INTRODUCTION 
 
 markable substance was Robert Wilhelm Bunsen, who occupied 
 himself with the problem during the period 1837-1843. 
 
 Bunsen prepared large quantities of Cadet's arsenical liquid 
 and separated from this solution the predominant organic 
 constituent. His investigations, published in several memoirs, 
 showed that the chief organic constituent of Cadet's liquid is a 
 compound consisting of arsenic, carbon, hydrogen, and oxygen. 
 The last of these elements could be replaced by the halogens, 
 cyanogen and sulphur, without altering the relative proportions 
 of carbon, hydrogen, and arsenic, so that it appeared as if these 
 three elements had coalesced to form a complex which remained 
 unchanged during the foregoing substitutions. Later Bunsen 
 isolated the complex itself. 
 
 The significance of this remarkable discovery was at once 
 appreciated by the Swedish chemist Berzalius, who recognised in 
 Bunsen 's oxygenated arsenical compound an analogue of the 
 alkali oxides in which the elementary alkali radical is replaced 
 by a compound organic radical. To this compound radical 
 isolated by Bunsen, Berzelius gave the name " cacodyl " on 
 account of the disagreeable stench of its compounds. The 
 isolation of cacodyl afforded substantial experimental support 
 for the compound radical theory of the constitution of organic 
 compounds, of which important generalisation the Swedish 
 philosopher was the most eminent protagonist. 
 
 Bunsen never attempted any dissection of the cacodyl complex, 
 but the inner constitution of this compound radical was explained 
 by E. Frankland in 1849 as the result of his brilliant investigations 
 on zinc alkyls and other compounds of the hydrocarbon radicals. 
 This promising intervention did not, however, inspire many 
 other English chemists to study the organic derivatives of 
 arsenic and antimony. The few who embarked on these 
 researches were as ran nantes ingurgite vasto, so that the British 
 contribution to this section of synthetic chemistry is of very 
 modest dimensions. 
 
 To France belongs the honour of the first pioneering efforts 
 both as regards the earliest known aliphatic arsenicated com- 
 pounds and the more useful discovery of an aromatic arsenical 
 drug. The latter advance was made by Be"champ during the 
 years 1860-63, but the significance of this research was not 
 appreciated at the time in France, where it has needed the painful 
 and costly stimulus of two sanguinary wars with the neighbours 
 across the Rhine in order to demonstrate that these chemical 
 
 xiv 
 
INTRODUCTION 
 
 tours de force are worthy of support by co-ordinated effort. At 
 present this effort is being supplied, and academic and industrial 
 chemists are collaborating in the work of making and improving 
 arsenicated drugs. Already Les fitablissements Poulenc Freres 
 have developed the manufacture of 3 : 3 '-diamino-4 : 4 '-dihydroxy- 
 arsenobenzene (Salvarsan) and its methylenesulphinate (Neo- 
 salvarsan) on an industrial scale, whilst Oechslin, Mouneyrat, 
 and Danysz have introduced improvements into the chemio- 
 therapy of these aromatic arsenicals. 
 
 In England the above-mentioned drugs are being manufactured 
 by Messrs. Burroughs Wellcome & Co. and by Messrs. May 
 and Baker, the latter firm working in association with Poulenc 
 Freres. The chemists of the former firm have also carried 
 through a considerable amount of research on atoxyl and its 
 derivatives. Similar steps are now being taken in America and 
 other industrialised countries where a home production of 
 arsenical medicaments is urgently needed to replace the excluded 
 German supply. These developments, however, all arise from 
 the necessities imposed on society by the world-war, and in order 
 to maintain a chronological sequence it is necessary to return to 
 the decade immediately following on Bunsen's researches on 
 cacodyl. 
 
 The experimental verification of Frankland and Kolbe's 
 views on this substance was initiated in the Swiss Federal 
 Polytechnic at Zurich, where Lowig and Schweitzer synthesised 
 the first organic derivative of antimony in 1850. The method 
 they employed was sufficiently general to be applied to the 
 arsenical series, with the result that Cahours and Riche employed 
 it in synthesising cacodyl in 1853. 
 
 Bunsen's work on cacodyl was revised, substantiated, and 
 greatly extended by Baeyer in 1858, who first prepared primary 
 methyl arsenicals by partially demethylating cacodyl trichloride, 
 in this way arriving at methylarsinic acid, the soluble salts of 
 which have been employed medicinally as " new cacodyl " and 
 " arrhenal." 
 
 In so far as organic arsenicals are concerned Bunsen and 
 Baeyer J s researches were individual efforts carried out with little 
 help from assistants and collaborators. The next stage in 
 advance illustrates the growth of co-ordinated efforts in German 
 scientific research. Twelve years after Bechamp's discovery of 
 the first aromatic arsenical, Michaelis began a systematic study 
 of the aromatic derivatives of phosphorus, arsenic, and antimony, 
 
 xv 
 
INTRODUCTION 
 
 establishing first at Karlsruhe and Aachen and then at Rostock 
 a school of chemistry in this particular branch of organic synthesis. 
 The chapters on aromatic arsenicals and antimonials indicate 
 the extent to which this field of inquiry was developed with the 
 assistance of many collaborators. Michaelis with the aid of La 
 Coste, Reese, and others devised general methods of preparation 
 for the compounds of both series and prepared the first aromatic 
 antimony derivatives. At first these laborious contributions to 
 our knowledge of organic derivatives of arsenic and antimony 
 were entirely of academic interest, but subsequently the technical 
 skill acquired in these researches has been utilised in the synthesis 
 of arsenical drugs and certain allied toxic chemicals. 
 
 Bechamp's compound, then supposed to be an anilide of 
 arsenic acid, began to be tried in therapeutics in or about the 
 year 1902. Thomas and Breinl at this stage employed the 
 compound in the treatment of sleeping sickness. Owing to the 
 comparatively non-toxic nature of the drug, to which circum- 
 stance it owes its name of " atoxyl," a certain degree of success 
 attended these pioneering efforts in the chemiotherapy of aro- 
 matic arsenicals, with the result that the compound was subjected 
 to systematic investigation by Ehrlich and many collaborators. 
 It was speedily shown in 1907 by Ehrlich and Bertheim that 
 atoxyl is truly an organo-arsenical, being the sodium salt of 
 />-arsanilic acid. Comprehensive researches were started in 
 special laboratories, notably at the Georg Speyer Hospital in 
 Frankfort and at the Hochst Farbwerke vormals Meister, Lucius, 
 und Briining. The Bechamp reaction was extended from aniline 
 to other similarly constituted bases and even to phenol. A 
 very active exploitation of aromatic arsenicals now commenced, 
 which continues at the present time. Atoxyl and its homologues 
 are organic derivatives of quinquevalent arsenic, in which con- 
 dition the metalloid is fully saturated in regard to principal 
 valency and exhibits residual affinity to a minimum extent. 
 Ehrlich noticed that aromatic compounds of tervalent arsenic 
 were much more efficacious in combating trypanosomiasis, 
 relapsing fever, and other diseases of protozoal origin. After 
 many trials, in the course of which it is stated that 605 com- 
 pounds were examined, Ehrlich arrived in 1909 at Salvarsan or 
 " 606." This substance, introduced into pharmacy in the form 
 of its dihydrochloride, exhibits a remarkably specific action on the 
 protozoal parasite to which the varied manifestations of syphilis 
 are attributed. In this application the drug carefully neutralised 
 
 xvi 
 
INTRODUCTION 
 
 with aqueous sodium hydroxide is injected intravenously. 
 Although when skilfully administered the drug produces favour- 
 able results in the great majority of cases, yet the preliminary 
 chemical treatment is a matter which needs careful adjustment. 
 On this account search was made for a drug which would combine 
 the valuable germicidal action of salvarsan with the property 
 of dissolving in water or physiological salt solution with a neutral 
 reaction. Ehrlich's solution of this problem resulted in the 
 production of another drug, Neosalvarsan, introduced into thera- 
 peutics in 1911. This compound is the sodium methylene- 
 sulphinate of salvarsan. At the present time these two drugs, 
 salvarsan and neosalvarsan, sold as such or under various syno- 
 nyms, are the substances chiefly relied on in the arsenical treat- 
 ment of syphilis. 
 
 Research has not, however, halted at the production of these 
 two medicaments, excellent though they have proved to be. 
 At the International Medical Congress held in London in 1913 
 Ehrlich announced a further significant development in the 
 chemistry and chemiotherapy of aromatic arsenicals. Salvarsan 
 and other derivatives of arsenobenzene possess the singular 
 property of coupling with the salts of copper, silver, gold, and the 
 metals of the platinum group in such a way that the ordinary 
 analytical properties of these metals are not apparent in the 
 resulting combinations which can be administered intra- 
 venously just like salvarsan itself. The intervention of the heavy 
 metal is beneficial, for, in these circumstances, it exerts a germi- 
 cidal action reinforcing that of the aromatic arsenical, while 
 the toxic effect on the patient is less than that of salvarsan. 
 Already one substance of this type has been employed clinically 
 in the form of the drug " Luargol," first prepared by Danysz 
 in 1913, and since used with considerable success in the French 
 Army. An alternative drug to neosalvarsan has been recom- 
 mended in the product " Galyl," a complex phosphamate of 
 salvarsan, synthesised by Mouneyrat in 1912. 
 
 Another development in progress at the present time is the 
 production of organic arsenicals containing also other metalloids, 
 such as antimony, selenium, tellurium, etc. The preparation 
 of these complex substances is greatly facilitated by the discovery 
 of a general reaction for which the United States deserve the 
 credit. 
 
 The chemists of the Old World had settled down to the belief 
 that primary and secondary arsines are incapable of existence 
 
 xvii 
 
INTRODUCTION 
 
 when Palmer and Dehn, two American chemists, exploded this 
 ill-founded prejudice by preparing dimethylarsine in 1894 and 
 methylarsine and phenylarsine in 1901, and by devising a general 
 method for obtaining other more complicated primary arsines. 
 Dehn also generalised the process for producing monoalkyl- 
 arsinic acids. 
 
 The primary aromatic arsines are of the greatest value in the 
 preparation of certain physiologically active organic arsenicals 
 possessing a dissymmetric configuration. 
 
 The synthesis of aromatic organo-metalloidal compounds has 
 been further facilitated by the discovery that these substances 
 are obtainable through the well-known diazo-reaction. This 
 process has been applied to aromatic arsenicals by H. Bart and 
 to aromatic antimonials by the Chemische Fabrik von Heyden 
 of Dresden. The latter development has been very prolific, 
 so that antimony analogues of the principal aromatic arsenicals 
 have already been prepared by this means. 
 
 Meanwhile new derivatives of arsenobenzene are being in- 
 vestigated by Karrer and by the firms of Meister, Lucius, und 
 Bruning and of C. F. Boehringer und Sohne. Attention is being 
 directed specially to certain partly methylated hexaminoarseno- 
 benzenes which have the noteworthy property of forming stable 
 solutions with soluble bicarbonates. The latter salts have the 
 same degree of alkalinity as that of normal blood serum, so 
 that the foregoing property may acquire important physiological 
 significance when the arsenical hexamine is injected into the 
 circulatory system. 
 
 xvui 
 
ABBREVIATED TITLES OF JOURNALS TO 
 WHICH REFERENCES ARE MADE. 
 
 ABBREVIATED TITLE. 
 Amer. Chem. J. 
 Amer. J. Pharm. . 
 Amer. J. Physiol. . 
 Amer. J. Sci. 
 Analyst .... 
 Annalen. 
 Ann. Chim. anal. . 
 
 Ann. Chim. Applicata 
 Ann. Chim. Phys. 
 Ann. Inst. Pasteur 
 Arch. expt. Path. Pharm. 
 
 Arch. Pharm. 
 Ber. . . . 
 
 Biochem. Bull. 
 Bio-Chem. J . 
 Biochem. Zeitsch. . 
 Boll, chim: farm. . 
 Chem. Zentr. 
 Chem. News . 
 Chem. Soc. Proc. . 
 Chem. Soc. Trans. 
 Chem. Zeit. . 
 Compt. rend. . 
 
 Gazzetta .... 
 
 /. Amer. Chem. Soc. . 
 
 J. Biol. Chem. 
 
 J. Chem. Soc. 
 
 J. Med. Research . 
 
 J. Path. Bad. 
 
 J. Pharm. 
 
 J. Pharm. Chim. . 
 
 J. Physiol. . 
 
 J. pr. Chem. . 
 
 JOURNAL. 
 
 . American Chemical Journal. 
 . American Journal of Pharmacy. 
 . American Journal of Physiology. 
 . American Journal of Science. 
 . The Analyst. 
 
 . Justus Liebig's Annalen der Chemie. 
 . Annales de Chimie analytique appliquee a 
 
 1'Industrie, a 1'Agriculture, a la Phar- 
 
 macie et a la Biologic. 
 . Annali di Chimica Applicata. 
 . Annales de Chimie et de Physique. 
 . Annales de 1'Institut Pasteur. 
 . Archiv fur experimentelle Pathologic und 
 
 Pharmakologie. 
 . Archiv der Pharmazie. 
 . Berichte der Deutschen chemischen Gesell- 
 
 schaft. 
 
 . Biochemical Bulletin. 
 . The Bio-Chemical Journal. 
 . Biochemische Zeitschrift. 
 . Bollettino chimico farmaceutico. 
 . Chemisches Zentralblatt. 
 . Chemical News. 
 
 . Proceedings of the Chemical Society. 
 . Transactions of the Chemical Society. 
 
 Chemiker Zeitung. 
 . Comptes rendus hebdomadaires des Seances 
 
 de 1'Academie des Sciences. 
 . Gazzetta chimica italiana. 
 . Journal of the American Chemical Society. 
 . Journal of Biological Chemistry, New York. 
 . Journal of the Chemical Society (London). 
 . Journal of Medical Research. 
 . Journal of Pathology and Bacteriology. 
 . Journal of Pharmacy. 
 . Journal de Pharmacie et de Chimie. 
 . Journal of Physiology. 
 . Journal fur praktische Chemie* 
 xix 
 
JOURNALS TO WHICH REFERENCES ARE MADE 
 
 ABBREVIATED TITLE. 
 /. Russ. Phys. Chem. Soc. 
 
 J. Soc. Chem. Ind. 
 Monatsh. 
 
 Pfluger's Archiv . 
 
 Pharm. J. 
 Pharm. Weekblad 
 Pharm. Zeit. . 
 Pharm. Zentr-h. . 
 Phil. Trans. . 
 
 Proc. Amer. Physiol. Soc. 
 
 Proc. Roy. Soc. 
 Quart. J. exp. Physiol. 
 
 Rec. trav. chim. 
 
 Trans. Path. Soc. . 
 Zeitsch. anal. Chem. 
 Zeitsch. angew. Chem. . 
 Zeitsch. anorg. Chem. . 
 Zeitsch. Biol . 
 Zeitsch. Nahr. Genussm. 
 
 Zeitsch. physikal. Chem. 
 Zeitsch. physiol. Chem. 
 Zeitsch. fur Chem. 
 
 JOURNAL.* 
 . Journal of the Physical and Chemical Society 
 
 of Russia. 
 
 . Journal of the Society of Chemical Industry. 
 . Monatshefte fiir Chemie und verwandte 
 
 Theile anderer Wissenschaften. 
 . Archiv fiir die gesammte Physiologic des 
 
 Menschen und der Thiere. 
 . Pharmaceutical Journal. 
 . Pharmaceutisch Weekblad. 
 . Pharmazeutische Zeitung. 
 . Pharmazeutische Zentralhalle. 
 . Philosophical Transactions of the Royal 
 
 Society of London. 
 . Proceedings of the American Physiological 
 
 Society. 
 
 . Proceedings of the Royal Society. 
 . Quarterly Journal of experimental Physio- 
 logy. 
 . Receuil des travaux chimiques des Pays-Bas 
 
 et de la Belgique. 
 
 . Transactions of the Pathological Society. 
 . Zeitschrift fiir analytische Chemie. 
 . Zeitschrift fiir angewandte Chemie. 
 . Zeitschrift fiir anorganische Chemie. 
 . Zeitschrift fur Biologic. 
 . Zeitschrift fiir Untersuchung der Nahrungs- 
 
 und Genussmitte. 
 . Zeitschrift fiir physikalische Chemie, Stoch- 
 
 iometrie und Verwandtschaftslehre. 
 . Hoppe-Seyler's Zeitschrift fiir physiologische 
 
 Chemie. 
 . Zeitschrift fiir Chemie. 
 
 ABBREVIATED TITLES 
 
 Eng. P 
 
 Fr. P 
 
 D.R.-P 
 
 U.S.P 
 
 M. L. and B. 
 
 Fabr. Heyden, 
 Poulenc . 
 
 PATENT LITERATURE. 
 English Patent. 
 French Patent. 
 German Patent. 
 United States Patent. 
 Farbwerke vormals Meister, Lucius und 
 
 Bruning. 
 
 Chemische Fabrik von Heyden. 
 Les tablissements Poulenc Freres. 
 
 XX 
 
ORGANIC COMPOUNDS OF 
 ARSENIC AND ANTIMONY 
 
 CHAPTER I 
 CACODYL 
 
 Earliest Researches on Organic Arsenicals. 
 
 THE large number and diverse types of organo-arsenical 
 compounds isolated and described during the last 150 years 
 furnish ample evidence that the metalloid arsenic is endowed 
 with a great capacity for combining with hydrocarbon radicals. 
 Nevertheless this affinity has not manifested itself by the pro- 
 duction of these compounds either in the mineral kingdom or 
 as a result of the vital activities of living organisms. The special 
 conditions under which this chemical attraction becomes effective 
 have been, without exception, established by the art of the 
 chemist. All the organo-arsenicals are synthetic products. 1 
 
 Section I. Cadet's Fuming Arsenical Liquid. 
 
 The earliest of these syntheses was brought about in a 
 remarkably unpremeditated manner. In 1760 the mineral 
 " cobolt " or smaltite, cobalt arsenide, became the subject of an 
 inquiry by L. C. Cadet de Gassicourt, who was chiefly interested 
 in extracting therefrom by the action of various acids cobalt 
 
 1 A possible exception to this generalisation is noted on p. 54, in 
 reference to the production of diethylarsine by the growth of moulds 
 on carpets and wall-papers containing arsenical pigments. It is con- 
 ceivable that this phenomenon might be realised with naturally occurring 
 arseniferous materials altogether apart from the intervention of human 
 activities, but hitherto this likely formation of organic arsenicals has not 
 been recorded. 
 
 I B 
 
OF ARSENIC AND ANTIMONY 
 
 salts suitable as a basis for 'sympathetic' ink. The circumstance 
 that smaltite is also a source of white arsenic led Cadet to 
 examine the latter substance, although, apart from the common 
 origin of the materials, there is no obvious connection between 
 the latter experiment and those on cobalt preparations. The 
 greater part of Cadet's memoir is devoted to the work on cobalt 
 inks, but his " Histoire d'une liqueur fumante, tiree de 1'arsenic " 
 has led in the hands of subsequent workers to such important 
 theoretical and practical results that it is of interest to record 
 his procedure in his own words. 
 
 " Je prends deux onces d'arsenic, je le mets en poudre tres fine 
 dans un mortier de marbre ; j'y ajoute deux onces de terre foliee 
 de tartre bien prepare, j'enferme aussitot ce melange dans une 
 cornue de verre lutee, que je place a nu dans un petit fourneau 
 de reVerbere. J'adapte a la cornue un recipient que je lutte, je 
 la chauffe par degre, il en sort quelque temps apres une liqueur 
 un peu coloree, qui r6pand 1'odeur d'ail la plus penetrante, il passe 
 ensuite une liqueur d'un rouge brun, qui remplit le ballon d'un 
 nuage 6pais. 
 
 En continuant la distillation, il se sublime au col de la cornue 
 une poudre noire, qui paroit etre de la nature de celle que les 
 Allemands appellent Musken giffi [Miicken Gift] ; en fran9ois, poison 
 des mouches : on y trouve aussi du re"gule d'arsenic et une matiere 
 qui brule comme le soufre lorsqu'on la presente a la flamme d'une 
 bougie. Independamment de tous ces produits, on retire encore du 
 col de la cornue un peu d'arsenic en forme de petits crystaux, et 
 le r6sidu de la distillation est une matiere charbonneuse qui repand 
 une odeur d'ail sur les charbons ardens. 
 
 La premiere liqueur qui passe dans la distillation fait une vive 
 effervescence avec 1'alkali fixe ; elle repand en meme temps une si 
 forte odeur d'ail, qu'il est impossible de la supporter : le vinaigre, 
 les odeurs les plus fortes ne peuvent pas detruire celle qui reste aux 
 vaisseaux lorsqu'ils en ont ete impregnes, elle ne se dissipe qu'en 
 la laissant plusieurs mois a 1'air libre. 
 
 La derniere liqueur qui est d'un rouge brun, depose au bout 
 d'un certain temps une matiere d'un beau jaune, que je souponne 
 etre une substance metallique qu'elle entraine dans la distillation, 
 et qui par son propre poids, 1'oblige de se precipiter au fond de la 
 premiere liqueur. Ce qui m'autorise a le croire, c'est que quand 
 elle a depos6 cette matiere, que je nomme metallique, elle prend 
 une couleur limpide et devient d'une si grande tegerete", qu'elle 
 surnage la premiere liqueur comme feroit une huile essentielle sur 
 1'eau. 
 
 Ces deux liqueurs ont une petite couleur ambree et sont tres- 
 claires : agitees ensemble, elles forment comme une espece de 
 
 2 
 
CACODYL 
 
 nutritum ; mais si on les laisse reposer, elles reprennent leur premiere 
 Iimpidit6 : si on les expose au contact de 1'air, elles fument d'abord 
 comme le phosphore, en repandant une tres-forte odeur d'ail. Ces 
 vapeurs ne s'enflamment pas a 1'approche d'une bougie allumee ; 
 mais en versant les deux liqueurs du recipient, elles ont enflamme 
 avec une promptitude singuliere le lut gras de ce premier vaisseau, 
 ce qui me surprit beaucoup. II est vrai que ce lut s'etoit si fort 
 desseche par 1'action du feu, que I'huile etoit devenue dans un etat 
 de resine. Quelques gouttes de la liqueur surnageante, raises dans 
 un flacon rempli d'une once d'eau, ont paru s'y dissoudre en partie 
 et ont communique a 1'eau la qualite de fumer continuellement 
 lorqu'elle eprouve 1'action de 1'air." 
 
 After summarising the results of his experiments on " cobolt " 
 and sympathetic inks, Cadet reverts to his researches on the 
 arsenical liquid in the following words : 
 
 " Qu'enfin par I'intermede de la terre foliee du tartre, 1 on tire 
 de 1'arsenic une liqueur fumante tres singuliere qui prouve bien la 
 grande volatilite de cette substance minerale que nous fournit le 
 cobolt." 
 
 Cadet's account of his experiment is an accurate description 
 of the appearances observed during the distillation of equal parts 
 by weight of arsenious oxide and potassium acetate in a glass 
 retort luted to a receiver of the same material. The proportions 
 in which the reagents were employed were maintained by later 
 investigators. 
 
 Two liquids passed over of which the more volatile exhibited 
 acid properties, whereas the less volatile and reddish-brown liquid 
 was specifically heavier and filled the receiver with thick fumes. 
 
 1 The origin of the term " terre foliee de tartre bien prepare " and its 
 German equivalent " gute blattrige Weinsteinerde " for potassium acetate 
 (Crell's Ncuestes Chemisches Archiv., Erstes Band, Weimar, 1798, p. 212) 
 is as follows. 
 
 At the time Cadet's experiment was performed the most esteemed form 
 of vegetal alkali was potassium carbonate, or as it was then termed " sel 
 de tartre " or "sel alkali fixe de tartre," the product of the calcination of 
 cream of tartar (potassium hydrogen tartrate). A superior quality of 
 potassium acetate was prepared by adding distilled vinegar to pure white 
 " sel de tartre," the product which crystallised on concentrating the 
 solution being then called " terre foliee de tartre." These terms were in 
 common use by contemporaries of Cadet (v. " lemns de Chymie tMorique 
 et pratique," 1778, Vol. Ill, p. 39, by Guyton de Morveau, H. Maret, et 
 Jean Franois Durande), and a current determination of the solubilities 
 in water of " creme de tartre, sel de tartre," and " terre foliee de tartre " 
 leaves no doubt as to the identity of these salts (he. cit., Vol. I, p. 356). 
 
 3 B 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Both liquids had an intensely disagreeable and persistent odour 
 resembling that of garlic. The heavier oily liquid deposited a 
 yellow solid impurity and then assumed an amber colour ; it 
 was slightly soluble in water, to which it imparted the property 
 of fuming in the air. When poured from the receiver it took 
 fire spontaneously in air at the ordinary temperature. Cadet 
 identified metallic arsenic and arsenious oxide as sublimation 
 products and detected arsenic in the carbonaceous residue. 
 
 This experiment was repeated in Dijon by Guyton de Morveau, 
 Maret, and Durande, who separated the two liquids and showed 
 that the heavier oily one had the more intolerable stench 
 and the property of inflammation in the air at the ordinary 
 temperature. 
 
 "La liqueur rouge conserve meme apres le refroidissement la 
 propriete de fumer toutes les fois que Ton debouche le flacon qui 
 la contient et repand la meme odeur atroce que rien ne peut 
 detruire. . . . 
 
 Nous voulions examiner cette partie de la liqueur rouge qui se 
 rassemble au fond du flacon. . . . Pour cela nous avions commence 
 a decanter le plus exactement qu'il etoit possible la liqueur sur- 
 nageante ; nous versames le reste sur un nitre de papier, a peine 
 passa-t-il quelques gouttes, il s'eleva tout-a-coup une fumee infecte 
 tres epaisse qui formoit une colonne depuis le vase jusqu' au plafond, 
 la matiere fait vers les bords un petit mouvement d 'ebullition, il 
 en partit alors une belle flamme de couleur de rose, qui dura quelques 
 instans ; il n'y eut qu'un des cotes du papier du nitre de brule." 
 
 Following on this graphic account of the spontaneous inflamma- 
 tion of Cadet's fuming liquid, the authors conclude that this 
 inflammability cannot be attributed merely to the concentra- 
 tion of vinegar by white arsenic, but rather to the union of 
 these two substances to form a new compound. This supposition 
 is confirmed by the red colour of the flame, by the formation of 
 a sublimate on burning, and by the absence of any inflammable 
 product (methane) on decomposing the liquid with caustic alkali. 
 In view of the physiological activities of organic arsenicals, it 
 is of interest to note the statement of these workers that 
 although subjected for some time to the abominable and pene- 
 trating stench of this fuming liquid they experienced no personal 
 inconvenience beyond a very disagreeable irritation of the throat. 
 
 The next investigation of Cadet's fuming arsenical liquid was 
 undertaken by Louis Jacques Thenard, 1 who found that carbon 
 
 1 Annales de chimie, 30 Vendemiaire An XIII [1804], 52, 54. 
 
 4 
 
CACODYL 
 
 dioxide and hydrocarbons were evolved during the distillation ; 
 potassium carbonate remained in the retort and crystals of 
 arsenious oxide were obtained by sublimation. Of the two 
 liquids, the upper one was a solution of the lower in water and 
 acetic acid. The horribly fetid odour and spontaneous inflamma- 
 bility noticed by Cadet and by the chemists of Dijon were due 
 to the denser oily liquid. The spontaneous inflammation of 
 this substance in air was regarded as being due to oxidation 
 and hydration, the former reaction being the more important. 
 After oxidation with chlorine the oily liquid gave the reactions 
 of carbonic and acetic acids and inorganic arsenic. Thenard 
 concluded that the fuming liquid was a complex arsenical acetate 
 containing partially deoxidised arsenious oxide produced by the 
 combination in the receiver of arsenious oxide, acetic acid, and 
 an oily substance not further specified. 
 
 " Cette liqueur est un compose d'huile, d'acide aceteux et d'arsenic, 
 que celui-ci y est probablement voisin de 1'etat metallique, et qu'elle 
 doit etre regardee comme une espece de savon a base d'acide et 
 d'arsenic ou comme une sorte d'acetite oleo-arsenical." 
 
 Section II. Cacodyl and its Derivatives. 
 
 Although the qualitative results obtained by the early French 
 chemists showed that Cadet's liquid was a product of considerable 
 chemical interest, yet no further information regarding its consti- 
 tution was forthcoming until Robert Wilhelm Bunsen undertook 
 the dangerous and unpleasant task of making a quantitative 
 examination of this malodorous and nauseating material. These 
 investigations, carried out during a period of six years, 1837-43, 
 are regarded as a classical model of organic research both on 
 account of the very great experimental difficulties which were 
 successfully overcome and because of the theoretical importance 
 of the results. 
 
 Bunsen published his researches in two treatises. The first 
 of these was a preliminary communication divided into two 
 parts on " A series of Organic Compounds containing Arsenic as 
 a Constituent/' 1 in which he described Cadet's fuming liquid 
 as " Alkarsin," ascribing to it the composition As(CH 3 ) 2 . This 
 name was chosen from the circumstance that the compound was 
 regarded as containing the elements of alcohol with the oxygen 
 
 1 Pogg. Ann., 1837, 40, 219, 42, 145 ; v. Annalen, 1837, 24, 271 ; 1839, 
 31, 175. 
 
 5 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 present in this substance replaced by arsenic. The initial letters 
 of the words " alkohol " and arsenic were taken to form the name 
 " alk-arsin " for the supposed arsenical analogue of alcohol. 
 
 Cadet's preparation was repeated on a considerable scale, a 
 kilogram of the mixture containing equal parts by weight of 
 arsenious oxide and potassium acetate being distilled from a 
 glass retort in one operation. The temperature of the retort was 
 gradually raised to redness; the two liquids distilled over 
 accompanied by an appreciable amount of reduced arsenic. 
 The gases evolved consisted principally of carbon dioxide, 
 methane, and olefiant gas. Contrary to Thenard's statement, 
 Bunsen could not detect hydrogen arsenide. The upper 
 liquid was a solution of alkarsin and arsenious acid in acetone, 
 acetic acid and water ; the lower brown oily layer was crude 
 alkarsin, of which more than 150 grams were obtained from a 
 kilogram of the heated mixture. 
 
 Berzelius, who had followed the course of these difficult 
 researches with the liveliest interest, suggested that alkarsin 
 contained oxygen. This anticipation was confirmed by Bunsen, 1 
 who subsequently estimated the arsenic as well as the carbon 
 and hydrogen in carefully purified samples of the fuming liquid, 
 and arrived at the molecular formula C 4 H ia As 2 O for the 
 substance. Berzelius, from the viewpoint of the theory of 
 radicals, regarded this compound as the oxide of a compound 
 radical, C 4 H 12 As 2 , for which he suggested the name " kakodyl " 
 in reference to the disagreeable odour of its derivatives. 2 
 
 Shortly after the publication of Bunsen's first treatise on 
 alkarsin, J. B. Dumas intervened with an analysis of this material 
 which appeared to confirm Bunsen's original view of the composi- 
 tion of the substance. The French chemist obtained the following 
 percentages : C = 23-60, H = 5-66, As = 69-0 ; total, 98'26. 3 
 In his Traitede Chimie, 1844, 5, 182, Dumas gives similar numbers, 
 but states that he does not regard these analytical data as 
 decisive owing to the experimental difficulties attending the 
 purification and analysis of the arsenical constituent of Cadet's 
 
 1 Bunsen, Annalen, 1839, 31, 175. 
 
 8 Kakodyl or cacodyl from /co/cis and &y. 
 
 Following the modern usage it is preferable to consider C 2 H 6 As as 
 the radical, cacodyl (symbol Kd), and C 4 H 12 As 2 as free cacodyl (Kd 2 ). 
 A similar notation is employed for the cyanogen radical (CN = or Cy), 
 whereas free cyanogen is C 2 N 2 or Cy 2 . 
 
 3 Annalen, 1838, 27, 148. 
 
 6 
 
CACODYL 
 
 liquid. Dumas also states (Traite de Chimie, 7, 273) that this 
 liquid contains cacodyl mixed with cacodyl oxide and may some- 
 times consist of almost pure cacodyl. Although this view is 
 scarcely confirmed by other workers, yet it is certain that the 
 relative proportions of the two constituents would be modified 
 by distillation. Fractionation would lead to separation of 
 cacodyl oxide (b.p. 120) from cacodyl (b.p. 170). Possibly 
 Bunsen's earlier analyses and Dumas's determinations were made 
 on the less volatile fractions. 
 
 Bunsen's second treatise on the arsenical liquid, which is 
 entitled " Researches in the Cacodyl Series," is divided into three 
 sections. 1 In the first he deals with cacodyl oxide and its deriv- 
 atives, in the second with free cacodyl, and in the third with 
 cacodylic acid, the oxidation product of cacodyl oxide. These 
 investigations, which were long afterwards extended by Baeyer, 
 have completely elucidated the nature of Cadet's liquid. 
 
 A systematic examination of this material showed that its 
 pungent constituents were two substances containing arsenic. 
 The main constituent was cacodyl oxide containing the metalloid 
 associated with carbon, hydrogen, and oxygen ; it has the com- 
 position and vapour density indicated by the formula As 2 C 4 H 12 O. 
 The second compound, which was present only in small amount, 
 is free cacodyl consisting of the three elements arsenic, carbon, 
 and hydrogen ; its empirical formula is AsC 2 H 6 , but the vapour 
 density corresponds with the molecular formula As 2 C 4 H 12 . 
 
 It is obvious from the observations of all the experimentalists 
 from Cadet downwards that the following equation does not 
 represent quantitatively the course of the distillation : 
 
 As 2 O 3 + 4CH 3 -CO 2 K = [As(CH 3 ) 2 ] 2 + 2K 2 CO 3 +2CO 2 
 Cacodyl oxide. 
 
 Reduction of arsenious oxide to metallic arsenic invariably 
 occurs, and the charring of the acetate is accompanied by an 
 evolution of methane and unsaturated hydrocarbons. A portion 
 of the cacodyl oxide also undergoes reduction with the formation 
 of a certain amount of free cacodyl, [As(CH 3 ) 2 ] 2 . It is to the 
 presence of this constituent that the fuming and inflammability 
 of Cadet's liquid are due. Pure cacodyl oxide (Bunsen's " para- 
 cacodyl oxide ") obtained by hydrolysing cacodyl chloride with 
 potassium hydroxide neither fumes nor takes fire in air. 2 
 
 1 Annalen, 1841, 37, 1-57 ; 1842, 42, 14-46; 1843, 46, 1-48. 
 
 2 Baeyer, ibid, 1858, 107, 282. 
 
 7 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Free cacodyl was most conveniently obtained by the following 
 series of reactions. Mercuric chloride added to crude cacodyl 
 oxide (Cadet's liquid) yielded the sparingly soluble mercuri- 
 chloride, [As(CH 3 ) 2 ] 2 O,2HgCl 2 . 
 
 This product, when distilled with fuming hydrochloric acid, 
 yielded a volatile oil having the molecular formula AsC 2 H 6 Cl, 
 and this chloride when heated with zinc in an inert atmosphere 
 lost its chlorine and became converted into free cacodyl, As 2 C 4 H 12 . 
 
 The following diagram illustrates the relationship between 
 the three arsenical substances : 
 
 AsCoH 6 Cl 
 
 \ 
 
 X 12^ "* n.t> 2 v, 4 .L.i. 12 
 
 (0 2 ) 
 
 These compounds contain the cacodyl group [AsC 2 HJ in 
 common, and groups such as this arsenical complex, which pass 
 without change in composition from one compound to another in 
 the course of chemical change, are called compound radicals. 
 This particular group is of special interest as being one of the 
 first compound radicals to be definitely recognised. 
 
 The recognition by Bunsen of the cacodyl complex, possessing 
 many properties comparable with those of the elementary radicals, 
 afforded striking experimental confirmation of the theory of 
 compound radicals which had then been recently advocated 
 by Berzelius. 1 The close analogy subsisting between the cacodyl 
 radical and the metallic elements potassium and thallium is 
 illustrated in the following series : 
 
 CACODYL. CACODYL OXIDE. 
 
 As 2 C 4 H 12 = [AsC 2 H 6 ] 2 [AsC 2 H 6 ] 2 
 
 Kd 2 Kd 2 
 
 1 Berzelius's estimate of the cacodyl research was expressed in the 
 following words : 
 
 " Bunsen hat durch diese Untersuchung seinen Namen in der Wissen- 
 schaft unvergesslich gemacht. Die Mitwelt ist es schuldig, ihm ihre 
 Erkenntlichkeit fur die Ausmittelung eines so wichtigen und so gefahrlich 
 zu bearbeitenden Gegenstandes auszudriicken, eine Forschung, von der 
 wchl mit Recht gesagt werden kann, dass sie wenig zu wiinschen iibrig 
 lasst."' (Berzelius? Jahresber., 1842, 21, 503.) 
 
 8 
 
CACODYL 
 
 METAL. METALLIC OXIDE. 
 
 2K K 2 
 
 T1 2 T1 2 
 
 CACODYL CHLORIDE. CACODYL TRICHLORIDE. 
 
 [AsC 2 H 6 ]Cl [AsC 2 H 6 ]Cl 3 
 
 KdCl KdCl 3 
 
 METALLIC CHLORIDE. METALLIC TRICHLORIDE. 
 
 KC1 T1C1, 
 
 T1C1 
 
 In an examination of Cadet's reaction, Dehn l distilled 
 250 grams of arsenious oxide and 250 grams of anhydrous 
 potassium acetate in a short-necked hard glass half-litre flask 
 placed in a hemispherical iron sand-bath, which was gradually 
 heated to redness over a period of 8-10 hours. The flask was 
 connected in series with a Liebig condenser, a filter flask receiver, 
 and several wash-bottles containing mercuric oxide. By the most 
 careful and long-continued heating the largest yield of cacodyl 
 oxide was 25 per cent., increased by the amount of cacodylic 
 acid present in the solutions to more than 30 per cent, of crude 
 cacodyl oxide, cacodyl, and cacodylic acid. This mixture was 
 utilised in the production of dimethylarsine (p. 37). 
 
 The distillate in the receiver separated as usual into three 
 layers, the two liquid layers and the lowest solid layer com- 
 posed of arsenic and polymerised products of arsenomethane 
 (p. 40). 
 
 Although spontaneously inflammable in air, cacodyl can be 
 oxidised without decomposition by the addition of a moderate 
 amount of oxygen, or preferably by the action of moist mercuric 
 oxide. Under these conditions it changes first to cacodyl oxide, 
 and then to an extremely soluble substance, which, having acidic 
 properties, is appropriately termed cacodylic acid. In his 
 preliminary treatise, Bunsen gave to this acid the name 
 " Alkargen," as being produced by addition of oxygen to 
 alkarsin. 
 
 Kd 2 + O = Kd 2 0. Kd 2 + O 2 + H 2 O = 2KdOOH. 
 
 Bunsen examined the physiological action of cacodyl and its 
 derivatives, and made the remarkable discovery that although 
 cacodyl and its oxide are both extremely poisonous, yet cacodylic 
 
 1 Amer. Chem. ]., 1906, 35, 2. 
 9 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 acid, containing 54 per cent, of soluble arsenic, is nevertheless 
 practically non-poisonous. In the form of its sodium salt, 
 cacodylic acid has been employed medicinally, although at present 
 it is largely superseded by arsenical preparations containing 
 aromatic groups. 
 
 Bunsen did not investigate further the constitution of the 
 cacodyl radical, and it should be remembered that at the time 
 his researches were carried out the hydrocarbon radicals had 
 not been recognised. Subsequent investigations by Frankland, 
 Kolbe, Cahours, Landolt, von Baeyer, and others elucidated the 
 inner constitution of cacodyl, so that it is now known to consist 
 of tervalent arsenic associated with two methyl radicals : 
 
 CH 3 CH 3 CH 3 
 
 \\s-As/ ^>As-Cl 
 
 CJH.3 ^HS Cxi 3 
 
 CACODYL, b.p. 170. CACODYL CHLORIDE, b.p. IOQ . 
 
 CH 3 CH 3 CH 3 O 
 
 \As-O-As/ / As \ 
 
 CH 3 CH 3 CH 3 OH 
 
 CACODYL OXIDE, b.p. I2O. CACODYLIC ACID. 
 
 In all these compounds but the last arsenic is tervalent ; in 
 cacodylic acid it is quinquevalent. 
 
 In addition to the foregoing cacodyl oxide and chloride Bunsen 
 described the bromide, iodide, cyanide, and mono- and di- 
 sulphides of cacodyl. The existence of these compounds empha- 
 sises still further the metallic character of the cacodyl radical. 
 
 Cacodyl^ [As(CH 3 ) 2 ] 2 , heavy oil with repulsive odour, sparingly 
 soluble in water ; b.p. 170 ; solidifying at 6 to square 
 plates ; vapour density 7-1 corresponding with double formula. 
 Obtained as a by-product in Cadet's reaction. Prepared by 
 heating cacodyl chloride with zinc in carbon dioxide at 100. 
 It is immediately inflammable in air or chlorine. By regulated 
 oxidation with moist air or preferably mercuric oxide it yields 
 successively cacodyl oxide and cacodylic acid. It behaves as 
 a univalent or tervalent radical combining with sulphur and 
 
 1 Bunsen, Annalen, 1842, 42, 14. 
 IO 
 
CACODYL 
 
 the halogens. Methyl iodide 1 interacts with cacodyl to yield 
 tetramethylarsonium iodide and cacodyl iodide, [As(CH 3 ) a ] 2 + 
 2CH 3 I = As(CH 3 )J + As(CH 3 ) 2 I. Methyl bromide reacts 
 similarly with cacodyl. At 400-500 cacodyl decomposes, 
 yielding arsenic and hydrocarbons but no free carbon. 
 
 Owing to the very inflammable nature of cacodyl, its isolation 
 from cacodyl chloride by the action of metals (zinc, iron, and tin) 
 and other reducing agents presents considerable experimental 
 difficulties. 
 
 The chloride, which must be perfectly dry and free from 
 cacodyl oxide, was first digested with fuming hydrochloric acid 
 
 FIG. i. 
 
 FIG. 2. 
 
 and dried over calcium chloride and quicklime in the bulb c of 
 the drying tube (Fig. i). This- tube was filled with dry carbon 
 dioxide and sealed up until required, when the upper end a was 
 opened and connected with an air pump ; the lower end b was 
 opened under the hydrochloric acid covering the cacodyl chloride 
 so that this liquid was drawn into the drying bulb, the ends of 
 which were again sealed. 
 
 The upper bulb a of the reduction apparatus Fig. 2 was 
 charged with carefully-cleaned zinc foil cut into small shavings 
 (this being the best reducing agent). The tube was filled with 
 carbon dioxide, dried cacodyl chloride drawn into bulb a, the 
 ends sealed off and the apparatus heated to 100 until the 
 bulb a on cooling showed a solid mass of zinc chloride. The 
 
 1 Cahours, Annalen, 1862, 122, 209. 
 II 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 heated tube was opened under cold boiled out water, the upper 
 bulb heated to drive out carbon dioxide and cooled to suck in 
 water which was tilted into the reduction bulb. Zinc chloride 
 dissolved and cacodyl formed a heavy layer which was drawn 
 off into drying bulb (Fig. i). The reduction was repeated with 
 fresh zinc in bulb a until no more action was observed, then the 
 cacodyl was distilled in carbon dioxide from the upper bulb a 
 to the lower. When pure it was a colourless oil crystallising at 
 -6V 
 
 The constitution of cacodyl was first determined by Cahours and 
 Riche, 2 who obtained this compound together with trimethyl- 
 arsine and tetramethylarsonium iodide by the action of methyl 
 iodide on the alloy of arsenic and sodium. 3 Frankland had 
 already suggested this structure for cacodyl based on the analogies 
 subsisting between the substance and the organo-metallic 
 compounds. 
 
 Cacodyl oxide, [As(CH 3 ) 2 ] 2 0, heavy oil, sp. gr. 1-462/15, not 
 fuming in air and non-inflammable when free from cacodyl ; 
 b.p. 120, crystallising at 25. Sparingly soluble in water, 
 intolerable tear-exciting odour. Vapour density = 7-55, 
 corresponding with the foregoing formula. Obtained as the 
 main constituent of Cadet's liquid ; prepared by distilling cacodyl 
 chloride with aqueous potassium hydroxide and subsequently 
 rectifying the dried oil in an atmosphere of carbon dioxide. 4 
 
 Cacodyl oxide mer curl-chloride , [As(CH 3 )a] 2 0,2HgCl2, rhombic 
 
 1 Bunsen, Annalen, 1842, 42, 28-30. 
 
 2 Compt. rend., 1854, 39, 541. 
 
 3 The simultaneous formation of cacodyl (tetramethyldiarsine) and tri- 
 methylarsine from sodium-arsenic alloy suggests the presence in this 
 material of two compounds, As-Na 2 and As-Na 3 . The latter has been 
 obtained in a crystalline condition by heating arsenic with excess of 
 sodium and removing the unchanged alkali metal with liquid ammonia. 
 An alloy approximating to this composition was utilised by Landolt in 
 the synthesis of ethylcacodyl and triethylarsine. An alloy with excess 
 of arsenic (3 parts As, i part Na) has been prepared, so that it is probably 
 from some compound of this type that cacodyl derivatives are formed by 
 the action of alkyl iodides. 
 
 Arsenical alloys of sodium and potassium, v. Gmelin-Kraut, Handbuch 
 der Anorganischen Chemie, 1908, III, 2pp., 514, 531. 
 
 Saunders, Chem. News, 1899, 79, 66; Soubeiran, /. Pharm., 1830, 16, 
 
 353- 
 
 Roscoe and Schorlemmer, Treatise on Chemistry, 1913, 2, pp. 219, 
 353; Meyer, Zeitsch. anorg. Chem., 1905, 18, 1382 
 4 Baeyer, Annalen, 1858, 107, 282. 
 
 12 
 
CACODYL 
 
 plates, by the direct combination of its generators in alcoholic 
 solution. Soluble in 28-8 parts of boiling water. Yields cacodyl 
 chloride on distillation with fuming hydrochloric acid. 
 
 The production of this mercurichloride l occurs quantitatively 
 in the presence of concentrated hydrochloric acid, and affords the 
 most practicable method of obtaining successively pure cacodyl 
 chloride and cacodyl oxide. 
 
 The crude Cadet's arsenical liquid is mixed with excess of 
 concentrated hydrochloric acid and treated with excess of 
 powdered mercuric chloride. The mixture sets to a thick, 
 crystalline magma which when rendered liquid by addition of 
 more hydrochloric acid is distilled. Cacodyl chloride passes 
 over and is dried with calcium chloride, and freed from excess 
 of hydrochloric acid with powdered calcium carbonate and 
 rectified. This purified cacodyl chloride when distilled with 
 aqueous potassium or sodium hydroxide yields cacodyl oxide, 
 which passes over in steam. The oily distillate, when dried 
 and rectified, consists of pure cacodyl oxide. 
 
 It is noteworthy that cacodyl chloride on treatment with 
 alkalis yields the oxide and not the hydroxide, As(CH3) 2 'OH ; 
 the latter product has not hitherto been isolated. 
 
 Cacodyl chloride, As(CH 3 ) 2 Cl, colourless ethereal non-fuming 
 liquid heavier than water and insoluble therein ; b.p. slightly 
 above 100 ; very penetrating and stupefying odour, and an 
 intensely irritating action on the eyes and nose ; vapour density 
 4-56, corresponding with empirical formula. Cacodyl bromide 
 and iodide yellow oils, the latter boils at i6o. 2 These cacodyl 
 halides show a great tendency to form compounds with cacodyl 
 oxide. The three compounds, corresponding with the general 
 formula 6As(CH 3 ) 2 Hal,As2(CH 3 ) 4 -O were described by Bunsen, 
 but their existence is questioned by Baeyer. 3 
 
 Co-ordinated Compounds with Metallic Salts. 
 
 With platinic chloride, cacodyl chloride yields a noteworthy 
 series of co-ordinated compounds, compared by Bunsen with 
 Reiset's platinammines. 4 
 
 1 Amer. Chem. J., 1908, 40, 127. Dehn suggests that this mercuri- 
 chloride is in reality a double compound of cacodyl chloride and mercuric 
 chloride. 
 
 2 Cahours and Riche, Compt. rend., 1854, 39, 541. 
 
 3 Ostwald's Klassiker der exakten Wissenschaften, 1891, 27, 145. 
 
 4 Berz. Jahresber., 1842, 21, 500. 
 
 13 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Cacodyl platinichloride, 2As(CH 3 ) 2 Cl,PtC] 4 , brick-red pre- 
 cipitate soluble in hot water to a colourless solution from which 
 the co-ordinated compound, As 2 (CH 3 )4O,PtCl2,H 2 O separates in 
 colourless needles, becoming dehydrated and yellow at 160. 
 Double decomposition with KBr, KI, and silver oxy-salts yields 
 respectively As 2 (CH 3 ) 4 O,PtBr2,H 2 O (colourless) ; 
 As 2 (CH 3 ) 4 0,PtI 2 ,H 2 O (yellow) ; 
 
 Kd 2 O,Pt(NO 3 ) 2 ,H 2 O and Kd 2 O,PtSO 4 ,H 2 O. 2KdCl,Cu 2 Cl 2> 
 white ppt. 
 
 Cacodyl cyanide, As(CH 3 ) 2 -CN. 1 
 
 Lustrous colourless prisms ; m.p. 33 ; b.p. 140. This 
 remarkable substance, the most poisonous of the cacodyl series, 
 is of theoretical interest as being composed of the first two 
 organic radicals to be recognised and isolated. It is produced 
 by double decomposition from cacodyl oxide and hydrocyanic 
 acid, but prepared more conveniently by the interaction of 
 cacodyl and mercuric cyanide. 
 
 [As(CH 3 ) 2 ] 2 O + 2HCN = H 2 O + 2As(CH 3 ) 2 -CN. 
 [As(CH 3 ) 2 ] 2 + Hg(CN) 2 = Hg + 2As(CH 3 ) 2 -CN. 
 
 The cyanide has a remarkable capacity for crystallising and 
 it sublimes readily at the ordinary temperature. Sparingly 
 soluble in water, it dissolves readily in alcohol or ether. A few 
 grains subliming into the atmosphere of a room produce rapidly 
 numbness of hands and feet, giddiness and stupor leading to 
 complete unconsciousness. These symptoms are nevertheless 
 only of short duration and without after effect providing that 
 exposure to this poisonous substance is not unduly prolonged. 
 
 Cacodyl sulphide, [As(CH 3 ) 2 ] 2 S, colourless oil with repulsive 
 odour of mercaptan and cacodyl oxide, b.p. well above 100, 
 distillable in steam, insoluble in water, miscible with ether or 
 alcohol : vapour density at 215 corresponding with foregoing 
 formula. Prepared by distilling barium hydrosulphide with 
 cacodyl chloride, or with the acid aqueous upper layer obtained 
 in Cadet's distillation. 2 
 
 2KdCl+Ba(SH) 2 =Kd 2 S+H 2 S+BaCl 2 . 
 Kd 2 0+2CH 3 C0 2 H+Ba(SH) 2 = 
 
 Kd 2 S+H 2 S+H 2 O+(CH 3 CO 2 ) 2 Ba. 
 
 1 Bunsen, Annalen, 1841, 37, 23. 
 
 2 Dumas, TraiU de Chimie, 1844, 7, 273. 
 
 14 
 
CACODYL 
 
 Cacodyl disulphide, 1 [As(CH 3 )2] 2 S2, white, rhombic plates; m.p. 
 50 ; odour of asafoetida produced by the direct combination of 
 the foregoing sulphide with sulphur and crystallised from dilute 
 alcohol below 40. Sulphuretted hydrogen passed through 
 aqueous and alcoholic solutions of cacodylic acid yields respec- 
 tively cacodyl sulphide and disulphide. 
 
 Cacodyl cupri-sulphide, 2 Kd 2 S,3CuS, crystallises from alcoholic 
 solutions of cacodyl sulphide and copper nitrate in well-defined, 
 lustrous octahedra. 
 
 Cacodylic acid,? Dimethylarsinic acid, As(CH 3 ) 2 OOH ; 
 inodorous, colourless, obliquely truncated prisms ; m.p. 200. 
 Solubility : i in o-5H 2 O, i in 4 alcohol 90 %. Obtained in almost 
 quantitative yield (95 %) by the oxidation of cacodyl oxide 
 (76 grams) with mercuric oxide (218 grams) under water. 
 Remarkably stable ; not decomposed by the most powerful 
 oxidising agents (HNO 3 , Cr0 3 , KMn0 4 , or aqua regia). Reduced 
 by phosphorous acid to cacodyl oxide ; this reducing agent acts 
 specifically on analogues of arsenic acid. Cacodylic acid is also 
 reduced by stannous chloride. 
 
 Experiments by Bunsen 4 on frogs and by Kurschner on rabbits 
 showed that cacodylic acid is not acutely poisonous even in large 
 doses. Six grains introduced into the stomach of a rabbit had no 
 ill effect ; 7 grains injected into the jugular vein of this animal 
 and 4 grains introduced into the lungs were similarly innocuous. 5 
 The acid and its salts pass through the system principally without 
 change, being excreted in the urine, but a portion undergoes 
 reduction to cacodyl oxide which is exhaled. 
 
 Cacodylic acid is monobasic ; its salts are soluble in water and 
 generally non-crystalline : it has a slightly acid taste and 
 reaction, being neutral to methyl orange and acid to 
 phenolphthalein, and it exhibits amphoteric properties yielding 
 the following unstable compounds with hydrogen halides : 
 As(CH 3 ).AH,HCl(HBr) ; the composition of the hydro fluoride 
 is doubtful. Prolonged treatment with hydrogen chloride 
 converts dry cacodylic acid into methylarsenious chloride, 
 As(CH 3 ) 2 O 2 H + 3HC1 = As(CH 3 )Cl 2 + CH 3 C1 + 2H 2 O. 
 
 1 Dumas, loc. cit., 282. 
 
 2 Bunsen, Annalen, 1841, 37, 18 ; 1843, 46, 18. 
 
 3 Bunsen, ibid., 1843, 46, 2. 
 
 4 Bunsen, ibid., 1843, 46, n. 
 
 5 Cf. Marshall and Green, Amer. Chem. /., 1886, 8, 128; Zeit. physiol. 
 Chem., 1905, 49, 410. 
 
 15 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The silver salts are crystallisable, As(CH 3 ) 2 OOAg, needles ; 
 As(CH 3 ) 2 O-OAg,2As(CH 3 ) 2 O 2 H, needles ; As(CH 3 ) 2 OOAg,AgNO 3 , 
 scales. Cacodylates of the rare earths, 1 [AsfCH^OJgR^HgO. 
 
 The following cacodylates 2 have been used in medicine : 
 
 Sodium Cacodylate (Ph. Helv.), As(CH3) 2 O 2 Na,3H 2 O. Arsenic 
 and water contents 35 and 18-25% respectively. Solubility, 
 i in o-5H 2 O. 
 
 Magnesium Cacodylate, [As(CH 3 )20 2 ] 2 Mg,?H 2 O. Solubility, 
 i in 3H 2 O. 
 
 Ferric Cacodylate, [As(CH 3 ) 2 O 2 ] 3 Fe, yellowish powder. Solu- 
 bility, i in I5H 2 O. 
 
 Strychnine Cacodylate, C 21 H 22 O 2 N 2 ,As(CH 3 ) 2 O 2 H. White, crys- 
 talline powder. 
 
 Guaiacol Cacodylate, As(CH 3 ) 2 O 2 H,HO-C 6 H 4 -OCH 3 . 
 
 3 Antipyrine Cacodylate, As(CH 3 ) 2 O 2 H,C n H 12 ON 2 , crystallising 
 from alcoholic solution of its generators. Soluble in water or 
 alcohol ; m.p. below 100. 
 
 In the presence of one molecular proportion of caustic soda, 
 cacodylic acid behaves as a monobasic acid, but with excess of 
 this alkali it functions in the tribasic form, (CH 3 ) 2 As(OH) 3 , but 
 only in strongly alkaline solutions. 4 
 
 Although free cacodylic acid is converted into cacodyl sulphides 
 by sulphuretted hydrogen in aqueous or alcoholic solution 
 (v. supra), its salts on similar treatment are transformed into 
 thiocacodylates which can also be prepared from cacodyl di- 
 sulphide and metallic salts. The thiocacodylates of the heavy 
 metals are remarkably crystalline and insoluble , the lead salt, 
 (KdS 2 ) 2 Pb, is colourless ; the cuprous, (KdS 2 ) 2 Cu 2 , bismuth, 
 (KdS 2 ) 3 Bi, antimony (KdS 2 ) 3 Sb, zndaurous, (KdS 2 )Au, are yellow. 
 
 The properties of these thiocacodylates suggest the presence 
 of a co-ordination complex, 
 
 (CH s ) 2 As/ \M 
 
 Cacodyl trichloride, (CH 3 ) 2 AsCl s , prisms or leaflets from ether; 
 fumes in air, hydrolysed by water and decomposed even at 
 40-50 into methylarsenious chloride, AsMeCl 2 , and methyl 
 chloride. Obtained either by passing chlorine into cacodyl 
 chloride in carbon bisulphide solution or by adding powdered 
 
 1 Whittemore and James, /. Amer. Chem. Soc., 1913, 35, 127 
 
 2 Martindale, Congress of Applied Chemistry, 1909. 
 
 3 Barthe, Pharm. J ., 1915, 94, 99. 
 
 4 Hantzsch, Ber , 1904, 37, 1076. 
 
 16 
 
CACODYL 
 
 cacodylic acid slowly to phosphorus pentachloride covered with 
 a layer of dry ether. 1 
 
 Bunsen described a complex product of the action of hydro- 
 chloric acid on cacodylic acid as " basic cacodyl superchloride." 
 It is probably the additive compound As(CH 3 ) 2 O 2 H,HCl (v. supra) 
 which on distillation yields a mixture of methylarsenious chloride 
 and cacodyl oxide . This mixture when redistilled with phosphoric 
 anhydride furnishes pure methylarsenious chloride. 2 
 
 Section III. Homologues of Cacodyl. 
 
 An important step in advance was made in 1853 when Landolt 
 showed that a homologue of cacodyl could be synthesised by 
 treating the alloy of arsenic and sodium with ethyl iodide. 3 This 
 process was afterwards applied by Cahours and Riche to the 
 synthesis of cacodyl itself and by other workers to cacodyl 
 homologues containing propyl, butyl, and amyl groups. 
 
 Ethylcacodyl. Tetraethyldiarsine, [As(C 2 H 6 ) 2 ] 2 . 
 
 Metallic arsenic in powder was heated in a furnace till it began 
 to fume ; small pieces of sodium were added slowly till the mixture 
 assumed a liquid consistence which occurred when the weight of 
 metal added was equal to that of the metalloid (As Na 8 = 
 75 : 69). The product on cooling was a silver- white alloy with 
 crystalline fracture. Being very oxidisable, the alloy was kept 
 in closely-stoppered bottles rilled with quartz sand ; it was 
 decomposed by water with evolution of arsine. 
 
 This sodium arsenide, powdered up with 4 to 5 times its weight 
 of quartz sand, was introduced into short-necked flasks, ethyl 
 iodide was added, and the flasks were filled with carbon dioxide 
 and fitted to a reflux apparatus. The reaction was so vigorous 
 that ethyl iodide distilled away and was replaced so long as 
 reaction ensued. About 2 oz. of mixed volatile ethyl arsenides 
 were obtained from a pound of ethyl iodide. This volatile product 
 on fractional distillation in an atmosphere of carbon dioxide 
 yielded ethylcacodyl boiling at 185-190 and triethylarsine 
 boiling at 1407736 mm. The former is also obtained by extract- 
 ing with ether the product of the reaction between excess of ethyl 
 iodide and sodium arsenide. The ethereal extract is mixed with 
 
 1 Baeyer, Annalen, 1858, 107, 263. 
 
 2 Baeyer, loc. cit., p. 273. 
 
 3 Hans Landolt, Inaug. Diss., Breslau, 1853; Annalen, 1854, 89, 316 ; 
 1854, 92, 365- 
 
 I 7 C 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 absolute alcohol, ether removed and the alcoholic residue diluted 
 with water, when ethylcacodyl is precipitated, whilst tetraethyl- 
 arsonium iodide (formed by the action of ethyl iodide on triethyl- 
 arsine) remains dissolved. 
 
 Ethylcacodyl is a pale yellow very refractive oil, heavier than 
 water, with disagreeable alliaceous odour. It rapidly absorbs 
 oxygen from the air, bursting into a dull flame which gives off 
 arsenious oxide. By concentrated nitric acid it is oxidised 
 completely with generation of light and heat. Dilute nitric acid 
 gives rise to a light red powder slowly turning brown, which on 
 exposure to the atmosphere finally becomes white. This product 
 is apparently analogous to Bunsen's " erytarsin," C^jjAseOg, 1 
 a red amorphous substance arising as a by-product in the prepara- 
 tion of cacodyl chloride or as a phase in the partial oxidation 
 of cacodyl or its oxide. 
 
 Unlike triethylarsine, ethylcacodyl has a powerful reducing 
 action on salts of silver, mercury, and the noble metals. It 
 combines directly with oxygen, sulphur, and the halogens. The 
 additive compounds [As(C 2 H 5 ) 2 ] 2 0, [As(C 2 H 5 ) 2 ] 2 S, and As(C 2 H 5 ) 2 Cl 
 are oily liquids with repulsive and tear-exciting odours. The 
 iodide, As(C 2 H 5 ) 2 I, an oil insoluble in water and boiling at 228-232, 
 regenerates ethylcacodyl with zinc amalgam. 
 
 Diethylarsinic acid, Ethylcacodylic acid? As(C 2 H 5 ) 2 0-OH, 
 lustrous leaflets ; m.p. 190 ; very soluble in water, and resembling 
 cacodylic acid in chemical properties. Acid barium salt, 
 [As(C 2 H 5 ) 2 O] 2 Ba,As(C 2 H 5 ) 2 O 2 H,2H 2 O, crystalline, very soluble 
 in water, less so in alcohol. This acid is prepared either by the 
 regulated oxidation of ethylcacodyl in alcoholic solution by 
 atmospheric oxygen, or according to Bunsen's process by shaking 
 ethylcacodyl under water with finely-divided mercuric oxide. 
 The solution of mercuric diethylarsinate treated with excess 
 of baryta water precipitates mercuric oxide ; the filtrate is 
 treated with carbon dioxide to precipitate excess of barium 
 hydroxide, and the solution of barium diethylarsinate carefully 
 acidified with sulphuric acid. On concentrating the filtrate from 
 barium sulphate, pure diethylarsinic acid separates. 
 
 Higher Aliphatic Homologues of Cacodyl. 
 
 The far-reaching results of Cadet's experiment as systemati- 
 cally investigated by Bunsen led naturally to other researches 
 
 1 Bunsen, Annalen, 1842, 42, 42 ; cf. page 41. 
 - Landolt, /. pr. Chem., 1854, 63, 283 ; Annalen, 1854, 92, 365. 
 
 18 
 
CACODYL 
 
 in which potassium acetate was replaced in this condensation by 
 the corresponding salts of homologous acids of the acetic series. 
 There is, however, very little definite evidence derivable from 
 the published results of these inquiries. 
 
 Wohler, 1 on distilling a mixture of equal parts by weight of 
 potassium butyrate and arsenious oxide, obtained, as in Cadet's 
 distillation, a mixture of two liquids together with a considerable 
 proportion of reduced arsenic and some malodorous gas. The 
 heavier oily liquid, although not spontaneously inflammable, 
 burnt with a white, smoky flame giving off an arsenical odour ; 
 it yielded a crystalline, white precipitate with mercuric chloride, 
 recalling the double compound of cacodyl and the mercury salt. 
 This inodorous product when boiled with hydrochloric acid and 
 zinc shavings evolved an odour resembling that of free cacodyl. 
 When boiled with concentrated hydrochloric acid the oily 
 distillate gave off a pungent odour affecting the mucous mem- 
 branes of the nose and eyes. These reactions are all highly 
 suggestive of cacodyl derivatives, but whether they are to be 
 attributed to cacodyl oxide itself, either alone or mixed with 
 free cacodyl, or whether they are due to homologues of these 
 compounds, has not been determined. 
 
 Similar inconclusive results were obtained by Gibbs 2 on dis- 
 tilling equal parts by weight of white arsenic and potassium 
 valerate. An oily, malodorous liquid was obtained yielding a 
 copious white precipitate with mercuric chloride, but no definite 
 chemical substances were isolated. 
 
 In the absence of further evidence on the formation of homo- 
 logous compounds, the production of cacodyl oxide and cacodyl 
 from potassium acetate and arsenious oxide is still to be regarded 
 as a unique reaction. 
 
 Mixed Cacodyl Derivatives. The discovery of secondary 
 aliphatic arsines has now furnished a synthetic method for pro- 
 ducing simple and mixed cacodyls. For instance, dimethyl- 
 arsine and dwsoamylarsenious chloride give rise to dimethyldiiso- 
 amylcdcodyl? 
 
 = (CH,),-As-As(C 5 H 11 ) t +HCl. 
 
 1 Annalen, 1848, 68, 127. 
 
 2 Sillimann's Amer. J., [ii], 15, 118 ; Annalen, 1853, 86, 222. 
 
 3 Dehn, Amer. Chem. J., 1908, 40, 123. 
 
 19 C 2 
 
CHAPTER II 
 
 ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 Syntheses of Alkyl Organo-metalloidal Compounds containing 
 Arsenic and Antimony 
 
 AFTER Bunsen's illuminating researches, the next advance 
 in the study of organic derivatives of arsenic and antimony 
 was made on -the theoretical side by E. Frankland, who in 1849, 
 as the result of his researches on hydrocarbon radicals, put for- 
 ward the view that cacodyl is a compound of arsenic and the 
 radical methyl. Frankland was led to this conclusion by his 
 discovery that the organo-metallic derivatives of zinc are 
 obtained by the action of this metal on alkyl iodides. Where- 
 upon he suggested that a similar reaction between arsenic and 
 methyl and ethyl iodides would probably lead to cacodyl and 
 its next homologue respectively. 1 
 
 Kolbe, who had previously collaborated with Frankland in a 
 study of the action of potassium on ethyl cyanide, 2 came sub- 
 sequently to a similar conclusion, and in 1850 3 gave in the 
 notation of that epoch the correct interpretation of the cacodyl 
 reaction 
 
 2KO(C 2 H 3 )C 2 3 -f As0 3 = (C 2 H 3 ) 2 AsO + 2KOC0 2 + 2CO 2 , 
 
 which corresponds with the modern equation given on page 7. 
 His views on the cacodyl radical itself were expressed as follows : 
 " Ich trage kein Bedenken diese Frage bejahend zu beantworten 
 und glaube vor Allem das Kakodyl als ein solches gepaartes 
 Radical ausprechen zu miissen, worin 2 Aeq. Methyl den Paar- 
 ling von i Aeg. Arsenik ausmachen : Kakodyl = (C 2 H 3 ) 2 As." 
 
 1 Frankland, Annalen, 1849, 71, 215. 
 ' 2 Frankland and Kolbe, Annalen, 1848, 65, 269. 
 3 Kolbe, Annalen, 1850, 75, 218 ; 76, 30. 
 20 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 Interpreted by modern notation this formulation gives 
 (CH 3 ) 2 As as the formula for cacodyl. 
 
 This hypothesis was confirmed in 1853 b Y the synthesis of 
 cacodyl by Cahours and Riche, but the initial step towards the 
 realisation of this prediction was taken by Lowig and Schweitzer, 1 
 who in 1850 prepared the first organic derivative containing 
 antimony. 
 
 Section /. General Reactions, i. Interaction of Alky I 
 Halides and Alloys of Arsenic and Antimony. 
 
 An alloy of antimony and potassium was prepared by igniting 
 at white heat in a covered crucible an intimate mixture of five 
 parts of crude potassium hydrogen tartrate (cream of tartar) 
 and four parts of antimony. After being cooled in the absence of 
 air the product formed a crystalline regulus having a distinctly 
 metallic lustre. The alloy containing 12 per cent, of potassium 
 was decomposed by water liberating hydrogen ; it oxidised on 
 exposure to air, taking fire when in pulverulent form. To avoid 
 this inflammation the alloy was ground up with two to three parts 
 of fine quartz sand and treated in small 2 to 3 oz. flasks with 
 sufficient ethyl iodide to moisten the solid mixture. The experi- 
 ment was conducted in an inert atmosphere ; a violent reaction 
 set in so that the excess of ethyl iodide boiled away. 
 
 The residue, rectified in an atmosphere of carbon dioxide, 
 yielded triethylstibine as a colourless, highly refractive liquid 
 having an unpleasant odour resembling that of onions. The 
 oil took fire in air at the ordinary temperature, burning with a 
 highly luminous white flame, and when projected in a fine stream 
 into oxygen gave a dazzling light. 
 
 The production of triethylstibine from the antimony-potassium 
 alloy was also effected with ethyl chloride and ethyl bromide, 
 but the iodide was preferred. It is probable that the crystalline 
 by-product noticed by Lowig and Schweitzer when ethyl iodide 
 was employed was tetraethylstibonium iodide. 
 
 This initial discovery in the antimony series was speedily 
 followed by a similar investigation by Landolt in i85i, 2 who 
 treated the antimony-potassium alloy with methyl iodide, thus 
 obtaining trimethylstibine and tetramethylstibonium iodide. 
 
 1 Mitth. d. Zurch. Naturforsch. Gesellschaft, 1850, 45, i ; Annalen, 
 1850, 75, 315. 327- 
 
 2 Annalen, 1851, 78, 91. 
 
 21 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The interaction of alkyl halides on antimony-potassium alloy 
 is a simpler chemical change than that arising from the corre- 
 sponding experiment in the arsenical series. In the latter con- 
 densation, 1 Landolt discovered three substances, triethylarsine, 
 tetraethylarsonium iodide, and ethylcacodyl. 2 Cahours and 
 Riche subsequently obtained a similar result using methyl 
 iodide, when they isolated tetramethylarsonium iodide, trimethyl- 
 arsine, and cacodyl. 
 
 In these syntheses of organic arsenicals the alloy of arsenic 
 and sodium or potassium was employed. Other arsenical alloys 
 have been utilised giving similar results. Methyl iodide 3 acting 
 on zinc and cadmium alloys of arsenic at 1*80 leads to the double 
 salts 2As(CH 3 ) 4 I,ZnI 2 and 2As(CH 3 )J,CdI 2 respectively. Ethyl 
 iodide 4 and these alloys yield the corresponding complex iodides 
 2As(C 2 H 5 ) 4 I,ZnI 2 and 2As(C 2 H 5 )J,CdI 2 . From these double 
 salts the quaternary iodide is obtained by treatment with 
 caustic alkali. 
 
 2. Interaction of Alkyl Halides and Arsenic or Antimony. 
 
 A further variant of this experiment is to employ free arsenic 
 with the alkyl iodide in sealed tubes at 160-200, when methyl 
 iodide 5 gives rise to the double salt As(CH 3 ) 4 I,AsI 3 , and ethyl 
 iodide 6 yields As(C 2 H 5 ) 4 I,AsI 3 . Treatment of these complex 
 iodides with caustic alkali decomposes the arsenious iodide into 
 potassium arsenite and iodide liberating the quaternary iodide. 
 
 Amorphous arsenic has since been recommended for this 
 purpose. It is prepared by reducing a solution of arsenious 
 oxide in hydrochloric acid with stannous chloride or sodium 
 hypophosphite. In the latter case concentrated solutions should 
 be employed and the solid hypophosphite added to the warm 
 liquid 
 
 As 4 O 6 + 3NaH 2 P0 2 = 4 As + 3NaH 2 PO 4 . 
 
 This form of arsenic reacts with methyl iodide at the ordinary 
 temperature. 7 
 
 The action of alkyl iodides on antimony has been much less 
 
 1 Annalen, 1854, 89, 321 ; v. Quart. J. Ch.em. Soc., 1854, 7, 258. 
 
 2 Annalen, 1854, 92, 361 ; Compt. rend., 1854, 39, 541. 
 
 3 Cahours, Compt. rend., 1859, 49, 87. 
 
 4 Cahours, Annalen, 1862, 122, 200. 
 
 5 Cahours, ibid., 198. 
 
 6 Cahours and Riche, Compt. rend., 1854, 39, 541. 
 
 7 Martindale, Congress Applied Chemistry, 1909. 
 
 22 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 extensively examined, but Buckton found that methyl iodide 
 and this metalloid at 140 yielded trimethylstibine iodide 
 Sb(CH,) 3 V 
 
 The production of tetra-alkyl quaternary arsonium iodides 
 was extended by Mannheim 2 who, after experiencing the con- 
 siderable experimental difficulties arising from the inflammable 
 and poisonous character of sodium arsenide, employed the general 
 method discovered by Cahours of heating finely divided arsenic 
 and alkyl iodides in sealed tubes at temperatures ranging from 
 160 to 235. The double iodide, R 4 AsI,AsI 8 , thus produced was 
 decomposed by aqueous caustic alkali to remove arsenious 
 iodide. The tetra-alkylarsonium iodides thus isolated were 
 compared very carefully with the products obtained by the 
 action of alkyl iodides on mercuric arsenide, Hg 3 As 2 , produced 
 in the wet way by passing hydrogen arsenide (arsine) into an 
 alcoholic solution of mercuric chloride (27-1 grams HgCl 2 in 
 2,000 c.c.). 3 The result of this systematic comparison was to 
 show that the supposed hexa-alkyldiarsonium halides and double 
 halides recorded by Partheil, Amort, and Gronover are in 
 reality tetra-alkylarsonium halides and double halides. These 
 hexa-alkyldiarsonium halides should accordingly be deleted from 
 the' list of organic arsenical compounds. 4 
 
 v v 
 ; IR 3 As AsR 3 I [non-existent]. 
 
 This correction brings arsenic into line with phosphorus and 
 antimony. Mercuric phosphide, Hg 3 P 2 , on treatment with alkyl 
 iodides 5 gave only tetra-alkylphosphonium iodides. Under 
 similar conditions mercuric antimonide yielded tetra-alkylsti- 
 bonium iodides. 6 
 
 Although this monograph furnishes many examples of organic 
 arsenicals containing pairs of arsenic atoms, doubly and singly 
 linked, yet it will be observed that in all these instances the 
 
 1 Journ. Chem. Soc., 1860, 13, 120; Jahresber., 1860, 374. 
 
 2 Annalen, 1905, 341, 196. 
 
 3 Partheil and Amort, Arch, Pharm., 1899, 237, 126. 
 
 4 Arch. Pharm., 1899, 237, 121 ; Amort, Inaug. Dissert., Heidelberg, 
 1898; Gronover, Inaug. Dissert., Heidelberg, 1899. 
 
 5 Partheil and van Haaren, Arch. Pharm., 1900, 238, 28 ; Van 
 Haaren, Inaug. Dissert., Bonn, 1900. 
 
 6 Arch. Pharw., 1900, 238, 166 ; Mannheim, Iriavg. Dissert., Bonn, 
 1900. 
 
 23 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 composition of the compounds is consistent with the view that 
 the arsenic is tervalent in these substances. 
 
 Singly-linked arsenic atoms. Doubly-linked arsenic atoms. 
 
 CH 3 -As-CH 3 Arsenobenzene, CgHg-AstAs-CpHs. 
 
 CH 3 .As.CH 3 (P- 87) 
 
 Single and doubly-linked arsenic atoms. 
 As:As-C,H 5 
 
 As:As.C 6 H 6 
 
 This tendency for arsenic to combine with itself in its organic 
 derivatives is undoubtedly to be correlated with the behaviour 
 of the free element which even in vaporous condition possesses 
 a tetratomic molecule, As^ 1 
 
 As:As 
 
 The absence of antimonial analogues of cacodyl is a note- 
 worthy difference in the chemical deportment of the two metal- 
 loids which may be correlated with their behaviour in their 
 inorganic compounds. 
 
 In the mineral kingdom arsenic frequently replaces sulphur 
 isomorphously, as for instance in the well-known pair of minerals 
 pyrite, FeS 2 , and cobaltite, CoAsS, which both crystallise in the 
 cubic system. Many varieties of pyrites are highly arseni- 
 ferous, showing a partial displacement of sulphur by arsenic. 
 Moreover, the two elements combine in atomic proportions in 
 the mineral realgar, As 2 S 2 . The close relationship between 
 arsenic and sulphur exhibited in these minerals is not shown 
 between the latter element and antimony. This apparent 
 bi valency of arsenic in realgar and cacodyl is probably due, 
 however, to a tendency for this metalloid to unite with itself 
 when in this state of combination. 
 
 As:S As(CH 3 ) a 
 
 As:S As(CH 3 ) 2 
 
 Realgar. Cacodyl. 
 
 1 The active yellow modification of elemental arsenic obtained by 
 suddenly cooling arsenic vapour is soluble in carbon bisulphide and gives 
 a molecular weight corresponding with As 4 . Grey and brown arsenic 
 are respectively As 2 and As 8 , whereas metallic arsenic is regarded as 
 being the monoatomic form As. (Erdmann and others, Zeitsch. anorg. 
 Chem., 1902, 32, 437 ; Annalen, 1908, 361, i ; cf. Jolibois, Compt. rend., 
 , 152, 1767.) 
 
 24 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 In this respect arsenic resembles phosphorus and nitrogen, 
 which give rise respectively to the hydrides P 2 H 4 and N 2 H 4 
 and their organic derivatives. 
 
 The groups PH 2 , NH 2 , and As(CH 3 ) 2 are univalent like the 
 hydrocarbon radicals methyl, CH 3 , ethyl, C 2 H 5 , etc. All these 
 univalent radicals exist in a state of freedom only as the double 
 (dimeric) molecules P 2 H 4 , N 2 H 4 , As 2 (CH 3 ) 4 , CH 3 'CH 3 , and 
 
 The trialkylstibines (and trialkylarsines) behave as bivalent 
 radicals comparable with ethylene, and like the latter they are 
 capable of existing in the free state as simple monomeric mole- 
 cules. Lowig and Schweitzer demonstrated this fact by deter- 
 mining the vapour density of triethylstibine, which showed that 
 this compound has in the gaseous state a molecular complexity 
 corresponding with the simplest formula, Sb(C 2 H 5 ) 3 . 
 
 The condensation between potassium-antimony alloy and 
 amyl iodide as studied by Berle 1 led to triamylstibine, and this 
 author supposed that on distilling the crude product of reaction 
 a diamylstibine was obtained. This substance did not, how- 
 ever, yield any crystalline derivatives, and it can scarcely be 
 conceded that the evidence for the existence of this antimony 
 analogue of amylcacodyl is conclusive. 
 
 Similar uncertainty still exists in regard to aliphatic antimonides 
 containing more than three alkyl groups. Buckton by the 
 action of zinc ethyl on tetraethylstibonium iodide obtained an 
 oily liquid distilling in coal gas at 160-170, and giving on analysis 
 higher percentage amounts of carbon and hydrogen than are 
 present in triethylstibine ; the antimony in the product was not 
 estimated. Buckton, who supposed that this liquid contained 
 tetraethylstibine, made a similar experiment with zinc methyl 
 and tetramethylstibonium iodide. The liquid obtained in this 
 instance was rectified when the fraction boiling at 86-96 gave 
 carbon and hydrogen values corresponding with the formula 
 Sb(CH 3 ) 4 ; the fraction boiling at 96-100 gave numbers on 
 combustion approximating to the formula Sb(CH 3 ) 5 . The 
 antimony was not estimated. If these results could be substan- 
 tiated the existence of tetra-alkyl and penta-alkyl derivatives of 
 antimony would be a fact of the highest theoretical importance. 
 Tetramethylstibine would be the only organic derivative of the 
 phosphorus-antimony family of elements capable of existence 
 in the free state in which one atom of the element is attached 
 1 Annalen, 1856, 97, 316. 
 25 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 solely to four hydrocarbon radicals without a fifth electro- 
 negative group as in the following examples : 
 
 N(CH 3 )J, P(C 2 H 5 ) 4 OH, 
 As(CH 3 ) 2 (C 2 H 5 ) 2 Br, and Sb(C 2 H 5 ) 4 OH. 
 
 Pentamethylstibine would be unique among organo-metallic 
 and organo-metalloidal compounds in containing one atomic 
 proportion of the metalloidal element attached to more than 
 four hydrocarbon radicals. 1 
 
 An impartial survey of the existing evidence shows, however, 
 that the case for bi-alkyl, tetra-alkyl-, and penta-alkyl-anti- 
 monides has not been substantiated. 
 
 The analogous experiment with tetramethylarsonium iodide 
 and zinc methyl was made by Cahours. 2 There was a violent 
 reaction ; zinc iodide was produced and gas evolved. Four- 
 fifths of the volatile product consisted of trimethylarsine ; the 
 remaining less volatile oily product gave on analysis numbers 
 for carbon and hydrogen approximating to the formula for 
 pentamethylarsine, As(CH 3 ) 5 . Further evidence was obtained 
 from the decomposition of the substance by iodine when it yielded 
 methyl iodide and tetramethylarsonium iodide. With hydro- 
 chloric acid the supposed pentamethylarsine gave methane and 
 tetramethylarsonium chloride. 
 
 3. Interaction of Metallic Alkyls and Halides of Arsenic and 
 
 Antimony. 
 
 A third general method of synthesising aliphatic arsenicals 
 and antimonials depends on the employment of zinc alkyls and 
 the halides of arsenic and antimony. 
 
 1 Compounds of nitrogen with five hydrocarbon residues. That sub- 
 stances containing five hydrocarbon groups associated with one non- 
 metallic atom are capable of existence is shown by the synthesis of 
 triphenylmethyltetramethylammonium, 
 
 (C 6 H 5 ) 3 C-Na + C1-N(CH 3 ) 4 = (C 6 H 5 ) 3 C'N(CH 3 ) 4 + Nad, 
 and an even simpler member of this new group of nitrogen penta-alphyls, 
 namely, benzyltetramethylammonium, 
 
 C 6 H 5 -CH 2 -Na + C1-N(CH 3 ) 4 = (C 6 H 5 )-CH 2 'N(CH 3 ) 4 + NaCl. 
 These remarkable compounds are intensely red, crystalline substances 
 with metallic reflex ; they are very sensitive to moisture and are decom- 
 posed by water into tetramethylammonium hydroxide and the corre- 
 sponding hydrocarbon (triphenylmethyl and toluene respectively) with 
 considerable generation of heat (Ber., 1916, 49, 605 ; 1917, 50, 275). 
 
 2 Annalen, 1862, 122, 338, 
 
 26 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 Zinc dimethyl and zinc diethyl acting on arsenious chloride give 
 rise respectively to trimethylarsine and triethylarsine. 1 These 
 reagents are specially useful for producing mixed arsines, thus 
 dimethylethylarsine is obtained from dimethylarsenious iodide, 
 As(CH 3 ) 2 I, and zinc diethyl, whereas methyldiethylarsine results 
 from the interaction of this zinc compound and methylarsenious 
 iodide. 2 
 
 These reactions are available for preparing the organic stibines. 
 Zinc dimethyl 3 and antimony trichloride give rise to trimethyl- 
 stibine, which also results from the action of mercury dimethyl 4 
 on the same chloride. 
 
 Mercury dimethyl has also been employed in synthesising 
 organic arsenicals containing only one alkyl radical. Ethyl- 
 arsenious chloride is produced by the interaction of arsenious 
 chloride and mercury diethyl. 5 
 
 AsCl 3 + Hg(C 2 H 5 ) 2 = C 2 H 5 -AsG 2 + C 2 H 5 -HgCl. 
 
 4. Grignard Reaction applied to the Synthesis of Aliphatic 
 Arsenicals and Antimonials. 
 
 The Grignard reaction, which comes under the category of the 
 foregoing general synthetic method, has so greatly facilitated 
 the process of producing organo-metallic and organo-metalloidal 
 derivatives that it merits a separate section. 
 
 Arsenious 6 bromide and magnesium methyl iodide interact 
 to yield trimethylarsine, providing that the Grignard reagent is 
 maintained in excess. The arsenious halide (50 grams) dissolved 
 in 100 c.c. of ether is added slowly at 20 to the Grignard 
 reagent (magnesium, 12-2 grams, methyl iodide, 71 grams, in 
 200-300 c.c. of pure ether) . A yellow precipitate is formed at first 
 which subsequently dissolves. The product is distilled from the 
 water-bath, and the trimethylarsine collected in the form of its 
 dibromide, (CH 3 ) 3 AsBr 2 ; the yield is over 70 per cent, of the 
 calculated amount. 
 
 Antimony trichloride (18-9 grams) in 80-100 c.c. of ether is 
 added slowly to the well-cooled Grignard reagent (magnesium, 
 
 1 Hofmann, Jahresber., 1855, 538; Annalen, 1857, 103, 357. 
 
 2 Cahours, ibid., 1862, 122, 220. 
 
 3 Hofmann, ibid., 1857, 103, 357. 
 
 * Buckton, Quart. J. Chem. Soc., 1863, 16, 22. 
 
 5 La Coste, Annalen, 1881, 208, 33. 
 
 6 Hibbert, Ber., 1906, 39, 160. 
 
 27 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 6-1 grams, methyl iodide, 35-5 grams, in 200-300 c.c. of pure 
 ether). The yellow intermediate product is precipitated and 
 redissolved when the solution forms two layers, an upper ethereal 
 layer and a lower oily layer which ultimately solidifies. The 
 mixture is distilled up to 170 in a current of carbon dioxide. 
 The yield of trimethylstibine weighed as crystalline dibromide 
 is 60-70 per cent, of the calculated amount. 
 
 The method gives rise to primary and secondary organic 
 derivatives of arsenic and primary compounds of antimony 
 when the Grignard reagent is employed in suitable proportions 
 (one mol. to one mol. of arsenic or antimony halide). In these 
 circumstances arsenious chloride and magnesium ethyl bromide 
 yield small amounts of ethylarsenious chloride, C 2 H 5 -AsCl 2 , 
 and diethylarsenious chloride, (C 2 H 5 ) 2 AsCl, which are obtained 
 together with arsenious chloride and bromide by distilling the 
 product of the Grignard reaction in vacuo after removing the 
 ether. These chlorides are identified as their corresponding 
 arsenic acids, C 2 H 5 -AsO 3 H 2 and (C ? H 5 ) 2 AsO 2 H. The principal 
 product is triethylarsine oxide, As(C 2 H 5 ) 3 O, isolated in the form of 
 sulphide by passing sulphuretted hydrogen through concentrated 
 aqueous solution of the residue left after the foregoing fractiona- 
 tion. 
 
 An ethereal solution of magnesium ethyl bromide (from 75 
 grams of ethyl bromide) is added at 18 to antimony trichloride 
 (200 grams) in 200 c.c. of ether. The product, after removing 
 ether, is distilled under 12 mm. pressure, when antimony tri- 
 chloride and tribromide are obtained together with ethyl- 
 antimonious chloride and bromide, C 2 H 5 -SbCl 2 and C 2 H 5 -SbBr a . 
 Excess of potassium iodide converts these four compounds into 
 antimony tri-iodide and ethylantimonious iodide. After 
 removing the former iodide by solution in dilute hydrochloric 
 acid, the latter, C 2 H 5 -SbI 2 , is obtained in golden-yellow leaflets, 
 m. p. 43 .i 
 
 5. Alkylation of Arsenical Oxy-compounds. 
 
 The synthetic methods described in the foregoing section 
 suffer from one grave disadvantage ; they require to be carried 
 out in the absence of moisture, and in some instances in an inert 
 atmosphere. These are serious defects when the manufacture 
 of organic arsenicals on an industrial basis is attempted. 
 These difficulties can, however, be avoided by an ingenious 
 process of alkylation due to G. Meyer. 2 
 
 1 Auger and Billy, Compt. rend., 1904, 139, 597. 2 Ber., 1883, 16, 1440. 
 
 28 
 
ALIPHATIC ARSENIC ALS AND ANTIMONIALS 
 
 Sodium arsenite and methyl iodide are heated together in 
 alkaline solution, when sodium methylarsinate is produced. 1 
 
 in v 
 
 As(OH) (ONa) 2 +CH 3 I+NaOH = CH 3 -AsO(ONa) 2 +NaI +H 2 O. 
 
 /ONa 
 
 NaO-As< +CH 8 I = 
 
 X ONa 
 
 NaO, /OjNa! 
 
 >As< I 
 CH/ 
 
 ONa" 
 
 /ONa 
 
 CH 3 -As4o . 
 \ONa 
 
 The process has been generalised by Dehn and McGrath so 
 that ethyl-, w-propyl-, ^soamyl- and benzyl-arsinic acids have 
 been synthesised. 2 
 
 Moreover, it has been found that this alkylation can be carried 
 further after reducing methylarsinic acid to methylarsenious 
 oxide, CH 3 -AsO, the sodium derivative, CH 3 As(ONa) 2 , of which is 
 similarly methylated to cacodylic acid. This compound on 
 reduction gives cacodyl oxide, the sodium derivative of which 
 is then methylated to trimethylarsine oxide. Trimethylarsine 
 obtained by the reduction of this oxide combines additively 
 with methyl iodide to form tetramethylarsonium iodide. By 
 this series of reactions we can obtain from sodium arsenite 
 by progressive methylation, organic arsenic derivatives con- 
 taining one, two, three, or four methyl groups. 3 
 
 6. Dealkylation of Tertiary Ar sines and their Derivatives. 
 
 Excluding the Grignard reaction, the foregoing general syn- 
 theses have led to organic antimony derivatives containing three 
 or four alkyl groups. In the arsenic series these synthetic pro- 
 cesses have in certain instances yielded tertiary arsines and 
 quaternary arsonium salts with cacodyl and its homologues as 
 by-products. It is now necessary to consider methods whereby 
 primary alkyl derivatives of arsenic have been produced by pro- 
 cesses of dealkylation from dialkyl compounds. 
 
 Among the earlier researches on organic arsenic derivatives 
 should be mentioned specially the work of Baeyer, whose in- 
 vestigations were an extension of Bunsen's study of cacodyl. 4 
 
 1 Cf. Klinger and Kreutz, Annalen, 1888, 249, 147. 
 
 2 Cf. Dehn, Amer. Chem. /., 1905, 33, 138 ; Dehn and McGrath, /. 
 Amer. Chem. Soc., 1906, 28, 351. 
 
 3 V. Auger, Compt. rend., 1903, 137, 925. 
 
 4 Annalen, 1858, 107, 282. 
 
 29 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Bunsen's preparations of cacodyl oxide (alkarsin) probably 
 contained varying proportions of free cacodyl, for when the 
 latter was allowed to become oxidised purer non-inflammable 
 specimens of the oxide were obtained which he designated 
 " paracacodyl oxide." By distilling Cadet's liquid with con- 
 centrated hydrochloric acid and mercuric chloride, Baeyer 
 obtained pure cacodyl chloride 
 
 (CH 3 ),AsO,HgCl a + 2HC1 = (CH 3 ) 2 AsCl 2 + H 2 O + HgCl 2 . 
 
 The distillation of this cacodyl chloride with caustic potash 
 furnished Baeyer with pure cacodyl oxide, a product having 
 properties identical with those of Bunsen's " paracacodyl oxide." 
 Cacodyl chloride was shown to be an unsaturated compound 
 combining with chlorine to form a trichloride, (CH 3 ) 2 AsCl 3 , 
 which on hydrolysis yielded cacodylic acid, and on warming 
 decomposed into methyl chloride and methylarsenious chloride 
 (IV.) :- 
 
 (CH 8 ) 2 AsCl 
 
 (CH 3 ) 2 AsOOH 
 
 CH 3 AsCl 2 + CH 3 Cl 
 IV 
 
 Methylarsenious chloride belongs to the series of organic 
 arsenic compounds containing only one alkyl group attached to 
 the metalloidal atom. With alkali it yields the corresponding 
 methylarsenious oxide, CH 3 -AsO, and with chlorine it combines, 
 forming the very unstable methylarsenic tetrachloride, CH 3 -AsCl 4 . 
 Hydrolysis of the tetrachloride or oxidation of the dichloride or 
 oxide leads to methylarsinic acid CH 3 AsO(OH) 2 : 
 
 CH 3 -AsCl 4 
 
 CH.-AsCl, 
 
 Oxidation with Ag 2 CH 3 -AsO(OH) 2 
 
 ^\ 
 , ^> 
 CHs-AsO 
 
 30 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 Dealkylation in the arsenical series can be brought about 
 by the distillation of the alkyl-arsenic chlorides in accordance 
 with the following scheme in which all the steps indicated by 
 unbroken lines have been realised. 
 
 v. 
 
 (CH 3 ) 4 AsCl 
 
 V. 
 
 (CH 3 ) 8 AsCl 
 
 v. 
 (CH 3 ) 2 AsQ 
 
 in. 
 (CH 3 ) 3 As 
 
 III. 
 
 (CH 3 ) 2 AsCl 
 
 m. 
 CH 3 -AsG 2 
 
 v. 
 CH 3 -AsCl 4 
 
 Dealkylation is also effected through the agency of iodine 
 derivatives. The periodides of the quaternary arsonium bases 
 decompose on heating to yield cacodyl derivatives. The follow- 
 ing reactions were first investigated by Cahours. 1 
 
 As(CH 3 ) 4 I 3 = As(CH 3 ) 2 I + 2 CH 8 I. 
 
 As(C 2 H 5 )J 3 = As(C 2 H 6 ) 2 I -f 2C 2 H 5 L 
 
 As(CH 3 ) 2 I + 2! = As(CH 3 )I 2 + CH 3 I. 
 
 As(C 2 H 5 ) 2 I -f 2! = As(C 2 H 5 )I 2 + C 2 H 5 I. 
 
 Cacodyl itself undergoes partial or complete demethylation 
 on distillation with iodine : 
 
 As 2 (CH 3 ) 4 + 3 I 2 = 2 As(CH 3 )I 2 + 2CH S I. 
 As 2 (CH 3 ) 4 + 5I 2 = 2 AsI 3 + 4CH,I. 
 
 Trimethylarsine undergoes similar changes. 
 
 As(CH 3 ) 3 +2l = As(CH 3 ) 2 I + CH 3 I. 
 As(CH 3 ) 3 + 4 I = As(CH 3 )I 2 + 2CH 3 I. 
 As(CH 3 ) 3 + 6I - AsI 3 + 3 CH,I. 
 
 These reactions can be reversed by the action of zinc dimethyl 
 on the arsenical products on the right-hand side of the foregoing 
 equations. 2 
 
 1 Cahours, Corn-pi, rend., 1860, 50, 1023. 
 
 2 Cahours, Annalen, 1862, 122, 218. 
 
 31 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section II. Aliphatic Arsenic Compounds. 
 i. Methyl Series. 
 
 (For Cacodyl Group, v. p. 10.) 
 
 Trimethylarsine, As(CH 8 ) 3 , liquid, b.p. below 100, obtained 
 from arsenious chloride and zinc dimethyl (Hofmann, loc. cit.) 
 and as a by-product from the interaction of methyl iodide and 
 sodium arsenide (Cahours, loc. cit.) ; prepared by distilling 
 tetramethylarsonium iodide or its double salts with dry potass- 
 ium hydroxide. It behaves as a bivalent radical combining 
 directly with oxygen, sulphur, and the halogens. Trimethyl- 
 arsine oxide, As(CH 3 ) 3 O, deliquescent crystals. Trimethyl- 
 arsine iodide, As(CH 3 ) 3 I 2 , decomposed on heating into cacodyl 
 iodide and methyl iodide. 
 
 Tetramethylarsonium iodide, As(CH 3 ) 4 I, colourless leaflets, 
 readily decomposing at 170-180, produced by the direct addition 
 of its generators, trimethylarsine and methyl iodide. Obtained 
 as chief product by treating sodium arsenide with excess of methyl 
 iodide (Cahours and Riche). 1 This compound, which Cahours 
 also prepared in the form of the double iodide, As(CH 3 ) 4 I,AsI 3 , 
 by the action of methyl iodide on elemental arsenic at 160-200, 
 has the properties of a soluble metallic iodide, such as potassium 
 iodide : 
 
 CH 3 CH 3 CH 3 CH 8 CH 8 
 
 \As-CH 3 -> CH 3 ^As<^ -> CH 3 X\s/ 
 
 CH 8 CH 8 I CH 3 OH 
 
 I. II. III. 
 
 Although not decomposed by aqueous caustic potash, tetra- 
 methylarsonium iodide (II.) reacts with moist silver oxide, yielding 
 silver iodide and a very soluble compound, tetramethylarsonium 
 hydroxide (III.). This complex hydroxide is a strongly caustic 
 substance resembling sodium or potassium hydroxide ; it com- 
 bines readily with acids, even carbonic acid, to form salts ; it 
 turns red litmus blue, precipitates hydroxides of heavy metals 
 from their soluble salts, and saponifies fats. Tetramethyl- 
 arsonium hydroxide behaves precisely as if it were the hydroxide 
 of an alkali metal, but its alkali radical or ion is complex and 
 
 1 Annalen, 1854, 92, 361. 
 * 32 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 consists of an arsenic atom combined with four alkyl or aliphatic 
 groups. 
 
 Tetramethylarsonium iodide combines with iodine to form a 
 periodide, As(CH 3 ) 4 I 3 , brown needles with metallic lustre. On 
 heating, the periodide decomposes into methyl iodide (2 molsJ 
 and cacodyl iodide. The quaternary bromide, As^Bg^Br^ 
 is a highly deliquescent salt produced by the interaction of 
 methyl bromide on cacodyl. 
 
 As 2 (CH 3 ) 4 + 2 CH 3 Br = As(CH 3 ) 4 Br + As(CH 3 ) 2 Br. 
 
 Tetramethylarsonium mercuri-iodide, 1 As(CH 3 ) 4 I,HgI 2 , yellow 
 needles, m.p. 184, produced by combining its components in 
 alcoholic solution : the mer cur i- chloride, colourless needles, 
 melts at 175-176. The platinichloride, yellow crystals, and the 
 aurichloride, yellow needles, are obtained through the quaternary 
 hydroxide. 
 
 Methylarsenious chloride? As(CH 3 )Q 2 , liquid, b.p. 133, re- 
 sulting from the decomposition of cacodyl trichloride even at 
 40-50, or, preferably, by the prolonged action of hydrogen 
 chloride on dry cacodylic acid. It neither fumes in air nor 
 is decomposed by water. The vapour has a terribly irritating 
 action on the mucous membrane. When inhaled, the eyes, 
 nose, and face become swollen, and a peculiar gnawing pain is 
 felt extending into the throat. It absorbs chlorine at 10 to 
 yield the crystalline methylarsenic tetrachloride, As(CH 3 )Q 4 , which 
 decomposes even at o into methyl chloride and arsenious chloride. 
 
 Methylarsenious sulphide, As(CH 3 ):S, leaflets, m.p. 110; in- 
 soluble in water, soluble in ether, alcohol, or carbon bisulphide ; 
 produced by the action of sulphuretted hydrogen either on the 
 chloride or on the following iodide. Methylarsenious iodide, 
 lustrous, yellow needles, m.p. 25, volatilises unchanged above 
 200. Sparingly soluble in water and more so in alcohol, ether, 
 or carbon bisulphide ; prepared by adding hydriodic acid to an 
 alcoholic solution of methylarsenious oxide. 
 
 Methylarsenious oxide, As(CH 3 ):O, cubical crystals sometimes 
 changing into a white, porcellanous variety, m.p. 95, odour of 
 asafcetida, slightly volatile in steam or alcohol vapour, but 
 decomposed on heating ; prepared by decomposing methyl- 
 arsenious chloride with saturated aqueous potassium carbonate, 
 the oxide being extracted with alcohol or carbon bisulphide. 
 
 1 Mannheim, Annalen, 1905, 341, 196. 
 
 2 Baeyer, ibid., 1858, 107, 272. 
 
 33 D 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Methylarsinic acid, CH 3 -AsO(OH) 2 , anhydrous, colourless, tabu- 
 lar aggregates of dendritic needles, m.p. 161, from alcohol, very 
 soluble in water. A strong acid decomposing carbonates and 
 forming an ammonium salt. Prepared from methylarsenious 
 chloride by the action of excess of moist silver oxide or from the 
 oxide by oxidation with mercuric oxide and warm water ; purified 
 through the barium salt. With sulphuretted hydrogen this acid 
 yields the j^ellow, viscid disulphide, CH 3 -As-S 2 , and with concen- 
 trated hydriodic acid the tetra-iodide, As(CH 3 )I 4 . 
 
 Sodium methylarsinate 1 (Arrhenal, New cacodyl), 
 
 CH 3 AsO(ONa) 2 ,H 2 O, 
 
 very soluble in water (i : i), only sparingly so in alcohol (90 per 
 cent.). Prepared by heating an aqueous solution of sodium 
 arsenite with methyl iodide and alcohol. 
 
 This salt was first recommended in therapeutics by Gautier, 
 who stated that it had a specific action on malaria ; 2 it is, how- 
 ever, without effect on trypanosomes. 
 
 Distinctive Reactions of Sodium Cacodylate and Sodium Methyl- 
 arsinate (Arrhenal)? 
 
 Reagent. (CH 3 ) 2 AsOONa,3H 2 O. CH 3 -AsO(ONa) 2 ,H 2 O. 
 
 Silver nitrate No ppt White, silky ppt. 
 
 Mercuric chloride...' ... White ppt Reddish-yellow ppt. 
 
 Baryta- water White ppt No ppt. 
 
 Potassium methylarsinate, CH 3 -AsO(OK) 2 ,#H 2 O, is readily 
 prepared by the action of methyl chloride on aqueous potassium 
 arsenite. 4 
 
 Calcium methylarsinate, CH 3 AsO0 2 Ca,H 2 O, soluble in dilute 
 acetic acid, crystallising from this solution after neutralising with 
 ammonia. The barium salt, CH 3 AsO-O 2 Ba,5H 2 O, and the 
 silver salt are crystalline. 
 
 The mercurous, mercuric, and iron salts have been employed 
 therapeutically. The methylarsinates of many alkaloids have 
 been prepared, and of these the two anhydrous quinine salts, 
 CH 3 -AsO(OH) 2 (C 20 H 24 2 N 2 ) 2 ,and CH 3 -AsO(OH) 2 ,C 20 H 24 O 2 N 2 , and 
 
 1 Auger, Compt. rend., 1903, 137, 925; Auger and Billy, Compt. rend., 
 1904, 139, 599; G. Meyer, loc. cit. ; Klinger and Kreutz, loc. cit. 
 
 2 Presse midicale, 1902, 791 and 824; Compt. vend., 1902,134,329; 
 Moore, Nierenstein and Todd, Ann. trop. medicine, 1908, 2, 269; cf. 
 Mouneyrat, Compt. rend., 1903, 136, 696. 
 
 3 Cf. Vitali, Chem. Centr., 1903, II, 1416. 
 
 4 Dehn and McGrath, /. Amer* Chem. Soc., 1906, 28, 347. 
 
 34 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 the two strychnine salts, CH 3 -AsO(OH)2,(C 21 H 22 O 2 N 2 ) 2 , and 
 CH3-AsO(OH)2,C 21 H2 2 2 N2, are of therapeutic interest. 1 
 
 PyroUsmethylarsinic acid* CH 3 -AsO(OH) -OAs(CPI 3 )OOH, 
 is produced by heating methylarsinic acid at 130. At higher 
 temperatures (170-180) this product decomposes into methyl 
 alcohol and arsenious oxide. 
 
 Magnesium methylarsinate* CH 3 -AsO-O 2 Mg,5H 2 O, small, 
 white crystals. Solubility in I litre of water : 2-118 grams at 
 22 and 3-085 grams at 99. Arsenious oxide (318 grams) and 
 caustic potash (540 grams) are dissolved in water, the solution 
 of potassium arsenite, diluted to 3 litres, is treated with a molecular 
 proportion of methyl iodide (iCH 3 I to iK 3 AsO 3 ) and sufficient 
 alcohol to produce a homogeneous solution. The mixture is left 
 in stoppered bottles for several days, and the solution, which 
 has a powerful odour of some arsine derivative, is distilled to 
 remove alcohol and acidified with dilute hydrochloric acid, when 
 a white precipitate of the compound, 2As 2 O 3 ,KI, is produced. 
 The filtrate is treated with chlorine until the dark colour due 
 to precipitation of iodine begins to clear. The nitrate from 
 iodine is rendered ammoniacal and treated with magnesia 
 mixture, when magnesium ammonium arsenate separates ; the 
 solution on warming gives magnesium methylarsinate. A better 
 yield is obtained by using potassium arsenite instead of the 
 corresponding sodium salt . A portion of the magnesium methyl- 
 arsinate is liable to be co-precipitated with magnesium 
 ammonium arsenate even in cold solutions. 4 
 
 Iodine Derivatives of Methyl- and Dimethyl-arsinic Acid. 
 
 Amorphous arsenic prepared by reducing a hydrochloric acid 
 solution of arsenious oxide with stannous chloride or hypo- 
 phosphorous acid is a very active chemical agent, combining 
 with methyl iodide at the ordinary temperature instead of at 
 160, as was found by Cahours to be the temperature required 
 for ordinary powdered arsenic. 5 In preparing this amorphous 
 arsenic with hypophosphorous acid it is preferable to work in 
 
 1 Meyer's Jahresber., 1904, 14, 269; Leprince, /. Pharm. Chem., 1903, 
 [vi], 17, 22 ; Chem. Centr., 1903, I., 280. 
 
 2 Vitali, Bull. chim. Farm, 1905, 44, 229. Chem. Centr., 1905, I, 1699. 
 
 3 Dehn, Amer. Chem. ]., 1905, 33, 136. 
 
 4 Cf. Klinger and Kreutz, Annalen, 1888, 249, 149. 
 
 5 Auger, Compt. rend., 1907, 145, 808. 
 
 35 D 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 warm concentrated solutions, adding solid sodium hypophos- 
 phite little by little. 1 
 
 Amorphous arsenic reacts in a remarkable manner on iodoform. 
 The two reagents warmed together without a diluent interact 
 explosively. When diluted with benzene or toluene at the 
 temperature of the water-bath the reaction goes more smoothly 
 and is completed after several hours. On distilling off the 
 solvent a dense black, oily, crystalline magma is left which is 
 oxidised to definite crystalline products by cold nitric acid. 
 
 3CHI 3 + 2As = CHI 2 -AsI 2 + (CHI 2 ) 2 AsI. 
 
 CHI 2 -AsI 2 + 4HNO 3 = CHI 2 -AsO(OH) 2 + 4NO 2 + H 2 O + I 2 . 
 
 (CHI 2 ) 2 AsI + 3HN0 3 = (CHI 2 ) 2 -AsOOH + 3NO 2 + H 2 O 2 + I 
 
 The oxidised product is extracted with cold water. The 
 aqueous solution on concentration at 40-50 deposits yellow 
 tabular crystals of di-iodomethylarsinic acid, CHI 2 'AsO(OH) 2 ,H 2 O ; 
 the sodium salt, CH 2 I-AsO(OH)-ONa,H 2 O, colourless crystals, 
 is very soluble in water ; the silver salt is a white precipitate. 
 
 The insoluble oxidised product freed from iodine with boiling 
 benzene or toluene is dissolved in ammonia and reprecipitated 
 by acid. This tetmiodocacodylic acid, (CHI 2 ) 2 AsOOH, forms 
 small, yellow crystals, soluble in hot acetic or nitric acid. Its 
 sodium salt, (CHI 2 ) 2 AsOONa,6H 2 0, is obtained from water- 
 alcohol solution in well-defined pale yellow crystals. 
 
 Reduction Products of the Methyl Series of Aliphatic Arsenicals. 
 
 Recent improvements in the technique of organic reductions 
 have rendered possible the isolation of the hitherto missing 
 primary and secondary alkyl arsines, AsH 2 -Alk and AsH(Alk) 2 , 
 and of highly reduced products containing arsenic combined only 
 with one alkyl group, [Alk.As]#. 
 
 Dimethylarsine? (CH 3 ) 2 AsH, colourless liquid, with character- 
 istic odour of cacodyl, b.p. 35-67747 mm. and 5571-74 atmos. 
 Di -213/29 ; vapour density corresponding with the fore- 
 going formula. Spontaneously inflammable in air ; precipitates 
 silver from aqueous silver nitrate. Prepared by adding cacodyl 
 chloride to a mixture of platinised zinc, alcohol and hydrochloric 
 acid. By the treatment of cacodyl oxide with these reagents 
 a mixture of dimethylarsine and cacodyl is obtained. Dimethyl - 
 
 1 Martindale, Congress of Applied Chemistry, 1909. 
 
 2 Palmer, Ber., 1894, 27, 1378 ; Dehn and Wilcox, Amev, Chem. J., 
 1906, 35, 3. 
 
 36 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 arsine is of great theoretical interest as being the parent hydride 
 of the cacodyl series. 
 
 Preparation of Dimethylarsine. 
 
 This secondary arsine can be conveniently prepared from 
 crude cacodyl oxide (Cadet's fuming arsenical liquid). A re- 
 duction flask containing amalgamated zinc dust (250 grams), 
 cacodyl oxide (50 grams), and alcohol (200 c.c.) is joined in 
 series with a water wash-bottle, a U-tube filled with soda- 
 lime, a condenser for dimethylarsine, a sulphuric acid wash- 
 bottle and a nitric acid wash-bottle, the connections throughout 
 being of glass and cork, because the arsines attack indiarubber. 
 The bulb condenser being surrounded with ice and salt, strong 
 hydrochloric acid is slowly added to the reduction flask through 
 a dropping funnel. A bright yellow substance forms indicating 
 partial reduction ; this colour disappears as reduction proceeds. 
 When air is present in the apparatus a red substance always 
 makes its appearance ; this product contains a polymeride of 
 arsenobenzene and is identical with Bunsen's " erytarsin." 
 
 Dimethylarsine inflames in air above 10 but not below o, 
 burning with a bluish-white arsenical flame giving rise to white 
 fumes and a black, solid deposit. It is soluble in the ordinary 
 organic solvents. The oxidation products are very numerous 
 and are formed in accordance with the following equations : 
 
 1. 4 (CH 3 ) 2 AsH + 2 = 4 (CH 3 -As)* + 2 C,H 6 + 2H 2 O. 
 
 2. 4 (CH 3 ) 2 AsH + 2 = As 4 + 4 C 2 H 6 + 2 H 2 O. 
 
 3. 2(CH.) t AsH + g0 2 = As 2 3 + 4CO 2 + 7H 2 O. 
 
 4. 6(CH 3 ) 2 AsH + 30 2 = (CH 3 -As) 4 , As 2 O 3 + 4C 2 H 6 + 2 H 2 O. 
 
 5. 4 (CH 3 ) 2 AsH + 2 - (CH,VAs-As(CH,) a + 2H 2 O. 
 
 6. 2(CH 3 ) 2 AsH + O 2 = [(CH 3 ) 3 As] 2 + H 2 O. 
 
 7. (CH 3 ) 2 AsH + 2 = (CH 8 ) 2 AsOOH. 
 
 The halogens combine additively 1 with dimethylarsine, these 
 additive compounds being dissociated by water or at high 
 temperatures into the corresponding cacodyl halide and the 
 hydrogen halide. The following equations illustrate the chemical 
 changes in the case of bromine. 
 
 (CH 3 ) 2 AsH + Br 2 = (CH 3 ) 2 AsBr,HBr = (CH 3 ) 2 AsBr + HBr. 
 
 Aqueous iodine solution oxidises dimethylarsine to cacodylic 
 acid. This secondary arsine possesses feebly basic properties 
 combining with the mineral acids to yield unstable salts. 
 1 Dehn, Amev. Chem. J., 1908, 40, 121. 
 37 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Dimethylarsonium sulphate, [(CHg^AsHJaHaSC^, colourless, pris- 
 matic crystals, is produced with generation of heat on mixing 
 dimethylarsine and concentrated sulphuric acid ; it decomposes 
 slowly in air and rapidly in water into its generators. 
 
 Dimethylarsine and cacodyl chloride interact at 100 in mole- 
 cular proportions to produce cacodyl and hydrogen chloride. 
 
 (CH 3 ) 2 AsH -f (CH 3 ) 2 AsCl - (CH 8 ) a As-As(CH,) a + HC1. 
 
 Oxidising agents convert dimethylarsine into cacodylic acid 
 with cacodyl as an intermediate stage in the oxidation. Sulphur 
 and this arsine give rise to cacodyl mono- and di-sulphides, 
 sulphur dioxide converts the arsine into methylarsenious sulphide, 
 cacodyl disulphide, trimethylarsine sulphide and cacodylic acid. 
 Stannic chloride and dimethylarsine yield dimethylarsine 
 trichlorostannide, (CH^As-SnCla, volatile colourless needles with 
 penetrating odour. 
 
 Methylarsine, 1 CH 3 -AsH 2 , a very volatile, colourless liquid, 
 of high refractive power, b.p. -f 2/755 and i7/ I i atmos. ; 
 odour of cacodyl ; very poisonous and fuming, but not spon- 
 taneously inflammable in air. Almost devoid of basic properties, 
 forming salts with acids either with great difficulty or not at all. 
 Produced by the reduction of methylarsinic acid with amal- 
 gamated zinc dust and alcoholic hydrochloric acid. 
 
 Methylarsine 2 is soluble in alcohol, ether, or carbon bisulphide 
 in all proportions, but in water it dissolves only to the extent 
 of 85 parts in 1,000,000. Iodine and water oxidise it to methyl- 
 arsinic acid ; aqueous silver nitrate behaves similarly, giving 
 methylarsinic and nitric acids with a deposit of silver. Methyl- 
 arsine and hydrogen chloride combine very slightly, if at all, 
 even when mixed for a period of two weeks. With methyl iodide 
 at 110, methylarsine interacts to form tetramethylarsonium 
 iodide and hydrogen iodide. 
 
 The oxidation of methylarsine by nitric acid is a somewhat 
 complex reaction, methylarsinic, formic, and arsenic acids 
 being among the products of this chemical change. When 
 passed into aqueous mercuric chloride, methylarsine is oxidised 
 to mercuric methylarsinate, while mercurous chloride is pre- 
 cipitated. Bromine dissolved in carbon bisulphide decomposes 
 methylarsine completely into arsenious bromide, methyl bro- 
 mide, and hydrogen bromide. 
 
 1 Palmer and Dehn, Ber., 1901, 34, 3594. 
 
 2 Dehn, Amer. Chem. ],, 1905, 33, 101. 
 
 38 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 . 
 
 Preparation of Methylarsine. 
 
 Amalgamated 1 zinc dust and sodium methylarsinate mixed 
 together in a large flask are treated with the necessary amount 
 of hydrochloric acid diluted with an equal quantity of alcohol. 
 The generator is connected in series with a wash-bottle con- 
 taining water, a drying tube filled with soda-lime, and 
 a condensation apparatus ABC (shown in the figure, 2 
 fixed in a wooden vessel charged with solid carbon dioxide. 
 The whole apparatus is filled with hydrogen in order to 
 exclude atmospheric oxygen from 
 the methylarsine which collects in 
 the bulb B and is drawn off from 
 time to time into the intermediate 
 receiver C. On closing the upper 
 and opening the lower tap of this 
 intermediate vessel, a portion of the 
 liquefied methylarsine is forced into 
 the capillary end of the tube D 
 which has previously been filled 
 with dry hydrogen. 
 
 The vapour density of methylarsine 
 corresponds with the simple formula 
 CH 3 -AsH 2 . One volume of the gas 
 over mercury absorbs an equal 
 volume of oxygen producing white 
 solid methylarsine oxide (m.p. 95). 
 After two weeks' exposure one 
 volume of the methylarsine absorbed 
 1-414 volumes of oxygen, but if the 
 
 water produced in the first phase of the process was absorbed 
 by fused calcium chloride no second absorption of oxygen 
 occurred. 
 
 i. CH 3 -AsH 2 + O 2 = CH 3 -AsO + H 2 O. 
 ii. 2CH 3 -AsH 2 + 3O 2 - 2CH 3 -AsO(QH) 2 . 
 
 The second product was distinctly acid and was identified as 
 methylarsinic acid (m.p. 161). This acid was also produced 
 by oxidising the primary arsine with strong nitric acid. Alcoholic 
 iodine gave with the arsine yellow needles of methylarsine 
 iodide. 
 
 1 Dehn, Amer. Chem. ]., 1905, 33, 120. 
 
 2 Palmer and Dehn, Ber., 1901, 34, 3595- 
 
 39 
 
 FIG. 3. 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Arsenomethane 1 (Methylarsenic), (CH 3 -As:As-CH 3 ) 2 , light 
 yellow heavy oil with intense garlic odour, b.p. I9O/I3 mm. 
 Prepared by reducing sodium methylarsinate with sodium 
 hypophosphite and sulphuric acid. Arsenomethane resembles 
 methylarsine in its behaviour towards oxidising agents, but 
 differs from the primary arsine in the ease with which it poly- 
 merises to a dark brown insoluble powder, [CH 3 -As]#. This 
 product when distilled in hydrogen decomposes quantitatively 
 into trimethylarsine and elemental arsenic. 
 
 3CH 3 -As==As(CH 3 ) 3 -}-2As. 
 
 In this decomposition the ^substance resembles arsenobenzene, 
 C 6 H 5 -As:As-C 6 H 5 , which on heating breaks down quantitatively 
 into triphenylarsine and free arsenic. A further analogy is 
 exhibited by the behaviour of arsenomethane on heating at 
 100 with methyl iodide, when it yields tetramethylarsonium 
 iodide and methylarsenious iodide (cf. p. 88). 
 
 A molecular weight determination of arsenomethane by the 
 cryoscopic method gives a molecular formula of (CH 3 -As) 4 , 
 probably corresponding with the above configuration in which 
 the substance is represented as a polymerised form of arseno- 
 methane. This view of its constitution is supported by its 
 colour and other physical properties and by its chemical reactions. 
 
 In connexion with the reduction of methylarsinic acid to the 
 foregoing substances it appears probable from the experimental 
 evidence that this operation takes place in two distinct phases, - 
 
 2CH 3 -HSO(OH) 2 + 8H = CH 3 -As:As-CH 3 + 6H 2 0. 
 CH 3 -A 3 :A3-CH 3 + 4H = 2CH 3 -AsH 2 . 
 
 In aqueous solutions as in the preceding reduction the oily 
 arsenomethane separates and polymerises to red and brown 
 solid compounds. When alcohol is present the oily arseno- 
 methane remains dissolved and subjected to further action of 
 the reducing agent. This circumstance explains the utility of 
 alcohol in the preparation of primary arsines. 2 
 
 Erythmrsine. Cadet noticed that the fuming arsenical liquid 
 had at first a reddish-brown colour and contained a yellow 
 substance, but with the deposition of these coloured materials 
 it slowly became clear and assumed a light amber colour. 
 
 Bunsen isolated the red substance, to which he gave the name 
 
 1 Auger, Compt. rend., 1904, 138, 1705. 
 
 2 Dehn, Amer. Chem. /., 1905, 33, 120. 
 
 4 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 " Erytrarsin," 1 from among the decomposition products of 
 cacodyl or impure cacodyl oxide and chloride. He subjected 
 it to analysis, obtaining numbers corresponding with the formula 
 (CH 3 -As) 4 ,As 2 O 3 . This composition of the red substance was 
 confirmed by Dehn and Wilcox, who identified the two com- 
 ponents. These investigators also observed the formation of a 
 yellow substance as the first stage in the reduction of cacodyl 
 oxide to dimethylarsine. These differently coloured materials, 
 including the black polymeride 2 obtained as above, and also 
 by the action of heat on dimethylarsine, 3 represent successive 
 stages in the polymerisation of arsenomethane. 
 
 2. Ethyl Series. 
 (Ethylcacodyl Group, v. p. 17.) 
 
 Triethylarsine, As(C 2 H 5 ) 3 , liquid with unpleasant odour ; 
 fuming in the air and taking fire on warming, b.p. i4o/736 mm. 
 with slight decomposition, 01-151/16-7. Insoluble in water ; 
 no reducing action on aqueous silver solutions (difference from 
 ethylcacodyl). Combines additively with sulphur and the 
 halogens. Obtained, together with ethylcacodyl and tetra- 
 ethylarsonium iodide, by the action of ethyl iodide on sodium- 
 arsenic alloy. 4 Pure triethylarsine is prepared by distilling tetra- 
 ethylarsonium iodide with solid caustic potash. 5 Also obtained by 
 the interaction of arsenious chloride and zinc diethyl. 6 Vapour 
 density of triethylarsine, 5-2783 corresponding with above 
 formula. 
 
 Triethylarsine di-iodide, 1 As(C 2 H 6 ) 3 I 2 , yellow, flocculent precipi- 
 tate, m.p. 160, b.p. 190 ; produced by direct addition and by 
 the distillation of the double iodide, As(C 2 H 6 ) 4 I,AsI 3 . 
 
 Triethylarsine sulphide? As(C 2 H 5 ) 3 S, large prismatic crystals, 
 m.p. 119-5. Prepared by digesting triethylarsine in ethereal 
 solution with flowers of sulphur or by boiling triethylarsine oxide 
 with aqueous potassium pentasulphide. Also obtained by 
 heating ethylarsine disulphide at 195 and formed by the inter- 
 action of ethylarsine and carbon bisulphide at 120 in alcoholic 
 solution. 9 
 
 1 Annalen, 1842, 42, 41. a Anger, loc. cit. 
 
 3 Dehn, loc. cit. * Landolt, Annalen, 1854, 89, 332. 
 
 5 Cahours, Annalen, 1862, 112, 202. 
 
 6 Hofmann, Annalen, 1857, 103, 357. 
 
 7 8 Cahours, Compt. rend., 1859, 49, 87 ; 1860, 50, 1023. 
 
 9 Dehn, Amer. Chem. /., 1905, 33, 135; Landolt, loc. cit. 
 
 41 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Triethylarsine oxide, 1 As(C 2 H 5 ) 3 O, oily liquid insoluble in 
 water, produced by aerial oxidation of triethylarsine in ethereal 
 solution. Insoluble in dilute hydrochloric or sulphuric acid, 
 combining with nitric acid to form a nitrate which is also pro- 
 duced from triethylarsine and concentrated nitric acid (Di-42) . 
 
 Co-ordination Compounds of Triethylarsine.' 2 
 
 On adding triethylarsine drop by drop to platinic chloride 
 solution reduction to the platinous condition occurs and two 
 isomeric compounds (cis- and ^nms-bistriethylarsine dichloro- 
 platinum), PtCl 2 ,2As(C 2 H 5 ) 3 , are formed. These product s, which 
 in all probability are stereoisomerides, 
 
 (C 2 H 5 ) 3 As., XI (C 2 H 5 ) 3 As, /Cl 
 
 Vpt/ and *"Ptc 
 
 (C 2 H 5 ) 3 As /< \C1 Cl/ X As(C 2 H 5 ) 3 
 
 ^-modification . ^raws-modification . 
 
 are separated by extracting the mixture with ether. The 
 isomeride soluble in this medium separates in amber-yellow 
 crystals and from alcohol in sulphur - yellow prisms. The 
 isomeride, insoluble in ether, crystallises from alcohol in long 
 pale yellow prisms. 
 
 It has not yet been established which of these isomerides 
 has the cis- and which the ^raws-configuration. 
 
 The foregoing isomeric compounds of triethylarsine and 
 platinous chloride are analogues of the isomerides obtained by 
 the interaction of triethylphosphine and platinic chloride. By 
 the action of excess of triethylarsine on these isomerides tetrakis- 
 triethylarsine platinous chloride, [Pt,4As(C 2 H 5 ) 3 ]C1 2 , is produced, 
 to which, in accordance with Werner's co-ordination theory, 
 the following configuration is ascribed : 
 
 x As(C 2 H 6 ),n 
 >Pt< Cl a . 
 
 [ (C 2 H 5 ) 3 As/ x As(C 2 H 5 ) 3 J 
 
 Palladium dichloride and triethylarsine react to yield bis- 
 triethylarsine dichloropalladium, PdCl 2 ,2As(C 2 H 6 ) 3 , transparent, 
 reddish-yellow prisms. 
 
 The aurous compound, AuCl,As(C 2 H 6 ) 3 , is unstable and deposits 
 gold on raising the temperature. 
 
 1 Cahours, Compt. rend., 1859, 49, 87 ; 1860, 50, 1023. 
 
 2 Cahours and Gal, Compt. rend., 1870, 70, 897, 1380. 71, 208 ; 
 Zeitsch. fur Chem., 1870, 6, 662. 
 
 42 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 Quaternary Arsonium Compounds containing Ethyl. 
 
 Tetraethylarsonium iodide, 1 As(C 2 H 5 ) 4 I, colourless crystals 
 darkened on exposure ; readily soluble in water and alcohol, 
 insoluble in ether. Prepared by the direct combination of 
 triethylarsine and ethyl iodide and obtained as a rapidly 
 crystallising oil by boiling with aqueous caustic potash the 
 double iodides, 2 As(C 2 H 5 ) 4 I,AsI 3 ; 2As(C 2 H 5 ) 4 I, ZnI 2 ; 
 2As(C 2 H 5 ) 4 I, CdI 2 , produced by the synthetic processes from 
 arsenic and the zinc-arsenic and cadmium-arsenic alloys respect- 
 ively (v.'p. 22). 3 
 
 Tetraethylarsonium mercuri-iodide, 4 As(C 2 H 5 ) 4 I,HgI 2 , yellow 
 needles, m.p. 112, from alcoholic solutions of its components ,' 
 mercurichloride, white needles, m.p. 139 ; platinichloride and 
 aurichloride are yellow crystalline compounds, melting respect- 
 ively at 224 and 171. 
 
 Tetraethylarsonium hydroxide, As(C 2 H 5 ) 4 -OH, highly caustic 
 white deliquescent mass, absorbing carbon dioxide from the air, 
 liberating ammonia from ammonium salts and precipitating 
 hydroxides of heavy metals from their soluble salts. Prepared 
 by the action of moist silver oxide on the preceding iodide. 
 
 Tetraethylarsonium chloride, As(C 2 H 5 ) 4 Cl,4H 2 O, very deli- 
 quescent crystals obtained by evaporating down the solution 
 of the quaternary hydroxide in hydrochloric acid ; platinichloride, 
 sparingly soluble orange-yellow crystals ; 3As(C 2 H 5 ) 4 Cl,2BiCl 3 , 
 colourless. Bromide, As(C 2 H 5 ) 4 Br, deliquescent crystals ; 
 3As(C 2 H 5 ) 4 Br,2BiBr 3 , lemon yellow 5 ; 3As(C 2 H 5 ) 4 I,2BiI 3 , 
 lustrous, brick-red, hexagonal plates; periodide, As(C 2 H 6 ) 4 I 3 , 
 brown needles ; hydrogen sulphate, As(C 2 H 6 ) 4 -HSO 4 , granular 
 crystals easily soluble in water -or alcohol. 
 
 Methyldiethylarsine, As(C 2 H 5 ) 2 -CH 3 , liquid ; Dimethylethyl- 
 arsine, As(CH 3 ) 2 -C 2 H 8 , liquid. These mixed bases are obtained by 
 the action of zinc diethyl on methylarsenious di-iodide, As(CH 3 )I 2 , 
 and dimethylarsenious iodide, As(CH 3 ) 2 I, respectively. 
 
 Dimethyldiethylarsonium iodide, (CH 3 ) 2 As(C 2 H 6 ) 2 I, colourless 
 prisms, obtained readily by the action of ethyl iodide on cacodyl. 
 As 2 (CH 3 ) 4 + 2C 2 H 5 I - (CH 3 )2 2 As(C 2 H 5 ) 2 I + As(CH 3 ) 2 I. * 
 
 1 Landolt, Annalen, 1854, 89, 331 ; 92, 364. 
 
 2 Cahours and Riche, Compt. rend,, 1854, 39, 541. 
 
 3 Cahours, Compt. rend., 1859, 49, 87. 
 
 4 Mannheim, Annalen, 1905, 341, 198. 
 
 5 Jorgensen, /. pr. Chem., 1871, [ii], 3, 336. 
 
 6 Cahours and Riche, Compt. rend., 1854, 39, 541. 
 
 43 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Ethyl bromide reacts similarly but more slowly. 
 
 Dimethyldiethylarsonium bromide 1 and chloride, very deli- 
 quescent needles ; periodide, (CH 3 ) 2 As(C 2 H 5 ) 2 l3, brown needles, 
 metallic lustre ; sulphate, [(CH 3 ) 2 As(C 2 H 5 )2] 2 SO4, octahedra, 
 soluble in water or alcohol ; nitrate, deliquescent granules ; 
 platinichloride, orange-red needles. 
 
 Triethylbromoethylarsonium bromide, 2 CH 2 Br-CH 2 'As(C 2 H 6 ) 3 Br, 
 rhombic dodecahedra, extremely soluble in water, sparingly so 
 in cold alcohol. This bromide is produced by the interaction 
 of triethylarsine and a large excess of ethylene bromide in sealed 
 tubes below 50. When treated successively with silver chloride 
 and platinic chloride it furnishes the platinichloride, 
 (C 2 H 4 Br-As(C 2 H 5 ) 3 Cl) 2 PtCl 4 ; 
 
 sparingly soluble needles. 
 
 Vinyltriethylarsonium hydroxide, CH 2 :CH-As(C 2 H 5 ) 3 -OH, ob- 
 tained readily from the preceding bromide by the action of excess 
 of moist silver oxide ; platinichloride, (C 8 H 18 AsCl) 2 PtCl 4 , moder- 
 ately soluble octahedra ; aurichloride, C 8 H 18 AsCl,AuCl 3 , 
 sparingly soluble, yellow crystals. 
 
 Trimethylethylarsonium iodide, well-defined, glistening needles, 
 softens at 300 and sinters at 320, soluble in water, chloroform, 
 or hot alcohol ; prepared by mixing ethylarsine and methyl iodide, 
 
 C 2 H 5 -AsH 2 + 3CH 3 I = C 2 H 5 As(CH 3 ) 3 I + 2HI. 
 
 Primary and Secondary Ethylarsenicals. 
 
 Ethylarsenious dichloride, As(C 2 H 5 )Cl 2 , liquid with faint fruity 
 odour ; b.p. 156. Prepared by the interaction of arsenious 
 chloride and mercury diethyl, 
 
 AsCl 3 + Hg(C 2 H 6 ) 2 - As(C 2 H 5 )Cl 2 + C.H.-HgCl. 
 Miscible in all proportions with ether, alcohol, or benzene, 
 very soluble in water. Extremely irritating action on the mucous 
 membrane of eyes and nose, leaving painful blisters on the skin. 8 
 
 Ethylarsenious di-iodide, As(C 2 H 5 )I 2 , obtained by the interaction 
 of diethylarsenious iodide and iodine, 4 
 
 As(C 2 H 5 ) 2 I + I 2 = As(C 2 H 5 )-I 2 + C 2 H B I. 
 
 Ethylarsinic acid, C 2 H 5 -AsO(OH) 2 , crystals from alcohol. 
 Prepared by treating the preceding iodide with excess of silver 
 
 1 Cahours and Riche, loc. cit. 2 Hofmann, Annalen, 1861, Spl. i, 313. 
 
 3 La Coste, Annalen, 1881, 208, 33. 
 
 4 Cahours, Compt. vend., 1860, 50, 1023. 
 
 44 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 oxide or by warming ethylarsenious chloride with moderately 
 concentrated nitric acid. 1 
 
 Also isolated in the form of its magnesium salt, 
 
 CH 3 -AsO 3 Mg,H 2 0, 2 
 
 by the interaction of ethyl iodide and aqueous potassium 
 arsenite. Arsenious oxide (318 grams), caustic potash (540 grams), 
 dissolved in water made up to 3 litres and mixed with ethyl 
 iodide (500 grams) and sufficient alcohol to render the solution 
 homogeneous when the reaction is complete after a few hours. 
 The spirit is distilled off, the residual aqueous solution acidified 
 with hydrochloric acid when the compound As 4 O 6 ,KI 3 is precipi- 
 tated. The nitrate is treated with chlorine in sufficient amount 
 to set free the remaining iodine and the final filtrate rendered 
 ammoniacal and treated with magnesia mixture in excess. 
 After 24 hours the precipitate of magnesium ammonium 
 arsenate is collected and the nitrate boiled. As the ammonia 
 evaporates small, globular masses of magnesium ethylarsinate 
 separate, the yield being about 40-50 per cent. 
 
 Potassium ethylarsinate, soluble in alcohol ; magnesium salt, 
 sparingly soluble in water or alkaline solutions, readily so 
 in acids; silver salt, yellowish-white, nacreous scales. 
 
 Ethylarsinic disulphide, C 2 H 6 -AsS 2 , 4 light yellow, viscid oil 
 with disagreeable odour; 01-836/24; insoluble in water, 
 alcohol, or ether. Soluble in chloroform, benzene, or carbon 
 bisulphide, very soluble in alkalis or alkali sulphides, precipitated 
 therefrom by acids. 
 
 Diethylarsine, (C 2 H 5 ) 2 AsH, not definitely isolated. 
 
 Diethylarsine appears to result from the action of certain 
 moulds, and it is probably owing to the formation of this arsine 
 that poisoning cases have been noticed in rooms furnished with 
 carpets or wall papers containing arsenic. This reaction is of 
 special interest as being the nearest approach to a natural 
 synthesis of an organic arsenical compound which has hitherto 
 been noticed. 
 
 Production of Volatile Arsenical Compounds by Moulds. 
 
 Various species of moulds (mucor and penicillium) , and especially 
 
 the so-called arsenical mould, Penicillium brevicaule, when 
 
 cultivated in a medium containing sodium arsenite evolve a 
 
 gas containing volatile poisonous arsenical compounds. In 
 
 1 La Coste, Annalen, 1881, 208, 34. 
 
 2 Dehn,Amer. Chem. /., 1905, 33, 132 ; /. Amer. Chem. Soc., 1906, 28, 347. 
 
 3 Riidorff, Ber., 1886, 19, 2668. 4 Dehn, loc. oil. 
 
 45 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 this way small quantities of the inorganic arsenic compound 
 become completely volatilised so that the non-volatile residue 
 is completely free from arsenic. 
 
 This phenomenon has been noted by several observers, who 
 have not, however, identified the volatile arsenic compound. 1 
 
 This gas has been more closely examined by P. Biginelli, 
 who passed it into a hydrochloric solution of mercuric chloride 
 when colourless, tabular, triclinic crystals separated, having 
 the composition AsH(C 2 H 5 ) 2 ,2HgCl 2 , or possibly the double 
 formula AsH(C 2 H 6 ),:AsH(C 2 H 5 ) 2 ,4HgCl 2 . This substance 
 sinters at 239-240 and decomposes at 255-256. With boiling 
 water this crystalline product dissolves and the solution on cooling 
 deposits (i) a small quantity of a compound decomposing at 
 250-251, (2) a substance of the composition 
 
 AsH(C 2 H 5 ) 2 
 
 0< | , 4 HgCl 2 , 
 
 \\sH(C 2 H 5 ) 2 
 
 which separates in shining scales, sintering at 270, but not 
 completely fused at 290. When treated successively with 
 concentrated aqueous caustic potash and with an ethereal 
 solution of iodine the mercurichloride furnishes the iodide, 
 
 x AsH(C 2 H 5 ) 2 I 
 O<f , m. p. 102, which with silver sulphate gives 
 
 \AsH(C 2 H 5 ) 2 I 
 
 the sulphate, (C4H n OAs) 2 SO 4 , m. p. 210. Moist silver oxide on 
 the iodide gives deliquescent needles of the dioxide, 
 
 /\ 
 
 AsH(C 2 H 5 ) 2 < >AsH(C 2 H 5 ) 2 . 
 
 \(X 
 
 Nitric acid and alkaline permanganate lead successively to the 
 
 compound, O[AsH(C 2 H 5 ) 2 -OH] 2 , KNO 3 , 
 
 hygroscopic, acicular prisms, m.p. 129-131, exploding at higher 
 
 temperatures. 
 
 When the arsenical gas evolved by P. brevicaule is passed into 
 mercuric nitrate solution, an insoluble, infusible, yellow powder, 
 AsH(C 2 H 5 ) 2 ,2Hg-NO 3 , is precipitated. 
 
 Although in these experiments the arsenical gas itself 
 was not isolated and identified, Biginelli concludes that 
 the production of the foregoing solid compounds is evidence 
 
 1 Maspmann, Pharm. Zentr.-h., 41, 666, and Chem. Centr., 1900, ii, 
 1187. Valeric and Strzyzowski, Pharm. Post., 33, 637 and 649; Chem. 
 Centr., 1901, i, 63. Emmerling, Ber., 1896, 29, 2728 ; 1897, 30, 1026. 
 Gorio, Ber., 1897, 30, 1024. . 
 
 4 6 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 that the gas developed by wall papers to which poisoning is due 
 is diethylarsine. 1 The question would be settled by the pre- 
 paration and isolation of diethylarsine from diethylarsinic acid 
 or some other derivative of the ethylcacodyl series, an operation 
 which is quite practicable by Palmer and Dehn's general method 
 (pp. 37 and 39). 
 
 Ethylarsine^ C 2 H 5 -AsH 2 , liquid, b.p. 36, 01-217/22, 
 obtained by the reduction of ethylarsinic acid and its salts with 
 amalgamated zinc dust and alcoholic hydrochloric acid ; odour 
 resembling cacodyl, very poisonous, almost devoid of basic 
 properties. 3 A freezing mixture of salt and ice can be employed 
 in the condensation of this arsine. The yield is quantitative, 
 although the amount condensed is only about 60 per cent. Its 
 solubility in water is 126 parts in 1,000,000 at 19. This arsine 
 is very poisonous ; a rat breathing a little of the vapour died 
 almost immediately. Its slow oxidation product with air is light 
 yellow. When the vapour of etl^larsiiie absorbs dry air the 
 reaction is mainly as follows : 
 
 C 2 H 6 AsH 2 + O 2 = C 2 H 5 AsO + H 2 O. 
 
 Silver nitrate oxidises this arsine to ethylarsinic acid ; con- 
 centrated nitric acid produces this acid together with acetic and 
 arsenic acids. 
 
 Arsenoethane* (Ethylarsenic), (C 2 H 5 -As:As-C 2 H 6 ) 2 , yellow oil 
 easily polymerising into solid forms. 
 
 Bromine and iodine interact with ethylarsine in accordance 
 with the following equation : 
 
 C 2 H 5 AsH 2 + X 2 = C 2 H 5 AsX 2 + H 2 . 
 Sulphur reacts to form the monosulphide, 
 
 C 2 H 5 AsH 2 + 2S = C 2 H 5 AsS + H 2 S. 
 
 Mercuric chloride and iodide and stannic chloride convert 
 ethylarsine into ethylarsenious chloride, C 2 H 5 -AsCl 2 , the other 
 products being mercury, mercurous iodide, andstannous chloride. 
 
 Arsenious chloride produces a more complex change, for in 
 addition to ethylarsenious chloride a yellow solid is produced 
 which changes to a curdy, brick-red solid which may contain 
 (C 2 H 5 -As) 4 and arsenic, or, conceivably, a more complex con- 
 densation product, C 2 H 5 -As(As:As-C 2 H 5 ) 2 . 
 
 1 P. Biginelli, Atti. R. Accad, Lincei, 1900, [v], 9, ii, 210, 242. 
 
 2 Palmer and Dehn, Ber., 1901, 34, 3594. 
 
 3 Dehn, Amer. Chem. J ., 1905, 33, 143. 
 
 4 Auger, Compt. rend,, 1904, 138, 1705. 
 
 47 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Antimony trichloride reacts similarly with ethylarsine, giving 
 a reddish-brown solid which slowly assumes a jet black colour. 
 On drying, this black product takes fire spontaneously. 
 
 3. Propyl Series. 
 
 Tetra-n-propylarsonium iodide* As(C 3 H 7 ) 4 I, is obtained in 
 the form of the double iodide, As(C 3 H 7 ) 4 I,AsI 3 , on heating 
 arsenic and w-propyl iodide together at 180 ; the quaternary 
 iodide forms colourless needles decomposing at 150. 
 
 Tri-n-propylarsine, 2 As(C 3 H 7 ) 3 , is prepared by distilling the 
 foregoing double iodide with dry caustic potash. 
 
 This tertiary arsine, oil, b.p. 167790 mm. and 158773 mm. 
 is obtained together with primary and secondary w-propyl arsen- 
 ious chlorides, by condensing w-propyl chloride and arsenious 
 chloride with sodium in ether. 
 
 Tetra - n - propylarsonium mercuri - iodide? As (C 3 H 7 ) 4 I , HgI 2 , 
 needles, m.p. 120. The mercurichloride forms colourless 
 needles, m.p, 169, the platini chloride, m.p. 189, and aurichloride, 
 m.p. 127, are all obtained from tetra-w-propylarsonium hydr- 
 oxide. 
 
 Tetraisopropylarsonium iodide, As(C 3 H 7 ) 4 I, colourless needles 
 darkening at 150, prepared by heating finely powdered arsenic 
 with isopropyl iodide at 100180 for 24-30 hours. The double 
 arseno-iodide is decomposed by caustic alkali leaving the quater- 
 nary salt. The mercuri-iodide, yellow needles, m.p. 114 is 
 obtained from its components in alcoholic solution. From aqueous 
 solutions of tetra^sopropylarsonium hydroxide the following 
 characteristic salts are obtainable: mercurichloride, m.p. 171, 
 platinichloride, decomposing at 211, and aurichloride, m.p. 
 186-188. 
 
 Tri-n-propylethylarsonium iodide* (C 3 H 7 ) 3 As(C 2 H 5 )I, m.p. 230- 
 237, results from the action of w-propyl iodide on ethylarsine 
 at 110. 
 
 Trusopropylethylarsonium iodide is similarly prepared ; it 
 decomposes at its melting point. 
 
 n-Propylarsine, C 3 H 7 -AsH a , volatile liquid produced by 
 reducing w-propylarsinic acid with amalgamated zinc dust 
 and hydrochloric acid according to Palmer and Demi's method. 
 
 n-Propylarsinic acid, 5 CH 3 -CH 2 'CH 2 -AsO 3 H 2 , colourless, 
 
 1 Cahours, Jahresber., 1873, 519. 2 Dehn, Amer. Chem. ]., 40, 119. 
 
 3 Mannheim, Annalen, 1905, 341, 200. 4 Amer. Chem. J., 1908, 40, 113. 
 6 Dehn and McGrath, /. Amer. Chem. Soc., 1906, 28, 352. 
 
 4 8 
 
ALIPHATIC ARSENIC ALS AND ANTIMONIALS 
 
 "~^x, 
 
 acicular crystals, is obtained by adding sulphuric acid in the cold 
 to its magnesium salt and then extracting with alcohol. It is 
 insoluble in ether, but very soluble in water ; a saturated solution 
 (100 parts) at 26 contains 43 parts of the acid. The disulphide, 
 C 3 H 7 AsS 2 , a viscid oil, is precipitated from acid solutions of the 
 acid by sulphuretted hydrogen. 
 
 Magnesium n-propylarsinate, C 3 H 7 -AsO 3 Mg,JH 2 or 
 
 [C 3 H 7 .As(OH)(0 2 Mg)] 2 0, 
 
 in the form of pearly white, soapy crystals, is the product of the 
 following reaction. Arsenious oxide (275 grams, i mol.) and 
 caustic potash (460 grams, 6 mols.) are dissolved together in 
 concentrated aqueous solution. Alcohol and propyl iodide (460 
 grams, 2 mols.) are added, and the mixture shaken, after adding 
 sufficient water or alcohol or both of the solvents to produce a 
 homogeneous solution. The following reactions take place : 
 As(OK) 3 + C 3 H 7 I = C 3 H 7 -AsO(OK) 2 + KI 
 C 2 H 5 OK + C 3 H 7 I = C 2 H 5 -OC 3 H 7 + KI. 
 
 After several days the alcohol and ether are distilled off, 
 hydrochloric acid is added till a precipitate appears, chlorine 
 is introduced until all the iodine is precipitated, and the nitrate 
 treated with magnesia mixture to remove arsenate. The nitrate 
 from magnesium ammonium arsenate, when boiled with more 
 magnesia mixture, forms magnesium w-propylarsinate, the yield 
 being 42 per cent. 
 
 Di-n-propylarsinic acid, lustrous leaflets or needles; m.p. 120. 1 
 
 4. Allyl Series. 
 
 Tetrallylarsonium mercuri-iodide, 2 As(C 3 H 6 ) 4 I,HgI 2 , m.p. 74, 
 is produced by warming allyl iodide and mercuric arsenide on the 
 water-bath. 
 
 Dimethylallylarsine, (CH 3 ) 2 -As-C 3 H 5 ; b.p. 160, obtained from 
 dimethylarsine and allyl iodide. 3 
 
 5. Butyl Series. 
 
 Tetm-n-butylarsonium iodide, 4 colourless needles decomposing 
 at 145-150. The quaternary hydroxide yields the character- 
 istic salts : mercuri-iodide, yellow needles, m.p. 109 ; plalini- 
 
 1 Partheil, Arch. Pharm., 1899, 237, 134. 
 
 2 Mannheim, Annalen, 1905, 341, 223. 
 
 3 Dehn and Wilcox Amer. Chem. /., 1906. 35, 20. 
 
 4 Mannheim, Annalen, 1905, 341, 204. 
 
 49 E 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 chloride, yellowish-red crystals darkening at 145, decomposing 
 at 220; auri chloride, sparingly soluble needles, m.p. 131. 
 
 6. Amy I Series. 
 
 Dimeihyldiisoamylarsonium iodide, As(CH 5 ) z (C 5 H n ) 2 l, leaflets, 
 obtained by the interaction of cacodyl and ^soamyl iodide at iSo . 1 
 
 As 2 (CH 3 ) 4 + 2C 5 H U I = A(CH 3 ) 2 (C 5 H U ) 2 I + As(CH,) a I. 
 Ethyltriisoamylarsonium iodide,* C 2 H 5 As(C5H 11 )3l, compact 
 crystals not melting below 250, prepared by mixing ethylarsine 
 with excess of ^soamyl iodide and heating for eight hours at 140. 
 
 Synthesis of Secondary Aliphatic Derivatives of Arsenic. 
 
 An important extension in the synthesis of aliphatic arsenicals 
 was first made in this series by Dehn and Wilcox 3 in 1906. 
 
 Before this date there was no ready means of obtaining 
 secondary aliphatic arsenic compounds. 
 
 Cadet's reaction still remains unique and restricted to the 
 methyl series. The action of alkyl iodides on sodium arsenide 
 is a more general reaction, but it gives rise to a mixture of pro- 
 ducts which are separated only with difficulty. A more promis- 
 ing process was discovered by Michaelis and Paetow (p. 114), 
 who found that when benzyl chloride (2 mols.) and arsenious 
 chloride (i mol.) are condensed by means of sodium the secondary 
 arsine derivative was the predominant product. Dehn and 
 Wilcox applied this reaction to the aliphatic series and found 
 that in the case of ^soamyl chloride the main product was 
 diisoamylarsine chloride, or its basic chloride, 
 
 6(C 5 H 11 ) 2 AsCl,[(C 5 H 11 ) 2 As]0. 
 
 Other alkyl halides, such as ethyl bromide and propyl iodide, 
 behave similarly. 
 
 Basic Diisoamylarsine chloride, 6(C 5 H 11 ) 2 AsCl,[(C 5 H 11 ) 2 As] 2 O, 
 colourless oil, b.p. 2637750 mm. and 148733 mm., is produced by 
 adding slowly a mixture of isoamyl chloride (148 grams = 2 
 mols.) and arsenious 'chloride (124 grams = i mol.) to 60 grams 
 of sodium wire (4 atoms) in 400-500 c.c. of dry ether in an 
 atmosphere of carbon dioxide. The reaction, which is very 
 violent, is complete in two hours. The filtered solution is frac- 
 tionated. A white, soapy solid, which separates during frac- 
 tionation, is probably dusoamylarsenious oxide. The red by- 
 
 1 Cahours and Riche, Compt. rend., 1854, 39, 541. 
 
 2 Amer. Chem. ]., 1905, 33, 146. 3 Amer. Chem. J., 1906, 35, 48. 
 
 50 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 * 
 
 product, which is invariably formed during the condensation in 
 quantities varying from 20 to 40 grams, is probably similar to 
 Bunsen's erythrarsine, for when treated with bromine followed 
 by ammonia it dissolves to form the ammonium salts of arsenious, 
 isoamylarsinic, and dh'soamylarsinic acids. The chloride is 
 insoluble in water but soluble in the ordinary organic media. 
 
 Diisoamylarsine chlorodibromide, (C 5 H n ) 2 AsClBr 2 , white, crys- 
 talline solid, m.p. 124-125, with an odour of chloral hydrate, 
 is produced by adding bromine to an ethereal solution of the 
 foregoing chloride. 
 
 Diisoamylarsine sulphide, [(C 6 H u )2As] 2 S, white needles, m.p. 
 29-30, insoluble in water but dissolving in ether, carbon bi- 
 sulphide, or alcohol, is prepared by passing sulphuretted hydrogen 
 into the chloride suspended in water. 
 
 Diisoamylarsinic acid, (C 6 H n ) 2 AsO-OH, large, flaky crystals, 
 m.p. 153-154. It is easily soluble in alcohol, less so in water, 
 but insoluble in ether. It is prepared in accordance with the 
 following equation : 
 
 (C 5 H u ) a AsCl + Br 2 -f 2H 2 = (C 6 H u ) 2 AsO-OH + HC1 + 2HBr. 
 The oily chloride changes to a yellow, crystalline solid, soluble in 
 ammonia. Magnesia mixture added to this solution precipitates 
 arsenious acid, the nitrate on boiling deposits magnesium iso- 
 amylarsinate (formed from ^soamylarsenious dichloride, 
 C 5 H n AsCl 2 ), and the final mother liquor made slightly acid 
 yields dmoamylarsinic acid. 
 
 Diisoamylarsine, (C 5 H n ) 2 AsH, oil, b.p. 150799 mm., is pre- 
 pared by reducing dusoamylarsinic acid with amalgamated 
 zinc dust and concentrated hydrochloric acid in the presence of 
 ether. This arsine has a characteristic odour more suggestive 
 of fc'soamyl alcohol than of arsi'ne. 
 
 fc'soAmylarsinic acid, 1 C 5 H u AsO(OH) 2 , pearly white crystals, 
 m.p. 194 : 100 c.c. of saturated aqueous solution at 28 con- 
 tains 0-82 gram; the same volume of saturated alcohol contains 
 2-2 grams ; it is insoluble in ether. The preparation is quite 
 similar to that of propylarsinic acid, potassium arsenite, K 3 AsO 3 , 
 and fc'soamyl iodide being used in molecular proportions. After 
 two or three days, the alcohol is removed by distillation, the solu- 
 tion carefully neutralised with hydrochloric acid, the double com- 
 pound, As 2 O 3 ,2Kl, collected, and the filtrate acidified, when iso- 
 amylarsinic acid separates slowly as a mass of scaly crystals. 
 isoAmylarsine disulphide, C 5 H n -AsS 2 , is a viscid, light yellow oil. 
 1 Dehn and McGrath, /. Amer. Chem. Soc., 1906, 28, 354. 
 51 E 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 7. Polyar sines. 1 
 
 The tertiary alkylarsines behave as unsaturated compounds 
 towards ethylene dibromide, one or two molecular proportions 
 of the arsine combining additively with this alkylene halide. 
 Hofmann, who discovered this reaction, was thus led to isolate 
 complex arsenical bromides containing one or two atoms of 
 arsenic. (Triethylbromoethylarsonium bromide I, v. p. 44.) 
 
 CH 2 Br-CH 8 -As(C 2 H 6 ) 8 Br I. 
 CH 8 -As(C 5 H 5 ) 3 -Br 
 
 CH 2 -As(C 5 H 5 ) 3 -Br 
 
 II. 
 
 Ethylenehexaethyldiarsonium dibromide? produced by the 
 second of the preceding reactions at 150, yields on debromination 
 with moist silver oxide a highly caustic solution of the diarsonium 
 hydroxide, C 2 H 4 [As(C 2 H 5 ) 3 -OH] 2 . The salts of this diacidic 
 base, especially the iodide, are remarkably crystalline, the 
 platinichloride, C 2 H 4 [As(C 2 H 6 ) 3 -Cl] 2 PtCl 4 , pale yellow, crystalline 
 precipitate; the aurichhride, C 2 H 4 [As(C 2 H 6 ) 3 Cl] 2 ,2AuCl 3 , lustrous 
 yellow leaflets from boiling hydrochloric acid. 
 
 8. Mixed Arsenical Bases. 1 
 Ethylenetriethylarsammonium dibromide, 
 CH 2 -As(C 2 H 6 ) 3 Br , 
 CH 2 -NH 2 HBr 
 
 is produced by the action of ammonia on bromoethyltriethyl- 
 arsonium bromide ; it forms a sparingly soluble platinichloride, 
 C 8 H 22 AsNPtCl 6 , 3 and an aurichloride C 8 H 22 AsNAu 2 Cl 8 , lustrous 
 yellow leaflets ; these salts crystallise from boiling hydro- 
 chloric acid. 
 
 Ethylenehexaethylphospharsonium dibromide, 
 
 CH 2 -P(C a H 5 ) 3 Br 
 CH 2 -As(C 2 H 5 ) 3 Br ' 
 
 obtained by the action of triethylarsine on bromoethyltriethyl- 
 phosphonium bromide, yields a platinichloride crystallising in 
 
 1 Cf. Hofmann, Phil. Trans., 1860, 150, 518. 
 
 2 Hofmann, Annalen, 1861, Spl. i, 316. 3 Hofmann, loc. cit., 306. 
 
 52 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 orange-red triclinic prisms. 1 The diquaternary base is decomposed 
 by boiling water, 
 
 HO-(C 2 H 5 ) 3 As-C 2 H 4 -P(C 2 H 6 ) 3 -OH = 
 
 As(C 2 H 6 ) 3 +C 2 H 6 -OP(C 2 H 5 ) ,-OH. 
 
 Section III. Aliphatic Antimony Compounds. 
 i. Methyl Series. 
 
 Trimethylstibine? Sb(CH 3 ) 3 , colourless liquid with odour of 
 onions, b.p. 80-6, 01-523/15 ; slightly soluble in water or 
 alcohol, more soluble in ether. Takes fire in chlorine, oxidised 
 easily in the air, spontaneously inflammable when in large 
 quantities. Combines additively with sulphur and the halogens 
 and reduces gold, mercury, and silver from aqueous solutions of 
 their salts. An alloy of antimony and sodium (i part Na -f- 
 4 parts Sb) mixed with an equal volume of sand to reduce its 
 inflammability is moistened with methyl iodide. After the 
 vigorous reaction has subsided the product is distilled, and tri- 
 methylstibine and methyl iodide pass over and recombine 
 in the receiver forming tetramethylstibonium iodide. The dried 
 quaternary iodide is distilled with an alloy of antimony and 
 potassium in a current of carbon dioxide, when pure trimethyl- 
 stibine is obtained. 
 
 Trimethylstibine oxide, Sb(CH 3 ) 3 O, obtained from the sulphate 
 Sb(CH 3 ) 3 SO 4 by the action of barium hydroxide; crystalline 
 mass easily soluble in water, reacts with hydrogen sulphide 
 and acids, but not with carbon dioxide. 
 
 Trimethylstibine dichloride, Sb(CH 3 ) 3 Cl 2 , hexagonal crystals, 
 sparingly soluble in cold water ; made by direct addition of 
 chlorine to trimethylarsine and by the interaction of antimony 
 trichloride and mercury dimethyl. 
 
 SbCl 3 +2Hg(CH 3 ) a =Sb(CH 3 ) 3 Cl a +Hg(CH 3 )-Cl+Hg. 
 
 Trimethylstibine di-iodide,^ Sb(CH 3 ) 3 I 2 , hexagonal prisms 
 produced by heating antimony with methyl iodide at 140. 
 The dibromide, Sb(CH 3 ) 3 Br 2 , is produced by direct addition of 
 bromine to trimethylstibine. The three dihalides each combine 
 with the oxide, giving compounds Sb(CH 3 ) 3 Hal 2 , Sb(CH 3 ) 3 O, 
 crystallising in octahedra ; the oxy-iodide has a yellow tint. 
 
 1 Hofmann, loc. cit., 318. 
 
 2 Landolt, Annalen, 1851, 78, 91 ; Jahresber., 1861, 569. 
 * Buckton, Quart. J. Chem. Soc., 1860, 13, 120. 
 
 53 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The nitrate, Sb(CH 8 ) 3 (NO 2 ) 2 and sulphate, Sb(CH 3 ) 3 S0 4 , are 
 crystalline and readily soluble in water. 
 
 The sulphides, Sb(CH 3 ) 3 S, scales, sparingly soluble in water, and 
 SSb(CH 3 ) 2 -S-Sb(CH 3 ) 2 -S, yellow, insoluble in water, are produced 
 on passing hydrogen sulphide through an ethereal solution of 
 t rimethylstibine . 
 
 Tetramethylstibonium iodide, 1 Sb(CH 3 ) 4 I, hexagonal plates, 
 soluble in 3-3 parts of water at 23 : produced by direct combina- 
 tion of trimethylstibine and methyl iodide, easily soluble in 
 alcohol, less so in ether ; saline taste, bitter after-taste. 
 
 Tetramethylstibonium hydroxide, Sb(CH 3 ) 4 -OH, prepared by 
 the action of moist silver oxide on the foregoing iodide. A 
 deliquescent, crystalline mass, slippery to the touch, closely 
 resembling caustic potash. It withdraws moisture and carbon 
 dioxide from the atmosphere, fumes with hydrochloric acid, 
 sublimes to a partial extent without decomposition, neutralises 
 the strongest acids ; it precipitates the metallic hydroxides, 
 including barium hydroxide, from aqueous solutions of their 
 salts; Tetramethylstibonium salts are crystalline and devoid of 
 emetic action. 
 
 Zinc hydroxide, when precipitated from solutions of zinc salts 
 by tetramethylstibonium hydroxide, is redissolved by excess 
 of the antimonial base. Copper hydroxide is insoluble in excess 
 of this precipitant. 
 
 Tetramethylstibonium chloride, Sb(CH 3 ) 4 Cl, prepared by 
 evaporating down the iodide with hydrochloric acid or by 
 treating the hydroxide with this acid ; also from the iodide 
 by double decomposition with mercuric chloride ; white, 
 deliquescent, hexagonal crystals easily soluble in water or alcohol, 
 insoluble in ether: platinichloride, [Sb(CH 3 ) 4 ] 2 PtQ 6 , orange- 
 yellow crystals, very slightly soluble in water. The nitrate, 
 Sb(CH 3 ) 4 ,NO 2 , the sulphate, [Sb(CH 3 ) 4 ] 2 SO 4 ,5H 2 O, m.p. 150, 
 and the hydrogen sulphate, Sb(CH 3 ) 4 -HSO 4 , are all crystalline 
 and very soluble in water. The hydrogen carbonate, Sb(CH 3 ) 4 -HCO 3 , 
 forms stellate aggregates of needles, and gives no precipitate 
 with neutral magnesium salts. 
 
 2. Ethyl Series. 
 
 Triethylstibine, Sb(C 2 H 6 ) 3 , colourless liquid with odour of 
 onions ; b.p. below 75/i6-i8 mm., 158-5/730 mm, ; D 
 
 1 Landolt, Annalen, 1852, 84, 44. 
 
 54 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 1-3244/16. Takes fire in air and burns with a white flame. 
 The liquid is insoluble in water, but miscible with ether and 
 alcohol ; its vapour density corresponds with the simple molecular 
 formula. Obtained by the action of ethyl iodide on an alloy of 
 antimony and potassium, 1 or by the interaction of antimony 
 trichloride and zinc diethyl 2 or mercury diethyl. 3 
 
 Triethylstibine is conveniently prepared by distilling tri- 
 ethylstibine di-iodide with zinc. 4 With fuming hydrochloric 
 acid the converse change occurs ; triethylstibine decomposing 
 this acid to form triethylstibine dichloride and free hydrogen. 
 
 Triethylstibine oxide, Sb(C 2 H 5 ) 3 O, is not easily obtained pure 
 by the aerial oxidation of triethylstibine because of the simul- 
 taneous formation of ethylstibinic acid. It is preferably prepared 
 by shaking an alcoholic solution of triethylstibine with finely 
 divided mercuric oxide ; mercury is set free and the organic oxide 
 results. The latter can be purified through its sulphate or 
 nitrate. The former salt (v. infra) dissolved in water is treated 
 with barium hydroxide, the barium sulphate removed, and the 
 filtrate evaporated to dryness on the water-bath. The residue 
 is taken up with alcohol and saturated with carbon dioxide 
 to remove barium as barium carbonate, and the final alcoholic 
 filtrate evaporated. 
 
 Triethylstibine oxide is thus obtained as a colourless, trans- 
 parent, viscid, non-volatile mass devoid of crystalline character. 
 After several days over concentrated sulphuric acid it becomes 
 moderately hard, but softens again on the water-bath. It is 
 easily soluble in water or alcohol, less so in ether. Its taste is 
 bitter, like quinine, and when taken internally it has no emetic 
 action and is not markedly poisonous. It couples directly with 
 mineral acids forming salts and precipitates metallic hydroxides 
 from solutions of their salts. Triethylstibine, which possesses 
 to a remarkable degree the chemical properties of a bivalent 
 metallic radical ; it combines directly with oxygen, sulphur, and 
 the halogens. 
 
 Triethylstibine dichloride, Sb(C 2 H 6 ) 3 C1 2 , a colourless, highly 
 refractive liquid, not solidified at 12. 01-540/17 ; 
 insoluble in water, soluble in alcohol or ether. It has a terpenoid 
 odour and bitter taste. Prepared by (i) direct combination of 
 
 1 Lowig and Schweitzer, Annalen, 1850, 75, 315. 
 
 2 Hofmann, Annalen, 1857, 103, 357. 
 
 3 Buckton, Quart. J. Chem. Soc., 1863, 13, 118. 
 
 4 Buckton, loc, cit., 116. 
 
 55 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 triethylstibine and chlorine : this reaction is very violent and, 
 unless controlled, leads to inflammation ; (2) triethylstibine and 
 hydrochloric acid; (3), the preferable method, by evaporating 
 down the crystalline nitrate, Sb(C 2 H 6 ) 3 (NO 3 ) 2 , with strong hydro- 
 chloric acid. 
 
 Triethylstibine dibromide, Sb(C 2 H 5 ) 3 Br 2 ; the foregoing methods 
 are available, the preferable process being to mix cooled alcoholic 
 solutions of triethylstibine and bromine. A colourless, trans- 
 parent, highly refractive liquid, solidifying at 10 to snow- 
 white crystals. Insoluble in water, easily soluble in ether or 
 alcohol. Unpleasant terpenoid odour ; on warming the liquid, 
 it becomes increasingly tear-exciting and causes vigorous sneezing. 
 
 Triethylstibine di-iodide, Sb(C 2 H 5 ) 3 I 2 , colourless, acicular crystals, 
 m.p. 70-5, subliming at 100. Prepared (i) by adding iodine 
 to an alcoholic solution of triethylstibine and purified by succes- 
 sive crystallisation from alcohol and ether ; (2) by heating 
 antimony with ethyl iodide at I4O . 1 
 
 These foregoing triethylstibine halides present many analogies 
 with the metallic halides. They are decomposed by strong 
 sulphuric acid with liberation of the corresponding halogen 
 hydride and formation of triethylstibine sulphate. The iodide 
 when treated with ammonia or with a molecular proportion of tri- 
 ethylstibine oxide furnishes an oxyiodide, Sb(C 2 H 5 ) 3 I 2 ,Sb(C 2 H 6 ) 3 O, 
 tetrahedral or octahedral crystals ; with mercuric chloride and 
 silver nitrate and sulphate this oxysalt gives rise respectively 
 to an oxychloride, oxynitrate, and oxysulphate. 2 
 
 Triethylstibine sulphide, Sb(C 2 H 6 ) 3 S, white, crystalline mass 
 with silvery lustre and faintly unpleasant odour recalling mer- 
 captan ; bitter taste ; soluble in water, alcohol, or hot ether, melts 
 at 100 to a colourless liquid. Preparation (i) action of hydrogen 
 sulphide on triethystibine oxide ; (2) direct combination of sulphur 
 and triethylstibine under water or preferably with ethereal 
 solution of latter reagent, heat is evolved, and on cooling a mass 
 of crystalline sulphide results. This compound resembles the 
 sulphides of alkali metals ; and it precipitates the sulphides of 
 the heavy metals and is decomposed by dilute mineral acids 
 evolving hydrogen sulphide. Its selenium analogue is soon 
 oxidised in the air. 
 
 Triethylstibine sulphate, Sb(C 2 H 5 ) 3 SO 4 , white, crystalline mass, 
 m.p. 100 ; bitter taste ; extremely soluble in water, less so in 
 
 1 Buckton, Quart. J. Chem. Soc., 1860, 13, 116. 
 
 2 Merck, Annalen, 1856, 97, 329. 
 
 56 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 alcohol. Preparation (i) by the action of sulphuric acid on 
 triethylstibine oxide and halides ; (2) best obtained by double 
 decomposition between triethylstibine sulphide and copper 
 sulphate. 
 
 Triethylstibine nitrate, well-defined rhomboidal crystals, m.p. 
 62-5, setting point 57, readily soluble in water, less so in nitric 
 acid, alcohol, or ether ; bitter taste ; not affected by hydrogen 
 sulphide. Easily purified and serves for the preparation of pure 
 triethylstibine oxide and its derivatives. Preparation (i) action 
 of nitric acid on triethylstibine oxide and halides ; (2) action of 
 triethylstibine on dilute nitric acid ; nitric oxide is evolved and 
 the nitrate crystallises from the acid solution. 
 
 Tetraethyhtibonium iodide, Sb(C 2 H 5 ) 4 I,iJH 2 O, well-defined 
 hexagonal prisms ; bitter taste ; 19-02 parts soluble in 100 parts 
 of water at 20, more soluble in alcohol, less so in ether. 
 
 Tetraethyhtibonium hydroxide, Sb(C 2 H 5 ) 4 -OH, obtained as an 
 extremely alkaline, viscid oil by the action of moist silver oxide 
 on the preceding iodide. It is miscible in all proportions in water 
 or alcohol, but insoluble in ether. It sets free ammonia from 
 ammonium salts, precipitates the hydroxides of the metals 
 excepting those of the alkaline earths ; the hydroxides of alu- 
 minium and tin are redissolved by excess of this quaternary 
 hydroxide. Its salts with the mineral and organic acids are 
 crystalline but generally hygroscopic. 
 
 Tetraethyhtibonium chloride, bromide, and nitrate form deli- 
 quescent needles. The bromide and iodide form with bismuth 
 halides, yellow to red double halides of the general formula 
 3 Sb(C 2 H 5 ) 4 X,2BiY 3 .i 
 
 The platinichloride, yellow crystals moderately soluble in 
 water or alcohol, has the normal constitution [Sb(C 2 H 5 ) 4 ] 2 PtCl 6 . 2 
 The double mercuri-iodide, 2Sb(C 2 H 6 ) 4 I,3HgI 2 , formed by 
 adding mercuric chloride to a solution of the quaternary iodide, 
 is a white, crystalline precipitate, insoluble in water or ether, 
 sparingly soluble in boiling alcohol, from which it separates in 
 colourless, hexagonal prisms. When melted under water at 70 
 red spots appear in the molten mass which changes to a red 
 modification crystallising in the regular system. When dis- 
 solved in boiling alcohol the red modification changes into the 
 colourless one, which separates again in hexagonal crystals. 3 
 
 1 Jorgensen, /. pr. Chem., 1871, [ii], 3, 342. 
 
 2 Buckton, Quart. J. Chem. Soc., 1860, 13, 119. 
 
 3 R. Lowig, /. pr. Chem., 1855, 64, 423 ; Annale.n, 1856, 97, 326, 
 
 57 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The hydrosulphide, a yellow oil, is produced by the action of 
 hydrogen sulphide on aqueous solutions of tetraethylstibonium 
 hydroxide. 
 
 Methyltriethylstibonium iodide, CH 3 -Sb(C 2 H 5 ) 3 I, prepared by 
 the action of methyl iodide on triethylstibine, rhombic prisms, 
 soluble in 2 parts of water at 20. Silver oxide gives the free 
 quaternary hydroxide, CH 3 -Sb(C 2 H 5 ) 3 -OH, as a viscid, highly 
 alkaline oil yielding crystallisable salts. The chloride, oxalate 
 and acid oxalate are acicular; the sulphate (m.p. 100) is ex- 
 tremely hygroscopic. 1 
 
 3. A my I Series. 
 
 Triamylstibine, Sb(C 6 H n ) 8 , produced by the action of amyl 
 iodide on potassium-antimony alloy, a fuming but not spon- 
 taneously inflammable liquid, heavier than water. Oxidised 
 to triamylstibine oxide, Sb(C 5 H n ) 3 -O, a brownish-yellow very 
 viscid mass, insoluble in water but dissolving in alcohol. Its 
 salts are oily with the exception of triamylstibine dinitrate, 
 Sb(C 5 H n ) 3 (NO 3 ) 2 . Stellate clusters of crystals, insoluble in water, 
 soluble in alcohol ; peculiar metallic taste. 2 
 
 Summary of the Results attained by the Study of Aliphatic 
 Arsenicals and Antimonials. 
 
 The foregoing chapters contain references to all the more 
 important organic derivatives of arsenic and antimony containing 
 aliphatic or open chain radicals, and before passing on to consider 
 the aromatic and other closed chain derivatives of these metal- 
 loids it is advisable, by way of summary, to indicate briefly 
 the salient features of interest revealed by these researches which 
 have now been carried on for more than 150 years. 
 
 The work of the earliest French chemists need not be recapitu- 
 lated because, although it was invaluable as a pioneering effort, 
 it led directly to no results of theoretical or practical importance. 
 The chemical significance of the cacodyl investigation began to 
 be apparent as the result of Bunsen's classical researches. At 
 that time chemists were engaged in the endeavour to establish 
 a theory of chemical affinity which should be applicable to 
 organic as well as to inorganic compounds. Lavoisier in 1789 
 
 1 Friedlander, Jahresber., 1857, 423. 
 
 2 Berl6, /. pr. Chem., 1855, 65, 385; Cramer, Jahresber., 1855, 590. 
 
 58 
 
ALIPHATIC ARSENICALS AND ANTIMJtflALS 
 
 had already contrasted the properties of inorganic and organic 
 acids in the following words. 
 
 " I have already remarked that in the mineral kingdom 
 nearly all the oxidisable and acidifiable radicals were simple ; 
 that in the vegetable kingdom on the contrary and above all 
 in the animal kingdom there exist scarcely any which were 
 composed of less than two substances, hydrogen and carbon ; 
 that often nitrogen and phosphorus were united with them, and 
 that there resulted radicals with four bases." 1 
 
 The existence of these compound radicals being postulated, 
 the chemical instinct of the chemists of the early years of the 
 nineteenth century led these workers to search for more definite 
 evidence of the presence of these hypothetical complexes either 
 by tracing them through a series of chemical changes or more 
 decisively by isolating the radicals themselves. Both forms of 
 evidence were speedily forthcoming in the case of cyanogen, 
 a compound radical of organic origin which was identified by 
 Gay-Lussac 2 in prussic acid and the cyanides and was also 
 shown by him to be capable of existence in the free state. The 
 remarkably close analogy between this compound organic radical 
 and the simple inorganic halogen radicals is shown by the follow- 
 ing table, in which chlorine is selected as the typical halogen. 
 
 Compound radical CN or Cy. 
 
 Free cyanogen, C 2 N 2 or Cy 2 . 
 Cyanogen iodide, CNC1 or Cyl. 
 Hydrogen cyanide, HCN or HCy. 
 Silver cyanide, AgCN or AgCy. 
 Mercuric cyanide, Hg(CN) 2 or 
 
 HgCy a . 
 C 2 N 2 + 2KOH = KCN + KCNO + 
 
 Simple radical Cl. 
 Free chlorine, C1 2 . 
 Iodine monochloride, Id. 
 Hydrogen chloride, HCl. 
 Silver chloride, AgCl. 
 Mercuric chloride, HgCl 2 . 
 
 C1 2 + 2KOH = Kd + KdO + 
 H 2 O. 
 
 Theory of Compound Radicals. 
 
 The researches by Berzelius and Hisinger and by Davy on the 
 effect of the electric current on inorganic compounds had shown 
 that very frequently this agent brought about the decomposition 
 of these complex substances into their component elements. 
 Water was decomposed into hydrogen and oxygen, dissolved 
 salts into acid and base, and the alkali hydroxides into metal, 
 
 1 Lavoisier, Traite bUmentaive de chimie, 1789, I., 209. 
 
 2 Ann. de chim., 1815, 95, 161. 
 
 59 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 hydrogen and oxygen. Inasmuch as the electric current proved 
 to be a specially suitable agent for decomposing compounds it 
 was inferred that the force of chemical affinity which promoted 
 the combination of elements to form compounds was electrical 
 in character. It was regarded as in the highest degree probable 
 " that substances on the point of combining exhibit opposite 
 electric charges/' and " that in all chemical combinations there 
 is a neutralisation of opposite electric charges." The generation 
 of heat and light, which often accompanies chemical combination, 
 was compared to similar phenomena accompanying electric 
 discharges. One characteristic of this electro-chemical theory 
 due to Barzelius is the combination of elements or compounds 
 in pairs, and for this reason it is frequently termed the " dualistic 
 theory." For example, potassium (electropositive) and oxygen 
 (electronegative) combine to form potassium oxide, K 2 O. Sulphur 
 (electropositive) and oxygen (electronegative) combine similarly 
 to form sulphur trioxide, SO 3 . 
 
 The potassium oxide (electropositive) and sulphur trioxide 
 (electronegative) compounds of the first order couple similarly 
 to produce potassium sulphate, a compound of the second order. 
 This salt (electropositive) can now pair with aluminium sulphate 
 (electronegative), another compound of the second order, to yield 
 dry alum or anhydrous potassium aluminium sulphate, a com- 
 pound of the third order. This double salt may finally unite 
 with water to produce ordinary alum, hydrated potassium 
 aluminium sulphate. At each of the successive steps in this 
 inorganic synthesis a combination between pairs of compounds 
 is observable. 
 
 Berzelius's dualistic electro-chemical theory could readily be 
 applied to mineral substances salts, acids, and bases because 
 these compounds were amenable to the action of the electric 
 current. But it could not be tested on organic compounds, 
 which were often non-conductors and not decomposed by the 
 electric current. Accordingly Berzelius assumed that the 
 difference was due to the presence in the organic materials of 
 compound radicals. 
 
 " In inorganic nature all oxidised bodies contain a simple 
 radical while all organic substances are oxides of compound 
 radicals. The radicals of vegetable substances consist generally 
 of carbon and hydrogen, and those of animal substances of carbon, 
 hydrogen and nitrogen " (Berzelius, Text-book, 1817, 1, 544). 
 
 At first Berzelius was indisposed to admit that oxygen could be 
 
 60 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 a component of an electropositive organic radical, although he 
 waived this reservation in the case of the compound radical 
 benzoyl identified by Wohler and Liebig (1832) in oil of bitter 
 almonds (benzaldehyde). Although this radical was not 
 isolated, it was traced through a series of chemical changes re- 
 sulting in the formation of the following group of organic com- 
 pounds. 
 
 Benzoyl radical C 7 H 5 O. 
 
 Benzaldehyde (benzoyl hydride) = C 7 H 5 OH. 
 
 Benzoic acid (benzoyl hydroxide) = C 7 H 6 OOH. 
 Benzoyl chloride (bromide or iodide) = GjHgOCI (or Br or I). 
 Benzoyl cyanide = C,H 5 OCN. 
 
 Benzamide = C 7 H 5 O-NH 2 . 
 
 The search for compound radicals was in full progress when 
 Bunsen took up the study of Cadet's fuming arsenical liquid, 
 and the identification and subsequent isolation of the compound 
 radical, cacodyl, was acclaimed with the utmost enthusiasm and 
 delight by Berzelius in terms which have already been cited 
 (p. 8). 
 
 Cacodyl had all the characteristics of a compound radical as 
 defined by Lavoisier and afterwards by Berzelius ; it contained 
 the two elements, carbon and hydrogen, common to nearly ail 
 organic radicals, and associated with them a third element, 
 arsenic. This radical had a further significance in the eyes of 
 Berzelius in that it was not oxygenated. Moreover, its isolation 
 in an uncombined condition proved conclusively that the complex 
 had a real existence. 
 
 The three complexes which were regarded by Berzelius as 
 affording the main support for his theory of compound radicals 
 were the following : 
 
 Molecular Elementary 
 
 complexity in or inorganic 
 Compound radical. Discoverers. free state. analogues. 
 
 Cyanogen, CN. Gay-Lussac. C 2 N 2 . Halogens, C1 2 , etc. 
 
 Benzoyl, COC 6 H 3 . Liebig and Wohler. Not isolated. Acidic groups, SO 3 , 
 
 NO 2 . 
 
 Cacodyl, As(CH,) 2 . Bunsen. [As(CH 3 ) 2 ] 2 . K, Na, or prefer- 
 
 ably Tl. 
 
 Of these three compound radicals, cacodyl undoubtedly exhibits 
 the most intimate relationship to its elementary analogues. 
 
 Further noteworthy examples of organic radicals of the type 
 recognised by Berzelius were subsequently forthcoming in the 
 tertiary stibines. The first of these, triethylstibine, discovered 
 by Lowig and Schweitzer (p. 55), presented very close analogies 
 
 61 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 with bivalent metals, such as zinc, as shown in the following 
 table : 
 
 Triethylstibine- 
 
 Triethylstibine radical. oxide. -sulphide. -chloride. 
 
 (C 2 H,) 3 Sb, existing also [(G^H^SbJO. [(C 2 H 5 ) 3 Sb]S. [(C 2 H 5 ) 3 Sb]Cl 3 . 
 in the free state. 
 
 Metal. Metallic-oxide. -sulphide. -chloride. 
 
 Zn (monatomic). ZnO. ZnS. ZnCL 2 . 
 
 Analogous reactions / ( C 2 H 5 ) 3 Sb + ?HC1 = (C 2 H fl ) 3 SbCl, + H 2 . 
 
 5 \ Zn + 2 HCl = ZnCl 2 +H 2 . 
 
 The great upholder of the radical theory scarcely lived long 
 enough to recognise the important bearing of the tertiary alkyl- 
 stibines on his generalisation, inasmuch as his death occurred in 
 the year in which Lowig and Schweitzer's results were published. 
 
 The next stage in the history of the aliphatic arsenicals was the 
 explanation of the inner constitution of cacodyl by Frankland. 
 This theoretical advance was speedily followed by the synthesis 
 of cacodyl and the preparation of many alkyl derivatives of 
 arsenic and antimony. 
 
 The dealkylation of these aliphatic arsenicals was first accom- 
 plished by Baeyer, who was thus led to methylarsinic acid and 
 its derivatives. Progressive alkylation of arsenious acid to 
 mono-, di-, and tri-alkyl derivatives was the joint contribution of 
 G. Meyer, of Klinger and Kreutz, of Auger and of Dehn. The 
 isolation of primary arsines was first accomplished by Palmer 
 and Dehn. As the result of all these researches on aliphatic 
 arsenicals this series has been very considerably extended and 
 completed. The available synthetic methods are now so 
 generalised that almost any required aliphatic arsenical should 
 be capable of preparation. 
 
 In the antimonial series progress has been much slower. The 
 experimental difficulties are considerably greater chiefly owing 
 to the fact that antimony differs from arsenic in possessing 
 much less affinity for the hydrocarbon radicals. Only the more 
 drastic synthetic processes are available, and these lead most 
 readily to tertiary stibines and quaternary stibonium halides. 
 The series of aliphatic antimonials is still very incomplete. 
 
 Bunsen's discovery that cacodylic acid was a comparatively 
 innocuous substance, has led to the use of its salts in 
 medicine. Therapeutic use has also been made of the salts 
 of methylarsinic acid, notably of sodium methylarsinate employed 
 under the names " arrhenal " and " new cacodyl." The pro- 
 
 62 
 
ALIPHATIC ARSENICALS AND ANTIMONIALS 
 
 cesses devised by G. Meyer and by Dehn for preparing methyl - 
 arsinic and other alkylarsinic acids render the production of these 
 drugs easily practicable. 
 
 In the main, however, these alkylarsenical drugs have been 
 superseded by more potent substances containing aromatic 
 groups. 
 
 The alkylantimonials have not hitherto been employed in 
 medicine. 
 
CHAPTER III 
 
 AROMATIC ARSENICALS 
 
 Arylar sines and their Immediate Derivatives 
 
 WE owe to France the original discovery of organic arsenical 
 compounds by Cadet de Gassicourt, and it was a French chemist 
 who, about one hundred years later, made the second pioneering 
 effort in this field of scientific inquiry which led to the isolation 
 of the first arsenic derivative containing an aromatic radical. 
 
 The second period in the history of organic arsenic and anti- 
 mony compounds is characterised by the discovery of derivatives 
 of these elements containing aromatic groups. Although these 
 researches attracted very little attention for many years, it can 
 now be seen that they led to great advances in our knowledge 
 of organo-metalloidal compounds and in the laboratory processes 
 for producing these substances. 
 
 The discovery of mauveine and magenta, which occurred 
 about the middle of last century, led chemists to study the 
 action of various oxidising agents on aniline and its homologues. 
 Arsenic acid, one of these oxidising agents, was employed for 
 many years in the manufacture of magenta from aniline containing 
 ortho- and para-toluidines. The conditions under which magenta 
 or fuchsine is produced from aniline and its homologues were 
 studied by Bechamp in i860, 1 who in one of his two publica- 
 tions of that year noted that aniline arsenate heated with excess 
 of aniline did not give rise to coloured products until a fairly 
 high temperature (190-200) was reached. At lower tempera- 
 tures aniline was eliminated from the normal arsenate so that 
 the acid salt, C 6 H 5 -NH 2) H 3 As02, became an intermediate product 
 which at higher temperatures underwent decomposition with 
 the elimination of water and the formation of a certain amount of 
 
 1 Compt. rend., 1860, 50, 870 ; 51, 356. 
 
 6 4 
 
AROMATIC ARSENIC ALS 
 
 magenta and other coloured substances together with arsenious 
 acid. The development of colour was less pronounced than might 
 have been expected, and the investigation of the colourless 
 products was carried further. 1 
 
 In 1863 Bechamp found that arsenic acid could react with 
 aniline without oxidising this base. By heating aniline arsenate 
 with excess of aniline at 190200 he obtained, besides colouring 
 matters, a colourless product which he supposed was an acidic 
 anilide, or anilic acid (VI.), comparable with oxanilic acid (V.). 
 
 C 6 H 5 -NH-COCOOH C 6 H 5 'NH-AsO(OH) 2 
 
 v. vi. 
 
 The sodium, potassium, silver, and barium salts of the com- 
 pound described by Bechamp showed that it was a monobasic 
 acid, and until 1907 it was regarded as having the constitution 
 (VI.) indicated by its discoverer. The sodium salt was intro- 
 duced into therapeutics under the name of atoxyl. The earliest 
 trials of the drug are associated with the names of Schild, Kionka, 
 Blumenthal, and Henius, whose experiments were initiated in 
 the year 1902. The employment of the drug in sleeping sickness 
 is due to Thomas and Breinl, of the Liverpool School of Tropical 
 Medicine, whose pioneering inquiry was a forerunner of Ehrlich's 
 systematic investigations on the treatment of diseases of 
 protozoal origin with atoxyl and other more efficacious 
 arsenicals. 
 
 The practical importance of atoxyl and its homologues and 
 derivatives justifies the special consideration of these substances 
 in a separate chapter (page 153) . The present chapter is devoted 
 to the aromatic arsines and their immediate derivatives. 
 
 Twelve years after Bechamp's observation, Michaelis began 
 his comprehensive studies of aromatic arsenic derivatives, 
 discovering two general methods of preparation. 
 
 In one of these processes advantage was taken of the fact 
 that mercury diaryl derivatives are readily obtained by the 
 interaction of sodium amalgam, and the bromo-derivatives of 
 aromatic hydrocarbons. 
 
 [Hg - 2Na] + 2C 6 H 5 -Br = Hg(C 6 H 6 ) 2 + 2 NaBr. 
 Similar results were obtained with bromotoluenes, bromo- 
 xylenes, and bromonaphthalenes, the condensation being usually 
 facilitated by the addition of a small proportion of ethyl acetate. 
 
 1 Compt. rend., 1863, 56, 1172. 
 
 65 F 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 With arsenious chloride the mercury diaryls react, giving 
 rise to primary and secondary aromatic derivatives of arsenic. 
 
 Hg(C 6 H 5 ) 2 + 2AsCl 3 = HgCl 2 + 2C 6 H 6 AsCl 2 . 
 Prolonged action leads to the further change : 
 
 Hg(C 6 H 5 ) 2 + 2 C 6 H 5 -AsCl 2 = HgCl 2 + 2 (C 6 H 5 ) 2 AsCl, 
 
 the products being phenylarsenious dichloride and diphenyl- 
 arsenious chloride. 
 
 I. MERCURY DIARYL METHOD. 
 Hg(C,H 5 ) I and AsCl, 
 
 / \ 
 
 C 6 H 8 AsCl 2 ( 
 
 hydrolysis ^\^^ addition of C1 2 
 
 C 6 H 5 -AsO ^%J>\ (C 6 H 5 ) 2 AsCl 3 
 distillation /0 /? hydrolysis 
 
 * i 
 
 As(C 6 H 5 ) 3 + As 4 O 6 (C 6 H 5 ) 2 AsOOH 
 
 These reactions were generalised by Michaelis, La Coste, and 
 other workers, with the result that a very large number of 
 primary and secondary aromatic derivatives of arsenic became 
 available for further research. 
 
 In a recent modification of the mercury aryl synthesis, arylmer- 
 curichlorides are employed. These substances are readily obtained 
 by treating benzene and its homologues and derivatives with 
 mercuric acetate in acetic acid solution. The resulting aryl- 
 mercuri-acetate is converted by double decomposition with 
 calcium chloride (or other suitable metallic chloride) into 
 arylmercurichloride, and the latter when heated at 100 with 
 arsenious chloride gives rise to the corresponding arylarsenious 
 chloride. Carboxyl, hydroxyl, and amino groups, if present, 
 must be protected by alkylation or acylation to prevent inter- 
 action with arsenious chloride. With this precaution the reaction 
 is general for para-substituted arylmercurichlorides. 1 The 
 ortho-substituted isomerides are less effective. 
 
 The second general method discovered by Michaelis and his 
 collaborators may be regarded as an adaptation of Fittig's 
 
 1 Roeder and Blase, Ber., 1914, 47, 2748. 
 66 
 
AROMATIC ARSENIC ALS 
 
 synthesis of hydrocarbons. It led to the production of tertiary 
 aromatic arsines, the simplest example being triphenylarsine, 
 which was prepared by adding sodium to an ethereal solution 
 of arsenious chloride and chlorobenzene. 
 
 AsCl 3 + 3C 6 H 5 C1 + 6Na = 6NaCl + As(C 6 H 6 ) 3 . 
 
 This reaction was extended to other aromatic chloro- and 
 bromo-compounds, giving rise to homologues and derivatives of 
 triphenylarsine. These tertiary aromatic arsines take up chlorine 
 or bromine, forming dihalides, which, on heating, furnish secondary 
 arsenious halides. 
 
 (C 6 H 5 ) 3 AsCl 2 = C 6 H 5 C1 + (C 6 H 5 ) 2 AsCl. 
 
 Diphenylarsenious 
 chloride. 
 
 The foregoing process constitutes a second method of obtaining 
 members of the secondary series. 
 
 The tertiary aromatic arsines can also be employed in preparing 
 primary derivatives, this result being attained by heating them 
 under pressure at 250 with arsenious chloride. A certain amount 
 of the secondary chloride is formed as a by-product. 
 
 (C 6 H 5 ) 3 As + 2AsCl 3 = 3C 6 H 5 AsCl a (main product). 
 2(C 6 H 5 ) 3 As + AsCl 3 = 3(C 6 H 5 ) 2 AsCl (by-product). 
 
 II; SODIUM METHOD. 
 
 (C 6 H 5 C1, AsCl 3 and Na) 
 
 v^ ^ 
 
 / 
 
 As(C 6 H 5 ) 3 
 
 I ~~| 
 
 Heating with AsCl 3 Chlorine addition 
 
 I | - As(C.H B ) 8 Cl a 
 
 C 6 H 5 AsCl 2 ^5^ (C 6 H 5 ) 2 AsCU- .Ration 
 
 ^ \ "^\ ^^X As(C 6 H 5 ) 3 (OH) 2 
 
 C 6 H 5 AsO, C 6 H 5 AsCl 4 (C 6 H 5 ) 2 AsCl 3 H [(C e H 5 ) 2 As] 2 O 
 
 I I ~\ 
 
 \ y /OH 
 
 C 6 H 5 AsO(OH) 2 (C 6 H 5 ) 2 AsO-OH As(C 6 H 5 ) 3 / 
 
 0-N0 2 
 
 It will be seen from the diagrams that each synthetic method 
 can be utilised for the production of primary, secondary, and 
 tertiary arsenic derivatives. 
 
 In certain instances Michaelis found that arsenic could be 
 
 67 F 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 introduced into the aromatic nucleus without the intervention 
 of mercury diaryls or sodium. 
 
 Phenylarsenious dichloride and diphenyl were produced by 
 passing the vapours of benzene and arsenious chloride through 
 a red-hot tube, but the separation of the products was difficult. 
 
 Dimethylaniline contains a reactive hydrogen atom which 
 is readily replaced by an arsenic radical. 
 
 i. C 6 H 5 N(CH 3 ) 2 + AsCl 3 - 
 ii. 3 C 6 H 5 N(CH 3 ) 2 + AsCl 3 - > [N(CH 3 ) 2 /~ 
 
 These reactions are not, however, general, and primary 
 and secondary aromatic amines do not invariably react smoothly 
 with arsenious chloride. The diagrams of the two synthetic 
 methods indicate the production of oxygenated aromatic deriv- 
 atives of arsenic. The reduction products of these derivatives, 
 examined by Michaelis, La Coste, and others are of great interest 
 as foreshadowing some of the more recent developments in 
 the production of arsenical drugs. 
 
 Triphenylarsine dihydroxide, when reduced with tin and 
 hydrochloric acid, yields triphenylarsine. 
 
 (C 6 H 5 ) 3 As(OH) 2 + 2 H = 2H 2 + As(C 6 H 5 ) 3 . 
 
 The secondary diarylarsenious oxides are reduced by phos- 
 phorous acid to arylcacodyl derivatives. 
 
 TT r* TT 
 
 \ 
 
 [(C 6 H 5 ) 2 As] 2 + H 3 P0 3 = H 3 P0 4 + ) As-As< 
 
 C 6 H/ X C 6 H 
 
 Unlike its alkyl analogues, phenylcacodyl is not inflammable 
 in air at the ordinary temperature, but it readily absorbs oxygen, 
 becoming converted into the anhydride of diphenylarsinic acid, 
 this acid being the aromatic analogue of cacodylic acid. 
 
 The primary arylarsenious oxides are reduced in alcoholic 
 solution by phosphorous acid, giving rise to arsenobenzene and 
 its homologues. 
 
 2C 6 H 5 AsO + 2H 3 PO 3 = 2H 3 P0 4 + C 6 H 5 -As:As-C 6 H 5 . 
 
 Arsenobenzene, also obtained by reducing phenylarsinic acid, 
 is a substance of great theoretical interest ; it is the analogue 
 of the colour principle, azobenzene, C 6 H 5 -N:N-C 6 H 5 , more- 
 over it is the parent substance of salvarsan. It crystallises in 
 yellowish needles, readily resinifies in solution, combines 
 
 68 
 
AROMATIC ARSENICALS 
 
 additively with chlorine and sulphur, and is readily oxidised 
 to phenylarsinic acid. The aliphatic analogues of arseno- 
 benzene have already been described (v. pp. 40, 47). 
 
 In his second detailed memoir on aromatic arsenic com- 
 pounds Michaelis 1 shows that the foregoing general methods are 
 applicable to the production of substances containing the 
 principal aromatic hydrocarbon groups. He also describes the 
 outstanding characteristics of the products. 
 
 Tertiary Aromatic Ar sines. 
 
 The sodium method of synthesis is the most generally useful. 
 The simple tertiary arsines are readily and quantitatively obtained 
 by the action of this metal on ethereal solutions of arsenious 
 chloride and the aryl halide, 
 
 3R-C1 + AsCl 3 4- 6Na = AsR 3 + 6NaCl. 
 
 The mixed tertiary aromatic arsines are produced in a similar 
 way by the action of sodium on ethereal solutions of monoaryl- 
 arsenious chloride and an aryl halide, 
 
 2R'C1 + AsRQ 2 -f 4Na - AsRR' 2 + 4NaCl. 
 
 These tertiary aromatic arsines are also obtainable by two other 
 processes : 
 
 i. The action of aromatic mercury compounds on the aryl- 
 arsenious dichlorides, HgR' 2 + RAsQ 2 = HgCl 2 + AsRR 2 '. 
 
 ii. The heating of arylarsenious oxides in sealed tubes, 
 
 3RAsO = AsR 3 + As 2 O 3 . 
 
 The second of these processes was the method whereby the 
 tertiary arylarsines were originally produced. 
 
 It is noteworthy that the method with sodium, which is so 
 generally available to the preparation of aromatic arsines 
 and stibines, gives only poor yields or fails entirely in the 
 production of the corresponding phosphines. 
 
 The following arsines have been obtained by the sodium 
 method. 
 
 Simple Tertiary Arsines. 
 
 Triphenylarsine, (C 6 H 6 ) 3 As, m.p. 59. 
 Tri-^>-anisylarsine, (CH 3 -OC 6 H 4 ) 3 As, m.p. 156. 
 Tri-^>-phenetylarsine, (C 2 H 5 -O-C 6 H 4 ) 3 As, m.p. 98. 
 Tribenzylarsine, (C fl H 5 -CH 2 ) 3 As, m.p. 104. 
 
 1 Michaelis, Annalen, 1902, 320, 271 ; 321, 141 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Tri-^-tolylarsine, (CH 3 -C 6 H 4 ) 3 As, m.p. 146. 
 Tri-w-tolylarsine, (CH 3 -C 6 H 4 ) 3 As, m.p. 96. 
 Tri-w-xylylarsine, [(CH 3 ) 2 -C 6 H 3 ] 3 As, m.p. 166. 
 Tri-^>-ethyrphenylarsine, (C 2 H 6 -C 6 H 4 ) 3 As, m.p. 78. 
 Tripseudocumylarsine, [(CH 3 ) 3 -C 6 H 2 ] 3 As, m.p. 223. 
 Trimesitylarsine, [(CH 3 ) 3 C 6 H 2 ] 3 As, m.p. 170. 
 Tri-^-cumylarsine, (C 3 H 7 -C 6 H 4 ) 3 As, m.p. 140. 
 Tritertiarybutylphenylarsine, (C 4 H 9 -C 6 H 4 ) 3 As, m.p. 235. 
 Tri-a-naphthylarsine, (C 10 H 7 ) 3 As, m.p. 252. 
 Tri-/?-naphthylarsine, (C 10 H 7 ) 3 As, m.p. 165. 
 
 Mixed Tertiary Ar sines. 
 
 Diphenyl-^-tolylarsine, (C 6 H 5 ) 2 AsC 6 H 4 -CH 3 , m.p. 50. 
 Phenyldi-^-tolylarsine, C 6 H 5 -As(C 6 H 4 -CH 3 ) 2 , m.p. 101. 
 Phenyldi-w-xylylarsine, C 6 H 5 -As[C 6 H 3 (CH 3 ) 2 ] 2 , m.p. 99. 
 Phenyldipseudocumylarsine,C 6 H 5 -As[C 6 H 2 (CH 3 ) 3 ] 2 , m.p. 138-5. 
 
 The tertiary arsines are well-defined, crystalline, inodorous 
 substances having no irritating effect on the skin. They are 
 insoluble in concentrated hydrochloric acid, but combine with 
 chloroplatinic acid in alcoholic solutions to give sparingly soluble 
 platinichlorides, (AsR 3 ) 2 ,H 2 PtQ 6 . They combine with mercuric 
 chloride to form the mercurichlorides, AsR 3 ,HgCl 2 , white 
 crystalline substances sparingly soluble in alcohol, dissolving 
 more readily in glacial acetic acid. 
 
 When treated with chlorine or bromine in carbon tetrachloride 
 solution these arsines combine additively with the halogen to 
 yield the corresponding dichloride, R 3 AsCl 2 , or dibromide, 
 R 8 AsBr 2 , the product being precipitated by ether. Alcohol 
 converts certain dihalides into hydroxyhalides, R 3 As(OH)-Cl or 
 R 3 As(OH)-Br, but in some cases the dihalides are stable in this 
 reagent. 
 
 By the interaction of alkalis on the dihalides or hydroxyhalides 
 the hydroxides or oxides of the arsines are obtained. Some of 
 these hydroxides crystallise with water, as, for example, 
 tripseudocumylarsine hydroxide, (C 9 H u ) 3 As(OH)2,4H 2 O. 
 
 Trinitro-compounds of the arsine oxides are produced by 
 the action of nitric-sulphuric acids on the arsines or their oxides. 
 These trinitro-compounds are reduced by phosphorous acid to 
 trinitroarsines, and by tin and hydrochloric acid to triamino- 
 arsines : triaminotriphenylarsine is very unstable, whereas 
 triaminotri-^-tolylarsme is quite stable. 
 
 70 
 
AROMATIC ARSENIC ALS 
 
 The sulphides, R 3 AsS, are obtained by three different methods : 
 (i) direct combination of the arsine and sulphur in carbon bi- 
 sulphide ; (ii) interaction of the arsine and alcoholic ammonium 
 polysulphide ; (iii) introduction of hydrogen sulphide into an 
 alcoholic solution of the oxide. 
 
 Triarylalkylarsonium iodides, R 3 As(alkyl)I. Contrary to the 
 earlier experiments, it has been found that the tertiary arylarsines 
 combine with methyl and ethyl iodides when warmed with excess 
 of these halides on the water-bath. The triarylarsines do not as 
 a rule combine with the higher alkyl iodides, but tri-m-tolylarsine 
 behaves exceptionally in giving quaternary iodides with great 
 facility ; it combines with methyl iodide in the cold and with 
 propyl iodide or benzyl chloride on warming gently. 
 
 Triarylmethylarsonium hydroxides, R 3 As(CH 3 )-OH, differ from 
 their phosphorus and nitrogen analogues in crystallising 
 from concentrated aqueous solutions. When evaporated in 
 the open air these solutions yield crystallisable bicarbonates, 
 R 3 As(CH 3 )-HCO 3 . When gently heated the triarylmethyl- 
 arsonium hydroxides lose methyl alcohol and regenerate the 
 tertiary arsine, differing in this respect from the corresponding 
 phosphonium compounds which lose a portion of the aromatic 
 constituent and leave a substituted phosphine oxide, 
 
 R 3 As(CH 3 )-OH = AsR 3 + CH 3 OH 
 R 3 P(CH 3 )OH = R 2 P(CH 3 ):O + R-H. 
 
 Arylarsine oxide carboxylates are produced by the oxidation of 
 arylarsines containing aliphatic side chains with dilute nitric 
 acid under pressure. The three tolyl derivatives, for example, 
 furnish the following oxidation products : 
 
 (C 6 H 5 ) 2 As-C 6 H 4 -CH 3 -> (C 6 H 5 ) 2 AsO-C 6 H 4 -CO 2 H. 
 
 Triphenylarsine oxide carboxylic acid. 
 
 6 H 4 -CH 3 
 
 C 6 H 5 -As(C 6 H 4 -CH 3 ) 2 _> C 6 H 6 -AsO 
 
 
 
 \C 6 H 4 -CO 2 H 
 Tolyldiphenylarsine oxide carboxylic acid. 
 
 C 6 H 5 -AsO(C 6 H 4 -CO 2 H) 2 . 
 Triphenylarsine oxide dicarboxylic acid. 
 
 As(C a H 4 -CH 3 ) , --> (HO) 2 As(C 6 H 4 -C0 2 H) 3 . 
 
 Triphenylarsine dihydroxide tricarboxylic acid. 
 
 When these acids are esterified with alcoholic hydrochloric 
 
 7 1 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 acid the oxygen attached to arsenic is replaced by chlorine. 
 For instance, the third of the foregoing carboxylic acids furnishes 
 
 the chloro-ester, C^As^ 
 
 ^(C 6 H 4 -C0 2 -C 2 H 5 ) 2 . 
 
 Arylarsenious Chlorides (Primary CJilor oar sines), R-AsQ 2 . 
 
 As already indicated, these chlorides are obtainable by three 
 general methods : 
 
 1. The mercury diaryl method (v. p. 78). 
 
 2. The arylmercurichloride method (v. p. 79). This process 
 is convenient because of the ease with which arylmercuri- 
 acetates can be produced. 
 
 3. Heating the corresponding tertiary arsine with excess of 
 arsenious chloride in sealed tubes at 150-300. 
 
 Owing to the ease with which tertiary arsines are prepared, 
 the third method is much to be preferred. 
 
 It is noteworthy that Friedel and Crafts' method of synthesis 
 with aluminium chloride, although rendering good service in 
 the preparation of aromatic phosphorous chlorides, is useless 
 in the case of the aromatic arsenious chlorides. In the latter 
 series only tarry products are obtained. 
 
 The lower homologues of the arylarsenious chlorides are 
 liquids, the higher members are colourless well-defined 
 crystalline solids. They can be boiled without decom- 
 position under the ordinary pressure, but it is preferable to 
 distil them under reduced pressure. They are very poisonous 
 and when dropped on the skin produce painful and slowly 
 healing wounds. Faintly odorous in the cold, they evolve a 
 penetrating and irritant odour on warming. Insoluble in 
 water, these arsenious chlorides are readily soluble in alcohol, 
 ether, or benzene. 
 
 The following arylarsenious chlorides have been prepared : 
 
 Phenylarsenious chloride, C 6 H 5 -AsCl 2 , b.p. 254, liquid. 
 Nitrophenylarsenious chloride, NO 2 -C 6 H 4 -AsCl 2 , m.p. 47. 
 ^>-Anisylarsenious chloride, CH 3 -OC 6 H 4 -AsCl 2 , b.p. 160, and 
 m.p. 48. 
 
 ^>-Phenetylarsenious chloride, C 2 H 6 -OC 6 H 4 -AsCl 2 , b.p. 198. 
 Benzylarsenious chloride, C 6 H 5 -CH 2 *AsCl 2 , b.p. i75/ioo mm. 
 p -Tolylarsenious chloride, CH 3 -C 6 H 4 -AsCl 2 , b.p. 267, m.p. 31. 
 w-Tolyl arsenious chloride, CH 3 -C 6 H 4 -AsCl 2 , b.p. 270. 
 
 72 
 
AROMATIC ARSENICALS 
 
 o-Tolylarsenious chloride, CH 3 -CeH 4 'AsCl 2 , b.p. 264. 
 i : 3-Xylyl-4-arsenious chloride, (CH 3 ) a C 6 H s -AsCl a , b.p. 278, 
 m.p. 41. 
 
 i : 4-Xylyl-2-arsenious chloride, b.p. 285, m.p. 63. 
 Pseudocumylarsenious chloride, b.p. I90/30 mm., m.p. 82-5. 
 ^-Cumylarsenious chloride, b.p. I70/30 mm. 
 Tertiarybutylphenylarsenious chloride, b.p. I77/2O mm. 
 a-Naphthylarsenious chloride, m.p. 63. 
 /3-Naphthylarsenious chloride, m.p. 69. 
 
 Arylarsenious Oxides, R-AsO. The foregoing arylarsenious 
 chlorides are only slightly attacked by water even on heating, 
 but with aqueous sodium carbonate they are converted into 
 oxides. These arylarsenious oxides are somewhat devoid of 
 crystalline habit. By hydrochloric acid they are reconverted 
 into arylarsenious chlorides. Hydrobromic and hydriodic acids 
 lead to arylarsenious bromides and iodides respectively. On 
 heating, these oxides give rise to triarylarsines and arsenious 
 oxide (v. p. 80). 
 
 Arylarsenious Acids, R-As(OH) 2 . These compounds are capable 
 of existence only when the aromatic nucleus contains acidic 
 constituents, which confer on the AsO group a greater affinity 
 for hydroxyl. There are no arylarsenious acids containing 
 simple aromatic nuclei. 
 
 /NO, /CO a H 
 
 C 6 H 4 < C 6 H 4 < 
 
 \As(OH) a X As(OH) a 
 
 Nitrophenylarsenious acid Benzarsenious acid 
 
 (v. p. 145). (v. p. 131). 
 
 This conferred power of hydration is very remarkable, inasmuch 
 as arsenious oxide does not form a stable hydroxide. 
 The esters of arylarsenious acids, 
 
 C 6 H 5 As(OCH 3 ) a and C 6 H 6 As(O-C 6 H 6 ) 2 , 
 
 produced by the action of sodium alkoxide or phenoxide on 
 arylarsenious chlorides, even when no acidic substituents are 
 present in the aromatic ring, are very sensitive to moisture, 
 which decomposes them into the arylarsenious oxide and alcohol 
 or phenol. 
 
 Arylarsenic chlorides, R-AsCl 4 , are for the most part crystalline 
 substances, though some, like w-tolylarsenic chloride, are liquid. 
 They are produced by the direct addition of chlorine to primary 
 arylarsenious chlorides. When the aromatic nucleus contains 
 
 73 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 an acidic constituent, as in the nitroarsenious chlorides, this 
 addition of chlorine occurs less readily, and in this respect these 
 nitro-derivatives resemble arsenious chloride. Arylarsenic oxy- 
 chlorides, RAsOCl 2 , are obtained similarly by the addition of 
 chlorine to the arylarsenious oxides. 
 
 Arylarsinic acids, R-AsO(OH) 2 , are well-crystallised, very 
 stable compounds, obtained by the action of water on the fore- 
 going tetrachlorides or oxychlorides. They are prepared more 
 easily when the arylarsenious chloride is suspended in water 
 and treated with chlorine until it is completely dissolved, 
 
 RAsCl a + Cl a + 3H 2 O = RAsO(OH) 2 + 4HC1. 
 
 An alternative method, which leads to products free from 
 chlorine, consists in dissolving the arylarsenious chloride in 
 glacial acetic acid and adding gradually hydrogen peroxide, 
 
 RAsCl a + H 2 a + H 2 O = RAsO(OH) a -f aHCl. 
 
 The composition of the metallic arylarsinates indicates that 
 the acids are dibasic. The corresponding esters are liquid and 
 rapidly hydrolysed by moisture into alcohol and arylarsinic 
 acids. 
 
 Arylarsinic anhydrides, R-As0 2 , corresponding in composition 
 with aromatic nitro-compounds, are obtained on heating the 
 arylarsinic acids ; the reverse change occurs on adding warm 
 water to these anhydrides. If electronegative (acidic) sub- 
 stituents are present in the nucleus of arylarsinic acids the 
 dehydration occurs much less readily (v. arylarsenious acids, 
 
 P- 73)- 
 
 The arylarsinic acids are not affected by chlorine or bromine, 
 but undergo nitration with concentrated nitric acid (100 per 
 cent. HN0 8 ) or with a mixture of concentrated nitric and 
 sulphuric acids. The nitroarylarsinic acids are well-defined crystal- 
 line compounds, either with high melting points or infusible until 
 they intumesce over the direct flame. In Michaelis's researches 
 these nitro-compounds were not reduced to the primary amino- 
 arylarsinic acids. The N-alkylated aminoarylarsinic acids are 
 producible directly from alkylamino-arylarsenious oxides. 
 For instance, dimethylaminophenylarsinic acid is obtained 
 from dimethylaminoarsenious oxide by oxidation with mercuric 
 oxide and water, 
 
 /AsO /AsO(OH) 2 
 
 C C H 4 < -> C 6 H / 
 
 X N(CH 3 ) 3 X N(CH 3 ) 2 
 
 74 
 
AROMATIC ARSENICALS 
 
 Oxidation of the methylated homologues of phenylarsinic 
 acid with alkaline permanganate or with dilute nitric acid 
 (D 1-2) in sealed tubes leads to benzarsinic acid and its homo- 
 logues. 
 
 Thio-derivatives of Arylarsinic Acids. 
 
 Saturation of ammoniacal solutions of arylarsinic acids with 
 hydrogen sulphide leads to the formation of ammonium aryl- 
 thioarsinates, R-AsS(SNH 4 ) 2 . These salts are decomposed by 
 mineral acids with the formation of arylarsenic sulphides, 
 
 R-AsS(SNH 4 ) 2 + 2HC1 = RAsS 2 + 2NH 4 C1 + H 2 S. 
 
 In some instances the disulphide is unstable and loses sulphur 
 with the production of a sesquisulphide, R 2 As 2 S 3 ; these sub- 
 stances are the organic analogues of P 2 S 4 and the hypothetical 
 As 2 S 4 . 
 
 Phenylarsinic acid, its nitro-derivative, and ^-tolylarsinic 
 acid furnish the following sesquisulphides : 
 
 (C 6 H 5 ) 2 As 2 S 3 , (NO a -C e H 4 ) 2 As 2 S 3 , and (C 7 H 7 ) ft As 2 S 3 , 
 
 whereas nitro-^>-tolylarsinic acid and ^-xylylarsinic acid give the 
 disulphides, NO 2 -C 7 H 6 -AsS a and C 8 H 9 -AsS 2 . 
 
 When the disulphides are not obtainable by the foregoing 
 process they may frequently be prepared by the direct addition 
 of sulphur to arylarseno-compounds. 
 
 Arylarsenious sulphides, R-AsS, are white, crystallisable com- 
 pounds prepared either by passing hydrogen sulphide into 
 alcoholic solutions of arylarsenious chlorides or oxides or by the 
 addition of sulphur to arylarseno-compounds. 
 
 Arylarseno-derivatives, R-As:As-R, result from the reduction 
 of arylarsenious oxides with phosphorous acid. They are also 
 prepared by the reduction of arylarsinic acids with aqueous 
 phosphorous acid in sealed tubes or by the action of sodium 
 amalgam or sodium and alcohol on the arylarsenious oxides or 
 chlorides. 
 
 These arylarseno-compounds, the analogues of the aromatic 
 azo-compounds, are yellowish-white to yellow compounds ; their 
 nitro-derivatives are yellowish-brown. They combine additively 
 with chlorine and bromine to form respectively di- and tetra- 
 chlorides, RAsCl 2 and RAsCl 4 , and the dibromides, RAsBr a . 
 With sulphur they give the disulphides, RAsS 2 , and with oxidising 
 agents (e.g. nitric acid) the arylarsinic acids. lodoarseno-deriv- 
 atives are characteristic yellowish-red unstable compounds 
 
 75 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 obtained either by adding iodine to the arseno-derivatives or 
 by reducing the arylarsenious iodides ; they correspond with 
 arsenious di-iodide, 
 
 C fl H 5 -AsI AsI 2 
 
 C 6 H 6 -AsI AsI 2 ' 
 
 Primary aromatic arsines, RAsH 2 , were not isolated in 
 Michaelis's investigations, his reduction experiments leading to 
 arseno-compounds. Yet frequently in these researches a 
 characteristic pungent odour was distinguishable, and this was 
 attributed to the formation of a small amount of primary arsine. 
 The conditions necessary for the preparation of aromatic 
 arsines were discovered by Palmer and Dehn, who isolated 
 phenylarsine, the first member of this series. 
 
 Synthesis of Mixed Aromatic-aliphatic Arsines (v. p. 90). 
 
 The arylarsenious chlorides subjected to the Grignard reaction 
 with magnesium alkyl iodides furnish mixed tertiary arsines 
 containing two aliphatic groups. These tertiary arsines give 
 dibromides which on heating evolve an alkyl bromide and leave 
 an arylalkylarsenious chloride. This secondary arsenic com- 
 pound yields with a second magnesium alkyl iodide a mixed 
 tertiary arsine containing dissimilar groups. This very elastic 
 method of synthesis may be indicated by the following equations, 
 where R and R' are aryl radicals : 
 
 1. C 6 H 6 -AsCl a + 2MgRI == C 6 H 5 -AsR a + MgCl a + MgI 2 . 
 
 2. C 6 H 6 -AsR 2 Br a = C a H 5 'AsRBr + RBr. 
 
 3. C 6 H 6 -AsRBr + MgR'I = C 8 H 6 -AsRR' + MgBrl. 
 
 In these syntheses the Grignard reagents may be replaced 
 by zinc dialkyls. 
 
 The products are colourless liquids of high boiling point ; they 
 possess a faint unpleasant odour. From these arylaliphatic 
 tertiary arsines can be obtained quaternary arsonium deriv- 
 atives, betaines of various types, 
 
 \ /C 6 H 4 \ 
 
 CO (C 2 H 6 ) 3 -As<; )CO, 
 
 \0 / 
 
 (C 2 H 6 ) 
 
 and also dialkylarsinobenzoic acids, 
 
 C0H 
 
 As(C 2 H 5 ), 
 76 
 
AROMATIC ARSENICALS 
 
 Secondary diarylarsenious chlorides, R 2 AsCl, are obtained by 
 several methods of formation, but a process giving a good yield 
 of these substances remains to be found. 
 
 (1) The heating of the tertiary arsine with a moderate excess 
 of arsenious chloride gives the diarylarsenious chloride, but 
 only in small yield. 
 
 For example, 50 grams of triphenylarsine and 25 grams of 
 arsenious chloride at 250 (not higher) for ten hours gives only 
 10-12 grams of diphenylarsenious chloride. 
 
 (2) The heating of the tertiary arsine dichloride under reduced 
 pressure gives only a small yield of diarylarsenious chloride, 
 
 (C 6 H 5 ) 8 AsCl a = (C 6 H 6 ) 2 AsCl + C 6 H 5 C1, 
 
 because a portion of the dichloride decomposes into chlorine 
 and tertiary arsine. 
 
 (3) The most preferable method is to heat the primary aryl- 
 arsenious chloride with the corresponding mercury diaryl, 
 
 2RAsCl a + HgR 2 = 2R 2 AsCl -f HgCl 2 . 
 
 (4) Another process, which has only been tried for di-^>-anisyl- 
 arsenious chloride, consists in heating the tertiary arsine with 
 hydriodic acid. The resulting secondary iodide is converted into 
 its oxide by alkalis and the oxide treated with hydrochloric 
 acid to furnish the diarylarsenious chloride, 
 
 R s As + HI = R 2 AsI -f RH. 
 2R 2 AsI + 2NaOH = (R 2 As) 2 O + 2NaI + H 2 O. 
 (R 2 As) 2 + 2HC1 - 2R 2 AsCl + H 2 O. 
 
 Probably this process is capable of further extension. 
 
 The diarylarsenious chlorides are, like the arylarsenious 
 chlorides, poisonous and very irritating to the skin. They are 
 not affected by water and only slowly by aqueous caustic 
 alkalis. Alcoholic alkalis convert them at once into the oxides, 
 (R 2 As) 2 0. These oxides are not soluble in aqueous alkalis, but 
 are reconverted into the chlorides, R 2 AsCl, by hydrochloric 
 acid. Hydrogen sulphide converts the oxides in alcoholic 
 solution into crystallisable diarylarsenious sulphides, (R 2 As) 2 S. 
 
 Although the hydroxides, R 2 As-OH, are not known, sodium 
 phenoxide and the diarylarsenious chlorides give rise to esters, 
 e.g. (C 6 H 6 ) 2 As-OC 6 H 5 , corresponding with these hypothetical 
 hy droxy-derivat ives . 
 
 The arylcacodyls, R 2 As'AsR 2 , are obtained by warming alcoholic 
 solutions of the diarylarsenious oxides with phosphorous acid. 
 
 77 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Their derivatives are readily oxidised and take up chlorine 
 or bromine to regenerate the diarylarsenious chloride, R a AsCl, or 
 bromide, R 2 AsBr. 
 
 The diarylarsenic trichlorides, R 2 AsCl 8 , which result from the 
 addition of chlorine to the diarylarsenious chlorides, are 
 hydrolysed by water into the corresponding diarylarsinic acids, 
 R 2 AsOOH. These crystallisable products are amphoteric, 
 behaving as monobasic acids towards strong bases and as weak 
 bases towards strong acids, nitric acid, for instance, giving the 
 nitrate, (C 6 H 6 ) 2 AsOON0 2 . 
 
 Dinitrodiarylarsinic acids, obtained from the diarylarsinic acids 
 by the action of nitric anol sulphuric acids, yield nitro-arylcacodyl 
 compounds on reduction with phosphorous acid. Reduction with 
 hydrogen sulphide and subsequent acidification gives rise to 
 diaminodiarylarsenious sulphides , 
 
 [(NH.-CJEU.A8lS. 
 
 Section I. Benzene Derivatives with One Aromatic Nucleus 
 attached to One Arsenic Atom. 
 
 Phenylarsenious chloride, C 6 H 5 -AsCl 2 , colourless, highly refrac- 
 tive, somewhat viscid liquid, b.p. 252-254. Its odour, which is 
 faintly unpleasant in the cold, becomes very pungent on warming. 
 It fumes only slightly in the air and is not decomposed by 
 water. It has a powerfully irritating action on the skin. Aqueous 
 caustic alkalis dissolve the dichloride, eliminating chlorine and 
 giving rise to unstable compounds of the type C 6 H 5 'As(OK)2 ; 
 these substances regenerate phenylarsenious chloride on warming 
 with concentrated hydrochloric acid. The dichloride combines 
 additively with chlorine but not with bromine. 
 
 Preparation. Phenylarsenious chloride, the starting point for 
 many monophenyl arsenicals, was first obtained by the repeated 
 passage of the vapours of benzene and arsenious chloride through 
 a heated tube. The reaction goes much less readily than in 
 the case of phosphorous chloride, and the products are diphenyl 
 and phenylarsenious chloride which are not . readily separated 
 by distillation or crystallisation. 1 Phenylarsenious chloride can, 
 however, be prepared by either of the three general methods 
 described on page 72. 
 
 (i) Mercury diphenyl (70 grams) is added with stirring to 
 800 grams of carefully-purified arsenious chloride and the 
 1 La Coste and Michaelis, Ber.. 1878, 11, 1883. 
 
 7 8 
 
AROMATIC ARSENICALS 
 
 mixture rapidly heated to 254. The mercury is converted 
 completely into the dichloride, 1 
 
 2AsCl 3 + Hg(C 6 H 5 ) 2 = 2C 6 H 5 -AsCl 2 + HgCl 2 . 
 
 At lower temperatures some phenylmercuric chloride is obtained, 
 (ii) Triphenylarsine, 2 when heated with arsenious chloride in 
 sealed tubes at 250 is converted readily into phenylarsenious 
 chloride, 
 
 (C 6 H 5 ) 3 As -f 2AsCl 3 = 3C 6 H 5 -AsCl 2 . 
 
 (iii) A third more recent synthesis 3 leads from arylmercuri- 
 chlorides to phenylarsenious chloride and its homologues. 
 Benzene (100 c.c.) is heated for five hours at 100 with mercuric 
 acetate in acetic acid solution. The filtrate is concentrated and 
 treated with alcoholic calcium chloride, when phenylmercuri- 
 chloride separates. This compound (30 grams) heated with 
 arsenious chloride (100 grams) at 100 for four to five hours 
 yields phenylarsenious chloride, 
 
 C 6 H 5 HgCl + AsCl 3 = HgCl 2 + C 6 H 5 AsCl 2 . 
 
 The reaction is a general one, but carboxyl and hydroxyl groups must 
 be protected by alkylation to prevent their hydrogen atoms 
 interacting with arsenious chloride to form hydrogen chloride. 
 
 Phenylarsenic chloride,* C 6 H 5 'AsCl 4 . Although arsenious 
 chloride does not combine with chlorine, this halogen is absorbed 
 by phenylarsenious chloride with considerable generation of 
 heat. The product solidifies at o to yellow flattened needles 
 melting at 45. When added to water the tetrachloride is 
 decomposed violently with a hissing sound, considerable heat 
 being generated. In this respect phenylarsenic chloride resembles 
 phosphenyl tetrachloride, C 6 H 5 -PC1 4 ; but towards organic acids 
 it behaves differently, acting as a chlorinating agent, whilst 
 the phosphorus compound forms acid chlorides by replacing 
 hydroxyl by chlorine, 
 
 CH 3 -CO 2 H + C 6 H 5 AsCl 4 = C 6 H 5 AsCl 2 + CH 2 C1-C0 2 H + HC1. 
 
 The foregoing reaction takes place on warming ; in the cold the 
 tetrachloride dissolves in the acid without interaction. 
 
 On warming, the tetrachloride dissociates into the dichloride 
 and free chlorine ; this change is facilitated by heating in a 
 
 1 La Coste and Michaelis, Annalen, 1880, 201, i 
 
 2 Michaelis and Reese, Ber., 1882, 15, 2873. 
 
 3 Roeder and Blas, Ber., 1914, 47, 2748. 
 * Michaelis, Ber., 1877, 10, 622. 
 
 79 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 stream of dry carbon dioxide. At 150 the tetrachloride is 
 decomposed completely into chlorobenzene and arsenious 
 chloride, a reaction recalling the behaviour of methylarsenic 
 chloride (v. p. 33), 
 
 C 6 H 5 AsCl 4 = C 6 H 5 C1 + AsCl 3 . 
 
 Phenylarsenic oxy chloride ^ C 6 H 5 AsOCl 2 , a white, crystalline 
 substance melting at 100 and hydrolysed by water or moist air 
 to phenylarsinic acid, is obtained by adding the requisite amount 
 of water to the foregoing tetrachloride, but is prepared more 
 readily by the addition of chlorine to phenylarsenious oxide. 
 At 150 it is decomposed into chlorobenzene and arsenious 
 oxychloride. The corresponding oxy bromide is produced, 
 together with bromobenzene, by the action of bromine on phenyl- 
 arsenious oxide. 
 
 Phenylarsenious bromide,' 2 ' C 6 H 5 -AsBr 2 , a colourless or faintly 
 yellow liquid, D = 2-0983/15, b.p. 285 (with slight decomposi- 
 tion), is prepared by warming phenylarsenious oxide with 
 concentrated hydrobromic acid. Bromine decomposes the 
 bromide into bromobenzene and arsenious bromide. 
 
 Phenylarsenious iodide, C 6 H 5 -AsI 2 , 3 a red oil obtained by treat- 
 ing phenylarsenious oxide with highly concentrated hydriodic acid 
 (D = 17), is reduced to di-iodoarsenobenzene, C 6 H 5 -AsrAsI-C 6 H 5 , 
 by phosphorous acid. 
 
 Phenylarsenious oxidef C 8 H 5 -AsO, colourless, crystalline crusts 
 from alcohol, m.p. 119-120, is obtained by adding sodium 
 carbonate to a suspension of phenylarsenious chloride in warm 
 water. In the cold the oxide has a characteristic odour resembling 
 anise ; on warming it becomes very irritant to the mucous 
 membrane of the nose. It is slightly volatile in steam, insoluble 
 in water, easily soluble in hot alcohol or cold benzene. Treat- 
 ment with hydrochloric acid regenerates phenylarsenious chloride. 
 It is scarcely soluble in ammonia, but dissolves readily in aqueous 
 sodium hydroxide to a saline substance, C 6 H 5 As(ONa) 2 , from 
 which the oxide is reprecipitated by acids. 
 
 Heated above its melting point it is decomposed into tri- 
 phenylarsine and arsenious oxide, 
 
 3 C 6 H 5 AsO = (C 6 H 5 ) s As + As 2 3 . 
 
 1 La Coste and Michaelis, Annalen, 1880, 201, 191. 
 
 2 Loc. cit. Michaelis, Ber., 1877, 10, 625. 
 
 3 Michaelis and Schulte, Ber., 1881, 14, 913. 
 
 4 Michaelis, Ber., 1877, 10, 623. 
 
 80 
 
AROMATIC ARSENICALS 
 
 When reduced with phosphorous acid the oxide is converted 
 into arsenobenzene ; other reducing agents, such as sodium 
 amalgam and zinc and hydrochloric acid, bring about the same 
 change. 
 
 Esters of Phenylarsenious Acid, 1 
 
 Although phenylarsenious acid, C 6 H 6 -As(OH) 2 , has not been 
 isolated except as its anhydride, phenylarsenious oxide, 
 C 6 H 5 -AsO, yet its alkyl and aryl esters have been prepared by 
 the action of alkali, alkyl- and aryl-oxides on phenylarsenious 
 chloride. 2 
 
 Methyl phenylarsenite, C 6 H 5 -As(OCH 3 ) 2 , colourless liquid with 
 characteristic odour, b.p. 220, with partial decomposition 
 under atmospheric pressure, Ii6/i8 mm. ; D = 1-343/20. 
 Immediately hydrolysed into phenylarsenious oxide by water 
 or alkalis. It absorbs dry chlorine, forming the additive compound, 
 C 8 H 5 AsCl 2 (O-CH 3 ) 2 , colourless crystals, m.p. 90, hydrolysed by 
 water or alcohol to phenylarsinic acid 
 
 C 6 H 5 -AsCl 2 (0-CH 3 ) 2 + 3 H 2 = 
 
 C 6 H 5 -AsO(OH) 2 + 2CH 3 -OH + 2HC1. 
 
 Ethyl phenylarsenite, C 6 H 5 -As(0-C 2 H 5 ) 2 , colourless liquid with 
 unpleasant odour, b.p. I22/I5 mm. This compound and the 
 preceding ester are prepared by adding phenylarsenious chloride 
 to sodium ethoxide and methoxide respectively suspended in 
 dry ether. Additive compound, C 6 H 5 AsCl 2 (OC 2 H 5 ) 2 , cubical 
 crystals, m.p. 95. 
 
 Phenyl phenylarsenite, C 6 H 5 'As(OC 6 H 5 ) 2 , colourless liquid, 
 b.p. 245/i5 mm. D == 1-32/20. Prepared by adding phenyl- 
 arsenious chloride to sodium phenoxide in dry ether. No chlorine 
 additive compound is obtainable since this halogen decomposes 
 the ester into phenylarsenic chloride and trichlorophenol, 
 C 6 Ha-As(0-C 6 H 5 ) 2 + 8C1 2 = C 6 H 5 -AsCl 4 + 2C 6 H 2 C1 3 -OH + 6HC1. 
 
 Bromine reacts similarly. 
 
 p-Cresyl phenylarsenite, C 6 H 5 -As(0-C 6 H 4 -CH 3 ) 2 , pale yellow oil, 
 b.p. 285712 mm. D = 1-2989/13. Prepared by adding phenyl- 
 arsenious chloride to sodium ^-tolyloxide suspended in xylene, 
 the condensation being completed by boiling. 
 
 Benzyl phenylarsenite, C 6 H 5 -As(O-CH 2 -C 6 H 4 ) 2 , light yellow oil, 
 
 1 Michaelis, Annalen, 1902, 320, 286. 
 
 2 Fromm, Inaug. Dissert., Rostock, 1896. 
 
 8l G 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 odour of benzyl alcohol, b.p. 296730111111. D = 1-2853/13. 
 Obtained as in the preceding preparation. 
 
 /3-Naphthyl phenylarsenite, C 6 H 5 -As(O-C 1( )H 7 ) 2 , colourless needles 
 from benzene-petroleum, m.p. 113-114, readily hydrolysed by 
 water. In this preparation phenylarsenious chloride is added to 
 an ethereal solution of sodium /8-naphthoxide. 
 
 /\ 
 
 Catechyl phenylarsenite, C 6 H 5 -As<^ \C 6 H 4 , colourless, crystal- 
 line mass, m.p. 83 ; b.p. 197-198715111111. ; easily hydrolysed 
 by water. Prepared by adding phenylarsenious chloride to the 
 dry lead (not sodium) salt of catechol suspended in anhydrous 
 xylene. 
 
 Phenylarsenimide, 1 C 6 H 5 -As:NH, colourless, crystalline mass 
 from benzene-ether, sintering at 265, m.p. -270. Prepared by 
 passing dry ammonia into phenylarsenious chloride in benzene 
 solution ; considerable heat is generated, the benzene boiling 
 during the separation of ammonium chloride. The imide is 
 readily soluble in benzene or xylene, dissolving sparingly in 
 ether or absolute alcohol. From the last solvent it separates 
 in well-defined leaflets. Hydrolysed by water or dilute acids, 
 
 C 6 H 5 -AsCl 2 + 3 NH 3 = C 6 H 5 -As:NH + 2NH 4 C1. 
 C 6 H 5 -As:NH + H 2 O = C 6 H 5 -AsO + NH 3 . 
 
 Organic amines also interact with phenylarsenious chloride. 
 Butylamine and dibutylamine give C 6 H 5 -AsCl-NHC 4 H 9 and 
 C 6 H 5 -AsCl-N(C 4 H 9 ) 2 . Aniline yields C 6 H 5 -AsCl-NH-C 6 H 5 , whilst 
 tertiary amines furnish additive compounds such as 
 
 C 6 H 5 AsCl 2 :N(C 2 H 5 ) 3 . 
 
 Phenylarsenious sulphide, 2 C 6 H 5 -AsS, white needles from 
 benzene, m.p. 152. Obtained by passing hydrogen sulphide into 
 an alcoholic solution of phenylarsenious oxide or phenylarsenious 
 chloride. Sparingly soluble in alcohol, ether, or cold benzene, 
 dissolving readily in hot benzene or carbon bisulphide. Not 
 attacked by hydrochloric acid, but oxidised by nitric acid, 
 yielding phenylarsinic acid ; sparingly soluble in ammonia 
 or colourless ammonium sulphide. It dissolves readily in yellow 
 ammonium sulphide, from which solution acids precipitate 
 phenylarsenic sesquisulphide, (C 6 H 5 -As) 2 S 3 . This higher sulphide 
 
 1 Michaelis, Annalen, 1902, 320, 291. 
 
 2 Schulte, Bey., 1882, 15, 1955- 
 
 82 
 
AROMATIC ARSENICALS 
 
 is also prepared by saturating with hydrogen sulphide an 
 ammoniacal solution of phenylarsinic acid and precipitating with 
 mineral acid, 
 
 C 6 H 5 -AsO(ONH 4 ) 2 + 3H 2 S = C 6 H 5 -AsS(SNH 4 ) 2 + 3 H 2 O. 
 2C 6 H 5 -AsS(SNH 4 ) 2 +4HCl-(C 6 H 5 -As) 2 S 3 +S+2H 2 S+4NH 4 CL 
 
 The sesquisulphide crystallises from benzene in light yellow 
 prisms and from glacial acetic acid in leaflets, m.p. 130. It 
 is easily soluble in carbon bisulphide, sparingly so in alcohol 
 or ether ; insoluble in ammonia, dissolving sparingly in aqueous 
 sodium hydroxide, and readily in sodium polysulphide to 
 yield sodium pJienyltrithioarsinate, C 6 H 5 -AsS(SNa) 2 ,6H 2 O ; well- 
 defined needles, which are easily soluble in water and precipi- 
 tated by alcohol. The free phenylthioarsinic acid does not 
 exist. 
 
 Phenylarsinic acid, 1 C 6 H 5 -AsO(OH) 2 , elongated, colourless 
 prisms from water. D = 1-840. Softening at 158, and passing 
 into phenylarsinic anhydride, C 6 H 5 -AsO 2 , a white, amorphous 
 powder regenerating the acid in water and decomposed on 
 heating without melting. The acid is soluble in absolute alcohol 
 and is extracted by ether from aqueous solutions containing 
 excess of mineral acid. It is very stable towards oxidising agents, 
 and is not affected by hot concentrated nitric acid or by chromic 
 acid. When treated with ordinary zinc in acid or alkaline 
 solution there is no very marked change, although the develop- 
 ment of a garlic odour suggests the formation of an arsine. It 
 has recently been shown by Palmer and Dehn (v. p. 89) that 
 phenylarsine can be produced by the reduction of phenylarsinic 
 acid. 
 
 Phosphorous acid at 180 reduces phenylarsinic acid to 
 arsenobenzene, and potash fusion leads to phenol and potassium 
 arsenite. This acid is distinctly poisonous, and the period 
 between the commencement of poisonous symptoms and the 
 death of the experimental animal is less than with arsenious 
 acid but similar to that of arsenic acid. 
 
 Phenylarsinic acid results from the interaction of phenyl- 
 arsenic chloride and water, but in this preparation it is quite 
 unnecessary to isolate the higher chloride. 
 
 Phenylarsenious chloride (25 grams) is suspended in water 
 (100 c.c.) and chlorine passed in until the oily drops of lower 
 chloride entirely disappear. With a rapid stream of the gas the 
 
 1 La Coste and Michaelis, loc. cit. ; Michaelis, Ber., 1877, 10, 626. 
 
 83 G 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 liquid becomes sufficiently heated to dissolve the product. The 
 solution of phenylarsinic acid is evaporated to dryness and 
 crystallised from alcohol. 
 
 This acid is also obtainable by Bart's reaction on adding 
 potassium arsenite to an aqueous solution of potassium benzene- 
 i'sodiazo-oxide, the mixture being stirred and heated till nitrogen 
 is evolved. The excess of alkali is then neutralised with acid, 
 the filtered solution evaporated to dryness, and potassium 
 phenylarsinate extracted from the residue with alcohol. From 
 this salt the free acid is precipitated with hydrochloric acid. 1 
 It is also obtained from benzenediazonium chloride, sodium 
 arsenite, sodium hydroxide, and cuprous oxide. 2 
 
 Phenylarsinic acid is prepared from ^-arsanilic acid by treating 
 the diazo-compound of the latter by Mai's method 3 with sodium 
 hypophosphite and dilute hydrochloric acid. In this process the 
 product is purified successively through its barium, zinc, and 
 sodium salts. 4 
 
 Salts of Phenylarsinic Acid. 5 Alkali salts amorphous. Acid 
 barium salt, (C 6 H 5 -AsO 3 H) 2 Ba, needles, less soluble in hot than 
 in cold water. Acid calcium salt, (C 6 H 5 'AsO 3 H) 2 Ca, prepared by 
 adding ammonia to a boiling solution of calcium chloride and 
 phenylarsinic acid ; nacreous leaflets with a greasy texture. 
 Normal calcium salt, C 6 H 5 -AsO 3 Ca,2H 2 O, acicular aggregates. 
 Copper salt, C 6 H 5 -As0 3 Cu, and lead salt are green and white 
 precipitates respectively. Silver phenylarsinate, C 6 H 5 -AsO(OAg) 2 , 
 colourless, microcrystalline powder from ammonium salt and 
 silver nitrate. 
 
 Esters of Phenylarsinic Acid. 6 
 
 Preparation : (i) By the action of sodium alkyloxide on phenyl- 
 arsenic oxychloride, 
 
 C 6 H 5 -AsOCl 2 + 2NaOR = C 6 H 5 -AsO(OR) a + 2NaCl. 
 (ii) Double decomposition between alkyl iodides and silver 
 phenylarsinate, 
 
 C 6 H 5 -AsO(OAg) a + 2RI = C 6 H 5 -As(OR) 2 + 2AgI. 
 The reaction sets in even at the ordinary temperature and 
 
 Bart, D.R.-P., 250264. 
 
 Chem. Fabrick von Heyden, D.R-P., 264924. 
 
 Ber., 1902, 35, 162. 4 Bertheim, Ber.. 1908, 41, 1854. 
 
 Michaelis and Loesner, Ber., 1894, 27, 265. 
 
 Michaelis, Annalen, 1902, 320, 294. 
 
AROMATIC ARSENIC ALS 
 
 is completed at 100 in a reflux apparatus. The calculated amount 
 of alkyl iodide must be used, because excess leads to liberation 
 of iodine and formation of alkyl phenylarsenites, 
 
 C 6 H 5 -AsO(OAg) 2 + 4 CH 3 I = 
 
 C 6 H 5 -As(OCH 3 ) 2 + 2AgI + I 2 + (CH 8 ) 2 0. 
 
 Methyl phenylarsinate, C 6 H 5 -AsO(OCH 3 ) 2 , colourless liquid of 
 unpleasant odour, b.p. i88/95 mm. D = 1-3946/23. Ethyl 
 ester, b.p. 168-170715 mm. D == 1-318/15. 
 
 Halogen Derivatives of Phenylarsinic Acid. 
 
 p-Chlorophenylarsinic acid, 1 C 6 H 4 Cl-AsO(OH) 2 , colourless crys- 
 tals obtained from ^>-arsanilic acid by the Gattermann diazo- 
 re act ion (hydrochloric acid and copper powder) ; it is charac- 
 terised by its barium salt, (C 6 H 4 Cl-AsO 3 H) 2 Ba, which separates 
 in white needles. 
 
 p-Bromophenylarsinic acid, 2 C 6 H 4 Br-AsO(OH) a , white needles, 
 sparingly soluble in water, is prepared by adding successively 
 sodium arsenite and caustic alkali to a solution of ^-bromo- 
 benzenediazonium chloride obtained by the ordinary diazotisa- 
 tion of ^-bromoaniline hydrochloride. The mixture is heated 
 until nitrogen is all evolved and the product isolated by acidifying 
 the filtered solution. 
 
 p-Iodophenylarsinic acid? C 6 H 4 -IAsO 3 H 2 , needles, slightly 
 soluble in water or cold alcohol, dissolving in caustic and car- 
 bonated alkalis, is prepared together with p-iodophenylarsenious 
 iodide, C 6 H 4 rAsI 2 , by treating diazotised atoxyl with a hydro- 
 chloric acid solution containing potassium iodide, copper sulphate, 
 and sodium thiosulphate. p-I-odophenylarsenious oxide is pro- 
 duced by the action of alkalis on the preceding iodide. Reduc- 
 tion with phosphorous acid at 120 for twelve hours leads to 
 4 : ^'-di-iodoarsenobenzene, I-C 6 H 4 -As:As-C 6 H 4 -I, yellow powder, 
 m.p. 145-150, insoluble in all organic media. 
 
 Phenylarsinic acid p-iodochloride* ICl 2 -C 6 H 4 -AsO(OH) 2 , is 
 precipitated as a yellow, crystalline powder on saturating with 
 chlorine a cold solution of />-iodophenylarsinic acid in glacial 
 acetic acid. p-Iodosophenylarsinic acid, IOC 6 H 4 -AsO(OH) 2 , is 
 obtained as a white, microcrystalline precipitate by adding 
 
 1 Bertheim, Bey., 1908, 41, 1854. 2 H. Bart, D.R.-P., 250264. 
 
 3 Mameli and Patta, Giorn. Farm. Chim., 1909, 58, 97 ; Arch. Farmacol. 
 sperim., 1909, 8, 395. 
 
 4 Karrer, Ber,, 1914, 47, 96. 
 
 85 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 dilute hydrochloric acid to a solution of the preceding chloride in 
 aqueous sodium hydroxide. It is a powerful oxidising agent 
 setting free iodine from acidified potassium iodide, decomposing 
 litmus and bleaching indigo. It explodes on heating and is 
 sparingly soluble in alcohol, acetic acid, or water, but dissolves 
 readily in alkalis or in sodium acetate. 
 
 p-Iodoxyphenylarsinic acid, I0 2 ! C 6 H 4 AsO(OH) 2 , a white, granular 
 substance obtained by oxidising ^>-iodophenylarsinic acid or 
 the preceding compound with chlorine and cold AT-sodium 
 hydroxide. It is extremely insoluble in the ordinary solvents, its 
 oxidising action is more pronounced than that of the iodoso- 
 compound, and it explodes sharply on heating. 
 
 Polyhalogenated Phenylarsinic Acids. 1 
 3 : 5-Dichlorophenylarsinic acid (I), 
 
 C L_ C L_ 
 
 / \AsO(OH) 2 I / \AsO(OH) 2 , 
 
 cr cr~ 
 
 I. II. 
 
 is obtained in well-defined snow-white leaflets by diazotising 
 3 : 5-dichloro-^>-arsanilic acid by Witt's method, 2 which consists 
 in mixing this acid with potassium pyrosulphite and adding the 
 mixture slowly to ice-cold nitric acid (D = 1-49). On adding, 
 ice a clear solution is produced from which the diazo-derivative 
 subsequently crystallises. The clear solution of the diazo-com- 
 pound is mixed with alcohol and a small amount of finely divided 
 copper is added. Effervescence sets in at the ordinary tempera- 
 ture and is completed by warming. When all the copper has 
 dissolved the solution is cooled, when 3 : 5-dichlorophenyl- 
 arsinic acid separates. 
 
 3 : ^-Dichloro-^-iodophenylarsinic Acid (II). The foregoing 
 crystalline diazo-derivative is dissolved in water and 
 treated with 10% potassium iodide solution. A vigorous 
 effervescence results and the product separates. When crystal- 
 lised from 50% acetic acid it takes the form of white, felted 
 needles, sparingly soluble in water. 
 
 The two foregoing polyhalogenated phenylarsinic acids when 
 injected into mice produce extremely acute jaundice, the 
 
 1 Karrer, Ber., 1914, 47, 1781. 2 Witt, Ber., 1909, 42, 2953. 
 
 86 
 
AROMATIC ARSENICALS 
 
 intensity of which exceeds that produced either by 4-iodo- 
 phenylarsinic acid or by the so-called " icterogen." l 
 
 / - v X C(CH 3 ):CH 
 H 2 3 As<( >N/ 
 
 x - X C(CH 3 ):CH 
 
 The toxicity of these halogenated compounds as shown towards 
 mice is of interest. 3 : 5-Dichlorophenylarsinic acid is much less 
 lethal than 3 : 5-dichloro-4-iodophenylarsinic acid or 4-iodophenyl- 
 arsinic acid, which have the same degree of toxicity. The 
 presence of halogen in the para-position with respect to arsenic 
 has a marked effect on the physiological action of these sub- 
 stances. 
 
 : $-dichlorophenylarsinic Acid, 
 
 =AsO(OH) a . 
 
 Cl 
 
 The crystalline diazo-derivative of 3 : 5-dichloro-^>-arsanilic 
 acid is treated with sodium azide in aqueous solution, when 
 the colourless triazo-compound results at the ordinary tem- 
 perature. 
 
 Arsenobenzene, 21 C 6 H 5 -As:As-C 6 H 5 , light yellow needles, m.p. 
 196 ; insoluble in water or ether ; very sparingly soluble in 
 alcohol, dissolving readily in benzene, chloroform, or carbon 
 bisulphide to solutions which readily resinify. It is prepared by 
 adding crystallised phosphorous acid in excess to a moderately 
 concentrated alcoholic solution of phenylarsenious oxide, 
 
 2C 6 H 5 AsO + 2H 3 PO 3 =2H 3 P0 4 + C 6 H 5 -As:As-C 6 H 5 . 
 
 It can also be obtained by reducing phenylarsinic acid with 
 phosphorous acid, but this reaction goes more slowly and requires 
 a higher temperature (180) . 
 
 On boiling the solution the arsenobenzene separates until the 
 liquid becomes pasty. It separates in well-defined crystals 
 from boiling xylene, but the mother liquor yields only tarry 
 products. 
 
 Arsenobenzene combines directly with chlorine or sulphur, 
 
 1 This dimethylpyrrole derivative of ^-arsanilic acid is referred to by 
 Ehrlich (Ber., 1909, 42, 39) as having been prepared by Schmitz from 
 acetonylacetone and ^-arsanilic acid. It is 20-30 times as toxic as the 
 latter compound and is lacking in curative value. On the other hand, 
 it induces fatal jaundice (icterus) in mice, rats, and guinea pigs. 
 
 2 Michaelis and Schulte, Ber., 1881, 14, 912 ; 1882, 15, 1952. 
 
 8? 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 yielding phenylarsenious chloride and phenylarsenious sulphide 
 respectively. With oxidising agents it gives rise to phenyl- 
 arsinic acid and with mercury diethyl at 150 it furnishes phenyl- 
 diethylarsine. On heating it changes completely into triphenyl- 
 arsine and arsenic (compare p. 40). 
 
 3 (C 6 H 6 As) a = 2(C 6 H 6 ) 3 As + As. 
 
 Co-ordination Compound with Cupric Chloride. 1 Phenylarsinic 
 acid (4 grams) and hydrated cupric chloride (1-7 grams) are heated 
 to boiling with 5oc.c. of 35 per cent, hypophosphorous acid ; the 
 product separates as a yellowish-brown precipitate, readily soluble 
 in pyridine. 
 
 Fission of Arsenobenzene and its Derivatives by Alkyl Iodides. 2 
 
 Arsenobenzene when heated with methyl iodide in a sealed 
 tube at 100 undergoes fission into two aromatic compounds, 
 each containing one atomic proportion of arsenic. The reaction 
 is a general one for methyl iodide and occurs also with the 
 aliphatic arseno-compounds arseno-methane and -ethane. The 
 reactions with the homologous alkyl iodides are more complicated. 
 The following equations indicate the analogies between this 
 fission process and other reactions of arsenic and its organic 
 derivatives, 
 
 A SEE ;As + CH 3 I = As(CH,)J,AsI, 
 
 3 CH 8 ! I (page 22) 
 
 CH 8 -As=!AsCH 3 + CH 3 I = As(CH 8 ) 4 I + CH 8 AsI 2 
 zCHj I (page 40) 
 
 (CH 3 ) 2 As :As(CH 3 ) 2 + CH 8 I = As(CH 3 ) 4 I + (CH 8 ) 2 AsI 
 CH 3 ' I (page u) 
 
 C 6 H 6 -As=:iAs-C 6 H 6 + CH 8 I = C 6 H 6 As(CH 3 ) 3 I + C 6 H 5 AsI 2 
 2CH 3 ; I 
 
 Arsenobenzene yields phenyltrimethylarsonium iodide and 
 phenylarsenious iodide, the latter being identified by conversion 
 into phenylarsenious oxide and phenylarsinic acid. 
 
 Arseno-^)-toluene behaves similarly, yielding ^-tolyltrimethyl- 
 arsonium iodide and ^-tolylarsenious iodide. 
 
 Di-iodo&rsenobenzene*CJ:{i'A.sI'AsI'CL 6 , bright yellow needles, 
 by reducing with phosphorous acid an alcoholic solution of 
 phenylarsenious iodide. A very unstable compound, oxidised 
 
 1 M. L. and B., D.R.-P., 270258. 2 Bertheim, Ber., 1914. 47, 271. 
 3 Mameli and Patta, he. cit., 1909. 
 
AROMATIC ARSENICALS 
 
 in the air : As 2 (C 8 H 5 ) 2 I 2 + O a -f H 2 O = C 6 H 5 AsI 2 + C,H 6 -AsO 3 H. 
 Oxidised by nitric acid to phenylarsinic acid; combining with 
 iodine to form phenylarsenious iodide ; decomposed on heating 
 as follows: 3As 2 (C 6 H 6 ) 2 I a =2As(C 6 H 5 ) 3 +2AsI 3 +2As. When 
 heated with methyl iodide at 100, di-iodoarsenobenzene 
 undergoes fission into p-iodophenyltrimethylarsonium iodide, 
 iridescent leaflets melting above 300, and ^-iodophenylarsenious 
 iodide identified as p-iodophenylarsinic acid* 
 p-Phenylenediarsinic acid, 2 
 
 (HO) 2 OAs/ \AsO(OH) 2 , 
 
 colourless crystals from water, is prepared from atoxyl (p. 158) 
 by Bart's reaction. Sodium ^-arsanilate is diazotised in dilute 
 hydrochloric acid and warmed gently with alkaline sodium 
 arsenite. The solution is then neutralised, filtered, and evapor- 
 ated to dryness with a slight excess of hydrochloric acid, and the 
 residue extracted with methyl alcohol. The alkali salts of this 
 acid are readily soluble in water but dissolve only sparingly in 
 alcohol. 
 
 Phenylarsine* C 6 H B -AsH,, colourless, highly refractive oil, 
 b.p. 1487760 mm., 93770 mm., 84755 mm., and 77733 mm. ; 
 odour resembling that of phenyl isocyanide, but on dilution like 
 that of hyacinths. Soluble in alcohol or ether. Vapour density 
 normal. 
 
 Phenylarsine is prepared by mixing in a reflux apparatus 
 purified calcium phenylarsinate 4 (v. p. 84) with excess of amal- 
 gamated zinc dust ; this mixture is covered with water and a 
 layer of ether. Hydrochloric acid is added at the rate of 5-10 
 drops per minute. The ethereal layer which contains the 
 phenylarsine is dried over calcium chloride and distilled; the 
 product passing over at 9377 mm - is collected in an atmosphere 
 of carbon dioxide. 
 
 Phenylarsine oxidises in the air to a mixture of phenylarsenious 
 oxide, phenylarsinic acid, and arsenobenzene, and in ethereal 
 solution to the last of these products, which separates in well- 
 defined, yellow crystals melting at 195-196. Oxidation 
 with nitric acid yields phenylarsinic acid and a yellow oil contain- 
 
 1 Bertheim, Bey., 1914, 47, 276. 2 H. Bart, D.R.-P., 250264. 
 
 3 Palmer and Dehn, Ber., 1901, 34, 3598; Amer. Chem. /., 1905. 
 33, 147- 
 
 4 La Coste and Michaelis, Annalen, 201, 203, 209 ; Michaelis and Loesner, 
 Ber., 1894, 27, 264. 
 
 8 9 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 ing nitrobenzene and arsenobenzene. Iodine in potassium iodide 
 solution oxidises phenylarsine partly to phenylarsinic * acid and 
 partly to phenylarsenious iodide. Methyl and ethyl iodides and 
 phenylarsine at 120 give rise to hydrogen iodide and to phenyl- 
 trimethylarsonium and phenyltriethylarsonium iodides re- 
 spectively. 
 
 Phenyldimethylarsine, 1 C 6 H 5 'As(CH 3 ) 2 , colourless, refractive, 
 moderately limpid liquid with repulsive odour, b.p. 200. In- 
 soluble in water, completely miscible with alcohol or benzene. 
 Prepared by the action of zinc dimethyl on phenylarsenious 
 chloride. 
 
 Phenyltrimethylarsonium iodide, C 6 H 5 As(CH 3 ) 3 -I, white needles, 
 m.p. 244, readily soluble in water or alcohol, insoluble in ether. 
 Prepared by the addition of methyl iodide to the foregoing 
 compound, 2 and by the interaction of phenylarsine and methyl 
 iodide ; the iodide dissociates into its generators when heated 
 in a current of carbon dioxide : platinichloride, red lamellae, 
 m.p. 219. 
 
 Phenyldiethylarsine? C 6 H 5 'As(C 2 H 5 ) 2 , colourless, highly re- 
 fractive liquid with faint unpleasant odour, b.p. 240. Prepared 
 by adding zinc diethyl slowly to phenylarsenious chloride 
 diluted with benzene or ether. The reaction is very vigorous 
 and the tertiary arsine is obtained after removing the solvent 
 and treating the residue with caustic alkali. This compound 
 is not affected by hydrochloric acid, but absorbs chlorine readily, 
 to yield the crystalline phenyldiethylarsinic chloride, 
 
 C 6 H 6 -As(C 2 H 5 ) 2 Cl 2 . 
 
 Phenyltriethylarsonium iodide* C 6 H 5 'As(C 2 H 5 ) 3 I. Ethyl iodide 
 and the preceding base do not interact at the ordinary tempera- 
 ture, but only at 100. The product forms colourless, prismatic 
 crystals of intensely bitter taste, m.p. 112-113 ; it dissociates into 
 its generators on heating in carbon dioxide. This quaternary iodide 
 is also obtained by the interaction of phenylarsine and ethyl 
 iodide at I2O. 5 Moist silver oxide liberates the highly caustic 
 phenyltriethylarsonium hydroxide obtained as a syrupy mass 
 absorbing carbon dioxide from the atmosphere. The corre- 
 
 1 Michaelis and Link, Annalen, 1881, 207, 205. 
 
 2 Dehn, Amer. Chem. /., 1905, 33, 152. 
 
 3 Michaelis and La Coste, Annalen, 1880, 201, 212. 
 
 4 La Coste and Michaelis, Ber., 1878, 11, 1884. 
 
 5 Dehn, Amer. Chem. ]., 1905, 33, 151. 
 
 9 
 
AROMATIC ARSENICALS 
 
 spending chloride is uncrystallisable ; the platinichloride forms 
 golden-yellow leaflets. 
 
 Phenylmethyldiethylarsonium iodide, C 6 H 5 ' As(C 2 H 5 ) 2 (CH 8 ) * I , 
 well-defined prisms, m.p. 122 ; chloride oily, platinichloride, m.p. 
 190. 
 
 Phenyltriethylarsonium dichloro-iodide, C 6 H 6 'As(C 2 H 6 ) 3 -ICl 2 , 
 lustrous dark yellow crystals, m.p. 79. Obtained by passing 
 chlorine into a glacial acetic acid solution of phenyltriethyl- 
 arsonium iodide. 
 
 Phenyliodomethyldiethylarsonium iodide, 
 
 crystallises in needles from dilute alcohol, m.p. 173. Sparingly 
 soluble in hot alcohol, acetone, or water, more so in methyl 
 alcohol ; prepared by warming on the water-bath phenyldi- 
 ethylarsine and methylene iodide. 
 
 Phenyltriisoamylarsonium iodide, 1 pearly white crystals, m.p. 
 163. Very soluble in chloroform or alcohol, but insoluble in 
 benzene, light petroleum, ether, or cold water. It is prepared 
 by heating phenylarsine and isoamyl iodide at 140-150. 
 
 The Asymmetric Arsenic Atom. 2 
 
 The following arsines and arsonium iodides were prepared in 
 the hope that the latter would be resolvable into optically active 
 components. This anticipation has not, however, been realised. 
 
 Phenyldimethylarsine 3 is conveniently made by the interaction 
 of phenylarsenious chloride and magnesium methyl iodide in 
 ether, or preferably petroleum ,(b.p. 30-40) ; in the former 
 medium the yield is 40 and in the latter 75 per cent. 
 
 Phenyldimethylarsine dibromide, C 6 H 5 -As(CH 3 ) 2 Br 2 , crystalline, 
 white solid, m.p. 128, is formed from the preceding base and 
 bromine, keeping the former in excess. If the bromine is in 
 excess, Phenyldimethylarsine tetrabromide, a compound of ex- 
 ceptional composition, C 6 H 5 -As(CH 3 ) 2 Br 4 , is produced, forming 
 dark red crystals melting at 65 and yielding at 160 phenyl- 
 arsenious dibromide and methyl bromide (z mols.). 
 
 Phenylmethylarsenious bromide, C 6 H 5 < As(CH 3 ) < Br, prepared by 
 heating the dibromide at 180, is a colourless liquid, b.p. 250. 
 
 1 Amer. Chem. J., 1905, 33, 152. 
 
 2 Winmill, Chem. Soc. Trans., 1912, 101, 722 ; c.f. Michaelis and Predari, 
 p. 109. 3 Michaelis and Link, Annalen, 1881, 207, 205. 
 
 91 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Phenylmethylallylarsine, C 6 H 5 -As(CH 8 )-C 3 H 5 , colourless liquid, 
 b.p. 192, is preferably obtained by adding magnesium powder to 
 a mixture of phenylmethylarsenious bromide and allyl iodide 
 (mol. proportions) in dry ether ; when very little diallyl is thus 
 produced, 
 
 Phenylbenzylmethylallylarsonium iodide, 
 
 C 6 H 6 CH 2 -As(C 6 H 5 )(CH 3 )(C 3 H 6 )I, 
 
 is made by mixing the foregoing tertiary base and benzyl iodide. 
 On crystallising from acetone, it is obtained in colourless crystals, 
 m.p. 100. 
 
 Phenylethyl-n-propylarsine, C 6 H 5 As(C 2 H 6 )-C 3 H 7 , colourless 
 liquid, b.p. 245, a very feeble base, characteristic odour, insoluble 
 in concentrated hydrochloric acid. Prepared by the following 
 series of reactions : 
 
 1. (C 6 H 5 ) 3 As + 2AsCl 3 (at 290-300) = 3C 6 H 5 AsCl 2 . 
 
 2. C 6 H 5 AsCl 2 +Zn(C 2 H 5 ) 2 = C 6 H 6 As(C 2 H 6 ) 2 + ZnCl 2 . 
 
 These reactions proceed smoothly, using light petroleum (b.p. 
 40-50) instead of ether. 
 
 3. Phenylethylarsenious bromide, C 6 H 5 As(C 2 H 5 )-Br, is obtained 
 by heating the dibromide of the preceding tertiary base ; the 
 corresponding chloride is similarly prepared from the dichloride. 
 
 Phenylethyl-n-propylarsine is produced by the action of zinc 
 dipropyl on the preceding bromide. When heated with benzyl 
 iodide (i mol.) at 40-50 it combines additively with this com- 
 pound, giving phenylbenzylmethyl-n-propylarsonium iodide, 
 
 C 6 H 5 -As(C 7 H 7 )(CH 3 )(C 3 H 7 )I, 
 
 colourless crystals, m.p. 128. The d-camphor-(3-sulphonate 
 from this quaternary iodide is readily soluble in water and organic 
 media ; it showed no signs of resolution into optically active 
 components during crystallisation. 
 
 Phenylethyl-n-propylallylarsonium iodide, produced by the 
 combination of phenylethyl-w-propylarsine and allyl iodide, crys- 
 tallises in colourless plates, and gives a d-a-bromocamphor-v 
 sulphonate which crystallises from alcohol-acetone in colourless 
 prisms, m.p. 189, and is not resolvable by fractional crystal- 
 lisation from this solvent. 1 The d-camphor-/?-surphonate is 
 syrupy and non-resolvable. 
 
 These experiments indicate that arsonium compounds of the 
 
 type I. are not resolvable into optically active components under 
 
 experimental conditions comparable with those in which this 
 
 1 Winmill, Chem. Soc. Trans., 1912, 101, 720. 
 
 92 
 
7 
 
 AROMATIC ARSENICALS 
 
 resolution was effected in the case of the analogously constituted 
 quaternary ammonium compounds II. 1 
 
 jC 6 H 5 -CH 2 \ ,C 3 H 5 1 
 
 CH 
 
 I. 
 
 Alkoxyarylarsenious Chlorides and their Derivatives. 
 
 p-Anisylarsenious chloride , 2 CH 3 -OC 6 H 4 -AsQ 2 , colourless, crys- 
 talline mass, m.p. 48, b.p. i6o/3O mm., 23O/ii7 mm. In the 
 ^>-anisyl series Michaelis selected the second general synthetic 
 method with sodium and ^-bromoanisole (made by the direct 
 bromination of anisole in 2j parts of carbon bisulphide). The 
 resulting tri-/>-anisylarsine is heated with excess of arsenious 
 chloride for 24 hours at 200. The latter reagent is distilled 
 off and the residue fractionated in vacuo. ^>-Anisylarsenious 
 chloride when distilled under the ordinary pressure is partially 
 decomposed. With caustic and carbonated alkalis it yields 
 ^>-anisylarsenious oxide, CH 3 -OC 6 H 4 -AsO, a colourless, crystalline 
 mass. It absorbs chlorine in the cold to form p-anisylarsenic 
 chloride, CH 3 -OC 6 H 4 -AsCl 4 , a viscid, yellow liquid decomposed 
 by water, yielding p-anisylarsinic acid, CH 3 -0-C 6 H 4 -AsO(OH) 2 , 
 colourless, hard, crystalline mass, m.p. 179-180, sparingly soluble 
 in cold water, dissolving more readily in alcohol or warm water. 
 Prepared free from chlorine by adding hydrogen peroxide to a 
 solution of ^>-anisylarsenious chloride in glacial acetic acid. 3 
 
 ^-Anisylarsinic acid 4 is more conveniently prepared by methyl - 
 ating sodium phenol-4-arsinate with methyl sulphate in aqueous 
 caustic soda. When maintained for several hours at 190-200 
 this acid furnishes the p-anisylarsinic anhydride (arsino-p-anisole) , 
 CH 8 -OC 6 H 4 -As0 2 . Silverp-amsylarsinate,CH 9 'Q'CJI t 'AsQ(QAg)t, 
 forms a white precipitate from neutral solutions. 
 
 Arseno-p-anisole, CH 3 -O-C 6 H 4 -As:As-C 8 H 4 -<>CH 8 , yellow, 
 amorphous powder, m.p. 200 (with decomposition), obtained 
 by heating ^-anisylarsinic acid with ten parts of aqueous phos- 
 phorous acid in sealed tubes at 100. When heated at this 
 temperature with methyl iodide the arseno-derivative undergoes 
 
 1 Pope and Peachey, Chem. Soc. Trans., 1899, 75, 1127. 
 
 2 Michaelis and Feitz, Ber., 1887, 20, 51 ; Michaelis, Annalen, 1902, 
 320, 298. 
 
 3 Michaelis, Annalen, 1902, 320, 299. * Bertheim, Ber., 1914, 47, 276. 
 
 93 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 fission into p-anisyl-trimethylarsonium iodide (colourless, acicular 
 prisms, m.p. 213) and j5>-anisylarsenious iodide, characterised 
 as ^>-anisylarsinic acid. 1 
 
 p-Phenetylarsenious chloride, 2 C 2 H 6 -OC 6 H 4 -AsCl 2 , colourless 
 liquid, b.p. 198728 mm., obtained by heating tri-^-phenetyl- 
 arsine with eight parts of arsenious chloride at 220 for 24 hours. 
 The oxide, C 2 H 5 -OC 6 H 4 -AsO, m.p. 105, from the preceding 
 chloride and aqueous sodium carbonate. 
 
 Arseno-p-phenetole, C 2 H 5 -O-C 6 H 4 -As:AsC 6 H 4 -(>C 2 H 6 , yellow 
 powder readily becoming resinous. 
 
 p-Phenetylarsinic acid, C 2 H 6 -0-C 6 H 4 -AsO(OH) 2 , colourless 
 crystals from water, m.p. 209-210, by passing chlorine into water 
 containing ^-phenetylarsenious chloride. Calcium, copper, and 
 silver salts are insoluble in water. This acid is also prepared 
 from p-a.Tsa.mlic acid by diazotising the latter with ethyl nitrite 
 in absolute alcohol. The diazo-compound, which is deposited 
 as a white precipitate, is decomposed into the ethoxy-derivative 
 on gently warming. 3 
 
 Mixed Aromatic- Aliphatic Arsinic Acids. 4 
 
 The secondary arsinic acids containing one aromatic and one 
 aliphatic group are conveniently prepared by an extension of 
 G. Meyer's reaction described by Ehrlich and Bertheim. 
 
 / \ 
 
 CH 3 
 ,ONa 
 
 \As< I 
 
 X 0;Na 
 
 Na 
 
 Nal. 
 
 Phenylmethylarsinic Acid, C 8 H 6 As (CH 3 )O- OH. Methyl iodide 
 (8 grams) added to an alcoholic solution (80 c.c.) of phenyl- 
 arsenious oxide (16-8 grams) and 20 c.c. of loN-sodium hydroxide 
 produces a vigorous action, and the mixture after twelve hours 
 is mixed with 300 c.c of water and treated with silver nitrate 
 (25 grams) in 50 c.c. of water and 50 c.c. of nitric acid (D = 1-12). 
 
 1 Bertheim, loc. cit. 2 Michaelis, Annalen, 1902, 320, 299. 
 
 3 Bertheim. Ber., 1908, 41, 1854. 4 Bertheim, Ber., 1915, 48, 350. 
 
 94 
 
AROMATIC ARSENICALS 
 
 The filtrate from silver iodide is decolorised by animal charcoal 
 and the silver salt of phenylmethylarsinic acid precipitated by 
 further addition of 25 grams of silver nitrate and 17 c.c. of con- 
 centrated ammonia. The yield of silver salt is 22 grams. 
 This compound is decomposed with 2A r -hydrochloric acid, 
 the filtrate from silver chloride evaporated to the crystallising 
 point, 20-8 grams of salt yielding 12-6 grams of free acid. Phenyl- 
 methylarsinic acid when dissolved in two parts of water crystal- 
 lises in silky needles (m.p. 179-5) on the addition of ten parts of 
 acetone. It is very soluble in alcohol, water, or glacial acetic 
 acid, but less so in acetone or ether ; its aqueous solution 
 is neutral to methyl orange, but can be titrated with barium 
 hydroxide in presence of litmus. The acid is amphoteric, forming 
 salts both with metallic bases and with mineral acids. The 
 nitrate, C 7 H 8 O 2 As,HNO s , is crystalline. 
 
 Phenylethylarsinic acid, C 6 H 5 As(C 2 H 6 )O-OH, prepared from 
 phenylarsenious oxide and ethyl iodide, separates from the 
 concentrated slightly acidified solution after removing iodine 
 with freshly prepared silver chloride and is crystallised from ethyl 
 acetate (8-4 grams of phenylarsenious oxide yield 7-8 grams 
 of the acid). It is very soluble in water, ethyl and methyl 
 alcohols, chloroform, or acetic acid, dissolves less readily in 
 acetone, benzene or ether, and melts at 108. 
 
 Phenylisoamylarsinic acid, C 6 H 6 As(C 5 H 11 )-AsO-OH, prepared 
 by the general method, resembles the foregoing compound in 
 solubility and melts at 108. 
 
 Phenylbenzylarsinic acid, C 6 H 5 As(CH 2 -C 6 H 6 )-AsO-OH, prepared 
 by adding freshly distilled benzyl chloride to an alcoholic alkaline 
 solution of phenylarsenious oxide (8-4 grams). After three 
 days the filtrate from sodium chloride is diluted with water, 
 freed from benzyl chloride by ether-extraction, and carefully 
 acidified with 27V-hydrochloric acid. The arsinic acid (n grams) 
 separates and is crystallised from alcohol in colourless, lustrous 
 needles, m.p. 206-207. Hot concentrated hydrochloric acid 
 decomposes this arsinic acid into benzyl chloride and phenyl- 
 arsenious chloride. 
 
 Section II. Benzene Derivatives with Two Aromatic 
 Nuclei Attached to One Arsenic Atom. 
 
 Diphenylarsenious chloride, (C 6 H 6 ) 2 AsCl, yellow, faintly odorous 
 oil, not fuming in air and less irritating to the skin than phenyl- 
 arsenious chloride ; b.p. 333 in a current of carbon dioxide ; 
 
 95 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 D = i 42231/15. Insoluble in water, dissolving readily in 
 ether, benzene, or absolute alcohol. It is insoluble in aqueous 
 ammonia or alkali carbonates and only slightly soluble in 
 caustic alkalis. It is formed as a by-product, together with a 
 small proportion of triphenylarsine, in the preparation of phenyl- 
 arsenious chloride from arsenious chloride and mercury diphenyl 1 ; 
 also prepared by adding mercury diphenyl (50 grams) to phenyl- 
 arsenious chloride (230 grams) heated to its boiling point. The 
 dark liquid decanted from a precipitate of mercuric chloride is 
 fractionated and the recovered phenylarsenious chloride again 
 treated as before with mercury diphenyl (50 grams) . Fractiona- 
 tion of the total product yielded 96 grams of diphenylarsenious 
 chloride. The main reaction is as follows : 
 
 2C 6 H 5 AsCl 2 + Hg(C 6 H 5 ) 2 = 2 (C 6 H 5 ) 2 AsCl + HgCl 2 , 
 
 although there is a certain amount (10-20 per cent.) of mercury 
 phenylchloride produced together with an appreciable quantity 
 of triphenylarsine. The addition of mercury diphenyl to excess 
 of phenylarsenious chloride maintained at its boiling point 
 minimises the formation of mercury phenylchloride. 2 
 
 Diphenylarsenious chloride is also obtainable by distilling 
 triphenylarsine chloride under 13-14 mm. pressure. 
 
 (C 6 H 6 ) 3 AsCl 2 - (C 6 H 5 ) 2 AsCl + C 6 H 6 C1. 
 
 In this way 2-5 grams of the monochloride (b.p. 230713-14 mm.) 
 were obtained from 8 grams of triphenylarsine. 
 
 Diphenylarsenic chloride, (C<jH 5 ) 2 AsCl 3 , colourless plates from 
 benzene, m.p. 174, is produced with generation of heat by the 
 addition of dry chlorine to diphenylarsenious chloride. This 
 substance readily dissociates in a current of carbon dioxide, 
 regenerating diphenylarsenious chloride and liberating chlorine. 
 When heated at 200 it decomposes into phenylarsenious chloride 
 and chlorobenzene. 
 
 (C 6 H 5 ) 2 AsCl 8 ~ (C 6 H 5 ) 2 AsCl + Cl a 
 (C 6 H 6 ) 2 AsCl 3 = C 6 H 6 -AsCl a + CJH.-Cl. 
 
 Diphenylarsenious chloride absorbs bromine to form an easily 
 decomposable chlorobromide, (C 6 H 6 ) 2 AsClBr 2 , a flesh-coloured 
 solid. Diphenylarsenious bromide, a viscid, yellow liquid; 
 b-p. 356 (with partial decomposition) ; obtained by heating 
 
 1 La Coste and Michaelis. Ber., 1878, 11, 1885; Annalen, 1880, 
 201, 215. 
 
 2 Michaelis and Link, Annalen, 1881, 207, 195. 
 
AROMATIC ARSENICALS 
 
 diphenylarsenious oxide with fuming hydrobromic acid in sealed 
 tubes. 
 
 Diphenylarsenious oxide, [(C 6 H 5 ) 2 As] 2 O, crystalline aggregates 
 from ether ; m.p. 91-92. Prepared by heating diphenylarsenious 
 chloride with alcoholic potash. Also obtained by the Grignard 
 reaction from powdered arsenious oxide and magnesium phenyl- 
 bromide in ethereal solution. 1 Combines with chlorine to form 
 diphenylarsenic oxychloride, [(C 6 H 6 ) 2 AsCl 2 ] 2 O, white powder, 
 m.p. 117. Soluble in benzene. 
 
 Diphenylarsinic acid, (C 6 H 5 ) 2 AsOOH, colourless needles, 
 m.p. 174 ; D = 1-545 ; produced by the action of water on the 
 preceding oxychloride or on diphenylarsenious chloride. Sparingly 
 soluble in cold water, ether, or benzene, dissolving more readily 
 in hot water or alcohol. No anhydride formed at 190-200, but 
 the acid shows a slight tendency to sublime. Not attacked by 
 hot nitric acid or by chromic acid. 
 
 Diphenylarsinic acid and its salts are poisonous, the toxic 
 action being somewhat more rapid than that of phenylarsinic 
 acid. 2 This circumstance has led to a revision of the often quoted 
 statement that cacodylic acid is not poisonous. A few decigrams 
 of sodium cacodylate injected subcutaneously into rabbits and 
 frogs caused within one to two days the death of these animals 
 with symptoms of arsenical poisoning. 
 
 Diphenylarsinates. The acid is comparatively weak and its 
 ammonium salt is completely dissociated over sulphuric acid. 
 Sodium salt, (C 6 H 6 ) 2 AsO 2 Na, hygroscopic powder. Barium salt, 
 [(C 6 H 5 ) 2 AsO 2 ] 2 Ba, very soluble mass, scarcely crystalline. 
 
 The copper salt is a light blue precipitate. The lead and silver 
 salts are white precipitates, the former slightly soluble in hot 
 water and crystallising therefrom in lustrous needles. 
 
 Phenylcacodyl 3 (Tetraphenyldiarsine), (C 6 H 5 ) 2 As-As(C e H 6 ) 2 , crys- 
 talline mass, m.p. 135 ; somewhat soluble in alcohol, less so in 
 ether. Prepared by boiling an alcoholic solution of diphenyl- 
 arsenious oxide with excess of phosphorous acid ; the cacodyl 
 derivative separates as an oil which solidifies on washing with 
 ether. It absorbs oxygen to form the anhydride (?) of diphenyl- 
 arsinic acid; chlorine converts it into diphenylarsenic chloride. 
 On distillation, it decomposes into triphenylarsine and free 
 
 1 Sachs and Kantorowicz, Ber., 1908, 41, 2767. 
 
 2 Schultz, Ber,, 1879, 12, 21 ; Archiv expev. Pathol. u. Pharmak., Q, 
 131 and 147. _ 
 
 3 Michaelis and Schulte, Ber., 1882, 15, 1954- 
 
 97 H 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 arsenic. It is also obtained by heating diphenylarsinic acid in 
 alcoholic solution with excess of phosphorous acid in sealed tubes 
 at 100. 
 
 Phenyl diphenylarsenite, 1 (C 6 H 6 ) 2 As-0-C 6 H 6 , colourless liquid, 
 b.p. 23o-23i/i5 mm. D = 1-3113/11. Although diphenyl- 
 arsenious acid has not been isolated, its phenyl ester is obtainable 
 by the action of sodium phenoxide on diphenylarsenious chloride 
 dissolved in xylene. This substance, which is isomeric with 
 triphenylarsine oxide, is hydrolysable and absorbs chlorine to 
 form the compound (C 6 H 5 ) 2 AsCl 2 -OC 6 H 5 , needles, m.p. 121-122 ; 
 the bromide, (C 6 H 5 ) 2 AsBr 2 OC 6 H 5 , yellowish-red crystals, melts at 
 100 and is readily hydrolysed. 
 
 Diphenylmethylarsine, 2 (C 6 H 5 ) 2 As-CH 3 , colourless, highly re- 
 fractive, oily liquid, b.p. 306, pungent fruity odour; insoluble in 
 water, dissolving readily in alcohol or benzene. Prepared by the 
 action of zinc dimethyl on diphenylarsenious chloride in cold 
 benzene solution in an atmosphere of carbon dioxide. It does not. 
 combine with ^'sobutyl iodide even at 120. 
 
 Diphenyldimethylarsonium iodide, (C 6 H 6 ) 2 As(CH 3 ) 2 I, colourless, 
 spicular crystals, m.p. 190, bitter taste, is produced even in the 
 cold by adding methyl iodide to diphenylmethylarsine. Sparingly 
 soluble in cold water, more so in hot water or alcohol, 
 insoluble in ether. The substance is sensitive to light and is 
 preferably crystallised from faintly alkaline solutions. It dis- 
 sociates into its generators when heated in a current of carbon 
 dioxide : platinichloride, flattened, reddish-yellow needles from 
 hot water. 
 
 Diphenylethylarsine* (C 6 H 8 ) 2 As-C 2 H 5 , colourless liquid, fruity 
 odour, b.p. 320, prepared by the general method with zinc 
 diethyl on diphenylarsenious chloride. The addition of dry 
 chlorine leads to diphenylethylarsine dichloride, needles from 
 benzene, m.p. 137, decomposed by water with elimination of 
 hydrogen chloride. 
 
 Diphenyldiethylarsonium iodide* (C 6 H 5 ) a As(C a H s )aI, colourless, 
 flattened needles, m.p. 184, prepared from diphenylethylarsine 
 and ethyl iodide at 100. 
 
 Diphenylmethylethylarsonium iodide, 5 (C 6 H 5 ) 2 As(CH 3 )(C 2 H 5 )I, 
 
 1 Michaelis, Annalen, 1902, 321, 143. 
 
 2 Michaelis and Link, Annalen, 1881, 207, 199. 
 
 3 Michaelis and Link, loc. cit. ; La Coste and Michaelis, Annalen, 1880, 
 201, 235. 4 La Coste and Michaelis, Ber., 1878, 11, 1886. 
 
 5 Michaelis and Link, loc. cit. 
 
 9 8 
 
AROMATIC ARSENICALS 
 
 rhombic prisms, m.p. 170, produced either by adding methyl 
 iodide to diphenylethylarsine or ethyl iodide to diphenylmethyl- 
 arsine, the combination being promoted by warming. The sub- 
 stance is readily soluble in alcohol or hot water ; it is sensitive 
 to light, and is preferably crystallised from slightly alkaline 
 solutions. It dissociates on warming in a stream of carbon 
 dioxide into diphenylmethylarsine and ethyl iodide. The free 
 base, diphenylmethylethylarsonium hydroxide, produced by the 
 action of moist silver oxide on the iodide, is a very soluble 
 syrupy mass with strongly alkaline reaction and bitter taste : 
 platinichloride and picrate form yellowish-red and yellow needles 
 respectively. 
 
 Diphenylarsenious sulphide, [(C 6 H 5 ) 2 As] 2 S, colourless, silky 
 needles, m.p. 67, obtained by passing hydrogen sulphide into 
 alcoholic solution of the corresponding oxide and chloride. 
 Insoluble in the alkalis and alkali monosulphides. 
 
 Tetraphenylarsenic disulphide, [(CeH 6 ) 2 As]aS2, w r hite leaflets 
 from hot alcohol, sinters at 60 ; m.p. 100. Like the monosulphide 
 soluble in the ordinary organic solvents, it dissolves readily in 
 yellow ammonium sulphide, probably to form an ammonium 
 diphenylthioarsinate. It is prepared by successively saturating 
 with hydrogen sulphide an ammoniacal solution of diphenyl- 
 arsinic acid, acidifying and extracting the precipitate with alcohol. 
 Also obtained by the action of hydrogen sulphide on diphenyl- 
 arsinic acid in glacial acetic acid. 
 
 Di-p-anisylarsenious chloride, 1 (CH 3 -OC 6 H 4 ) 2 AsCl, slender pale 
 yellow needles from ether, m.p. 79-80. This substance was not 
 prepared by either of the general methods, but by an experiment 
 which had for its object the demethylation of tri-^-anisylarsine. 
 On warming this base with hydriodic acid (D = 1-56) a heavy, 
 red oil was produced which when treated with aqueous caustic 
 soda yielded a solid di-^>-anisylarsenious oxide crystallisable 
 from alcohol or benzene (m.p. 130), and this compound on 
 mixing with concentrated hydrochloric acid gave the corre- 
 sponding chloride. The first reaction is represented by the 
 following equation : 
 
 (CH 3 -OC 6 H 4 ) 3 As + HI = C 6 H 5 -OCH 3 + (CH 3 -O-C 6 H 4 ) 2 AsI. 
 
 More drastic heating with hydriodic acid carries this decom- 
 position to the final stage of arsenious iodide and three molecular 
 proportions of ^-anisole. 
 
 1 Michaelis and Weitz, Ber., 1887, 20, 50. 
 
 99 H2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Diphenylarsine, 1 (C 6 H 5 ) 2 AsH 2 , colourless oil, b.p. 174*725 mm., 
 with an odour recalling that of phenylarsine but less pleasant. It is 
 prepared by adding, with energetic agitation, concentrated 
 hydrochloric acid to diphenylarsinic acid mixed with excess of 
 amalgamated zinc dust and covered with a layer of ether. The 
 ethereal solution is dried over calcium chloride and distilled in an 
 atmosphere of carbon dioxide. The arsine is soluble in etlier, 
 alcohol, and other organic solvents, but insoluble in water. The 
 diphenylarsinic acid required for this preparation is most readily 
 obtained in the following manner : triphenylarsine (z mols.) and 
 arsenious chloride (i mol.) are heated at 220 for thirty hours, 
 the product is poured into water, and the mixture saturated with 
 chlorine. The filtered solution is treated with excess of magnesia 
 mixture, boiled, and filtered. On adding hydrochloric acid to 
 the final filtrate, diphenylarsinic acid separated as an oil changing 
 to colourless needles. After one crystallisation from water the 
 acid is obtained in a state of purity, the yield being more than 
 40 per cent. 
 
 Diphenylarsine is oxidised in the air to diphenylarsine oxide 
 (phenylcacodyl oxide) and diphenylarsinic acid. With bromine 
 and iodine it yields the corresponding diphenylarsenious halide, 
 
 (C 6 H 5 ) 2 AsH + X 2 = (C 6 H 6 ) 2 AsX + HX. 
 
 Section III. 'Benzene Derivatives with Three Aromatic 
 Nuclei attached to One Arsenic Atom. 
 
 Triphenylarsine,' 2 ' (C 6 H 5 ) 3 As, colourless, vitreous, triclinic plates 
 from alcohol, m.p. 58-60 ; D = 1-306 ; b.p. above 360, without 
 decomposition in carbon dioxide. It is obtainable by both 
 general methods of synthesis, being produced in small amount 
 during the action of mercury diphenyl on phenyl arsenious 
 chloride, and also by prolonged heating of phenylarsenious oxide 
 at 180-200. 3C 6 H 5 AsO = (C 6 H 5 ) 3 As-f As 2 O 3 . Preferably it is 
 prepared by adding sodium (80 grams) to a mixture of chloro- 
 benzene (101 grams) or bromobenzene (140 grams), arsenious 
 chloride (54 grams), and ether (4 volumes). 3 After an interval 
 a vigorous reaction sets in so that the mixture requires cooling 
 and stirring. In two hours the process is mainly over ; after six 
 to eight hours the filtered solution is distilled and the residual 
 
 1 Dehn and Wilcox, Amer. Chem. ] ., 1906, 35, 45. 
 
 2 La Coste and Michaelis, he. cit. ; Michaelis, Annalen, 1902, 321, 160. 
 
 3 Philips, Ber., 1886, 19, 1031. 
 
 100 
 
AROMATIC 
 
 triphenylarsine allowed to solidify. In some instances the onset 
 of the reaction is unduly delayed and may be induced by the 
 addition of a small amount of dry ethyl acetate ; the most 
 favourable results and the best yields are obtained, however, 
 when this chemical change proceeds spontaneously. 1 
 
 Triphenylarsine is readily prepared by the Grignard reaction. 
 Arsenious chloride 2 (10 grams) is added to an ethereal solution 
 of phenylmagnesium bromide (from 4-1 grams Mg and 26 grams 
 CflHgBr). The reduction product is mixed with water, extracted 
 with ether, and the ethereal solution dried over calcium chloride 
 and concent rated when 9-5 grams of triphenylarsine are obtainable. 
 
 Powdered arsenious oxide (4-9 grams) is added to 2-4 grams of 
 magnesium dissolved in 157 grams of bromobenzene and 30 c.c. 
 of dry ether. The mixture is heated for three hours on the water- 
 bath. Triphenylarsine (27 grams) is isolated by extraction with 
 ether after removing diphenyl by distillation in steam. 3 
 
 Triphenylarsine is extremely soluble in ether or benzene, 
 sparingly so in cold alcohol ; insoluble in water or the halide 
 acids. It forms a mercurichloride, (C 6 H 5 ) 3 As,HgCl 2 , nacreous 
 leaflets, easily soluble in absolute alcohol, less so in dilute spirit . 
 This product may be employed in separating triphenylarsine 
 from diphenylarsenious chloride ; from the mercurichloride the 
 arsine is regenerated by the action of hydrogen sulphide or of 
 cold alcoholic potash. When warmed with aqueous caustic 
 potash, the mercurichloride yields triphenylarsine hydroxide, 
 (C 6 H 5 ) 3 AsHgCl 2 + 2KOH ^ (C 6 H 5 ) 3 As(OH) a + 2KC1 + Hg. 
 
 Platinichloride, (C 6 H 5 ) 3 As,H 2 PtCl 6 , formed from its generators 
 in alcoholic solution, separates in pale yellow leaflets melting at 
 
 285. 
 
 Triphenylarsine dichloride, (C 6 H 5 ) 3 AsQ 2 , colourless plates from 
 benzene, sintering at 158 and melting at 204-205. Prepared 
 by passing chlorine over triphenylarsine, heat is generated, the 
 base melts, and the dichloride subsequently solidifies. When 
 heated at 280 the dichloride loses chlorobenzene, 
 
 (C 6 H 5 ) 3 AsCl 2 = C 6 H 5 C1 + (C 6 H 5 ) 2 AsCl. 
 
 Triphenylarsine dihydr oxide* (C 6 H 6 ) 3 As(OH) 2 , plates or needles 
 from water, m.p. 115-116; soluble in alcohol. At 189 it 
 loses one molecular proportion of water. Prepared either by 
 
 1 Michaelis and Loesner, Ber., 1894, 27, 264. 
 
 2 Pfeiffer, Ber., 1904, 37, 4621. 
 
 3 Sachs and Kantorowicz, Ber., 1908, 41, 2767. 
 
 4 Philips, Ber., 1886, 19, 1032. 
 
 101 
 
ORGANIC COMPOtfftVS OF ARSENIC AND ANTIMONY 
 
 boiling the preceding dichloride with dilute ammonia or by 
 successively adding bromine to triphenylarsine dissolved in 
 glacial acetic acid and pouring the solution of triphenylarsine 
 dibromide into concentrated aqueous caustic soda. On cooling 
 the crude dihydroxide is obtained as a brown cake and is purified 
 by dissolving in alcohol, treating again with ammonia and pre- 
 cipitating with water. Reduced to triphenylarsine by tin and 
 alcoholic hydrochloric acid. Triphenylarsine hydroxy nitrate, 
 (C 6 H 5 ) 3 As(OH)-NO 3 , from the hydroxide and dilute nitric acid ; 
 lustrous needles, m.p. 160-161, easily soluble in alcohol. Tri- 
 phenylarsine sulphide, (C 6 H 5 ) 3 AsS, lustrous needles, m.p. 162, 
 insoluble in water, alkali sulphides, acids, or ether ; crystallising 
 from hot alcohol. Prepared by melting together sulphur and 
 triphenylarsine, by boiling triphenylarsine dichloride with yellow 
 ammonium sulphide, and by passing hydrogen sulphide into an 
 alcoholic solution of triphenylarsine hydroxide. 1 
 
 The dichloride is converted by atmospheric moisture into the 
 more stable triphenylarsine hydroxy chloride, m.p. 171, 
 
 (C 6 H 5 ) 3 As(OH)-Cl, 
 
 a substance readily obtained by saturating with chlorine a solu- 
 tion of triphenylarsine in commercial chloroform. After remov- 
 ing excess of chlorine with carbon dioxide, addition of dry ether 
 precipitates the hydroxychloride in vitreous crystals (yield 
 90 per cent.). This substance reacts with platinic chloride in 
 alcoholic solution to give a complex platinichloride of excep- 
 tional composition, [(C 6 H 5 ) 3 As(OH)Cl] 3 PtCl4, which crystallises 
 in yellow needles, m.p. 180-182. 
 
 Triphenylarsine dibromide, (C 6 H 5 ) 3 AsBr 2 , colourless crystals, 
 sintering at 165 and melting at 215 ; triphenylarsine tetra- 
 iodide, (C 6 H 5 ) 3 AsI 4 , steel blue needles, m.p. 142-144, are ob- 
 tained by direct addition of the halogen in carbon tetrachloride ; 
 the analogous compound, (C 6 H 5 ) 3 AsBr 2 I 2 , yellowish-red needles, 
 m.p. 120-121, separates from chloroform-ether. 
 
 Triphenylarsine nitrate, (C 6 H 5 ) 3 As(NO 3 ) 2 , radiating aggregates, 
 m.p. 99-100, obtained by evaporating to dryness a solution of 
 triphenylarsine hydroxide or oxide in concentrated nitric acid. 
 
 Triphenylarsine hydroxy chromate, (C 6 H 5 ) 3 As(OH)O-HCr0 3 , 
 yellowish-red precipitate from the hydroxychloride and potass- 
 ium chromate. 
 
 Triphenylarsine oxide trisulphonic acid, 2 0:As(C 6 H 4 -SO 3 H) 3 . 
 
 1 Philips, loc. cit. 2 Michaelis, Annalen, 1902, 321, 186. 
 
 102 
 
AROMATIC ARSENICALS 
 
 When triphenylarsine is warmed on the water-bath with con- 
 centrated sulphuric acid there is no sulphonation, but the pro- 
 duction of triphenylarsine hydroxide, 
 
 (C 6 H 5 ) 3 As + H 2 S0 4 = (C G H 5 ) 3 As(OH) 2 + SO 2 . 
 
 By further heating to the boiling point of sulphuric acid this 
 hydroxide undergoes sulphonation. The barium salt of the 
 resulting trisulphonic acid is a white, crystalline powder easily 
 soluble in water. 
 
 Triphenylalkylarsonium derivatives. 1 Although the first ex- 
 periments on triphenylarsine had seemed to indicate that this 
 tertiary aromatic arsine did not combine with alkyl iodides even 
 on heating in sealed tubes, yet addition occurs with excess of 
 methyl iodide on prolonged boiling under the ordinary pressure. 
 This reaction also occurs, although with less facility, with ethyl 
 iodide, but not with the higher alkyl iodides. 
 
 Triphenylmethylarsonium iodide, (C 6 H 5 ) 3 As(CH 3 )T, pale yellow 
 leaflets from alcohol or colourless, feathery needles from water, 
 m.p. 176 ; it dissolves readily in alcohol or ether, but only 
 sparingly in water. The iodochloride, B-IC1 2 , is a yellow, crystal- 
 line mass from alcohol, m.p. 144. 
 
 Triphenylmethylarsonium chloride, colourless needles, m.p. 
 121, very soluble in water or alcohol, obtained by neutralising 
 with hydrochloric acid an aqueous solution of the hydroxide 
 or by digesting the iodide with silver chloride ; platinichloride, 
 yellowish-red needles, m.p. 224-225. 
 
 Triphenylmethylarsonium hydroxide, (C 6 H 5 ) 3 As(CH 3 )-OH, trans- 
 parent, elongated, prismatic crystals, m.p. 125-126, is produced 
 by digesting aqueous or preferably alcoholic solutions of the 
 iodide with moist silver oxide when spontaneous evaporation 
 of the filtrate leads to the separation of the crystalline hydroxide. 
 These crystals are extremely soluble in water to an alkaline 
 solution in which the hydroxide decomposes on heating on 
 the water-bath. At 100 the solid hydroxide loses methyl 
 alcohol and leaves pure triphenylarsine. The solution absorbs 
 carbon dioxide from the air and on evaporation deposits colour- 
 less, transparent plates of the hydrated hydrogen carbonate, 
 (C 6 H 5 ) 3 As-HCO 3 ,H 2 O; this salt effervesces with acid, gives a 
 white precipitate with baryta water, and reddens phenolphthalein 
 only slightly in the cold and more markedly on boiling. 
 
 1 Michaelis, Annalen, 1902, 321, 166 ; Gimborn, Jnaug. Dissert., Rostock, 
 1891. 
 
 103 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Triphenylmethylarsonium nitrate, (C 6 H 5 ) 3 As(CH 3 )-NO 3 , needles 
 from alcohol-ether, is nitrated with considerable difficulty when 
 added to concentrated sulphuric acid (5 parts) containing fuming 
 nitric acid (2 parts). The product poured into water and the 
 precipitate extracted with alcohol leaves a red residue ; the alco- 
 holic extract deposits a yellow powder of trinitrotriphenylmethyl- 
 arsonium nitrate, m.p. 195. 
 
 Triphenylethylarsonium iodide, (C 6 H 5 )3As(C 2 H 5 )I, lustrous 
 needles, m.p. 158, produced by prolonged boiling of triphenyl- 
 arsine with ethyl iodide, is easily soluble in alcohol and sparingly 
 so in water ; platinichloride, m.p. 221 
 
 Triphenyliodomethylarsonium iodide, (C 6 H 5 ) 3 As(CH 2 I)I, silvery 
 needles from alcohol, m.p. 227, is preferably obtained by heating 
 triphenylarsine (15 grams) and methylene iodide (17 grams) 
 for thirty minutes at 130. Insoluble in ether, sparingly soluble in 
 water, dilute alcohol, glacial acetic acid, and chloroform. Chlorine 
 passed into the hot solution of this iodide in acetic acid gives 
 the iodochloride, (C 6 H 5 ) 3 As(CH 2 Cl)ICl 2 , forming intensely yellow 
 crystals from alcohol. When heated with aqueous caustic soda 
 this iodochloride is decomposed into triphenylarsine dihydroxide 
 and iododichloromethane. 
 
 (C 6 H 5 ) 3 As(CH 2 Cl)ICl 2 + 2NaOH = 
 
 (C H 5 ) 3 As(CH 2 Cl)I + NaOCl + NaCl + H 2 O. 
 (C 6 H 6 ) 3 As(CH 2 Cl)ICl 2 + NaOCl + NaOH = 
 
 (C 6 H 6 ) 3 As(OH) 2 + CHIC1 2 -f 2NaCl. 
 
 Triphenyliodomethylarsonium chloride ( Triphenylarsinomethyl- 
 choline chloride], (C 6 H 5 ) 3 As (CH 2 I)C1, lustrous needles, m.p. 208, 
 obtained by treating the iodide with freshly precipitated silver 
 chloride. Decomposition of the iodide with silver oxide leads 
 to the replacement of both iodine atoms by hydroxyl. The 
 hydroxide, (C 6 H 5 ) 3 As(CH 2 -OH)-OH, is a syrup, but the addition 
 of hydrochloric acid gives the crystalline chloride, 
 
 (C 6 H 5 ) 3 As(CH 2 -OH)Cl, 
 
 m.p. 112: platinichloride, m.p. 224 ; the iodide, 
 (C 6 H 5 ) 3 As(CH 2 -OH)I, 
 
 yellow, flattened needles, m.p. 171,. very soluble in water or 
 alcohol. 
 
 Triphenylhydroxyethylarsonium chloride ( Triphenylarsinocholine 
 chloride), (C 6 H 5 ) 3 As(CH 2 -CH 2 'OH)Cl, colourless needles, m.p. 215, 
 produced by boiling triphenylarsine with ethylenechlorohydrin. 
 
 104 
 
AROMATIC ARSENICALS 
 
 Tri-p-anisylarsine, 1 (CH 8 -OC 6 H 4 ) 3 As, colourless, cubical, trans- 
 parent crystals (from benzene and alcohol), m.p. 156, prepared 
 by adding sodium parings (20 grams) to ^-bromoanisole and 
 arsenious chloride (30 grams) in four volumes of ether. After the 
 addition of a little ethyl acetate a vigorous reaction ensues. 
 The precipitate, when freed by water from unattacked sodium, 
 is extracted with hot benzene from which the arsine (15 grams) 
 crystallises on cooling. With this arsine the absorption of chlorine 
 and bromine occurs less readily than with triphenylarsine. 
 
 Tri-p-phenetylarsine, (C 2 H 5 -O-C 6 H 4 ) 3 As, obtained in very poor 
 yield from ^-bromophenetole, arsenious chloride, and sodium, 
 m.p. 88-89, very soluble in ether. 
 
 Section IV. Toluene Derivatives with One Aromatic Nucleus 
 attached to One Arsenic Atom. 
 
 G-Tolylarsenious chloride,' 2 ' C 7 H 7 -AsQ 2 , colourless liquid, b.p. 
 264 in a current of carbon dioxide, obtained by boiling mercury 
 di-o-tolyl (m.p. 107) with excess of arsenious chloride. In- 
 soluble in water, dissolving readily in ether, alcohol, or benzene ; 
 absorbs chlorine (but not bromine) to yield o-tolylarsenic chloride, 
 C 7 H ? AsCl 4 , dark yellow, syrupy liquid decomposed by water 
 into o-tolylarsinic and hydrochloric acids. 
 
 o-Tolylarsenious oxide, C 7 H 7 -AsO, m.p. 145-146, obtained by 
 warming o-tolylarsenious chloride with aqueous sodium car- 
 bonate. Easily soluble in hot water, sparingly so in alkalis. 
 Absorbs chlorine and bromine to yield the corresponding oxyhalide 
 C 7 H 7 -AsOX 2 , and regenerates o-tolylarsenious chloride on treat- 
 ment with concentrated hydrochloric acid. 
 
 Q-Tolylarsinic acid, CH 3 -C 6 H 4 -AsO(OH) 2 , aggregates of colour- 
 less needles, m.p. 159-160. Prepared by the action of water 
 on the preceding oxyhalides, or on o-tolylarsenic chloride. When 
 maintained at its melting point, the acid slowly loses water and 
 forms its anhydride, light yellow, crystalline mass. 
 
 o-Tolylarsinates : Calcium, C 7 H 7 -AsO 3 Ca, and acid barium, 
 (C 7 H 7 AsO 3 H) 2 Ba salts, colourless, crystalline precipitates, less 
 soluble in hot than in cold water ; silver salt, C 7 H 7 -AsO 3 Ag 2 , 
 white amorphous precipitate. 
 
 m-Tolylarsenious chloride* CH 3 -C 6 H 4 -AsCl 2 , colourless liquid, 
 
 1 Michaelis and Weitz, Ber., 1887, 20, 49- 
 
 2 La Coste and Michaelis, Annalen, 1880, 201, 246. 
 
 3 Michaelis, A nnalen, 1902, 321, 326; Eisenlohr, Inaug. Dissert., Ros- 
 tock, 1893. 
 
 105 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 b.p. 270, prepared by heating tri-w-tolylarsine with arsenious 
 chloride (10 parts) at 300 : yield 40%. 
 
 m-Tolylarsenious oxide, stringy mass produced by the action 
 of aqueous sodium carbonate on the preceding compound, 
 reduced in alcoholic solution by phosphorous acid to arseno-m- 
 toluene, CH 3 'C 6 H 4 \\s:As-C 6 H 4 -CHg, white, amorphous powder, 
 m.p. 106, insoluble in the ordinary solvents except carbon 
 bisulphide and warm cymene. m-Tolylarsenic chloride, 
 
 CH 3 -C 6 H 4 -AsG 4 , 
 
 crystalline mass, m.p. 38, hydrolysed by water to m-tolylarsinic 
 acid, C 7 H 7 AsO(OH) 2 , acicular aggregates from hot water, m.p. 
 150, changing to m-tolylarsinic anhydride, C 7 H 7 -AsO 2 , at 
 220-230. 
 
 Salts : Acid ammonium salt, C 7 H 7 -AsO(OH)'ONH 4 , crystalline 
 mass ; acid phenylhydrazinesa.lt, C 7 H 7 AsO(OH)'O-NH 3 -NH'C 6 H 6 , 
 lustrous leaflets ; calcium salt, sparingly soluble in hot water ; 
 silver salt, C 7 H 7 AsO(OAg) 2 , white precipitate ; the other salts 
 of the heavy metals are insoluble. 
 
 p-Tolylarsenious chloride, CH 3 -C 6 H 4 AsCl 2 , colourless highly 
 refractive tablets, pungent aromatic odour, m.p. 31, b.p. 267 
 in a current of carbon dioxide, obtained from mercury di-p-toly\ 
 (m.p. 235) and arsenious chloride. Preferably prepared by 
 heating tri-^>-tolylarsine with 10 parts of arsenious chloride at 
 230-240 for sixty hours ; the yield is nearly quantitative. Addition 
 of chlorine leads to p-tolylarsenic chloride, C 7 H 7 AsCl 4 , and treat- 
 ment with alkali carbonates to p-tolylarsenious oxide, m.p. 156. 
 
 p-Tolylarsinic acid, C 7 H 7 -AsO(OH) 2 , colourless needles from 
 water, darkens at 300 without melting. Preparation : (i) action 
 of chlorine on ^-tolylarsenious chloride in water ; (ii) hydrogen 
 peroxide added to the chloride dissolved in glacial acetic acid ; 
 (iii) oxidation of chloride with nitric acid. The first two methods 
 give quantitative yields ; in the third process a portion of the acid 
 undergoes nitration, (iv) 1 ^-Tolylarsinic acid is obtainable also 
 by Bart's reaction when a solution of />-toluenediazonium chloride 
 is neutralised with caustic soda, treated with aqueous sodium 
 arsenite, and warmed till nitrogen is evolved, when the product is 
 precipitated by mineral acid from the filtered solution. 
 
 Concentrated nitric acid yields a nitro-^>-tolylarsinic acid. Per- 
 manganate oxidises the methyl substituent with the production 
 of benzarsinic acid (/>-carboxyphenylarsinic acid). 
 
 1 Bart, D.R.-P., 250264. 
 
 106 
 
AROMATIC ARSENICALS 
 
 p-Tolylarsinates : Potassium salt, uncrystallisable ; acid 
 calcium, (C 7 H 7 -AsO 3 H) 2 Ca, and acid barium, (C 7 H 7 -AsO 3 H) 2 Ba, 
 salts, colourless needles from water ; silver salt, C 7 H 7 -AsO 3 Ag 2 , 
 white precipitate, rendered crystalline by boiling with alcohol ; 
 copper and lead salts, C 7 H 7 -AsO 3 R", bluish-green and white 
 precipitates respectively. 
 
 Arseno-p-toluene, 1 CH 3 -C 6 H 4 -As:As-C 6 H 4 -CH 3 , lustrous needles 
 from chloroform, m.p. 184, obtained by heating ^-tolylarsenious 
 oxide with excess of phosphorous acid at 100. Chlorine converts 
 the arseno-compound successively to dichloride and tetrachloride. 
 Nitric acid oxidises it to ^-tolylarsinic acid. 
 
 p-Tolylarsenious sulphide, CH 3 -C 6 H 4 As-S, lustrous, colourless 
 crystals from benzene-ether, m.p. 146, obtained by passing 
 hydrogen sulphide into alcoholic solutions of ^-tolylarsenious 
 oxide. 
 
 CH 8 -C 6 H 4 -AsSv 
 
 p-Tolylarsenic sesquisulphide, \S, white needles 
 
 CH 3 -C 6 H 4 -AsS/ 
 
 from benzene-alcohol, m.p. 119. Acidification of an am- 
 moniacal solution of ^-tolylarsinic acid after saturation with 
 hydrogen sulphide, 
 
 2CH 3 -C 6 H 4 -AsS(SNH 4 ) 2 + 4 HC1 = 
 
 (CH 3 -C 6 H 4 -AsS) 2 S + 4NH 4 C1 + 2SH 2 + S. 
 
 Mixed Tertiary Ar sines containing a Tolyl Radical. 2 
 
 p-Tolyldimethylarsine, CH 3 -C 6 H 4 -As(CH 3 ) 2 , colourless liquid, 
 unpleasant odour, b.p. 220 in carbon dioxide. This arsine or the 
 following homologue is prepared by the action of pure zinc 
 dimethyl (or diethyl) in excess on ^-tolylarsenious chloride 
 diluted with dry ether. p-Tolyldiethylarsine, b.p. 250. 
 
 p-Tolyltrimethylarsonium iodide, CH 3 -C 6 H 4 -As(CH 3 ) 3 I, plates, 
 m.p. 274-275, dissociating into its generators on heating ; 
 platinicliloride, reddish-yellow needles, m.p. 225. 
 
 p-Tolylmethyldiethylarsonium iodide, CH 3 -C 6 H 4 -As(CH 3 ) (C 2 H 5 ) 2 I, 
 colourless leaflets, m.p. 220. 
 
 p-Tolyltriethylarsonium iodide, colourless, prismatic crystals, 
 m.p. 230 ; chloride, crystal Usable only with difficulty, platini- 
 chloride, m.p. 210. 
 
 1 Michaelis, Annalen, 1902, 320, 301. 
 
 2 Michaelis, Annalen, 1902, 320, 304 ; Klatt, Inaug. Dissert., Rostock, 
 1893. 
 
 107 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section V. Toluene Derivatives with Two or Three Aromatic 
 Nuclei attached to One Arsenic Atom. 
 
 i. Diaryl Series. 
 
 Di-p-tolylarsenious chloride, 1 (CHVCoHJgAsCl, colourless crys- 
 tals, m.p. 45, b.p. 340-345, prepared by boiling together 
 mercury di-p-tolyl and />-tolylarsenious chloride (3-4 parts), 
 and also by distilling tri-^>-tolylarsine dichloride under reduced 
 pressure. 2 Decomposed by repeated distillation 
 
 2(C 7 H 7 ) 2 AsCl = C,H 7 -AsCl a + (C 7 H 7 ) 3 As. 
 
 Not affected by aqueous sodium carbonate, but decomposed 
 by boiling alcoholic potash to yield di-p-tolylarsenious oxide, 
 [(C 7 H 7 ) 2 As] 2 O, silky needles from ether ; m.p. 98, giving tri-p- 
 tolylarsine on heating. 
 
 Di-p-tolylarsenic chloride, (C 7 H 7 ) 2 AsCl 3 , pale yellow mass ob- 
 tained by passing dry chlorine into di-^>-tolylarsenious chloride ; 
 when added to water the trichloride is readily decomposed, giving 
 first an oxychloride and then di-p-tolylarsinic acid, granular 
 crystals from alcohol, m.p. 167, very sparingly soluble in hot 
 water, and dissolving readily in alcohol ; its salts are generally 
 soluble in water. Silver salt, white precipitate. 
 
 Phenyl-p-tolylarsenious chloride? C 6 H 5 (C 7 H 7 )AsCl 2 , colourless 
 oily liquid not affected by moisture, b.p. 2i5~237/29 mm. 
 and 215-240750 mm. ; prepared by adding 30 grams of 
 mercury-_-ditolyl (m.p. 238) to phenylarsenious chloride 
 (180 grams) ; the mixture, which becomes brown and deposits 
 mercuric chloride, is heated to boiling for five hours, decanted from 
 solid and mixed with dehydrated light petroleum (b.p. 50), 
 when a dark brown oil separates and subsequently solidifies 
 (mercury-/>-tolyl chloride). The filtrate is fractionated in carbon 
 dioxide. Unaltered phenylarsenious chloride comes over up to 
 300 ; at 347 the pressure is reduced to 29 mm., and the 
 secondary chloride obtained and redistilled. Yield 41 per cent, 
 on the weight of mercury-/>-ditolyl. 
 
 Phenyl-p-tolylarsenious oxide, [C 6 H 6 -(C 7 H 7 )As] a O, an oil obtained 
 
 1 La Coste, Annalen, 1881, 208, 18. 2 Michaelis, Annalen, 1902, 
 
 321, 1 60. 
 
 3 Michaelis, Annalen, 1902, 321, 155; Predari, Inaug. Dissert., Rostock, 
 1894- 
 
 108 
 
AROMATIC ARSENIC ALS 
 
 by the action of alcoholic potash on the preceding chloride ; 
 addition of chlorine leads to the oxychloride, 
 
 [C 6 H 5 (C 7 H 7 )As] a OCl 4 , 
 
 colourless, fan-shaped aggregates of needles. Phenyl-p-tolyl- 
 arsenious sulphide, [C 6 H 5 -(C 7 H 7 )As] 2 S, is an oily substance. 
 
 Phenyl-p-tolylarsinic acid, C 6 H 5 (C 7 H 7 )AsOOH, colourless,felted 
 needles, m.p. 158-160. Soluble in hot water, alcohol, benzene, 
 or concentrated nitric acid, dissolving sparingly in cold water 
 or ether. Silver salt, white precipitate. For a satisfactory 
 preparation of this acid pure phenyl-^>-tolylarsenious chloride is 
 necessary, otherwise the product is tarry. 
 
 Phenyl-p-tolylethylarsine, C 6 H 5 (C 7 H 7 )As-C 2 H 5 , colourless oil 
 with fruity odour, b.p. 2io-225/5o mm. This mixed tertiary 
 arsine with three dissimilar hydrocarbon groups is prepared 
 by the action of zinc diethyl on phenyl-^>-tolylarsenious chloride ; 
 the dichloride, C 6 H 6 (C 7 H 7 )As(C 2 H 5 )Cl2, colourless needles from 
 benzene, m.p. 148. The tertiary arsine combines readily with 
 alkyl iodides, in the cold with methyl iodide and with its 
 homologues on the water-bath. 
 
 Phenyl-p-tolylmethylethylarsonium iodide, 
 
 C 6 H 6 (C 7 H 7 )As(CH 8 )(C 2 H 6 )I, 
 
 V 
 
 colourless, monoclinic acicular prisms, m.p. 150-151 from water, 
 and 145 from alcohol. This quaternary arsonium iodide is 
 noteworthy because it contains arsenic associated with five 
 different radicals ; it should accordingly exist in two stereo- 
 isomeric forms. Michaelis and Predari state that in alcoholic 
 solution this arsonium iodide exhibits a slight optical activity ; 
 they were not, however, able to resolve the substance into 
 optically active isomerides by means of tartaric or aspartic 
 acid. Moreover, these arsenical iodides are toxic towards 
 moulds, so that these organisms could not be employed 
 in isolating one of the active forms (compare Winmill, 
 p. 92). 
 
 The corresponding chloride is not crystallisable ; the platini- 
 chloride forms yellowish-red, triclinic prisms, m.p. 214 
 
 Phenyl-p-tolyldiethylarsonium iodide, C 6 H 5 (C 7 H 7 )As(C 2 H 5 ) 2 I, 
 monoclinic crystals from water, m.p. 148. The n-propyl and 
 isopropyl derivatives form monoclinic crystals melting in- 
 definitely ; the benzyl iodide forms rhombic crystals, m.p. 150* 
 and the benzyl chloride is uncrystallisable. 
 
 109 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 2. Triaryl Series. 
 
 Tri-p-tolylarsine, 1 (CH 3 -C 6 H 4 ) 3 As, large colourless rhombic 
 crystals (from ether), m.p. 145-146, b.p. above 360 without 
 decomposition. Derived from both general synthetic methods, 
 (i) ^>-Tolylarsenious oxide heated in a sealed tube to 300 and 
 extracted from the product by means of ether, 
 
 3 C 7 H 7 -AsO = (C 7 H 7 ) 3 As + As 2 3 . 
 
 (ii) 2 Most conveniently prepared by adding sodium shavings 
 or wire (40 grams) to ^-bromotoluene (100 grams) and arsenious 
 chloride (45 grams) dissolved in 500 grams of anhydrous ether. 
 The violent reaction, which is regulated by cooling, is completed 
 in 36 hours. The filtered solution is evaporated to dryness, a 
 small amount of yellow impurity removed with alcohol, and the 
 residue dried over sulphuric acid, when 69-70 per cent, of the 
 calculated quantity of colourless tri-^>-tolylarsine is obtained. 
 
 (iii) It is also obtained in the Grignard condensation by the 
 interaction of arsenious oxide and magnesium ^-tolyl bromide 
 in ethereal solution. 3 
 
 Less soluble in alcohol than in ether, chloroform, or benzene. 
 Oxidised by alkaline permanganate to tribenzarsinic (tri-^>- 
 carboxyphenylarsinic) acid. Absorbs chlorine in chloroform 
 solution to yield tri-p-tolylarsine chloride, (C 7 H 7 ) 3 AsCl 2 , m.p. 
 228-230, yielding, with hot water, the hydroxy chloride, 
 
 (C 7 H 7 ) 3 As(OH)Cl, 
 
 feathery crystals, m.p. 185 from chloroform-ether. Aqueous 
 alkali converts the dichloride or hydroxychloride into tri-p- 
 tolylarsine dihydroxide, (C 7 H 7 ) 3 As(OH) 2 , flattened needles, 
 m.p. 96. 
 
 The mercurichloride (C 7 H 7 ) 3 As,HgCl 2 , is a white, crystalline 
 powder, m.p. 246, sparingly soluble in hot glacial acetic acid. 
 
 Tri-p-tolylarsine dibromide, colourless, thick crystals, m.p. 245, 
 and tri-p-tolylarsine di-iodide, reddish-yellow needles-, m.p. 172, 
 are obtained by direct addition of the halogen in carbon tetra- 
 chloride, an excess of iodine leading to the tetraiodide, steel 
 grey needles, m.p. 153. 
 
 Tri-p-tolylarsine sulphide, (CH 3 -C 6 H 4 ) 3 AsS, lustrous leaflets, 
 m.p. 170-171, is not obtained pure by direct addition of its 
 
 1 La Coste, Annalen, 1881, 208, 26. 
 
 2 Michaelis, Annalen, 1902, 321, 201. 
 
 3 Sachs and Kantorowicz, Ber., 1908, 41, 2767. 
 
 IIO 
 
AROMATIC ARSENIC ALS 
 
 generators in carbon bisulphide, but by passing sulphuretted 
 hydrogen into an alcoholic solution of the oxychloride. 
 
 Tri-p-tolylmethylarsonium iodide, 1 (C 7 H 7 ) 3 As(CH 3 )I, m.p. 179, 
 is prepared like its phenyl homologue (v. p. 103) and further 
 characterised by the chloride, transparent crystals, m.p. 87, 
 platinichloride, reddish-brown, refractive prisms, and iodochloride, 
 (C 7 H 7 ) 3 As(CH 3 )-ICl 2 , reddish-yellow crystals, m.p. 146. 
 
 Tri-p-tolyliodomethylarsonium iodide, (C 7 H 7 ) 3 As(CH 2 I) I 
 (v. p. 104), crystallises from alcohol in transparent, colourless 
 crystals, m.p. 215. 
 
 Tri-p-tolylallylarsonium bromide, (C 7 H 7 ) 3 As(C 3 H 5 )I, colourless 
 prisms from water, lustrous crystals from dilute alcohol, m.p. 82, 
 easily soluble in the ordinary solvents except ether. The bromide 
 is prepared by five hours' heating of equal parts of tri-p-tolyl- 
 arsine and allyl bromide in a reflux apparatus ; the corresponding 
 chloride is oily, the platinichloride forms a red powder, m.p. 225, 
 and the iodide crystallises from dilute alcohol in colourless prisms, 
 m.p. 141. Tri-p-tolyldibromoallylarsonium bromide, 
 
 (C 7 H 7 ) 3 As(C 3 H 5 Br 2 )Br, 
 
 snowlike mass, m.p. 112, obtained by adding bromine to the 
 foregoing bromide in alcoholic solution. 
 
 Tri-m-tolylarsine, 2 (CH 3 -C 6 H 4 ) 3 As. For this preparation pure 
 w-bromotoluene is required (Wroblewski, Annalen, 1870, 
 156, 74 ; Grete, loc. cit., 1875, 177, 2), 50 grams being 
 mixed with arsenious chloride (18 grams) and sodium 
 (30 grams) in 300 grams of anhydrous ether. Only two- 
 thirds of this sodium is added at first, and the remainder 
 as the reaction slackens. The ,crude arsine left after distilling 
 off the ether is purified by crystallisation. Colourless leaflets 
 from alcohol, prismatic and tabular crystals of the rhombic 
 system from ether ; m.p. 96, D = 1-31/18 ; easily soluble in 
 the ordinary solvents except light petroleum. The following 
 derivatives are obtainable by the general methods : - 
 
 Mercurichloride (C 7 H 7 ) 3 As,HgCl 2 , sparingly soluble, m.p. 174 ; 
 hydroxy chloride (C 7 H 7 ) 3 As(OH)Cl, m.p. 205 ; hydroxybromide, 
 rhombic crystals, m.p. 190 ; oxide, (C 7 H 7 ) 3 AsO, white, crystalline 
 mass, m.p. 170, by the action of hot caustic soda on hydroxy- 
 bromide ; sulphide, (C 7 H 7 ) 3 AsS, silvery needles, m.p. 186, by 
 direct addition of sulphur to the arsine. 
 
 1 Michaelis, Annalen, 1902, 321, 204. 
 
 2 Michaelis, Annalen, 1902, 321, 216. 
 
 Ill 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Quaternary alkyl iodides. Tri-w-tolylarsine possesses in a 
 special degree the capacity for combining with alkyl iodides. 
 Unlike the other tertiary aromatic arsines, it combines with 
 methyl iodide even in the cold, and on warming with the higher 
 alkyl halides, including benzyl chloride. 
 
 Tri-m-tolylmethylarsonium iodide, (C 7 H 7 ) 3 As(CH 3 )I, prisms or 
 plates of the rhombic system, m.p. 181, from water or alcohol ; 
 the chloride is oily, the platinichloride a pale yellow precipitate. 
 
 Tri-m-tolylethylarsonium iodide, (C 7 H 7 ) 3 As(C 2 H 5 )I, separates 
 from dilute alcohol in distorted rhombohedra of the triclinic 
 system, m.p. 130 ; tri-m-tolyl-n-propylarsonium iodide, 
 
 (C 7 H 7 ) 3 As(C 3 H 7 )I, 
 
 needles, m.p. 143, obtained by the prolonged interaction of its 
 generators at the ordinary temperature : tri-m-tolyUsQpropyl- 
 arsonium iodide, m.p. 162 ; tri-m-tolylbenzylarsonium chloride, 
 (C 7 H 7 ) 3 As(CH 2 -C 6 H 5 )-Cl, obtained, not by boiling, but by allowing 
 its generators to interact at 30-40 ; easily soluble in water, 
 dissolving sparingly in water, m.p. 102. 
 
 Diphenyl-p-tolylarsine, 1 (C 6 H 5 ) 2 As-C 7 H 7 , colourless crystals, 
 m.p. 50, somewhat difficult to obtain in solid condition. 
 />-Tolylarsenious chloride (30 grams), bromobenzene (42 grams), 
 and 24 grams of sodium in thin slices are brought together in 
 500 grams of dehydrated ether. The reaction begins at the 
 ordinary temperature and is completed by warming for about 
 three days. The syrupy residue left after removing the ether 
 separates in oily drops from alcoholic solution unless the liquid 
 is maintained for weeks at low temperatures. The oily arsine 
 suffices, however, for the preparation of derivatives. Mercuri- 
 chloride, (C 6 H 5 ) 2 As-C 7 H 7 ,HgCl 2 , crystals from glacial acetic acid, 
 m.p. 147 ; platinichloride, yellow precipitate, m.p. 233. 
 
 Diphenyl-p-tolylarsine dihydroxide, (C 6 H 6 ) 2 As(C 7 H 7 )-OH, m.p. 
 68 ; prepared by successively adding bromine to the foregoing 
 arsine in glacial acetic acid solution, treating the cooled solution 
 of the dibromide with aqueous caustic potash, and finally boiling 
 for i hours. Dissolved in hot dilute nitric acid, the dihydroxide 
 yields the basic nitrate, (C 6 H 5 ) 2 As(C 7 H 7 )(OH)-NO 3 , yellow needles 
 from water or alcohol-ether, m.p. 125. 
 
 Diphenyl-p-tolylarsine sulphide, (C 6 H 5 ) 2 As(C 7 H 7 )S, granular 
 crystals, m.p. 135, from sulphuretted hydrogen and an alcoholic 
 solution of the hydroxide. 
 
 1 Michaelis, Annalen, 1902, 321, 187; F. Lauterwald, Inaug. Dissert., 
 Rostock, 1897. 
 
 112 
 
AROMATIC ARSENICALS 
 
 Diphenyl-p-tolylmethylarsonium iodide, (C 6 H 6 ) 2 As (C 7 H 7 ) (CH 3 ) I , 
 m.p. 152 (preparation, v. p. 103) ; the chloride is oily ; platini- 
 chloride, pale red crystals, m.p. 209. 
 
 Diphenyl-p-tolylethylarsonium iodide only obtained as an oil ; 
 platinichloride, pink crystals, m.p. 220. 
 
 Phenyldi-p-tolylarsine, 1 (C 7 H 7 ) 2 As-C 6 H 5 , colourless, well-defined 
 rhombohedra, m.p. 101, easily soluble in ether, chloroform, 
 benzene, or hot alcohol, less so in cold spirit or glacial acetic 
 acid. Phenylarsenious chloride (20 grams), ^-bromo toluene 
 (31 grams), finely-divided sodium (17 grams) in 200 c.c. of dry 
 ether interacts at the ordinary temperature, the condensation 
 being regulated by external cooling. The solid residue, after 
 removing ether, is crystallised from alcohol. Mercurichloride, 
 A,HgCl 2 , white crystals from hot alcohol, m.p. 210 ; platini- 
 chloride, A 2 ,H 2 PtCl 6 , yellow crystals from alcoholic hydrochloric 
 acid, m.p. 256. 
 
 Phenyldi-p-tolylarsine dichloride, (C 7 H 7 ) 2 As(C 6 H 5 )Cl 2 , preferably 
 obtained by passing dry chlorine through a chloroform solution of 
 the arsine ; on evaporating in vacuo a transparent, hard mass is left 
 which sinters at 186 and melts at 194. Very easily hydrolysed 
 by moisture to hydroxy 'chloride, (C 7 H 7 ) 2 As(C 6 H 6 )(OH)-Cl, white 
 powder, soluble in alcohol or hot water, but not in ether. The 
 dichloride yields a platinichloride, m.p. 201. 
 
 Phenyldi-p-tolylarsine oxide, (C 7 H 7 ) 2 AsO(C 6 H 5 ), from the 
 chlorides by the action of alkalis, white powder, m.p. 81, dis- 
 solving in dilute nitric acid to form the basic nitrate, 
 
 (C 7 H 7 )As(C 6 H 5 )(OH)-N0 3 , 
 
 rosettes of intertwined needles, m.p. 94. 
 
 Nitration of the oxide has hitherto yielded only tarry products. 
 
 Phenyldi-p-tolylarsine sulphide, (C 7 H 7 ) 2 AsS(C 6 H 5 ), prepared by 
 the general method, m.p. 144. 
 
 Phenyldi-p-tolylmethylarsonium iodide, (C 7 H 7 ) 2 As(C 6 H 5 ) (CH 3 ) I, 
 colourless needles, m.p. 84, turning yellow in the light ; 
 (preparation, v. p. 103) ; platinichloride, golden-yellow needles, 
 m.p. 222. Phenyldi-p-tolylethylarsonium iodide, 
 (C 7 H 7 ) 2 As(C 6 H 6 )(C 2 H 6 )I, 
 
 oily from hot aqueous solutions, slowly solidifying to yellowish- 
 white crystals, m.p. 125. 
 
 1 Michaelis, Annalen, 1902, 321, 192. 
 
 113 I 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section VI. Benzyl Derivatives.* 
 
 The starting point in the preparation of benzyl arsenical deriv- 
 atives is the interaction between benzyl chloride (2mols.),arsenious 
 chloride (i mol.), and sodium suspended in dry ether. The 
 addition of a small proportion of pure ethyl acetate determines 
 the onset of a very vigorous reaction, in which tribenzylarsine, 
 tribenzylarsine dichloride, and dibenzylarsine trichloride are 
 produced. 
 
 3C 6 H 6 -CH 2 C1 + AsCl 3 + 6Na = (C 6 H 5 -CH 2 ) 3 As + 6NaCl. 
 3C 6 H 5 -CH 2 C1 + AsQ 3 + 4Na = (C 6 H 5 -CH 2 ) 3 AsCl 2 + 4NaCl. 
 2C 6 H 5 -CH 2 C1 -f AsCl 3 + 2Na = (C 6 H 5 -CH 2 ) 2 AsC] 3 + 2NaCl. 
 
 Tribenzylarsine, As(CH 2 -C 6 H 5 ) 3 , colourless, transparent mono- 
 clinic prisms from alcohol, m.p. 104, not distillable without 
 decomposition. Insoluble in water, dissolving sparingly in 
 alcohol and easily in ether, benzene, or glacial acetic acid. Benzyl 
 chloride (100 grams), arsenious chloride (72 grams), diluted with 
 500 c.c. of dry ether and treated with sodium parings (50 grams) 
 and 5 c.c. of ethyl acetate distilled over sodium. After the first 
 vigorous reaction has subsided, and the mixture has cooled, more 
 ethyl acetate (3 c.c.) is added, and generally the process is com- 
 pleted in eighteen to twenty hours. The yields from the fore- 
 going quantities are tribenzylarsine (15-20 grams), dibenzylarsinic 
 acid (10 grams), and tribenzylarsine oxide (5-7 grams). After 
 distilling off the ether the syrupy residue is mixed with alcohol, 
 when tribenzylarsine and a portion of the dibenzylarsine di- 
 hydroxychloride, (C 6 H 5 CH 2 ) 2 As(OH) 2 Cl, separate, whilst the re- 
 mainder of the latter product and tribenzylarsine hydroxy- 
 chloride, (C 6 H 5 -CH 2 ) 3 As(OH)-Cl, remain dissolved. The pre- 
 cipitate is dissolved in boiling alcohol containing ammonia ; 
 on cooling tribenzylarsine crystallises, whilst ammonium di- 
 benzylarsinate remains in solution. Tribenzylarsine combines 
 with the halogens, yielding unstable dihalides decomposed by 
 water into hydroxyhalides ; it combines with sulphur and 
 alkyl iodides, but not with hydrochloric acid. With hot dilute 
 nitric acid it is oxidised to arsenic and benzoic acids. 
 
 Tribenzylarsine mercurichloride, (C 6 H 5 -CH 2 ) 3 As,HgC] 2 , crystal- 
 line, white precipitate from ethereal solutions of its generators. 
 White needles melting at 159 from boiling alcohol. 
 
 1 Michaelis and Paetow, Annalen, 1886, 233, 60 ; Paetow, Inaug. Dissert., 
 Rostock, 1885. 
 
 114 
 
AROMATIC ARSENIC A LS 
 
 Tribenzylarsine oxide, (C 6 H 5 -CH 2 ) 3 AsO, colourless prisms from 
 cold dilute alcohol, m.p. 219-220. Easily soluble in alcohol 
 and glacial acetic acid, sparingly so in cold water, ether, 
 or benzene. Prepared by treating tribenzylarsine chloride 
 with alcohol, also by concentrating the alcoholic mother liquor 
 from the preparation of tribenzylarsine (see above) and adding 
 ether when tribenzylarsine hydro xychloride and dibenzylarsine 
 dihydroxychloride are precipitated. This precipitate, when 
 boiled with aqueous caustic soda and then cooled, gives insoluble 
 tribenzylarsine oxide ; the other product dissolving as sodium 
 dibenzylarsinate, from which solution dibenzylarsinic acid is 
 precipitated by hydrochloric acid. 
 
 Tribenzylarsine oxide is reduced to tribenzylarsine by zinc and 
 glacial acetic acid containing hydrochloric acid ; hydriodic acid 
 and red phosphorus convert it into tetrabenzylarsonium iodide. 
 
 The following hydroxy-derivatives containing acidic radicals 
 are obtained by adding mineral acids to aqueous solutions of 
 tribenzylarsine oxide : (C 6 H 5 -CH 2 ) 3 As(OH)Cl, colourless crystals, 
 m.p. 162-163 ; (C 6 H 5 -CH 2 ) 3 As(OH)Br, colourless, tabular 
 crystals, m.p. 128-129 ; (C 6 H 5 -CH 2 ) 3 As(OH)I,H 2 O, colouiless 
 tetragonal plates, m.p. 78 ; (C 6 H 5 -CH 2 ) 3 As(OH)-NO 3 , colourless 
 needles, m.p. 170 with decomposition. 
 
 Tribenzylarsine sulphide, (C 6 H 5 -CH 2 ) 3 AsS, colourless, trans- 
 parent, rhombic prisms, m.p. 212-214, sparingly soluble in hot 
 chloroform or glacial acetic acid, insoluble in alcohol, ether, benz- 
 ene, or carbon bisulphide. It is prepared by addition of sulphur to 
 tribenzylarsine in warm glacial acetic acid or by passing hydrogen 
 sulphide into an alcoholic solution of tribenzylarsine oxide. 
 
 Tribenzylalkylarsonium iodides- are readily prepared by heating 
 tribenzylarsine with alkyl iodides in sealed tubes at 100. 
 
 Tribenzylmethylarsonium iodide, colourless needles and rhombic 
 crystals, m.p. 143. 
 
 Tribenzylethylarsonium iodide, colourless leaflets, m.p. 148. 
 
 Tribenzylpropylarsonium iodide, colourless, monocliuic plates, 
 m.p. 145-146. 
 
 Tribenzylisopropylarsonium iodide, colourless, tabular crystals, 
 m.p. 143. 
 
 The first of this series treated with moist silver oxide yields a 
 solution of the highly caustic base, tribenzylmethylarsonium 
 hydroxide, which rapidly absorbs carbon dioxide, and on heating 
 with concentrated aqueous caustic soda decomposes, with form- 
 ation of toluene. 
 
 115 I 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Tetrabenzylarsonium chloride, (C 6 H 5 -CH 2 ) 4 AsCl,H 2 O, triclinic 
 crystals from dilute hydrochloric acid, m.p. 160, obtained by 
 heating tribenzylarsine and benzyl chloride in sealed tubes at 
 170-175. The corresponding bromide, needles, m.p. 173, 
 iodide, transparent needles, m.p. 168, periodide, (C 7 H 7 ) 4 AsI 3 , 
 lustrous red leaflets, m. p. 149-150. 
 
 Tetrabenzylarsonium hydroxide, (C 6 H 6 -CH 2 ) 4 As-OH, obtained 
 from the iodide and moist silver oxide as a syrup with alkaline 
 reaction, rapidly becomes solid by absorbing atmospheric carbon 
 dioxide, and on heating with alkalis it loses toluene and becomes 
 converted into tribenzylarsine oxide, 
 
 (C 7 H 7 ) 4 AsOH = C 7 H 8 + (C 7 H 7 ) 3 AsO. 
 
 Tetrabenzylarsonium hydroxide l yields the following charac- 
 teristic salts : mercuri-iodide, m.p. 163 ; mercurichloride, 
 white needles, m.p. 176 ; platinichloride, m.p. 198 ; and 
 aurichloride, yellow needles, m.p. 130 (indefinite). 
 
 Dibenzylarsinic acid, (C 6 H 5 -CH 2 ) 2 AsOOH, nacreous leaflets 
 from alcohol, m.p. 210, very sparingly soluble in cold alcohol, 
 ether, acetone, or benzene. Obtained by treating dibenzylarsinic 
 trichloride with caustic soda (for its preparation see tribenzyl- 
 arsine and tribenzylarsine oxide). This acid has a saline, bitter 
 taste, it is greasy to the touch, and has a very irritating effect 
 on the mucous membrane. Above 210 it decomposes : 
 
 2(C e H 5 -CH 2 ) a AsO-OH = 2As -f 2H 2 O + 2C 6 H 5 -COH + 2C 7 H 8 , 
 with the formation of benzaldehyde and toluene. Concentrated 
 hydrochloric acid decomposes it completely, forming benzyl 
 chloride, toluene, and arsenious chloride, 
 
 (C 6 H 5 -CH 2 ) 2 AsOOH + 4HC1 = 
 
 C 6 H 6 -CH 2 C1 + C 6 H 5 -CH 3 + AsCl 3 + 2H 2 O. 
 
 Dibenzylarsinic acid is reduced by zinc and alcoholic hydro- 
 chloric acid or by stannous chloride to a white, sparingly soluble 
 powder which on exposure to air regenerates dibenzylarsinic acid. 
 This product may possibly be the cacodyl derivative, 
 
 (C 7 H 7 ) 2 As-As(C 7 H 7 ) 2 , 
 but it has not been obtained pure. 
 
 The metallic dibenzylarsinates are well denned salts, indi- 
 cating that the acid is monobasic. The alkali salts are very 
 soluble. The calcium, [(C 7 H 7 ) 2 As0 2 ] 2 Ca,6H 2 O, and barium, 
 [(C 7 H 7 ) 2 AsO 2 ] 2 Ba,8H 2 0, 
 
 1 Mannheim, Annalen, 1905, 341, 208. 
 
 116 
 
AROMATIC ARSENICALS 
 
 salts are soluble in water and crystallise from alcohol. Silver 
 salt, (C 7 H 7 ) 2 AsO 2 Ag, white, amorphous precipitate. 
 
 Dibenzylarsinic acid has a constitution similar to that of 
 cacodylic acid, and, like the latter, it exhibits amphoteric 
 properties, combining with acids as well as with bases. In its 
 basic phase it probably reacts as the ortho-compound, 
 
 (C 7 H 7 ) 2 As(OH) 3 , 
 
 and exchanges one of these three hydroxyl groups for an acid 
 radical. 
 
 Dibenzylarsinic acid hydrochloride, (C 8 H 6 -CH 2 ) 2 As(OH) 2 Cl, white 
 needles, m.p. 128, prepared by boiling powdered dibenzylarsinic 
 acid with dilute hydrochloric acid. It corresponds with Bunsen's 
 "cacodyl superchloride," (CH 3 ) 2 AsOOH,HCl. The hydro- 
 bromide, (C 6 H 6 -CH 2 ) 2 As(OH) 2 Br, and the hydrochloride both 
 decompose, liberating benzyl bromide and chloride respectively. 
 The n^>^,(C 6 H 5 -CH 2 ) 2 As(OH) 2 -N0 3 , silky needles, m.p. 128-129, 
 is more stable than the preceding halide compound. 
 
 A compound having the composition (C 6 H 6 -CH 2 ) 2 As'OH,H a O, 
 lustrous leaflets, m.p. 215-216, is produced by applying the 
 Grignard reagent, magnesium benzyl chloride, to arsenious oxide 
 in ethereal solution. 1 
 
 Dibenzylthioarsinic acid, (C 6 H 6 -CH 2 ) 2 AsOSH, white, nacreous 
 leaflets from alcohol, m.p. 197-199. Hydrogen sulphide is 
 passed into an alkaline solution of dibenzylarsinic acid and the 
 liquid then acidified. The precipitate is soluble in benzene or 
 glacial acetic acid. 
 
 Benzylarsenious chloride, C 6 H 6 -CH 2 -AsCl 2 , liquid, b. p. 
 I 75/5 mm., prepared by heating tribenzylarsine (10 grams) 
 with arsenious chloride (30 grams) for ten to twelve hours at 
 160-180. Decomposes in the air, 
 
 C 6 H 6 CH 2 AsCl a + O = C 6 H 6 CH 2 -C1 + AsOCl. 
 
 Water decomposes the chloride into benzaldehyde (benzoic acid) 
 and arsenious oxide. Chlorine also destroys it, giving benzyl 
 chloride and arsenious chloride. Benzylarsenious chloride 
 produces painful blisters on the skin. This chloride is far 
 less stable than purely aliphatic or aromatic arsenious 
 chlorides. 
 
 1 Sachs and Kantorowicz, Ber,, 1908, 41, 2769. 
 117 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Benzylarsinic acid, 1 C 6 H 6 -CH 2 -AsO(OH) 3 , colourless, glistening 
 needles, m.p. 167, is readily obtained by dissolving in dilute 
 alcohol the reagents indicated by the following equation : 
 
 2C 6 H 6 -CH 2 I + As 2 O 3 + 6KOH = 
 
 2C 6 H 6 -CH 2 -AsO(OK) 2 + 2KI + 3 H a O. 
 
 The solution, freed from alcohol by distillation, is neutralised, 
 filtered, and then acidified cautiously with hydrochloric acid, 
 when benzylarsinic acid is precipitated to the extent of 60 per 
 cent. The disulphide, C 7 H 7 -AsS 2 , a heavy, bright yellow oil, is 
 formed by the action of sulphuretted hydrogen on an aqueous 
 solution of benzylarsinic acid. This acid dissolves only sparingly 
 in cold water ; 100 c.c. of saturated aqueous solution at 22-5, 
 27, and 97 contain respectively 0-34, 0-39, and 3-50 grams ; 
 100 c.c. of saturated alcohol at 23 and 70 contain 0-87 and 
 5-91 grams. 
 
 Benzylarsinic acid, like the dibenzyl compound (p. 116), is 
 decomposed by strong mineral acids, 
 
 2C 6 H 5 -CH 2 -AsO(OH) 2 + 2HC1 = 2C 6 H 6 -CH 2 -C1 + As 2 O 3 + 3H 2 O. 
 
 Sulphuric acid gives dibenzyl, benzaldehyde, and arsenious oxide. 
 On heating, this arsinic acid decomposes into benzyl alcohol, 
 benzaldehyde, stilbene, arsenious oxide, and water. 
 
 Benzylarsine, 2 C 6 H 5 CH 2 -AsH 2 , faintly yellow liquid, b.p. 
 I40/26o mm., is prepared by reducing benzylarsinic acid with 
 amalgamated zinc dust and concentrated hydrochloric acid in 
 the presence of ether, 
 
 C 6 H 6 CH 2 -AsO 3 H 2 -f 6H = C 6 H 6 -CH 2 -AsH 2 + 3H 2 O. 
 
 A red condensation product is deposited on the walls of the 
 reduction flask. This substance is probably identical with the 
 red compound obtained by the aerial oxidation of benzylarsine, 
 this reaction giving rise to benzylarsinic acid (m.p. 167) and 
 arsenophenylmethane, 
 
 (C 6 H 6 CH 2 -As:As-CH 2 -C 6 H 6 ) 2 . 
 
 A black polymeride of the latter product is obtained by heating 
 benzylarsine at 250 in vaciw. 
 
 1 Dehn and McGrath, /. Amer. Chem. Soc., 1906, 28, 354. 
 8 Dehn, Amer. Chem. /., 1908, 40, 113. 
 
 1x8 
 
AROMATIC ARSENICALS 
 
 Section VII. Aromatic Arsenicals containing Higher Aryl 
 
 Groups, 
 
 i. Compounds containing One Aryl Group to One Arsenic Atom. 1 
 
 m-Xylylarsenious chloride, (CH 3 ) 2 C 6 H 3 -AsCl 2 , colourless needles, 
 m.p. 42-43, b.p. 2787760 mm. and 2157320 mm. Obtained 
 by the general methods : 
 
 (i) mercury di-w-xylyl, added slowly to ten parts of arsenious 
 chloride, and after twenty-four hours the nitrate from mercuric 
 chloride fractionated. 
 
 (ii) Tri-w-xylylarsine heated at 240 with 40 parts of arsenious 
 chloride and the product fractionated. 
 
 " m-Xylyktrseniow oxide, (CH 3 ) 2 C 6 H 3 -AsO, granules, m.p. 220, 
 readily obtained from the chloride by alkaline hydrolysis ; 
 absorbs chlorine, forming m-xylylarsenic oxy chloride, colourless, 
 flattened needles, m.p. 150. 
 
 m-Xylylarsenious sulphide, (CH 3 ) 2 C 6 H 3 -AsS, colourless needles 
 from ether or benzene-alcohol, m.p. 169, by the action of 
 hydrogen sulphide on the preceding oxide or chloride in alcoholic 
 solution. 
 
 Arseno-m-xylene, C 8 H 9 -As:As-C 8 H 9 , white needles from chloro- 
 form-ether, m.p. 194-196 ; addition of iodine in alcoholic solu- 
 tion leads to iodoarseno-m-xylene, C 8 H 9 -AsI-AsI*C 8 H 9 , yellow 
 crystals, m.p. 89. 
 
 m-Xylylarsenic chloride, C 8 H 9 AsCl 4 , colourless, crystalline 
 mass, hydrolysed to oxychloride and arsinic acid. 
 
 m-Xylylarsinic acid, (CH 3 ) 2 C 6 H 3 -AsO(OH) 2 , rectangular crystals 
 from dilute alcohol, m.p. 210, obtained by hydrolysis of the 
 preceding chloride or by adding hydrogen peroxide to w-xylyl- 
 arsenious chloride in glacial acetic acid. Acid ammonium salt, 
 soluble crystals, m.p. 136. 
 
 Chloro-m-xylylarsinic acid, (CH 3 ) 2 C 6 H 2 Cl'AsO(OH) 2 , needles, 
 m.p. 165, by passing chlorine into w-xylylarsenious chloride 
 suspended in water : dichloro-m-xylylarsinic acid, m.p. 193, 
 produced by chlorinating the dichloride in glacial acetic acid. 
 
 These results show that chloro-derivatives are much more 
 readily obtained in the xylene than in the toluene and benzene 
 series. 
 
 m-Toluarsinic acid, CO 8 H-CeH 8 (CH 8 )-AsO(OH) a , is obtained by 
 
 1 Michaelis, Annalen, 1902, 320, 330; Seemann, Inaug. Dissert., Ros- 
 tock, 1891. 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 oxidising w-xylylarsinic acid with the calculated amount of 
 permanganate, at 190 it changes into the anhydride, 
 
 C0 2 H-C 6 H 8 (CH 3 )-As0 2 . 
 
 isoPhthaloarsinic acid, (CO 2 H) a C 6 H 3 -AsO(OH) 2 , colourless 
 crystals, when double the amount of permanganate is employed ; 
 this acid decomposes without melting. 
 
 p-Xylylarsenious chloride, 1 
 
 CH 3 
 
 <( )>AsCl 2 , 
 
 ~CH 3 
 
 prepared by the general methods, the process from tri-^-xylyl- 
 arsine and five parts of arsenious chloride at 230 giving the best 
 yield ; tufts of colourless needles ; m.p. 63, b.p. 285/76o mm. 
 The iodide obtained by dissolving the oxide in strong hydriodic 
 acid (b.p. 127), yellow crystals, m.p. 45 ; the oxide, m.p. 165 ; 
 oxychloride, needles, m.p. 178. 
 
 Arseno-p-xylene, C 8 H 9 -As:As-C 8 H 9 , white powder, m.p. 208, 
 takes up iodine to form iodoarseno-p-xylene, C 8 H 9 -AsI'AsI-C 8 H 9 , 
 m.p. 97. 
 
 p-Xylylarsenious sulphide, C 8 H 9 -AsS, yellow needles, m.p. 
 188 ; disulphide, C 8 H 9 -AsS 2 , white precipitate obtained by 
 saturating ammoniacal solution of ^-xylylarsinic acid with 
 hydrogen sulphide and adding hydrochloric acid. 
 
 p-Xylylarsinic acid, white needles from hot water, m.p. 223, 
 prepared from the chloride by the general method, is oxidised 
 to p-toluarsinic acid, CO 2 H-C 7 H 6 -AsO(OH) 2 , white crystals from 
 alcohol or ether, m.p. 208. Silver salt indicates dibasicity. 
 
 Pseudocumylarsenious chloride, 2 (CH 3 ) 3 C 6 H 2 -AsCl 2 , [3CH 3 : AsG 2 
 = 1:2:4:5], prepared by heating tri-pseudo-cumylarsirie with 
 four parts of arsenious chloride for forty-eight hours at 200, 
 and fractionating the product under 30 mm. pressure ; colour- 
 less needles, m.p. 82-5, b.p. igo/^o mm. 
 
 Pseudocumylarsinic acid, C 9 H n -AsO(OH) 2 , colourless needles 
 from alcohol or water, m.p. 224. Silver salt, C 9 H n -AsO(OAg)2. 
 
 p-Cumylarsenious chloride, C 8 H 7 -C 6 H 4 -AsCl 2 ,obtamedby heating 
 tri-^>-cumylarsine with four parts of arsenious chloride for 
 forty-eight hours at 170 ; oil, b.p. I7O/3O mm. 
 
 p-Cumylarsinic acid, C 8 H 7 -C 6 H 4 AsO(OH) 2 , snow-white, silky 
 needles from warm alcohol or hot water, m.p. 152, oxidised by 
 
 1 Michaelis, Annalen, 1902, 3.20, 336. 2 Michaelis, loc. cit., 339. 
 
 I2O 
 
AROMATIC ARSENICALS 
 
 alkaline permanganate to ^-benzarsinic acid, the propyl group 
 being destroyed. 
 
 Tertiary butylphenylarsenious chloride, (CH 3 ) 3 C-C 6 H 4 -AsCl 2 , 
 prepared by heating for twenty-four hours at 200 tii-tert.- 
 butylphenylarsine with seven parts of arsenious chloride, 
 colourless liquid, b. p. i75-i8o/2O mm., converted by aqueous 
 sodium carbonate into the oxide, colourless crystals, m.p. 89, 
 which on reduction with phosphorous acid gives arsenotertiary- 
 butylbenzene, m.p. 198. 
 
 The arsinic acid, (CH 3 ) 3 C-C 6 H 4 -AsO(OH) 2 , is best prepared by 
 adding hydrogen peroxide to the chloride dissolved in glacial 
 acetic acid ; tufts of colourless needles, m.p. 193. 
 
 2. Compounds containing Three Aryl Groups to One Arsenic 
 
 Atom. 
 Tri-m-xylylarsine, l 
 
 As 
 
 This arsine is produced in quantitative yield by the interaction 
 of bromo-w-xylene (61 grams), arsenious chloride (20 grams), 
 and sodium (30 grams) in dry ether, the reaction going to com- 
 pletion without external heating ; from alcohol-petroleum in 
 colourless, transparent prisms, m.p. 166 ; easily soluble in the 
 ordinary organic solvents, although dissolving only sparingly 
 in alcohol. The following derivatives can be employed in 
 characterising this arsine : mercurichloride, m.p. 257 ; oxide, 
 (C 8 H 9 ) 3 AsO, from the bromide by aqueous alkalis, colourless 
 crystals of hydroxide losing water at 100 ; sulphide, (C 8 H 9 ) 3 AsS, 
 silky prisms, m.p. 145, from the arsine and sulphur ; meth- 
 iodide, (C 8 H 9 ) 3 As(CH 3 )I, lustrous crystals, m.p. 179 ; methi- 
 chloride, uncrystallisable ; platinichloride, reddish-brown crystals, 
 m.p. 245. 
 
 Tri-p-xylylarsine, 
 
 As 
 
 L CH { 
 This arsine, prepared like its preceding isomeride from bromo- 
 
 1 Michaelis, Annalen, 1902, 331, 220. 
 121 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 p-xylene, crystallises from the mixture, alcohol-light petroleum- 
 benzene, in lustrous, colourless prisms, m.p. 157 ; mercuri- 
 chloride, m.p. 236 ; methiodide, colourless, tabular crystals, 
 m.p. 175 ; platinichloride, pale yellow needles, m.p. 250 ; no 
 combination with ethyl iodide. 
 Di-m-xylylphenylarsine, x 
 
 Phenylarsenious chloride (46 grams), bromo-w-xylene (77 grams), 
 and sodium (38 grams) in 400 c.c. of ether lead to the production 
 of this dissymmetric arsine (45 grams or 60 per cent, of theory), 
 the product crystallising from ether-alcohol in tridinic crystals, 
 m.p. 99, dissolving sparingly in alcohol and easily in other 
 organic solvents : mercurichloride, (C 8 H 9 ) 2 AsC 6 H 6 ,HgCl 2 , from 
 alcohol-chloroform in lustrous needles, m.p. 224 ; platini- 
 chloride, (C 8 H 9 ) 2 As-C 6 H 5 ,H 2 PtCl 6 , yellow, felted needles, m.p. 
 above 300 ; dichloride, m.p. 176, very easily hydrolysed to 
 hydroxy chloride, m.p. 186 ; periodide, (C 8 H 9 ) 2 As(C 6 H 5 )T 4 , red- 
 dish-violet crystals, m.p. 127 ; hydroxide, m.p. 112, and passing 
 into oxide, m.p. 120 ; hydroxy nitrate, transparent crystals, 
 m.p. 126, by the action of hot dilute nitric acid on the last 
 two compounds ; methiodide, lustrous, colourless crystals, m.p. 
 184 ; di-m-xylylphenylarsonium hydroxide, m.p. 122 ; eth- 
 iodide, m.p. 157 ; trinitrodi-m-xylylphenylarsine oxide from the 
 arsine and nitro-sulphuric acid, separates from alcohol in pale 
 yellow crystals, m.p. 245. 
 Tri-p-ethylphenylarsine, 2 
 
 As / \C,H 
 
 is prepared from ^-bromoethylbenzene (in grams), arsenious 
 chloride (42 grams), and sodium (50 grams) in 500 grams of dry 
 ether, m.p. 78, easily soluble in ether, less so in alcohol : 
 mercurichloride, m.p. 132 ; bichloride, m.p. 246 ; dibromide, 
 m.p. 212 ; hydroxide, m.p. 180 ; sulphide, m.p. 123 ; meth- 
 iodide, m.p. 126 ; Jnwfro-derivative, [NO 2 -(CH 3 )C 6 H 3 ] 3 AsO, 
 m.p. 232. 
 
 1 Michaelis, he. c4t., 223. 2 Ibid., 226. 
 
 122 
 
AROMATIC ARSENICALS 
 
 Tripseudociimylarsine, 1 
 
 r c Ji_ 
 
 As / >CH 
 
 CH 3 _. 
 
 This arsine is readily prepared by mixing bromopseudocumene 
 (50 grams), arsenious chloride (16 grams), and sodium (21 grams) 
 in 250 c.c. of dry ether, the reaction being completed by pro- 
 longed heating on the water-bath ; the product is practically 
 insoluble in ether, sparingly soluble in alcohol and light petroleum, 
 and easily so in benzene ; snow-white needles, m.p. 223 ; 
 dibromide, yellow powder, m.p. 224-225, hydrolysed to hydroxy- 
 bromide, m.p. 108, and dihydroxide, (C 9 H n ) 3 As(OH) 2 ,4H 2 O, 
 needles from dilute alcohol losing 5H 2 O at 120, leaving the 
 oxide, m.p. 227-228. 
 
 Dipseudocumylphenylarsine, 
 
 CH 3 
 
 C.H.-AS'/ 
 
 is produced by adding sodium (30 grams) to phenylarsenious 
 chloride (30 grams) and bromopseudocumene (53-5 grams) in 
 300 c.c. of dry ether. After 45 hours' boiling in a reflux apparatus 
 the reaction is complete (35 grams of arsine 70 per cent, of 
 theory), m.p. 138-5, soluble in the usual organic solvents; 
 platinichloride, [(C 9 H n ) 2 As-C 6 H 6 ] 2 H 2 PtCl 6 , yellow rosettes, m.p. 
 287 ; aurichloride, (C 9 H n ) 2 As-C 6 H 5 ,HAuCl4, colourless aggre- 
 gates melting at 177 to a golden-yellow mass ; mercurichloride, 
 (C^n^AsCsHg.HgCLj, silvery leaflets from hot glacial acetic 
 acid, m.p. 223 ; dichloride, m.p. 217 ; hydroxy chloride, 
 transparent crystals, m.p. 173-175 ; hydroxybromide, m.p. 
 177 ; di-iodide, yellowish-red crystals, m.p. 163-5 '> hydroxy- 
 iodide, pale yellow precipitate, m.p. 153 ; dihydroxide, colour- 
 less, transparent prisms, m.p. 113-114, obtained by the action 
 of alcoholic potash on the preceding halide derivatives, loses 
 water in the desiccator at 100, giving the oxide, m.p. 162-5 i 
 the sulphide, (C 9 H 11 ) 2 AsS-C 6 H 5 , m.p. 135, from the arsine 
 and alcoholic yellow ammonium sulphide at 110 ; methiodide, 
 m.p. 179 ; methochloride, m.p. 192 ; platinichloride, m.p. 
 266-5 ; dipseudocumylphenylmethylarsonium hydroxide, 
 
 (C 9 H u ) 2 As(C.H.)(CH,)-OH, 
 
 1 Ibid., 227. 
 
 123 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 from iodide in alcoholic solution with silver oxide, colourless 
 needles, softening at 147, m.p. 151 ; ethiodide, colourless 
 crystals, m.p. 189 ; trinitrodipseudocumylphenylarsine oxide, 
 
 NO a -C,H 4 
 
 ">AsO, prepared from the arsine or its oxide and 
 (N0 2 -C 8 H, 1 )/ 
 
 nitrosulphuric acid, pale yellow crusts from alcohol, m.p. 163. 
 Tri-p-cumylarsine, l 
 
 \ / -- \ /CH 3 
 
 As CH 
 
 is prepared by condensing />-bromocumene (40 grams), 
 arsenious chloride (12 grams), and sodium (30 grams) in 300 c.c. 
 of dry ether ; colourless prisms from ether-alcohol, m.p. 139-140 ; 
 mercurichloride, (C 9 H 11 ) 3 As,HgCl 2 , white needles, m.p. 243; 
 dichloride, colourless needles, m.p. 276 ; platinichloride, 
 
 [(C,H u ) 3 AsCl 4 ] a PtCl,, 
 
 golden-yellow needles from platinichloride and dichloride in 
 alcoholic solution ; dibromide, m.p. 142 ; oxide, white needles, 
 m.p. 129, dissolving in dilute nitric acid to the hydroxy nitrate, 
 (C 9 H 11 ) 3 As(OH)-NO 8 , m.p. 147 ; trinitrotricumylarsine oxide, 
 (NO 2 -C 9 H 10 ) 3 AsO, yellowish-white needles, m.p. 245, by dis- 
 solving the arsine in nitrosulphuric acid, the sulphide, (C 9 H n ) 3 AsS, 
 silky white crystals, m.p. 149-5, by leading sulphuretted hydro- 
 gen into the alcoholic solution of the oxide ; methiodide, 
 
 (C,H u ),As(CH,)I, 
 
 colourless rosettes, m.p. 103 ; ethiodide, m.p. 138. 
 Trimesitylarsine , 2 
 
 CH 3 T 
 
 / - 
 
 CH 
 
 The production of this arsine occurs less readily than that of 
 the lower homologues ; bromomesitylene (30 grams), arsenious 
 chloride (9 grams), and sodium (20 grams) in dry ether are heated 
 in a reflux apparatus ; tufts of colourless prisms from alcohol, 
 m.p. 170 : hydroxy chloride, colourless prisms, m.p. 100 ; 
 dibromide, very well denned tabular crystals of the rhombic 
 system from alcohol, m.p. 237 ; oxide, m.p. 203-204 ; meth- 
 
 1 Ibid., 235. 2 Ibid., 238. 
 
 124 
 
AROMATIC ARSENICALS 
 
 iodide, (C9H n ) 8 As(CH 3 )I, colourless prisms, m.p. 186, readily 
 obtained from its generators, on the water-bath ; methochloride, 
 tufts of crystals, m.p. 192 ; platinichloride, yellowish-red, 
 monociinic crystals, m.p. 237. 
 Tri-tertiary-butylphenylarsine. 
 
 The ter/.-butylbenzene required is obtainable in 60 per cent, 
 yield from benzene, ^'sobutyl chloride, and aluminium chloride ; 
 bromination with iodine as carrier leads to biomo-terl. -butyl- 
 benzene (m.p. 13, b.p. 230). The bro mo-derivative (50 grams) 
 heated in ethereal solution with arsenious chloride and sodium 
 yields 30 grams of arsine crystallising from benzene, m.p. 235 ; 
 oxide, m.p. above 360 ; methiodide, m.p. 125 ; /n'-tert.- 
 butylphenylmethylarsonium hydroxide, 
 
 [(CH 8 ) 3 C-C 6 H 4 ]sAs(CH 8 ).OH, 4 H a O, 
 
 rhombohedral crystals, m.p. 136, is exceptionally crystallisable 
 for a quaternary hydroxide ; the water of crystallisation cannot 
 be removed without decomposing the compound. 
 
 Section VIII. Arsenical Derivatives of Naphthalene. 
 
 a-Naphthylarsenious chloride, 1 C 10 H 7 -AsCl 2 , white, crystalline 
 powder, m.p. 63, easily soluble in alcohol, benzene, or other 
 organic solvents, is prepared by heating tri-a-naphthylarsine 
 with 20 parts of arsenious chloride at 270 for forty hours ; the 
 product, after distilling under reduced pressure to remove excess 
 of this reagent, is extracted with ether. The crude a-naphthyl- 
 arsenious chloride is purified by repeated crystallisation from 
 alcohol or light petroleum. It is not affected by water, but 
 caustic or carbonated alkalis convert it into a-naphthyl- 
 arsenious oxide, C 10 H 7 -AsO, white powder, m.p. 245, insoluble 
 in water, benzene, or ether, dissolving sparingly in boiling alcohol. 
 By dry distillation it yields, not trinaphthylarsine, but naphtha- 
 lene, elemental arsenic, and carbon. 
 
 Arseno-a-naphthalene, C 10 H 7 -As:As-C 10 H 7 , yellow needles, 
 m.p. 221, is insoluble in water or ether and dissolves only 
 sparingly in alcohol, benzene, carbon bisulphide, or chloroform. 
 It is prepared by boiling an alcoholic solution of a-naphthyl- 
 arsenious oxide with solid phosphorous acid, when the arseno- 
 
 1 Michaelis and Schulte, Ber., 1882, 15, 1954 > Annalen, 1902, 302, 342 ; 
 Biischler, Inaug. Dissert., Rostock, 1893. 
 
 125 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 derivative separates as a yellow, crystalline powder. With 
 chlorine, arseno-a-naphthalene combines additively to form 
 a-naphthylarsenious chloride ; with sulphur it yields a-naphthyl- 
 arsenious sulphide ; nitric acid oxidises it to a-naphthylarsinic 
 acid. 
 
 a-Naphthylarsinic acid, 1 C 10 H 7 -AsO(OH) 2 , well denned colour- 
 less needles from water, m.p. 197, prepared by the following 
 series of reactions : mercury di-a-naphthyl dissolved in arsenious 
 chloride leads to a strongly exothermic reaction with separation 
 of mercuric chloride, the condensation being completed in a reflux 
 apparatus. The product diluted with benzene is filtered from 
 this precipitate, the solution evaporated, and the oily residue 
 treated with chlorine so long as the gas is absorbed with genera- 
 tion of heat. Water is then added, when hydrogen chloride is 
 evolved and the arsinic acid separates in a crystalline form, 
 
 2AsQ 3 + Hg(C 10 H 7 ) 2 = HgCl 2 + 2C 10 H 7 -AsCL. 
 
 C 10 H 7 AsCl 2 + 2C1 = C 10 H 7 AsCl 4 . 
 C 10 H 7 AsQ 4 + 3H 2 = 4HC1 + C 10 H 7 AsO(OH) 2 . 
 
 fi-Naphthylarsenious chloride, 2 warty aggregates of needles, 
 m.p. 69, soluble in ether, benzene, or alcohol. As tri-/?-naphthyl- 
 arsine is difficult to obtain, the other general method of prepara- 
 tion is adopted, and mercury di-/?-naphthyl is boiled for one 
 hour in a reflux apparatus with seven parts of arsenious chloride. 
 The excess of the latter reagent is removed by distillation, the 
 residue extracted with ether, and the soluble product crystallised 
 repeatedly from light petroleum. This chloride, treated with 
 alcoholic potash, yields the oxide, C 10 H/AsO, a white, granular, 
 sparingly soluble powder, m.p. 270. 
 
 Arseno- ^-naphthalene, C 1 oH 7 'As:As-C 1 oIi 7 , yellow needles from 
 xylene, m.p. 234, prepared by heating alcoholic solutions of 
 the preceding chloride or oxide with phosphorous acid. 
 
 p-Naphthylarsinic add, C 10 H 7 -AsO(OH) 2 , colourless needles 
 from hot water, m.p. 155, obtained by converting the above 
 dichloride into tetrachloride with chlorine and by hydrolysing 
 the latter chloride with water ; this acid closely resembles the 
 a-isomeride ; it is easily soluble in alcohol, sparingly so in cold 
 water. 
 
 The reaction between the bromonaphthalenes, arsenious 
 chloride (in ether), and sodium takes place far less smoothly 
 than with the chloro- and bromo-derivatives of the benzenoid 
 
 1 Kelbe, Ber., 1878, 11, 1503. 2 Michaelis, Annalen, 1902, 320, 342. 
 
 126 
 
AROMATIC ARSENICALS 
 
 hydrocarbons ; tarry by-products are formed to a considerable 
 extent. 1 
 
 Tri-a-naphthylarsine , 
 
 As 
 
 \ 
 
 a-Bromonaphthalene (51 grams), arsenious chloride (15 grams), 
 and sodium (20 grams) are mixed in dry ether and after 24 hours 
 the mixture is heated on the water-bath for 15-20 hours. The 
 oily mass left after distilling off the ether is freed from tar by 
 extraction with a little of this solvent, the residual solid is 
 dissolved in hot benzene, and to the solution an equal volume of 
 alcohol is added, when tri-a-naphthylarsine crystallises on 
 cooling in slender prisms (yield 20 %). When recrystallised 
 from benzene the arsine separates in rhombic plates, m.p. 252 ; 
 it is easily soluble in carbon bisulphide, sparingly so in 
 chloroform, ether, or alcohol. Unlike the other tertiary aromatic 
 arsines, it does not form a mercurichloride. Addition of 
 bromine to the arsine in" benzene leads, not to the dibromide, but 
 to a tetrabromo-deriv&tive. in which probably two bromine atoms 
 have entered a naphthalene nucleus. When bromine is added 
 to a benzene solution of the arsine rendered turbid by dilute 
 alcohol, the hydroxybromide is formed, m.p. 155, which is 
 changed into the dihydroxide, (C 10 H 7 ) 3 As(OH) 2 ,2H 2 O, colourless 
 needles from hot alcohol, melting above 300 ; when dried at 
 110 this compound loses 3H 2 and leaves the oxide. 
 Tri-ft-naphthylarsine, 
 
 Prepared from /3-bromonaphthalene, the procedure being the 
 same as that employed for the a-isomeride. The residue after 
 condensation is extracted successively with alcohol and light 
 petroleum to remove naphthalene and tarry impurity. The 
 crude arsine remaining as a light yellow powder is further purified 
 through its mercurichloride (leaflets, m.p. 247) ; this derivative, 
 after crystallisation from glacial acetic acid, is decomposed by 
 sulphuretted hydrogen when dissolved in the same solvent ; 
 
 1 Michaelis, Annalen, 1902, 321, 242. 
 127 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 mercuric sulphide is precipitated, and tri-/?-naphthylarsine 
 separates in colourless crystals, m.p. 165, readily soluble in 
 benzene, carbon bisulphide, or chloroform, sparingly so in ether ; 
 the dibromide is tarry and on treatment with alcoholic potash 
 yields the anhydrous tri-ft-naphthylarsine oxide, (C 10 H 7 ) 3 AsO ; the 
 sulphide, (C 10 H 7 ) 8 AsS, m.p. 162, well-defined tablets from 
 dilute alcohol is formed by passing sulphuretted hydrogen 
 through an alcoholic solution of the dibromide. This sulphide 
 is easily soluble in benzene or carbon disulphide, and when its 
 solution in the former is boiled with mercury, the sulphur is 
 removed, and pure tri-/3-naphthylarsine is regenerated. 
 
 Section IX. Benzarsinic Acids and their Derivatives. 1 
 
 This section contains a description of a series of arsenical 
 carboxylic acids derived by oxidation from aromatic arsenic 
 derivatives containing methylated benzenoid nuclei. 
 
 The arsenical toluene and xylene derivatives contain the 
 metalloid so firmly united to the aromatic nucleus that the 
 methyl group can be oxidised to carboxyl without detaching 
 the arsenic radical. In this way aromatic derivatives of arsenic 
 acid are obtained in which three hydroxyl groups are successively 
 replaced by the univalent radical -C 6 H 4 -C0 2 H. 
 
 AsO(OH) 8 
 
 CO 2 H-C 8 H 4 -AsO(OH) 2 (CO 2 H-C 6 H 4 ) 2 AsO(OH) (CO 2 H-C 6 H 4 ) 8 AsO 
 Benzarsinic acid Dibenzarsinic acid Tribenzarsinic 
 
 (carboxyphenyl- (dicarboxydiphenyl- acid (tricarboxy- 
 arsinic acid). arsinic acid): triphenylarsinic 
 
 acid); 
 
 The ^-tolyl compounds were selected by La Coste for the study 
 of this reaction. ^-Tolylarsinic acid remained unchanged after 
 continuous boiling for a week with a large excess of nitric acid 
 in a reflux apparatus. Chromic acid in warm glacial acetic acid 
 solution eliminates arsenic from this organic acid in the form of 
 arsenic acid. The desired oxidation was achieved by the use 
 of alkaline permanganate, 
 
 CH 3 -C 6 H 4 AsO(OK) 2 + 2KMnO 4 = 
 
 CO 2 K-C 6 H 4 AsO(OK) 2 + 2MnO 2 -f KOH + H 2 O. 
 
 1 La Coste, Annalen, 1881, 208, i. 
 128 
 
ROMATIC ARSENICALS 
 
 Similar changes can be effected with di--tolylarsinic acid and 
 tri-/>-tolylarsine or its dihydroxide. 
 
 These benzarsinic acids undergo reduction on treatment with 
 hydriodic acid and phosphorus, giving rise to substituted 
 arsenious iodides, which on successive treatment with aqueous 
 sodium carbonate and dilute mineral acid furnish aromatic 
 arsenious acids, substances of considerable theoretical interest 
 as being derivatives of ortho-arsenious acid, As(OH) 3 , in which 
 the hydro xyl groups become successively replaced by C 6 H 4 -CO 2 H 
 groups. 
 
 As(OH) 3 
 
 ! 
 
 ! I 
 
 CO 2 H-C 6 H 4 -As(CH) 2 (CO 2 H-C 6 H 4 ) 2 As-OH (CO 2 H-C 6 H 4 ) 3 As 
 
 Benzarsenious acid Dibenzarsenious acid Tribenzarsemous acid 
 (carboxyphenyl- (dicarboxydiphenyl- (arsinotribenzoic 
 arsenious acid) . arsenious acid) . acid) . 
 
 The tervalent arsenic of the first two compounds is very excep- 
 tional in retaining its hydroxyl group and in not forming the 
 anhydride, R-AsO or R 2 As-OAs-R 2 . This remarkable stability 
 of the hydroxylated compounds is undoubtedly due to the pre- 
 sence of an acidic carboxyl group in the aromatic nucleus. The 
 foregoing property, which is noticeable in certain of the nitro-aryl- 
 arsenious compounds, corresponds with the stabilising effect 
 produced on aa-dihydroxycarbon complexes, -C(OH) 2 -, by the 
 presence of neighbouring acidic groups as in mesoxalic and 
 dihydroxytartaric acids or in chloral hydrate and its analogues. 
 
 I. Toluene Series. 
 
 p-Benzarsinic acid (p-Carboxyphenylarsinic acid), 
 CO 2 H-C 6 H 4 -AsO(OH) 2 , 
 
 colourless transparent plates, sparingly soluble in water, 
 scarcely so in alcohol or glacial acetic acid. 
 
 Preparation : i. A solution of potassium permanganate 
 (14 grams) in 750 c.c. of water is added slowly to ^-tolylarsinic 
 acid (10 grams) and potassium hydroxide (6 grams) in 250 c.c. 
 of water. After some days the colourless solution is filtered, 
 concentrated, acidified with acetic acid, evaporated to dryness, 
 and extracted with alcohol to remove potassium acetate. The 
 residual acid potassium ^-benzarsinate (about 10 grams) is 
 
 129 K 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 decomposed by concentrated hydrochloric acid at 60, when the 
 free acid separates in well defined crystals. 
 
 2. A simpler and quicker mode of preparation is afforded by 
 the action of dilute nitric acid (D = 1-2) when ^-tolylarsinic 
 acid is heated for twelve hours in sealed tubes at 150 with 13-14 
 parts of this oxidising agent. The residue from the tubes after 
 evaporation to dryness is extracted with dilute alcohol. 1 A 
 practically quantitative yield is obtained by heating ^>-tolyl- 
 arsinic acid with nitric acid (D = 1-2) for three hours at 170. 2 
 
 3. A third method of preparation is available through p-ars- 
 anilic acid. This substance is diazotised in the presence of 
 cuprous cyanide, the intervening ^>-cyanophenylarsinic acid 
 being hydrolysed by concentrated aqueous caustic potash. 3 
 
 At 210 this acid loses water and passes into arsinoxybenzoic 
 acid, CO 2 H-C 6 H 4 -AsO 2 , yellowish-white powder, soluble in boiling 
 alcohol and separating in ill-defined crystalline crusts. Alkali 
 fusion of />-benzarsinic acid gives rise to phenol. The potassium 
 salt yields with phosphorus pentachloride an unstable chloride, 
 regenerating the acid on treatment with water ; phosphorus tri- 
 chloride furnishes benzarsenious chloride. Benzarsenious iodide is 
 obtained from benzarsinic acid by the action of hydriodic acid. 
 
 Salts of p-benzarsinic acid : Acid potassium salt, 
 
 CO 2 H-C 6 H 4 -AsO(OH) a ,C0 2 K-C 6 H 4 AsO(OH) 2 , 
 
 triclinic plates, produced by dissolving the foregoing oxidation 
 product in hot water and allowing the solution to evaporate at 
 50-60 ; loses 2H 2 at 160-170. Insoluble in absolute alcohol. 
 Calcium salt, CaC 7 H 6 O 5 As,H 2 O, nacreous leaflets, sparingly 
 soluble in cold water. Silver salt, AgC0 2 -C 6 H 4 AsO(OAg) 2 , white 
 precipitate, soluble in nitric acid or ammonia. Methyl ester, 
 CH 3 -CO 2 -C 6 H 4 AsO(OH) 2 , colourless, crystalline mass obtained by 
 the action of methyl iodide at 100 on the preceding silver salt ; 
 probably the normal ester is first produced, but quickly hydrolysed 
 by moist air to this more stable acid ester. 
 
 p-Benzarsenious iodide (carboxyphenylarsenious iodide), 
 
 CO 2 H-C 6 H 4 -AsI 2 , 
 
 yellow, felted needles from chloroform, m.p. 153 (La Coste), 
 172 (Bertheim), soluble in alcohol or ether, prepared by heating 
 benzarsinic acid with concentrated hydriodic acid containing 
 
 1 Michaelis, Annalcn, 1902, 320, 303; Ber., 1915, 48, 870. 
 8 Sieburg, Arch. Pharm., 1916, 254, 224. 
 3 Bertheim, Ber., 1908, 41, 1854. 
 130 
 
AROMATIC ARSENICALS 
 
 red phosphorus. Decomposed by boiling with water into 
 hydriodic acid and benzarsenious acid. This decomposition is 
 facilitated by the presence of sodium carbonate, when the 
 product dissolves and is precipitated by dilute hydrochloric 
 acid. 
 
 p-Benzarseniom acid (carboxyphenylarsenious acid), 
 
 C0 2 H-C 6 H 4 -As(OH) 2 , 
 
 colourless needles, changes without melting at 145-146 into its 
 anhydride, CO 2 H-C 6 H 4 -AsO. This oxide, which is ten times more 
 toxic than the hydroxide, can be prepared by acidifying a sodium 
 carbonate solution of p -benzarsenious iodide ; it is only very 
 slowly hydrated by aqueous alkalis. 1 Calcium salt, 
 
 [As(OH) 2 .C 6 H 4 COJ 2 Ca, 
 
 the free acid is boiled with calcium carbonate, nacreous leaflets, 
 soluble with difficulty in hot water. At 200 it loses water and 
 forms (AsOC 6 H 4 CO 2 )Ca. Silver salt, AsOC 6 H 4 -CO 2 Ag, white 
 precipitate dried at 70-80. 
 
 p-Benzarsenious chloride, CO 2 H'C 6 H 4 -AsCl 2 , colourless needles, 
 m.p. 157-158, obtained by heating an ethereal solution of the 
 iodide at 100 with freshly precipitated dry silver chloride, or 
 preferably by acting on benzarsinic acid with phosphorus 
 trichloride. 
 
 C0 2 H-C 6 H 4 -AsO(OH) 2 + 2PC1. = 
 
 COCl-C 6 H 4 AsCl 2 + POC1 3 + H 3 P0 3 . 
 
 The product is distilled at 100 to remove phosphorus trichloride ; 
 the residue extracted with benzene, water added to decompose 
 phosphorus oxychloride, the extract dried and concentrated to 
 the crystallising point. 
 
 Dichloro-p-arsinobenzoyl chloride, 2 Cl 2 As-C 6 H 4 -COCl, mobile 
 liquid fuming in air, b.p. i89-i90/i9 mm., is obtained in 
 practically quantitative yield by adding slowly phosphorus 
 trichloride (280 grams) in chloroform (500 c.c.) to benzarsinic 
 acid (250 grams) dissolved in the same solvent (600 c.c.). The 
 reaction is completed on the water-bath, and the solution when 
 decanted from a layer of phosphoric acid deposits on cooling 
 crystals of benzarsenious chloride, to which are added at once 
 210 grams of phosphorus pentachloride. This second reaction is 
 completed by warming, when chloroform and the volatile 
 
 1 Sieburg, Arch. Pharm., 1916, 254, 224. 
 
 2 Poulenc, Fr. P., 441, 215. 
 
 131 K 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 phosphorus chlorides are removed by distillation and the residue 
 fractionated in vacuo. The trichloride is also obtainable by 
 treating benzarsenious acid either with phosphorus tri- and 
 penta-chlorides successively, or with the pentachloride alone ; 
 it is also produced by the interaction of benzarsenious chloride 
 and phosphorus pentachloride. This product is soluble in 
 chloroform, ether, or benzene, giving, with water, a white pre- 
 cipitate. It resembles benzoyl chloride in its behaviour towards 
 alcohols, phenols, amino-alcohols, ammonia, and alkaloids like 
 quinine or morphine possessing alcoholic or phenolic functions. 
 Di-p-benzarsinic acid l (Di-p-carboxydiphenylarsinic acid), 
 
 (CO 2 H-C 6 H 4 ) 2 -AsO-OH, 
 
 lustrous, colourless leaflets, decomposed at high temperatures 
 without melting, is practically insoluble in water, slightly soluble 
 in hot concentrated hydrochloric acid or alcohol. The oxidation 
 of di-^)-tolylarsinic acid requires four molecular proportions of 
 alkaline permanganate and is effected in moderately concen- 
 trated solutions at 50-60. Di-^>-benzarsinic acid is precipitated 
 from the colourless nitrate by adding dilute hydrochloric acid. 
 The salts of this arsinic acid crystallise badly and vary in composi- 
 tion between normal and acid salts. The mixture of silver 
 salts (CO 2 Ag-C 6 H 4 ) 2 AsO-OH and (CO 2 Ag-C 6 H 4 ) 2 -AsOOAg, 
 heated with methyl iodide at 100, yields the acid ester, 
 HO-OAs(C 6 H 4 -C0 2 -CH 3 ) 2 , yellowish-white "crusts from alcohol. 
 
 Di-p-benzarsenious iodide, (CO 2 H-C 6 H 4 ) 2 Asl, yellowish-white, 
 ill denned crystals melting above 280, prepared by heating the 
 preceding acid with concentrated hydriodic acid and red phos- 
 phorus. 
 
 Di-p-benzarsenious acid, (CO 2 H-C 6 H 4 ) 2 As-OH, white, crystalline 
 precipitate, obtained by dissolving the preceding iodide in 
 aqueous sodium carbonate and adding hydrochloric acid. Calcium 
 salt, HO-As(C 6 H 4 -CO 2 ) 2 Ca,2H 2 O, white, pulverulent precipitate 
 from water on addition of alcohol. 
 
 Tri-p-benzarsinic acid, (HO) 2 As(C 6 H 4 -C0 2 H) 3 , colourless, 
 granular crystals from ether ; loses water without melting ; 
 produced by oxidising tri-^-tolylarsine with alkaline per- 
 manganate. This acid is a derivative of orthoarsenic acid, 
 As(OH) 5 . The potassium salt, 0:As(C 6 H 4 -CO 2 K) 3 , easily soluble 
 crystals, and the calcium salt, [O:As(C 6 H 4 )CO 2 ] 2 Ca 3 ,i--2H 2 O, 
 soluble in water and precipitated by alcohol, indicate that the 
 
 1 La Coste, loc. cii., p. 23. 
 132 
 
AROMATIC ARSENICALS 
 
 acid is tribasic ; the silver salt gives numbers approximating to 
 HO-As(OAg)(C 6 H 4 -C0 2 Ag) 3 . 
 
 Tri-p-benzarsenious acid (Arsinotribenzoic acid), 
 
 As(C 6 H 4 -CO 2 H) 3 , 
 
 colourless needles from ether, melting with decomposition at 
 high temperatures, is produced by heating the preceding acid 
 with hydriodic acid and red phosphorus, purified by dissolving 
 in aqueous sodium carbonate containing animal charcoal and 
 reprecipitating by hydrochloric acid. 
 
 Sodium salt, As(C 6 H 4 -CO 2 Na) 3 ,2H 2 0, only once obtained in 
 colourless needles ; silver salt, yellowish -white precipitate. 
 
 m-Benzarsinic acid, 1 CO 2 H-C 6 H 4 -AsO(OH) 2 , colourless, lustrous 
 leaflets, easily soluble in water or alcohol; prepared by the 
 oxidation with alkaline permanganate of m-tolylarsinic acid. 
 It passes without melting into the anhydride, CO 2 H-C 6 H 4 -As0 2 , 
 
 ,CO 2 Cav 
 yellowish-white powder. Calcium salt, C 6 H 4 <^ J>O, 
 
 \AsO(OHK 
 
 soluble rectangular plates ; silver salt, CO 2 Ag-C 6 H 4 -AsO(OAg) 2 , 
 white precipitate. 
 
 o-Benzarsinic acid, 2 colourless needles from water, is obtained 
 by adding aqueous sodium arsenite to a solution of diazotised 
 anthranilic acid. The mixture is neutralised with alkali, warmed 
 and evaporated to dryness. The by-products are extracted with 
 methyl alcohol, the residue acidified, the solution filtered from 
 impurities and evaporated to dryness. From the final residue 
 o-benzarsinic acid is extracted with methyl alcohol ; its sodium 
 and aniline salts are readily soluble. 
 
 Diethylarsinoxybenzoic acid hydrochloride, 
 
 /OH 
 
 C0 2 H-C 8 H 4 -As(C 2 H 5 ) 2 < , 
 \C1 
 
 colourless crystals from alcohol-ether, m.p., 162, very soluble 
 in water. Prepared by shaking ^-tolyldiethylarsine with aqueous 
 potassium permanganate (2 parts) at first in the cold and then 
 as the oxidation slackens at 30-40. The mercurichloride, 
 C0 2 H-C 6 H 4 -AsEt 2 (OH)-Cl,HgCl 2 , colourless crystals from water, 
 m.p. 182, is produced by mixing aqueous solutions of its 
 generators. 
 
 1 Michaelis, Annalen, igp2, 320, 329. 2 Bart, D.R.-R, 250, 264. 
 
 133 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Diethylarsinosulphidobenzoic acid, CO 2 H-C 6 H 4 AsS(C 2 H 5 ) 2 , 
 colourless, transparent needles from hot water, m.p. 184, 
 produced by passing hydrogen sulphide into an aqueous solution 
 of the preceding hydrochloride. 
 
 Diethylarsinebenzoic acid, (C 2 H 5 ) 2 As-C 6 H 4 -CO 2 H, colourless 
 needles, m.p. 58, easily soluble in ether, alcohol, or other 
 volatile solvents, excepting water or light petroleum. Prepared 
 by reducing the foregoing hydrochloride with tin and hydro- 
 chloric acid. Removal of the tin by hydrogen sulphide leads to 
 the preceding sulphide, and accordingly the product is isolated 
 as a yellow oil by diluting the acid solution with water. This 
 compound combines the properties of an arsine and an acid. 
 With the exception of the alkali derivatives, its metallic salts 
 are insoluble in water : barium salt [(C 2 H 6 ) 2 As-C 6 H 4 CO 2 ] 2 Ba and 
 lead salt are white precipitates ; ammonium salt, a soluble crystal- 
 line mass. 
 
 As a tertiary arsine, diethylarsinebenzoic acid combines with 
 mercuric chloride, the halogens, and methyl iodide : the mercuri- 
 chloride, CO 2 H-C 6 H 4 -As(C 2 H 5 ) 2 ,HgCl 2 , colourless, silky crystals, 
 m.p. 171-172, insoluble in alcohol, sparingly soluble in water. 
 Addition of the halogens takes place conveniently in chloroform 
 solution, and the dihalogen compounds are obtained in a crystal- 
 line form on evaporation. Access of moisture converts them at 
 once into hydroxy -halogen derivatives ; the hydrochloride is 
 described above. The hydrobromide, CO 2 H-C 6 H 4 -As(C 2 H 6 ) 2 O,HBr, 
 colourless needles, m.p. 144-145 ; the hydriodide, brown leaflets 
 from alcohol, m.p. 84. 
 
 The methiodide, CO a H-C 6 H 4 -As(C a H 5 ) 2 (CH 3 )I, colourless needles 
 from alcohol, m.p. 131, obtained by heating the arsine with 
 excess of methyl iodide. 
 
 Diphenylbenzarsinic acid (Triphenylarsineoxidecarboxylic acid) 1 , 
 (C 6 H 5 ) 2 AsO-C 6 H 4 -C0 2 H, crystalline crusts from alcohol, m.p. 
 253-254, insoluble in water or ether, dissolves readily in 
 alcohol, alkalis, or in excess of mineral acids. Diphenyl-/>- 
 tolylarsine (10 grams) is oxidised with permanganate ( 13 grams) 
 at 60 for four or five weeks. A more rapid oxidation leads 
 only to tarry substances, although possibly heating with 
 nitric acid (D = 1-2) in sealed tubes might give the product 
 more quickly. Silver salt, OAs(C 6 H ) 2 -C 6 H 4 -CO 2 Ag, pulveru- 
 lent precipitate affected by light ; acid barium salt, white 
 powder. 
 
 ' l Michaelis, Annalen, 1902, 321, 192. 
 134 
 
AROMATIC ARSENICALS 
 
 Ethyl diphenylbenzarsinaie dichloridc, 
 
 Cl 2 As(C 6 H ) 2 -C 6 H 4 .C0 2 -C 2 H 6 , 
 
 results from the passage of hydrogen chloride through an alcoholic 
 solution of the acid ; well-defined colourless crystals, m.p. 133. 
 
 Diphenyl sulphidobenzarsinic acid, SAs(C 6 H 6 ) 2 -C 6 H 4 -CO 2 H, 
 colourless crystals, m.p. 178, produced by passing sulphuretted 
 hydrogen through an alcoholic solution of the acid ; the product 
 separates in oily drops on evaporating the solvent. 
 
 Phenyl di-p-benzarsinic acid (Triphenylarsineoxide-di-p-carb- 
 oxylic acid), (I), 1 
 
 /C 6 H 5 ,C 6 H 5 
 
 OAsC 6 H 4 -CO 2 H OAs C 6 H 4 -CO 2 H, 
 
 \C 6 H 4 -CO,H \C 6 H 4 -CH 8 
 
 I. II. 
 
 colourless, crystalline powder from glacial acetic acid, not melting 
 below 300, is insoluble in water, ether, or chloroform, but 
 dissolves in hot alcohol, glacial acetic acid, or aqueous alkalis. 
 As the starting material, phenyldi-^>-tolylarsine is oxidisable 
 in two stages, two products are theoretically possible, and both 
 have been obtained. The dicarboxylic acid represents the final 
 stage involving oxidation of both methyl groups. Alkali perman- 
 ganate (22 grams) is added gradually to the finely divided tertiary 
 arsine (10 grams) suspended in 500 c.c. of water containing 
 caustic potash. The oxidation proceeds very slowly, and in 
 spite of warming the mixture to 50-60 with repeated shaking 
 it requires eight weeks for completion. The filtrate from manganese 
 hydroxides is concentrated and the dicarboxylic acid precipitated 
 by hydrochloric acid. The basicity of this acid is determined by 
 the composition of its silver salt, 0:As(C 6 H 5 )(C 6 H 4 -CO 2 Ag) 2 , white, 
 crystalline powder, and copper salt, 
 
 0:As(C 6 H 5 )(C 6 H 4 -CO 2 ) 2 Cu,H 2 0, 
 
 blue powder, losing water at 105. The acid barium salt, 
 [O:As(C 6 H 5 )(C 6 H 4 -CO 2 H)(C 6 H 4 CO 2 )] 2 Ba, colourless crystals, is 
 easily soluble in water. 
 
 Ethyl phenyldi-p-benzarsinate dichloride, 
 
 Cl 2 As(C 6 H 4 ) (C 6 H 4 'C0 2 -C 2 H 6 ) 2 , 
 warty aggregates of needles, m.p. 176, has a pungent not dis- 
 
 1 Michaelis, Annalen, 1902, 321, 196. 
 135 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 agreeable odour ; it results from the action of alcoholic hydro- 
 chloric acid on the dicarboxylic acid. 
 
 Phenyl-p-tolylbenzarsinic acid (Diphenyl-p-tolylarsineoxide-p- 
 carboxylic acid) (II), crystalline powder resembling the preceding 
 dicarboxylic acid in not melting below 300 ; it is, however, 
 much more soluble in alcohol, this solvent effecting a separation 
 of these two oxidation products. Phenyldi-/>-tolylarsine 
 (10 grams), oxidised as in the preceding experiment, but with 
 only 12-6 grams of permanganate, yields both acids, but the 
 monocarboxylic acid predominates. The silver salt, 
 0:As(C 6 H 5 )(C 7 H 7 )-C 6 H 4 -C0 2 Ag, 
 
 needles, turning brown on exposure, indicates the basicity of 
 the acid. Ethyl phenyl-p-tolyl-p-benzarsinate dichloride, 
 
 Cl 2 As(C 6 H 5 )(C 7 H 7 )-C 6 H 4 -C0 2 -C 2 H 5 , 
 
 hygroscopic, m.p. 94, results from the simultaneous action of 
 alcohol and hydrogen chloride on the acid. 
 
 2. Xylene Series. 1 
 
 Di-w-xylylphenylarsine heated with the calculated amounts 
 of nitric acid (D 1-2) in sealed tubes at 110-170 gives rise 
 to two acids. 
 
 Phenylditolylarsin eoxidedicarboxylic acid, 
 
 V./6.H.5 AS v^ 6 i.. 3 v i , 
 
 \co a nj a 
 
 purified from alcohol, crystallises as a pale yellow powder, 
 m.p. 196, sparingly soluble in water ; dibasic. 
 
 Triphenylarsineoxidetetracarboxylic acid, 
 
 /C0 2 H- 
 C 6 H 5 -As C 6 H 3 < 
 
 A L XX) 2 U J2 
 
 is less soluble in alcohol than the preceding acid, but dissolves 
 moderately easily in hot water ; m.p. 213 ; tetrabasic. 
 
 3. Pseudocumene Series. 2 
 
 Dipseudocumylphenylarsine is not smoothly oxidised by 
 alkaline permanganate, but on heating with increasing quantities 
 1 Michaelis, Annalen, 1902, 321, 226. 
 a Ibid., 233. 
 
 136 
 
AROMATIC ARSENIC ALS 
 
 of dilute nitric acid in sealed tubes at 110-180 it is converted 
 progressively into di-, tetra-, and hexa-carboxylic acids, the final 
 product being the most easily obtained. 
 Phenyldixylylarsineoxidedicarboxylic acid, 
 
 C 6 H 5 - As[C 6 H 2 (CH 3 ) 2 -C0 2 H] 2 , 
 
 ii 
 O 
 
 is obtained by heating the arsine (2 grams) with 4-7 grams of 
 nitric acid (D = 1-2) for twelve hours at 120-180 ; pale yellow 
 powder, m.p. 199, very soluble in alcohol, insoluble in water, 
 ether or benzene ; it is dibasic. 
 
 Phenylditolylarsineoxidetetracarboxylic acid, 
 
 C e H 5 -As C a H/ 
 
 5 I ^(C0 2 H)J 2 
 
 formed as in the preceding experiment, but using a double 
 proportion of dilute nitric acid. 
 
 Triphenylarsineoxidehexacarboxylic acid, 
 
 C 6 H 5 -As[C 6 H 2 (C0 2 H) 3 ] 2 , 
 
 6 
 
 prepared from the arsine (2 grams) with 16 grams of dilute 
 nitric acid at 110-150 for thirteen hours (1-3 grams obtained) ; 
 hard, white crystals from hot dilute alcohol, m.p. 275. The 
 composition of the silver salt and ethyl ester (silky needles, 
 m.p. 193) suggests that the acid exists in the form of its partial 
 anhydride, {C 6 H 6 -AsO[C 6 H 2 (CO 2 H) 3 ][C 6 H 2 (CO 2 H) 2 -CO]} 2 O. 
 
 Reduction Products of Benzarsinic Acids.' 1 
 
 ^>-Benzarsinic acid, prepared by oxidising ^-tolylarsinic acid 
 with nitric acid (D = 1-2) at 150, is reduced by hydriodic acid 
 and phosphorus to ^-benzarsenious acid. The latter arsenical 
 compound, when reduced in strong aqueous solution with solid 
 phosphorous acid, yields p-arsenobenzoic acid, an insoluble, yellow 
 powder forming soluble alkali salts with a neutral reaction. 
 
 o-Arsenobenzoic acid is prepared by a similar series of reactions. 
 Both arsenobenzoic acids are very toxic and cause pronounced 
 glycosuria and albuminuria. 
 
 Phenylarsine-p-carboxylic acid, C0 2 H-C 6 H 4 -AsH 2 , colourless 
 prisms, m.p. 79-80, is prepared by reducing a methyl-alcoholic 
 
 1 Michaelis, Ber., 1915, 48, 870. 
 137 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 solution of ^>-benzarsinic acid with hydrochloric acid (D-i-ig) 
 and zinc dust, the product being removed by distillation in 
 steam. It is very sensitive to atmospheric oxygen, becoming 
 oxidised to ^>-arsenobenzoic acid. x 
 
 Section X. Betaines of Aromatic Arsenicals. 
 
 This section deals with a group of aromatic compounds 
 containing a quinquevalent arsenic atom involved in a cyclic 
 complex analogous to that obtaining in ordinary betaine, 
 
 MCB S ) 3 
 CH 2 <' ")O,H 2 O, the naturally occurring trimethyl- 
 
 glycine. 
 Phenyldiethylarsenibetaine hydrochloride, 2 
 
 y CH 2 -C0 2 H 
 
 C 6 H 5 -As(C 2 H 5 ) 2 <^ 
 
 colourless needles from alcohol-ether, m.p. 135, is obtained by 
 heating for several hours at 100 equal weights of phenyldiethyl- 
 arsine and chloroacetic acid ; platinichloride, 
 
 [C 6 H 5 -As(C 2 H 5 ) 2 (CH 2 .C0 2 H)] 2 PtCl 6 , 
 
 red, lustrous crystals, m.p. 161. The free betaine is isolated by 
 passing carbon dioxide into an alcoholic solution of the hydro- 
 chloride and caustic potash. The nitrate from potassium chloride 
 and carbonate contains the betaine, (I). The betaine ethyl ester, 
 C 6 H 5 As(C 2 H 5 ) 2 (CH 2 -CO 2 -C 2 H 5 )Cl, an oil prepared by heating 
 together phenyldiethylarsine and ethyl chloroacetate at 100, 
 yields a crystalline platinichloride (m.p. 125) and picrate 
 (m.p. 90), 
 
 x As(CH 3 ) 2x / As(CH 3 ) 3x 
 
 CH 2 ( >0 C 6 H 4 <( \0. 
 
 \ CO / -CO 
 
 I. II. 
 
 Trimethylarsenibenzobetaine (II). The hydrochloride 
 CO 2 H-C fl H 4 -As(CH 3 ) 3 Cl 
 
 of this betaine, clusters of colourless needles from water, is 
 produced by oxidising />-tolyltrimethylarsonium chloride with 
 
 1 Sieburg, Arch. Phann., 1916, 254, 224. 
 - Michaelis, Annalen, 1902, 320, 297. 
 
 138" 
 
AROMATIC ARSENICALS 
 
 alkaline permanganate at 50 for ten days. At 400* it decom- 
 poses into phenyltrimethylarsonium chloride (platinichloride, 
 m.p. 219) and carbon dioxide. The free betaine obtained from 
 its hydrochloride by sodium carbonate crystallises from dilute 
 alcohol in thin plates containing 2^H 2 O ; this water is evolved 
 at 100. Prolonged boiling with alcoholic potash decomposes 
 the betaine into trimethylarsineoxide and benzoic acid. 
 
 With acids the betaine furnishes well-defined salts : 
 
 Hydrobromide, CO 2 H-C 6 H 4 -As(CH 3 ) 3 Br, needles decomposed at 
 270. 
 
 Nitrate, C0 2 H-CeH 4 -As(CH 3 ) 3 -NO 3 , leaflets, m.p. 230. 
 
 Platinichloride ,JBftCl 9 , pale yellow needles, m.p. 255. 
 
 Aurichloride, BAuCl 4 , golden -yellow needles, m.p. 198. 
 
 Acid sulphate, colourless needles. 
 
 Triethylarsenibenzobetaine, C 6 H 4 (' V), extremely 
 
 \ CO / 
 
 hygroscopic, tabular crystals with bitter taste, forms no salts 
 with alkalis and, unlike trimethylphosphoribenzobetaine, is 
 very resistant to potassium hydroxide, and is completely 
 decomposed only after twenty hours' boiling with alcoholic potash, 
 yielding trimethylarsineoxide and potassium benzoate. , It is 
 prepared by evaporating to dryness a solution of its hydro- 
 chloride and sodium carbonate, the residue being extracted 
 with alcohol. 
 
 The hydrochloride of this substance, the first arsenical betaine 
 to be prepared, is obtained by oxidising ^-tolyltriethylarsonium 
 chloride with the calculated amount of permanganate in alkaline 
 solution at 50, the reaction requiring eight to ten days. The 
 filtrate from manganese hydroxides is acidified, evaporated to 
 dryness, and extracted with absolute alcohol, when the salt 
 separates from alcohol or water in very hygroscopic, acicular 
 crystals : 
 
 Platinichloride, B 2 PtCl 6 , light yellow leaflets, m.p. 225. 
 
 Aurichloride, BAuQ 4 , golden-yellow needles, m.p. 165. 
 
 Picrate, (NO 2 ) 3 C 6 H 2 -OH,B, golden-yellow plates, m.p. 155. 
 
 Triphenylarsenibetaine. 1 The chloride of this arsonium base 
 is obtained in quantitative yield by heating equal parts of 
 triphenylarsine and chloroacetic acid at 100 until a homo- 
 geneous, viscid mass is obtained, which is rendered solid by 
 
 1 Michaelis, Annalen, 1902, 321, 174. 
 139 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 stirring with ether and crystallised from a mixture of this 
 solvent and alcohol ; colourless needles, m.p. 145 ; platinichloride, 
 light red powder, m.p. 194. 
 
 The free betaine, prepared by treating the chloride with 
 alcoholic potash, is isolated, after removing the excess of alkali 
 by carbon dioxide, by concentrating the solution over sulphuric 
 acid. It crystallises from alcohol-ether in colourless needles, 
 m.p. 125. Its solutions are neutral. At 100 this hydrated 
 betaine loses water and passes into the anhydride, 
 
 /CHo'CO 2 H yCH 2 v 
 
 (C 6 H 5 ) 3 As< --> (C 6 H 5 ) 3 As CO. 
 
 \ 
 
 Triphenylarseniketobelaines. 1 
 
 These compounds are produced by condensing triphenylarsine 
 with monohalogenated ketones. 
 
 Triphenylacetonylarsonium Chloride (I). This salt is prepared 
 by heating triphenylarsine (6 grams) with chloroacetone (4 
 grams) at 120, and crystallised from alcohol-ether, rectangular 
 crystals very soluble in water or alcohol, m.p. 172. 
 
 The free triphenylmethylarseniketobetaine (II) 
 /CH 2 -CO-CH 3 /C 
 
 (c 6 H 5 ) 3 A< (c 6 H 5 ) 3 As< 
 
 X C1 \- 
 
 I. II. 
 
 obtained from the chloride by means of aqueous alkali hydroxide 
 or carbonate, separates in nacreous rhombic plates, insoluble in 
 cold water, but dissolving readily in hot water, alcohol, or benzene 
 and sparingly in ether. It melts at 123, becomes solid on further 
 heating, and melts again at 194 ; these changes represent the 
 formation of the anhydride, 
 
 /CH 2 \ xCH 2 v 
 
 (C e H 5 ) 3 A S \C_0-C >As(C,H 6 ) 8 ; 
 
 ' 
 
 this product crystallises unchanged from benzene, but in hydrated 
 solvents it reverts to the ketobetaine (m.p. 123). 
 
 Triphenylacetonylarsonium bromide, (CH 3 -CO 'CH 2 ) *As(C 6 H 5 ) 3 Br, 
 colourless crystals, m.p. 165, results from the addition of hydro- 
 bromic acid to alcoholic solutions of the ketobetaine, precipitated 
 by ether ; the iodide, m.p. 161. 
 
 1 Michaelis, Annalen, 1902, 321, 176 
 140 
 
AROMATIC ARSENICALS 
 
 Triphenylphenacylarsonium bromide, 
 
 /CH a -CO-C 6 H 5 
 
 1C TT \ Ac/ 
 
 silky, felted needles from water, m.p. 178, produced by heating 
 equal parts of triphenylarsine and bromoacetophenone on the 
 water-bath. The free tetraphenylarseniketobetaine, 
 
 'C 6 H 5 
 
 '\OH ' 
 
 obtained by decomposing the preceding salt with sodium hydr- 
 oxide or carbonate, crystallises from dilute alcohol in colourless 
 needles, m.p. 176, characterised by the following salts : chloride, 
 m.p. 166 ; platinichloride, m.p. 191 ; iodide, m.p. 157 ; 
 nitrate, colourless needles, m.p. 184, insoluble in cold water, 
 soluble in alcohol. 
 
 Tri-p-tolylarseniketobetaines. 1 
 
 Tri-p-tolylmethylarsenibetaine is obtained in the form of its 
 chloride by heating tri-^-tolylarsine on the water-bath with 
 chloroacetic acid ; the addition occurs much less readily than with 
 
 X CH 2 -C0 2 H 
 triphenylarsine. This chloride, (CH 3 -C 6 H 4 ) 3 As<^ , forms 
 
 a colourless, crystalline mass, m.p. 146 ; platinichloride, yellow 
 precipitate, m.p. 206. 
 
 Tri-p-tolylmethylarseniketobetaine, 
 
 XH.-CO-CH3 
 
 The chloride, (C 7 H 7 ) 3 As<; , of this ketobetaine is pre- 
 
 \C1 
 
 pared by heating molecular proportions of tri-^>-tolylarsine 
 and chloroacetone in sealed tubes at 85, it crystallises from 
 alcohol-ether, m.p. 170 ; platinichloride, sparingly soluble yellow 
 leaflets, m.p. 210 ; bromide, needles, m.p. 159 ; iodide, 
 m.p. 144. 
 
 The free ketobetaine, obtained by the action of alkali on the 
 
 chloride, is insoluble in water and dissolves in ether, benzene, or 
 
 alcohol, separating from the last in lustrous needles, m.p. 113. 
 
 1 Michaelis, Annalen, 1902, 321, 208. 
 
 141 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 Tri-p-tolylphenylarseniketobetaine, 
 
 (CH 8 -C 6 H 4 ) 3 As< 
 
 \OH 
 
 X CH 2 -COC 6 H 5 
 The chloride, (C 7 H 7 ) 3 As<^ , of this ketobetaine is 
 
 produced by heating tri-/>-tolylarsine and chloroacetophenone 
 at 85, the product being crystallised from alcohol-ether, colour- 
 less needles, m.p. 159 ; platinichloride, yellowish-red needles, 
 m.p. 205; bromide, m.p. 182; iodide, m.p. 148. The free 
 ketobetaine crystallises from alcohol on adding water in tufts 
 of lustrous needles, m.p. 160. 
 
 Section XI. Nitro- derivatives of Aromatic Arsenicals. 
 
 A separate section is devoted to the nitration products of 
 aromatic arsenical compounds because of their increased import- 
 ance as starting points in the production of amino-arylarsenicals 
 having useful germicidal properties. 
 
 In the earliest experiments made on these derivatives by 
 Michaelis and others the influence of the arsenical group on 
 orientation was not elucidated. But by means of the Bechamp 
 reaction applied to ^>-nitroaniline a nitro-amino-arsinic acid of 
 known constitution has been obtained. Elimination of the 
 ammo-group by the agency of the diazo-reaction leaves m-nitro- 
 phenylarsinic acid, which turns out to be identical with Michaelis's 
 nitro-compound produced by direct nitration of phenylarsinic 
 acid. This identification (page 144) shows that the arsinic group 
 determines the entry of the nitro-group into the meta-position. 
 The stibinic group has been shown to induce the same orienta- 
 tion, and this substitution probably holds for the phosphinic 
 group. These results show that Crum Brown and Gibson's rule 
 for substitution holds not only for the acidic groups NO 2 , CO 2 H, 
 SO 3 H, but also for the univalent acidic groups PO 3 H 2 , AsO 3 H 2 , 
 SbO 3 H 2 . It also holds, in all probability for the bivalent groups 
 
 >POOH, \AsO-OH; NsbO-OH, 
 
 and for the tervalent groups 
 
 \ \ \ 
 
 and ^ 
 
 142 
 
AROMATIC ARSENICALS 
 
 inasmuch as the correctness of this generalisation has been 
 demonstrated in the case of the three antimonial groups (p. 296) 
 m-Nitrophenylarsinic acid 1 (v. page 157), 
 
 NO 2 
 
 "\AsO(OH) 2 , 
 
 rhombic leaflets from water, no definite melting point ; the acid 
 evolves water on heating and then intumesces, leaving a carbon- 
 aceous residue. Easily soluble in hot water at 1 8, one part requires 
 50 parts of water for complete solution. It dissolves in alcohol, 
 only sparingly in benzene or chloroform, and is insoluble in ether 
 or light petroleum. Prepared by adding phenylarsinic acid 
 (10 grams) to absolute nitric acid 2 (100 per cent. HN0 3 ) and 
 distilling the mixture until two-thirds of the acid has passed 
 over ; the residue is poured into 75 c.c. of water, when nitro- 
 phenylarsinic acid separates in small leaflets. This nitration 
 may also be effected with nitric acid dissolved in concentrated 
 sulphuric acid. The acid mother liquors from the first crop of 
 nitrophenylarsinic acid contain a mixture of this acid with the 
 nitrate C 6 H 5 -As(OH) 3 -ONO 2 ; this product is worked up with 
 subsequent nitrations. Aqueous solutions of the nitro-acid 
 give white and blue precipitates with lead acetate and copper 
 sulphate respectively, especially on warming. With silver nitrate 
 and mercuric chloride white precipitates only in ammoniacal 
 solutions ; soluble barium, calcium, and magnesium salts give 
 similar results on warming. 
 
 The alkali salts of the acid arc not crystallisable. Calcium 
 m-nitrophenylarsinate, NO 2 -C8H 4 -AsO 3 Ca,H 2 O, produced on boiling 
 calcium carbonate with an aqueous solution of the acid ; lustrous 
 leaflets still retaining the water of crystallisation at 110. It 
 probably has the constitution N0 2 -C 6 H 4 -AsO(OH)-OCa-OH. 
 
 Acid barium m-nitrophenylarsinate, [NO 2 -C 6 H 4 'AsO(OH)-O] 2 Ba, 
 crystalline crusts obtained by dissolving the nitro-acid in excess 
 of baryta water, passing in carbon dioxide and evaporating the 
 filtered solution. 
 
 Copper m-nitrophenylarsinate, NO 2 -C 6 H 4 -AsO 3 Cu,H 2 0, probably 
 N0 2 -C 6 H 4 -AsO(OH)-OCu-OH, since it does not lose water on 
 heating ; blue, crystalline precipitate produced by boiling 
 together in aqueous solution copper sulphate and nitrophenyl- 
 arsinic acid. 
 
 1 Michaelis and Loesner, Ber. t 1894, 27, 265. 
 
 2 Valentiner and Schwarz, D.R.-P., 63207. 
 
 143 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Silver m-nitrophenylarsinate, NO a -C 8 H 4 AsO(OAg) 2 , white, amor- 
 phous powder, soluble in ammonia or nitric acid. 
 
 The reduction of nitrophenylarsinic acid with tin and hydro- 
 chloric acid does not lead to definite products ; stannous chloride 
 yielded on one occasion a small amount of crystalline material, 
 apparently NH 2 -C 6 H 4 AsO(OH) 2 ,HCl,SnQ 2 ,H 2 O. 
 
 Phosphorous acid reduces only the arsinic group, giving 
 dinitroarsenobenzene. Aqueous hydrogen sulphide furnishes 
 nitrophenylarsinic sesquisulphide, whereas ammonium sulphide 
 followed by dilute acid leads to aminophenylarsenious sulphide. 
 The constitution of this nitrophenylarsinic acid (II) has been 
 substantiated by producing it synthetically from two isomeric 
 nitro-arsanilic acids (I) and (III). 1 
 
 As0 3 H 2 As0 3 H 2 As0 3 H 2 
 
 NH 5 
 
 lNO s 
 
 N0 a 
 
 NO 2 
 
 NH 2 
 I. II. III. 
 
 An isomeride of this nitrophenylarsinic acid, 2 insoluble in 
 water, is obtained on heating in sealed tubes for three hours at 
 155-165 one part of phenylarsinic acid, five parts of concen- 
 trated nitric acid, and ten parts of concentrated sulphuric 
 acid. The mixture of acids is extracted with boiling water, 
 when the isomeric acid remains undissolved ; it is produced 
 only in small amount and intumesces on heating without 
 melting. 
 
 The production of w-nitrophenylarsinic acid from 3-nitro-4~ 
 aminophenylarsinic acid is described under m-aminophenyl- 
 arsinic acid. The nitro-acid is also obtained from 5-nitro-2- 
 aminophenylarsinic acid. In this case the 2-amino-group is 
 diazotised by adding 2]V-sulphuric acid to an aqueous solution 
 of sodium 5-nitro-2-aminophenylarsinate and nitrite. An equal 
 volume of alcohol is added to the diazo-solution and the elimina- 
 tion of the diazo-group is facilitated by the addition of 9 per cent, 
 of copper-bronze The filtered solution is concentrated to a small 
 bulk and the mineral acid neutralised with sodium hydroxide 
 when m-nitrophenylarsinic acid separates. 3 
 
 1 Bertheim and Benda, Ber., 1911, 44, 3298. 
 
 2 Michaelis, Annalen, 1902, 320, 294. 
 
 5 Bertheim and Benda, Ber., 1911, 44, 3299. 
 144 
 
AROMATIC ARSENIC ALS 
 
 o-Nitrophenylarsinic acid* NO 2 -C 6 H 4 -AsO(OH) 2 , white needles 
 from alcohol or water, intumesces without melting. 
 
 Sodium o-nitrobenzene^'sodiazo-oxide (1-8 parts) and sodium 
 arsenite (2 parts) are heated in 4 parts of water until nitrogen is 
 no longer evolved. The solution is evaporated to dryness and 
 the product extracted from the residue by alcohol. 
 
 p-Nitrophenylarsinic acid,' 1 NO 2 -C 6 H 4 -AsO(OH) 2 . An acid or 
 alkaline solution of arsenious acid is added to a solution of 
 ^-nitrobenzenediazonium chloride, the mixture is warmed, 
 and after evolution of nitrogen has ceased, the filtered solution 
 is evaporated to dryness and the product extracted with alcohol. 
 The yield is better when alkaline arsenite is employed. 
 
 Di-p-nitrodiphenylarsinic acid, (NO 2 -C 6 H 4 ) 2 AsOOH, whitish- 
 yellow precipitate, sparingly soluble in water or alcohol, and 
 giving yellow alkali salts, is prepared by adding an alkaline 
 solution of ^-nitrophenylarsenious acid to a solution of p-mtro- 
 diazonium chloride. Nitrogen is evolved, and acids precipitate 
 the product from the filtered solution. The p-nitrophenylarsenious 
 acid required in this condensation is prepared by reducing the 
 preceding compound with sulphurous acid, using hydriodic acid 
 as catalyst. It is an insoluble powder dissolving in caustic soda 
 solution. 
 
 m-Nitrophenylarsenious acid, 2 NO 2 -C 6 H 4 As(OH) 2 , white 
 flocculae, darkening on heating, and intumescing without melting. 
 Prepared by dissolving nitrophenylarsenious chloride or bromide 
 in aqueous alkalis and then acidifying either by passing in 
 carbon dioxide or preferably by adding hydrochloric acid, taking 
 care to keep the solution cool. It is of interest to compare the 
 composition of the product with that of the substance obtained 
 by acting on phenylarsenious chloride with aqueous alkali. In 
 the latter case phenylarsenious oxide is produced, but no arsenious 
 acid derivative. The presence of the acidic nitro-group in the 
 aromatic nucleus increases the tendency towards the retention of 
 hydroxyl groups and the formation of an aromatic arsenious 
 oxide (compare Benzarsenious acid, p. 131). 
 
 Nitrophenylarsenious acid is easily soluble in caustic alkalis, 
 and sparingly though appreciably so in carbonated alkalis ; it is 
 insoluble in water, but soluble in alcohol. 
 
 m-Dinitroarsenobenzene* .NO 2 -C 6 H 4 -As:As-C 6 H 4 -NO 2 , heavy 
 
 1 H. Bart, D.R.-P., 250264. 
 
 2 Michaelis and Loesner, Bev., 1894, 27, 269. 
 
 3 Ibid., 268. 
 
 145 L 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 yellow powder, intumesces with melting ; insoluble in all volatile 
 organic solvents. Oxidation with nitric acid regenerates nitro- 
 phenylarsinic acid. Prepared by heating in a sealed tube for 
 twelve hours at 115 10 grams of the foregoing acid with water 
 and 40 grams of crystallised phosphorous acid. Combines 
 additively with the halogens and sulphur. 
 
 m-Nitrophenylarsenious chloride, 1 NO 2 -CH 4 -AsCl 2 , colourless 
 crystals from chloroform, m.p. 46-47, is not affected by water. 
 
 Chlorine passed into a suspension of dinitroarsenobenzene in 
 chloroform leads to complete solution, and, on evaporating the 
 solvent, long needles of nitrophenylarsenic chloride separate, 
 which are rapidly converted by moist air into nitrophenylarsinic 
 acid. When the chloroform solution of nitrophenylarsinic 
 chloride is treated with excess of dinitroarsenobenzene, the oily 
 residue left after removing the solvent b}^ distillation yields 
 the crystalline nitrophenylarsenious chloride, 
 
 (NO 2 -C 6 H 4 -As) 2 + 2NO 2 -C 6 H 4 -AsCl 4 = 4NO 2 -C 6 H 4 -AsCl 2 . 
 
 m-Nitrophenylarsenious 6rom^,NO 2 -C 6 H 4 -AsBr 2 , white crystals 
 easily soluble in chloroform, sparingly so in petroleum, obtained 
 by adding bromine to dinitroarsenobenzene suspended in light 
 petroleum (b.p. 50) ; the solution is filtered and concentrated 
 under reduced pressure. The corresponding iodide has not been 
 obtained crystalline. 
 
 m-Nitrophenylarsenic sulphide? NO 2 'C 6 H 4 -AsS 2 , white powder, 
 melting at 80 (approx.) and intumescing at higher temperatures, 
 is insoluble in water, ether, or chloroform, sparingly soluble in 
 alcohol or benzene, dissolving readily in ammonia or aqueous 
 alkalis. Dinitroarsenobenzene is suspended in water and boiled 
 for one hour with flowers of sulphur ; the mixture is then rendered 
 ammoniacal, filtered and acidified when the sulphide is precipi- 
 tated. 
 
 m-Nitrophenylarsenic sesquisulphide, 
 
 NO a -C 6 H 4 -AsS-AsS-C 6 H 4 -NO 2) 
 
 V 
 
 yellow leaflets from benzene-alcohol, melting at 119, and under 
 boiling water, is prepared by passing hydrogen sulphide repeatedly 
 into a solution of nitrophenylarsinic acid (10 grams) in 200 c.c. 
 of water at 50-60 and allowing the mixture to remain for 
 twelve hours, after which ammonia is added to dissolve out the 
 1 Michaelis and Loesner, Ber., 1894, 27, 269. z Ibid., 270. 
 
 146 
 
AROMATIC ARSENICALS 
 
 sesquisulphide from the precipitated sulphur, the product being 
 precipitated by mineral acid. 
 
 o-Nitrophenylarsenious chloride, produced by dissolving 
 o-nitrophenylarsenious oxide in wet ether and adding alcoholic 
 hydrochloric acid, forms a faintly yellow solution which on 
 exposure to strong sunlight for several weeks gives a yellowish- 
 brown, crystalline deposit which has the properties of an arsinic 
 acid, but differs from 2-nitrophenylarsinic acid. It is regarded 
 by Karrer as being a highly polymerised form of the nitroso- 
 compound produced by the migration of oxygen from the nitro- 
 group to the arsenious radical in the presence of water. 1 
 
 AsO 2 As0 3 H 2 
 
 /\ NO 
 
 2 : ^-Dinitrophenylarsinic acid, 2 
 
 \AsO(OH) 2 . 
 
 The introduction of arsinic groups into aromatic nuclei by 
 Bart's process through the diazo-reaction takes place usually 
 in alkaline or neutral solution. With diazotised 2 : 4-dinitro- 
 aniline, however, this synthesis does not occur under these 
 conditions, but on the contrary a good yield of 2 : 4-dinitrophenyl- 
 arsinic acid is obtained when the reaction is carried out in the 
 presence of excess of acid. Dinitroaniline (18-5 grams) is added 
 to a mixture of concentrated, sulphuric acid (30 grams) and 
 23 grams of vitriol containing 59 per cent, of nitrosylsulphate 
 cooled below 25. The brown solution is poured on to ice (250 
 grams) and treated with a solution of sodium arsenite (25 grams) 
 in 50 c.c. of water. The evolution of diazo-nitrogen occurs even 
 in the cold and may be completed by heating with steam. 
 So soon as the diazo-reaction has practically disappeared the 
 hot solution is treated with animal charcoal and filtered ; 
 2 : 4-dinitrophenylarsinic acid separates in felted needles (m.p. 
 199-200). The product is moderately soluble in cold water 
 and dissolves readily in aqueous alkalis or sodium acetate, glacial 
 acetic acid, or the alcohols. The aqueous solution turns Congo 
 red paper violet. 3 
 
 1 Karrer, Ber., 1914, 47, 1783. 2 M. L. and B., D.R.-P., 266944- 
 
 3 M. L. and B., A.P., 1075537, 1075538. Benda, Eng. P., 24667/1912. 
 
 147 L 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Dinitrodiphenylarsinic acid, 1 (N0 2 'C 6 H 4 ) 2 As(>OH, aggregates of 
 yellowish-white, monoclinic prisms from glacial acetic acid, 
 m.p. 256 without losing water. Only sparingly soluble in hot 
 water or alcohol, dissolving more readily in hot glacial acetic acid. 
 
 The salts with the alkali metals and those of the alkaline 
 earths are soluble. Barium salt, [(NO 2 -C 6 H 4 ) 2 -AsO 2 ] 2 Ba, 
 yellowish- white scales. Silver salt, (NO 2 -C 6 H 4 ) 2 AsO 2 Ag, white 
 precipitate. Copper salt has the composition 
 
 (N0 2 -C 6 H 4 ) 2 AsO-OCu-OH. 
 
 Tetranitrotetraphenyldiarsine, (N0 2 -C 6 H 4 ) 2 As-As(C eH^NG^, glis- 
 tening leaflets insoluble in all ordinary solvents, m.p. 200 to 
 a pale yellow liquid, prepared by adding a moderate excess of 
 phosphorous acid to a solution of the preceding acid in glacial 
 acetic acid. The mixture is boiled until the diarsine separates. 
 This compound combines additively with chlorine, bromine, or 
 sulphur. 
 
 Dinitrodiphenylarsenious sulphide, [(NO 2 -C 6 H 4 ) 2 As] 2 S, warty 
 aggregates of yellow needles, m.p. 156, produced by warming 
 the preceding compound (in slight excess) with sulphur dissolved 
 in benzene. Excess of sulphur leads to tetranitrotetraphenyldi- 
 
 2 . 4 
 
 arsenious sulphide, ^As 2 S 3 , yellow powder, m.p. 69. 
 
 (N0 2 -C 6 H 4 )/' 
 
 Dinitrodiphenylarsenious chloride, (N0 2 -C 8 H 4 ) 2 AsCl, yellowish- 
 white needles from benzene-petroleum, m.p. 112, obtained by 
 passing chlorine into a slight excess of tetranitrotetraphenyl- 
 diarsine suspended in benzene. Dinitrodiphenylarsenic chloride 
 is formed as an intermediate product, but, being unstable, it is 
 reduced by the excess of diarsine to the required monochloride. 
 The bromide consists of colourless leaflets, m.p. 93. 
 
 Tri-p-nitrotriphenylarsinic acid, 
 
 This compound is prepared by an extension of Bart's diazo- 
 reaction from di-p-nitrodiphenylarsenious acid, 
 
 (N0 2 -C 6 H 4 ) 2 AsO(OH) 2 , 
 
 white, felted needles, m.p. 149, salts unstable ; this intermediate 
 product is produced by the mild reduction of di-^>-nitrodiphenyl- 
 arsinic acid with hydriodic acid in glacial acetic acid. 
 1 Michaelis, Annalen, 1902, 321, T5 1 - 
 
AROMATIC ARSENICALS 
 
 Sodium ^-nitrobenzenei'sodiazo-oxide in aqueous solution is 
 added to a solution of sodium di-_/>-nitrodiphenylarsenite 
 the mixture being slowly heated to 75-80 ; nitrogen is evolved, 
 and after filtration a brown precipitate is obtained on adding 
 hydrochloric acid. This product is boiled in water with barium 
 carbonate to remove unchanged di-/>-nitrodiphenylarsenious 
 acid, which becomes soluble. The residue, freed from excess of 
 barium carbonate by hydrochloric acid, is crystallised from 
 glacial acetic acid and alcohol. It is obtained in brown crystals, 
 insoluble in aqueous sodium carbonate, but dissolving in caustic 
 soda to brownish-yellow solutions. 1 
 
 Tri-3-nitrotriphenylarsine oxide, 2 (NO a -CH 4 ) 3 AsO, colourless or 
 slightly yellow crystals, m.p. 254, intumescing on heating ; 
 insoluble in alcohol or ether, easily soluble in glacial acetic acid. 
 Prepared by dissolving triphenylarsine (20 grams) in a warm 
 mixture of fuming nitric acid (40 grams) and concentrated 
 sulphuric acid (100 grams) ; the product is poured on to ice, 
 extracted with hot alcohol to remove a red, tarry impurity, 
 dissolved in glacial acetic acid and precipitated with alcohol. 
 The reddish product stated by Philips to be an isomeride has 
 not been analysed or identified. 
 
 Tri-3-nitrotriphenylarsine, B (N0 2 -C 8 H 4 ) 3 As, yellow, crystalline 
 powder, m.p. 250, produced by warming trinitrotriphenylarsine 
 oxide in alcohol with crystallised phosphorous acid, is twice as 
 soluble in alcohol as the original oxide. Addition of bromine to 
 a chloroform solution of this arsine gives rise to trinitrotriphenyl- 
 arsinedibromide, reddish-yellow precipitate, m.p. 204. Addition 
 of chlorine leads to trinitrotrichlorophenylarsinedichloride, colour- 
 less crystals, m.p. 228 ; this product treated with concentrated 
 potassium hydroxide gives the oxide, colourless, crystalline mass, 
 m.p. 257, which by reduction with phosphorous acid furnishes 
 trinitrotrichlorotriphenylarsine, white powder, m.p. 252, moder- 
 ately soluble in alcohol, chloroform, or glacial acetic acid, charac- 
 terised by its yellow dibromide, m.p. 209. 
 
 3-Nitro-4-tolylarsinic acid,* 
 
 CH 3 / \AsO(OH) tf 
 
 crystallises from hot water in long, silky, acicular prisms of the 
 
 i Bart, D.R.-P., 254345. 
 
 z Philips, Ber., 1881, 19, 1033. Michaelis, Annalen, 1962, 321, 180 
 3 Michaelis, Annalen, 1902, 321, 180. 4 Ibid., 320, 321. 
 
 149 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 rhombic system ; it remains unchanged at 300, intumescing at 
 higher temperatures ; prepared by adding gradually ^-tolylarsinic 
 acid (5 parts) to a mixture of concentrated sulphuric acid (25 parts) 
 and fuming nitric acid (20 parts) at summer temperature. 
 The mixture is stirred vigorously to prevent local heating and 
 then poured into 6 volumes of cold water, when the nitro-deriv- 
 ative separates slowly in lustrous needles. 
 
 Salts : Alkali salts not crystallisable ; silver salt, 
 
 NO a -C 7 H 6 -AsO(OAg) 2 , 
 
 white powder from ammoniacal solution of the acid ; acid 
 bariim salt, [NO a -C 7 H 6 -AsO(OH)-0] a Ba, by dissolving the acid 
 in baryta water, precipitating excess of alkali with carbon 
 dioxide and concentrating the nitrate. The calcium, copper, 
 and cobalt salts have the general composition 
 
 NO a -C 7 H 6 -AsO,R,H 2 O ; 
 
 the water of hydration is so tenaciously held that it is not 
 eliminated without partial decomposition of the compound, so 
 that Michaelis suggests the constitution 
 
 NO a -C 7 H 8 -AsO(OH)-O-R'OH, 
 
 Reduction Products of ^-Nitro-^-tolylarsinic Acid. 
 
 3 : s'-Dinitroarseno-p-tohiene, NO a 'C 7 H 8 t As:As-C 7 H fl -N0 2 , yellow 
 powder, m.p. 165 ; insoluble in all solvents, is prepared by the 
 action of phosphorous acid on the preceding nitrotolylarsinic acid. 
 When suspended in chloroform it absorbs bromine (z mols.), 
 forming s-nitro-^-tolylarsenious dibromide, NO a -C 7 H 9 -AsBr 8 , 
 lustrous, brownish-white scales from chloroform, m.p. 260. 
 
 S-Nitro-^-tolylarsenious sulphide, NO a -C 7 H fl -AsS, yellow needles, 
 from benzene-alcohol, m.p. 141-142 ; is obtained by passing 
 hydrogen sulphide into an aqueous solution of 3~nitro-4-tolyl- 
 arsinic acid at 70. Sulphur and the sulphide are precipitated. 
 The latter is extracted with ammonia and reprecipitated from 
 the nitrate with hydrochloric acid. 
 
 S-Amino-^-tolylthioarsinic acid, NH a -C 7 H fl -S(SH) a , is produced 
 by saturating with hydrogen sulphide an ammoniacal solution of 
 3-nitro-4-tolylarsinic acid, evaporating to dryness, and extracting 
 with very dilute hydrochloric acid. This compound is then 
 precipitated in the form of its sparingly soluble sulphate by the 
 addition of dilute sulphuric acid to the acid extract. This salt 
 
 150 
 
AROMATIC ARSENICALS 
 
 decomposes at 155 ; it is insoluble in the ordinary solvents, but is 
 dissolved by dilute alkalis. 
 
 3-Nitrobenzarsinic acid, CO 2 H-C 6 H 3 (N0 2 )-AsO(OH) 2 , colourless 
 needles, very soluble in water, less so in alcohol, and insoluble 
 in ether or chloroform, m.p. above 300, is prepared by the 
 oxidation of 3-nitro-4-tolylarsinic acid with alkaline perman- 
 ganate at 60-70. The acidified filtrate from manganese 
 hydroxides is evaporated to dryness and extracted with alcohol. 
 The alcoholic extract furnishes the acid, which is purified further 
 by adding strong hydrochloric acid to its concentrated aqueous 
 solution, when it slowly crystallises. 
 
 Tri-3-nitrotri-^-tolylarsine oxide, 2 
 
 0:As 
 
 Tri-^>"-tolylarsine (10 grams) is added to a cooled mixture of 
 fuming nitric acid (20 c.c.) and concentrated sulphuric acid (40 
 c.c.) ; the liquid is added to a large volume of cold water, when the 
 nitro-compound separates as a white, flocculent precipitate 
 (12 grams), which is dissolved in alcohol, treated with animal 
 charcoal, and allowed to crystallise from the filtered solution ; 
 yellow, highly refractive monoclinic crystals, m.p. 212, easily 
 soluble in glacial acetic acid or hot alcohol, sparingly so in cold 
 spirit, insoluble in ether. When the foregoing nitration is per- 
 formed on tri-^>-tolylarsine (5 grams) with the warm acids in 
 the foregoing proportions oxidation takes place simultaneously 
 and trinitrotri-p-tolylarsine dinitrate, [NO a -C 6 H 3 (CH 3 )] 8 As(NO 8 ) 2 , 
 is obtained, colourless crystals from glacial acetic acid, m.p. 265, 
 converted by caustic potash into the foregoing oxide (m.p. 
 212). 
 
 Trinitrotri-p-tolylarsine, [NO a -C 6 H 3 (CH 3 )] 3 As, colourless needles 
 from hot alcohol, m.p. 201, obtained from the trinitrated oxide 
 and phosphorous acid (large excess) in alcoholic solution. Chlorine 
 passed into its chloroform solution gives rise to trinitrotrichloro- 
 tri-p-tolylarsine dichloride, [NO 2 -C 6 H a Cl(CH 3 )] s AsCl a , m.p. 170, 
 By reduction with tin and hydrochloric acid this derivative loses 
 its chlorine and yields triaminotri-^-tolylarsine (v. p. 223). 
 
 Nitro-m-xylylarsinic acid, 2 NO a -C 8 H 8 -AsO(OH) 2 , colourless 
 needles from water, m.p. 207, sparingly soluble in alcohol or 
 
 1 Michaelis, Annalen, 1902, 321, 211. 2 Ibid., 320, 334- 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 ether. Prepared by dissolving w-xylylarsinic acid in cold fuming 
 nitric acid. Silver salt, NO 2 -C 8 H 8 -AsO(OAg) 2 . 
 
 Nitro-p-xylylarsinic acid, white needles from alcohol, m.p. 205, 
 prepared by adding ^-xylylarsinic acid to a large excess (8-9 parts) 
 of 100 per cent, nitric acid. By heating this acid in sealed tubes 
 with phosphorous acid nitroarseno-p-xylene is obtained, as a 
 yellow powder sintering at 165. 
 
 152 
 
CHAPTER IV 
 ATOXYL 
 
 The Bechamp Reaction and its Extensions 
 
 IT was pointed out in the introduction to the section on 
 aromatic derivatives of arsenic that the earliest observation on 
 this group of substances is due to Bechamp (loc. cit.), who during 
 the years 1860-63 isolated a colourless condensation product 
 of the interaction of aniline and arsenic acid. He noted that 
 this substance had the functions of a monobasic acid, giving rise 
 to well-defined metallic salts, and was not hydrolysed by aqueous 
 caustic potash. Nevertheless he concluded that the compound 
 was an anilide or, on account of its acid functions, " phenarsenyl- 
 ammonium." In these considerations Bechamp was hindered 
 rather than assisted by the theoretical conceptions current 
 among French chemists of that time. The obscurity in which 
 their theories of molecular configuration involved these organic 
 substances may be shown by giving the formulae ascribed by 
 Bechamp to the compound and its salts. 1 
 
 Old Notation. Modern Notation. 
 
 -Arsanilic acid 
 
 [(C 12 H 5 H 2 AsO 4 )N]O,HO. [(C 6 H 5 H 2 AsO 2 )N] 2 O,H 3 O. 
 
 Sodium salt (atoxyl) 
 
 [(C 12 H 5 H 2 AsO 4 )N]O,NaO, ic-HO. [(C 6 H 5 H 2 AsO 2 )N] 2 O,Na 2 O, ioH 2 O. 
 Silver salt 
 
 [(C 12 H 5 H 2 As0 4 )N]0,AgO. [(C 6 H 5 H 2 AsO 2 )N] 2 O,Ag 2 O. 
 
 Not only was Bechamp prevented from arriving at a correct 
 interpretation of his experimental results, but other contempor- 
 aneous chemists failed to recognise that his arsenical compound 
 of aniline was in reality a true organo-arsenic derivative. It 
 is probably for this reason that in giving a resume of earlier 
 1 Bechamp, Bull. Soc. chim., 1863, 5, 518. 
 153 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 researches on organo-arsenical compounds La Coste and 
 Michaelis, in their first detailed memoir (1880, loc. cit.), omit 
 any reference to the work of Bechamp, although they refer to 
 the earlier researches of Cadet and Thenard. 
 
 The third period in the history of organic arsenic and antimony 
 compounds commenced in 1907, when Ehrlich and Bertheim 
 demonstrated the true constitution of atoxyl. These workers 
 showed that the action of arsenic acid on aniline is comparable 
 with that of sulphuric acid on the same base. In both cases 
 the acidic group enters the aromatic nucleus, giving rise to 
 ^-aminophenylarsinic acid and ^-aminophenylsulphonic acid 
 respectively. The latter of these acids is generally termed 
 sulphanilic acid (I), and, accordingly, the former has been called 
 arsanilic acid (II). 
 
 NH 2 NH 2 
 
 SO, 
 
 yOH AsO(OH) 2 
 
 I. II. 
 
 Atoxyl is therefore sodium arsanilate, the commercial product, 
 NH 2 -C 6 H 4 AsO(OH)-ONa,#H 2 O, containing an amount of water 
 which varies between 2 and 6H 2 0, depending on the conditions 
 of crystallisation. 
 
 The constitution of />-arsanilic acid was demonstrated in 
 three stages : 
 
 (i) Its diazotisability showed the presence of a free amino- 
 group. 
 
 (ii) Its stability towards boiling aqueous caustic alkalis 
 proved that it was neither an amide nor an anhydride. 
 
 (iii) Its conversion into ^-iodoaniline by boiling hydriodic 
 acid demonstrated the orientation of the arsenic atom in the 
 nucleus with respect to the amino-group. 
 
 The proof that this compound is really an organo-metalloidal 
 derivative containing arsenic directly attached to the aromatic 
 nucleus rendered practicable the improvement of the drug by 
 the synthesis of other compounds of similar type. At first the 
 substances contained quinquevalent arsenic, but later syntheses 
 were aimed at the production of derivatives containing arsenic 
 in the more active tervalent condition. The latter are dealt 
 with in a subsequent chapter on salvarsan. 
 
 154 
 
ATOXYL 
 
 Derivatives containing Quinquevalent Arsenic. 
 
 Following on Ehrlich and Bertheim's demonstration, the 
 Beehamp condensation was applied to other aromatic amines 
 having a free para-position. Ortho-toluidine gave rise to 
 2-aminotolyl-5-arsinic acid, whilst fl-naphthylamine furnished 
 i-aminonaphthyl-4-arsinic acid. 
 
 It was already known that aniline and phenetidine could be 
 converted by acetylation into less toxic but nevertheless thera- 
 peutically active substances, e.g. the drugs antifebrin (acetanilide) 
 and phenacetin. Accordingly, atoxyl was treated similarly with 
 acetic anhydride, and the sodium salt of the acetyl derivative 
 thus obtained was introduced as a drug by Messrs. Meister, 
 Lucius, & Briining under the name of arsacetin, the formula 
 for the salt being 
 
 CH 3 -CO-NH-C 6 H 4 -AsO(OH)-ONa,3 4H a O. 
 
 This product is less toxic than atoxyl, and its solutions can 
 be sterilised by heat without decomposition. Orsudan is the 
 ortho-tolyl analogue of arsacetin. 
 
 The use of these drugs led to the preparation of other acyl 
 derivatives of atoxyl. Benzenesulphonylatoxyl, 
 
 C 6 H 6 -SO 2 -NH-C 6 H 4 AsO(OH) -ONa, 
 
 was described by Mouneyrat in a French patent (No. 401586 of 
 1908) and introduced as a drug under the name of hectine. 
 At the Seventh Congress of Applied Chemistry, held in 1909, 
 Dr. Martindale and the author described toluene--sulphonyl- 
 arsanilic acid obtained from arsanilic acid and toluene-^>- 
 sulphonic chloride, the latter reagent being a by-product in 
 the manufacture of saccharin. lodoacetyl-arsanilic acid, 
 CH 2 I-CO-NH-C 6 H 4 AsO(OH) 2 , and its homologues have been 
 patented by Messrs. Schering (D.R.-P., 268983). Allied to the 
 acyl derivatives of atoxyl are the glycine derivatives patented 
 by Messrs. Meister, Lucius, & Briining (D.R.P., 204664). 
 Phenylglycinearsinic acid, 
 
 NH-CH 2 -C0 2 H 
 
 AsO(OH) 2 
 
 is produced by either of the following processes : (i) Interaction 
 
 155 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 of arsanilic acid and chloroacetic acid ; (2) hydrolysis of the 
 nitrile, CN-CH 2 -NH-C 6 H 4 -AsO(OH) 2 , produced by condensing 
 together arsanilic acid, formaldehyde, and prussic acid. 
 
 The alkyl derivatives of atoxyl have been examined, but 
 without finding therapeutic employment. Dimethylarsanilic 
 acid was obtained by Michaelis on oxidising dimethylaniline- 
 arsenious oxide with mercuric oxide or alkaline permanganate. 
 
 N(CH 3 ) 2 -C 6 H 4 -AsO > N(CH 3 ) 2 -C 6 H 4 -AsO(OH) 2 . 
 
 The Bechamp condensation was studied systematically by 
 Benda and by Pyman and Reynolds, who discovered indepen- 
 dently that in this process by-products were formed by the 
 introduction of a second aromatic nucleus into the arsenic acid 
 complex. From aniline and o-toluidine were obtained respec- 
 tively, in small amount, di-^-aminodiphenylarsinic acid (III.) 
 and 2-diaminoditolyl-5 -arsinic acid (IV.). 
 
 NH 2 NH 2 NH 2 NH 2 
 
 /\ /\ /\ 
 
 X CH 8 
 
 O OH O OH 
 
 III. IV. 
 
 These acids had no marked effect on trypanosomes, although 
 their reduction products, the corresponding oxides, e.g., 
 HO-As(C 6 H 4 -NH 2 ) 2 , were very active in vitro (Ber., 1908, 41, 
 1672 ; Chem. Soc. Trans., 1908, 93, 1180). 
 
 Benda next extended Bechamp's condensation to the case 
 of para-substituted amines, such as para-toluidine, and found 
 that small yields of aromatic arsinic acids could be obtained 
 containing the arsinic radical in the ortho-position with respect 
 to the amino-group (Ber., 1909, 42, 3619). 
 
 Contrary to expectation, ^-nitroaniline reacted readily with 
 arsenic acid, giving rise to 2-amino-5-nitrophenyl-i-arsinic acid 
 (V.) ; diazotisation followed by elimination of the diazo-complex 
 and the reduction of the resulting w-nitrophenylarsinic acid 
 (VI.) led to meta-arsanilic acid (VII.), which was also obtained 
 by nitrating Michaelis's phenylarsinic acid and reducing the 
 nitro-compound (VI.) with sodium amalgam. 
 
 This synthesis of m-arsanilic acid demonstrates incidentally 
 the constitution of the nitrophenylarsinic acid (p. 143) first 
 
 156 " 
 
ATOXYL 
 
 obtained by Michaelis and Loesner and shows that the arsinic 
 group favour substitution in the meta-position. It therefore 
 resembles the other acyl groups, CO 2 H, SO 3 H, and NO 2 , and, 
 like these complexes, conforms to Crum Brown and Gibson's 
 rule of substitution. 
 NH 2 
 
 AsO(OH) 2 
 
 /\AsO(OH) 2 \AsO(OH) 2 
 
 NO 2 
 V. 
 
 N0 2 NH 2 
 
 VI. VII. 
 
 Benda obtained the remaining isomeride, o-arsanilic acid 
 (XIV., Ber., 1911, 44, 3304), by converting 2-amino-5-nitro- 
 phenyl-i -arsinic acid into its oxanilide, and then carrying out 
 the following succession of chemical changes : 
 
 AsO(OH) 2 AsO(OH) 2 
 
 CO-NH < 
 CO-NH < 
 
 \NO., 
 
 CO-NH 
 
 NNH, 
 
 ~> 
 
 NO, 
 
 CO-NH / 
 
 CO 
 
 AsO(OH), 
 AsO(OH) O 
 
 L I 
 
 NH-/ > N 2 
 
 AsO(OH) 2 
 AsO(OH) 2 
 
 CO-NH < 
 
 CO-NH ( 
 
 > N, 
 
 AsO(OH)- 
 
 CO-NH / 
 
 v O(OH) 2 
 
 NH 8 <(" 
 
 AsO(OH) 2 
 Vlll. 
 
 Comparative experiments with the three (ortho-, meta- and 
 para-) arsanilic acids showed that the para-compound was the 
 most efficacious trypanocide. 
 
 The diazo-derivatives of ^-arsanilic acid and its homologues 
 couple with phenols and aromatic amines, forming coloured 
 
 157 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 azo-derivatives (Ehrlich and Bertheim, Ber., 1907, 40, 3297 ; 
 Barrowcliff, Pyman, and Remfry, Chem. Soc. Trans., 1908, 93, 
 1893). But neither these azo-derivatives nor the phenazines 
 produced by oxidising arsanilic acid with persulphuric acid had 
 any very marked effect on trypanosomes. 
 
 Section I. p- Arsanilic Acid and its N-Acyl and N-Alkyl 
 Derivatives. 
 
 4-Aminophenyl-i-arsinic acid 1 (p- Arsanilic Acid), 
 NH,/ \\sO(OH) 2 . 
 
 Aniline (186 grams), mixed with 140 grams of arsenic acid, is 
 slowly heated up to 170-200 in a vessel fitted with an efficient 
 stirrer, the temperature being maintained at 190-200 for one to 
 two hours. The product is mixed with water, rendered alkaline, and 
 the excess of base distilled off in steam. The residue is allowed 
 to cool, filtered, concentrated, and neutralised with hydrochloric 
 acid, when the crude arsinic acid separates on cooling. This 
 product is dissolved in aqueous caustic soda ; the solution, which 
 should be only faintly alkaline, is boiled with animal charcoal 
 and filtered into alcohol, when the sodium salt (atoxyl) separates 
 in a crystalline form. The by-product, di-4-aminodiphenyl- 
 arsinic acid, remains dissolved, its sodium salt being soluble 
 in alcohol. Free p-arsanilic acid, liberated from atoxyl by dilute 
 hydrochloric acid, is sparingly soluble in water or ethyl alcohol, 
 more so in methyl alcohol, insoluble in ether, benzene, or 
 chloroform. 2 It is appreciably amphoteric, dissolving in excess 
 of mineral acid. From this acid solution it is, however, reprecipi- 
 tated by sodium acetate. The hydrochloride, C 6 H,ANAs,HCl, 
 obtained by evaporating its generators to dryness on the water- 
 bath, is partially hydrolysed by water. 
 
 Sodium p-Arsanilate, Atoxyl. Synonyms 2 : Arsamin, Soamin, 
 Natrium Arsanilicum. 
 
 , 
 
 - x ,011 
 
 >AsO< ,5H 2 0. 
 \ 
 
 NHo 
 
 The content of water in this salt is somewhat variable. Ehrlich 
 and Bertheim state that the salt is obtainable with 2 and 6H 3 0, 
 
 1 O. and K. Adler, Ber., 1908, 41, 932 ; Benda and Kahn, ibid., 1674, 
 2370. 2 Ehrlich and Bertheim, Ber., 1907, 40, 3292. 
 
 158 
 
ATOXYL 
 
 according to the solvent used in crystallising the compound. 
 The more hydrated forms lose water by efflorescence and 
 commercial specimens give amounts of water ranging from 
 3 to 5H 2 0. The product introduced by Burroughs Wellcome 
 and Co. under the name of " Soamin " takes the form of well- 
 defined, colourless crystals containing 5H a O. Dr. Martindale's 
 preparation contains approximately sHaO. 1 
 
 The adherence of arsinic groups to the aromatic nucleus has 
 been studied by E. Schmitz, who heated solutions of atoxyl 
 with various proportions of aqueous alkalis at 100 and at 130. 
 The maximum decomposition was obtained by heating solutions 
 containing one molecule of ^-arsanilic acid with 0-8 molecule 
 of sodium hydroxide. This instability rapidly diminishes when 
 more alkali is added and the salt approaches its maximum 
 stability when an extra half-molecule of sodium hydroxide is 
 present. With an extra molecule of alkali there is no hydrolysis. 
 The instability of the molecule of atoxyl is traced to some inter- 
 action between the ammo-group and the second hydroxyl radical 
 of the arsinic complex. Other alkalis, such as lithia, and even 
 carbamide, behave similarly and the stabilising effect is due to 
 the saturation by the alkali of the second hydroxyl radical. 
 The acyl derivatives of atoxyl are more stable inasmuch as the 
 combining power of the amino-group is diminished considerably 
 by acylation. 2 
 
 Alkaloidal Salts of p-Arsanilic Acid. 3 
 
 Quinine ^-arsanilate, produced by mixing solutions of atoxyl 
 and quinine hydrochloride ; white needles, m.p. 202, soluble 
 in hot alcohol or methyl alcohol. Solubilities i in 635 water, 
 i in 534 physiological salt solution, and I in 133 glycerol. 
 Cinchonine salt decomposes at 180, soluble in alcohol, insoluble 
 in water or anhydrous solvents. 
 
 Mercuric p-arsanilate* " Asyphil," [NH 2 -C 6 H 4 AsO(OH)-O] 2 Hg, 
 a white powder, sparingly soluble in water, dissolves in aqueous 
 sodium chloride, and is accordingly useful for injections ; prepared 
 
 1 Congress of Applied Chemistry, 1909, (Pharmaceutical Chemistry 
 Section). Schmitz, Ber., 1914, 47, 363. 
 
 3 Vereinigte chemische Werke, Aktiengesellschaft in Charlottenburg, 
 D.R.-P., 203081. 
 
 4 May and Baker and Bates, Eng. P., 8959 and 24428/1908 ; Fr. P., 396192, 
 Allschul, A. P., 938939. M. L. and B., D.R.-P., 237787. 
 
 159 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 by triturating />-arsanilic acid with freshly precipitated mercuric 
 oxide or by double decomposition from atoxyl and mercuric 
 chloride. A basic mercuric salt, NH 2 -C 6 H 4 -AsO(OH)-OHg-OH, 
 has also been prepared. 
 
 N-Acyl Derivatives of p-Arsanilic Acid. 1 
 
 Formyl-p-arsanilic acid, COH-N-C 6 H 4 -H'AsO(OH) 2 , colourless 
 needles from hot water or methyl alcohol, insoluble in ether. 
 Prepared by heating atoxyl dried at 140 with excess of formic 
 acid for two hours in a reflux apparatus, afterwards distilling 
 off excess of volatile acid. 
 
 Acetyl-p-arsanilic acid, CH3-CO-NH-C 6 H 4 'AsO(OH) 2 , colourless 
 leaflets from water, prepared either by warming atoxyl with 
 acetic anhydride or by heating this salt with glacial acetic 
 acid in a reflux apparatus. Easily soluble in aqueous sodium 
 carbonate, dissolving only sparingly in dilute hydrochloric acid. 
 
 Sodium A cetyl-p-ar sanitate, " Arsacetin," " Acetylatoxyl," 
 
 CH 3 -CONH-C 6 H 4 -AsO(OH) -ONa,3-4H 2 O, 
 
 solubility i in 10 parts of cold water, insoluble in alcohol. 
 Acetyl-^>-arsanilic acid is also obtained by Bart's reaction by 
 adding aqueous sodium arsenite to ^-aminoacetanilide diazotised 
 in dilute hydrochloric acid. The mixture is rendered just alkaline 
 by caustic soda and warmed. The filtered solution is concen- 
 trated until sodium acetyl-^>-arsanilate separates. The salt 
 crystallises from dilute methyl alcohol in colourless needles. 2 
 
 Chloroacetyl-p-arsanilic acid, CH 2 Cl-CO-NH-C 6 H 4 -AsO(OH) 2 , 
 prepared by dissolving ^>-arsanilic acid in warm chloroacetyl 
 chloride and adding the solution to water ; the product is soluble 
 in cold aqueous sodium carbonate and reprecipitated with hydro- 
 chloric acid : i f odoacetyl-p-arsanilic acid (needles decomposing at 
 196) zndiodopropionyl derivative (needles decomposing at 214). 3 
 
 Butyryl-p-arsanilic acid, C 3 H 7 -CO-NH-C 6 H 4 AsO(OH) 2) prepared 
 by (i) warming atoxyl with butyric anhydride or (2) adding 
 butyryl chloride to an equal weight of ^-arsanilic acid dissolved 
 in 10 parts of dry pyridine. After 16 hours in the cold the 
 product is precipitated with ether and the precipitate treated 
 successively with water and dilute hydrochloric acid, the final 
 residue being the butyryl derivative. 
 
 1 Ehrlich and Bertheim (M. L. and B.), U.S.P., 907016/1908. 
 
 2 H. Bart, D.R.-P., 250264 ; Eng. P., 568/1911. 
 
 3 Schering, D.R.-P., 268983. 
 
 160 
 
ATOXYL 
 
 The carbamide derivative, CO[NH-C 6 H 4 AsO(OH) 2 ] 2 , is prepared 
 by shaking a well-cooled 10 per cent, aqueous solution of atoxyl 
 with the calculated amount of carbonyl chloride dissolved in 
 toluene (20% solution). The resulting paste is washed succes- 
 sively with water and alcohol, and the residual carbamide 
 dissolved in aqueous sodium carbonate and precipitated by hydro- 
 chloric acid. 
 
 Malonyl-p-arsanilic acid is obtained by heating ^>-arsanilic 
 acid and ethyl malonate in a reflux apparatus. 
 
 Benzoyl-p-arsanilic acid is prepared by the Schotten-Baumann 
 reaction from ^-arsanilic acid, benzoyl chloride and aqueous 
 sodium hydroxide, and separated from benzoic acid after 
 acidifying by extraction with hot alcohol, in which the latter 
 acid is more soluble. 
 
 Oxalyl-p-aminophenylarsinic acid, Oxalyl-p-arsanilic acid, 1 
 
 C0 2 H-CO-NH-C 6 H 4 -AsO(OH) 2 , 
 
 white, crystalline powder not melting below 360, soluble in 
 hot water, caustic or carbonated alkalis, sparingly so in 
 methyl alcohol, but insoluble in acids. Prepared by heating 
 to 120-130 an intimate mixture of 347 grams of crystallised 
 atoxyl " (sodium ^-arsanilate) and 378 grams of crystallised 
 oxalic acid until the greater part of the water is eliminated. 
 The pasty mass is then heated further to 160 until it becomes 
 pulverulent. The crude product is mixed with 3 litres of water 
 and 350 c.c. of hydrochloric acid (D = 1-12) and the precipitate 
 then dissolved in 700 c.c. of cold water and 200 c.c. of ioiV-caustic 
 soda. The filtered solution, when acidified with 390 c.c. of 
 hydrochloric acid (D = 1-12), .yields the oxalyl derivative as 
 a white, crystalline meal. 
 
 A llylthiocarbamino-p-arsanilic acid, 
 
 C 3 H 5 -NH-CS-NH-C 6 H 4 -AsO 3 H 2 , 
 
 m.p. 185 (decomp.), and the homologue (decomp. 170) from 
 methyl-^>-arsanilic acid are produced by treating the arsenical 
 acid with allylthiocarbimide in methyl alcohol. The products 
 have the combined therapeutic action of allyl and arsenic 
 compounds without the toxic character of the latter. 2 
 
 Carbamino-p-arsanilic acid (I.). 8 Glacial acetic acid (480 c.c.) 
 
 1 M. L. and B., D.R.-P., 206037, 231969. 2 Thorns, D.R.-P., 294632. 
 
 3 M. L. and B., D.R.-P., 213155, addition to D.R.-P., 191548. Fr. P., 
 392857, Eng. P., 17139/1908. Ehrlich and Bertheim, U.S. P., 937929. 
 A. Mouneyrat, Fr. P., 401586. 
 
 l6l M 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 is added to an aqueous solution (3-6 litres) of sodium ^-arsani- 
 late (620 grams) and potassium cyanate (480 grams). After 
 24 hours the solution is acidified with 1560 c.c. of hydro- 
 chloric acid (D = 1-124). The crystallisation of the product 
 is promoted by rubbing the side of the vessel. 
 
 NH 2 -CO-NH/ \\sO(OH) 2 
 L~ 
 
 NH 2 -CS-NH/ 
 
 II. 
 
 Thiocarbamino-p-arsanilic acid (II.). A solution of 60 grams 
 of potassium thiocyanate and 78 c.c. of hydrochloric acid 
 (D = 1-124) i s saturated with ^>-arsanilic acid (about 83 grams) 
 and evaporated to dryness. The residue is heated on the 
 water-bath for two hours and mixed with 300 c.c. of water 
 and 150 c.c. of zoN-caustic soda, the product being pre- 
 cipitated from the filtrate by means of dilute hydrochloric 
 acid. 
 
 Methylcarbamino-p-arsanilic acid, 
 
 CH 3 -NH-CO-NH-C 6 H 4 -AsO 3 H 2 , 
 
 is prepared by adding 14 grams of methyl isocyanate to atoxyl 
 (40 grams) in 240 c.c. of water, the solution being cooled 
 in ice. After twelve hours in the ice-chest 52 c.c. of hydro- 
 chloric acid (D = 1-12) are added to precipitate the crystalline 
 product. 
 
 Phenylcarbamino-p-arsanilic acid, 
 
 C 6 H 5 -NH-CO-NH-C 6 H 4 - AsO 3 H 2 , 
 
 results from the addition of phenyl ^'socyanate (18 grams) to 
 31 grams of atoxyl in 300 c.c. of water. The mixture is well 
 stirred and kept ice-cold for twelve hours, being then extracted 
 with ether, and the solution filtered. The aqueous layer is 
 acidified with 40 c.c. of hydrochloric acid (D=i-i4), when 
 the phenylcarbamino-derivative is precipitated. A further 
 quantity is obtained by extracting the insoluble products 
 with aqueous sodium carbonate and afterwards acidifying the 
 alkaline extract. 
 
 Methyl-atoxyl and its carboxyl oxidation product, when 
 treated with potassium cyanate and acetic acid, and after twenty- 
 four hours with excess of hydrochloric acid, yield respectively 
 
 162 
 
ATOXYL 
 
 2-carbaminomethyl-^-arsinic acid (I.) and 2-carbamino-i : 5- 
 benzarsmic acid (II.). 
 
 CH 3 C0 2 H 
 
 NH.-CO-NH/ NH a 'CO-NH/\ 
 
 I. II. 
 
 p-Sulphomethylaminophenylarsinic acid, 
 
 S0 3 H-CH 2 -NH/ \AsO(OH) 2 , 
 
 needles, decomposing at 148, prepared by treating atoxyl with 
 formaldehyde and sodium bisulphite in concentrated aqueous 
 solution. The free acid is precipitated by hydrochloric acid. It is 
 much less toxic than atoxyl, but also much less trypanocidal. 1 
 
 Phthalyl-p-arsanilic acid, C0 2 H-C 6 H 4 -CO-NH-C 6 H 4 -AsO(OH) a , 
 is prepared by the Schotten-Baumann reaction, using phthalyl 
 chloride ; the product is precipitated by adding concentrated 
 hydrochloric acid very slowly to the alkaline solution. 2 
 
 Benzenesulphonyl-p-arsanilic acid, 8 
 
 C 6 H 5 -SO 2 -NH'C 6 H 4 -AsO(OH) 2 , 
 
 prepared by the Schotten-Baumann reaction, using benzene- 
 sulphonic chloride. Sodium salt, " Hectine." 
 p-Toluenesulphonyl-p-arsanilic acid* 
 
 C 7 H 7 -S0 2 -NH-C 6 H 4 -AsO(OH) 2 , 
 
 colourless crystals from hot water, prepared by the Schotten- 
 Baumann reaction, using toluene-/>-sulphonic chloride. Sodium 
 salt, very soluble in water, slightly so in alcohol. 
 
 The foregoing acyl-/>-arsanilates no longer give the following 
 characteristic reactions of atoxyl : 
 
 (1) ^-Dimethylaminobenzaldehyde in hydrochloric acid forms, 
 with atoxyl, an intensely yellow condensation product. 
 
 (2) /3-Naphthaquinone-4-sulphonic acid and atoxyl in the 
 presence of aqueous sodium carbonate yield an intense reddish- 
 orange coloration of a naphthaquinone derivative soluble in 
 alkalis and dissolving only sparingly in acids. The acyl-#- 
 arsanilic acids are hydrolysed by warming with 30 per cent. 
 
 1 Abelin, Biochem. Zeitsch., 1916, 78, 191. 2 D.R.-R, I9I54 8 - 
 
 3 Mouneyrat, Fr. P., 401586/1908. 
 
 4 Martindale and Morgan, Seventh International Congress of Applied 
 Chemistry, 1909. 
 
 163 M 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 sulphuric acid or concentrated aqueous alkalis, when the regener- 
 ated atoxyl gives the above colour reactions. 
 
 The toxicity of these acyl derivatives of atoxyl is generally 
 stated to be less than that of the latter salt itself. In trypanocidal 
 effect they are somewhat similar. 
 
 Aldehydic Condensation Products of Atoxyl. 
 
 The condensation of aldehydes with ^-arsanilic acid leads to 
 products having diminished toxicity. 
 p-Hydroxybenzylidene-p-arsanilic acid, 
 
 HO-C 6 H 4 -CH:N-C 6 H 4 -AsO(OH) 2 , 
 
 yellow crystals insoluble in .ether, sparingly soluble in water or 
 alcohol, dissolving readily in aqueous sodium carbonate but 
 hydrolysed by concentrated caustic soda. Prepared by heating 
 at 140 a mixture of ^-arsanilic acid and ^-hydroxybenzaldehyde 
 in molecular proportions. Similar products are obtainable from 
 ^>-arsanilic acid and dimethyl-^-aminobenzaldehyde or resorcyl- 
 aldehyde and from other aliphatic and aromatic aldehydes. 1 
 p- Dimethylaminophenylarsinic acid, 2 
 
 (CH 3 ) 2 N/~ ~\AsO(OH) 2 , 
 
 crystallises from water or alcohol in colourless needles, .subliming 
 without melting ; produced by heating together dimethyl- 
 aminophenylarsenious oxide and red mercuric oxide (slight 
 excess) suspended in water ; the acid separates from the filtrate 
 on evaporation. 
 
 (CH 3 ) 2 N-C 6 H 4 AsO + HgO -f- H 2 O = 
 
 (CH 3 ) 2 N-C 6 H 4 -AsO(OH) 2 + Hg. 
 
 A more convenient method of preparing this acid is as follows : 
 A mixture of 15 grams of dimethylaniline and 25 grams of 
 arsenious chloride heated for two hours on the water-bath is 
 poured into 300-400 c.c. of cold water. Excess of aqueous 
 caustic soda is added until ^-dimethylaminophenylarsenious 
 oxide is dissolved. After removing unaltered dimethylaniline 
 with light petroleum, excess of 30 per cent, hydrogen peroxide 
 is added and ^-dimethylaminophenylarsinic acid precipitated 
 by acetic acid. It is sparingly soluble in cold water or 
 
 1 D.R.-P., 193542, Kuratorium des Georg und Franziska Speyerschen 
 Studienstiftung in Frankfurt A/M. 
 a Michaelis, Annalen, 1902, 320, 295. 
 
 164 
 
ATOXYL , 
 
 alcohol, dissolving readily in hot alcohol, hot dilute acetic acid, 
 mineral acids or alkalis. Sodium salt, (N-Dimethylatoxyl) , 
 (CH 3 ) 2 N-C 6 H 4 -AsO(OH)ONa,5H 2 O, leaflets. 1 
 
 Phenytgtycinearsinic Acid and its Homologues. 
 Phenylgtycine-p-arsinic acid, 
 
 f / \. 
 
 This important derivative of ^-arsanilic acid is prepared by the 
 following methods - 
 
 (1) Atoxyl (27-5 parts) dissolved in 80 parts of hot water is 
 mixed with chloroacetic acid (16 parts) in 20 parts of water, the 
 mixture being heated in a reflux apparatus for six to eight hours. 
 On cooling, the glycine derivative crystallises and is washed with 
 dilute hydrochloric acid to remove unchanged arsanilic acid. 
 The residual phenylglycine-^>-arsinic acid is sparingly soluble 
 in cold, easily so in hot, water. It is easily soluble in con- 
 centrated hydrochloric acid, but in the dilute acid only on 
 warming ; it dissolves readily in alkali hydroxides, carbonates 
 and acetates. 
 
 (2) ^-Arsanilic acid (7 parts), sodium cyanide (2 parts), and 
 2-2 parts of 40 per cent, formalin solution are dissolved in 35 parts 
 of water and heated in an autoclave at 100 for one to two hours. 
 After cooling the solution is neutralised cautiously with dilute 
 hydrochloric acid; the nitrite, CN-CH a -NH-C 6 H 4 -AsO(OH) 2 , 
 crystallises and is boiled with aqueous sodium hydroxide, when 
 ammonia is evolved. The alkaline solution on acidifying with 
 dilute hydrochloric acid yields phenylglycine-^>-arsinic acid . The 
 homologous arylglycinearsmic acids from 2-aminotolyl-5-arsinic 
 acid, 5-aminotolyl-2-arsinic acid, and 2-ammo-^-xylyl-5-arsimc 
 acid are obtained in a similar manner. 
 
 These glycine derivatives are distinguished from atoxyl by 
 their feebler toxicity. Although an Af-acetyl group lowers the 
 toxicity of atoxyl, this diminution of toxic effect is noticeable 
 only in certain animal species and not with horses or guinea pigs 
 In these cases the animal organism exerts a more or less complete 
 hydrolysis of the acetyl compound, but the glycine group is 
 more firmly attached and resists this hydrolytic action. 2 
 
 1 Michaelis, D.R.-P., 200065; Ber., 1908, 41, 1514. 
 
 2 M.L. and B., D.R.-P., 204664. Berliner Klinischen Wochenschrift, 
 1907, 44, 283. 
 
 165 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 o-Tolylglycine-p-arsinic acid, 
 
 CH 3 
 CO 2 H-CH 2 -NH/~ ~\As0 3 H 2 , 
 
 melts and decomposes at 220, crystallises from hot water, soluble 
 in alcohol or aqueous alkalis, insoluble in hydrochloric acid. 
 
 Phenylmethylglycine-p-arsinic Acid and its C-Esters. 1 
 
 The starting materials for these arsenical compounds are 
 obtained by heating dimethylaniline with the esters of chloroacetic 
 acid, the product being fractionated in vacuo : C-ethylphenyl- 
 methylglycine-^-arsinic acid AsO(OH) 2 -C 6 H 2 N(CH 3 ) -CHyCCVCaHg, 
 boils at I7i/3o mm., the propyl ester boils at I74/2O mm. ; 
 both are colourless liquids having a faint agreeable odour. 
 
 C-Propylphenylmethylglycine-^-arsinic acid, 
 
 AsO(OH) 2 / \N(CH 3 )-CH 2 -C0 2 'C 3 H 7 , 
 
 white, crystalline mass, m.p. 153154, blackening at 190 ; 
 sparingly soluble in water, ether, or mineral acids, but dissolving 
 more readily in alcohol, acetone, or acetic acid ; prepared by 
 heating the propyl ether of phenylmethylglycine (200 grams) for 
 1 1 hours at 90-110 with arsenious chloride (250 grams) or 
 arsenious bromide (430 grams). The hot solution is then poured 
 into water and the intermediate product, 
 
 AsCl 2 -C C H 4 N(CH 3 ) -CH 2 -CO 2 -C 3 H 7 , 
 
 or the corresponding bromide is oxidised with hydrogen peroxide. 
 The crystalline precipitate is dissolved in aqueous sodium car- 
 bonate, the solution decolorised with animal charcoal and 
 acidified with excess of hydrochloric acid, when the precipitated 
 arsinic acid is crystallised from 20 per cent, acetic acid. 
 Phenylmethylglycine-^-arsinic acid, 2 
 
 AsO(OH), N(CH 3 ) -CH 2 -CO 2 H, 
 
 white, crystalline powder evolving carbon dioxide at high tempera- 
 tures and yielding 4-dimethylaminophenylarsinic acid. 
 
 The foregoing propyl ester or the corresponding amyl compound 
 (50 grams) is dissolved in 4 per cent, aqueous sodium hydroxide 
 
 1 Poulenc and K. Oechslin, Fr. P., 450214. 2 Ibid., Fr. P., 462276. 
 
 166 
 
ATOXYL 
 
 (200 c.c.), 100 grams of 36 per cent, alkali are added, and the 
 mixture heated to 60. Amyl alcohol separates and the acidified 
 aqueous solution yields the free glycine. 
 
 p-A Ikylaminophenylarsinic and Bis-p-alkylaminophenylarsinic 
 acids, 1 
 
 NHR/ \\sO(OH) 2 NHR/ \ I AsOOH. 
 \ / L \ / Ja 
 
 In addition to the dialkylanilines studied by Michaelis and 
 Rabinerson, it was found subsequently that the monoalkyl- 
 anilines and arylglycines also undergo condensation with arsenious 
 chloride to furnish derivatives of phenylarsenious dichloride, 
 NHR-C 6 H 4 -AsCl 2 ,, and diphenylarsenious chloride, 
 
 (NHR-C 6 H 4 ) 2 AsCl, 
 
 especially in the presence of pyridine. 
 
 Amylaniline (163 grams) dissolved in at least 79 grams of 
 dry pyridine is added to arsenious chloride (180 grams) and the 
 mixture heated for one to two hours at 106-108 for the mono- 
 phenyl derivative and at 115-120 for the diphenyl compound. 
 The solution is poured into water (400 c.c.) and oxidised in acid 
 or alkaline solution with hydrogen peroxide in moderate excess. 
 The alkali soluble product is reprecipitated by mineral acid 
 added till the mixture is faintly acid to Congo red. The mono- 
 phenylated acid is isolated by dissolving the mixture in absolute 
 alcohol and then adding ether, when it separates in a crystalline 
 mass which recrystallised from hot water forms colourless 
 lamellae decomposing at 172. It is slightly soluble in water, 
 but dissolves in alcohol, acids or alkalis. The diphenylated 
 acid remaining in the ether-alcohol mother liquors is very 
 soluble in alcohol but insoluble in water ; it dissolves in acids 
 or alkalis. 
 
 Similar products are obtainable from methyl- and ethyl- 
 aniline and from phenylglycine and phenylmethylglycine. 
 
 Section II. Isomerides of p-Arsanilic Acid. 
 m-Aminophenylarsinic Acid (m-Arsanilic Acid). 2 
 
 ^>-Oxanilarsinic acid is produced by heating a mixture of 
 />-arsanilic acid (21-7 grams) and oxalic acid (37-8 grams) heated 
 
 1 Poulenc and K. Oechslin, Fr. P., 473704. 
 
 2 Benda, Ber., 1909, 42, 3619. 
 
 167 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 to 130-140 until the liquid mass thickens when the temperature 
 is raised to 160. The fused mass is extracted with water acidi- 
 fied with hydrochloric acid to remove unchanged ^-arsanilic acid 
 and the crude oxanilic compound dissolved in aqueous sodium 
 hydroxide and reprecipitated with hydrochloric acid. The 
 product crystallised from 50 per cent, acetic acid has the composi- 
 tion AsOsH-CeH^NH-CO-COaliHA m.p. above 200. A 
 solution of 116 grams of this substance dissolved in 300 c.c. of 
 concentrated sulphuric acid is nitrated at 15-20 with 26 c.c. 
 of nitric acid (D = 1-4) and 26 c.c. of concentrated sulphuric 
 acid. The nitration solution is poured into 1-5 litres of water 
 and the whole mixture boiled in a reflux apparatus, when 
 3-nitro-4-aminophenylarsinic acid is produced, the yield being 
 86 per cent, of theory. 
 
 When dissolved in 400 c.c. of water and 100 c.c. of loJV-caustic 
 soda the foregoing nitro-acid (131 grams) is diazotised with sodium 
 nitrite (35 grams) in 175 c.c. of water. The diazo-solution when 
 diluted with 650 c.c. of water and 390 c.c. of hydrochloric acid 
 (D = 1-12) is added to 265 grams of sodium hypophosphite in 
 500 c.c. of water and 325 c.c. of hydrochloric acid (D = 1-12). 
 The w-nitrophenylarsinic acid, produced by eliminating the 
 diazo-group, is isolated successively through the barium, zinc, 
 and sodium salts, when by this synthetic method the yield of 
 45 per cent, is obtained. 1 
 
 NH 2 
 
 \ 
 
 AsO(OH) 2 . 
 
 w-Arsanilic acid containing the amino-group in the meta- 
 position to the arsinic radical is obtained by the reduction of 
 w-nitrophenylarsinic acid, produced either by the foregoing 
 process from ^-arsanilic acid or by direct nitration of phenyl- 
 arsinic acid (p. 143). A practical difficulty arises in this opera- 
 tion owing to the tendency of the arsinic group to undergo 
 reduction simultaneously with the nitro-group. 
 
 w-Nitrophenylarsinic acid (99 grams) dissolved in 2 litres of 
 methyl alcohol is treated with 4 per cent, sodium amalgam at 
 50 until the evolution of hydrogen ceases. The nitrate from 
 mercury is distilled to remove methyl alcohol ; the residue 
 extracted with 8-9 litres of water, the solution neutralised with 
 
 1 Bertheim and Benda, Ber., ign, 44, 3298. 
 168 
 
ATOXYL 
 
 acetic acid, excess of zinc acetate added, and the precipi- 
 tated zinc w-aminophenylarsinate decomposed with sodium 
 carbonate. The filtrate from zinc carbonate is neutralised 
 with hydrochloric acid and acidified with glacial acetic acid, 
 when w-aminophenyl-i-arsinic acid separates as a white 
 powder. 
 
 w-Arsanilic acid, or 3-aminophenyl-i-arsinic acid, is sparingly 
 soluble in hot water, and crystallises therefrom in colourless 
 prisms melting at 212-214 ; it is moderately soluble in 
 methyl alcohol, sparingly so in ethyl alcohol, glacial acetic 
 acid, or ether, and dissolves readily in aqueous alkalis 
 or mineral acids. With magnesia mixture this acid 
 gives a white precipitate ; moreover, the acid is readily 
 diazotised. 
 
 When w-nitrophenylarsinic acid is reduced with ammonium 
 sulphide in alcoholic solution, the nitro- and arsinic groups are 
 both affected, a sulphur-containing compound, NH 2 -C 6 H 4 'AsS, 
 being produced. The sulphur in this substance can be eliminated 
 in the following manner, A solution of w-nitrophenylarsinic acid 
 (200 grams) in 1-4 litres of 25 per cent, ammonia is saturated with 
 hydrogen sulphide and heated for tv/elve hours on the water- 
 bath, the treatment with hydrogen sulphide being repeated 
 several times. The solution is evaporated to dryness, the residue 
 is extracted repeatedly with very dilute hydrochloric acid, the 
 extract diluted to 10 litres and heated to boiling after adding 
 1-4 litres of loN-sodium hydroxide. Decinormal copper 
 sulphate is added till a filtered portion gives no precipitate of 
 lead sulphide on boiling with lead acetate. The precipitate 
 of copper sulphide is removed, the filtered solution neutralised 
 with acetic acid, and w-arsanilic acid obtained through the 
 zinc salt. 1 
 
 In the reduction with sodium amalgam and methyl alcohol 
 the roundabout purification through the zinc salt may be avoided 
 by distilling off the alcohol, adding water and ij vols. of strong 
 hydrochloric acid. Sodium chloride and by-products are 
 precipitated, and sodium acetate is added to the filtrate until the 
 colour of Congo red paper is no longer changed. On rubbing the 
 sides of the vessel w-arsanilic acid separates and is purified by 
 crystallisation from water. 2 
 
 1 M.L. and B., D.R.-P., 206344, Cf. Michaelis, Ber., 1894, 27, 265 
 and 271 ; Annalen, 1902, 320, 277 and 294. 
 2 
 
 271 ; nnaen, 1902, , 277 an 294. 
 Ber., 1908, 41, 1657, and 1911, 44, 3299. 
 
 169 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 m-Aminophenylarsenious sulphide,' 1 NH 2 -C 6 H 4 -AsS, white, un- 
 crystallisable powder, softening at 182 and melting at 188 
 to a yellow liquid. Nitrophenylarsinic acid dissolved in strong 
 aqueous ammonia is saturated with hydrogen sulphide and the 
 solution warmed on the water-bath. Fresh ammonia is added 
 and the whole operation repeated. Finally the solution is 
 taken to dryness, the residue extracted with water and acidified 
 in the cold with dilute hydrochloric acid. The filtrate from 
 precipitated sulphur, rendered ammoniacal, gives aminophenyl- 
 arsenious sulphide as a voluminous white precipitate (n grams). 
 Probably ammonium aminophenylthioarsinate is the intermediate 
 product which is decomposed by acid. 
 
 NH 2 -CH 4 -AsS(SNH 4 ) 2 + 2HC1 = 
 
 NH a -C 6 H 4 AsS + S + H 2 S + 2NH 4 C1. 
 
 o-Aminophenylarsinic acid (o-Arsanilic acid), 2 
 
 / p>AsO(OH) 2 . 
 
 5-Nitro-2-aminophenylarsinic acid (104 grams) is converted 
 into the corresponding oxaniride (v. p. 157) by heating with 
 oxalic acid (200 grams) and 40 c.c. of iV-sodium hydroxide at 
 110-130 and finally at 160-165 '> this product is reduced with 
 iron powder and dilute acetic acid. The oxanilide of 2 : 5-di- 
 aminophenylarsinic acid containing a free (5-) amino-group 
 is diazotised and the diazo-compound warmed at 55-60 
 with alcohol and copper-bronze. The product, which separ- 
 ates in the filtrate as a brown, crystalline precipitate, is 
 hydrolysed with 2./V-sulphuric acid, when o-arsanilic acid is 
 produced and purified through its barium salt. This ortho- 
 isomeride of ^>-arsanilic acid melts at 152-153, and is very soluble 
 in water even at the ordinary temperature. It dissolves readily 
 in aqueous alkalis or acids, in the alcohols, and in glacial acetic 
 acid. Its silver salt shows a characteristic reaction. Silver 
 nitrate added to sodium o-arsanilate gives a caseous, white 
 precipitate which in a few seconds and without stirring changes 
 suddenly into well-defined lustrous needles. o-Arsanilic acid, 
 when warmed at 80 with potassium iodide and dilute sulphuric 
 acid, rapidly yields o-iodoaniline. 
 
 1 Michaelis and Loesner, Ber., 1894, 27, 271. 
 
 2 Benda, Ber., 1911, 44, 3304. 
 
 170 
 
ATOXYL 
 
 Section III. Homologues and Substitution Products of 
 p-Arsanilic Acid. 
 
 i. Homologues. 
 
 The Aminotolylarsinic Acids. 1 
 2- A minotolyl-$-arsinic A cid, 
 
 CH_ 
 
 Powdered arsenic acid (24 parts) is added to o-toluidine 
 (90 parts) heated at 100 in a vessel fitted with stirrers. The 
 temperature is gradually raised so that after one hour the fused 
 mass is at 165-168 ; water and o-toluidine distil off, the tempera- 
 ture is increased further and maintained for one hour at 185-190. 
 The solution is cooled to 150 and blown into water, neutralised 
 with sodium hydroxide and rendered strongly alkaline with 
 calcium or barium hydroxide. The excess of o-toluidine is dis- 
 tilled off in steam, the residual solution saturated with sodium 
 chloride and filtered after 24 hours. Hydrochloric acid and a 
 few drops of methyl-orange are now added till the colour of 
 the solution changes to red, a tarry by-product separates, and 
 after 20 hours or longer 2-aminotolyl-5-arsinic acid crystallises 
 and is dissolved in a little hot water The solution neutralised 
 with sodium hydroxide is cleared with animal charcoal and 
 treated with i| volumes of alcohol, when the sodium salt separates 
 in crystalline form. On acidifying with hydrochloric acid a 
 concentrated aqueous solution of the sodium salt, 2-aminotolyl- 
 5-arsinic acid (m.p. 198-200) crystallises in needles, sparingly 
 soluble in cold, more soluble in hot, water. This acid dissolves 
 sparingly in alcohol and is insoluble in benzene or ether ; it is 
 easily soluble in excess of dilute mineral acids or in aqueous 
 solutions of alkali hydroxides or carbonates. The diazo-deriv- 
 ative of the acid, which is prepared in the usual way, couples 
 with alkaline phenols. 
 
 1 M.L. and B., D.R.-P., 219210 (20/7/07); Eng. P., 14937 (14/7/08). 
 L. Benda and M.L. and B., U.S.P., 913940 (2/3/09). H. S. Wellcome 
 and F. L. Pyman, Eng. P., 855 (14/1/08). O. and R. Adler, Ber., 1908, 41- 
 931. Benda and Kahn, Ber., 1908, 41, 1672. 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Sodium 2-aminotolyl-$-arsinate, " Kharsin," 
 NH 2 -C 6 H 3 (CH 3 ) - AsO(OH) -ONa, 
 
 dissolves readily in water, but is more sparingly soluble in alcohol J 
 it is insoluble in ether or benzene. From water this salt separates 
 with 5H 2 O of crystallisation, but when its concentrated aqueous 
 solution is mixed with three volumes of alcohol it is obtained in 
 glistening, tabular crystals containing 3jH 2 O. 
 5-^4 minotolyl-2-arsinic acid, 
 
 As0 3 H 
 
 m.p. 180 
 NH 
 
 The interaction of arsenic acid and w-toluidine at 170-190 
 gives rise to 5-aminotolyl-2-arsinic acid, which is extracted 
 from the mixture in the same manner as its isomeride. 
 Sodium Acetyl-2-aminotolyl-$-arsinate, " Orsudan," 1 
 
 / OH 
 CH 3 -CO-NH< >As< , 5 or 7H 2 O. 
 
 Acetyl-2-aminotolyl-5-arsinic acid is prepared by (i) adding 
 acetic anhydride to sodium 2-aminotolyl-5-arsinate or (2) treating 
 2-aminotolyl-5-arsinic acid with this anhydride and a little 
 concentrated sulphuric acid. The free ace tylamino -acid crystal- 
 lises from water in acicular prisms ; at 260 it turns brown and 
 decomposes with frothing at 306. 
 
 The sodium salt introduced into pharmacy by Messrs. 
 Burroughs Wellcome & Co. under the name of " orsudan " 
 crystallises from 50 per cent, alcohol with 5H 2 O and from water 
 with 7H 2 O. 
 
 Acetyl-$-aminotolyl-2-arsinic acid is prepared by mixing 
 5-aminotolyl-2-arsinic acid (50 grams), acetic anhydride 
 (100 c.c.), and 2-5 c.c. of concentrated sulphuric acid, the 
 mixture being warmed on the water-bath till a clear solution 
 is produced. This acetyl derivative, which is more soluble 
 than the foregoing isomeride, crystallises from water in 
 colourless prisms which become discoloured at 240, but not 
 entirely melted at 350. 
 
 1 Pyman and Reynolds, Chem. Soc. Trans., 1908, 93, 1181; Wellcome 
 and Pyman, Eng. P, 855/1908. 
 
 172 
 
ATOXYL 
 
 2- A mino-p-xylyl-5-arsinic A cid, 
 
 CH 8 _ 
 NH,/ \AsO 3 H 2 , m.p. 210. 
 
 "CH 3 
 
 ^>-Xylidine contains an unsubstituted hydrogen atom in the para- 
 position to the amino-group, and accordingly a mixture of this 
 base and arsenic acid when heated for several hours at 170-190 
 yields 2-amino-^-xylyl-5-arsinic acid, the properties of which 
 resemble closely those of ^-arsanilic acid. 
 
 The acetyl derivative crystallises from water in prisms, 
 becoming brown at 240 and decomposing with frothing at 278. 
 
 2. Alkoxyaryl Derivatives. 
 
 o-Anisidine-^-arsinic A cid (/[-Amino-^-methoxyphenylarsinic 
 Acid), 1 
 
 AsO(OH) t . 
 
 2 
 
 b 
 
 en, 
 
 When subjected to Bechamp's reaction o-anisidine yields only 
 a very small amount of arsinic acid, so that this derivative is 
 preferably obtained by an indirect process from 3-nitro-4-amino- 
 phenylarsinic acid. This nitroamine is diazotised and treated 
 with excess of sodium acetate until the diazo-derivative (I.) has 
 lost its capacity for coupling with R-salt and yields a red instead 
 of a yellow azo-compound with resorcinol. This change arises 
 from the elimination of the nitro-group. At this stage the 
 diazo-product (II.) is coupled .with alkaline /8-naphthol when 
 the sodium salt of a crystalline, coppery-red azo-/3-naphthol 
 derivative (III.) is precipitated. 
 
 AsO 3 H 2 AsO 3 H 2 AsO 3 H 2 
 
 /\ /\ 
 
 \ /N0 2 v /-O 
 
 Yd Xd 
 
 /OH 
 
 ' OH 
 
 y 
 
 I. II. III. 
 
 This azo-compound is methylated with methyl toluene-^>- 
 
 sulphonate in methyl alcohol containing sodium carbonate. 
 
 1 Benda, Ber., 1914, 47, 995^ 
 
 173 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 On reducing the methylated azo-derivative with alkaline hydro- 
 sulphite, o-anisidine-4-arsinic acid is obtained in lustrous, colour- 
 less needles easily soluble in hot water. Its diazo-derivative is 
 quite colourless. The acetyl compound produced by the action 
 of acetic anhydride on an alkaline solution of o-anisidine-4-arsinic 
 acid furnishes on nitration the following isomeric nitro-deriv- 
 atives : 
 
 AsO 3 H a 
 
 NH-COCHs 
 I. Less soluble. 
 
 OCH 3 
 
 NH-CO-CH, 
 II. More soluble. 
 
 These isomerides on alkaline hydrolysis yield the corresponding 
 nitro-o-anisidine-4-arsinic acids. The ammo-derivative from I. 
 reduces to a diaminoarsinic acid which loses the arsenical group 
 on treatment with diazo-compounds 
 
 As0 3 H ; 
 
 ,N 2 R 
 
 NH 
 
 NH 2 
 
 As0 8 H 2 
 NO/\ 
 
 X/ JOCH, l/OCH, l/OCIV 
 
 NH 2 NH 2 NH 2 
 
 The amino-derivative from II. yields a diazo-derivative which 
 on warming to 40-50 loses its methoxyl group and passes into 
 a deep orange diazo-oxide. 
 
 AsO 3 H 2 AsO 3 H 2 As0 3 H 2 
 
 NO 2 /\ NO 2 
 
 H 3 
 
 N 2 OH 
 
 3. Naphthalene Homologue. 
 
 i-Aminonaphthyl-^-arsinic acid, 1 NH 2 -C 10 H 6 -AsO(OH) 2 , prisms, 
 m.p. 173-175, produced by heating to 190 four parts of a-naph- 
 thylamine and three parts of arsenic acid ; the mixture is stirred 
 thoroughly and next heated till the mass is violet red. The 
 
 1 W. Adler, D.R.-P., 205775; O. and R. Adler, Ber., 1908, 41, 934; 
 Benda and Kahn, ibid., 1676. 
 
 174 
 
ATOXYL 
 
 melt is extracted with aqueous alkali, the solution filtered from 
 a-naphthylamine and concentrated when the arsinic acid is 
 precipitated with mineral acid. The product is easily soluble 
 in hot water or alcohol, sparingly so in ether, insoluble in 
 petroleum or chloroform. The alkali salts are very soluble in 
 water, being precipitated in a crystalline form by alcohol. 
 
 4. The Aminobenzarsinic Acids. 
 
 The acylamino-derivatives of the benzarsinjc acids are prepared 
 by the general method first employed by La Coste in the produc- 
 tion of the unsubstituted benzarsinic acids (v. p. 129) . The intro- 
 duction of a carboxyl group into the aromatic nucleus of the 
 acylaminoarylarsinic acids results in a lessened toxicity of the 
 product. These acylaminoarylbenzarsinic acids are colourless, 
 well-crystallised substances, sparingly soluble in cold water, 
 dissolving more readily in hot water or alcohol, insoluble in ether. 
 With alkali carbonates they form well-defined salts. On 
 hydrolysis they yield the aminobenzarsinic acids. 
 
 2-Acetylamino-i : ^-benzarsinic acid, 
 
 CH.-CO-NH/ \AsO,H a . 
 COaH 
 
 Potassium permanganate (10 parts) in aqueous solution is added 
 with stirring to acetyl-2-aminotolyl-5-arsinic acid (8-2 parts) 
 dissolved in 900 parts of water at 75. Oxidation is completed in 
 three hours by warming to 85-90. The mixture is then heated to 
 boiling, the manganese hydroxides separated, and the concentrated 
 filtrate acidified with acetic acid to precipitate any unaltered 
 tolylarsinic acid ; the product is precipitated in the final filtrate 
 by hydrochloric acid. 
 
 2-Acetylamino-i : 5-benzarsinic acid decomposes at 230 ; acid 
 or alkaline hydrolysis leads to 2-amino-i : 5-benzarsinic acid, 
 NH 2 -C 6 H 3 (CO 2 H)-AsO 3 H 2 , decomposing at 245. 
 
 3-Acetylamino-i : 6-benzarsinic acid decomposes at about 260 ; 
 it is produced from w-toluidine through the intermediary of 
 3-aminotolyl-6-arsinic acid. 
 
 ^>-Xylidine gives rise successively to 2-amino-^>-xylyl-6-arsinic 
 acid and the acetyl derivative of this compound. The latter 
 substance on oxidation furnishes successively 3-acetylamino-i- 
 methyl-^ : 6-benzarsinic acid, decomposing at 255, and 2-acetyl- 
 
 175 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 aminoterephthal-6-arsinic acid, turning brown and decomposing 
 at 340 . 1 
 
 5. Halogen Derivatives of p-Arsanilic Acid. 
 
 2-Chloro-i-aminophenyl-4-arsinic acid, NH a -C 6 H 3 Cl-AsO(OH) 2 , 
 white crystals, m.p. 305 ; prepared from o-chloroaniline and 
 arsenic acid. 2 Also obtained by chlorinating acetyl-/>-arsanilic 
 acid either with chlorine in glacial acetic acid or with sodium 
 hypochlorite in presence of water. It is sparingly soluble even 
 in hot water, but more so in the alcohols. 
 
 2-Bromo-i-aminophenylarsinic acid, prepared by treating 
 ^>-arsanilic acid in glacial acetic acid with half the calculated 
 amount of bromine ; white needles, not melting below 255. 
 
 The iodo-compound is obtained in colourless needles by 
 iodinating ^-arsanilic acid with iodine in methyl alcohol in the 
 presence of mercuric oxide, 
 
 Dichloro-p-arsanilic acid, produced by chlorinating />-arsanilic 
 acid in glacial acetic acid ; the dibromo-compound is prepared 
 from ^>-arsanilic acid and aqueous sodium hypobromite ; the 
 di iodo-compound is obtained by adding a 4 per cent, potassium 
 iodide solution to a hot solution of ^-arsanilic acid, potassium 
 iodate, and sulphuric acid ; these dihalogenated ^-arsanilic acids 
 crystallise in colourless needles, not melting below 25o. 3 
 
 6. Thio -derivatives of p-Arsanilic Acid and its Homologues and 
 
 Derivatives. 4 ' 
 
 These thio-derivatives are of three types : 
 v r- / v v 
 
 Sesquisulphides. Monosulphides. 
 
 They are white or yellowish-white substances, to some extent 
 crystallisable from organic media, soluble in alkali sulphides 
 or hydroxides and reprecipitated by acids, dissolving only 
 sparingly in aqueous alkali carbonates and accordingly precipi- 
 tated by carbon dioxide from alkaline solutions (unless containing 
 
 1 M.L. and B., D.R.-P., 203717 ; O. and R. Adler, Ber., 1908, 41, 933- 
 
 2 Benda, Ber., 1908, 41, 1676. 3 Bertheim, Ber., 1910, 43, 53- 
 
 * M.L. and B., D.R.-P., 205617; cf. Ber., 1882, 15, 1955 ; 1894, 27, 
 270. 
 
 176 
 
ATOXYL 
 
 carboxyl or sulphonic substituents) . On heating they melt 
 without decomposition. These properties are comparable with 
 those of the non-aminic organic sulphides of arsenic (v. pp. 75 
 and 82), and are further illustrations of the well-known 
 affinity of this metalloid for sulphur. 
 
 These ^-aminoarylarsenical sulphides have a higher toxicity 
 than the corresponding oxygen compounds, and show a higher 
 trypanocidal action. 
 
 p-Aminophenylarsenious sulphide, NH 2 'C 6 H 4 -AsS, yellowish- 
 white, crystalline powder, sinters at 165, m.p. 180 ; sparingly 
 soluble in alcohol or acetone, easily so in aniline or pyridine, 
 insoluble in benzene, chloroform, carbon bisulphide, or glacial 
 acetic acid, is prepared by dissolving ^>-arsanilic acid in hydro- 
 chloric acid (D, 1-19 in 2oH 2 O) and saturating the solution with 
 sulphuretted hydrogen. Reduction and thionation proceed con- 
 currently, so that sulphur and monosulphide are both precipitated; 
 the former is extracted with carbon bisulphide. The latter is 
 also prepared by dissolving ^-aminophenylarsenious oxide 1 in 
 cold methyl alcohol and passing in sulphuretted hydrogen so long 
 as a precipitate is produced. This monosulphide dissolves in warm 
 aqueous caustic alkalis and is precipitated therefrom by mineral 
 acids, which redissolve it in excess. Concentrated hydrochloric 
 acid precipitates the hydro chloride AsS-C 6 H 4 -NH 2 ,HCl. 
 
 It was formerly stated that arsenic is so lightly held in atoxyl 
 that arsenious sulphide is produced by the action of sulphuretted 
 hydrogen. 
 
 A cetyl-p-aminophenylarsenic sesquisulphide, 
 
 CH 3 -CO-NH >AsS, 
 
 Acetyl-^>-arsanilic acid (80 grams) dissolved in 800 c.c. of 25 per 
 cent, ammonia; the solution saturated with sulphuretted hydrogen 
 diluted with water to 8 litres and acidified with hydrochloric 
 acid. The snow-white precipitate when crystallised from alcohol 
 separates in lustrous needles, m.p. 208. The sesquisulphide 
 dissolves readily in aniline or pyridine, less in alcohol or glacial 
 acetic acid, and sparingly in toluene or chloroform. 
 
 Phenylglycine-p-arsenic disulphide, CO 2 HCH 2 -NH-C 6 H 4 -AsS 2 , 
 
 1 Eng. P., 17619/1907. 
 
 I 77 N 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 yellowish-white powder, sintering at 70, decomposing at 142, is 
 prepared by dissolving phenylglycine-_/>-arsinic acid (p. 165) in 
 50 parts of water and saturating the solution with sulphuretted 
 hydrogen. The disulphide is only sparingly soluble in organic 
 media, excepting the basic solvents ; it turns yellow on exposure 
 to light. 
 
 Section IV. Homologues and Derivatives of o-Arsanilic Acid. 
 
 4~Aminotolyl-3-arsinic acid (I) l 
 
 CH 3 CH 3 Cl 
 
 /\ 
 
 l x/ As0 3 H 2 CH 3X/ As0 3 H 2 x ^ / AsO 3 H 2 
 
 NH 2 NH 8 NH 2 
 
 I. II. 
 
 ^>-Toluidine (240 grams) is melted and mixed with powdered 
 arsenic acid (60 grams) at 60-70 ; the temperature of the mass 
 is then raised to 195-200 within half an hour. Water and 
 p-tolmdine distil away and the residue is added to water and 
 rendered alkaline with caustic soda. The unchanged ^-toluidine 
 is removed partly mechanically and partly with ether ; the 
 aqueous solution is freed from arsenious and arsenic acids by 
 addition of barium hydroxide. The filtrate is saturated with 
 sodium chloride and just neutralised by hydrochloric acid (slight 
 reddening of methyl-orange paper) . The tarry impurity is rapidly 
 removed when the clarified solution yields 4-aminotolyl-2- 
 arsinic acid. Recrystallised from 50 per cent, alcohol, this 
 product separates in colourless, felted needles, melting at 
 176. It is easily soluble in hot water or the alcohols, 
 sparingly so in ether, and insoluble in benzene. Reduced 
 with sodium hydrosulphite, it yields a yellow arseno- 
 derivative. 
 
 ^-Amino-i : 3-xylyl-$-arsinic acid (II), from m-xylidine by the 
 Bechamp reaction, is a microcrystalline precipitate, m.p. 
 199-200. It is converted by potassium iodide and dilute 
 sulphuric acid at 100 into 5-iodo-4-amino-i : 3-xylene. 
 
 4-Chloro-o-arsanilic acid (III) from ^-chloroaniline. This 
 and the foregoing acid have properties similar to those of 
 4-aminotolyl-3-arsinic acid. 
 
 1 Benda, Ber., 1909, 42, 3621. 
 
 178 
 
ATOXYL 
 
 Section V. Nitroso-, Azo-, Diazo-, and Triazo-phenyl- 
 arsinic Acids and their Derivatives. 
 
 Benzenediazonium-^-arsinate, 1 
 
 />-Arsanilic acid is diazotisable in the ordinary way to a soluble 
 diazonium compound which is precipitated as a sparingly soluble 
 white double salt by phosphotungstic acid. The diazo-derivative 
 gives the usual reactions of diazonium salts : (i) on boiling with 
 dilute sulphuric acid it furnishes phenolarsinic acid ; (2) copper 
 powder and hydrochloric acid lead to 4-chlorophenyl-arsinic 
 acid ; (3) it couples with phenols and reactive aromatic bases 
 (e.g., 2 : 4-tolylenediamine) . 
 
 p-Nitrosophenylarsinicacid,NO-C ( flt-AsO 3 H.z. Atoxyl(iograms) 
 is added to an ice-cold solution of neutralised Caro's acid (mono- 
 persulphuric acid, H 2 SO 5 , 200 c.c. = i-67O 2 ) and the liquid 
 rendered faintly alkaline by sodium carbonate. After 30 minutes 
 sufficient acid is added to redissolve any unchanged atoxyl, whilst 
 the nitroso-compound separates in yellow crystals (yield 50 per 
 cent, of theory). />-Nitrosophenylarsinic acid is readily soluble in 
 alkalis, but dissolves only sparingly in the organic media. 
 It reacts quantitatively with phenylhydrazine (2 mo Is.), setting 
 free the nitrogen (2N 2 ) from this reducing agent. It is reduced 
 by alkaline hydrosulphite and magnesium chloride to 4 : 4'-di- 
 aminoarsenobenzene. 2 This nitrosoarsinic acid has no curative 
 properties. 
 
 Azo-derivatives of p-Arsanilic Acid. 8 
 
 Diseases produced by the absorption and development in the 
 system of certain pathogenic protozoa as in sleeping sickness 
 have been treated on the one hand with a series of azo-dyes 
 (e.g., trypan red) and on the other with aromatic arsenicals 
 (particularly atoxyl), and with the object of combining these two 
 modes of attack azo-dyes have been prepared from the diazotisable 
 ^-arsanilic acid containing arsenic attached to benzene nuclei. 
 
 Monoazo-dyes. ^>-Arsanilic acid is diazotised and coupled 
 
 1 Kuratorium der Georg und Franziska Speierschen Studienstiftung in 
 Frankfort A/M., D.R.-P., 205449. 2 Karrer, Bey., 1912, 45, 2065. 
 
 3 Aktien Gesellschaft fiir Anilin Fabrikation, D.R.-P., 212018, 212304, 
 222063, 216223 ; cf. Noelting, Bull. Soc. chim., 1916 [iv], 19, 361 (Mor- 
 dant dyes from ^-arsanilic acid). 
 
 179 N 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 with alkaline /3-naphthol, /3-naphthol-3 : 6-disulphonic acid 
 (R salt), 8-amino-a-naphthol-3 : 6-disulphonic acid (H acid 
 in alkaline or acid solution), or naphthionic acid. 
 
 Polyazo-dyes. A para-diamine, such as benzidine, diazotised 
 and coupled with 8-amino-a-naphthol-3 : 6-disulphonic acid 
 (H acid) in acid solution. The violet diazo-dye is dissolved in 
 sodium carbonate and coupled with diazotised atoxyl (i or 
 2 mols.). An isomeric dye is produced by coupling diazotised 
 atoxyl with H acid in acetic acid and then treating the resulting 
 monoazo-dye (2 mols.) with diazotised benzidine (i mol.). 
 
 Further variations in the composition of these polyazo-dyes 
 are produced by changing the diamine (replacing benzidine by 
 tolidine or dichlorobenzidine) and by substituting for H acid 
 some other double coupling middle component such as 2-amino- 
 5-naphthol-7-sulphonic acid (J acid), i : 8-aminonaphthol-4-sul- 
 phonic acid (S acid), and i : 8-dihydroxynaphthalene-3 : 6-disul- 
 phonic acid (chromotrope acid). 
 
 The following diagram gives a general representation of the 
 constitution of these polyazo-dyes containing arsenic : the arrows 
 indicate the direction in which the diazotised component is 
 coupled. 
 
 double coupling 
 component (i mol.) 
 para-Diamine 
 
 double coupling 
 component (i mol.) 
 
 These polyazo-arsenical dyes have a greater trypanocidal action 
 than the monoazo-dyes and are 2\ times less lethal than atoxyl 
 to the host of the trypanosomes. 
 
 The following monoazo-derivatives of 2-aminotolyl-5-arsinic 
 acid are only slightly active towards trypanosomes. 1 
 
 4.-Hydroxybenzene-2-azotoluene-$-arsinic acid (I.), 
 
 HO/ X Na '\ / As ( H )a 
 
 V 
 
 (CH s ) a N 
 
 CH 
 II. 
 
 1 Barrowcliff, Pyman, and Remfry, Chem. Soc. Trans., 1908, 93, 1899. 
 
 180 
 
ATOXYL 
 
 ^-Dimethylaminobenzene-2 r -azotoluene-$'-arsinic acid (II.) . 
 
 Nitrosophenylarsinic acid 1 (p. 179) serves for the preparation 
 of azo-derivatives of ^-arsanilic acid. 
 
 Azobenzene-^-arsinic acid (I.), brown, amorphous powder, 
 soluble in alkalis, is prepared by condensing the nitroso-deriv- 
 ative with aniline in boiling glacial acetic acid. 
 
 Azobenzene-^\^-diarsinic acid (II.) 
 
 \/ 
 
 V 
 
 AsO 3 H 
 
 As0 3 H 2 
 
 \/ 
 
 AsO 3 H s 
 
 I. 
 
 II. 
 
 is similarly obtained from the nitroso-derivative and ^-arsanilic 
 acid, a dark brown powder easily soluble in alkalis to a yellowish- 
 green solution. 
 
 Disazobenzene-^i^'-diarsinic acid (III.) and Disazobenzene- 
 ^:2" :^'"-triarsinic acid (IV.) are prepared from the nitroso- 
 derivative and ^>-phenylenediamine and ^-phenylenearsinic acid 
 respectively. 
 
 AsO 3 H 
 
 III. 
 
 IV. 
 
 Benzeneazo-2i^-tolylenediamirio-^'-arsinic acid (V.), 
 
 /CH, 
 
 (V.) 
 
 Prepared by coupling />-diazobenzenearsinic acid and m-tolylene- 
 diamine or by condensing this base with nitrosophenylarsinic 
 acid and hydro xylamine in alkaline solution. Of the foregoing 
 azoarsinic acids, No. V. is the most toxic and No. II. the least. 2 
 
 1 Karrer, Ber., 1912, 45, 2065. 
 
 2 Mcmoa^o-derivatives of -arsanilic acid, v. Ehrlich and Bertheim, 
 Ber., 1907, 40, 3297; D.R.-P., 205449; Eng. P., 3929/1907; L. Benda, 
 Ber., 1911, 44, 3878, 3295, 3300. 
 
 181 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Triazo-derivatives of Phenylarsinic Acid. 
 
 4-Triazophenylarsinic acid, N 3 -<^ \AsO 3 H 2 , stout, colour- 
 less crystals obtained by adding sodium azide to diazophenyl- 
 arsinic acid. 
 
 3-Nitro-^-triazophenylarsinic acid (I.), yellow, crystalline powder 
 from diazotised 3-nitro-4-aminophenylarsmic acid and sodium 
 azide, loses nitrogen at 75 and changes into 3 : ^-dinitrosophenyl- 
 arsinic acid (II.), which in turn condenses with dimethylamine to 
 form 2 (or ^}-dimethylaminophenazine-y-arsinic acid, 
 
 NIL 
 
 NH ; 
 
 a blue dye soluble in acetic acid or in aqueous alkalis. 
 N, NO M 
 
 \/ 
 
 As0 3 H 2 
 I. 
 
 NO 
 
 As0 3 H 2 
 II. 
 
 AsOH, 
 
 III. 
 
 3-Nitro-4-triazophenylarsinic acid and o-phenylenediamine 
 condense in acetic acid to the brick-red acetate of the yellow 
 base 2 : 3-diaminophenazine-j-arsinic acid (III.). 1 
 
 Phenazine-2 : j-bisarsinic acid, 
 
 H 2 3 As x /x /x /AsOjHj.H.O 2 
 
 \/ \"^J/ ^' 
 
 Powdered ammonium persulphate (23 grams) is slowly added 
 to ^-arsanilic acid dissolved in warm water (100 c.c.) and 15 c.c. 
 of concentrated sulphuric acid. On gently heating a brisk evolu- 
 tion of gas occurs and light brown, leafy crystals separate. This 
 phenazine derivative is insoluble in water and dissolves only 
 sparingly in alcohol or acetic acid ; it does not melt below 
 300. Its homologue from 2-aminotolyl-5-arsinic acid is prepared 
 by the same method and has similar properties. Both acids 
 give a deep red coloration with concentrated sulphuric acid. 
 They have but little trypanocidal action. 
 
 1 Karrer, Ber., 1913, 46, 249; cf. Barrowcliff. 
 
 2 Pyman and Remfry, Chem. Soc. Trans., 1908, 93, 1893. 
 
 182 
 
ATOXYL 
 
 Section VI. Organo-mercurial Compounds of p-Arsanilic Acid 
 and its Derivatives. 
 
 The beneficial results accruing in syphilis from the joint 
 application of mercurial drugs and organic arsenical com- 
 pounds have led to attempts to combine these useful effects 
 in the same drug. With this end in view atoxyl and its deriv- 
 atives have been condensed with mercuric acetate, it being well 
 known that mercuriacetate groups are readily introduced into 
 the aromatic nucleus when amino- and hydroxy-groups are 
 already present. 
 
 Aniline, for instance, when heated with mercuric acetate 
 gives rise to a mixture of di- and tri-mercuriacetate derivatives, 
 
 NH 2 NH 2 
 
 Hg-C0 2 -CH 3 CH 3 -C0 2 -Hg/\Hg-CCVCH 3 
 
 \/ \/ 
 
 Hg-CO 2 -CH 3 Hg-C0 2 -CH 3 
 
 Atoxyl (329 grams) in water (1700 c.c.) is mixed with mercuric 
 acetate (636 grams) dissolved in 1800 c.c. of water. The mixture 
 is heated at 100 for five hours, the precipitated solid a mercuric 
 salt of the organomercurial compound is boiled with 1200 c.c. 
 of 10 per cent, aqueous sodium hydroxide, and the filtered 
 solution is acidified with 120 grams of glacial acetic acid. The 
 complex organomercurial acids thus precipitated are dissolved 
 in a slight excess of aqueous sodium hydroxide ; the solution 
 when gradually concent rated, yields successively sodium 3 : $-dihy- 
 droxymercuri-^-aminophenylarsinate, C 6 H 6 O 5 NAsHg 2 Na 2 ,4H 2 O, 
 sparingly soluble needles, and sodium ^-hydro%ymercuri-^-amino- 
 phenylarsinate, C 6 H 6 O 4 NAsHgNa 2 ,i4H 2 O, readily soluble 
 crystals. The corresponding free acids have the following consti- 
 tutional formulae : 
 
 NH 2 NH 2 
 
 HO-Hg/NHg-OH 
 
 \/ \/ 
 
 O:As(OH) 2 O:As(OH) 2 
 
 They are obtained in flattened crystals on treating the foregoing 
 sodium salts with acetic acid. A similar treatment applied to 
 methylatoxyl (Kharsin) leads to the production of a monohy- 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 droxymercuri-compound of which the free acid 3-hydroxy- 
 mercuri-2-aminotolyl-5-arsinic acid has the composition I. ; its 
 sodium salt, C 7 H 8 O 4 NAsHgNa 2 ,9H 2 O, needles, is soluble in 
 one part of water. 
 
 NH 2 OH 
 
 CH/\Hg-OH HO-Hg/\Hg-OH 
 
 \/ \/ 
 
 0:AS(OH) 2 - 0:As(OH) 2 . 
 
 I. II. 
 
 4-Hydroxyphenylarsinic (phenol-4-arsinic) acid yields 3 : 5-di- 
 hydroxymercuri-4-hydroxyphenylarsinic acid, II., a crystalline, 
 insoluble compound forming a sodium salt, 
 
 C 6 H 4 6 AsHg 2 Na 3 ,5H 2 0, 
 
 soluble in 3 parts of water. Similar mercuri-derivatives were 
 obtained from 2-hydroxytolyl-5-arsinic acid and from the azo- 
 compound, HO'C 6 H 4 N 2 -C 6 H 3 (CH 3 )-AsO(OH) 2 , having respectively 
 the compositions HO-HgC 6 H 3 (CH 3 )(OH)-AsO(OH) 2 and the 
 latter (HO-Hg) 2 C 6 H 2 (OH)-N 2 -C 6 H 3 (CH 3 )-AsO(OH) 2 . The sodium 
 salts of these insoluble acids are readily soluble in water. 1 
 
 The mercury in the foregoing compounds is in a non-ionised 
 condition. These compounds, which do not coagulate albumin, 
 are satisfactory as regards toxicity and are suitable for hypo- 
 dermic injection. 
 
 A further addition to the list of organomercurials is the 
 product of the interaction of mercuric oxide and " orsudan." 
 This complex derivative, which has been tested clinically under 
 the name of " Hydryl," has the composition 
 
 N -Kg N 
 
 j, CH/^Hg-OH 
 
 Hg-OH 
 iO 8 Na, AsO 3 Na 2 . 
 
 On physiological tests this substance gave promising results 
 but clinical experiments failed to establish its value in protozoal 
 diseases. 2 
 
 The orientation of the hydroxymercuri-group in the foregoing 
 compounds is ascertained by treatment of the sodium salts 
 
 1 Wellcome and Barrowcliff, Eng. P., 12472/1908. 
 
 2 Jowett, private communication. 
 
 184 
 
ATOXYL 
 
 with iodine dissolved in aqueous potassium iodide when the 
 mercuri-groups were displaced by iodine. Further treatment with 
 hot hydriodic acid leads to the removal of the arsenical group, 
 this giving rise to a polyiodo-compound of known constitution. 
 These reactions take the following course in the case of the 
 dihydroxymercuri-derivative of ^-arsanilic acid, 
 
 NH 2 NH 2 NH 2 
 
 /\ /\ 
 
 HOHg Hg-OH 
 
 KI 
 
 I I 
 
 
 AsO 3 H 2 AsO 3 H 2 
 
 The other mercurated arsenical compounds undergo similar 
 successive iodinations. 
 
 Section VI I. ^\^ f -Diaminodiarylarsinic Acids. 
 
 These acids were discovered as the result of a systematic study 
 of the Bechamp reaction as applied to aniline and o-toluidine, 
 
 4 '.^.'-Diaminodiphenylarsinic acid, (NH 2 'C 6 H4) 2 AsO > OH, colour- 
 less matted needles, m.p. 248-249 (232), is very sparingly soluble 
 in water or the ordinary organic solvents. It is moderately 
 soluble in glacial acetic acid and readily so in dilute alkalis or 
 mineral acids in excess. 
 
 This acid is a by-product of the Bechamp condensation with 
 aniline arsenate and aniline at 180. The crude product is 
 extracted with 10 per cent, aqueous sodium carbonate, the 
 extract concentrated and acidified with hydrochloric acid. The 
 precipitate digested with just 'sufficient aqueous caustic soda 
 to give a faintly alkaline solution leaves undissolved the crude 
 diaminodiphenylarsinic acid, which is converted into barium salt, 
 the latter being crystallised from water with addition of animal 
 charcoal until colourless. The purified barium salt is then decom- 
 posed with the calculated amount of hydrochloric acid, when the 
 acid is obtained as a dense, white precipitate of matted needles. 
 The yield is about 2-3 per cent, of the calculated quantity. 1 
 This by-product 2 is also isolated by dissolving the whole of 
 crude arsinic acids in hot caustic soda, decolorising with animal 
 charcoal and pouring the filtered solution into 2 volumes of alcohol, 
 when sodium ^>-arsanilate (atoxyl) is for the most part precipi- 
 tated, whereas the secondary diphenylarsinate remains entirely 
 
 1 Pyman and Reynolds, Chem. Soc. Trans., 1908, 03, 1184. 
 
 2 Benda, Ber., 1908, 41, 2367. 
 
 185 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 dissolved. After twelve hours the atoxyl is collected, the filtrate 
 evaporated to a small bulk and treated with excess of alcohol 
 to precipitate the remainder of the primary arsinate. The ni- 
 trate is evaporated to remove alcohol and treated with hydro- 
 chloric acid when the crude secondary arsinic acid evaporates. 
 This material is redissolved in dilute caustic soda and reprecipi- 
 tated in pulverulent form by acidifying cautiously with hydro- 
 chloric acid. The product is then crystallised from 50 per cent, 
 acetic acid. 
 
 With 4:4 / -diaminodiphenylarsinic acid, sulphuric acid and 
 potassium iodide yield />-iodoaniline ; silver nitrate in neutral 
 solution furnishes a white precipitate, barium chloride gives no 
 precipitate, and magnesia mixture in ammoniacal solution gives 
 no precipitate even on warming (unlike ^-arsanilic acid) . 
 
 Sodium 4 : 4 '-diaminodiphenylarsinate, 
 
 (NH 2 -C 6 H 4 ) 2 AsO-ONa,2,5-6H 2 0, 
 
 monoclinic plates soluble in an equal weight of water to an 
 alkaline solution and very soluble in alcohol. Barium salt, 
 Ba[O-OAs(C 6 H 4 -NH 2 ) 2 ] 2 ,7|H 2 O, soluble in twice its weight of 
 water and sparingly soluble in alcohol. 
 
 Diacetyl derivative, rosettes of needles, m.p. 275, readily 
 soluble in hot water, crystallising therefrom with 3H 2 O. Sodium 
 salt, prismatic needles, contains gH 2 O. 
 
 2 : 2 '-Diaminoditolyl-5-arsinic acid, 
 
 [NH 2 -C 6 H 3 (CH 3 )] 2 AsO-OH, 
 
 highly refractive acicular prisms from hot water or 35 per cent, 
 acetic acid, m.p. 247-249. 
 
 The yield of this acid is about 3 per cent, from the Bechamp 
 condensation with 200 grams of o-toluidine arsenate and 400 
 grams of o-toluidine at 180-190. The product is extracted with 
 10 per cent, aqueous sodium carbonate and the solution con- 
 centrated to the crystallising point. Sodium 2-aminotolyl-5- 
 arsinate separates and is washed with alcohol ; the nitrates are 
 concentrated and the crude secondary arsinic acid precipitated 
 by hydrochloric acid. The precipitate is dissolved in aqueous 
 sodium hydroxide and the sodium salt allowed to separate, after 
 which it is recrystallised from water. The acid, when boiled 
 with dilute sulphuric acid and potassium iodide, furnishes a 
 good yield of 5-iodo-o-toluidine. 
 
 The sodium salt, [NH 2 -C 6 H 3 (CH 3 )] 2 AsO-ONa,7|H 2 O, dissolves 
 in if times its weight of water to an alkaline solution ; it dissolves 
 very readily in alcohol. 
 
 186 
 
ATOXYL 
 
 Diacetyl-2 : 2 '-diaminotolyl-$-arsinic acid, 
 
 [CH 3 -CO-NH-C 6 H 3 (CH 3 )] 2 As-OH, 
 
 from hot water in refractive prisms, m.p. 242-244, containing 
 2/3H 2 O. The sodium salt is soluble in twice its weight of cold 
 water and is very soluble in alcohol ; it contains 6H 2 O. 
 
 Triaminotriarylarsine Oxides . x 
 
 A small yield of an uncrystallisable substance having the 
 properties of a triaminotriphenylarsine oxide was obtained by 
 prolonged boiling of aniline (750 grams) and arsenious chloride 
 (150 grams) in benzene (500 grams) or in toluene. This triamine 
 }delded a tribenzoyl and a triacetyl derivative melting respectively 
 at 130-140 and 140-150. 
 
 Section VIII. Mixed Aromatic-aliphatic p-Amino-arsinic Acids. 2 
 
 p-A minophenylmethylarsinic acid, 
 
 NH 2 -C 6 H 4 As(CH 3 )OOH, 
 
 crystalline powder, m.p. 201, is obtained by the general method 
 from ^>-aminophenylarsenious oxide and methyl iodide. The 
 iodine is preferably removed by the moist silver chloride method, 
 the arsinic acid obtained direct from the filtrate and crystallised 
 from alcohol-ether. 
 
 A cetyl-p-aminophenylmethylarsinic acid, 
 
 CO-CH 3 -NH-C 6 H 4 As(CH 3 )(>OH, 
 
 prepared in good yield by the general method, crystallises from 
 hot water in prisms melting at 260. 
 
 These secondary arsinic acids are all well crystallised compounds 
 extremely resistant to oxidation by the action of nitric acid. 
 
 Section IX. Nitro-derivatives of the Arsanilic Acids. 
 
 $-Nitro-2-aminophenylarsinic acid? 
 
 NH 2 
 \AsO(OH) 2 . 
 
 Although, as a rule, para-substituted aromatic bases give 
 
 1 Morgan and Micklethwait, Chem. Soc. Trans., 1909, 95, 1474. 
 
 2 Bertheim, Ber., 1915, 48, 350. 
 
 3 M.L. and 6.243693 and Eng. P., 29196/1911; &enda.,Ber., 1911,44,3294. 
 
 187 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 unfavourable results in the B6champ condensation (v. p. 178), 
 yet ^>-nitroaniline behaves exceptionally in giving a relatively 
 good yield of arsinic acid. This base (70 parts) is thoroughly mixed 
 with arsenic acid (20 parts) and heated to 210. Water distils 
 off ; the viscid mass is then added to water (250 parts) and ren- 
 dered alkaline with sodium carbonate (20 parts). The filtered 
 solution is saturated with salt, extracted with ether and then 
 carefully acidified with hydrochloric acid, when 5-nitro-2-amino- 
 phenylarsinic acid separates as a lemon - yellow powder 
 crystallising from hot water in yellow needles, m.p. 235-236. 
 It is readily soluble in ammonia, in alkali hydroxides, car- 
 bonates or acetates, or in warm alcohol ; sparingly soluble 
 in cold mineral acids. The diazonium compound, prepared 
 by adding sodium nitrite to the arsinic acid suspended 
 in acid, is almost colourless and couples readily to form 
 azo-derivatives. 
 2-Nitro-^-aminophenylarsinic acid 1 (6-Nitro-m-arsanilic acid) , 
 
 NH 2 
 
 <^ )>As0 8 H . 
 
 N0 2 
 
 3-Aminophenylarsinic acid (w-arsanilic acid) is converted 
 into its oxalyl derivative, which crystallises from water in 
 acicular aggregates. When dissolved in 3 parts by weight of 
 concentrated sulphuric acid and nitrated at o to 5 with the 
 calculated amount of nitric-sulphuric acid (26 per cent. HN0 3 ) 
 this oxalyl compound is converted into a nitro-derivative 
 isolated by pouring the mixture on to ice. 6-Nitro-3-amino- 
 phenylarsinic acid is prepared by boiling this product with 10 
 parts of 27V-hydrochloric acid when it separates from solution in 
 light yellow needles. By boiling this compound with strong 
 aqueous caustic potash, the amino-group is eliminated 
 and 2-nitro-5-hydroxyphenylarsinic acid is obtained, which, 
 with warm sodium hydrosulphite, undergoes reduction to 
 2 : 2 '-diamino-5 : 5 '-dihydroxyarsenobenzene, an isomeride of 
 salvarsan. 
 
 The mother liquors of the above nitration contain a very 
 small amount of the isomeric 2-nitro-3-aminophenylarsinic 
 acid. 
 
 1 M.L. and B., D.R.-P., 261643. 
 
 188 
 
ATOXYL 
 
 z-Nitro-^-aminophenylarsinic acid, l 
 
 NH,/ \\sO(OH) a . 
 
 [0 2 
 
 2-Nitro-4-acetyl-^-phenylenediamine 2 (4 kilos.) dissolved in 
 concentrated hydrochloric acid (10 litres) and water (15 litres) 
 is diazotised with sodium nitrite and treated with sodium arsenite 
 (5 grams) in 10 litres of water, the mixture being gradually warmed 
 by the introduction of steam. So soon as the diazo-reaction has 
 disappeared, the filtered solution is heated in a reflux apparatus 
 for several hours, when 2-nitro-4-aminophenylarsinic acid 
 separates on cooling in orange-yellow needles, darkening at 240, 
 decomposing at 258. This compound is sparingly soluble in 
 cold water, dilute mineral acids, or alcohol, dissolving more 
 readily in methyl alcohol, glacial acetic aci'd, alkalis or sodium 
 acetate. The acetyl derivative which arises as an intermediate 
 product in the foregoing reaction crystallises in yellowish-white, 
 acicular crystals readily soluble in hot water, alcohol, glacial 
 acetic acid, or alkalis, and only sparingly so in dilute mineral 
 acids. 
 z-Nitro-^-aminophenylarsinic acid? 
 
 NH 2 NO 2 
 
 / \AsO(OH) 2 . 
 
 The compound is obtained indirectly from w-aminophenylarsinic 
 acid, which is converted into urethane derivative, 
 AsO(OH) a -C 6 H 4 -NH-C0 2 -C 2 H 6 , 
 
 by adding ethyl chlorocarbonate to its solution in dilute hydro- 
 chloric acid at o to 5. This product is precipitated with more 
 hydrochloric acid ; it crystallises from hot water in well-defined 
 needles, decomposing at 180. 
 
 This urethane derivative (289 grams) is dissolved in 5 parts of 
 cold concentrated sulphuric acid and nitrated at o to 5 with 245 
 grams of nitric-sulphuric acid (26 per cent. HNO 3 ). After an 
 hour at 15 the solution is poured on to ice, when the nitro- 
 urethane derivative slowly separates as a yellow, crystalline 
 powder, sparingly soluble in water, dissolving easily in alkalis 
 to yellowish-red solutions. This product is hydrolysed by heating 
 with 8-10 parts of concentrated sulphuric acid at 70-80 until the 
 
 1 M.L. and B., D.R.-P., 267307. 2 Ber., 1897, 30, 980. 
 
 3 M.L. and B., D.R.-P., 256343. 
 
 l8q 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 evolution of carbon dioxide ceases, when the solution is poured 
 on to ice. 2-Nitro-3-aminophenylarsinic acid separates and is 
 purified by dissolving in dilute aqueous alkali, and reprecipitating 
 with acid it forms orange-yellow needles sparingly soluble in 
 hot water or in dilute mineral acids. 
 ^-Nitro-^-aminophenylarsinic acid, l 
 
 N0 2 
 
 NH/ \\sO(OH) 2 . 
 
 The nitration of acetyl-^-arsanilic acid does not proceed smoothly 
 and no homogeneous nitro-product is obtainable, but the reaction 
 is readily effected with oxalyl-_/>-arsanilic acid (p. 161) . A mixture 
 of 26 c.c. of nitric acid (D 1-4) and 26 c.c. of concentrated 
 sulphuric acid is slowly added with stirring to 115-6 grams of 
 oxalyl-^>-arsanilic acid in 300 c.c. of concentrated sulphuric acid 
 at 10-20. The strongly acidic solution is then added to 1500 c.c 
 of water, when a white, crystalline mass of the mononitro-com- 
 pound, CO 2 H-CO-NH-C 6 H 3 (NO 2 )-AsO(OH) 2 , separates. The mix- 
 ture is boiled in a reflux apparatus for one hour and the yellow solu- 
 tion filtered, when 3-nitro-4-aminophenylarsinic acid separates on 
 cooling as a bulky precipitate of pale sulphur-yellow needles. 
 It is moderately soluble in methyl alcohol or 50 per cent, acetic 
 acid, sparingly so in glacial acetic acid or acetone, and 
 dissolves readily in aqueous alkalis or hot concentrated hydro- 
 chloric acid. 
 
 3-Nitro-4-aminophenylarsinic acid is also prepared through the 
 urethane derivative of ^>-arsanilic acid. 
 
 Urethane derivative, C 2 H 5 -OCO.NH-C 6 H 4 -AsO(OH) 2 . />-Arsanilic 
 acid (217 grams) and 57 grams of caustic soda solution (D = 1-375) 
 are dissolved in I litre of ice-cold water and treated with 130 
 grams of ethyl chlorocarbonate and 114 grams of caustic soda solu- 
 tion (D = 1-375) so that the liquid remains alkaline. The urethane 
 is precipitated by acid in felted needles, decomposing at 230-240. 
 This compound (289 grams) dissolved in 1500 grams of concen- 
 trated sulphuric acid is treated at 0-5 with 245 grams of con- 
 centrated nitric-sulphuric acids containing 26 per cent. HNO 3 . 
 The mixture is stirred at 15 for half an hour and then poured 
 on to ice, when the nitro-urethane derivative separates as a pale 
 yellow powder crystallising from alcohol in yellowish needles, 
 sparingly soluble in hot water and dissolving readily in aqueous 
 
 1 M.L. and B., D.R.-P., 231969, 232879; Bertheim, Ber., 1911, 44 
 
 3093- 
 
 190 
 
ATOXYL 
 
 alkalis to an intensely yellow solution. It is hydrolysed by heating 
 at 60-80 with 10 parts of concentrated sulphuric acid till all 
 the carbon dioxide has been evolved. The solution is then poured 
 on to ice and the crude 3-nitro-4-aminophenylarsinic acid crystal- 
 lises from dilute acetic acid in yellow needles, deflagrating on 
 heating. 
 
 3-Nitro-4-aminophenylarsinic acid 1 is also obtained by heating 
 o-nitroaniline and arsenic acid at 200-210 for ten minutes, being 
 extracted from the mixture with 10 per cent, aqueous caustic soda 
 and reprecipitated by acid. Crystallised from hot water it is a 
 yellow, microcrystalline powder soluble in the ordinary organic 
 solvents. When treated with hydriodic acids it yields succes- 
 sively 2-nitro-i-aminophenylarsenious iodide and 4-iodo-2-nitro- 
 aniline. 
 
 3 : 5-Dinitro-p-arsanilic acid, 2 
 
 N0 
 
 N0 2 
 
 ^-Arsanilic acid (44 grams) dissolved at 5-10 in concentrated 
 sulphuric acid (120 c.c.) is nitrated with 56 grams of mixed nitro- 
 sulphuric acid (447 per cent. HNO 3 ), the temperature rising to 
 10-15. After three hours the mixture is added to 500 grams of 
 ice ; the solid product consists of 3 : 5-dinitro-/>-arsanilic acid and 
 2:4: 6-trinitroaniline, the latter being removed by ether whilst 
 the liquid contains />-diazobenzenearsinic acid. 
 
 3 : 5-Dinitro-^>-arsanilic acid purified by dissolving in alkali, 
 reprecipitating by mineral acid and crystallising from 50 per cent . 
 acetic acid, separates in brownish-yellow needles or leaflets. 
 
 With 40-50 per cent, caustic potash this dinitro-compound 
 develops a violet coloration changing to brownish-red. It is not 
 diazotisable and gives no characteristic coloration with alcoholic 
 potash. Bromine added to an alkaline solution removes the 
 arsenical group, producing 4-bromo-2 : 6-dinitroaniline. 
 
 Nitro-derivatives of p-Dimethylaminophenylarsinic Acid? 
 
 ^-Dimethylaminophenylarsinic acid nitrates smoothly to a 
 series of definite compounds, and in this respect differs greatly 
 
 1 Mameli, Boll. Chim. Farm., 1909, 48, 682. 
 
 2 Benda, Ber., 1912, 45, 53. 
 
 3 Poulenc and K. Oechslin, Fr. P., 449373, 451078 ; Cf. Eng. P., 
 22521/1914- 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 from />-arsanilic acid, the nitro-derivatives of which are obtainable 
 only by a circuitous route, generally through the oxanilido- 
 compound. The importance of these nitrations lies in the facts 
 that (i) ^-dimethylaminophenylarsinic acid is readily prepared 
 from easily accessible reagents, dime thy laniline and arsenious 
 chloride ; (2) the dimethylamino-complex is removable quanti- 
 tatively by hydrolysis, the products being nitrophenolarsinic 
 acids available for the preparation of salvarsan and its analogues 
 (v. p. 230).! 
 ^-Dimethylamino-^-nitrophenylarsinic acid, 
 
 (CH 3 ) 2 N/ \AsO(OH) a> 
 
 ' 
 
 golden - yellow needles, m.p. 204, sparingly soluble in alcohol 
 or hot water. In its preparation a mixture of nitric acid 
 (D 1-49, 35 grams) and 60 per cent, sulphuric acid (150 grams) 
 is added slowly to ^-dimethylaminophenylarsinic acid (100 grams) 
 dissolved in 60 per cent, sulphuric acid (250 grams). The 
 temperature is allowed to rise to 35-40 ; the mixture is main- 
 tained for half an hour at 30-35, and then poured on to broken 
 ice. The yellow precipitate is dissolved in aqueous sodium 
 carbonate, reprecipitated from the filtered solution by very 
 dilute mineral acid, and the product purified further by crystal- 
 lisation from hot water. When heated with dilute aqueous 
 sodium hydroxide this compound is hydrolysed to 3-nitro-4- 
 hydroxyphenylarsinic acid (v. p. 201). The foregoing nitration 
 may also be effected in concentrated sulphuric acid by keeping 
 the temperature below 15 ; the same proportions of reagents 
 are employed, and the purification is carried out in a similar 
 manner. 
 
 ^.-Methylnitrosoaminophenylarsinic acid, 
 
 N0 \ y \ 
 
 >N-<; >AsO(OH) 2 , 
 
 almost colourless crystals, decomposing at 190, obtained by 
 nitrating ^-dimethylaminophenylarsinic acid in more dilute 
 solutions. A solution of sodium nitrate (190 grams) in i litre 
 of sulphuric acid (i to 4) is added to 500 grams of p-di- 
 methylaminophenylarsinic acid in 2 litres of dilute sulphuric 
 acid (i to 4), the mixture being slowly heated to 85-90. The 
 
 1 Meyer and Oechslin, Fr. P., 474056. 
 192 
 
ATOXYL 
 
 yellow solution assumes a brown colour, and after one hour 
 the liquid is allowed to cool, when the nitrosoamine separates 
 in yellowish-brown, spear-shaped crystals. This product is 
 dissolved in aqueous sodium carbonate and reprecipitated from 
 the filtered solution by dilute mineral acid. The mother liquor 
 from which the nitrosoamine has separated contains a certain 
 amount of the preceding nitro-compound. 
 
 In the first of the patents cited and in the provisional 
 specification of the English patent this nitrosoamine is 
 described as an isomeric dimethylaminonitrophenylarsinic acid 
 (v. p. 191). 
 
 4-Methylnitrosoaminophenylarsinic acid 1 is prepared in a 
 state of purity and free from nitro-compounds by adding sodium 
 nitrite (84 grams) in 500 c.c. of 60 per cent, sulphuric acid to 
 ^-dimethylaminophenylarsinic acid dissolved in 300 c.c. of 
 60 per cent, sulphuric acid at o. The reaction is accompanied 
 by evolution of gas, and the liquid when poured on to ice gives 
 a precipitate of the almost colourless nitrosoamine. The concen- 
 tration of the sulphuric acid may be varied considerably, or it 
 may be replaced by hydrochloric acid. 
 
 Isomeric ^-Dimethylaminodinitrophenylarsinic Acids. 
 
 Nitric acid (1400 c.c. of 30 per cent. HNO 3 ) is added 
 to 100 grams of ^-dimethylaminophenylarsinic acid in 600 c.c. 
 of dilute sulphuric acid (i to 4). The mixture is heated at 40 
 for two hours, then left in the cold for three days, when a golden- 
 yellow precipitate is obtained. This product dissolved in aqueous 
 sodium carbonate, reprecipitated by dilute sulphuric acid and 
 crystallised from hot water, alcohol, or acetone, separates in 
 rosettes of bright yellow, prismatic crystals and melts at 161 
 with decomposition. 
 
 The mother liquor from the yellow dinitro-compound yields 
 small, red, four-sided plates, less soluble than the yellow 
 compound in hot water, and melting with decomposition at 
 158. Both products are dinitro-compounds, but it has 
 not been ascertained whether they are chromo-isomerides 
 having the same orientation of substituent groups or whether 
 the nitro-groups occupy different positions in the aromatic 
 nucleus. 
 
 1 Poulenc, Eng. P., 22522/1914, Fr. P., 479646. 
 
 193 o 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The amyl ester of N-nitrosophenylmethylglycine-^-arsinic acid, 
 
 /NO 
 AsO(OH) 2 -<( >N< 
 
 \CH 2 -C0 2 -C 6 H U 
 
 colourless crystals from hot dilute acetic acid (i : 4) decomposing 
 at 150, is prepared by adding sodium nitrite to phenylmethyl- 
 glycine-4-arsinic acid in dilute sulphuric acid. The intermediate 
 product is obtained by warming dimethylaniline with amyl 
 chloroacetate when methyl chloride is eliminated. These 
 nitrosoamines of phenylarsinic acid lose the nitroso-group by 
 heating with strong hydrochloric acid and yield 7V-monoalkyl- 
 aminophenylarsinic acids. On reduction they yield hydrazine 
 derivatives. 
 
 Ortho- and Meta-nitro-derivatives of Phenylalkylglycinearsinic 
 Acids and their Reduction Products.* 
 
 The phenylalkylglycinearsinic acids and their C-esters 
 (esterified in the glycine group) are readily nitrated in sulphuric 
 acid, and the orientation of the nitro-group depends on the 
 concentration of this acid. 
 
 The following esters are produced by nitrating the C-amyl 
 ester of phenylmethylglycinearsinic acid. 
 
 \ 
 
 AsO(OH) N(CH,)-CH 2 -CO a -C 6 H n . 
 
 NOT' 
 
 I. 
 
 AsO(OH)/ ^>N(CH 3 ) CH.-CCVC.Hn. 
 ~ 
 
 II. 
 
 No. I. is produced by adding nitric acid (i mol.) in 30 grams of 
 sulphuric acid (3 : 2) to the C-amyl ester (50 grams) dissolved in 
 228 grams of strong sulphuric acid and 152 grams of water. It is 
 an intensely yellow substance, sparingly soluble in hot water, dis- 
 solving easily in alcohol, and melting at 130. No. II. is produced 
 by adding nitric acid (i mol.) in 30 grams of sulphuric acid (i : 3) 
 to the C-amyl ester (50 grams) dissolved in 300 grams of 
 sulphuric acid and 100 grams of water. When hydrolysed with 
 excess of aqueous sodium hydroxide these esters yield the corre- 
 sponding free glycinearsinic acids. These substances behave 
 very differently on reduction with alkaline sodium hydrosulphite. 
 1 Poulenc and K. Oechslin, Fr. P., 473705. 
 194 
 
ATOXYL 
 
 The free acid of No. I. gives rise to the reduction product III., 
 whilst the acid of No. II. furnishes an internal amide which is 
 
 NH 2 
 
 AS-/ NNCCH,) -CH 2 -co a H 
 
 ii \ / 
 
 As-/~ ~V( CH 3KH 2 -C0 2 H 
 
 
 NH a 
 
 III. 
 
 AS v. yk V/iA 2 
 
 \NH-(io 
 /CH, 
 
 As-/" "V \-CH t 
 
 IV. 
 
 insoluble in the acids, alkalis, and ordinary organic solvents. 
 Reduction product No. III. is soluble in alkalis and its alkali 
 salt is precipitated by alcohol. 
 
 Section X. Diaminophenylarsinic Acids. 
 
 2 : ^-Diaminophenylarsinic acid, 1 (NH 2 ) 2 C 8 H 3 -AsO 3 H 2 , melting 
 and decomposing at 205-208, is produced by the mild reduction 
 of 2-nitro-3-aminophenylarsinic acid (p. 189) with sodium 
 hydrosulphite at the ordinary temperature. This diamine gives 
 an azoimide with nitrous acid. 
 
 3 : ^.-Diaminophenylarsinic acid, 2 
 
 AsO 3 H 2 AsO 3 H 2 
 
 /\ 
 
 -NH-v 
 
 \ X CO 
 
 x_NH-/ 
 
 I. II. 
 
 3-Nitro-4-aminophenylarsinic acid is reduced with alkaline 
 hydrosulphite at 1, the temperature rising to -{-28. After 
 boiling with animal charcoal the filtered solution is cooled, 
 
 1 M. L. and B., D.R.-P., 256343. * Bertheim, Ber., 1911, 44, 3092. 
 
 195 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 neutralised with hydrochloric acid, and concentrated when 
 3 : 4-diaminophenylarsinic acid (I.) separates in colourless prisms 
 containing JH 2 0. The product behaves as a typical orthodiamine 
 yielding with nitrous acid a diazoimine, with phosgene a 
 carbamide derivative II., and with phenanthraquinone an azine. 
 
 This diamino-acid is 25 times less toxic than atoxyl ; it 
 exhibits a healing effect in sleeping sickness, but the curative 
 dose produces certain nervous disorders as a secondary action. 
 
 p-Phenylenediaminearsinic acid,' 1 
 
 XT 
 
 NH 2 
 
 > 
 
 \/ \/ V 
 
 NH 2 NH 2 NH 2 
 
 I. II. III. 
 
 5-Nitro-2-aminophenylarsinic acid (78 grams) dissolved in water 
 (900 c.c.) and loN-sodium hydroxide (480 c.c.) is treated 
 slowly with 500 c.c. of 20-6 per cent, ferrous chloride solution, 
 the mixture being kept alkaline to turmeric. The nitrate treated 
 with sulphuric acid until it turns Congo red paper brown slowly 
 deposits ^>-phenylenediaminearsinic acid in colourless needles 
 soluble in hot water, dilute mineral acids, alkalis, or aqueous 
 sodium acetate, but dissolving only sparingly in alcohol. At 
 210-215 it decomposes ; when exposed to light it assumes a 
 violet tint. When diazotised it requires only one molecular 
 proportion of nitrite ; its diazo-derivative II. couples readily 
 with resorcinol and /3-naphthol, but only slowly with R-salt. 
 The aqueous solution of diazo-compound when treated in the cold 
 with alcohol and copper powder is decomposed, yielding 
 w-arsanilic acid, which is purified by diazotising, coupling with 
 alkaline /?-naphthol and reducing the azo-derivative with alkaline 
 hydrosulphite. 
 
 Section XI. The Hydroxyphenylarsinic Acids. 
 Phenol-p-arsinic Acid and its Homologues. 2 
 
 An extension of Bechamp's reaction to phenol showed that 
 arsenic can be introduced into the aromatic nucleus of this 
 compound under experimental conditions similar to those 
 obtaining in the ^-arsanilic acid condensation. 
 
 1 Benda, Ber., 1911, 44, 3300 ; M. L. and B., D.R.-P., 248047. 
 
 2 M. L. and B., D.R.-P., 205616. 
 
 196 
 
ATOXYL 
 
 Phenol-p-arsinic acid, 
 HO< 
 
 Phenol (94 parts) and crystallised arsenic acid (151 parts) 
 are stirred together and heated at 150 for four hours. The dark 
 mass obtained is extracted with 1,000 parts of warm water and 
 the filtered solution evaporated in a vacuum and the residue 
 extracted repeatedly with cold acetone. After evaporating 
 off this solvent the crude arsinic acid is left as an oil which 
 gradually solidifies. It crystallises from glacial acetic acid in 
 small, yellow prisms, decomposing at 173-174 ; it is readily 
 soluble in cold water, alcohol, acetone, or dilute mineral acids, 
 and slightly soluble in ether or ethyl acetate. The alkali salts 
 are readily soluble in water and crystallise in needles from 
 alcohol. 1 They are useful in purifying the crude free acid, which 
 is otherwise inclined to remain syrupy. This acid is identical 
 with the compound obtained by boiling the diazo-derivative of 
 ^-arsanilic acid with acidified water. Hence it is the para- 
 compound. Sodium nitrite (74 parts) is added to ^-arsanilic 
 acid (217 parts) in 4,000 parts of 5 per cent, sulphuric acid, the 
 solution being heated on the water-bath till all the nitrogen is 
 evolved. The sulphuric acid is removed with barium hydroxide, 
 the filtrate evaporated to dryness invacuo, and the residue extracted 
 with dilute alcohol; the sodium salt crystallising from this 
 medium is decomposed with the calculated amount of sulphuric 
 acid, and the free phenol-^-arsinic acid is extracted with acetone 
 from the residue after evaporation. 2 
 
 A third method of preparation of phenol-^>-arsinic acid is 
 available, based on Bart's reaction. ^-Aminophenol is diazotised 
 in hydrochloric acid and warmed with alkaline sodium arsenite. 
 The neutralised solution is filtered, boiled with animal charcoal, 
 and concentrated ; sodium phenol-^>-arsinate separates and is 
 crystallised from alcohol. 3 
 
 o-Cresol-^-arsinic acid, H0< \AsO(OH) a . o-Cresol 
 
 (108 parts) and 151 parts of powdered arsenic acid are 
 thoroughly mixed and heated to 140. A reaction sets in 
 and the mass, which soon solidifies, is heated for 15 minutes, 
 
 1 Mouneyrat, Eng. P., 3087/1915 ; Kay, Eng. P., 6322/1915. 
 
 2 M. L. and B., D.R.-P. 205616. 3 D.R.-P., 250264, 268172. 
 
 197 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 cooled, powdered, and extracted with aqueous sodium carbonate. 
 The aqueous solution is extracted with ether to remove unaltered 
 o-cresol, then rendered acid to Congo red and evaporated to 
 dryness in a vacuum. The arsinic acid is extracted from the 
 residue with acetone, and after removing this solvent the crude 
 product is crystallised from glacial acetic acid, when it separates 
 in yellowish crystals, sintering at 150 and decomposing at 
 172 ; o-cresol-4-arsinic acid is sparingly soluble in cold water, 
 insoluble in benzene, but readily soluble in alcohol, acetone, 
 aqueous alkalis, or mineral acids. o-Cresol-4-arsinic acid is also 
 prepared by boiling in acidified water the diazo-compound of 
 2-aminotolyl-5-arsinic acid ; this preparation melts at 180, 
 but in all other respects is identical with the product of the 
 Bechamp condensation. 1 
 
 m-Cresol-4-arsinic acid, H0<^ \A.sO(OH) 2 , is prepared as 
 
 ~ru 
 CH 3 
 
 in the foregoing example, the condensation occurring at 170 ; 
 it sinters at 160, decomposes at 183-185, and resembles the 
 preceding isomeride in its physical and chemical properties. 
 
 a-Naphthol-^-arsinic acid, 2 HO-C 10 H 6 -AsO(OH) 2 , colourless 
 leaflets or needles, is produced by adding an ice-cold solution 
 of sodium nitrite (250 grams) to a solution of one kilogram of 
 i-aminonaphthyl-4-arsinic acid dissolved at 5 in 10 litres of 
 15 per cent, sulphuric acid. Steam is blown in to decompose 
 the diazo-compound, the red product is converted into sodium 
 salt, the latter precipitated with alcohol and decomposed with 
 acid. The free acid is readily soluble in hot water or alcohol, 
 but insoluble in ether, chloroform, or petroleum ; its alkali salts 
 are readily soluble in water, its salts with the heavy metals 
 are insoluble. The sodium salt crystallises from alcohol in well- 
 defined; colourless needles. 
 
 2 -Hydroxy-i : $-benzarsinic acid 3 (salicyl-^-arsinic acid), 
 
 HO/ \AsO(OH) 2 , 
 
 colourless needles, m.p. over 300, is prepared by the following 
 series of reactions : 2-acetylaminotolyl-5-arsinic acid is oxidised 
 by alkaline permanganate to 2-acetylamino-i : 5-benzarsinic acid ; 
 
 1 Benda and Kahn, Ber., 1908, 41, 1678. 
 ~ O. and R. Adler, Ber., 1908, 41, 933. 
 
 3 W. Adler, D.R.-P., 215251.; O. and R. Adler, Ber., 1908, 41, 933. 
 
 198 
 
ATOXYL 
 
 the latter is hydrolysed to 2-amino-i : 5-benzarsinic acid with hot 
 10 per cent, caustic soda. The amino-compound is diazotised 
 in dilute sulphuric acid, and the diazo-compound decomposed 
 by blowing steam into the solution. On concentrating this 
 solution 2-hydroxy-i : 5-benzarsinic acid separates and is purified 
 by crystallisation from hot water or alcohol. It is moderately 
 soluble in methyl alcohol or acetone. Its alkali salts are very 
 soluble and are precipitated in crystalline form by alcohol ; 
 the copper, iron, silver, and barium salts are sparingly soluble 
 in hot water. The sodium salt is less toxic than atoxyl. 
 
 Under the name of " enesol," mercuric salicylarsinate has 
 been employed in the combined arseno-mercurial treatment of 
 syphilis. 
 
 2 : ^-Dihydroxyphenylarsinic acid (Resorcinolarsinic acid) , 
 
 HO/ \\sO(OH) 2 HO/ \AsO(OH) 2 . 
 
 ~~OH ~~OCH, 
 
 I. II. 
 
 This acid I. is prepared by heating resorcinol with arsenic 
 acid for two days on the water-bath, the solid product being 
 recrystallised from dilute acetic acid, 
 
 CH 8 0<^~ "\AsO(OH) 2 . 
 
 ~~OCH 3 
 III. 
 
 2-Methoxy-4-hydroxyphenylarsinicacid (II.) and 2\^-dimethoxy 
 phenylarsinic acid (III.) are prepared by heating the corre- 
 sponding mono- and cli-ethers of resorcinol with arsenic acid 
 at 100 for several days. 1 
 
 3 : ^-Dihydroxyphenylarsimc acid, 2 
 
 AsO(OH) 2 . 
 OHT 
 
 Phenol-4-arsinic acid (120 grams) in 1800 c.c. of water is treated 
 successively with ioiV-caustic soda (200 c.c.) and 135 grams of 
 powdered potassium persulphate . After being stirred for 48 hours 
 the liquid is mixed with 650 c.c. of hydrochloric acid (D = I 12) 
 and heated to boiling for 15 minutes. The solution is mixed 
 with concentrated ammonia (500 c.c.) and excess of magnesia 
 mixture, stirred at the ordinary temperature with animal charcoal, 
 
 1 Bauer, Ber., 1915, 48, 509; cf. M. L. and B., D.R.-P., 272690. 
 a M. L. and B., D.R.-P., 271892. 
 
 199 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 filtered, and heated to boiling, when magnesium 3 : 4-dihydroxy- 
 phenylarsinate separates as a microcrystalline powder. The 
 free acid is obtained by mixing IT grams of the salt with 13 c .c. 
 of hydrochloric acid (D = 1-12), when it crystallises out on stirring. 
 This arsinic acid is extremely soluble in water, and differs from 
 phenol-4-arsinic acid in its powerful reducing action on cold 
 ammoniacal silver solution, and by giving with acid ferric chloride 
 the green coloration characteristic of a catechol derivative. 
 4 : q'-Dihydroxydiphenylarsinic acid, 
 
 OH. 
 
 4 : 4 / -Diaminodiphenylarsinic acid (p. 185} is diazotised in dilute 
 hydrochloric or sulphuric acid, and the diazo-derivative de- 
 composed in solution by blowing in steam. The solution is 
 then saturated with sodium chloride and the acidity diminished 
 by adding sodium acetate. The dihydroxyarsinic acid, which is 
 thus precipitated, is crystallised from 50 per cent, acetic acid, 
 when it separates in thin plates with cracked surfaces, m.p. 239. 
 It is readily soluble in boiling water, warm N-hydro chloric acid, 
 alcohol, or glacial acetic acid. Magnesia mixture gives no pre- 
 cipitate. 1 
 
 2 : 2 '-Dihydroxyditolyl-5-arsinic acid, HOAsO(C 6 H 4 -OH) 2 , 
 colourless, crystalline powder from 75 per cent, acetic acid, 
 m.p. 247, is prepared by a similar process to that of the former 
 compound from 2 : 2 '-diaminoditolyl-5-arsinic acid, but, being less 
 soluble, it is precipitated without the use of sodium chloride. 
 It is only sparingly soluble in hot water, but dissolves more 
 readily in warm alcohol, hot glacial acetic acid, or Af-hydrochloric 
 acid, 
 
 Section XII. Nitro-derivatives of the Hydroxyphenylarsenic 
 
 Acids. 
 3-Nitro-4.-hydroxyphenylarsinic acid 2 (z-Nitrophenol-^-arsinic 
 
 acid), 
 
 NO 2 
 
 A mixture of 39 c.c. of nitric acid (D = 1-4) and 39 c.c. 
 
 1 Benda, Per., 1908, 41, 2371. 
 
 2 M. L. and B., D.R-.P., 224953 ; Benda and Bertheim, Ber., 1911, 44, 
 3445, 3451- 
 
 2OO 
 
ATOXYL 
 
 of concentrated sulphuric acid is added slowly to a solution 
 of 144 grams of sodium phenolarsinate, HO-C 6 H 4 -As(OH)-ONa, 
 dried at 80 and dissolved in 450 c.c. of concentrated 
 sulphuric acid at o. After the addition of the nitric acid 
 the temperature is allowed to rise to -fio and the acid 
 solution poured into 2,250 c.c. of cold water. 3-Nitro-4- 
 hydroxyphenylarsinic acid, collected after 24-48 hours, is a 
 yellowish-white powder deflagrating on heating ; it is moderately 
 soluble in hot water, and dissolves readily in alcohol, acetone, or 
 glacial acetic acid. Its soluble alkali salts are intensely yellow. 
 Yield 65-75 per cent, of the calculated quantity. This compound 
 is also obtainable from 3-nitro-4-aminophenylarsinic acid by 
 warming the latter with aqueous caustic potash (D = 1-324) at 
 80 until it is no longer diazotisable. The solution is diluted with 
 water and saturated with hydrogen chloride, when 3-nitro-4- 
 hydroxyphenylarsinic acid separates. 1 Furthermore, 3~nitro-4- 
 hydroxyphenylarsinic acid can be synthesised by Bart's diazo- 
 reaction from alkaline arsenite and diazotised o-nitro-^>-amino- 
 phenol. 2 
 
 3-Nitro-4-hydroxyphenylarsinic acid 3 can be obtained by a 
 third process from the readily prepared 4-dimethylaminopheny]- 
 arsinic acid, which is smoothly nitrated to 4-dimethylamino-3- 
 nitrophenylarsinic acid (p. 192) . This nitro-compound (500 grams) 
 is dissolved in aqueous potassium hydroxide (500 grams KOH 
 to 1,500 c.c. H 2 O), and the solution maintained at 80-90 until the 
 mixture becomes nearly solid ; ice-cold water (2,000 c.c.) and 
 concentrated hydrochloric acid are added successively, the 
 precipitate is dissolved in hot water, and the filtered solution 
 treated with sodium acetate (i mol.) and washed animal charcoal. 
 The final filtrate is acidified with hydrochloric acid, when 3-nitro~4- 
 hydroxyphenylarsinic acid separates either in yellow, rhombo- 
 hedral plates or in tufts of almost colourless needles. The fore- 
 going preparations also exhibit this dimorphism. 
 
 3-Nitro-2-hydroxytolyl-$-arsinic acid, 
 
 HO- 
 
 a yellowish-white powder intumescing on heating, is produced as 
 
 1 M. L. and B., D.R.-P., 235141. 2 Bart, D.R.-P., 250264. 
 
 3 Oechslin and Poulenc, Fr. Pat., 451078. 
 
 201 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 in the foregoing nitration. It is sparingly soluble in cold water, 
 dissolving more readily in hot water, alcohol, or glacial acetic 
 acid ; yield 90 per cent. 
 
 ^-Nitro-2 -hydroxyphenylarsinic acid, 
 
 OH 
 
 _ 
 
 i \ 
 
 AsO(OH) a , 
 
 pale yellow crystals from alcohol, decomposing violently on 
 heating ; prepared by Bart's method by diazotising 4-nitro-2- 
 aminophenol in hydrochloric acid and warming the diazo- 
 solution with alkaline sodium arsenite till the diazo-nitrogen 
 is all evolved. The solution is neutralised, filtered, and evaporated 
 to dryness with excess of hydrochloric acid. The residue is 
 extracted with alcohol, and the solution boiled with animal 
 charcoal and evaporated to the crystallising point. 1 
 2-Nitro-^-hydroxyphenylarsinic acid, z 
 
 OH NO a 
 / )>AsO(OH) 2 , 
 
 is produced by heating the corresponding nitroamino-acid 
 (p. 189) with strong caustic potash solution. On exhaustive 
 reduction with sodium hydrosulphite this compound is con- 
 verted into 2 : 2 f -diamino-3 : z'-dihydroxyarsenobenzene, an 
 isomeride of salvarsan base. 
 5-Nitro-2-hydroxyphenylarsinic acid, 
 
 AsO 3 H a AsO s H 2 
 
 /\, 
 
 NO 2 
 
 NO 5 
 
 NO 2 
 
 I. II. 
 
 5-Nitro-2-aminophenylarsinic acid (20 grams), when warmed 
 with 90 c.c. of potassium hydroxide solution (36 Be".), loses 
 ammonia and passes into the intensely yellow dipotassium salt 
 of 5-nitro-2-hydroxyphenylarsinic acid. The monopotassium 
 salt is obtained by adding hydrochloric acid to an ice-cold solution 
 of the dipotassium salt, when it separates in almost colourless 
 needles or leaflets containing iH 2 0. The free acid (I.) separates 
 
 1 Bart, D.R.-P., 250264. 2 M. L. and B. ( D.R.-P., 256343. 
 
 202 
 
ATOXYL 
 
 from more strongly acidified solutions of the foregoing salts in 
 the form of amber-yellow crystals sparingly soluble in cold 
 water ; it decomposes at 247-248. 
 
 3 : 5-Dinitro-2-hydroxyphenylarsinic acid (II.) x separates in the 
 form of pale yellow needles (m.p. 237-238) on pouring on to 
 ice the product of the nitration of the foregoing compound with 
 nitric and sulphuric acids. Its solution in alkali is even more 
 intensely coloured than that of the mononitro-compound, and 
 addition of a little hydrosulphite develops a deep red coloration 
 due to reduction to nitroamino-derivatives. 
 
 3 : ^-Dinitro-^-hydroxyphenylarsinic acid 2 (2 : 6-Dinitrophenol-^- 
 arsinic acid), 
 
 AsO(OH) a , 
 
 HO/ 
 
 NO 
 
 lustrous, pale yellow leaflets decomposing with a flash on heating, 
 sparingly soluble in cold water, and dissolving easily in hot water 
 or methyl alcohol to a yellow solution. Prepared by nitrating 
 phenol-^>-arsinic acid with excess of nitric acid (D = 1-52) in 
 concentrated sulphuric acid at 15-20. Its alkaline solution is 
 reddened by sodium hydrosulphite (distinction from mononitro- 
 phenol-^>-arsinic acid). This acid is also produced by heating 
 3 : 5-dinitro-^-arsanilic acid with 10 per cent, caustic potash at 
 90 until ammonia is eliminated, the product being precipitated 
 on adding hydrochloric acid. 3 It dyes wool in clear yellow 
 shades much more intense than those obtained by means of the 
 isomeric 3 : 5-dinitro-2-hydroxyphenylarsinic acid. 4 
 
 4-Hydroxy-2-methylphenylarsimc acid 5 nitrates to yield 
 successively the following nitro-compounds :- - 
 
 AsO 3 H 2 
 
 and 
 
 NO, 
 
 NO 
 
 H 
 
 The second of these, on warming with aqueous caustic soda, 
 
 1 Benda, Ber., 1911, 44, 3294. 
 
 2 M. L. and B., D.R.-P., 224953 ; Benda and Bertheim, Ber., igii, 44, 
 3448. 3 Benda, Ber., 1912, 45, 58. 
 
 4 Benda, Ber., 1911, 44, 3296. 5 Karrer, Ber., 1915, 48, 307. 
 
 203 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 yields stilbene colouring matters; the former compound does 
 not undergo this change, and for this reason the nitro-group 
 is regarded as being in the 3-position rather than in the 
 5-position. 
 
 $-Nitro-2 : ^.-dihydroxyphenylarsinic acid [5-Nitroresorcinol- 
 arsinic acid (I.)], 
 
 NO 2 NO 2 
 
 HO/~ \AsO 3 H 2 HO/ \As0 3 H 2 , 
 
 OH N0 2 OH 
 
 I. II. 
 
 is prepared by nitrating resorcinolarsinic acid below o. Above 
 60 3 : $-dinitro-2 : ^-dihydroxyphenylarsinic acid (II.) is produced. 
 Alkaline hydrosulphite reduces the mononitro-compound to an 
 amino-acid of which the acetyl derivative is freely soluble in 
 water. Further reduction leads to 5 : 5 '-diamino-2 '.4:2' i^'-tetra- 
 hydroxyarsenobenzene, 
 
 The hydrochloride is freely soluble in water. Caustic soda 
 precipitates the base, which redissolves in excess to a solution 
 which becomes blue on exposure to air. The foregoing acetyl 
 compound dissolved in hypophosphorous acid containing a trace 
 of hydriodic acid becomes reduced to the diacetylated arseno- 
 benzene. 
 
 The dinitro-compound reduces to 3 : 5 : 3 ' : 5 '-tetramino- 
 2:4:2' : 4'-tetrahydroxyarsenobenzene, the hydrochloride of 
 which gives with alkalis the very oxidisable base soluble in 
 excess to solutions rapidly undergoing oxidation. 
 
 2-Methoxy-4-hydroxyphenylarsinic acid (p. 199) is reduced with 
 hypophosphorous acid containing potassium iodide to 2 : 2 '-di- 
 methoxy-4 : ^.'-dihydroxyarsenobenzene. The methoxy-compound 
 nitrates to $-nitro-2-methoxy-4-hydroxyphenylarsinic acid, which 
 on reduction with hydrosulphite gives the hydrochloride 
 of 5 : 5' '-diamino-2 : 2 r -dimethoxy-^ : ^.'-dihydroxyarsenobenzene. 
 This hydrochloride on boiling with water loses its arsenic, 
 yielding 2-aminoresorcinol-$-methyl ether. l 
 
 1 Bauer, Ber., 1915, 48, 509 ; cf. M. L. and B., D.R.-P., 272690. 
 
 204 
 
ATOXYL 
 
 Section XIII. Arsinic Acids of the Aminophenols. 
 
 ^-Amino-^-hydroxyphenylarsinic acid 1 (2-Amino-phenol-^ 
 arsinic acid], 
 
 AsO(OH) 2 , 
 
 colourless leaflets or minute prisms darkening and decomposing 
 at 170 without melting. Prepared by the action of reducing 
 agents on 3-nitro-4-hydroxyphenylarsinic acid. 
 
 Sodium amalgam (840 grams of 4 per cent. Na) is added to 
 the nitro-acid (31-6 grams) in 600 c.c. of methyl alcohol at 60-70. 
 About 5/6ths of the alcohol is distilled off, the residue taken up 
 with 120 c.c. of water, and after removing mercury, the solution 
 is acidified with 150 c.c. of hydrochloric acid (D = 1-19). After 
 twelve hours the impurity is filtered off, the filtrate boiled with 
 animal charcoal, and the clear solution treated with 52 c.c. of 
 loIV-caustic soda, when 3-amino-4-hydroxyphenylarsinic acid 
 crystallises. It is very slightly soluble in water or organic 
 solvents, but dissolves easily in ammonia, caustic or carbonated 
 alkali, or in mineral acids. Alkaline hypochlorite develops a 
 deep green coloration, whilst acid bichromate produces an 
 intense red coloration. 
 
 This reduction is also effected by adding with continuous stir- 
 ring 130-140 grams of dry sodium hydrosulphite to 2-nitro- 
 phenol-4-arsinic acid (66 grams) in 700 c.c. of water containing 
 125 c.c. of 2 J /V-sodium hydroxide. The hydrosulphite is added till 
 the yellow colour is destroyed, - and throughout reduction the 
 temperature is not allowed to exceed 30. The solution on 
 cooling to o, deposits 2-aminophenol-4-arsmic acid, especially 
 on seeding with crystals of the same substance. 
 
 The sodium salt, C 6 H 7 4 NAsNa, is very soluble in water 
 to a neutral solution and less so in alcohol ; it crystallises with 
 one or two molecules of water. 
 
 The urethane derivative, 
 
 OH 
 C 2 H 5 -OCONH/ \ 
 
 ~AsO 8 H 2 
 
 1 M. L. and B., D.R.-P., 224953 ; Ehrlich and Bertheim, U.S. P. 
 986148. Cf. Benda and Bertheim, Ber., 1908, 41, 1657 ; Bertheim and 
 Benda, Ber., 1911, 44, 3299. 
 
 205 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 is obtained by adding alkaline sodium arsenite and copper paste 
 to a diazotised solution of 5-amino-2-hydroxyphenylurethane. 1 
 
 3- A mino-2-hydroxytolyl-^-arsinic acid (3- A mino-o-cresol-^- 
 arsinic acid), 
 
 NH, 
 
 HO/ \AsO(OH) 2 , 
 
 CHT' 
 
 prepared in a similar manner to its lower homologue, is more easily 
 soluble in water than the latter and is salted out from aqueous 
 solution. 
 
 4-Amino-3-hydroxyphenylarsinic acid, 2 
 
 NH/" \AsO(OH) 2 , 
 OH~ 
 
 colourless crystals sparingly soluble in cold water or alcohol, 
 easily so in alkalis, ammonia, and excess of dilute acids, 
 prepared by reducing the azo-compound (p. 232) from 3-nitro- 
 4-aminophenylarsinic acid with alkaline sodium hydrosulphite, 
 and after removing the i-amino-a-naphthol, allowing the 
 solution to become oxidised by air or oxygen. On acidifying, 
 the arsinic acid is precipitated. 
 
 (^-Amino-2-hydroxyphenylarsinic acid 3~Aminophenol-6-arsinic 
 acid II.), 
 
 AsO 3 H 2 As0 3 H 2 AsO 3 H a 
 
 \/ \/ 
 
 NO, NH 2 NH-CO 2 -C 2 H 5 
 
 I. II. III. 
 
 i. From m-aminophenol. This compound is converted into 
 the carbethoxyl derivative by dissolving (2 mols.) in ether and 
 adding ethyl chlorocarbonate. 
 
 A violent reaction sets in and w-aminophenol hydrochloride 
 is precipitated, the nitrate is distilled, and carbethoxy-w-amino- 
 phenol (m.p. 97) is precipitated in the residue on adding light 
 petroleum. 
 
 Carbethoxy-3-aminophenol-6-arsinic acid (III.) is prepared by 
 heating on the water-bath for a week carbethoxy-m-aminophenol 
 and syrupy arsenic acid (83 per cent.). The hard product, after 
 
 1 Bart, D.R.-P., 268172. 
 
 2 M. L. and B., D.R.-P., 244166; Benda, Ber. 1911, 44, 3580. 
 
 206 
 
ATOXYL 
 
 washing with water to remove arsenic acid, is dissolved in aqueous 
 ammonia, and the liquid saturated with ammonia gas. The 
 ammonium salt separates and is converted into the free arsinic 
 acid (m.p. 213) by addition of mineral acid. 
 
 3-Aminophenol-6-arsinic acid is produced from the preceding 
 compound by alkaline hydrolysis (dilute NaOH) and precipitated 
 on addition of 2AT-sulphuric acid. Crystallised from water it 
 melts at 173. It is also soluble in the alcohols and in acetone. 
 
 2. From 3-nitro-6-aminophenol. This aminophenol (77 grams) 
 in hydrochloric acid (170 c.c. of D = 1-12) and 350 c.c. of water 
 is diazotised with sodium nitrite (36 grams) . The red, sparingly 
 soluble diazo-oxide is mixed with aqueous sodium arsenite (65 
 grams) and gradually rendered alkaline with 2AT-sodium hydroxide. 
 A dark solution results accompanied by elimination of nitrogen. 
 Acidification with hydrochloric acid throws down a slight im- 
 purity. The filtrate is rendered ammoniacal and heated to 
 boiling after adding magnesia mixture. The yellow magnesium 
 salt of the 3-nitrophenol-6-arsinic acid (I.) is precipitated and 
 treated with hydrochloric acid, when the free acid crystallises 
 out on rubbing (yield 72 grams); m.p. 250 with decomposition. 
 
 This nitro-compound when reduced with iron filings and dilute 
 acetic acid yields 3-aminophenol-6-arsinic acid (II.). 1 
 
 4~Dimethylamino-2-hydroxyphenylarsinic acid, 2 
 
 (CH 3 ) 2 N/~ \AsOJH,. 
 ~OH 
 
 2-Nitro-4-dimethylaminophenylarsinic acid (i part) is added 
 to 0-5 part of carbamide in 10 parts of 60 per cent, sulphuric 
 acid. Carbon dioxide and nitrogen are evolved, and after partial 
 neutralisation 4-dimethylamino-2-hydroxyphenylarsinic acid is 
 precipitated. 
 
 3 : $-Diamino~4-hydroxyphenylar$inic acid, 3 
 
 NH a 
 
 HO/ \AsO(OH) a , 
 X 
 
 silver grey needles darkening and decomposing at 170, easily 
 soluble in aqueous alkalis or dilute acids. Chromic acid develops 
 a dark olive green coloration. The diamino-acid is prepared by 
 reducing 3 : 5-dinitro-4-hydroxyphenylarsinic acid with sodium 
 amalgam or sodium hydrosulphite at low temperatures. 
 
 *H. Bauer, Ber. t 1915, 48, 1579. 2 Meyer and Oechslin, Fr. P., 474056. 
 
 :j M. L. and B., D.R.-P., 224953. 
 
 207 
 
CHAPTER V 
 
 SALVARSAN 
 
 Aromatic Derivatives containing Tervalent Arsenic 
 PART I 
 
 BUNSEN found that the cacodyl derivatives containing tervalent 
 arsenic were much more active physiologically than cacodylic 
 acid and its salts in which the arsenic is a pentad. A similar con- 
 nection was traced by Ehrlich among the aromatic derivatives 
 of arsenic, those containing tervalent arsenic being much more 
 potent trypanocides and spirochaetocides than the compounds 
 of quinquevalent arsenic. 
 
 The aromatic compounds with tervalent arsenic are usually 
 obtained by the reduction of atoxyl and its derivatives. After 
 trying 605 arsenical preparations Ehrlich arrived at salvarsan 
 (No. 606). 
 
 Phenylglycinearsinic acid, which has already been mentioned, 
 yields on reduction with sodium hydrosulphite the therapeutically 
 important compound arsenophenylglycine. Its sodium salt is 
 the drug " spirarsyl " (I.), No. 418 in Ehrlich 's experimental 
 series, which, on account of its low toxicity and high trypanocidal 
 power, constituted an important advance on atoxyl and its 
 immediate derivatives. 
 
 CO 2 Na-CH 2 -NH/ 
 
 Early in the study of these arsenicals it was found by Bertheim, 
 Benda, and Kahn, in Germany, and independently by Barrow- 
 cliff, Pyman, and Remfry, in England, that ^-hyclroxyarsinic 
 acid (III.) is produced by boiling in aqueous solution the diazo- 
 compound (II.) of ^-arsanilic acid(I.),the homologues of this amino- 
 
 208 
 
SALVARSAN 
 
 acid giving rise to the homologous hydro xyarsinic acids (Ber., 
 1908, 41, 1678, 1854 J Chem. Soc. Trans., 1908, 93, 1893). 
 
 It was also found by Messrs. Meister, Lucius, and Briining that 
 ^>-hydroxyarsinic acid (III.) and its homologues can be obtained 
 directly from arsenic acid and phenol, and its homologues by the 
 Bechamp condensation. 
 
 On nitration, />-hydroxyarsinic acid yields a mono-nitro-com- 
 pound (IV.), which can undergo reduction in various ways. With 
 reagents affecting only the nitro-group the first reduction product 
 is 3-amino-4-hydroxyphenylarsinic acid (V.). Further reduction 
 leads to 3-amino-4-hydroxyphenylarsenious oxide (VI.), a highly 
 toxic substance, and finally the complete removal of oxygen 
 leads to a doubling of the molecule and the formation of 
 3 :3'-diamino-4:4'-dihydroxyarsenobenzene (VII.), or salvarsan 
 (No. 606), introduced into pharmacy in the form of its 
 dihydrochloride, 
 
 f HOv >OH 
 
 JHC1,NH/ 3 \NH 2 ,HC1 
 
 AsO(OH 2 ) AsO(OH) s 
 
 + 2H 2 
 
 AsO(OH) 2 
 /\ 
 
 NH 2 
 I. 
 
 AsO(OH) 2 
 /\ 
 
 OH 
 III. 
 
 AsO 
 
 N0 2 
 
 N 2 -OH 
 II. 
 
 AsO(OH) 2 
 
 NH 2 
 
 OH OH 
 
 V. VL 
 
 As = As 
 
 VH 
 
 IV. 
 
 NH 2 
 
 OH OH 
 VII. 
 
 Several variations on this process have been patented (v. pp 
 224-231), and five isomerides of salvarsan have been synthesised 
 (p. 232). 
 
 209 P 
 
 NH 2 
 
 \/ 
 
 
 \/ 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Acetylatoxyl or arsacetin is not readily nitrated, but oxalyl- 
 atoxyl furnishes a mono-nitro compound, in quantitative yield. 
 In this product the oxalylamino-group is in a sympathetic ortho- 
 para-position with respect to the acidic nitro- and arsinic groups. 
 This orientation renders the oxalylamino-complex very labile, 
 alkaline hydrolysis removes first the oxalic group, and then the 
 amino-group itself, giving rise to 3-nitro-4-hydroxyarsanilic 
 acid. This compound when reduced at 55-60 with excess of 
 sodium hydrosulphite yields salvarsan. 
 
 AsO,H 2 As0 3 H 2 AsO 3 H 2 
 /\ ' 
 
 \/ 
 
 NH-COCOoH 
 
 As0 3 H 2 
 /\ 
 
 NO 2 
 H 
 
 The next advance was the very important discovery made by 
 Bart, who found that the arsinic group can be introduced into 
 the ring through the agency of the diazo-reaction (Eng. P., 
 568, 1911, D.R.-P., 250264, 254345). When benzenediazonium 
 chloride or preferably potassium tsodiazo-oxide is -treated with 
 alkaline sodium arsenite the arsinic group enters the aromatic 
 nucleus in the place of the diazo-radical to form phenylarsinic 
 acid, just as other elements and groups can be introduced by 
 the well-known Sandmeyer and Gattermann reactions. The 
 reaction is a general one, and both mono- and di-arylarsinic 
 acids can be synthesised. In general the ^'so-diazo- (anti-di&zo-) 
 compounds interact in this process more readily than the corre- 
 sponding normal (syn-) diazo-derivatives. If, however, the 
 aromatic nucleus is substituted, the reactivity of both normal 
 diazo- and i'sodiazo-compounds is increased. The reaction goes 
 best in alkaline solutions, but also occurs in neutral media. 
 With acids present, the yield diminishes with the concentration 
 of hydrogen ions. 
 
 C 6 H 5 N 2 -OK + K 2 HAsO 3 -> N 2 + C 6 H 5 AsO(OH)OK 
 C 6 H 5 N 2 -OK + C 6 H 5 As(OK) 2 -> N 2 + (C 6 H 5 ) 2 AsO-OK 
 
 In this way ^>-chloroaniline can be converted into ^-chloro- 
 
 210 
 
SALVARSAN 
 
 phenylarsinic acid ; this substance can be nitrated, and the 
 following series of changes again leads to salvarsan. 
 
 Cl OH OH 
 
 ^ 
 
 V \/ \/ 
 
 AsO(OH), AsO(OH) 2 AsO(OH). 
 
 N ^V.H 5 -As : As-r.H./9.?. 
 
 The introduction of the arsenical group is facilitated by the 
 presence of copper compounds (Sandmeyer reaction), and in these 
 circumstances the interaction between alkali arsenite and alkali 
 aryldiazo-oxide takes place in the absence of free alkali. 1 
 
 The use of metallic catalysts, copper, silver, nickel, or cobalt 
 (Gattermann reaction) as well as their salts, facilitates the removal 
 of diazo-nitrogen at low temperatures and obviates the formation 
 of by-products. 2 
 
 Pregrtstivt 
 
 Arsenic. 
 
 The progressive reduction of aromatic nitro-arsenicals furnishes 
 an exceptionally interesting illustration of the action of different 
 reducing agents on aromatic compounds. 
 
 ^-Arsanilic acid and its homologues and derivatives containing 
 quinquevalent arsenic are reducible to derivatives of tervalent 
 arsenic, the chemical nature of the products depending on the 
 reducing agent employed. 
 
 Sulphurous acid, with hydriodic acid as catalyst, phenyl- 
 hydrazine, thionyl chloride and phosphorus trichloride give amino- 
 arylarsenious oxides, e.g., NH 2 -C 6 H 4 -AsO. 
 
 Electrolytic reduction 3 or various metals and concentrated 
 acid solutions, especially in the presence of methyl or ethyl 
 alcohol, lead to derivatives of the aromatic primary arsines. 4 
 
 By a judicious selection of reducing agent, reduction of either 
 nitro-group or arsenical radical can be effected at will, more 
 drastic treatment leading to simultaneous reduction of both these 
 oxygenated complexes. 
 
 i. The chief difficulty is to reduce the nitro-group without 
 affecting the arsenical complex. This reduction is brought about 
 
 Fabr. Heyden, D.R.-P., 264924. 2 Bart, D.R.-P., 268172. 
 Bart, D.R.-P., 270568. 4 D.R.-P., 251571 and 267082 
 
 211 P 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 by ferrous compounds, especially ferrous hydroxide, or by using 
 the calculated amount of sodium amalgam. 
 
 2. The arsenical group is reduced without affecting the nitro- 
 group by phosphorous and hypophosphorous acids which have a 
 specific action on arsinic and arsenious groups, converting these 
 into arsenoaryl complexes. The calculated quantity of stannous 
 chloride reduces arylarsenious oxides to the same condition, and 
 this reducing agent activated by hydriodic acid will also reduce 
 arylarsinic acids to a similar extent. Sulphuretted hydrogen 
 in neutral solution reduces arylarsinic acids and arylarsenious 
 oxides to sesqui- and mono-sulphides without altering the nitro- 
 group. In acid and alkaline solutions this group becomes in- 
 volved. 
 
 3. In the reduction of both nitro- and arsino-groups the cata- 
 lytic agent of hydriodic acid is very noteworthy. In addition to 
 its employment with sulphurous acid it is used in conjunction with 
 stannous chloride and with great advantage, in activating hypo- 
 phosphorous acid, preferably in acetic acid solution. 
 
 Sodium hydrosulphite is the specific reducing agent used in the 
 production of salvarsan and similar arsenoaryl compounds. 
 The metals (tin and zinc) and concentrated acids lead to primary 
 arsines, but it is claimed that, in the presence of sulphurous acid, 
 reduction stops at the arsenobenzene stage. 
 
 These aminoaryl derivatives containing tervalent arsenic 
 are of great therapeutic interest. In vitro atoxyl in i per cent. 
 solution did not kill a certain strain of trypanosomes, which, 
 however, were destroyed by ^-aminophenylarsenious oxide in 
 dilutions of I in 1,000,000. Mice affected with very virulent 
 trypanosomes (Nagano ferox) were healed with atoxyl (i in 300) 
 only in 5-6 per cent, of cases studied ; all cases were healed with 
 ^>-arsenophenylglycine (i in 600), and this arsenical drug kills 
 in the organism parasites which are immune to atoxyl. 
 
 Section I. Reduction Products of p-Hydroxyphenylarsinic Acid 
 (Phenol-p-arsinic Acid) and its Derivatives. 
 
 p-Hydroxyphenylarsenious oxide, 
 HO/ 
 
 white, crystalline mass unchanged by heat below 240, easily 
 soluble in water, methyl or ethyl alcohol, acetone, glacial acetic 
 acid or ethyl acetate, sparingly so in benzene, chloroform, 
 
 212 
 
SALVARSAN 
 
 or carbon bisulphide. Prepared by saturating with sulphur 
 dioxide at 18, a solution of sodium phenol-^>-arsinate and potass- 
 ium iodide acidified by dilute sulphuric acid. The solution is 
 then saturated with sodium chloride and extracted with ether ; 
 the ethereal extract is shaken with saturated sodium carbonate 
 to remove phenolarsinic acid and the ethereal solution concen- 
 trated till the product crystallises. 
 
 Other rnild reducing agents, such as phenylhydrazine, thionyl 
 chloride, or phosphorus trichloride, reduce phenol-^>-arsinic acid 
 to ^>-hydroxyphenylarsenious oxide, and this substance warmed 
 with a neutral solution of sodium hydrosulphite gives yellow 
 flakes of arsenophenol. 1 
 
 The Arsenophenols.' 2 ' 
 
 Phenol-^-arsinic acid and its homologues and derivatives are 
 reducible to arsenophenols by strong reducing agents, such as 
 stannous chloride, tin and hydrochloric acid and sodium hydro- 
 sulphite. Milder reducing agents, such as hydriodic acid, sul- 
 phurous acid, and phenylhydrazine, give rise to hydroxyaryl- 
 arsenious oxides, which by further treatment, for instance with 
 sodium amalgam, are reduced ultimately to arsenophenols. 
 
 From the phenolarsinic acids, these arsenophenols (in the form 
 of their soluble alkali derivatives) are distinguished by their 
 greater biological action, toxicity, and trypanocidal power (effect 
 on trypanosomes and spirilla). Animals greatly infected with 
 trypanosomes are healed by a single injection of sodium 
 arsenophenoxide. Their alkyl ethers, arseno-_-anisole and arseno- 
 ^-phenetole (p. 93), on the contrary, are inactive compounds, 
 insoluble in water, and unsuitable for use in therapeutics. 
 
 p- Arsenophenol, 
 
 HO/ ">As : As/ \OH, 
 
 yellowish-brown powder, darkening and decomposing above 
 200, is easily soluble in alcohol, acetone, ether, or aqueous caustic 
 alkali, insoluble in benzene, chloroform, or dilute mineral acids. 
 Prepared by adding phenol-^>-arsinic acid (10 grams) dissolved 
 in water to a solution of sodium hydrosulphite (50 grams) in 
 250 c.c. of water neutralised with 25 grams of crystallised 
 
 1 M. L. and B., D.R.-P., 213594. 
 
 2 M. L. and B., D.R.-P., 206456 ; Eng. P., 9855/1908 ; Ehrlich and 
 Bertheim (M. L. and B.), U.S. P., 907978 and 909380. 
 
 213 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 magnesium chloride and 12 c.c. of loN-caustic soda. On warming 
 (not boiling) the mixture for three-quarters of an hour the 
 product separates in yellow flakes. 
 
 Sodium p-arsenophenoxide is a yellow powder precipitated by 
 alcohol from concentrated aqueous solutions, sparingly soluble in 
 methyl or ethyl alcohol, dissolving readily in water. 
 4- A rseno-o-cresol, 
 
 CH 3 CH, 
 
 ~ 
 
 yellowish-red powder, produced by digesting at 50 an aqueous 
 solution of sodium o-cresol-4-arsinate and 10 parts of sodium 
 hydrosulphite neutralised by magnesium hydroxide. 
 
 Halogenated Arsenophenols. 1 
 
 The halogenated arsenophenols yield neutral soluble alkali 
 salts having a more pronounced bactericidal action than the 
 unhalogenated compounds. They are produced by successively 
 halogenating ^-hydroxyphenylarsinic acid (phenol-_-arsinic acid) 
 and its homologues and reducing the product to the arseno-stage. 
 
 Sodium ^>-hydroxyphenylarsinate in 10 per cent, aqueous 
 solution is added to dilute hypochlorous or hypobromous acid 
 solutions containing four atomic proportions of the halogen. After 
 twelve hours the solution is cooled and stirred with hydrochloric 
 acid. After separating the trihalogenated phenol with ether the 
 precipitate consists of dichloro- or dibromo-p-hydroxyphenylarsinic 
 acid, sparingly soluble in cold water, insoluble in ether or chloro- 
 form, dissolving readily in acetone or the alcohols, not decom- 
 posed at 260. 
 
 The ^'-^0-compound HO-C 6 H 2 I 2 -As0 3 H2 is prepared by 
 adding aqueous potassium iodide to a dilute solution of sodium 
 phenol-^>-arsinate and potassium iodate acidified with sulphuric 
 acid and heated at 80. On cooling, the di-iodo-compound is 
 precipitated. Its solubilities are similar to 'those of the other 
 dihalogenated products. 
 
 Tetrachloroarsenophenol, 
 
 q_ _ci 
 
 HO/ \As:As/ NoH. 
 
 CJ~ ~C1 
 
 An aqueous solution (1500 c.c.) of sodium hydrosulphite (285 
 
 1 M. L. and B., D.R.-P., 235430. 
 
 214 
 
SALVARSAN 
 
 grams) and magnesium chloride (58 grams) is added to dichloro- 
 phenol-_/>-arsinic acid (58 grams) and sodium hydroxide (12 grams) 
 in 1150 c.c. of water. The mixture is digested at 50 until the 
 deposition of the arseno-compound is complete. Tetrachloro-, 
 tetrabromo-, and tetraibdo-arsenophenol are yellow precipitates 
 dissolving in aqueous alkalis to form salts with a neutral reaction. 
 S-Nitro-^-hydroxyphenylarsenic sesquisulphide, 
 
 N0 2 
 [HO/__>As] s S 3 
 
 is produced by saturating with sulphuretted hydrogen at the 
 ordinary temperature an aqueous solution of sodium 3-nitro-4- 
 hydroxyphenylarsinate. The product is crystallised from 
 acetone-water and from boiling xylene ; it separates in hard, 
 warty aggregates of yellow crystals, decomposing at 160, and 
 dissolving in alkalis to a reddish-brown solution. 
 
 The reduction product of the foregoing nitro-sulphide is 
 obtained from 3-amino-4-hydroxyphenylarsinic acid with sulphur- 
 etted hydrogen in acid or alkaline solutions ; the product 
 furnishes a sparingly soluble sulphate, and loses its sulphur on 
 boiling with lead sulphate in alkaline solution. 
 
 w-Aminophenylarsenious sulphide, 1 even in large doses, has 
 no curative action, and the sulphide from ^-aminophenylarsinic 
 acid manifests a slight healing effect in quantities which are 
 close to the lethal dose. The aminohydroxysulphide derived 
 from 3-nitro-^-hydroxyphenylarsinic acid and its reduction 
 products heal with doses only one-third of the lethal amount. 
 
 Glycyl Derivatives of Arsenophenol and Arsenothiophenol. 
 
 The following arsenobenzene derivatives possess such pro- 
 nounced trypanocidal powers that they cure animals infected 
 with highly resistant strains of trypanosomes. 2 
 
 A rsenobenzene-bis-^-oxymethylenecarboxylic acid, 
 
 As-C 6 H 4 -O-CH 2 -CO 2 H 
 
 Is. 
 
 C 6 H 4 -0-CH 2 -CO 2 H, 
 is a yellow, voluminous precipitate reducing ammoniacal silver 
 solutions in the cold; it dissolves in aqueous alkalis to yield 
 
 1 M. L. and B., D.R.-P, 253757. 
 
 2 M. L. and B., D.R.-P., 216270, addition to D.R.-P., 206456. 
 
 215 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 the yellow alkali (sodium) salts which are readily soluble in 
 water and only sparingly so in alcohol. 
 
 Anhydrous sodium hydrosulphite (80 grams) and magnesium 
 chloride (40 grams) are dissolved in 400 c.c. of water and 
 mixed with 20' grams of ioA 7 -caustic soda. To the solution, 
 after filtering off magnesium hydroxide, is added the sodium salt 
 of glycyloxyphenyl-4-arsinic acid and the mixture thoroughly 
 stirred for one hour at 45. The precipitated arseno-compound 
 is purified through its sodium salt. 
 
 Carboxymethyleneoxyphenyl-^-arsinic acid, 
 
 CO 2 H-CH 2 -O-C 6 H 4 -AsO 3 H, 
 
 spicules or plates from water or glacial acetic acid, sinters at 
 150 and carbonises at higher temperatures. It is prepared by 
 adding successively chloroacetic acid (188 grams) in 300 c.c. of 
 water and 400 grams of 35 per cent, caustic soda to sodium 
 phenol-_-arsinate (240 grams) in 480 c.c. of water. The mixture 
 is heated for three hours in a reflux apparatus, then cooled and 
 cautiously acidified with hydrochloric acid ; the product which 
 crystallises from water is also soluble in the alcohols, but not 
 in ether or benzene. 
 
 Carboxymethylenethiophenyl-^-arsinic acid, 
 
 CO 2 H-CH 2 -S-C 6 H 4 -AsO 3 H, 
 
 yellowish needles from water, sintering at 170 and melting 
 with decomposition at 187. It is prepared from ^-arsanilic 
 acid by the following application of the diazo-reaction. 
 
 Sodium nitrite (74 grams) is added to ^-arsanilic acid (217 grams) 
 dissolved in 2 litres of water and 260 grams of concentrated 
 hydrochloric acid at 4-8. The diazo-solution is introduced into 
 a solution of potassium xanthate (217 grams) and sodium 
 carbonate (420 grams) in 4-2 litres of water at 80. Caustic 
 soda (126 grams) is then added, and the mixture warmed for 
 several hours at 90-100, and afterwards treated with a solution 
 of chloroacetic acid (282 grams) and 35 per cent, caustic soda 
 solution (430 grams) in 650 c.c. of water, the whole solution 
 being evaporated to a small bulk. Carboxymethylenethiophenyl- 
 ^>-arsinic acid separates on acidification with hydrochloric acid. 
 
 A rsenobenzene-bis-^-thiomethylenecarboxylic acid, 
 As-C 6 H 4 -S-CH 2 -CO 2 H 
 
 As-C 6 H 4 -S-CH 2 -CO 2 H, 
 
 a yellow powder dissolving in aqueous alkalis to yellow salts, 
 
 216 
 
SALVARSAN 
 
 readily soluble in water and sparingly so in alcohol. This arseno- 
 benzene derivative is obtained by reducing the preceding com- 
 pound either with sodium hydrosulphite, or, in two stages, by 
 phenylhydrazine to the arylarsenious oxide and to the arseno- 
 aryl stage by sodium amalgam. 
 
 Section II. Aminoctryl Derivatives containing Tervalent Arsenic. 
 
 p-Aminophenylarsenious oxide, 1 NH 2 -C 6 H 4 -AsO,2H 2 O, well- 
 defined, colourless needles softening at 80, sparingly soluble in 
 ammonia, sodium carbonate, ether, chloroform, or benzene, 
 dissolving readily in aqueous caustic alkalis, dilute acids, alcohol, 
 acetone, or glacial acetic acid. Prepared by reducing atoxyl 
 with sulphurous and hydriodic acids. Atoxyl (311 grams) is 
 dissolved in 1-8 litres of water containing 520 grams of potassium 
 iodide, I litre of sulphuric acid (i : 5) is added, and sulphur dioxide 
 passed in until the colour of iodine has disappeared. The reduc- 
 tion product crystallises from the solution when rendered slightly 
 alkaline with ammonia. 
 
 Hydrochloric acid (420 c.c. of D = 1-12) is added to atoxyl 
 (62 grams) dissolved in 100 c.c. of hot water ; the precipitated 
 sodium chloride is removed and the solution saturated with 
 sulphur dioxide. After twelve hours, crystallisation of the 
 compound AsC] 2 -C 6 H 4 'NH 2 ,HCl commences; the solution is then 
 saturated with hydrochloric acid, the precipitated hydrochloride 
 is added to 200 c.c. of cold water and treated with strong 
 aqueous caustic soda till alkaline. The solution is saturated with 
 sodium chloride and the product collected after several hours. 
 
 p-A.rs3i.mlic acid dissolved in 12 parts of methyl alcohol is 
 boiled for two hours with phenylhydrazine, nitrogen is evolved, 
 the alcohol is removed, and water and ether added to the residue ; 
 the latter removes phenylhydrazine, and the aqueous solution, on 
 evaporation, deposits ^-aminophenylarsenious oxide. 
 
 As-Dihydroxydi-p-aminoarsenobenzene, 2 
 
 NH 2 -C fi H 4 -As(OH) As(OH) -C 6 H 4 -NH 2 , 
 
 pale yellow flakes, m.p. 227, soluble in hydrochloric acid, an 
 intermediate stage in the production of diaminoarsenobenzene, is 
 obtained by adding sodium amalgam to a methyl-alcoholic 
 solution of ^-aminophenylarsenious oxide. The molecular 
 weight of the product corresponds with the above formula. 
 
 1 M. L. and B., D.R.-P., 206057. 2 M. L. and B., D.R.-P., 206057. 
 
 217 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 p-Acyl Derivatives of p-Aminophenylarsenious Oxide. 
 
 ^>-Arsanilic acid and ethyl chlorocarbonate yield a urethane 
 derivative ; this substance furnishes a* nitro-compound. The 
 two substances on reduction give rise to the carbethoxy- 
 compounds, 
 
 C 2 H 5 -0-COo-NH-C 6 H 4 -AsO and 
 C 2 H 6 -OCO 2 -NH-C 6 H 3 (NH 2 ) 2 -AsO. 
 
 These products are stated to be useful in the treatment of swine 
 fever. 1 
 
 2-Aminotolyl-^-arsenious oxide, 2 NH 2 *C 6 H3(CH 3 )-AsO, white 
 crystals softening under 100, melting at about 160 to a clear 
 liquid. Prepared by adding to 156 grams of sodium 2-amino- 
 tolyl-5-arsinate dissolved in 2\ litres of water 500 c.c. of 
 6-Af-sulphuric acid and 30 grams of potassium iodide in strong 
 aqueous solution. The mixture is cooled and sulphur dioxide 
 passed in until precipitation begins, when, on cooling and 
 rendering ammoniacal, the oxide is precipitated. This product 
 is soluble in hot water, alcohol, acetone, dilute hydrochloric acid, 
 or aqueous caustic alkalis. 
 
 2-Acetylamino-i : $-benzarsenious oxide, 
 
 CH 3 .CO-NH-C 6 H 3 (C0 2 H) -AsO, 
 
 is produced when equal parts of 2-acetylamino-i : 5-benzarsenic 
 acid and phenylhydrazine are boiled together for two hours in 
 methyl-alcoholic solution. After removing the greater part of 
 the solvent, the residue is dissolved in water and extracted with 
 ether to remove phenylhydrazine. The aqueous portion, concen- 
 trated in vacuo at 30-40, is saturated with sodium chloride, cooled 
 in ice and acidified with dilute acetic acid, when the product 
 separates as a white, crystalline precipitate, decomposing at about 
 300, easily soluble in hot dilute hydrochloric acid or aqueous 
 alkalis, slightly soluble in water or glacial acetic acid, insoluble 
 in alcohol or ether. 
 
 Displacement of Arsenic from Aromatic Arsenicals* 
 
 It was shown by La Coste and Michaelis (p. 78) that mercury 
 di-aryls and arsenious chloride give rise to aromatic arsenicals 
 containing tervalent arsenic. The reverse change is practicable, 
 and triadic arsenic can be replaced by mercury in its aromatic 
 
 1 Parke Davis & Co., U.S. P., 1119279. 
 
 2 M. L. and B., D.R.-P., 212205, addition to D.R.-P., 206057. 
 
 3 M. L. and B., D.R.-P., 272289; Eng. P., 2314/1914. 
 
 218 
 
SALVARSAN 
 
 compounds. This displacement takes place in alkaline, neutral, 
 or acid solutions, and the mercury derivatives produced belong 
 to one or other of the types ArHgX or Ar-Hg-Ar (where 
 Ar = aryl and X = negative radical), depending on the nature 
 of the original aryl-arsenical. 
 
 1. Phenylarsenious oxide boiled with mercuric chloride in 
 aqueous caustic soda yields mercury diphenyl. 
 
 2. ^-Aminophenylarsenious oxide, mercuric oxide, and aqueous 
 caustic soda yield mercury dianiline, Hg(C 6 H 4 -NH 2 ) 2 . 
 
 3. Phenylglycine-4-arsenious chloride and mercuric chloride 
 yield phenylglycine-4-mercuric chloride,CO 2 H-CH 2 -NH-C 6 H 4 -HgCl. 
 
 4 : ^'-Diaminoarsenobenzene, 1 
 
 NH 
 
 pale yellow flakes, m.p. 130-140, insoluble in water and the 
 ordinary organic media, dissolving in dilute hydrochloric acid. 
 
 1. Atoxyl (250 grams) dissolved in 1-4 litres of water is added 
 to 800 grams of crystallised stannous chloride in 800 c.c. of 
 hydrochloric acid (D = 1-19) and the solution digested for 
 several days at a temperatnre not exceeding 40. The yellow 
 double tin salt which separates is dissolved in hot JV-hydro- 
 chloric acid, and sufficient caustic soda is added to decompose 
 this salt and redissolve tin hydroxide when the product is pre- 
 cipitated in yellow flakes. 
 
 2. On mixing dilute hydrochloric acid solutions of 4-amino- 
 phenylarsine (p. 263) and 4-aminophenylarsenious oxide (p. 257) 
 the liquid assumes a yellow colour, and the addition of sodium 
 acetate in the cold determines the precipitation of 4:4 / -diamino- 
 arsenoben zene . 2 
 
 4 : ^'-Dioxalyldiaminoarsenobenzene, 
 
 CO 2 H-CO-NH-C 6 H 4 -As:As-C 6 H 4 -NH-CO-CO 2 H. 
 
 Oxalyl-^>-arsanilic acid (100 grams) and 150 grams of crystal- 
 lised sodium acetate in 500 c.c. of water are added to i litre of 
 saturated sodium chloride solution. One kilogram of sodium 
 hydrosulphite in 4 litres of water is mixed with 10 litres of 
 saturated sodium chloride. The two solutions, cooled to 15, 
 are mixed and the mixture left for 24 hours at this temperature, 
 when the product separates as a pale yellow precipitate insoluble 
 in organic media, soluble in aqueous alkalis and converted into 
 an insoluble compound on warming these solutions. 
 
 1 M. L. and B., D.R.-P., 206057. 2 M. L. and B., D.R.-P., 254187. 
 
 219 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Azo-compounds containing an Arsenobenzene Residue. 
 
 Aminoarsenobenzene and its derivatives are not readily 
 diazotised and converted into azo-colouring matters because the. 
 nitrous acid acts as an oxidising agent towards the arseno-group. 
 The azo-derivatives of arsenobenzene can, however, be readily 
 obtained by starting out from the aminoarsinic acids and the 
 corresponding aminoarsenious oxides. These amino-derivatives 
 are diazotised, coupled with phenols or reactive amines, and 
 the resulting azo-compound reduced with hypophosphorous 
 acid. This reducing agent acts preferentially on the arsinic or 
 arsenious radical without affecting the azo-group, and in this 
 way complex azo-dyes based on arsenobenzene are produced. 
 
 m-Arsanilic acid diazotised and coupled with /3-naphthyl- 
 amine-3 : 6-disulphonic acid gives the azo-dye I., and this com- 
 pound, reduced by boiling with aqueous hypophosphorous acid 
 yields the arseno azo-dye II. 
 
 AsO 3 H 
 
 NH 5 
 
 SOH 
 
 As: As 
 
 \ 
 
 SO.H NIL 
 
 V 
 S0 3 H 
 
 x/ 
 
 N 
 
 NH 2 SO 3 H 
 / \ 
 
 y 
 v 
 
 S0 3 H 
 
 II. 
 
 Similar products are obtainable from diazotised ^-arsanilic 
 acid and i-amino-8-naphthol-3 : 6-disulphonic acid (H acid) and 
 from 3-amino-4-hydroxyphenylarsinic acid and phlorogmcinol. 1 
 
 p - Dimethylaminophenylarsenious oxide 2 (Dimethylaniline- 
 arsenious oxide), (CH 3 ) 2 N-C 6 H 4 -AsO, white powder, m.p. 75, easily 
 soluble in chloroform or hot alcohol, insoluble in water, is produced 
 by mixing dimethylaniline (15 grams) and arsenious chloride 
 (25 grams). Considerable heat is generated, and the reaction is 
 
 1 M. L. and B., D.R.-P., 271271. 
 
 2 Michaelis and Rabinerson, Annalen, 1892, 270, 139- 
 
 22O 
 
SALVARSAN 
 
 completed on the water-bath. The resulting syrupy liquid is 
 poured into 700 c.c. of water, treated with excess of aqueous 
 caustic soda, and filtered from a small residue of hexamethyl- 
 triaminotriphenylarsine. The filtrate is acidified with hydro- 
 chloric acid and the main product precipitated with aqueous 
 sodium carbonate. ^-Dimethylaminophenylarsenious oxide is 
 basic towards dilute acids, and behaves as a weak acid with 
 strong bases, for this reason dissolving in excess of concentrated 
 aqueous caustic soda. 
 p-Dimethylaminophenylarsenious chloride hydrochloride, 
 
 AsCl a -C 6 H 4 N(CH 3 ) 2 ,HCl, 
 
 colourless needles, m.p. 116, is obtained by adding concentrated 
 hydrochloric acid to a saturated solution of the foregoing oxide 
 in dilute hydrochloric acid ; the corresponding hydrobromide, 
 
 AsBr 2 -C 6 H 4 N(CH 3 ) 2 ,HBr, 
 
 is similarly prepared ; the hydriodide is a yellow precipitate rapidly 
 undergoing decomposition. 
 
 p-Dimethylaminophenylarsenious sulphide, (CH 3 ) 2 N-C 6 H 4 -AsS, 
 colourless needles, m.p. 187, dissolving in cold dilute hydro- 
 chloric acid without change ; strong hydrochloric acid evolves 
 hydrogen sulphide and gives the preceding hydrochloride. 
 Prepared by passing hydrogen sulphide either into an alcoholic 
 solution of the oxide or into a neutral solution of the hydro- 
 chloride. The sulphide is insoluble in water or aqueous alkalis. 
 
 Tetramethyldiaminoarsenobenzene, 
 
 (CH 3 ) 2 -N-C 6 H 4 -As:As-C 6 H 4 -N(CH 3 ) 2 , 
 
 yellow, granular, crystalline powder, m.p. 202, insoluble in water 
 or alcohol, readily soluble in chloroform or dilute acids. Prepared 
 by shaking a warm alcoholic solution of dimethylaminophenyl- 
 arsenious oxide with a large excess of 3-4 per cent, sodium 
 amalgam. After twelve hours the precipitated arseno-derivative 
 is collected, dissolved in chloroform, and precipitated therefrom 
 with alcohol. It is easily oxidised in the air either when dry or 
 in solution, regenerating dimethylaminophenylarsenious oxide. 
 With concentrated hydrochloric acid in sealed tubes at 150 
 it is completely decomposed, giving dimethylaniline,arsenious 
 chloride, and elemental arsenic. Its hydrochloride is a red, crystal- 
 line mass easily soluble in water and very oxidisable to the salt 
 of the foregoing arsenious oxides. 
 
 Diethylaminophenylarsenious oxide, (C 2 H 5 ) 2 N-C 6 H 4 -AsO, light 
 
 221 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 yellow powder, m.p. 58, easily soluble in hot alcohol or dilute 
 mineral acid. Diethylaminophenylarsenious chloride hydro- 
 chloride, AsCl 2 -C 6 H 4 -N(C 2 H 5 ) 2 ,HCl, snow-white needles, extremely 
 soluble in water, m.p. 139. 
 
 Diethylaminophenylarsenious sulphide, N(C 2 H 5 ) 2 -C 6 H 4 -AsS, white 
 needles, m.p. 155, very soluble in chloroform, insoluble in alcohol. 
 
 Teiraethyldiaminoarsenobenzene, 
 
 (C 2 H 5 ) 2 N-C 6 H 4 -As:As-C 6 H 4 -N(C 2 H 5 ) 2 , 
 
 yellow, crystalline powder, m.p. 180, very soluble in chloroform, 
 but not in alcohol ; hydrochloride, a red, crystalline salt easily oxi- 
 dised by air to the foregoing oxide. In the case of diethylaniline 
 the tertiary arsine base was not obtained (cf. p. 224). 
 3 : 3 '-Diaminodiphenylarsenious sulphide, 
 
 (NH 2 -C 6 H 4 ) 2 As\ s 
 (NH 2 -C 6 H 4 ) 2 As/ b ' 
 
 white, amorphous powder, m.p. 110, obtained by the reduction 
 of 3 * 3'-dinitrodiphenylarsinic acid with ammonium sulphide. 
 
 (NO 2 -C 6 H 4 ) 2 AsOONH 4 + 8(NH 4 ) 2 S > (NH 2 -C 6 H 4 ) 2 AsS-SNH 4 . 
 
 On adding hydrochloric acid to the solution in the cold the 
 aminosulphide is obtained in the form of its soluble hydro- 
 chloride, 
 
 2(NH 2 -C 6 H 4 ) 2 AsS-SNH 4 + 6HC1 = 
 
 [(NH 2 -C 6 H 4 ) 2 As] 2 S,4HCl + 2NH 4 C1 + H 2 S + S a . 
 
 The nitrate, rendered ammoniacal, yields the monosulphide as 
 a voluminous, white precipitate ; the sulphate, (R 2 As) 2 S,2H 2 S0 4 , 
 snow-white needles; the acetyl derivative (m.p. 175), 
 
 [(CH 3 -CO-NH-C 6 H 4 ) 2 As] 2 S, 
 
 Tetraminotetraphenyldiarsine, (NH 2 -C 8 H 4 ) 2 As As(C 6 H 4 -NH 2 ) a , 
 uncrystallisable, white flocculae, readily becoming grey, is obtained 
 by reducing tetranitrotetraphenyldiarsine with excess of phos- 
 phorous acid in glacial acetic acid solution. A portion becomes 
 acetylated and separates as a more stable, white powder, 
 m.p. 162. 
 
 Tri-3-aminotriphenylarsine, 1 (NH 2 -C 6 H 4 ) 3 As, crystalline, m.p. 
 176 (Philips), white, flocculent precipitate turning grey in the 
 air (Michaelis), insoluble in water, moderately soluble in alcohol, 
 produced by treating with tin and hydrochloric acid, a solution 
 of 3 * 3' : 3 "-trinitrotriphenylarsine oxide in glacial acetic acid. 
 
 1 Michaelis, Annalen, 1902, 321, 183. 
 222 
 
SALVARSAN 
 
 Its hydrochloride is (NH 2 'C 6 H 4 ) 3 As,3HCl, crystalline and readily 
 soluble in water or alcohol. Platinichloride, 
 
 [(NH a -C 6 H 4 ) 3 As,3HCl] 2 (PtCl 4 ) 3 , 
 
 yellow precipitate ; acid sulphate, 2(NH 2 -C 6 H 4 ) 3 As,3H 2 SO 4 , 
 crystalline, very insoluble in water, but dissolving readily in 
 dilute hydrochloric acid. Triacetyl derivative, 
 
 (CH 3 -CO-NH-C 6 H 4 ) 3 As, 
 
 colourless needles, m.p. 233, sparingly soluble in alcohol, more 
 so in acetic acid ; prepared by treating the preceding tria- 
 mine with acetic anhydride ; tribenzoyl derivative, crystalline 
 powder, m.p. 276, insoluble in all ordinary solvents. Sulphur- 
 etted hydrogen passed into a glacial acetic acid solution of 
 trinitrotriphenylarsine produces partial reduction to form the 
 nitroamine, NH2'CH 4 -As(C 6 H 4 -NO 2 ) 2 , m.p. 205. 
 Tri-s-amino-tri-^-tolylarsine, 1 
 
 As 
 
 )>CH 3 
 
 NH 2 
 
 Tri-3-nitrotri-4-tolylarsine oxide is reduced with hydrochloric 
 acid and two parts by weight of tin (10 grams of nitro-compound 
 yield 7 grams of aminoarsine). This amino-derivative is precipi- 
 tated from acid solution by caustic soda and crystallised from 
 hot alcohol ; colourless prisms, stable on exposure, m.p. 198, 
 almost insoluble in ether or water. The hydrochloride, 
 As[C 6 H 3 (CH 3 )-NH 2 ] s , 3 HCl, 
 
 colourless needles, is precipitated by concentrated hydrochloric 
 acid ; the sulphate, 2As[C 6 H 3 (CH 3 )-NH 2 ] 3 ,3H 2 SO 4 , a crystalline 
 precipitate, is almost insoluble in water and dissolves only 
 sparingly in hot dilute hydrochloric acid. 
 
 The triacetyl derivative, As(C 7 H 6 -NH-COCH 3 ) 3 , prepared by 
 dissolving the aminoarsine in acetic anhydride, crystallises from 
 alcohol, m.p. 228; the sulphide, (NH 2 -C 7 H 6 ) 3 AsS, insoluble in 
 all organic solvents, dissolves in dilute mineral acids, obtained 
 by saturating successively with ammonia and sulphuretted 
 hydrogen, a hot alcoholic solution of the aminoarsine. 
 
 Hexamethyl-q. : ^'i^'-triaminotriphenylarsine, [(CH 3 ) 2 N-C 6 H 4 ] 3 As, 
 
 colourless needles from alcohol, m.p. 240, very soluble in 
 
 chloroform, sparingly so in cold alcohol, dissolved by dilute acids 
 
 and reprecipitated unchanged by alkalis. Prepared by mixing 
 
 dimethylaniline (15 grams) and arsenious chloride (25 grams) 
 
 1 Michaelis, Annalen, 1902, 321, 213. 
 
 223 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 without application of external heat. The syrupy mass is stirred 
 into water, the solution filtered and mixed with excess of concen- 
 trated caustic soda. The tertiary base, precipitated as a white, 
 caseous mass, is taken up with chloroform. 
 
 Hexam ethyltriaminotritolylmethylarsonium iodide, 
 
 [(CH 8 ),N-C 7 H.] 8 As(CH,)I, 
 
 is produced by heating the aminoarsine with methyl iodide in a 
 reflux apparatus. After removing excess of iodide, the residue 
 dissolved in water is precipitated with caustic soda ; white powder, 
 m.p. 135, easily soluble in alcohol, but dissolving only sparingly 
 in water. 
 
 Section III. Salvarsan. 
 
 Synonyms : Kharsivan, Arsenobenzol, Arsenobillon. 
 Ehrlich 606. 
 
 3 1 ^'-Diamino-^. : 4' -dihydroxyarsenobenzene, 1 
 
 NH 2 _NH 2 
 
 HO/ \As:As/ \OH. 
 
 The free base of salvarsan is a pale yellow powder, soluble in 
 dilute hydrochloric acid or aqueous sodium hydroxide or car- 
 bonate, and reprecipitated from alkaline solutions by acetic acid. 
 The observation that 4-hydroxyphenylarsinic acid and its 
 reduction product, #-arsenophenol, has a beneficial influence on 
 the spirilla (relapsing fever) of mice 2 led Ehrlich to examine 
 many other substances of similar constitution with the object 
 of increasing this spirillocidal effect to a maximum, while at the 
 same time diminishing the harmful effect on the host of the 
 spirilla to a minimum. The atomic grouping HOC 6 H 4 -As was 
 varied in many ways, and ultimately it was found that the 
 most beneficial results were obtained, not only in relapsing fever 
 but also in human syphilis, with the hydrochloride of 3 : 3 '-diamino- 
 4 : ^'-dihydroxyarsenobenzene (Salvarsan), 
 
 As = As 
 
 OH OH 
 
 1 M. L. and B., D.R.-P., 224953 ; Eng. P., 13485/1910. 
 
 2 P. Ehrlich and S. Hata, " Experimental Chemotherapy of Spirilloses," 
 1911, 18. 
 
 224 
 
SALVARSAN 
 
 Ehrlich and Bertheim 1 obtained this product from 3-nitn>4- 
 hydroxyphenylarsinic acid (p. 200) by reducing the nitro- 
 compound either in successive stages or in one operation. 
 Although many experimental modifications of these processes 
 have been devised and new methods of synthesis discovered, it 
 is from this nitro-compound that salvarsan has hitherto been 
 manufactured. 
 
 Progressive Reduction of ^-Nitro-4-hydroxyphenylarsinic Acid. 
 
 The first two stages lead successively to 3-amino-4-hydroxy- 
 phenylarsinic acid and 3-amino-4-hydroxyphenylarsenious oxide, 
 and these processes are described under the heading of these 
 compounds (pp. 205, 228). 
 
 Salvarsan is obtainable from the second of these reduction 
 products by the following method, in addition to processes based 
 on the use of stannous chloride or sodium hydrosulphite. Sodium 
 amalgam (28-8 grams of 4 per cent. Na) is added to 30 c.c. of 
 water and 32 c.c. of 2JV-acetic acid containing 4-98 grams of 
 3-amino-4-hydroxyphenylarsenious oxide. A yellow precipitate 
 is produced, and when the amalgam is used up a further addition 
 is made of 25 c.c. of 2iV-acetic acid and 28-8 grams of sodium 
 amalgam. This treatment is again repeated. The reduction is 
 now complete, as shown by a test with hydrosulphite. The 
 precipitate is dissolved in 60 c.c. of methyl alcohol, the calculated 
 amount of methyl-alcoholic hydrochloric acid is added, and the 
 salvarsan hydrochloride is precipitated by adding ether to the 
 filtered solution ; the yield is 56 per cent, of theory. This prepara- 
 tion contains methyl alcohol and has the composition 
 
 [HCl,NH 2 -C 6 H 3 (OH)As:] 2 ,CH s -OH. 
 It blackens and decomposes at 185-195. 
 
 Direct Reduction of ^-Nitro-^-hydroxyphenylarsinic Acid. 
 
 An enamelled vessel (30 litres capacity) placed in a water- 
 bath and fitted with a wooden cover, stirring gear, and thermo- 
 meter, is charged with water (13 litres), crystallised magnesium 
 chloride (513 grams), and sodium hydrosulphite (2950 grams of 
 80 per cent.). Into this mixture is introduced a cold solution 
 of 3-nitro-4-hydroxyphenylarsinic acid (197 grams, 075 mol.) 
 in water (4-5 litres) and loN-caustic soda (135 c.c.) . The tempera- 
 
 1 Ber., 1912, 45, 756. 
 
 225 Q 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 ture is raised to 55-60 when a microcrystalline, yellow precipi- 
 tate begins to form. The reduction, which is tested by warming a 
 filtered sample until no further deposit occurs, is usually completed 
 in i -2 hours, the mixture being thoroughly stirred throughout 
 the operation. The precipitate is washed with water and pressed. 
 At this stage the crude diaminodihydroxyarsenobenzene is 
 contaminated by mineral ash, sulphurous acid, and small 
 quantities of sulphurised arsenical compounds. The moist 
 preparation is dissolved in 1700 c.c. of methyl alcohol and the 
 calculated quantity of methyl-alcoholic hydrochloric acid 
 (075 mol. HC1) is added ; ether added to the filtered solution 
 precipitates salvarsan hydrochloride, which is collected and dried 
 in vacuo or in an inert atmosphere, the average yield being 
 82 per cent, of theory. 
 
 3 : 3 '-Diamino-4 : 4 '-dihydroxyarsenobenzene dihydrochloride. 
 The commercial product, which is now made in I5oo-gram 
 batches, appears in the market as a bulky, pale yellow, micro- 
 crystalline powder, permanent when dry and preserved in 
 loosely-stoppered vessels. This salt is easily soluble in water, 
 methyl alcohol, ethylene-glycol, or glycerol, slightly so in ethyl 
 alcohol, very slightly so in glacial acetic acid, acetone, ether, 
 or concentrated hydrochloric acid. 
 
 Commercial samples of salvarsan contain impurities and vary 
 one from another in respect of their arsenic content. In few 
 cases does the composition of the product agree with the formula 
 
 C 12 H 12 O 2 N 2 As 2 ,2HCl,2H 2 O. 1 
 
 The yellow, aqueous solution is acid to litmus and turns Congo 
 red to a violet hue. On adding gradually sodium or potassium 
 hydroxide there is at first no turbidity ; but precipitation begins 
 when i mol. of caustic alkali has been employed for I mol. of 
 dihydrochloride. When 2 mols. of caustic alkali are added the 
 free base 3 :3-diamino-4:4'- dihydroxyarsenobenzene is precipi- 
 tated, the liquid being neutral. With further caustic alkali the 
 precipitate begins to dissolve and a clear solution is reached with 
 sufficient alkali to form the monosodium phenoxide 
 HO-C 6 H 3 (NH 2 )-As:As-C 6 H 3 (NH 2 )-ONa.2 
 
 The clear, moderately alkaline solution yields a precipitate with 
 carbon dioxide, and for this reason becomes turbid in the air. 
 
 1 Ewins, Chem. Soc. Trans., 1916, 109, 1355. 
 
 2 Neutralisation of salvarsan; cf. Bongrand, /. Pharm. Chim., 1913, 
 [vii], 7, 49- 
 
 226 
 
SALVARSAN 
 
 The free diaminodihydroxyarsenobenzene is only slightly soluble 
 in sodium carbonate ; it is insoluble in sodium bicarbonate. Its 
 sulphate is very sparingly soluble in water, and even in dilute 
 solutions the hydrochloride yields a yellowish-white precipitate 
 with sulphuric acid and soluble sulphates. 
 
 With ^-dimethylaminobenzaldehyde in dilute hydrochloric 
 acid, salvarsan gives an orange coloration and then an orange 
 precipitate. This reaction is noticeable even at consider- 
 able dilution ; it is rendered sharper by adding mercuric 
 chloride, and is then suitable for detecting salvarsan in animal 
 tissues. 
 
 Like other derivatives of arsenobenzene, salvarsan is 
 very oxidisable in air. This point is of extreme importance 
 in connection with its employment as a drug, because the 
 oxidation product, 3-amino-4-hydroxyphenylarsenious oxide, 
 is 20 times as toxic as salvarsan. Oxidation with iodine or 
 hydrogen peroxide converts salvarsan into 3-amino-4-hydroxy- 
 phenylarsinic acid, the yield being about 66-5 per cent, of theory. 
 Although stable in the dry condition when kept in closed vessels, 
 salvarsan is very decomposable in aqueous, methyl-alcoholic, 
 and especially in alkaline solutions, even in the absence of air, 
 These liquids become red, ultimately depositing intense reddish- 
 brown precipitates which have completely new properties. It 
 is important to realise that these changes represent the later 
 phases of a decomposition process. The earliest stages are 
 scarcely to be detected by physical and chemical means. Bio- 
 logical and toxicological tests, however, are capable of detecting 
 the slightest alteration in salvarsan by a rise in the toxicity of 
 the preparation. The toxic properties vary considerably and 
 unexpectedly. Colour is no criterion of safety, for, when tested 
 on rabbits, samples of clear yellow tint have sometimes proved 
 so toxic that the experimental animals have succumbed during 
 injection. 
 
 Sodium salvarsan is prepared by precipitating with alcohol a 
 solution of salvarsan in aqueous sodium hydroxide in the presence 
 of a stabiliser, which may be sodium hydrosulphite, sodium 
 formaldehyde-sulphoxylate, mannitol, or other polyhydric alcohol 
 containing more than three hydroxjd groups. This preparation 
 is stated to have proved satisfactory in the ambulatory treat- 
 ment of syphilis. 1 
 
 1 M. L. andB., Eng. P., 15931/1912, 24152/1914; Munch. Med. Wochen- 
 schr., 1915, 177. 
 
 227 Q 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Copper salvarsan, useful in sleeping sickness, is prepared by 
 adding sodium hydroxide to a solution of salvarsan and a copper 
 salt (cf. co-ordination compounds, p. 280). 1 
 
 Various albumin compounds of salvarsan are of therapeutic 
 utility. 2 
 
 2. />-Arsanilic acid, when diazotised in excess of hydrochloric 
 acid and treated with copper powder, yields 4-chlorophenylarsinic 
 acid, 3 which, when nitrated in concentrated sulphuric acid, 
 gives rise to ^-nitro-^-chlorophenylarsinic acid, white leaflets 
 from dilute alcohol. The nitro-compound, when boiled with 
 5 parts of aqueous caustic potash (D = 1-32) for several hours, 
 loses its chlorine and gives an intense yellowish-red solution, 
 which, on acidifying, gives 3-nitro-4-hydroxyphenylarsinic acid 
 (p. 200). The reduction of this product leads again to salvarsan. 
 This synthesis is valid for the next homologue. 5-Amino-tolyl-2- 
 arsinic acid diazotised and decomposed in the presence of 
 cuprous chloride gives ^-chlorotolyl-2-arsinic acid, m.p. 180. 
 This substance nitrates to 5-chloro-4-nitrotolyl-2-arsinic acid 
 (needles from alcohol, m.p. 310), which, on boiling with caustic 
 alkali, yields 5-hydroxy-4-nitrotolyl-2-arsinic acid. 4 On reducing 
 this hydroxy-compound with sodium hydrosulphite, methyl- 
 salvarsan is produced. 
 
 3. 4-Hydroxy-3-aminophenylarsinic acid (230 grams) in 2000 
 c.c. of water and 1000 c.c. of 22V-sulphuric acid with 50 grams 
 of potassium iodide in 50 c.c. of water is reduced to 4-hydroxy-3- 
 aminophenylarsenious oxide by saturating the solution with 
 sulphur dioxide. 4-Hydroxy-3-aminophenylarsine (185 grams) 
 is dissolved in 2000 c.c. of alcohol, and 2000 c.c. of .ZV-hydro- 
 chloric acid. The two solutions are mixed in the cold, when 
 3 : 3'-diamino-4 : 4'-dihydroxyarsenobenzene is precipitated forth- 
 with as a greyish-yellow precipitate. 5 
 
 3- A mino-^-hydroxyphenylarsenious oxide, 6 
 
 HO/~ 
 
 NH 2 
 
 a colourless, microcrystalline precipitate, is obtained on reducing 
 3-amino-4-hydroxyphenylarsinic acid by saturating its cold dilute 
 
 1 M. L. and B., Eng. P., 1247/1914. 2 Bering, D.R.-P., 261542. 
 
 3 Bey., 1908, 41, 1856. * M. L. and B., D.R.-P., 245536. 
 
 5 M. L. and B., D.R.-P., 251571 and 254187. 
 
 6 M. L. and B., D.R.-P., 235391. 
 
 228 
 
SALVARSAN 
 
 sulphuric or hydrochloric acid solution containing potassium 
 iodide with sulphur dioxide. The solution is rendered distinctly 
 ammoniacal and the deposition of the oxide is completed by the 
 addition of common salt. 1 
 
 This oxide yields a very soluble hydrochloride, giving 
 a neutral reaction. The salt condenses with sodium /8-naphtha- 
 quinonesulphonate to a dark red product, soluble in 
 alkali, and also yields condensation products with phenol- 
 aldehydes. 
 
 4. 2 This method of preparation contains an improvement 
 in the mode of reduction. Phosphorous or hypophos- 
 phorous acid, used in conjunction with hydriodic acid and 
 preferably in the presence of acetic acid, reduces very readily 
 and smoothly the generators of salvarsan containing nitro- 
 groups. 
 
 i. 3-Nitrophenol-4-arsinic acid (20 grams), hypophosphorous 
 acid (100 c.c. of 25 per cent, solution), and 70 c.c. of glacial acetic 
 acid are heated in a stirring apparatus. 3 :3'-Dinitro-4:4'-di- 
 hydroxyarsenobenzene separates as a yellow, crystalline magma ; 
 potassium iodide (12 grams) is now added, a vigorous reaction 
 ensues, and the precipitate redissolves to a pale yellow solution. 
 Phosphorous acid may be employed instead of hypophosphorous 
 acid. 
 
 ii. The foregoing reduction goes even more readily with 3-nitro- 
 hydroxyphenylarsenious oxide. 
 
 The reduction product of the foregoing processes is isolated 
 in one or other of three ways. 
 
 i. The solution is neutralised with sodium carbonate when 
 salvarsan base is precipitated. It is washed with water and 
 converted into the dihydrochloride by methyl-alcoholic hydro- 
 chloric acid. 
 
 ii. The reduction solution is poured into alcohol when salvarsan 
 hypophosphite separates as a yellowish-white powder soluble 
 in water, alkalis, or dilute hydrochloric acid. 
 
 iii. The reduction solution is added to concentrated hydrochloric 
 acid ; salvarsan dihydrochloride separates and is washed with 
 strong hydrochloric acid, alcoholic hydrochloric acid, and finally 
 with ether. 
 
 1 Ehrlich and Bertheim, Ber., 1912, 45, 761. 
 
 2 M. L. andB., D.R.-P., 271894, addition to D.R.-P., 206456; compare 
 D.R.-P., 216270, 235430, 269886, 269887. 
 
 229 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 5 . A Iternative method of reductio n . ! 
 
 NMe 2 NMe 2 OH 
 
 /\N0 2 /Vo, 
 
 AsO 3 H 8 As0 3 H 2 As0 3 H 2 
 
 I. II. III. 
 
 The 3-nitro-4-hydroxyphenylarsinic acid (III.) required in 
 this alternative method may be prepared by the methods outlined 
 on p. 200, or by Oechslin and Poulenc's method from dimethyl- 
 ^-arsanilic acid (I.). One hundred grams are dissolved in 500 c.c. 
 of water with sufficient sodium hydroxide to produce a neutral 
 solution, 50 grams of zinc chloride or acetate are then added, 
 followed successively by a concentrated solution of sodium sulphite 
 (100 grams), glacial acetic acid (150 c.c.), and zinc dust (200 
 grams), the emulsion being thoroughly stirred. Five hundred 
 c.c. of hydrochloric acid (18 per cent.) are then added very 
 slowly, the temperature being between 25 and 35. The 
 resulting clear solution is warmed to 50 and treated gradu- 
 ally with a further 570 c.c. of hydrochloric acid (18 per cent.). 
 After 20-30 minutes the solution is filtered rapidly and the product 
 precipitated by adding magnesium sulphate, when bright yellow 
 3 : 3 / -diamino-4 : 4'-dihydroxyarsenobenzene sulphate is obtained. 
 It is claimed that in this process the presence of sulphurous acid 
 prevents the reduction going beyond the arsenobenzene stage to 
 primary arsine. 
 3 : ^'-Dinitro-^ : ^.'-dihydroxyctrsenobenzene, 2 
 
 N0 2 _N0 2 
 
 HO/ \Vs:As ' 
 
 This compound, which is referred to incidentally in the fourth 
 preparation of salvarsan (p. 229), is prepared in the following 
 way : 
 
 3-Nitro-4-hydroxyphenylarsinic acid (5-3 grams) , dissolved in 
 20 c.c. of methyl alcohol, is added slowly, with stirring, to a 
 well-cooled solution of stannous chloride (10 grams) in 40 c.c. of 
 hydrochloric acid (D = 1-19) and i c.c. of hydriodic acid (D = 17). 
 
 Precipitation of 3 : 3'-dinitro-4 : 4'-dihydroxyarsenobenzene 
 
 1 Poulenc, Eng. P., 21421/1914 ; cf. Eng. P., 11625/1911. 
 
 2 M. L. and B., D.R.-P., 269886. 
 
 230 
 
SALVARSAN 
 
 commences immediately, and the product, when washed with 
 methyl alcohol and dried in vacuo, is a bright yellow powder which 
 becomes electrified by friction and is insoluble in water, but dis- 
 solves in dilute aqueous alkalis, the salts being somewhat 
 sparingly soluble in excess of these reagents. The compound 
 requires careful handling, as when quite dry it is prone to spon- 
 taneous inflammation. It can also be conveniently prepared 
 from 3-nitro-4-hydroxyphenylarsenious oxide by reduction with 
 the calculated amount of stannous chloride in methyl alcohol 
 at 15 to 10. In this instance the addition of hydriodic 
 acid as catalyst is unnecessary. A yield of 77-5 per cent, of the 
 calculated amount is obtainable. This reduction 1 is also brought 
 about by adding 10 grams of 3-nitro-4-hydroxyphenylarsinic acid 
 or 3-nitro-4-hydroxyphenylarsenious oxide to 50 grams of hypo- 
 phosphorous acid (D = 1-15) and 50 c.c. of water, the mixture 
 being stirred and heated on the water-bath in the absence of air. 
 After one hour's heating the mixture is poured into 2 litres of 
 warm water. 
 
 Salvarsan from Dimethylaniline. 
 
 ^-NitrG-^-dimethylaminophenylarsinic acid. Finely powdered 
 ^-dimethylanilinearsinic acid (23-5 grams) is suspended in glacial 
 acetic acid (300 c.c.) and dissolved with 62 per cent, nitric acid 
 (9-8 grams) added at the ordinary temperature. The solution 
 becomes yellow on adding 20 c.c. of acetic anhydride and rapidly 
 deposits a thick precipitate of the pure nitro-compound (yield 
 20 grams) . 
 
 3-Nitro-4-hydroxyphenylarsinic acid is obtained in good 
 yield by warming the preceding compound with 2 J parts of 
 40 per cent, aqueous caustic soda at 85 for 3-4 hours ; it is 
 reduced to salvarsan as in the foregoing preparations. 
 
 When the nitrodimethylamino-compound is reduced with alka- 
 line hydrosulphite in the presence of magnesium chloride, 4:4'- 
 tetramethyl-3 : ^ : 3' i^'-tetraminoarsenobenzeneis produced and pre- 
 cipitated by methyl-alcoholic hydrochloric acid as its tetra- 
 hydrochloride. 
 
 This arsenobenzene derivative has no curative effect on mice 
 affected with Trypanosoma brucei. Methylation of salvarsan 
 greatly reduces its healing powers. 2 
 
 1 D.R.-P., 269887. 2 Karrer, Bey., 1913, 46, 515. 
 
 231 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section IV. Isomerides of Salvarsan. 
 
 Of the nine theoretically possible isomerides of salvarsan 
 having a symmetric constitution, the two aromatic nuclei being 
 similarly substituted, the following have been prepared. In 
 every instance the curative value of the isomeride is decidedly 
 less than that of salvarsan itself. 
 
 4: 4 '-Diamino-3 : s'-dihydroxyarsenobenzene, 
 
 HO_ OH 
 
 NHa v /" 
 
 As:As 
 
 NH, 
 
 \ / 
 
 3-Nitro-4-aminophenylarsinic acid (130 grams) is dissolved 
 in 400 c.c. of 2Af-sodium carbonate and 500 c.c. of TV-sodium 
 nitrite and treated with 2550 c.c. of 2A/"-sulphuric acid at the 
 ordinary temperature, after which 1400 grams of crystallised 
 sodium acetate are added and the diazo-solution kept at 18 
 until coupling with R-salt (/2-naphthol-3 : 6-disulphonic acid) no 
 longer occurs. The brown solution is then poured into an alka- 
 line solution of 80 grams of /8-naphthol containing 556 c.c. of 
 ioA7"-caustic soda, 500 grams of sodium carbonate, and 3 litres 
 of water, the mixture being stirred at 20-25 for two hours, 
 when the azo-colour is partly precipitated and partly separated 
 by adding hydrochloric acid and salt. 
 
 NO/\ 
 
 N 2 
 
 A 
 
 /.AsO(OH) 
 
 AsO(OH) 2 AsO(OH) 2 
 
 The azo-compound (100 grams) is dissolved in i^ litres of water 
 and 100 c.c. of ioN-caustic soda with 500 c.c. of 2Af-sodium 
 acetate at 25 ; 500 grams of dry sodium hydrosulphite are added 
 and warmed to 35-38. When the colour disappears the solution 
 is cooled to 10 and the precipitated i-amino-/3-naphthol 
 separated. The nitrate is saturated with carbon dioxide, more 
 amino-/3-naphtholis removed, and the nitrate warmed to 65-70, 
 when 4 : 4'-diamino-3 : 3 '-dihydroxyarsenobenzene gradually 
 separates in yellow flakes. 
 
 This preparation may be varied by isolating 4-amino-3-hydroxy- 
 phenylarsinic acid (v. p. 205) and then reducing this substance 
 
 232 
 
SALVARSAN 
 
 with alkaline hydrosulphite at 60-65, when yellow flakes of the 
 arseno-compound are deposited. 1 
 
 The dried product is a yellow powder scarcely soluble in water, 
 but very easily so in aqueous alkalis or dilute acids. The 
 hydrochloride is best prepared by dissolving the arseno-derivative 
 in alcoholic hydrochloric acid and precipitating the salt from 
 the filtered solution with ether (air being excluded). From 
 solutions of the hydrochloride, sodium carbonate or acetate 
 precipitates the free base. The hydrochloride diazotises to an 
 intensely yellow diazo-derivative which couples to a blue azo- 
 colour with i-amino-8-hydroxynaphthalene-4-sulphonic acid in 
 alkaline solution. The very sparingly soluble sulphate is precipi- 
 tated by adding sulphuric acid or a soluble sulphate to the 
 solution of hydrochloride. 
 
 ^-Amino-^-hydroxyphenylarsenious oxide, a white powder, 
 is obtained from the corresponding arsinic acid by reducing the 
 latter with sulphurous acid and a small amount of hydriodic 
 acid. 
 
 5 : 5 '-Diamino-2 : 2 '-dihydroxyarsenobenzene, 2 
 NH 2 NH 2 
 
 OH OH 
 
 The dihydrochloride of this compound is isomeric with salvarsan. 
 It is produced by drastic reduction of 5~nitro-2-hydroxyphenyl- 
 arsinic acid with alkaline hydrosulphite. The free base is a 
 yellow powder, soluble in acids or aqueous caustic alkalis. The 
 alkaline solution oxidised together with ^-xylenol by sodium 
 hypochlorite develops an intense cornflower blue coloration of 
 the corresponding indophenolarsinic acid. 
 2 : 2 r -Diamino-'$ : 3' -dihydroxyarsenobenzene, 3 
 HO NH 2 NH 2 OH 
 
 This isomeride is produced indirectly from 2-nitro-3-amino- 
 phenylarsinic acid (p. 189). This substance on boiling with 
 strong aqueous caustic potash loses its amino-group, becoming 
 3-nitro-3-hydroxyphenylarsinic acid, and the latter on reduction 
 with alkaline hydrosulphite yields the consecutively substituted 
 diaminodihydroxyarsenobenzene . 
 
 1 M. L. and B., D.R.-P., 243648, 244166, 244789, 244790 ; Benda, Ber., 
 1911, 44, 3582, 2 Benda, Ber.. 1911, 44, 3296. 3 D.K.-P., 256343. 
 
 233 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 2 : 2 ' -Diamino-^ : 5 '-dihydroxyarsenobenzene, 
 HO OH 
 
 .-,/ \. -- 
 
 NH a NH 2 
 
 2-Nitro-5-aminophenylarsinic acid becomes converted into 
 2-nitro-5-hydroxyphenylarsimc acid by boiling with strong 
 aqueous caustic potash, and the latter hydroxyarsinic acid on 
 reduction with warm alkaline hydrosulphite yields the arseno- 
 derivative (cf. p. 188). 
 
 4 : 4' '-Diamino-2 : 2' -dihydroxyarsenobenzene, 1 
 OH H0 
 
 :As-/ 
 
 The hydrochloride of this isomeride of salvarsan is obtained by 
 reducing 3-ammophenol-6-arsinic acid (p. 206) in hydrochloric 
 acid at 5 with stannous chloride, glacial acetic acid, and a small 
 amount of hydriodic acid. The product is drained in an atmo- 
 sphere of carbon dioxide and washed with acetic acid and alcohol. 
 
 This hydrochloride dissolves to a light yellow solution. Sodium 
 hydroxide sets free the base as a yellow precipitate soluble in 
 excess to a yellow solution. The sulphate of the arseno-base is 
 sparingly soluble. 
 
 Its carbethoxy-derivative is obtained by the reduction of 
 carbethoxy-3-aminophenol-6-arsinic acid as a yellow precipitate 
 soluble in aqueous caustic soda to a yellow solution. The thera- 
 peutic value of 4 :4'-diamino-2 12 '-dihydroxyarsenobenzene is 
 far less than that of its isomeride, salvarsan. 
 
 Section V. Derivatives and Homologues of Salvarsan. 
 
 i. N '-Methyl Derivatives of Salvarsan. 2 
 
 The starting point in the production of N-alkylated salvar- 
 sans is preferably 3-amino-4-hydroxyphenylarsinic acid, direct 
 alkylation of the arsenobenzene derivative being attended by 
 complications due to the unsaturated nature of this compound. 
 ^-Methylamino-^-hydroxyphenylarsinic acid I. 
 OH OH OH 
 
 S[(CH 3 ) 3 -OH 
 
 As0 3 H AsO 8 H 2 As0 3 H 2 
 
 I. II. III. 
 
 1 Bauer, Ber., 1915, 48, 1581. 2 Bertheim, Ber., 1912, 45, 2130. 
 
 234 
 
SALVARSAN 
 
 This compound is produced by adding dimethyl sulphate (0-2 
 mol.) to an alkaline solution of 3-amino-4-hydroxyphenyl- 
 arsinic acid (0-4 mol.) ; crystallisation sets in, and after the mixture 
 has become heated, it is cooled again, when hydrochloric and acetic 
 acids are added and the unchanged aminohydroxyphenyl- 
 arsinic acid separated by nitration. The filtrate, on concentra- 
 tion in vacuo, yields the crystalline methyl compound separating 
 with |H 2 O. The product is very soluble in water, the alcohols, 
 acetic acid, aqueous alkalis, and mineral acids ; it melts with de- 
 composition at 263-263-5, and its aqueous solution is oxidised 
 by air, giving coloured tarry products. 
 
 Sym.-3 : 3 '-Dimethylamino-^. : 4 '-dihydroxyarsenobenzene (IV.) . 
 
 As=As 
 /\ /\ 
 
 CH.-NH 
 
 NH-CH, 
 
 OH OH 
 IV. 
 
 The foregoing methylated arsinic acid is reduced in the custom- 
 ary manner (p. 225) with hydrosulphite and the precipitated arseno- 
 base converted into dihydrochloride, a greyish or yellowish-white 
 microcrystalline powder. With ^-dimethylaminobenzaldehyde 
 it gives a brownish-orange liquid, but, unlike salvarsan, no sub- 
 sequent precipitate. Its solution yields with sulphuric acid a 
 sparingly soluble sulphate ; caustic soda furnishes a precipitate 
 of the free base which passes into a yellow solution with more of 
 the alkali. 
 
 Z-Dimethylamino-^-hydroxyphenylarsinic acid (II .) . 3-Amino- 
 4-hydroxyphenylarsinic acid (46-6 grams) in water (300 c.c.) 
 and io.ZV-sodium hydroxide (21-2 c.c.) is mixed with 20 c.c. 
 of dimethyl sulphate at the ordinary temperature. Heat is 
 generated, and as the mixture cools crystallisation commences, and 
 a further 20 c.c. of alkali and 20 c.c. of dimethyl sulphate are added. 
 When crystallisation no longer occurs, glacial acetic acid (12 c.c.) is 
 added, and the solution is seeded with a little of the starting 
 material. After two days a crop of 3-amino-4-hydroxyphenyl- 
 arsinic acid is removed, and the filtrate yields totally dissimilar 
 transparent prisms when concentrated in vacuo, the total yield 
 being 537 per cent, of theory. The dimethylated acid is soluble 
 in water, the alcohols, or acetic acid, but dissolves only slightly 
 in acetone, and is insoluble in ether ; its decomposition point 
 is 119-121. 
 
 235 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 3 : ^'-Tetramethyldiamino-^ : 4.' -dihydroxyarsenobenzene results 
 from the hydrosulphite reduction of the preceding compound ; its 
 dihydrochloride is a yellowish-grey powder, easily soluble in water 
 or methyl alcohol. Sulphuric acid precipitates it from aqueous 
 solution, but only slowly. 
 
 3-Trimethylammonium-4-hydroxyphenylarsinic acid (III.), lus- 
 trous, colourless prisms decomposing at 262-264. 3-Amino-4- 
 hydroxyphenylarsinic acid (21 grams) is shaken with methyl 
 alcohol (210 c.c.),ioJV-sodium hydroxide (9 c.c.), and methyl iodide 
 (6 c.c.). After several hours, a further addition of the same 
 quantities of alkali and iodide is made, and after a day this addi- 
 tion is repeated. The crystals separating (25-3 grams) are a 
 mixture of quaternary iodide and quaternary base, and these 
 constituents are separated by crystallisation from water when the 
 more soluble iodide remains dissolved. The quaternary ammo- 
 nium compound loses water at 110-114, passing probably into 
 
 X N(CH 3 ) 3 
 the inner anhydride, As0 3 H 2 -C fl H 3 <^ 
 
 The ammonium hydroxide itself dissolves readily in water with 
 an acid reaction ; it is less soluble in the alcohols or acetone ; 
 it dissolves readily in aqueous alkalis or acids. Unlike the un- 
 methylated and mono- and di-methylated arsinic acids, it does 
 not give a red coloration with a drop of bichromate in acid 
 solution. Reduced with hydrosulphite it furnishes ^is'-hexa- 
 methyldiammonium-^i^'-dihydroxyarsenobenzene, a light yellow 
 powder, insoluble in water, but dissolving in dilute hydrochloric 
 acid or aqueous caustic soda. 
 
 These methylated salvarsans are all much more toxic than 
 salvarsan itself. The di- and tetra-methyl derivatives have equal 
 toxicity and are 10 times as toxic on mice as salvarsan. The 
 hexamethyl compound is about 3-5 times as toxic as the latter 
 drug. The curative effect on trypanosomes is diminished by 
 methylation. The hexamethylsalvarsan is inactive on these 
 organisms. The tetramethyl compound in half the lethal dose 
 gives very little useful result ; a similar concentration of 
 dimethylsalvarsan renders animals free from trypanosomes 
 only for a few days, whereupon recurrence sets in. These 
 results may be correlated with the influence of methyl 
 groups in general, not only in the arsenical drugs but in the 
 rosaniline and acridine series. A methyl group produces a 
 dystherapeutic effect. 
 
 236 
 
SALVARSAN 
 
 2. C-M ethyl Derivatives of Salvarsan. 
 3 : 3 '-Diamino-2 : 2 '-dihydroxy-$ : 5 '-arsenotoluene, 
 
 NH, _NH 2 
 
 HO/ VsrAs/ ^OH, 
 
 CH 3 CH 3 
 
 a pale yellow powder, melting and decomposing at 165-167, 
 is prepared in a similar manner to salvarsan ; it is sparingly 
 soluble in water or organic media, but dissolves readily in aqueous 
 alkalis or dilute acids. 1 
 4 : ^'-Diamino-$ : $'-dihydroxy-2 : 2' -arsenotoluene (v. p. 228), 
 
 _CH, CH 8 
 
 > As:As -<C ~> 
 
 NH 2 NH 
 
 NR 
 
 3. Carboxylated Derivatives of Salvarsan, 2 
 
 As. -=-As As 
 
 CO 2 H 
 
 .H 
 
 NH 2 NH a 
 
 5\ / VyW 2 iJ-\. y-J.lJJ.JJ 11J.J-2N. / 
 
 OH OH OH OH 
 
 I. II. 
 
 C0 2 H 
 
 The starting material for the first of these carboxylic acids is 
 5-nitroanthranilic acid, of which 18 grams diazotised in 100 c.c. 
 of hydrochloric acid and 50 c.c. of water give, on treatment with 
 sodium arsenite (26 grams) in 50 c.c. of water and careful 
 addition of sodium hydroxide till the acid reaction on Congo red 
 has disappeared, a granular precipitate of 2-carboxy-^-nitro- 
 phenylarsinic acid (yield 22 grams). This nitro-acid dissolved in 
 aqueous caustic soda is added at once to a solution of ferrous 
 sulphate. The concentrated filtrate from iron hydroxides, 
 rendered acid, is decanted from separated sodium chloride, and 
 the 2-carboxy-4-aminophenylarsinic acid diazotised in solution 
 and the diazo-compound decomposed by heating on the water- 
 bath. The resulting 2-carboxy-4-hydroxyphenylarsinic acid is 
 reduced in solution with 35 per cent, hypophosphorous acid 
 containing potassium iodide, when 2 :2'-dicarboxy~4 : ^'-dihydroxy- 
 
 1 M. L. and B., D.R.-P., 224953 ; Ehrlich and Bertheim, U.S. P., 
 986148. 2 Karrer, Bey., 1915, 48, 1058. 
 
 237 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 arsenobenzene separates as a yellow precipitate. This substance, 
 when freed by washing from all inorganic impurities, is oxidised 
 with 30 per cent, cooled hydrogen peroxide, yielding 2-car boxy-^- 
 hydroxyphenylarsinic acid, which is produced but not isolated 
 in an earlier stage of the synthesis. This compound (3-9 grams), 
 which crystallises in very soluble colourless needles, is dissolved 
 in 20 c.c. of concentrated sulphuric acid, cooled below o, and 
 treated with 1-3 grams of nitric acid (D = 1-42) and 5 c.c. of 
 water. The temperature rises to 10, and the mixture is poured 
 on to 75 grams of ice. ^-Nitro-2-carboxy-^-hydroxypnenylarsinic 
 acid separates in colourless needles decomposing at 350-355. 
 
 5 : 5 '-Diamino-^ : 4 '-dihydroxy-2 : 2 '-dicarboxy arsenobenzene (I .) 
 is preferably obtained from the preceding nitro-compound by 
 reduction with hypophosphorous acid and hydriodic acid. The 
 nitro-compound (2-2 grams) is mixed with 20 c.c. of hypophos- 
 phorous acid (25 per cent.) and 10 c.c. of glacial acid and heated 
 to boiling with stirring. 
 
 The arsenical group is reduced and dinitrodihydroxydicarboxy- 
 arsenobenzene is precipitated. On adding 2-3 grams of potassium 
 iodide a violent action sets in. The acid is then partially neutra- 
 lised with alkali and the yellow arseno-compound collected. It is 
 easily soluble in alkalis and sodium acetate, but only slightly so in 
 hydrochloric acid. When heated on the water-bath for ten hours 
 with water containing sodium acetate the substance is hydrolysed, 
 losing its arsenic and yielding 4-amino-3-hydroxybenzoic acid. 
 
 The isomeride (II.) of the foregoing substance is produced from 
 4-aminosalicylic acid by arsinating this substance to salicyl- 
 arsinic acid and successively nitrating and reducing this com- 
 pound to the arsenobenzene stage. 
 
 The toxic dose of isomeride I. on mice is 1/1500 gram per 
 20 grams of body weight. 
 
 4. Chloro-derivative of Salvarsan, 
 
 5 : 5'-Dichloro-4 : ^'-diamino-^ : 3' -dihydroxy arsenobenzene. The 
 diazo-solution from 3 : 5-dichloro-^-arsanilic acid diluted with 
 ice-cold water is treated with sodium acetate and stirred till 
 the coupling with R-salt (sodium /3-naphthol-3 : 5-disulphonate) 
 no longer takes place. At this stage the diazo-oxide is produced 
 by removal of one chlorine atom. The product is now coupled 
 with alkaline /3-naphthol, the azo-compound collected, redissolved 
 in water, and the free azo-acid precipitated by mineral acid. 
 
 238 
 
SALVARSAN 
 
 This product dissolved in sodium hydroxide containing sodium 
 acetate is reduced with sodium hydrosulphite at 40-50. The 
 cooled liquid precipitates i-amino-/3-naphthol, and the filtrate 
 reduced further with more hydrosulphite at 60 gradually 
 deposits the arseno-compound in yellow flakes. The product is 
 soluble in aqueous caustic soda or mineral acid, the hydrochloride 
 being precipitated by concentrated hydrochloric acid. 
 
 5. Arsenonaphthalene Derivatives. 1 
 
 i-Nitronaphthyl-^-arsinic acid (I). 
 NO 2 
 
 /v 
 
 AsO 3 H 2 
 
 I. 
 
 The nitration of a-naphthylarsinic acid leads to i-nitronaphthyl- 
 4-arsinic acid, crystallising in yellow needles and containing the 
 arsenical group so firmly attached that it is not replaced by 
 iodine and only slightly by bromine. With concentrated hydro- 
 chloric acid at 120 a-nitronaphthalene is produced ; alkali 
 fusion leads to a-naphthol, and treatment with phosphorus 
 pentachloride to 4-chloro-i-nitronaphthalene. 
 
 4 : 4'-Diamino-a-arsenonaphthalene (II.), produced by reducing 
 the preceding compound with acid stannous chloride in methyl- 
 alcoholic solution ; its hydrochloride is a pale yellow powder 
 readily oxidised in moist air. 
 
 3 : 3'-Diamino-4 : ^'-dihydroxy-a-arsenonaphthalene dihydro- 
 chloride (II.), the naphthalene analogue of salvarsan, is a brownish- 
 yellow powder produced by nitrating 4-hydroxy-a-naphthyl- 
 arsinic acid and reducing the nitro-compound (III.) with acid 
 stannous chloride. 
 
 OH 
 
 \ 
 
 AsO 3 H s 
 III. 
 
 OH OH 
 
 /\/\NH 2 NH 
 
 As 
 
 2HC1. 
 
 IV. 
 
 1 N. Andrew, /. Russ. Phys. Chem. Soc., 1913, 45, 1980. 
 239 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 6. Stilbene Analogues of Salvarsan. 
 
 $-Nitro-2-methylphenylarsinic acid (I.), 1 
 
 AsO 3 H As0 3 H 2 As0 8 H 2 
 
 /V- CH:CH 
 
 NO^/ N0 2X/ J X/ N0 2 
 
 I. II. 
 
 o-Tolylarsinic acid (5 grams) is added to a mixture of concen- 
 trated sulphuric acid (25 grams) and nitric acid (20 grams, 
 D 1-49) at 20-35, and after 15 minutes the mixture is poured 
 into 6 volumes of water. The sulphuric acid is almost neutralised 
 with concentrated caustic soda solution, when the nitro-arsinic 
 acid separates on cooling in white, felted needles, becoming brown 
 at 230 and melting at 261. This nitroarsinic acid undergoes 
 a series of complicated changes when heated at 90 with aqueous 
 alkalis, giving rise to arsenicated stilbene dyes of the Mikado 
 brown type. These reactions are due to intramolecular oxidation 
 of the methyl group by the nitro-group in the presence of alkalis, 
 the resulting products being a mixture of dinitroso-, azoxy-, and 
 azo-stilbenediarsinic acids. A homogeneous product is obtained 
 by heating to 90 for five minutes 5-nitro-2-methylphenylarsinic 
 acid (5 grams), 50 c.c. of ioJV-caustic soda, 50 c.c. of water, and 
 35 c.c. of sodium hypochlorite (Cl = 5-5 per cent.), when acid 
 precipitates a thick, crystalline mass of colourless 5 : $'-dinitro- 
 2 : 2 f -stilbene-i : i r -arsinic acid (II.). 
 
 2 5 : $'-Diamino-2 :2 f -stilbene-i : i '-diarsinic acid (I.) and 5:5'- 
 diamino-i : i'-arseno-2 : 2 '-stilbene (II.), 
 
 AsO 3 H 2 AsO 3 H 2 
 
 -CH=CH ' 
 
 NH 
 
 INK. 
 
 I. 
 
 As, 
 
 :AS 
 
 NH, 
 
 \ 
 CH:CH /N 
 
 y 
 
 II. 
 
 \ 
 
 NH 2 
 
 The arsenicated stilbene colouring matters obtained in solution 
 
 1 Karrer, Ber., 1915, 48, 311. 2 Ibid. 313- 
 
 240 
 
SALVARSAN 
 
 by heating at 90 with caustic alkali, are reduced by the addition 
 of zinc dust until the decolorised solution no longer becomes 
 brown on exposure to air. Sodium hydrosulphite is introduced, and 
 the hot solution added to excess of dilute hydrochloric acid. 
 The brown precipitate is redissolved in aqueous sodium carbonate, 
 and boiled with more hydrosulphite until the solution is completely 
 decolorised, when the nitrate on cooling deposits the disodium 
 salt of 5 : 5 '-diamino-2 : 2 '-stilbene-i : i '-diarsinic acid. The free 
 acid (I.) separates from an acid solution of the salt in yellow flakes ; 
 it yields a Schiff base with ^-dimethylaminobenzaldehyde. 
 
 5:5 f -Diamino-i:i'-arseno-2:2 f -stilbene (II.) is produced by 
 the energetic reduction of the preceding compound with excess of 
 hydrosulphite ; it separates in yellow flakes insoluble in alkalis 
 and dissolving only sparingly in excess of mineral acid. 
 
 o-Tolylarsinic acid is conveniently prepared by Bart's 
 synthesis in the following manner : o-toluidine (53 grams) in 
 500 c.c. of water and 165 c.c. of hydrochloric acid (D = 1-19) is 
 diazotised at 5 with sodium nitrite (35 grams) in 140 c.c. of 
 water. To this diazo-solution are added successively with 
 continual stirring, sodium arsenite (130 grams) in 260 c.c. of 
 water and 100 c.c. of loiV-sodium hydroxide. The mixture is 
 then left for several hours, decanted from tar, and treated 
 successively with strong ammonia (300 c.c.), 30 per cent, hydrogen 
 peroxide (75 c.c.), and 2/3lV-magnesia mixture (2 litres), when 
 all the inorganic arsenic, present is precipitated as magnesium 
 ammonium arsenate. The nitrate on boiling deposits magnesium 
 o-tolylarsinate, which is sparingly soluble in hot water. The free 
 acid crystallises in colourless needles (m.p. 160) on decom- 
 posing this salt with moderately strong hydrochloric acid, the 
 yield being 20 grams. 
 
 $-Chlorotolyl-2-arsinic acid, CHg-CgHsCl-AsOsHa, white needles, 
 softening at 195 and melting at 199, is prepared by the" fore- 
 going process from 5-chloro-2-toluidine, 45 grams of this base 
 yielding 8 grams of the magnesium salt. 1 
 
 5 : 5'-Diamino-4 : ^'-dihydroxy-i :i'-arseno-2 : z'-stilbene (III.), 2 
 AsO 3 H 2 AsO 3 H 2 AsO 3 H 2 
 
 :CH /\ 
 
 NO N0 2 / X/ N0 2 
 
 Cl Cl 
 
 I; II. 
 
 1 P. Karrer, Ber., 1915, 48, 310, 314. 2 Karrer, Ibid., 314. 
 
 241 R 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 5-Chlorotolyl-2-arsinic acid is nitrated at 30-40 by a mixture 
 of concentrated nitric and sulphuric acids, the product being 
 isolated by pouring the acid solution into water. 
 
 4-Nitro-$-chlorotolyl-2-arsinic acid (I.), crystallising from hot 
 water in colourless, lustrous leaflets, m.p. 215, undergoes the 
 stilbene condensation on heating on the water-bath for 20 minutes 
 with 5Af-sodium hydroxide and an equal volume of sodium hypo- 
 chlorite (Cl = 5-5 per cent.), the hot solution being then acidified 
 with hydrochloric acid, when 4 : 4'-dichloro-$ : $'-dinitro-2 : 2 r -stil- 
 bene-i :i'-diarsinic acid (II.) is precipitated as a white, crystalline 
 powder. 
 
 5 : s'-Diamino-^i^'-dihydroxy-i :i'-arseno-2 : 2' -stilbene (III.), an 
 analogue of salvarsan, containing its arsenic in an eight -membered 
 ring, is produced by heating the preceding compound with 
 loAf-sodium hydroxide and a little sodium hypochlorite, pre- 
 cipitating 5 : 5'-dinitn>4 : 4'-dihydroxy-2 : 2 '-stilbene-diarsmic 
 acid and reducing the latter with alkaline hydrosulphite or 
 stannous chloride containing potassium iodide. The resulting 
 yellowish-brown arseno-compound is insoluble in acids, and 
 dissolves in aqueous caustic soda. 
 
 7. Mixed Aromatic-aliphatic Cacodyl Analogue of Salvarsan. 
 
 3 : 3 '-Diamino-4 : 4 '-dihydroxydiphenyldimethyldiarsine (III.), 1 
 CHs-AsOOH CH 3 -AsOOH CH 3 -As As-CH 3 
 
 NO a 
 
 \/ 
 
 NH 
 
 /\ /\ /\ 
 
 NH av / x /NH 2 
 
 OH OH "OH OH 
 
 I; II; III. 
 
 The starting point of this mixed aromatic-aliphatic cacodyl 
 
 derivative, an analogue of salvarsan, but without the double 
 
 linking of arsenobenzene, is s-nitro-^-hydroxyphenylmethylarsinic 
 
 acid (I.), prisms from 50 per cent, acetic acid, m.p. 232-233, 
 
 1 Bertheim, Ber., 1915, 48, 357. 
 
 242 
 
SALVARSAN 
 
 prepared in good yield by Ehrlich and Bertheim's general 
 method from 3-nitro-4-hydroxyphenylarsenkms oxide, methyl- 
 alcoholic caustic soda, and methyl iodide. Its reduction is 
 preferably effected in two stages. The nitro-arsinic acid (i part) 
 caustic soda (2 mols.), dissolved in 10 parts of water at 5, and 
 treated at once with 2\ parts of sodium hydrosulphite. The 
 warm filtered solution mixed with I part of concentrated hydro- 
 chloric acid yields the crude ^-amino-^-hydroxyphenylarsinic 
 acid (II.), which, when crystallised from water, decomposes at 
 206-207. With sodium nitrite it gives a lemon-yellow, soluble 
 diazo-compound. 
 
 3:3'- Diamino - 4 ; 4' - dihydroxydiphenyldimethyldiarsine is 
 obtained in the form of its colourless, crystalline hypophosphite 
 by treating the preceding aminoarsinic acid with hypophosphorous 
 acid (D =1-136) containing I per cent, of strong hydriodic acid. 
 This hypophosphite dissolves readily in aqueous caustic alkalis 
 or acids. With sodium nitrite it yields a yellow diazo-derivative. 
 When shaken with methyl-alcoholic hydrochloric acid the hypo- 
 phosphite is converted into hydrochloride, which is precipitated 
 as a white, crystalline powder on adding excess of strong hydro- 
 chloric acid. This salt dissolves in water to a clear solution 
 neutral to Congo red paper. Both the hypophosphite and hydro- 
 chloride have an irritating effect on the mucous membrane. 
 This substituted aromatic diarsine and its salts differ from 
 salvarsan and its salts in being devoid of colour and highly 
 crystalline. The toxicity of the diarsine is much greater than 
 that of salvarsan, whilst its therapeutic effect is less. Since 
 the aromatic nuclei are similarly substituted in both compounds, 
 the foregoing differences are to be attributed to the disappearance 
 of the arsenical double linking in the diarsine series. 
 
 Section VI. Tetraminoarsenobenzenes. 
 Reduction Products of 2 : <\-Dinitrophenylarsinic Acid. 1 
 
 2 : ^.-Dinitrophenylarsenious oxide, (NO 2 ) 2 C fl H3-AsO, crystalline, 
 yellow crusts obtained by adding phosphorus trichloride to 
 
 2 : 4-dinitrophenylarsinic acid suspended in ether. The ethereal 
 solution is washed with water (2 vols.), then shaken up with 
 
 3 vols. of water, and the mixture allowed to evaporate. The 
 product is soluble in ether or alcohol containing hydrochloric 
 acid with the formation of 2 : 4-dinitrophenylarsenious chloride ; 
 
 1 Karrer, Ber., 1914, 47, 2275. 
 
 243 R 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 it is, however, insoluble in water or dilute acids. In excess of 
 aqueous sodium hydroxide it dissolves to a yellow solution. 
 
 2:4:2': ^.'-Tetranitroarsenobenzene, 
 
 (N0 2 ) 2 C 6 H 3 -As:As-C 6 H 3 (N0 2 ) 2 , 
 
 is produced in reddish-brown flakes by shaking an alkaline solution 
 of the preceding compound with excess of hypophosphorous acid 
 and a few drops of aqueous potassium iodide as catalyst at 50-60. 
 On account of the oxidisability of the product the reduction 
 goes best in an inert atmosphere. 
 
 2:4:2': ^'-Tetraminoarsenobenzene, 
 
 (NH 2 ) 2 -C 6 H 3 -As:As-C 6 H 3 (NH 2 ) 2 , 
 
 is an extremely oxidisable substance obtained in the form of its 
 double tin salt (yellowish-white flakes) by warming at 70-80 
 2 : 4-dinitrophenylarsinic acid with stannous chloride in hydro- 
 chloric acid containing a few drops of potassium iodide solution. 
 The liquid is cooled to 40 and poured into glacial acetic acid 
 when the double chloride is precipitated. This compound is 
 not stable in aqueous solution, but the arseno-compound is 
 produced from it by dissolving in 2-3AMiydrochloric acid and 
 adding successively excess of glacial acetic acid and ether until 
 a bulky, yellowish- white precipitate separates. 
 
 This tetraminoarsenobenzene behaves like a meta-diamine, 
 coupling with diazo-compounds (without loss of arsenic) and 
 yielding with nitrous acid an azo-dye of the Bismarck brown 
 type. It is rapidly decomposed hydrolytically by cold water, 
 yielding arsenious and arsenic acids, w-phenylenediamine 
 (25 per cent, of the theoretical amount), and a reddish-brown, 
 insoluble product containing a large amount of combined arsenic. 
 Like other aromatic meta-diamines, whether containing arsenic 
 or not, the foregoing base is soluble in excess of carbonic acid, 
 this solubility being probably due to the formation of a complex 
 carbamic acid. 
 
 3 5 3' $'~Tetr<tmino-4 : ^.'-dihydroxyarsenobenzene, 1 
 NH 2 _NH 2 
 
 HO/ \As:As/ \OH, 
 ' 
 
 NH 8 
 
 pale yellow powder, decomposing and blackening at 155-157, 
 insoluble in water or organic media, and dissolving readily in 
 aqueous alkalis or dilute acids, is obtained by reducing 3 : 5-di- 
 nitro-4-hydroxyphenylarsinic acid. 
 
 1 M. L. and B., D.R.-P., 224953. 
 244 
 
SALVARSAN 
 
 Section VII. 5 : $'-Dictmino-2 : 4 : 2' : ^-tetrahydroxyarseno- 
 benzene and its Derivatives. 
 
 These compounds are obtained from resorcinol and its methyl 
 ethers. 
 2 : ^-Dihydroxyphenylarsinic acid (I.), 1 
 
 As0 3 H 2 AsO 3 H 2 AsO 3 H 2 
 
 OH /\ OH /NX OH 
 
 YH 
 
 NO a 
 
 \ 
 
 NO. 
 
 NO, 
 
 )H OH OH 
 
 I. II. III. 
 
 Resorcinol (no grams) heated on the water-bath with arsenic 
 acid solution (180 grams of 75 Be., 83 per cent.) forms a 
 solution from which crystals slowly separate in the course 
 of several hours. After two days a yield of 145 grams of 
 2 : 4-dihydroxyphenylarsinic acid is obtained. This acid crystal- 
 lises from dilute acetic acid ; it is very soluble in water 
 and the alcohols, but insoluble in ether, benzene, or petroleum. 
 With ferric chloride it gives a dark red coloration, but 
 does not reduce warm ammoniacal silver nitrate. It nitrates 
 in stages to yield successively $-nitro-2 : 4-dihydroxyphenyl- 
 arsinic acid (II.) and 3 : $-dinitro-2 : 4-dihydroxyphenylarsinic 
 acid (III.). These products on bromination lose their arsenical 
 complex, giving rise respectively to 2 : 6-dibromo-4-nitro- 
 resorcinol and 2 : 4-dinitro-6-bromo-resorcinol. The arsenical 
 group is also removed by coupling the compounds with diazotised 
 ^-nitroaniline. 
 
 The foregoing nitro-compounds on drastic reduction give rise 
 to derivatives of arsenobenzene. 
 
 $-Amino-2 : ^-dihydroxyphenylarsinic acid (needles, decomposing 
 at 150) is an intermediate compound obtained from the mono- 
 nitro-acid and alkaline hydrosulphite. Acetylation of the sodium 
 salt gives $-acetylamino-2 : ^-dihydroxyphenylarsinic acid, which 
 on reduction with hypophosphorous acid (0 = 1-136) and a small 
 amount of hydriodic acid furnishes 5 : 5 '-diacetyldiamino- 
 2:4:2': 4' -tetrahydroxyarsenobenzene, a yellow, insoluble powder 
 dissolving in aqueous caustic soda. 
 
 5 : 5'-Diamino-2 : 4 : 2 ' : 4' -tetrahydroxy arsenobenzene is produced 
 by reducing the mononitro-acid to the ammo-acid by stannous 
 chloride, afterwards activating this reducing agent with hydriodic 
 1 M. L. and B., D.R.-P., 272690 ; Bauer, Ber., 1915. 48, 59- 
 
 245 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 acid so that the arsinic group is also reduced. In the presence 
 of acetic and hydrochloric acids the arsenobenzene derivative 
 is precipitated in the form of its yellow dihydrochloride. This 
 salt is easily soluble in water ; sodium hydroxide precipitates 
 the free base, but redissolves it in excess, this solution turning 
 blue on exposure to air. 
 
 3 : 5 : 3' : 5'-Tetramino-2 : 4 :2 f -4'-tetrahydroxyarsenobenzene, pre- 
 cipitated from solutions containing excess of hydrochloric acid in 
 the form of its tetrahydrochloride, is produced by reducing the 
 foregoing dinitro-acid first with stannous chloride alone, and 
 then with this reagent activated by hydriodic acid. The product 
 is a dull yellow powder dissolving in water to a dark yellow 
 solution. The solution in hydrochloric acid is light yellow, but 
 on warming, the arseno-compound is hydrolysed, losing arsenic 
 and yielding 2 : 4-diaminoresorcinol. In mineral acid the arseno- 
 benzene derivative gives a light yellow diazo-derivative coupling 
 to a red azo-dye with resorcinol. With acetic acid and sodium 
 nitrite it furnishes a deep brown precipitate, which is probably 
 an aminoazo-dye of the Bismarck brown type. 
 
 2-Methoxy-^-hydroxyphenylarsinic acid (I.), 
 
 AsO 3 H 2 AsO 3 H 2 Asm As 
 
 )CH S // \OCH S 
 
 H OH OH OH 
 
 I. II. III. 
 
 Resorcinol monomethyl ether (100 grams) heated for fifty hours 
 with arsenic acid (160 grams of 75 Be.) on the water-bath yields 
 on extraction with acetic acid 63 grams of arsinic acid (m.p. 209, 
 crystallised from water). Nitration of this product is effected 
 preferably in acetic acid and leads to $-nitro-2-methoxy-^-hydroxy- 
 phenylarsinic acid (II.). Unlike resorcinol-4-arsinic acid, the 
 monomethyl ether can be reduced with hypophosphorous and 
 hydriodic acids to a stable arsenobenzene derivative (III.), 
 separating as a yellow powder, soluble in caustic but not in 
 carbonated alkali. 
 5 : 5 '-Diamino-2 : 2 '-dimethoxy-q. : 4 '-dihydroxy arsenobenzene, 
 
 NH^ _NH 2 
 
 HO/ \As : As/ \OH. 
 ~ CH 3 O" 
 
 246 
 
SALVARSAN 
 
 This arsenobenzene derivative is produced by reducing 5-nitro- 
 2-methoxy-4-hydroxyphenylarsinic acid in two stages. The 
 first with alkaline hydrosulphite leads to ^-amino-2-methoxy- 
 ^.-hydroxyphenylarsinic acid, colourless needles with 2H 2 O, 
 darkening at 120, sparingly soluble in water. The second stage, 
 effected on the preceding aminoarsinic acid with hypophosphorous 
 acid and potassium iodide, furnishes the arseno-compound pre- 
 cipitated as hypophosphite by adding acetone, or as hydrochloride 
 by excess of hydrochloric acid. The latter salt in warm solution 
 undergoes hydrolysis to 4-aminoresorcinol i-methyl ether, thus 
 demonstrating the accuracy of the foregoing formula. 
 
 2 : ^-Dimethoxyphenylarsinic acid is obtainable in good yield by 
 heating resorcinol dimethyl ether and syrupy arsenic acid on 
 the water-bath for eight days. It crystallises from water in silky 
 needles, m.p. 242-243. This arsinic acid is also produced by 
 the methylation of resorcinol-4-arsinic acid with dimethyl 
 sulphate (excess) in presence of aqueous caustic soda at 
 90-100. 
 
 Section VIII. Hexaminoarsenobenzene and its Derivatives. 
 
 Since the introduction of salvarsan much activity has been 
 shown in the production of other analogously constituted deriv- 
 atives of arsenobenzene. Among these researches a promising 
 field has been opened up in the polyaminoarsenobenzenes, which 
 exhibit useful therapeutic properties. 
 
 The starting points in these syntheses are the nitrated ^-arsinic 
 and alkyl-^>-arsinic acids, produced either by direct nitration of 
 />-arsinic acid or its alkyl and acyl derivatives, or by replacing 
 chlorine by ammo- and alkylamino-groups in the nitrated 
 />-chlorophenylarsinic acids (I. and III.). 
 
 Cl 
 
 NO, 
 
 AsO 3 H 2 
 I. 
 
 NH 2 * Cl NH 2 * 
 
 2 NO t /\N0 8 NO/'NNO, 
 
 \/ 
 AsO 3 H 2 
 
 II. 
 
 \/ 
 
 AsO 3 H 2 
 
 III. 
 
 AsO s H 2 
 IV. 
 
 The NH 2 group (asterisked) is alternatively replaceable by 
 NHR or NR 2 groups. 1 
 
 1 C. F. Boehringer and Sohne, Eng. P., 29546/1913. 
 247 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 3 : 4 : 5 : 3' : 4' : $'-Hexaminoarsenobenzene (II.), 1 
 
 AsO 3 H 2 
 /\ NH a _ NH 2 
 
 -* NH/ \As:As/ \NH 
 
 NH a 
 I. II. 
 
 The starting material for this arsenobenzene derivative is 
 3 : 5-dinitro-^-arsanilic acid (p. 203), this substance being re- 
 ducible in two stages. 
 
 3:4: 5-Triaminophenylarsinic acid (I.). The dinitro-compound 
 (92-4 grams) is dissolved in water (1400 c.c.) and loTV-caustic 
 soda (200 c.c.) at the ordinary temperature and reduced with 
 an acid ferrous chloride solution (1050 c.c. of 19-6 per cent. Fe) 
 diluted with 2000 c.c. of water. During addition of the iron 
 solution the mixture is kept alkaline to turmeric by means of 
 caustic soda. The filtered solution is acidified, concentrated, 
 partially neutralised with caustic soda, a dark impurity removed 
 by filtration, and the mineral acid neutralised by more alkali 
 (Congo red test) ; the arsinic acid separates in brown needles 
 (total yield 72 per cent . of theory) . When recrystallised it becomes 
 colourless (decomposing point 170-175) ; it is very sparingly 
 soluble in cold, more so in hot, water, almost insoluble in 
 alcohol, but dissolves in dilute mineral acids, aqueous alkalis, 
 warm sodium acetate and 50 per cent, acetic acid. 
 
 Nitrous acid produces a yellow diazo-compound ; oxidising 
 agents (K 3 FeCy and NaCIO) give red, transient colorations ; the 
 ammoniacal solution reduces silver nitrate, and a drop of nitric 
 acid added to the solution in concentrated sulphuric acid develops a 
 brown coloration, changing quickly to olive green and blue. 
 This triamino-acid and its generator, the dinitro-compound, 
 are both reducible to the arsenobenzene derivative by acid 
 reduction. 
 
 3 : 5-Dinitro-4-aminophenylarsinic acid is reduced in acid 
 solution (Sn + HC1) to 3 : 4 : 5 : 3' : 4' : 5'-hexaminoarsenobenzene, 
 which is stated to possess very powerful spirillicidal effects with 
 comparatively low toxicity . 2 This reduction can be effected in two 
 or more stages. 3 Sodium hydrosulphite leads to 3 : 4 : 5-triamino- 
 benzenearsinic acid, reducible further by hypophosphorous acid 
 
 1 Benda, Ber., 1914, 47, 1316. 2 Eng. P., 7488 and 8041/1913. 
 
 3 Eng. P., 8137/1913. 
 
 248 
 
SALVARSAN 
 
 to the hexamino-base. Furthermore, 3 : 5-dinitro-4-ammophenyl- 
 arsinic acid is reduced to 4 :4'-diamino-3 :5 : 3 ' : 5 '-tetranitro- 
 arsenobenzene by 50 per cent, alcoholic phosphorous acid, the 
 final stage to hexamino-base being effected by stannous chloride 
 and hydrochloric acid. 
 
 The hexamino-base (III.) is obtainable from 3 : 5-dinitro- 
 4-aminophenylarsinic acid I. by various other methods of 
 reduction. 1 
 
 Both trkminophenylarsinic acid (II.) and the hexamino-base 
 are comparatively slightly toxic, and the latter has a powerful 
 spirillocidal action. 
 
 NH 2 NH 2 NH a NH 2 
 
 NH,/\NH a 
 
 \/ 
 
 AsO 3 H 2 AsO 3 H 2 As As 
 
 I. II. III. 
 
 3 : 5-Dinitro-4-methylaminophenylarsinic acid reduced with 
 tin and hydrochloric acid furnishes 4 : ^' -dimethyl-^ : 4 : 5 : 3 ' : 4' : 5 '- 
 hexaminoarsenobenzene decomposing at 95 . 2 
 
 3 : 5-Dinitro-4-methylnitroaminophenylarsinic acid (II.) affords 
 another means of obtaining this base (III.). 
 
 CH 3 -N-R 
 
 CHN-N0 
 
 CH 3 -NH 
 
 NH /NX 
 
 NH-CH S 
 
 2; J.>V^2 J -^ JL - 1 2| 
 
 NH 2 
 
 AsO 3 H 2 
 I. 
 
 AsO 3 H 2 
 II. 
 
 \/ 
 
 As- 
 
 III; 
 
 It is prepared from any arsinic acid of the type I. when 
 R == hydrogen, methyl, or an acyl group. 3 The hydrochloride 
 Ci 4 H 20 N 6 As 2 ,4HCl is yellowish-green. The base has a pro- 
 nounced action on trypanosomes and other pathogenic protozoa ; 
 its toxic effect on the human organism is less marked than that 
 of other organic arsenicals. 
 
 The nitroamino-acid (II.) when reduced with acid stannous 
 chloride below 50 yields an intermediate complex hydrazine, 
 
 [NH a .N(CH s )-C,H 2 (NH 2 ) 2 -As =] 
 which also exhibits pronounced trypanocidal action. 4 
 
 1 F. Boehringer and Sohne, D.R.-P., 286854, 286855. 
 
 2 C. F. Boehringer and Sohne, U.S. P., 1075279, 1081079. 
 
 3 Swiss P., 64347. 4 D.R.-P., 285572, 285573, 
 
 249 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 This base has the remarkable property discovered by Karrer 
 and Giemsa of dissolving in soluble bicarbonates to form a 
 complex carbonate, which can be isolated by precipitation by 
 alcohol or acetone. 1 This carbonate is very stable, whilst that 
 from hexaminoarsenobenzene decomposes in a few seconds. 
 
 The bismethylamino-base (III.), which has valuable thera- 
 peutic properties, is obtainable from its generator (II.) in a 
 great variety of ways. 2 
 
 3 : 5-dinitro-4-dialkylaminophenylarsinic acids whn reduced 
 yield 4 : 4 / -tetralkyldiamino-3 : 5 : 3 ' : 5 '-tetraminoarsenobenzenes 
 having a higher therapeutic value and more pronounced action 
 on certain pathogenic parasites than the corresponding dialkyl 
 compounds. 
 
 4 : ^'-Tetramethyl-s : 4 : 5 : 3' : 4' : ^'-hexaminoarsenobenzene, the 
 corresponding tetraethyl derivative, and 4 : 4' ' -dipiperidino- 
 3 5 : 3 ' 5 '-tetraminoarsenobenzene are examples of this promising 
 series of tervalent arsenic compounds. 3 
 
 Halogenated Polyaminoarsenobenzenes. 
 
 2-Chloro-^-dimethylaminophenyl-i-arsinic acid is prepared by 
 condensing w-chlorodimethylaniline with arsenious chloride, the 
 intermediate 2-chloro-^-dimethylaminophenylarsenious oxide being 
 oxidised with hydrogen peroxide, permanganate, or mercuric oxide. 
 Tne final product has greater therapeutic activity than dimethyl- 
 atoxyl and is less poisonous. 4 
 
 Other alkylated derivatives of w-chloroaniline are utilisable in 
 this condensation, for instance those having the general formula 
 Cl-CeH^NRJRfl, where R x = alkyl and R a = alkyl or hydrogen. 5 
 
 This product, halogenated in the ortho-position with respect 
 to the arsinic group, can be nitrated to yield dinitro-alkylamino- 
 arsinic acids which are reducible to polyaminoarsenobenzene 
 derivatives 6 containing halogen atoms in the aromatic nuclei. 
 
 1 D.R.-P., 269660; Eng. P., 1667/1914 and 8759/1915. 
 
 2 D.R.-P., 286667 and 286668. 3 M. L. and B., D.R.-P., 294276. 
 
 4 C. F. Boehringer and Sohne, D.R.P., 286546. 
 
 5 M. L. and B., U.S. P., 1156045. 6 D.R.-P., 285604, 292546. 
 
 250 
 
CHAPTER VI 
 NEOSALVARSAN 
 
 Aromatic Derivatives containing Tervalent Arsenic 
 PART II 
 
 ON account of its combined phenolic and feebly basic properties, 
 salvarsan fails to give neutral salts with either mineral acids or 
 alkali bases. In the form of the free base it is very insoluble 
 in water or in physiological salt solution. The preparation of 
 an approximately neutral solution from salvarsan dihydrochloride 
 is a matter of careful adjustment to be made immediately before 
 the drug is injected intravenously. This preliminary neutralisa- 
 tion complicates the use of the substance in therapeutics, and 
 on this account many attempts have been made to convert 
 salvarsan into a substance yielding soluble salts giving a neutral 
 reaction in solution. From these endeavours have come the 
 drugs " Neosalvarsan," " Galyl," and " Ludyl." 
 
 The idea of using an arsenobenzene derivative sufficiently 
 acidic to furnish soluble neutral salts is foreshadowed in the 
 employment by Ehrlich, of the drug arsenophenylglycine in the 
 form of its sodium salt, " Spirarsyl " or " 418." This substance 
 was the most successful remedy among the arsenicals which 
 preceded salvarsan. For this -reason arsenophenylglycine has 
 been grouped with the neosalvarsan series. 
 
 Section I. Neosalvarsan. 
 " Ehrlich 914." 
 
 Synonyms : Neokharsivan, Novarsenobillon, Novarsenobenzol. 
 Sodium 3 : ^'-Diamino-^ : 4'-dihydroxyarsenobenzene-N-methylene- 
 
 sulphinate. 
 
 NH^ _NH-CH 2 -OSONa 
 
 HO/ \As:As/ \OH 
 
 Salvarsan dihydrochloride (25 grams) in 250 c.c. of water, 
 is treated successively with sodium formaldehyde-sulphoxylate 
 
 251 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 (12-5 grams = i mol.) in 10 per cent, aqueous solution, and 
 after one hour with 80 c.c. of 10 per cent, sodium carbonate and 
 then with 100 c.c. of 12 per cent, hydrochloric acid ; 3 : 3 / -diamino- 
 4 :4'-dihydroxyarsenobenzene-AT-methylenesulphinic acid is pre- 
 cipitated. This acid is also obtained if in the foregoing con- 
 densation 2 molecular proportions of sodium formaldehyde- 
 sulphoxylate are employed. The sodium salt of this acid is 
 obtained by mixing 20 grams of the complex sulphinic acid in 
 80 c.c. of water with 20 c.c. of 2-ZV-caustic soda ; the solution 
 poured in a thin stream into I litre of alcohol gives a precipitate 
 of the sodium salt (neosalvarsan) . 
 
 Salvarsan base (21 grams) is added to sodium formaldehyde- 
 sulphoxylate (25 grams) in 60 grams of water, the mixture is 
 heated on the water-bath until a clear solution is obtained and 
 25 c.c. of concentrated hydrochloric acid are added to precipitate 
 the product. In these circumstances, the precipitated acid 
 contains two methylenesulphinic groups. 1 
 
 The formation of neosalvarsan is facilitated by operating in 
 solutions of the mono- and poly-hydric alcohols, the following 
 solvents being cited : methyl and ethyl alcohols, ethylene glycol, 
 and glycerol. 
 
 Sodium formaldehyde-sulphoxylate (31 parts) dissolved in 
 150 parts of water is stirred into 50 parts of salvarsan (dihydro- 
 chloride) in 200 parts of ethylene glycol. Sodium carbonate is 
 added till the solution is neutral. Alternatively, the salvarsan 
 base may first be set free with (12-5 per cent.) aqueous sodium 
 carbonate added to salvarsan dissolved in ethylene glycol con- 
 taining 12 per cent, of water and the suspension stirred with 
 the foregoing proportion of sodium formaldehyde-sulphoxylate 
 (50 per cent, aqueous solution) until the precipitate is dissolved. 
 These solutions when added to acetone, alcohol, or ether-alcohol 
 give a light yellow precipitate of neosalvarsan. The foregoing 
 reactions can also be effected in the entire absence of water. 2 
 
 The starting material in the production of neosalvarsan 
 need not necessarily be the very oxidisable salvarsan ; the prepara- 
 tion can be simplified by operating directly on 3-nitro-4~hydroxy- 
 benzenearsinic acid (p. 200) or the corresponding amino-derivative 
 (p. 205) . 3 The nitro-compound (i part) dissolved as sodium 
 salt in 5 parts of water is gently warmed with sodium formalde- 
 hydesulphoxylate (2 parts) in 10 parts of water, when a yellow 
 
 1 M. L. and B., D.R.-P., 245756 ; Eng. P., 7865/1912. 
 
 2 M. L. and B., D.R.-P., 260235. 3 D.R.-P., 263460. 
 
 252 
 
NEOSALVARSAN 
 
 precipitate of the free sulphinic acid of neosalvarsan slowly 
 separates. 
 
 Sodium 3-amino-4-hydroxyphenylarsinate is similarly reduced 
 with 2 parts of sodium formaldehydesulphoxylate, the free 
 sulphinic acid of neosalvarsan being precipitated by mineral acid. 
 
 The arylarsenious oxides corresponding with the starting 
 materials of the preceding preparations also furnish a means of 
 arriving at neosalvarsan 1 , and its homologues. ^-Nitro-^- 
 hydroxyphenylarsenious oxide, produced from the above nitro- 
 arsinic acid with sulphurous and hydriodic acids, is dis- 
 solved as mono-sodium salt and reduced with 2 parts of sodium 
 formaldehydesulphoxylate in warm aqueous solution for about 
 two hours. After cooling, the free acid of neosalvarsan is precipit- 
 ated by dilute mineral acids. 3-Amino-4-hydroxyphenylarsenious 
 oxide (p. 228) is similarly reduced with formaldehydesulphoxylate 
 at 50-60 and the product precipitated as before. 2 
 
 Another useful variant on the foregoing preparations arises 
 from the use of the stable 3 :3'-dinitro-4:4'-dihydroxyarseno- 
 benzene (p. 230), I part of which, warmed in 5 per cent, aqueous 
 solution with sodium hydroxide (2 parts) and sodium formalde- 
 hydesulphoxylate (2 parts) for two hours, yields neosalvarsan, the 
 product (free acid) being precipitated by dilute sulphuric acid 
 from the cold filtered solution. 
 
 Neosalvarsan or sodium 3 : ^'-diamino-^. : ^.'-dihydroxyarseno- 
 benzene-N-methylenesulphinate, as produced by the foregoing 
 processes, is a pale yellow powder usually containing somewhat 
 less arsenic (about 24 per cent.) than is required by the formula 
 Ci3H 13 O 4 N 2 As 2 SNa (with 2H 2 O). Commercial samples generally 
 contain small proportions of inorganic salts ; the aqueous 
 solutions are quite neutral. Neosalvarsan may be prepared from 
 salvarsan and the crude formaldehyde additive compound of 
 sodium hydrosulphite, as well as from sodium formaldehyde- 
 sulphoxylate (rongalite). As in practice the arsenical content 
 of the drug is rather lower than that of salvarsan, the average 
 dose is somewhat larger, but on account of the greater simplicity 
 of its application, neosalvarsan is becoming the more popular 
 remedy. The curative effect is very similar in both cases. The 
 efficacy of the preparations must always be ascertained by the 
 intravenous injection of samples into live animals. Rabbits used 
 in these tests are injected through a prominent vein in the ear. 
 Among the earlier attempts made to convert salvarsan into 
 1 M. L. and B., D.R.-P., 264014, 271893. 2 Ibid. 
 
 253 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 substances yielding neutral solutions in water may be cited the 
 following examples. The first product appears to be a N- 
 methylene-sulphonate, and the second an intermediate additive 
 compound. The processes are, however, only of historic 
 interest. 
 
 Salvarsan x (i part) suspended in water (3 parts) with 0-3 part 
 of formalin solution (40 per cent.) and I part of sodium bisulphite 
 (40 per cent.) was gently warmed on the water-bath till dissolved 
 to a clear solution. Hydrochloric acid precipitates a monosul- 
 phonic acid, NH 2 -CeH 3 (OH)-As:As-C 6 H 3 (OH)-NH-CH 2 -SO 3 H } as a 
 yellowish -red powder insoluble in water, alcohol, ether, benzene, 
 acetone, or acids, dissolving readily in alkali hydroxides or 
 carbonates to yellowish-red or reddish-brown salts, precipitated 
 from strong aqueous solutions by alcohol or acetone. The alkali 
 salts of this 2V-methylenesulphonate dissolve in water to a 
 neutral solution. 
 
 Another attempt to convert salvarsan into a stable material 
 dissolving in water to a neutral solution consisted in converting 
 salvarsan dihydrochloride in methyl alcohol into its soluble 
 disodium salt by means of loTV-caustic soda (4 mols.), then adding 
 sodium formaldehydesulphoxylate and pouring the ice-cold 
 mixture into ether-alcohol. In this way the disodium salt of 
 salvarsan and the alkali sulphoxylate are co-precipitated. The 
 preparation is carried out in an inert atmosphere, and the product, 
 when dried over sulphuric acid in vacuo, is a light yellow powder 
 readily soluble in water with alkaline reaction. Salvarsan is 
 regenerated by treating the product successively with hydro- 
 chloric acid and sodium carbonate. 2 
 
 The Glycine Derivatives of Salvarsan? 
 
 OH/ \As:As/ \OH j 
 
 NHT / ~~NH'CH 2 -CO 2 H 
 
 OH/ \As:^ 
 CO 2 H-CH 2 -NlF' ~NH-CH 2 -CO 2 H 
 
 These compounds are of interest as giving with alkalis readily 
 soluble salts with a neutral reaction. They were originally 
 suggested as substitutes for salvarsan in therapeutics. 
 
 The former (I.) is prepared by adding chloroacetic acid in water 
 
 1 M. L. and B., D.R.-P., 249726. 2 M. L. and B., D.R.-P., 264266. 
 8 M. L. and B., D.R.-P., 250745. 
 
 254 
 
NEOSALVARSAN 
 
 to salvarsan dihydrochloride dissolved in methyl alcohol 
 neutralised with caustic soda (2 mols.). The mixture is warmed 
 at 60-65 i n an inert atmosphere, the reaction being accelerated 
 by the addition of potassium iodide. The precipitated salvarsan 
 base passes into solution, and on partial neutralisation of the 
 acid solution with caustic soda, the product is precipitated. 
 Sodium chloroacetate may be used in this condensation instead 
 of chloroacetic acid. The alkaline solution, slightly acidified, 
 yields the monoglycine derivative as a yellow powder soluble 
 in alkalis or in excess of acids, but insoluble in organic media. 
 
 The sodium salt gives a yellowish-brown solution with neutral 
 reaction, insoluble in alcohol or acetone. The potassium and 
 ammonium salts are similar, but the latter slowly dissociates 
 at the ordinary temperature. 
 
 The diglycine derivative (II.) is obtained by further action of 
 chloroacetic or bromoacetic acid on the monoglycine. Its 
 disodium salt is yellowish-brown, readily soluble to a neutral 
 aqueous solution ; insoluble in alcohol or acetone. A higher 
 homologue of the monoglycine is produced by condensing 
 salvarsan base suspended in methyl alcohol with a-bromopro- 
 pionic acid at 60-65 until the base dissolves. After cooling, 
 aqueous caustic soda is added until the solution is slightly acid, 
 when the product is precipitated as a yellow powder insoluble in the 
 ordinary media, but dissolving readily in alkali or excess of acid. 
 
 Section II.Galyl. 4 : 4 '-Dihydr oxyarsenobenzene-$ : 3 '-phos- 
 phamic Acid ("No. 1116 " of Mouneyrat' s Series). 
 
 This arsenical medicament, which was discovered by 
 Mouneyrat, belongs to the neosalvarsan series of drugs inasmuch 
 as it is an acidic substance dissolving in aqueous sodium carbonate 
 to a neutral solution. This property renders the preparation a 
 very suitable solution for intravenous injection in the treatment 
 of syphilis and other protozoal diseases. 
 
 Galyl is prepared from 3-amino-4-hydroxyphenylarsinic acid 
 (I.), which for this purpose is obtained by Mouneyrat by the 
 electrolytic reduction of 3-nitro-4-hydroxyphenylarsinic acid 1 
 (alkaline solution) in a double cell (2 amperes at 3-5-4 volts) 
 with mercury cathode and nickel anode. Condensation with 
 phosphorus oxychloride in the presence of aqueous caustic 
 soda converts the aminohydroxy-acid into a phosphamic acid 
 1 Mouneyrat, Eng. P., 3087/1915. 
 255 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 derivative (II.), and this compound, on reduction with sodium 
 hydrosulphite, yields the phosphamic acid derivative of salvarsan, 
 namely, Galyl (III.). This compound, dissolved in sodium 
 carbonate, gives a precipitate of its sodium salt on adding alcohol 
 or sodium chloride. 1 
 
 OH P(OH )OH 
 
 OH 
 /\- 
 
 OH 
 
 
 IT t Jl g 
 
 
 IX n. JL> JTL 
 
 
 
 \/ 
 
 
 \/ 
 
 
 \/ 
 
 
 AsO 3 H, AsO 3 H 2 AsO 3 H 2 
 
 I. II. 
 
 /\ 
 
 NH NH 
 
 As 
 
 :As 
 
 III. 
 
 In the foregoing reduction it is obvious that the arsenic 
 atoms of two separate molecules of compound II. may coalesce, 
 giving rise to a more complex molecule which has also been 
 
 O.x X)H 
 
 OH 
 
 OH 
 
 \/ 
 
 As 
 
 As 
 /\ 
 
 \/ 
 
 As 
 
 As 
 
 /\ 
 
 \/ 
 OH 
 
 NH 
 
 NH 
 
 \/ 
 OH 
 
 ascribed to this substance. Galyl contains 35-3 per cent, of 
 arsenic and 7-2 of phosphorus ; it is very slightly toxic and has 
 marked spirillicidal and trypanocidal properties. 
 
 Ludyl (" 1151 " of Mouneyrat's Series). 
 
 Benzene-m-^' : ^'-disulphamino-bis-^-amino-^ : ^'-dihydroxy- 
 arsenobenzene, 
 
 HO/" ^AsrAs/ ^OH 
 -S0 2 -NH-\ / 
 
 /\ 
 
 \/ 
 
 >OH 
 
 NH 2 
 
 1 Eng. P., 9234/1915. 
 256 
 
NEOSALVARSAN 
 
 is a yellow or yellowish-grey powder insoluble in water, but dis- 
 solving in aqueous sodium carbonate to a yellowish-brown 
 solution. This complex disulphonamide is produced by the 
 Schotten-Baumann reaction from benzene-w-disulphonic chloride 
 and salvarsan . The product, " ludyl," belongs to the neosalvarsan 
 series of arsenical drugs, since it is an acidic substance yielding 
 alkali salts having a neutral solution. When air is excluded this 
 solution remains unchanged for several days and yields a pre- 
 cipitate of the sodium salt of ludyl on the addition of alcohol 
 or sodium chloride. With ferric salts, sodium ludyl gives a 
 violet -brown coloration. This drug is administered like galyl 
 by intravenous injection and is recommended for the treatment 
 of protozoal diseases. 
 
 Galyl and ludyl are prescribed in the treatment of syphilis ; 
 they have a very energetic spirillicidal action, are feebly toxic, 
 and are well tolerated. They show an absence of congestive 
 action on the organs of the body and have no secondary ill 
 effect on the nervous system. Their action on the blood and 
 on general nutrition is favourable. 
 
 Section III. A rsenoarylglycines. 
 A rsenophenyl-p-glycine, x 
 
 CO 2 H-CH 2 -NH/ \As:As/ \NH-CH 2 -C0 2 H. 
 
 Phenylglycine-^>-arsinic acid (200 grams) dissolved in 4 litres 
 of boiling water is added to a solution of 2 kilos, of sodium 
 hydrosulphite in 10 litres of water after the latter solution has 
 been previously treated successively with 600 c.c. of lO^V-sodium 
 hydroxide and i kilo, of crystallised magnesium chloride and 
 filtered from magnesium hydroxide. After three-quarters of an 
 hour on the water-bath the precipitate is separated and dissolved 
 in excess of very hot dilute aqueous sodium carbonate. On 
 adding acetic acid, arsenophenyl-^>-glycine is obtained as a 
 reddish-brown precipitate, drying to a reddish-brown powder 
 easily soluble in aqueous sodium carbonate to a yellow solution ; 
 it dissolves in aniline or pyridine, but not in alcohol, ether, 
 benzene, or dilute mineral acids. 
 
 Sodium arsenophenylglycinate, " Spirarsyl," " 418 " (in Ehrlich's 
 experimental series)/ As 2 (C 6 H 4 -NH-CH a -CO 2 Na) 2 , is the yellow, 
 
 1 M. L. and B., D.R.-P., 206057 ; Eng. P., 17619/1907. Ehrlich and 
 Bertheim (M. L. and B.), U.S. P., 888321 and 907016/1908. 
 Ehrlich, Ber... 1909, 42, 36. 
 
 257 s 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 soluble sodium salt of arsenophenylglycine ; it gives in water a 
 neutral yellow solution and has a pronounced trypanocidal and 
 spirillicidal action with low toxicity. 
 
 p-Arseno-o-tolylglycine(II.),ihe next homologue of arsenophenyl- 
 p-glycine, is prepared by reducing o-tolylglycine-^-arsinic acid (I.) 
 with alkaline hydrosulphite in the presence of magnesium 
 chloride. 1 
 
 NH-CH 2 -CO a H CO a H-CH 2 -NH NH-CH a -CO 2 H 
 
 3 CH/N 
 
 \/ \/ \/ 
 
 As0 8 H 2 As As 
 
 I. II. 
 
 p-Arsenophenyl-N-methylglycine (II.), 2 is a yellow powder 
 insoluble in acids or the ordinary organic solvents, but dissolving 
 in aqueous alkalis. Phenylmethylglycine-^>-arsinic acid (I.) (30 
 grams), in 300 c.c. of water and 210 c.c. of AT-sodium hydroxide, 
 is added to a solution of sodium hydrosulphite (300 grams) in 
 1200 c.c. of water previously neutralised with sodium carbonate. 
 After warming for three hours at 55 the clear yellow solution is 
 treated with glacial acetic acid (120 c.c.), when the product is 
 obtained as a flocculent, yellow precipitate. From the golden- 
 yellow neutral solutions of this substance in sodium hydroxide 
 or carbonate, alcohol or acetone precipitates the sodium salt, 
 which readily becomes pulverulent. 
 
 Arsenophenylmethylglycine (II.) shows marked trypanocidal 
 action when injected into mice affected with Trypanosoma 
 Evansii and Tr. Rhodesiense. B 
 
 CH 8 N-CH 2 -C0 2 H CO t H-CH a -N-CH 8 CH 8 -N'CH a -CO a H 
 
 /\ /\ /\ 
 
 AsO 3 H 2 
 
 I. II. 
 
 Acyl Derivatives of Arseno-p-phenylglycine* 
 
 Arsenophenylglycine and its salts become coloured very 
 rapidly on exposure to the air, but their acyl derivatives are 
 much more stable either when dry or in solution. 
 
 1 D.R.-P., 212205. * Poulenc and K. Oechslin, Fr. P., 462276. 
 
 3 Oechslin, Ann. Chim., 1914 [ix], 1, 239. Poulenc and K. Oechslin, Fr. 
 P., 473704. 4 Poulenc, Eng. P., 18/1915. 
 
 258 
 
NEOSALVARSAN 
 
 x Diacetylarseno-p-phenylglycine. 
 
 Acetylanilinoacetonitrile, C 3 H 5 -N<^pTT *.QJ' prepared by the 
 
 interaction of acetanilide, formaldehyde, and hydrocyanic acid, 
 is condensed with arsenious chloride. The complex chloride, 
 AsCl 2 -C 6 H 4 -N(CO-CH 3 )-CH 2 -CN, is oxidised to the corresponding 
 arsinic acid and the nitrile group hydrolysed without removing 
 the acetyl radical. The resulting acetylphenylglycine-^>-arsinic 
 acid (50 grams) is reduced with sodium hydrosulphite (500 grams) 
 in 2500 c.c. of water for two hours at 45-55. The addition of 
 acetic acid (70 c.c.) precipitates diacetylarsenophenylglycine in 
 light yellow flakes. 
 
 >N(CO-CH 3 )-CH 2 -CO 2 H 
 
 As /" \N(COCH 8 ) -CH 3 -C0 2 H 
 
 Alternatively, arseno-/>-phenylglycine (100 grams) is dissolved in 
 1000 c.c. of 8 per cent, sodium carbonate, excluding air ; the 
 solution is cooled to 5, and 100-150 c.c. of acetic anhydride are 
 gradually added with vigorous shaking. The addition of excess 
 of 10 per cent, hydrochloric acid precipitates the acetylated arseno- 
 ^>-phenylglycine as a light yellow powder not changing in the air. 
 
 These reactions have been generalised. 
 
 5-^4 rsenotolyl-2-glycine, 1 
 
 /->TT r*tr 
 
 V/Jtl 3 v^ils 
 
 CO 2 H-CH 2 -NH/ V- As:As / \NH-CH a -CO a H, 
 
 yellowish-brown, insoluble powder, is obtained by adding tolyl-2- 
 glycine-5-arsinic acid (39 grams) dissolved in 800 c.c. of water 
 and 150 c.c. of Af-sodium hydroxide to 400 grams of sodium 
 hydrosulphite in 2 litres of water neutralised with magnesium 
 hydroxide. The mixture is digested at 50 until a filtered sample 
 remains clear on boiling, when the precipitated arseno-derivative 
 is collected ; it is easily soluble in aqueous alkalis and sparingly 
 so in the ordinary organic media except aniline and pyridine. 
 2 : 2 '-Diacetyldiamino-$-arsenobenzoic acid, 
 
 CHa-CO-NH/ 
 
 ~CO 2 H COjl' 
 1 M. L. and B., D.R.-P., 212205. 
 
 259 S 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 a pale yellow, insoluble powder dissolving in aqueous alkalis, and 
 also in alcohol when freshly precipitated, is obtained by dissolving 
 100 grams of 2-acetylamino-i : 5-benzarsinic acid and 150 grams 
 of crystallised sodium acetate in 1-25 litres of hot water, cooling 
 to 50, and adding the solution to I kilogram of sodium hydro- 
 sulphite in 4 litres of cold water, the mixture being digested at 
 30-40 till no further precipitation occurs. 
 
 Formaldehyde Derivative of Arsenophenyl-p-glycine. 1 
 
 The object of this preparation is to increase the stability of 
 arsenophenyl-^>-glycine. Phenylglycine-arsinic acid (10 grams) is 
 reduced with 80 grams of sodium hydrosulphite in 350 c.c. of water 
 containing 8 grams of dry sodium carbonate. After warming 
 at 45-48 for two hours the arsenophenyl-/>-glycine is precipitated 
 with 20-25 c.c. of glacial acetic acid. The precipitate, collected 
 quickly, is dissolved in aqueous sodium carbonate (6 per cent.), 
 the liquid is almost neutralised with acetic acid, and treated 
 with 5 c.c. of formaldehyde solution (40 per cent.). The solution 
 is poured into 60 c.c of cooled absolute alcohol, which pre- 
 cipitates a light yellow salt far more stable than the salt of 
 arsenophenyl-/>-glycine . 
 
 Section IV. Arsenohippuric Acid, 
 
 CO a H-CH 2 -NH-CO CONH-CH a -CO,H. 
 
 /\ /\ 
 
 The starting point in the synthesis of arsenohippuric acid is 
 />-benzarsinic acid, first prepared by La Coste by perman- 
 ganate oxidation from />-tolylarsinic acid (p. 129). Successive 
 treatment of this oxidation product with phosphorus tri- 
 and penta-chlorides leads to ^-dichloroarsinobenzoyl chloride, 
 
 AsO(OH) a -CH 4 -CO a H ^AsCl a -C fl H 4 -CO a H ^AsQa-C^-COCI 
 a mobile fuming liquid (b.p. 189-1 90/ig mm.). This acid 
 chloride condensed with glycine in presence of N-sodium hydrox- 
 ide, gives rise to the alkali salt of a complex arylarsenious acid, 
 
 1 Poulenc, Eng. P., 17/1915. 
 260 
 
NEOSALVARSAN 
 
 the free acid, As(OH) a -C 6 H 4 -CO-NH-CH 2 -C0 2 H (with benzarsenious 
 acid), being precipitated with dilute hydrochloric acid. This 
 mixture oxidised with alkaline hydrogen peroxide gives 
 hippuroarsinic acid AsO(OH) a -C 6 H 4 -CO-NH-CH 2 -CO 2 H (with 
 ^>-benzarsinic acid). The former remains in solution, and on 
 adding successively caustic soda and alcohol, trisodium hippuro- 
 arsinate, Na 2 As0 3 -C 6 H 4 -CO-NH 2 -CH 2 -C0 2 Na,4H 2 O is precipitated 
 in colourless needles. Hippuroarsinic acid when reduced with 
 hydrosulphite by Ehrlich and Bertheim's method yields arseno- 
 hippuric acid, a yellow powder giving unstable solutions with 
 alkali carbonates or phosphates, but stable solutions with caustic 
 alkalis in absence of air. Arsenohippuric acid has a toxicity 
 similar to that of salvarsan. 1 
 
 />-Arsenobenzoic acid injected into the animal organism is 
 eliminated partly in the form of hippuroarsinic acid. ^-Dichloro- 
 arsinobenzoyl chloride has been condensed with the following 
 degradation products of albumin : alanine, phenylalanine, 
 tyrosine, leucine, aspartic acid, glutamic acid, pentamethylene- 
 diamine. The products, R-NH-COC 6 H 4 -AsO, are oxidised to the 
 corresponding crystalline arsinic acids, R-NH-CO-C G H 4 -AsO(OH) 2 , 
 and reduced to yellow, amorphous arseno-compounds, 
 
 As 2 [C 6 H 4 -CO-NHR] 2 . 
 
 />-Dichloroarsinobenzoyl chloride condenses in benzene solution 
 in the presence of pyridine with the higher alcohols, myricyl 
 alcohol and cholesterol ; the resulting arsine oxides are oxidised to 
 arsinic acids and reduced to arseno-compounds. 2 
 
 1 Fourneau and Oechslin, Bull. Soc. chim., 1912 [iv], 11, 909. Hugounenq 
 and Morel, /. Pharm. Chim., 1913 [yii], 7, 383.- 
 
 2 Sieburg, Arch. Pharm., 1916, 254, 224. 
 
 26l 
 
CHAPTER VII 
 AROMATIC PRIMARY ARSINES 
 
 Synthesis of Dissymmetric Arsenobenzene Derivatives 
 THE preparation of phenylarsine by the energetic reduction of 
 phenylarsinic acid, an important discovery due to Palmer and 
 Dehn (v. p. 89), has since led to a valuable synthetic method of 
 preparing complex derivatives of arsenobenzene. The most 
 characteristic property of the primary aromatic arsines is their 
 extreme oxidisability. Exposure to atmospheric oxygen rapidly 
 leads to the production of symmetrical arsenoaryl compounds, 
 
 2R-AsH a + O = R-As:AsR + H a O. 
 
 They also react with arylarsenious oxides or chlorides, giving 
 rise to symmetrically or dissymmetrically substituted arsenoaryls, 
 as illustrated by the following equations : 1 
 i. NH 8 _NH 2 
 
 HO/ \AsH a + OAs/ ^>OH = H.O + 
 
 (salvarsan base). 
 \ / v ' 
 
 2. NH, ' 
 
 The reactivity of these primary arsines has been utilised, more- 
 ver, in the synthesis of mixed arsenostibino-derivatives. 2 
 
 Cl 2 Sb 
 
 HO/ \As:Sb/ 
 
 It can readily be seen from the foregoing illustrations that 
 these condensations increase very considerably the means of 
 synthesising homologues and analogues of salvarsan and its 
 derivatives. 
 
 Salvarsan and its nine symmetrically substituted isomerides 
 1 M. L. and B., D.R.-P., 251571, 254187. 
 262 
 
AROMATIC PRIMARY ARSINES 
 
 could be thus synthesised, and, providing that the ten theoretically 
 possible compounds of the formulae 
 
 HOC 6 H 3 (NH 2 )-AsH 2 and HOC 6 H 8 (NH 2 )-AsO 
 
 are available, then in addition no fewer than 45 dissymmetrically 
 substituted isomerides of salvarsan could also be produced. 
 
 Section I. Substituted Primary Arylarsines. 
 ^-Hydroxyphenylarsine, 1 H0<^ \A.sH 2 , white powder, 
 
 y 
 
 darkening at 70 and decomposing at 135, sparingly soluble in 
 water, alcohol, or ether, dissolving in aqueous caustic soda. 
 
 Phenol-^-arsinic acid (218 grams) is dissolved in 2,500 c.c. of 
 methyl alcohol, and zinc dust (400 grams) is added and 1-5 litres 
 of hydrochloric acid (D 1-19) slowly introduced with stirring. 
 The nitrate from undissolved zinc is extracted with ether, the 
 ethereal extract shaken with aqueous caustic soda, and the 
 primary arsine precipitated from the alkaline solution by passing 
 in carbon dioxide. The product on oxidation becomes yellow 
 and finally red owing to the formation of 4:4'-dihydroxyarseno- 
 benzene. 
 
 4-Aminophenylarsine* NH 2 <^ \AsH 2 , colourless, very 
 
 oxidisable oil, b.p. i32/io mm., readily soluble in ether, alcohol, 
 or glacial acetic acid, dissolving sparingly in water. 
 
 Zinc dust and strong hydrochloric acid are added successively 
 to />-arsanilic acid dissolved in methyl alcohol. The filtrate from 
 zinc is rendered alkaline, distilled in steam, and the distillate 
 extracted with ether. The oily product left after distilling off 
 the solvent speedily becomes oxidised to 4:4 / -diaminoarseno- 
 benzene. 
 
 It is noteworthy that this ^-aminoarsme, unlike its analogue 
 />-phenylenediamine, is volatile in steam from aqueous solutions. 
 Its N-acetyl derivative, NHAc-C 6 H 4 -AsH 2 , forms a co-ordination 
 compound with cupric chloride. 
 
 Phenylglycine-p-arsine, B CO 2 H-CHyNH<^ \A.sH 2 , pale 
 
 yellow precipitate, rapidly darkening on exposure to air, de- 
 composed at 100 ; it is sparingly soluble in water, alcohol, or 
 
 ether. 
 
 1 M. L. and B., D.R.-P., 269743, 269744. 
 
 8 and 8 M. L. and B., D.R.-P., 251571, 
 
 263 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Phenylglycine-/>-arsinic acid is reduced with zinc dust and 
 strong hydrochloric acid in the cold ; a yellow precipitate forms, 
 dissolving to a yellow solution which finally becomes colourless. 
 The filtered solution yields, on addition of sodium acetate, the 
 white, insoluble zinc salt of phenylglycine-^>-arsine. This product 
 is warmed with aqueous sodium carbonate ; the solution, filtered 
 from zinc carbonate, is acidified when the free phenylglycine-^>- 
 arsine is precipitated. 
 
 3-^4 mino-q-hydroxyphenylarsine, 1 
 
 HO/ \AsH 2 . 
 
 3-Nitro-4-hydroxyphenylarsinic acid is reduced with strong 
 hydrochloric acid and zinc dust, keeping the mixture cool. 
 The precipitate first formed dissolves to a dark solution. Water 
 is added and the solution warmed until colourless. On cooling 
 the filtered solution the double zinc salt separates as a white 
 precipitate, soluble in water. This compound is decomposed 
 with sodium acetate and the product extracted with ether ; 
 the arsine is removed from the ether by caustic soda, and then 
 precipitated by acetic acid from the alkaline solution as a greyish- 
 white powder, darkening at 100 and decomposing completely 
 at 135 ; soluble in caustic alkali, acid, alcohol, or ether, dissolving 
 only sparingly in water. 
 The urethane derivative of the foregoing arsine is 
 
 H 2 As/ \OH 
 
 ~ NH-CO a -C 2 H 6 , 
 
 a crystalline, white powder, m.p. 155-160, is produced by the 
 electrolytic reduction of the corresponding substituted arsinic 
 acid, C 2 H 5 -CO 2 -NH-C 6 H 3 (OH)-AsO 8 H 2 . Treatment with sul- 
 phurous acid, followed by hydrolysis, gives rise to the foregoing 
 base. 2 
 
 Co-ordination Compounds. 
 
 The urethane derivative gives a co-ordination compound with 
 palladous chloride, and 3-amino-4-hydroxyphenylarsine combines 
 with auric chloride, silver nitrate, and copper chloride. 3 
 
 1 M. L. and B., D.R.-P., 275216. 2 H. Bart, D.R.-P., 267082. 
 8 M. L. and B., D.R.-P., 275216. 
 
 264 
 
AROMATIC PRIMARY ARSINES 
 
 Section II. Dissymmetrically Substituted Arsenobenzenes. 
 
 i. Synthesis from Primary Ar sines. 
 3- A mino-^-hydroxyarsenobenzene hydrochloride, 
 
 NH 2 ,HC1 
 
 a yellow powder, is obtained by adding 3-amino-4-hydroxyphenyl- 
 arsine, dissolved in alcohol containing hydrogen chloride, to a 
 cooled benzene solution of phenylarsenious oxide. The yellow, 
 caseous precipitate is soluble in water or alkali, and with an 
 equivalent of caustic soda it gives a precipitate of free 3-amino- 
 4-hydroxy-arsenobenzene, dissolving in excess of alkali. 
 4- A mino-4 '-hydroxyarsenobenzene, 
 
 
 yellow powder, decomposing at 200, soluble in hydrochloric 
 acid or caustic soda, insoluble in water and the ordinary organic 
 media, is prepared by mixing 4-hydroxyphenylarsenious oxide 
 (methyl-alcoholic solution) and /j-aminophenylarsine (dissolved 
 in dilute hydrochloric acid). After several hours the product is 
 precipitated by sodium acetate. 1 
 
 3- A mino-^-hydroxyarsenophenyl-q. '-glycine, 
 
 HO/ \\s:As/ \NH-CH 2 -CO a H, 
 NH 2 ~ / 
 
 yellow powder, darkening at 120 and decomposing completely 
 at 150 ; insoluble in water, alcohol, or the ordinary organic 
 media, but dissolving in hydrochloric acid or aqueous alkalis. 
 
 i. Phenylglycine-^-arsinic acid (275 grams), dissolved in 
 methyl alcohol (2-5 litres) and 2.ZV-sulphuric acid (i litre), is 
 reduced by adding potassium iodide (50 grams) in an equal 
 weight of water and saturating the solution with sulphur 
 dioxide. To the cold solution of phenylglycine-^>-arsenious oxide 
 thus produced is added 4-hydroxy-3-aminophenylarsine (185 
 grams) dissolved in 2 litres of alcohol and i litre of AT-hydro- 
 chloric acid. The product separates as a brownish-yellow pre- 
 cipitate. 
 
 i M. L. and B., D.R.-P., 254187. 
 265 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 ii. Phenylglycine-p-arsenious chloride hydrochloride, 
 AsCl 2 -C c H 4 -NH-CH 2 -C0 2 H,HCl, 
 
 white crystals, decomposing at 120, easily soluble in water, 
 methyl-alcohol, or aqueous alkalis, is precipitated by saturating 
 with sulphur dioxide at 10 a solution of phenylglycinearsinic 
 acid in concentrated hydrochloric acid containing a small amount 
 of hydrogen iodide. This salt is dissolved in water and added to 
 3-amino-4-hydroxyphenylarsine in methyl-alcoholic hydrochloric 
 acid. After twelve hours 3-amino-4-hydroxyarsenophenyl-4'- 
 glycine is precipitated by sodium acetate. 1 
 
 2. Synthesis from Two Dissimilar Arylarsinic Acids or 
 A rylarsenious Oxides . 
 
 The arylarsinic acids and arylarsenious oxides give on reduc- 
 tion symmetrically substituted arsenoaryls, 
 
 2R-AsO 3 H 2 _ v 
 
 R-As:As-R. 
 2R-AsO 
 
 When a pair of dissimilar compounds is employed in the fore- 
 going reductions, dissymmetrically substituted arsenoaryls are 
 produced. 
 
 R-AsO 3 H 2 + R'-As0 3 H 2 
 
 R-As:As-R'. 
 R-AsO + R'-AsO ~ 
 
 This interaction gives a method of synthesis for these arsenoaryls 
 which is supplementary to the general method based on the 
 employment of aromatic primary arsines (v. p. 264). The 
 practicability of the method is greater than might at first sight 
 be expected, inasmuch as the tendency to form the dissymmetric 
 compound R-As:AsR' is much greater than that leading to the 
 production of the two symmetric derivatives R-AsiAs-R and 
 R'-As:As-R'. 
 
 NH 2 
 
 a pale yellow powder, insoluble in water, chloroform, benzene, 
 or aqueous sodium carbonate and dissolving in alcohol, acetone, 
 dilute hydrochloric acid, or caustic soda, is prepared by reducing 
 a mixture of phenylarsenious oxide and 3-amino-4-hydroxy- 
 phenylarsenious oxide. 
 
 1 M. L. and B., D.R.-P., 254187. 2 M. L. and B., D.R.-P., 251104. 
 
 266 
 
AROMATIC PRIMARY ARSINES 
 3 iq.'-Diamino-^-hydroxyarsenobenzene, 1 
 
 NH 2 / \ AsrAs <^ ^>OH 
 
 ~~NH 2 . 
 
 I. This compound is obtained in the form of its dihydrochloride 
 by adding at 10 to -5 solution a of mixed arsinic acids to 
 solution b, containing the reducing agents. 
 
 a. 4-Aminophenylarsinic acid (21-7 grams) and 3-amino-4- 
 hydroxybenzenearsinic acid (23-3 grams) in methyl alcohol 
 (100 c.c.) and 39 c.c. of hydrochloric acid (D 1-12). 
 
 6. Stannous chloride (100 grams) and hydriodic acid (10 c.c. of 
 D = i7) in alcohol (300 c.c.) and 500 c.c. of alcoholic hydrochloric 
 acid saturated at 15. The dihydrochloride obtained as a yellow, 
 microcrystalline precipitate is washed with alcoholic hydro- 
 chloric acid and ether. It is very slightly soluble in organic 
 media, but dissolves in water to a clear solution which gives no 
 precipitate on neutralisation with alkali, thus indicating the 
 complete absence of the symmetrically constituted salvarsan 
 base. Dilute sulphuric acid gives an insoluble, light yellow, 
 flocculent sulphate. 
 
 2. The dihydrochloride is even more readily obtained by mixing 
 the following solutions a and b at 10. 
 
 a. 4-Aminophenylarsenious oxide (21-9 grams) and 3-amino- 
 /j-hydroxyphenylarsinic acid (23-3 grams) in alcohol (90 c.c.) 
 and alcoholic hydrochloric acid (60 c.c.). 
 
 b. Stannous chloride (75 grams) and 5 c.c. of hydriodic acid 
 (D 1-7) in alcohol (200 c.c.) and alcoholic hydrochloric acid 
 (400 c.c.). 
 
 3- A mino-4-hydroxyarsenophenyl-4 '-glycine, 
 
 HO/ \As:As/~ ~\NH-CH 2 -C0 2 H. 
 
 NHT' 
 
 A solution of 3-amino-4-hydroxyphenylarsenious oxide 
 (24-9 grams) and phenylglycine-^-arsenious chloride hydro- 
 chloride (41-6 grams) in 200 c.c. of methyl alcohol is mixed with 
 500 c.c. of N-sodium hydroxide and diluted with 2 litres of 
 water. Anhydrous sodium hydrosulphite (200 grams) is added 
 while the solution is thoroughly stirred, when the arseno-com- 
 pound separates as yellowish-brown paste. The product is an 
 amphoteric substance ; as an amine it dissolves in dilute hydro- 
 
 1 M. L. and B., D.R.-P., 251104. 
 
 267 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 chloric acid, and as a carboxylic acid it is soluble in aqueous 
 alkalis, even in sodium hydrogen carbonate. 
 3': $'-Dichloro-3-amino-$ : ^'-dihydroxyarsenobenzene, 
 
 Cl 
 
 Cl NH 2 
 
 Anhydrous sodium hydrosulphite (200 grams) is added, with 
 stirring, to a solution of 3 : 5-dichloro-4-hydroxyphenylarsenious 
 oxide (33 '9 grams) and 3-amino-4-hydroxyphenylarsenious oxide 
 (24-9 grams) in methyl alcohol (200 c.c.), Af-sodium hydroxide 
 (125 c.c.), and water (2300 c.c.). The solution sets to a yellow 
 paste of arseno-compound, insoluble in water, dissolving in 
 acetone, alcohol, ether, dilute hydrochloric acid, or aqueous 
 alkalis. 
 
 3 : s-Dichloro-^-hydroxyphenylarsenious oxide, colourless prisms 
 sparingly soluble in water, and dissolving easily in alcohol or 
 aqueous alkalis, is prepared by the mild reduction of 3 : 5-dichloro- 
 4-hydroxyphenylarsinic acid (p. 214). 
 
 The foregoing examples suffice to show the application of the 
 second synthetic method of preparing dissymmetric arsenoaryls, 
 but this reaction is not restricted to the aromatic series. Mixed 
 aliphatic-aromatic arseno-derivatives can be obtained, and, 
 what is even more remarkable, the oxygenated arylarsenical 
 derivatives can be reduced in the presence of inorganic compounds 
 of arsenic to give rise to reduction products containing a large 
 proportion of combined arsenic. These products are of thera- 
 peutic interest and have been tried in trypanosomiasis. 
 
 3- A mino-^-hydroxybenzenearsenomethane, * 
 
 NH a 
 \ 
 >As:As-CH s . 
 
 This product, a yellow powder soluble in dilute hydrochloric 
 acid or aqueous caustic soda, is prepared by the following 
 methods : 
 
 i. 3-Amino-4-hydroxyphenylarsenious oxide (20 grams) in 
 methyl alcohol (100 c.c.) and methylarsenious oxide (10-6 grams) 
 in 50 c.c. of the same solvent are added to 2-5 litres of water and 
 reduced together by adding 200 grams of anhydrous sodium 
 hydrosulphite, when the product separates as a light yellow 
 
 precipitate. 
 
 1 M. L. and B., D.R.-P., 253226. 
 268 
 
AROMATIC PRIMARY ARSINES 
 
 2. 3-Amino-4-hydroxyphenylarsinic acid (sodium salt) and 
 sodium methylarsinate, (CH 3 -AsO 8 Na a ,6H a O), in aqueous solution, 
 are reduced together with sodium hydrosulphite in presence of 
 magnesium chloride at 50 until the precipitation is complete. 
 
 3. The hydrochloride of 3-amino-4-hydroxybenzenearseno- 
 methane is obtained by reducing 3-amino-4-hydroxyphenylarsinic 
 acid and methylarsenious oxide with stannous chloride and 
 hydriodic acid at 20 to 10 in acetone and methyl-alcoholic 
 solution containing hydrochloric acid. The product is obtained 
 as a yellow precipitate. 
 
 3. Synthesis by Intermolecular Rearrangement from Two Sym- 
 metrical Arsenobenzene Derivatives. 
 
 Aromatic arsenobenzene derivatives of dissymmetric constitu- 
 tion are produced by (i) condensation between a primary arsine 
 and an arylarsenious oxide, 
 
 RAsH a + R'AsO = RAs:AsR' -f H 2 0. * 
 
 (2) Simultaneous reduction of two arylarsenious oxides or 
 two arylarsinic acids, 
 
 RAs0 8 H. + R'As0 8 H a + 4H a = RAs:AsR' + 6H 2 0. 2 
 This second method may in reality be a variant of the third 
 process, inasmuch as the two symmetric arsenoaryls would 
 interact to give the dissymmetric arseno-derivative. 
 
 (3) Interaction of two symmetrically constituted arseno- 
 benzenes in warm solution. 
 
 RAsiAsR + R'As:AsR' = 2R-As:AsR'. 
 
 The third process goes remarkably readily and to a quantitative 
 extent. 3 
 The dissymmetric compound, 
 
 NH 2 
 
 is produced quantitatively by warming rapidly to 80 
 3*4*5*3 /: 4'- 5 '-hexaminoarsenobenzene tetrahydrochloride 
 (20 grams) and 3 : 3 / -diamino-4 : 4'-dihydroxyarsenobenzene di- 
 hydrochloride (salvarsan) in 400 c.c. of water. The solution 
 poured into 4 litres of hydrochloric acid (D = 1-12) yields 
 
 1 D.R-.P., 254187. 2 D.R.-P., 251104. 
 
 3 Karrer, Ber., 1916, 49, 1648; M. L. and B., Eng. Pat., 17482/1915. 
 
 269 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 the trihydrochloride in light yellow flakes. The product 
 resembles salvarsan in its solubility in aqueous caustic soda ; 
 it is also like the hexaminoarsenobenzene in dissolving in aqueous 
 sodium bicarbonate. 
 
 The dissymmetric compound, 
 
 NH a 
 
 is prepared similarly from hexaminoarsenobenzene hydrochloride 
 and 4 : 4 / -dimethylamino-3 : 5 13': 5 '-tetraminoarsenobenzene 
 hydrochloride ; it forms a stable bicarbamate derivative. 
 
 Section III. Poly arsenical Compounds containing Aromatic 
 
 Groups. 1 
 
 These compounds are trypanocides and also serve as starting 
 materials in the production of other active substances. 
 
 One molecular proportion of an arylarsinic acid or oxide can 
 be condensed on reduction with one or more molecules of in- 
 organic arsenical compounds. The higher the content of arsenic 
 in the product the darker is its colour. 
 
 1. a. Phenylarsinic acid (20 grams) in water (400 c.c.) and 
 2./V-sodium hydroxide (50 c.c.). 
 
 b. Sodium arsenite-(i3 grams) in 500 c.c. of water. 
 
 Solutions a and b are mixed, neutralised with 50 c.c. of 
 2-ZV-acetic acid, and their contents reduced with 200 grams of 
 sodium hydrosulphite and magnesium chloride (40 grams) 
 dissolved in a litre of water. After 24 hours' stirring the light 
 yellow precipitate is collected, washed with water, and dried 
 
 in vacuo. 
 
 As:As-C 6 H 6 
 
 As:As'C 6 H 6 . 
 
 The product is insoluble in water, mineral acids or alkalis, 
 sparingly soluble in the majority of organic solvents, dissolving 
 most readily in chloroform ; it contains 54 per cent, of arsenic. 
 
 2. Molecular proportions of 3-amino-4-hydroxyphenylarsinic 
 acid and sodium arsenite are dissolved in water containing a 
 slight excess of caustic soda ; the solution is neutralised with 
 dilute acetic acid and added to a solution of sodium hydro- 
 sulphite and magnesium chloride, the mixture being digested 
 
 1 M. L. and B., D.R.-P., 270254. 
 270 
 
AROMATIC PRIMARY ARSINES 
 
 and stirred at 50-60 until there is no further precipitation of 
 the orange-yellow polyarsenide. This product, which contains 
 48-9 per cent, of arsenic, is readily soluble in aqueous caustic 
 soda or dilute hydrochloric acid and forms a sparingly soluble 
 sulphate. 
 
 3. The reagents of example 2 are taken, but with two molecular 
 proportions of sodium arsenite to one of the arylarsinic acid. 
 The polyarsenide is darker and dries to a brownish-red powder 
 (As = 57 per cent.). It is readily soluble in dilute caustic soda, 
 and the solution remains clear when acidified with hydrochloric 
 acid ; this acid solution gives a precipitate with sulphuric acid. 
 
 4. Molecular proportions of />-aminophenylarsenious oxide and 
 arsenious chloride are dissolved in methyl alcohol and added to 
 a well-cooled solution of stannous chloride in methyl alcohol 
 and concentrated hydrochloric acid. The product separates as 
 a brownish-yellow precipitate (As = 45 per cent.), dissolving in 
 moist pyridine or hot dilute hydrochloric acid ; the latter solution 
 yields precipitates with dilute sulphuric acid or caustic soda. 
 
 Although the arsenic contents of these polyarsenides do not 
 agree with any simple formulation for these products, yet it is 
 at least possible that they are compounds of tervalent arsenic 
 corresponding with the two following general types : 
 
 As:AsR As v 
 
 II >AsR 
 As' 
 
 I. II. 
 
 The first results from the interaction of molecular proportions 
 of R-As0 3 H 2 and sodium arsenite (or arsenious chloride) ; the 
 second from the simultaneous reduction of R-As0 3 H a (i molecule) 
 and sodium arsenite (2 molecules). 
 
 Aromatic Arseno-phosphides, Polyarsenides, Arseno-antimo- 
 nides, Arseno-selenides, and Arseno-tellurides. 1 
 
 p-Aminophenylarseno-selenide and -telluride Hydrochlorides, 
 HCl,NH a / \-AsSe HC1,NH 8 , 
 
 These compounds are produced respectively by passing a rapid 
 stream of hydrogen selenide or hydrogen telluride through an 
 alcoholic solution of ^-aminophenylarsenious oxide or />-amino- 
 
 1 M. L. and B., D.R.-P., 269699, 269700. 
 271 
 
 L 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 phenylarsenious chloride hydrochloride. The selenide is an 
 orange powder and the telluride a reddish-brown compound ; 
 both are moderately soluble in dilute hydrochloric acid. 
 
 Under similar conditions hydrogen phosphide and antimonide 
 yield arylarseno-phosphides and arylarseno-antimonides, whilst 
 hydrogen arsenide gives rise to aryl polyarsenides, also producible 
 by the reduction method (see p. 270). 
 
 Co-ordination compounds of the aryl arseno-phosphides 1 and 
 arylarseno-antimonides are stated to be of therapeutic value. 
 
 Arsenoantimonides containing Aromatic Radicals. 2 
 
 The synthetic method of reduction illustrated in the preceding 
 section (p. 270) has been extended to the preparation of mixed 
 stibino-arsenicals containing aromatic radicals which exhibit a 
 marked curative effect in diseases induced by protozoal parasites. 
 
 Bis-3~ A mino-^-hydroxyphenylarsenoantimonide (I . ) . 
 
 NH a 
 H. 
 
 3-Amino-4-hydroxyphenylarsinic acid (23-3 grams) in 400 c.c. 
 of water and 60 c.c. of 2iV-caustic soda is mixed with tartar emetic 
 (33-2 grams) in 650 c.c. of water and the resulting solution added 
 to sodium hydrosulphite (500 grams) and magnesium chloride 
 (100 grams) in 2-5 litres of water ; the mixture is digested and 
 stirred at 50-53 until precipitation is complete. The product 
 is a reddish-brown powder soluble either in dilute hydrochloric 
 acid or aqueous caustic soda. 
 
 The complex arseno-antimonide (II.), 
 
 _CCVCH 3 
 ~ >:AS \__ 
 
 As/~~ 
 ' \_ 
 
 Sb:As/ 
 
 CO a -CH 3 
 
 II. 
 
 1 M. L. and B., D.R.-P., 270259. 2 M. L. and B., D.R.-P., 270255. 
 
 272 
 
AROMATIC PRIMARY ARSINES 
 
 is a brown powder sparingly soluble in water or methyl alcohol, 
 produced from antimony oxychloride in glacial acetic acid and 
 methyl anthranilylarsine (a yellow, sparingly soluble powder). 1 
 
 The hydrochloride of a similar arsenostibino-compcund is 
 produced by the agency of the primary arylarsine synthesis. 2 
 
 A methyl-alcoholic solution of 3-amino-4-hydroxyphenyl- 
 arsine (p. 264) containing a small proportion of hydrogen chloride 
 is mixed with antimony trichloride (i mol.) dissolved in the same 
 solvent. The solution assumes an intense brownish-red colour, 
 and ether precipitates the product as a reddish-brown powder 
 soluble in water, caustic alkalis, dilute hydrochloric acid, the 
 alcohols, glycerin, and glycol. It forms a sparingly soluble 
 sulphate. The product is probably a mixture of 
 
 HO/ \As:SbCl and 
 NHo.HCl 
 
 H0 
 
 NH 2 ,HC1 
 
 A < > H 
 
 NH,HC1 
 
 2 , 
 
 3-Amino-4.-hydroxyarsenostibinobenzene, B 
 HO/ 
 
 NI 
 
 
 This compound is obtained in the form of its hydrochloride by 
 bringing together in methyl alcohol containing hydrochloric acid 
 molecular proportions of 3-amino-4-hydroxyphenylarsine and 
 phenylstibine dichloride. The- brownish-red solution, when 
 poured into ether, yields the hydrochloride as a yellowish-brown, 
 flocculent precipitate, easily soluble in water, aqueous alkali, 
 dilute mineral acid, and the hydro xylic solvents. 
 
 The free base is prepared by reducing a mixture of the 
 appropriate pair of aromatic arsenic and antimony derivatives as 
 follows : 
 
 Solution a. 3 - Amino - 4 - hydroxyphenylarsenious oxide 
 (10 grams) in 60 c.c. of methyl alcohol, 200 c.c. of water, and 
 50 c.c. of AT-sodium hydroxide. 
 
 Solution b. Phenylstibinic acid (12-3 grams) in 300 c.c. of 
 water and 50 c.c. of AT-sodium hydroxide. 
 
 1 M. L. and B., D.R.-P., 269744. 
 
 2 Ehrlich. and Karrer, Ber., 1913, 46, 3569. 
 
 3 M. L. and B., D.R.-P., 269743. 
 
 273 T 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Solutions a and b are mixed and stirred at the ordinary tempera- 
 ture with sodium hydrosulphite (200 grams) and magnesium 
 chloride (40 grams) in I litre of water until a filtered sample 
 remains clear on warming. The brownish-yellow precipitate, 
 obtained in quantitative yield, is readily soluble in moist 
 pyridine, aqueous caustic soda, or methyl alcohol containing 
 hydrochloric acid. 1 The hydrochloride yields co-ordination 
 compounds with gold and osmium chlorides, which are respec- 
 tively yellowish-brown and brownish-green powders insoluble 
 in ether and dissolving readily in water. 2 
 
 ^-Hydroxyphenylarsenostibinobenzene? 
 
 HO/ NAs:Sb/ 
 
 is a brown powder soluble in aqueous alkali produced by adding 
 phenylstibine oxide dissolved in hot glacial acetic acid to a 
 methyl-alcoholic solution of ^-hydroxyphenylarsine. 
 4 :<\'-Dihydroxystibinoarsenobenzene* 
 
 \Sb:As/ \OH. 
 
 Molecular proportions of sodium phenol-^>-arsinate and sodium 
 phenol-^>-stibinate in dilute aqueous solution are reduced with 
 sodium hydrosulphite until precipitation is complete. The 
 product, a brownish-black powder, is insoluble in water, but 
 dissolves in alcohol, acetone, pyridine, or aqueous caustic soda. 
 4 '-A cetylaminophenylstibinoarseno-^-phenylglycinef 
 
 >NH-CH 2 -CO 2 H. 
 
 This compound, a brownish -black powder, is produced by reduc- 
 ing with sodium hydrosulphite a solution containing molecular pro- 
 portions of phenylglycine-^>-arsinic acid and 4-acetylamino- 
 phenylstibinic acid in slight excess of aqueous caustic soda. The 
 product is insoluble in water, alcohol, or acetone, but dissolves in 
 aqueous alkalis or in moist pyridine. 
 
 3-^4 mino-^-hydroxyarseno-^ '-acetylaminostibinobenzene hydro- 
 
 \Vs:Sb/ \NH-CO-CH 8 , is an amor- 
 
 chloride^ 
 
 phous, dark brown powder produced by adding 3-amino-4-hydr- 
 
 1 MX. and B., D.R.-P., 270255; U.S. P., 1111821. 
 
 2 M. L. and B., D.R.-P., 270259. 3 M. L. and B., D.R.-P., 269744. 
 1 M. L. and B., D.R.-P., 270255. 5 M. L. and B., D.R.-P., 270255. 
 6 Ehrlich and Karrer, Ber., 1913, 46, 3568. 
 
 274 
 
AROMATIC PRIMARY ARSINES 
 
 oxyphenylarsine (0-8 gram) in methyl-alcoholic hydrochloric acid 
 to ^-acetylaminophenylantimonious iodide, NHAc^C 6 H 4 SbI 2 , 
 (1-64 grams), in glacial acetic acid. It is precipitated by ether and 
 is soluble in water or methyl alcohol, dissolving in alkalis to a clear 
 solution. Of the arsenostibine aryls, this compound gives the 
 best therapeutic results on animals infected with trypanosomes. 
 4-^4 cetylaminophenylarsenoantimonious bromide, 
 
 \As:SbBr. 
 
 The ^-acetylaminophenylarsine, CH 3 -CO-NH-C 6 H 4 -AsH 2 , re- 
 quired in this preparation is a white powder, soluble in methyl 
 alcohol or dilute hydrochloric acid, obtained by reducing acetyl- 
 ^>-arsanilic acid with zinc dust and hydrochloric acid. 
 
 . When mixed in molecular proportions with antimony tribromide 
 in methyl alcohol containing hydrochloric acid, the foregoing 
 arsine yields the condensation product, a reddish-brown powder 
 precipitated by ether and soluble in water or dilute hydrochloric 
 acid. 1 
 
 The corresponding arsenoantimonious chloride yields a co- 
 ordination compound with cupric chloride, which is easily soluble 
 in aqueous alkalis or dilute mineral acids. 2 
 
 3-^4 mino-^-hydroxyphenylarsenoantimonious acetate hydro chloride, 
 
 CH 3 -CO-OSb:As-C 6 H 8 (OH),NH 2 ,HCl. 
 
 Antimony oxy-salts as well as antimony halides can condense 
 with primary aromatic arsines, and, in the present instance, the 
 compound results from the interaction of 3-amino-4-hydroxy- 
 phenylarsine in methyl alcohol and tartar emetic dissolved in 
 hot glacial acetic acid. The product, a brownish-yellow, flocculent 
 precipitate, is very soluble in water, aqueous alkalis, or dilute 
 hydrochloric acid. Sulphuric acid yields a sparingly soluble 
 sulphate and dimethylaminobenzaldehyde a slightly soluble 
 Schiff base. 3 
 
 Aromatic Arseno-bismuth Halides, 4 
 CHjj-CO-NH^ \As:BiBr. 
 
 I. 
 
 p-Acetylaminophenylarsenobismuth bromide (I.), a black, 
 sparingly soluble powder, is obtained by bringing together bismuth 
 
 1 M. L. and B., D.R.-P., 269743. * D.R.-P., 270259. 
 
 8 D.R.-P., 269744. 4 M. L. and B., D.R.-P., 269745. 
 
 275 T 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 bromide and ^-acetylaminophenylarsine (prepared by reducing 
 acetyl-^>-arsanilic acid) in methyl-alcoholic hydrobromic acid, the 
 product being precipitated by ether. 
 
 Tris-3 - amino - 4 - hydroxyphenylarsenodibismuthdihydrochloride 
 (II.), a black precipitate, sparingly but completely soluble in 
 water, is prepared by the interaction of 3-amino-4~hydroxy- 
 phenylarsine and bismuth chloride in methyl alcohol containing 
 hydrogen chloride. It is decomposed by alkalis or acids or by 
 boiling the aqueous solution. 1 
 
 ,/ 
 
 \ 
 
 NH 2 ,HC1 
 
 II. 
 
 NOH 
 
 NH 2 ,HC1J S 
 
 Arsenobenzene and its Analogues. 
 
 In addition to the aromatic stibino -compounds described in 
 a later chapter (p. 323), we are now acquainted with the follow- 
 ing six types of organic compounds containing doubly-linked 
 atoms of the nitrogen family of elements : 
 
 R-P:P-R' 
 
 light yellow 
 phospho-chromophor. 
 
 R-Sb:Sb-R' 
 
 yellow stibino- 
 
 chromophor. 
 
 R-As:As-R' 
 
 yellow arseno- 
 chromophor. 
 
 R-As:Bi-R' 
 
 black arseno-bis- 
 mutho-chromophor. 
 
 R-N:N-R' 
 
 red azo- 
 chromophor. 
 
 R-As:Sb-R' 
 orange to yellow- 
 ish-brown arseno- 
 stibino-chromophor. 
 
 The aromatic azo-compounds contain a well-marked chromo- 
 phor. The weaker colour effect in the phospho- and arseno- 
 compounds is possibly due to the greater tendency to polymerisa- 
 tion which would result in the disappearance of the double 
 linking. 2 
 
 The weakest chromophor of the whole series is the phospho- 
 group, P:P, and from this group to the arseno-bismutho-group 
 the colour increases as the unsaturated character of the molecule 
 becomes more pronounced. 3 
 
 1 Ehrlich and Karrer, Ber., 1913, 46, 3569. 
 
 2 Michaelis and Schafer found by the cryoscopic method in dry phenol 
 that in this solvent the molecular weight of arseno-^-toluene corresponds 
 with C 7 H 7 As:AsC 7 H 7 , Ber., 1913, 46, 1742. 
 
 3 Ehrlich and Karrer, loc. cit. 
 
 276 
 
CHAPTER VIII 
 
 LUARGOL 
 
 Co-ordination Compounds of Aromatic Arsenicals 
 
 THE arsenoaryl compounds exhibit considerable residual 
 affinity, and in this respect resemble the aliphatic tertiary arsines 
 which long ago were shown by Cahours and Gal (p. 42) to give 
 rise to co-ordination compounds with the chlorides of platinum, 
 palladium, and gold. 
 
 In the course of his researches on salvarsan, Ehrlich was led 
 to examine the interaction of this drug and various metallic 
 salts, with the result that he discovered a new series of co-ordina- 
 tion compounds in which one or two molecular proportions of 
 the metallic salt enter into such intimate combination with the 
 arsenoaryl derivative that the metal is held in the new complex 
 in a non-ionisable condition, whereby many of its ordinary 
 analytical (ionic) interactions become masked. 
 
 This interaction is a very general one ; it is manifested not only 
 by all arsenoaryls whether substituted in the nucleus or not, 
 but is also exhibited by organic arsenious oxides and arsines. 1 
 
 On the other hand, this combination occurs with the salts of 
 copper, silver, gold, mercury, palladium, iridium, ruthenium, 
 and osmium. The tendency for aromatic arsenious oxides, 
 RAsO, to form these co-ordination compounds with metallic 
 salts is less pronounced than in the case of arsenobenzene and 
 its derivatives. In the oxides the residual affinity of the arsenic 
 is less effective, and appears also to be greatly influenced by the 
 substituents of the aromatic nucleus. With the primary arsines, 
 such as 4-amino-3-hydroxyphenylarsine, for example, the residual 
 affinity is very strong ; but so also is the tendency for these 
 
 1 Even quinquevalent arsenic exhibits a capacity for forming co- 
 ordinated compounds with such associating groups as MoO 4 or Mo 2 O 7 . 
 Rosenheim and Bulecki, Ber., 1913, 46, 539- 
 
 277 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 arsines to act as reducing agents. The metallic co-ordination 
 compounds are produced momentarily, but the metal is forth- 
 with precipitated by the reducing action of the organic arsine. 
 
 On account of their therapeutic importance, it is chiefly the 
 co-ordination compounds of salvarsan which have been studied, 
 but similar products have been obtained from other arsenoaryls, 
 and even from arsenobenzene itself. These facts throw light 
 on the constitution of the arsenical co-ordination complexes. 
 
 If these products were peculiar to salvarsan and its analogues, 
 there would be some justification for the view that the sub- 
 stituent groups OH and NH 2 were more or less responsible for 
 these combinations. The following formulae indicate two ways 
 in which this influence of the substituents might be manifested. 
 Residual affinity as distinct from principal valency is represented 
 conventionally in the formulae by dotted lines. 
 
 As. As As. As 
 
 /\ /\ /\\ /\\ 
 
 NH, 
 
 NH 
 
 H 'MeX OH MeX 
 
 I. 
 
 OH- -MeX 
 
 2 \/ 
 OH---1V] 
 
 MeX 
 
 II. 
 
 In the first arrangement the substituents alone are involved in 
 the co-ordination complex, but this constitution is not convincing, 
 inasmuch as it does not explain the non-formation of similar 
 additive compounds from the metallic salts, MeX, and amino- 
 phenylarsinic acids, AsO 3 H 2 -C 6 H 3 (NH 2 )-OH. 
 
 The second configuration suggests the intervention of the 
 unsaturated arsenic atoms, but does not indicate the formation 
 of co-ordination compounds from unsubstituted arsenobenzene, 
 This fact is, however, taken into account in the third alternative, 
 in which the co-ordination is represented as taking place entirely 
 between the unsaturated arsenic atoms and the metallic salts 
 (2 mols.). 
 
 As- --MeX 
 
 MeX 
 
 II. Salvarsan co-ordination 
 compounds. 
 
 278 
 
 MeX 
 
 As- --MeX 
 
 IV. Arsenobenzene co- 
 ordination compounds. 
 
LUARGOL 
 
 This formulation suggests a maximum of two molecules of 
 metallic salt to each molecular proportion of arsenoaryl 
 (=2 atoms of As). The experimental results show, however, 
 that complexes exist with only one molecular proportion of the 
 metallic salt, in which, therefore, according to the foregoing 
 view, the residual affinity of only one arsenic atom is saturated. 
 fR-As---Me~]X 
 
 R-As 
 
 Arseno-compounds containing even a smaller proportion of 
 the metallic salt have been recognised, notably the important 
 drug " Luargol." 
 
 The discovery of these arsenoaryl metallic compounds was first 
 made known publicly by Ehrlich at the International Congress 
 of Medicine held in London in 1913, although his earliest patent 
 application was dated July, 1912. A fuller communication on 
 the subject in collaboration with Karrer was published post- 
 humously in 1915. 1 
 
 Shortly after Ehrlich's earliest communication, Danysz, 
 working independently, noticed the formation of a metallic 
 complex from salvarsan and silver nitrate. His earliest note on 
 this observation was published in 1913, and a fuller account of 
 the co-ordination compounds of salvarsan with silver chloride, 
 bromide, and iodide was given in 1914. a 
 
 As an illustration of the great tendency which exists to form 
 these co-ordination complexes from the arsenoaryls and salts 
 of the noble metals, it may be mentioned that when the latter 
 are present during reduction of the generating arylarsinic acids, 
 the noble metals are not precipitated by the reducing agent, 
 but are found in the co-ordination complex at the close of the 
 reduction. 
 
 The experimental difficulties in the way of studying these 
 salvarsan metallic complexes are considerable. The products 
 show little tendency to crystallise, and their solubility is not very, 
 different from that of the generating arseno-compound. The 
 copper compounds were found to be most readily separated. 
 
 1 ^Ehrlich and Karrer, Ber., 1915, 48, 1634. 
 
 2 Danysz, Compt. rend,, 1913, 157, 644 ; 1914, 158, 199. 
 
 279 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Copper Derivatives. 
 
 i. CuHjaOaNaAs^HC^CuCl-j : Salvarsan (100 grams) in 
 1600 c.c. of methyl alcohol and 16 c.c. of saturated alcoholic 
 hydrochloric acid is treated with 35-8 grams of crystallised copper 
 chloride (CuQ 2 ,2H 2 O) in 400 c.c. of methyl alcohol. The 
 copper derivative separates, the mixture is poured into 8 litres 
 of ether, and the brick-red precipitate washed and dried in vacuo. 
 The whole operation is conducted preferably in an atmosphere 
 of carbon dioxide or nitrogen. 
 
 This copper derivative is a reddish to orange-yellow powder, 
 moderately soluble in water, more readily in glycerol or glycol. 
 It dissolves in 27V-sodium hydroxide without precipitation of 
 copper hydroxide until the liquid is heated for some 
 time. 
 
 The compound is strongly toxic to trypanosomes. When 
 tried on mice infected with Trypanosoma brucei the ratio of 
 healing dose to the lethal dose is only 15 per 1,000. This sub- 
 stance has also given promising results in various human 
 diseases. 1 
 
 2. C 12 H 12 O 2 N2As 2 ,2HCl,2CuCl2 : This copper derivative is 
 prepared as in the preceding experiment, but the amount of 
 copper salt is doubled. The great tendency which exists to 
 form these salvarsan co-ordination compounds is illustrated in 
 a striking manner by an alternative method of preparation. 
 Sadium 3-ammo-4-hydroxyphenylarsinate and copper chloride 
 are dissolved in water in molecular proportions and reduced at 
 50 with alkaline hydrosulphite. Reduction of arsinic acid to 
 arseno-compound and formation of the co-ordination complex 
 proceed concurrently, and yellowish-brown flocculae of the 
 copper compound are precipitated. The product is very soluble 
 in dilute hydrochloric acid or aqueous sodium hydroxide. 
 
 Silver Derivatives. 
 
 i. C 12 H 12 O 2 N 2 As 2 ,2HCl,2AgNO 3 : A brown, flocculent pre- 
 cipitate produced by pouring into ether the reddish-brown 
 solution obtained by mixing methyl-alcoholic solutions of 
 salvarsan and silver nitrate. It is easily soluble in water, aqueous 
 sodium hydroxide, or methyl alcohol. The silver present is not 
 
 1 Arch. Schiffs- und Tropenhygiene, 17, 845 ; 18, 743; Miinchener med. 
 Wochenschrift, 1914, 61, i ; 1915, 62, 147, 149. 
 
 280 
 
LUARGOL 
 
 precipitated by chlorides. Sodium chloride throws down a 
 brownish-yellow precipitate moderately soluble in water. 
 
 R-As - - AgN0 3 R-As - - AgCl 
 
 II *% II +2NaN0 8 
 
 R-As AgNO 8 R-As AgCl 
 
 A compound with only one AgN0 3 is similarly prepared. 
 
 Mercury Derivatives. (i) With HgQ 2 : yellow, granular powder 
 from methyl alcohol. Decomposed by water or aqueous sodium 
 hydroxide with separation of metallic mercury. 
 
 (2) The mercuric iodide compound is more stable than the 
 preceding ; it dissolves readily in water. 
 
 Gold Derivatives. Compounds are formed with one and two 
 molecular proportions of gold chloride. These brownish-yellow 
 powders are easily soluble in water, alcohol, or aqueous alkalis. 
 Addition of more than two molecular proportions of gold chloride 
 to an aqueous solution of the compound with 2AuCl 3 determines 
 the sudden precipitation of all the gold present in the metallic 
 state. 
 R-As,AuCl 3 
 
 || + 2/3AuCl 3 +6H 2 0=2R-AsO 3 H 2 +8HCl + 2 2/3 Au. 
 
 R-As,AuCl s 
 
 The platinum and palladium compounds are brown powders 
 soluble in water. 
 
 Arsenobenzene in pyridine gives, with aqueous silver nitrate, 
 a deep brown solution from which ether-alcohol precipitates a 
 black co-ordination compound. The copper compound, a 
 reddish-brown, insoluble powder, is obtained by adding hypo- 
 phosphorous acid to a solution of copper chloiide and phenyl- 
 arsinic acid. 1 
 
 Section I. -Co-ordination Compounds of Arsenobenzene and its 
 
 Derivatives.* 
 
 Arsenobenzene and Silver Nitrate. Arsenobenzene in pyridine 
 and concentrated aqueous silver nitrate in molecular propor- 
 tions give a brownish-black solution from which ether-alcohol 
 precipitates the black product which is insoluble in water. 
 
 Arsenophenylglycine and Auric Chloride. A dilute solution of 
 auric chloride (0-25 gram) is added slowly to 1-5 grams of arseno- 
 
 1 Ehrlich and Karrer, Ber., 1915, 48, 1644. 
 
 2 M. L. and B., D.R.-P., 268220, 268221, 270253, 270256, 270257, 
 270258, 270259. 
 
 28l 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 phenylglycine in water. The additive compound, which is precipi- 
 tated by alcohol-ether, is a greyish-yellow powder easily soluble in 
 water or aqueous alkalis ; it retains the gold very tenaciously. 
 
 4 : ^'-Dihydroxyarsenobenzene and Auric Chloride. Molecular 
 proportions of these substances are mixed in sufficient aqueous 
 caustic soda to dissolve the arseno-compound, which is precipi- 
 tated by alcohol-ether as a brownish-black powder readily 
 soluble in water. 
 
 3 : 4 i^'i^'-Tetramino-arsenobenzene-'N-methylenesulphinate and 
 Cupric Chloride. The additive compound is a yellowish-red 
 powder soluble in alkalis. 
 
 Co-ordination Compounds of Arylarsenical Derivatives and the 
 
 Metals. 1 
 
 On mixing the salts of gold or the platinoid metals with solu- 
 tions of salvarsan dihydrochloride, soluble co-ordination com- 
 pounds are produced, in which the metal is no longer precipi- 
 tated by electrolytes such as acids, bases or salts. The solutions 
 of these co-ordination compounds are more stable than those 
 of salvarsan itself. These compounds are quite different fiom the 
 product of the interaction of gold chloride and sodium 
 ^>-arsanilate. 2 
 
 Introduced into the animal organism, these co-ordination 
 compounds combine the haptophoric capacity of the arseno- 
 compound and the specific physiological reaction of the metal. 
 
 Salvarsan-Gold Compound. To 5 c.c. of 5 per cent, aqueous 
 solution of salvarsan dihydrochloride are added 2 c.c. of 10 per 
 cent, gold chloride. A clear dark brown solution is obtained 
 of acid reaction ; it gives no precipitate of auric hydroxide with 
 alkali. The alkaline solution does not give a precipitate of gold 
 when reduced with formaldehyde or sodium hydrosulphite. 
 
 A similar co-ordination compound is prepared by adding 2 c.c. 
 of 5 per cent, sodium aurate to 5 c.c. of an aqueous 5 per cent, 
 solution of disodium salvarsan. 
 
 The salvarsan-gold compound can be obtained solid by con- 
 centrating the solution in vacuo or by precipitation with alcohol- 
 ether or alcohol-acetone. 
 
 Two varieties of salvarsan-platinum compound are obtained 
 as in the following examples. 
 
 1 M. L. and B., D.R.-P., 268220; cf. Eng. P., 1247/1914. 
 
 2 D.R.-P., 206343. 
 
 282 
 
LUARGOL 
 
 a. 3 c.c. of 10 per cent, aqueous platinic chloride to 5 c.c. of 
 5 per cent, salvarsan dihydrochloride. 
 
 b. 2 c.c. of 10 per cent, platinic chloride rendered alkaline 
 with sodium hydroxide to 5 c.c. of 5 per cent, disodium salvarsan. 
 
 Co-ordination Compounds of Salvarsan. 
 
 1. With Mercuric Chloride. 1 Molecular proportions of salvar- 
 san dihydrochloride and mercuric chloride are dissolved in methyl 
 alcohol, the solution of the arsenical reagent slightly acidified 
 with methyl-alcoholic hydrochloric acid and mixed with mercuric 
 solution. The colour changes from light yellow to deep orange, 
 and ether precipitates the compound as a pale yellow powder 
 readily soluble in glycerin, ethylene glycol, methyl alcohol, or 
 acidified potassium iodide solution. It is decomposed by water, 
 especially on warming. 
 
 2. With Silver Nitrate. i. On mixing methyl-alcoholic solutions 
 of salvarsan dihydrochloride and silver nitrate in molecular pro- 
 portions the mixture assumes a reddish-brown colour, and ether 
 precipitates the product as a brownish-yellow powder, very 
 soluble in water, methyl alcohol, or glycerin. The silver 
 present is a non-ionisable condition and is not eliminated by 
 reducing agents. 
 
 ii. A dark brown product, obtained as in the preceding experi- 
 ment by using two molecular proportions of silver nitrate, dissolves 
 in water with an intense reddish-brown colour. 
 
 3. With Silver Nitrate and Auric Chloride. Silver nitrate and 
 auric chloride in molecular proportions and dissolved in methyl 
 alcohol are added successively to a methyl-alcoholic solution of 
 salvarsan dihydrochloride. Ether precipitates the triple com- 
 pound as a brownish-red powder, easily soluble in water, glycerin, 
 or other hydro xylic solvents. 
 
 4. With Cuprous or Cupric Chloride. i. A methyl-alcoholic 
 solution of salvarsan hydrochloride (i mol.) is added to cuprous 
 chloride (i mol.) dissolved in methyl-alcoholic hydrochloric 
 acid, the product being precipitated by ether. It is a brick-red 
 powder easily soluble in water. 
 
 ii. A methyl-alcoholic solution of salvarsan hydrochloride, 
 
 slightly acidified, is added to hydrated cupric chloride dissolved 
 
 in the same solvent. The solution becomes brownish-red and 
 
 the co-ordinated compound begins to crystallise, the precipita- 
 
 1 M. L. and B., D.R.-P., 270253. 
 
 283 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 tion being completed with ether. The orange-yellow product is 
 readily soluble in water, glycerin, or ethylene glycol. In the 
 cold, aqueous alkalis do not precipitate copper hydroxide ; 
 only on warming is the copper eliminated as oxide. 
 
 An alternative mode of preparation of these co-ordination 
 compounds of salvarsan is to mix the generator of this organic 
 arsenical with the metallic salt before adding the reducing 
 agent. 1 
 
 With Cupric Chloride. i. 3-Amino-4-hydroxyphenylarsinic acid 
 (10 grams) and hydrated cupric chloride (3-64 grams) in 100 c.c. 
 of water and 43 c. of 2^-hydrochloric acid are treated succes- 
 sively at 50 with sodium hydrosulphite (50 grams) in 150 c.c. 
 of water and 43 c.c. of 2JV-caustic soda. The brownish-red 
 precipitate is readily soluble in dilute hydrochloric acid or 
 caustic soda. 
 
 ii. 3-Amino-4-hydroxyphenylarsenious oxide (2 mols.) and 
 cupric chloride (i mol.) are dissolved in hydrochloric acid and 
 the arsenical compound reduced with stannous chloride. The 
 hydrochloride of the copper additive compound is precipitated. 
 
 3. With Auric Chloride. 3-Amino-4-hydroxyphenylarsenious 
 oxide hydrochloride (2 mols.) and auric chloride (i mol.) in 
 aqueous solution are treated with sodium hydrosulphite, when 
 the auric chloride additive compound of 3 :3'-dia,mmo-4 :4'-di- 
 hydroxyarsenobenzene is obtained as a golden-yellow precipitate. 
 
 4. With Platinic Chloride. As in the foregoing experiment 
 the additive compound of platinic chloride and salvarsan separ- 
 ates at once as a yellowish-brown precipitate readily soluble 
 in pyridine or in ^-hydrochloric acid. 
 
 Co-ordination Compounds of Neosalvarsan. 2 
 
 1. With Cupric Chloride. Sodium 3:3 / -diamino-4:4'-dihy- 
 droxy-arsenobenzene-N-methylenesulphinate (3 parts) and 
 hydrated cupric chloride, CuCl 2 ,2H 2 O (07 part), are mixed in 
 strong aqueous solutions and the additive compound precipitated 
 as a yellow, voluminous powder on adding the mixed solution to 
 ether-alcohol. In the cold the product no longer gives the reaction 
 of copper, the combination being broken up only on boiling. 
 
 2. With Silver Nitrate. The product, a black powder, is 
 precipitated by ether-alcohol from an aqueous solution of its 
 generators, which are mixed in molecular proportions. The 
 
 1 M. L. and B., D.R.-P., 270258. z M. L. and B., D.R.-P., 268221. 
 
 284 
 
LUARGOL 
 
 aqueous solution of this silver compound is markedly 
 fluorescent. 
 
 3. With Gold Chloride. The generators are mixed in molecular 
 proportions and the very soluble brownish-red product is pre- 
 cipitated from its aqueous solution with ether-alcohol. 
 
 4. With Platinic Chloride. The brown product from molecular 
 proportions of platinic chloride and neosalvarsan is readily 
 soluble in water and is precipitated therefrom by ether-alcohol 
 
 Section II. Luargol : " 102 " of Danysz's Series. 
 
 3 : s'-Diamino-q. : ^'-dihydroxyarsenobenzene-silver-bromide-anti- 
 monyl Sulphate, [C 12 H 12 O 2 N 2 As 2 ] 2 ,AgBr,SbO(H 2 SO 4 ) 2 . The im- 
 portance of the combinations of salvarsan and metallic salts 
 was first made public by Ehrlich on the 8th August, 1913, at 
 the International Medical Congress held in London. On the 
 2Oth October of the same year Danysz described the therapeutic 
 and antiseptic effects of salvarsan silver derivatives, one of these 
 being a combination of the organic arsenical with silver nitrate. 1 
 Subsequently he described a method of making the corresponding 
 silver halide combinations which consisted in adding drop by 
 drop a solution of the silver halide in potassium cyanide to a 
 solution of salvarsan. A precipitate forms, which dissolves to 
 a dark limpid solution, hydrogen cyanide being evolved. In 
 this way one molecule of silver halide can be combined with one 
 molecule of salvarsan. If precipitation occurs before this 
 proportion is reached, hydrochloric acid is added. Finally, 
 the complex product is precipitated by sulphuric acid in the 
 form of its sparingly soluble sulphate, which can be freed from 
 potassium cyanide and chloride. The product is an orange- 
 yellow to dark brown powder, dissolving in water rendered 
 alkaline by soda. The chlorine derivative is less active than 
 the iodine and bromine compounds. The toxicity of the bromo- 
 compound is equal to that of salvarsan, whereas its sterilising 
 power in vitro or in vivo is much greater. 
 
 The bromide combinations are much more active than those 
 with silver chloride or nitrate and less toxic than the iodide 
 compounds. 
 
 Even though the mercury, gold, and platinum combinations 
 are a little more active than those of silver, they are less stable 
 and relatively more toxic. 
 
 Continuing his researches, Danysz found that a triple combina- 
 1 Compt. rend., 1913, 157, 644 ; 1914, 158, 199. 
 
 285 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 tion could be produced of salvarsan, silver bromide, and tervalent 
 antimony having the above empirical formula. 
 
 It has been found that antimony compounds have a beneficial 
 effect in refractory cases of trypanosomiasis and in arsenic- 
 resisting cases of syphilis. In " Luargol " the antiseptic properties 
 of salvarsan are increased by the co-ordinated silver bromide, and 
 these are reinforced by the specific action of the antimony. 
 
 The drug has the following percentage composition : 
 C, 19-84 ; Ag, 7-40 ; Br, 5-52 ; As, 20-60 ; Sb, 8-19 ; S, 8-87.1 
 
 Luargol is very efficacious in experimental cases of Trypanosoma 
 surra and Tr . gambiense ; the ratio of maximum tolerated to 
 trypanocidal dose is 80 or 100 : i, whereas with salvarsan it is 
 10 : i. In sleeping sickness luargol is stated to be ten times as 
 active as salvarsan. Very promising results have been obtained 
 in a large number of cases of human syphilis. 2 
 
 Luargol is insoluble in water and is rendered soluble by the 
 addition of caustic soda (0-4 gram NaOH to i-o gram luargol). 
 The solution thus prepared should be injected intravenously ; 
 ill-effects are produced by subcutaneous exhibition. The 
 substance and its solutions are comparatively stable, and the 
 alkaline preparation can be heated for two to three hours 
 without losing its efficacy. 
 
 Section HI. Co-ordination Compounds of Aromatic 
 Poly arsenides. 3 
 
 The polyarsenical compound (3 grams) described on page 270, 
 which probably has the constitution 
 
 As:As-C 6 H 8 (OH)-NH 2 
 
 Is: 
 
 ;:As-C 6 H 8 (OH)-NH 2 , 
 
 is dissolved in methyl alcohol containing hydrochloric acid 
 (D = i -12) and treated with one or other of the following 
 reagents : 
 
 i. Cuprous chloride (i gram) in methyl-alcoholic hydrochloric 
 acid, the additive compound being precipitated from the dark 
 red solution by ether. The product is soluble in water to a 
 solution from which sulphuric acid precipitates a sparingly 
 
 1 Danysz, Compt. rend., 1914, 159, 452. 
 
 z Renault, Fournier, and Guenot, Compt. rend., 1915, 161, 685. Dalimier 
 and Levy-Franchel, ibid., 1916, 162, 440. 
 3 M. L. and B., D.R.-P., 270256. 
 
 286 
 
LUARGOL 
 
 soluble sulphate. The copper present is not precipitated by 
 caustic alkali. 
 
 2. Mercuric chloride (27 grams) in methyl alcohol. An orange 
 precipitate separates and the deposition is completed by ether. 
 The product is not soluble in water or methyl alcohol and is 
 blackened by caustic soda. 
 
 3. Silver Nitrate (0-85 gram). The brown product is readily 
 soluble in methyl alcohol or water and is precipitated by ether. 
 It does not give the ionic reactions of silver. 
 
 Cupric Chloride. The hydrated chloride, CuCl 2 ,2H 2 O, 
 (17 grams) in methyl alcohol (5 c.c.) and arsenious chloride 
 (1-8 grams) are added successively to 3-amino-4-hydroxy-phenyl- 
 arsenious oxide (2 grams) in 10 c.c. of alcohol, and this solution 
 added to a well-cooled solution of stannous chloride (5 grams) 
 in 20 c.c. of hydrochloric acid (D 1-19) and 20 c.c. of glacial 
 acetic acid. The hydrochloride of the copper additive compound 
 of the foregoing polyarsenide is precipitated as a brown powder, 
 soluble in water or aqueous alkalis. 1 
 
 Other Co-ordination Compounds of Organic Arsenicals : 
 
 I. Aliphatic Series. 
 
 1. Cacodyl oxide compounds (v. p. 13). 
 
 2. Metallic thiocacodylates (v. p. 16). 
 
 3. Trialkylarsine compounds (v. p. 42). 
 
 II. Aromatic Series. 
 
 1. Copper salvarsan (v. p. 228). 
 
 2. Compounds of the primary arylarsines (v. p. 263, 264). 
 
 3. Compounds of the aryl arseno-phosphides and -antimonides 
 (v. p. 272, 274). 
 
 Application of Drugs containing Tervalent Arsenic. 
 
 Even the barest summary of the voluminous literature which 
 has developed round the medical application of organic arsenical 
 compounds would be quite beyond the scope of this treatise. 
 Moreover, much of the subject matter is still in the controversial 
 stage. It seems, however, definitely established that compounds 
 containing tervalent arsenic are far more efficacious against 
 
 1 M. L. and B., D.R.-P., 270258. 
 287 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 pathogenic protozoa than the corresponding derivatives of 
 quinquevalent arsenic and, in efficacious doses, are much less 
 toxic and dangerous to the host of these organisms. 
 
 Atoxyl, which was originally stated to be forty times less toxic 
 than potassium arsenite (Fowler's solution), was at first extensively 
 used in psoriasis, anaemia, syphilis, sarcoma, elephantiasis, 
 relapsing fever, malaria, tuberculosis, and trypanosomiasis, but 
 its poisonous effects are cumulative, leading to disturbance of 
 vision and later complete blindness through optic atrophy. The 
 toxic action on the kidneys, though delayed, showed eventually 
 the effect of arsenic on these organs. 
 
 Ehrlich's investigations were directed to the production of an 
 arsenical drug in which the ratio of curative dose to toxic dose 
 should be as small as possible and in any case less than one-third. 
 The most promising results were obtained successively with 
 sodium arsenophenyl-^>-glycinate (" 418 ") and with 3:3 '-diamino- 
 4:4'-dihydroxyarsenobenzene dihydrochloride ("606"). The 
 latter drug came nearest to Ehrlich's ideal of " Therapia sterilisans 
 magna," the extermination of all the parasites at " one fell 
 swoop." This procedure would have the great practical advantage 
 of killing off the specific pathogenic germs before successive 
 generations of these organisms had acquired an immunity to 
 smaller doses. This ideal of a single curative dose has not been 
 realised in practice, although the effect of salvarsan and allied 
 drugs is extremely rapid and well marked, even after very few 
 repetitions. 
 
 Among the drugs containing quinquevalent arsenic which 
 for a time had a vogue in the treatment of sleeping sickness, 
 syphilis, and relapsing fever may be mentioned Arsacetin (sodium 
 acetyl-^>-arsanilate), Orsudan (sodium acetyl-2-aminotolyl-5- 
 arsinate), and Pectine (sodium benzenesulphonyl-^-arsanilate) . 
 These drugs were less toxic than atoxyl, and their solutions, 
 unlike those of atoxyl, could be sterilised by boiling or even by 
 heating under pressure at 130, without the occurrence of 
 destructive hydrolysis leading to the production of poisonous 
 arsenic acid. 
 
 As the result of exhaustive trials on animals and numerous 
 clinical tests, medical practice has now concentrated on the 
 use of salvarsan and its modern substitutes. 
 
 In Great Britain salvarsan, also sold as kharsivan and arseno- 
 billon, and neosalvarsan, also purveyed as neokharsivan and 
 novarsenobillon, are approved by the Local Government Board 
 
 288 
 
LUARGOL 
 
 for issue under the Public Health (Venereal Diseases) Regula- 
 tions, 1916, provided that none of these drugs shall be offered 
 for sale until the preparations have been examined and passed 
 by a committee of experts appointed by the Board of 
 Trade. 
 
 The two drugs are very similar in curative action, and not 
 only have they a specific action in all stages of syphilis, but they 
 are also beneficial in other diseases due to spirillosae. Favourable 
 results are obtained in recurrent fever, frambcesia (yaws, pian), 
 filaria, malaria, plague, leprosy, Vincent's angina, and pernicious 
 anaemia. Amongst diseases of animals, salvarsan and neo- 
 salvarsan exercise a specific influence in the pleuro-pneumonia 
 of horses, in African glanders (lymphangitis epizootica), and in 
 anthrax. 
 
 These drugs are administered by injection either intra- 
 venously, intramuscularly (into the gluteal muscles), or subcu- 
 taneously (into the tissues adjoining bases of shoulder blades), 
 and intrarectal injection has also been employed. The prevailing 
 method is that of intiavenous injection, a procedure which is 
 far more readily carried out with neosalvarsan than with salvarsan. 
 It is for this reason that the former drug, which dissolves in 
 water to a neutral solution ready immediately for injection, is 
 rapidly gaming in popular favour. This tendency is brought out 
 in a remarkable manner by the following summary, which 
 indicates the practice of the French Military Medical Service. 
 
 The following table shows that in nearly 95,000 intravenous 
 injections, 77 per cent, of these applications were made with 
 neosalvarsan either used as such or employed under the synonym 
 of novarsenobillon. About 9-7 per cent, of the cases were treated 
 with salvarsan (arsenobillon) . Galyl, the complex phosphamate 
 of salvarsan discovered by Mouneyrat, was used in 9-2 per cent, 
 of the cases, the technique adopted being similar to that employed 
 with neosalvarsan. 
 
 Nearly 4 per cent, of the injections were made with luargol, 
 the salvarsan co-ordination compound with silver bromide and 
 antimony oxide introduced by Danysz. This drug, like salvarsan, 
 needs before injection a preliminary treatment with caustic 
 soda. 
 
 The report is a striking testimony alike to the vast scale on 
 which organic arsenical drugs are now employed, and to the 
 comparative freedom from untoward ill-effects arising from their 
 exhibition. 
 
 289 u 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 The Intravenous Injection of Organo-arsenical Compounds. 
 
 [A summary of 95,000 intravenous injections of arsenical compounds per- 
 formed by the French Military Medical Service during the first two years 
 of the war.] 
 
 In August, 1916, the French Under- Secretary of State for 
 Military Hygiene addressed a circular to the various military 
 commands asking for detailed information as to the number, 
 results, etc., of the intravenous injections of arsenical compounds 
 performed during the first two years of the war. The replies 
 were summarised by M. Paul Ravaut and his report was published 
 in the November, 1916, issue of the " Archives de Medecine et de 
 Pharmacie Militaire." 
 
 The total number of medical officers who had performed 
 personally injections of the nature specified was 185, and their 
 reports dealt with 94,762 injections. The preparations used 
 were : 
 
 Novarsenobillon . . . . . . in 37,352 cases. 
 
 Neosalvarsan . . . . . . 35,826 ,, 
 
 Salvarsan and arsenobillon . . ,, 9,215 
 
 Galyl 8,846 
 
 Luargol 3,523 
 
 No fatal case was reported among the 94,762 injections and 
 comparatively few serious accidents. These may be summarised 
 as follows : 
 
 Salvarsan 
 
 Nov- Neosal- and 
 
 arseno. varsan. Arseno. Galyl. Luargol. 
 
 Transient coma . . . . i 
 
 Epileptiform. crisis and delirium i 
 
 Grave nitritoid crises . . 4 
 
 Meningeal reaction . . 2 
 
 Facial paralysis . . . . 2 
 
 Epileptic crisis .... i i 
 
 Albuminaria . . . . 2 4 i 3 i 
 
 Icterus . . . . . . 7 8 i 2 2 
 
 Acute dermatitis i 
 
 Total 9 19 2 10 4 
 
 Percentage 0-025 0*051 0-021 0-113 0-113 
 
 290 
 
LUARGOL 
 
 Of the less important incidents recorded the following is an 
 analysis : 
 
 Salvarsan 
 
 Nov- Neosal- and 
 arseno. varsan. Arseno, Galyl. Luargol. 
 
 Mild nitritoid crises . . 9 1 1 5 Frequent . 
 
 Herxheimer reaction (cutaneous) 15 2 
 
 Vertigo and cephalalgia . . 8 15 3 Frequent 
 
 Erythema, pruritus and urticaria 7 13 2 4 4 
 
 Oedema of the face . . . . 6 4 
 
 Vomiting and diarrhoea . . 16 cases not analysed. 
 
 Although the list of accidents and incidents appears long, it 
 should be considered only in conjunction with the large number 
 of injections performed. 
 
 The following conclusions are cited from M. Ravaut's report : 
 
 A . All medical officers except two recognise the efficacy and 
 necessity of the employment of intravenous injections of arsenical 
 compounds in the treatment of syphilis. Their principal reasons 
 are : 
 
 1. Rapid superficial healing and cicatrisation of contagious 
 lesions attained much more rapidly than with mercury. It is 
 claimed that a rapid cure can be effected with two or three 
 injections, but that it is insufficient, for, under such conditions, 
 relapses are almost constant. 
 
 2. Many doctors report the rapid cicatrisation of lesions under 
 the influence of arsenic which have resisted treatment with 
 mercury ; some patients, on the point of being discharged, have 
 been able to return to duty as the result of an arsenical treatment. 
 
 3. If the established rules are followed, the employment of 
 the remedy is without danger. " Treatment by arsenical com- 
 pounds is much less dangerous than intensive mercurial treatment 
 and infinitely more efficacious." 
 
 B. Almost all the doctors insist on the necessity of associating 
 arsenic and mercury in the treatment of syphilis, the two remedies 
 being complementary. 
 
 C. The technique generally employed is that of concentrated 
 injections. The question of the water to be employed is satis- 
 factorily settled for sterilised water, even when not fresh, and 
 boiled water are used impartially and without inconvenient results. 
 
 D. To prevent or to treat vaso-dilatory accidents and nitritoid 
 crises numerous doctors record the good effects of adrenaline 
 (by the mouth : 30 drops of a i in 1000 solution ; hypo- 
 dermically : i c.c. of the same solution). 
 
 291 u 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 E. General criticism of the various arsenical compounds 
 employed : 
 
 Novarsenobillon. Preferred to all others. All find it at 
 least equal to neosalvarsan and sometimes superior. The 
 incidents attendant on injection appear less frequent. 
 
 Neosalvarsan. Very good. 
 
 Arsenobillon and Salvarsan. -Are considered very active. 
 Have only been used in default of the preceding the injection 
 of which is much simpler and more rapid. One doctor only has 
 used them systematically. 
 
 GalyL Very active according to some. Complaint is made 
 of irregularities in quality, of variations in solubility, and of the 
 frequency of small accidents following on injection. Owing to 
 this last fact, a dose of 0-2 gram has rarely been exceeded, and 
 this has diminished the efficacy of the treatment. 
 
 Luargol. An arsenobenzol reinforced with silver and antimony. 
 Some doctors find it extremely active. Complaint is made that 
 it has given rise to indurations of the veins of the arm in conse- 
 quence of too high a content of caustic soda in the solvent. 
 
 The foregoing report, which certainly does not show bias in 
 favour of arsenical drugs of French origin against those of German 
 manufacture, has for this reason been selected as an epitome of 
 existing medical practice and testimony in regard to the utility 
 of organo-arsenical medicaments. 
 
 292 
 
CHAPTER IX 
 
 AROMATIC ANTIMONIALS 
 
 PART I. 
 
 Aromatic Stibines and their Immediate Derivatives. 
 General Reactions. 
 
 THE method by which Michaelis and Reese first prepared 
 aromatic antimony compounds leads chiefly to the triaryl- 
 stibines and only in a lesser degree to substances containing 
 two aryl groups attached to one antimony atom. More recently, 
 the Grignard reaction has been applied to the preparation of 
 aromatic antimony derivatives, and, with the magnesium aryl 
 bromides or iodides, only tertiary stibines and their halide 
 derivatives have been isolated. Certain aryl-antimony deriv- 
 atives containing amino-groups such as the antimony analogues 
 of atoxyl and salvarsan are prepared by special methods based 
 on the discovery made by the Chemische Fabrik von Heyden 
 that antimonial groups can be introduced into the aromatic 
 nucleus through the agency of the diazo-reaction (v. Part II.). 
 The processes due to Michaelis are illustrated by the following 
 diagram (I., p. 294), which is drawn up with special reference to 
 the phenyl compounds. 
 
 The method of synthesis is analogous to that employed by 
 Michaelis for the arsenic compounds. The sodium process is 
 available, but the reaction is considerably complicated by the 
 greater tendency possessed by antimony of passing from the 
 triadic to the pentadic condition. When antimony trichloride 
 and chlorobenzene are heated in benzene solution with sodium 
 for 24 hours the products are triphenylstibine, triphenylstibine 
 dichloride, and diphenylstibine trichloride. Triphenylstibine 
 dichloride can be converted into triphenylstibine sulphide, a 
 
 293 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 substance which has been used in skin diseases under the name 
 of " sulphoform." Triphenylstibine when heated under pressure 
 with antimony trichloride yields phenylstibine dichloride, 
 and thus the primary, secondary, and tertiary series of aromatic 
 antimony derivatives are obtainable from the products of 
 the sodium condensation. This method was generalised so 
 that aromatic antimony compounds were synthesised containing 
 tolyl, anisyl, and phenetyl groups. 
 
 I. SODIUM METHOD. 
 C 6 H 6 C1, SbCl 3 , and Sodium 
 
 (C 6 H 5 ) 3 Sb 
 Heating with SbCl, 
 
 (C 6 H 5 ) 2 SbCl s (C 6 H 6 ) 3 SbCl a 
 
 S 
 
 C 6 H 5 -SbCl a 
 C 6 H 5 -SbCl, 
 
 6 H 5 ) 2 SbCl 
 
 C 6 H 5 -SbO(OH) 2 (C 6 H 6 ) 2 SbOOH (C 6 H 6 ) 3 Sb(OH) 2 
 
 The Grignard reaction gives rise mainly to triphenylstibine 
 or its dihalide derivatives, but the following diagram shows 
 how the diphenyl and monophenyl series of antimony compounds 
 are obtainable from the tertiary stibine. 
 
 II. GRIGNARD REACTION FOR ARYL ANTIMONY COMPOUNDS. 
 C 6 H 5 MgBr and SbBr 3 (or SbCl s ) 
 
 (C 6 H 5 ) 3 Sb and (C 6 H 5 ) 3 SbX 2 
 
 I. 
 Addition of chlorine 
 
 (C 6 H 5 ) 3 SbCL 
 
 (C 6 H 5 ) 3 Sb(OH) 2 
 
 Heating with SbCl 3 
 
 (C 6 H 5 ) 2 SbCl 
 (C 6 H 5 ) 2 SbCl 3 
 (C a H 5 ),SbOOH 
 
 C 6 H 5 -SbCl 2 
 C 6 H 5 -SbCl 4 
 C 6 H 5 -SbO(OH) 2 
 
 294 
 
AROMATIC ANTIMONIALS 
 
 Antimony Analogues of Atoxyl and Salvarsan. 
 
 Before referring to organo-antimony derivatives of therapeutic 
 interest it should be pointed out that salts of antimonyl tartaric 
 acid have figured largely in recent researches on the treatment 
 of diseases of protozoal origin. Lithium antimonyl tart rate 
 has been extensively used by Dr. Plimmer in his investigations 
 on sleeping sickness. Potassium ammonium antimonyl tar- 
 trate has been introduced, under the name of antiluetin, by 
 Tsuzuki, 1 and the use of sodium antimonyl tartrate and aniline 
 antimonyl tartrate 2 has also been suggested. Dr. Martindale 
 has prepared a 10 per cent, solution of antimonious oxide in 
 glycerin. This preparation (injectio antimonii oxidi), which 
 probably contains a glyceryl antimonite, is diluted to a definite 
 strength with water ; it has been tried with promising results 
 by intramuscular and intravenous injections in trypanosomiasis, 
 kala azar, and other tropical diseases. 3 Sodium antimony dithio- 
 glycinate, CO 2 Na-CH 2 -S-Sb-S-CH 2 -C(>O, and the triamide of 
 
 antimony trithioglycine, Sb[S-CH 2 'CO-NH 2 ]3, when injected into 
 animals, have afforded protection from trypanosomes. 4 
 
 Although the therapeutic application of organic derivatives 
 of antimony has not hitherto reached the prominence attained 
 by the arsenical compounds, yet great advances have been made 
 in the synthesis of the aromatic antimonials, and, in most cases, 
 the antimony analogues of the important aromatic arsenical 
 drugs have been prepared. The modern improvements which 
 have facilitated the production of aryl-antimony derivatives 
 are twofold. First, we have the application of the Grignard 
 reaction to the production of triphenylstibine and its homologues 
 (Ber., 1904, 36, 4620 ; Chem. Soc. Trans., 1911, 99, 2290), a 
 process which is also applicable to the synthesis of tertiary 
 aromatic arsines. As regards the antimony compounds, the 
 writer in collaboration with Miss Micklethwait showed how it 
 was possible to pass from triphenylstibine to the primary and 
 secondary series by heating the base with antimony trichloride 
 
 1 Deutsch. Med. Wochensch., 1913, p. 947. 
 
 2 Pharm. Zeit., 1909, 54, 919. 
 
 3 American leishmaniasis has been cured in many instances by 
 subcutaneous, intramuscular, and intravenous administration of this 
 preparation, which keeps well and does not produce the general effects 
 or local irritation of tartar emetic.' Lancet, Sept. i, 1917, p. 355. 
 
 4 /. Pharm. , 1910, 144, 101. 
 
 295 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 when both phenylstibine dichloride and diphenylstibine chloride 
 were produced. 
 
 The following diagram shows how these initial products were 
 converted successively into stibinic acids, nitrostibinic acids, 
 and the reduction products of the latter. These experiments 
 demonstrated that the stibinic groups induce substitution in 
 the meta-position. Accordingly the reduced products, two of 
 which were obtained independently by P. May, all contained 
 their amino-groups in the meta-position with respect to anti- 
 mony. These bases and their salts are characterised by their 
 irritating action on the mucous membrane of the nose and 
 throat ; they have a slight trypanocidal action, but are very 
 irritant when administered subcutaneously. (Plimmer, Fry, 
 and Ranken, Proc. Roy. Soc., 1911, 83B, 144.) 
 3 Mg(C 6 H s )-Br+SbCl 3 
 
 C 6 H 6 -SbCl 4 (C 6 H 6 ) 2 SbCl 3 (C 6 H 6 ) 3 SbCl 2 
 
 C 6 H 8 -SbO(OH) 2 (C 6 H 5 ) 2 SbO(OH) (C 6 H 6 ) 3 Sb(OH) 2 
 
 NOT 
 
 NH 2 
 ~\ 
 
 /' 
 
 Sb(OH) 2 
 
 H a 
 
 The second recent improvement in the synthesis of aromatic 
 antimony compounds was the discovery made by the Chemische 
 Fabrik von Heyden that antimony groups could be introduced 
 into the aromatic nucleus through the agency of the diazo- 
 reaction. This discovery led first to the synthesis of antimony 
 atoxyl, and more recently to that of the antimony analogue 
 of salvarsan. 
 
 Acet}7l-/)-phenylenediamine (I.) when diazotised and treated in 
 alkaline solution with antimony trichloride becomes converted 
 into acetyl-^-aminophenylstibinic acid (II.) This product on 
 hydrolysis yields ^-aminophenylstibinic acid (II A), 
 
 296 
 
AROMATIC ANTIMONIALS 
 
 the sodium salt of which is the analogue of atoxyl (D.R.-P., 
 270488). 
 
 NH-COCH 3 NH-COCH 3 NH-CO-CH 3 
 
 NH 3 
 
 I. 
 
 OH 
 
 Sb( 
 
 bO(OH) 2 
 III. 
 
 NH/\ 
 
 OH 
 /\ 
 
 NH 2 
 
 SbO(OH) 2 
 IV. 
 
 \/ 
 
 1 Sb=Sb i 
 
 V. 
 
 The acetylated derivative gave, on nitration, the compound 
 (III.), and this substance, when boiled with caustic alkalis, 
 underwent hydrolysis, a hydroxyl group replacing the acetyl- 
 amino-complex ; 3-nitro-4-hydroxyphenylstibinic acid (IV.) 
 when reduced with alkaline hydrosulphite gave rise to the 
 unstable 3 : 3 / -diamino-4 : 4'-dihydroxystibinobenzene (V.), ob- 
 tained as a reddish-brown precipitate readily soluble in acids 
 or alkalis, and becoming white by aerial oxidation (Fabr. 
 Heyden, D.R.-P., 268451). 
 
 The diazo-process for obtaining aromatic stibinic acids is a 
 general one, and remarkably complex antimony derivatives 
 can be synthesised. 1 
 
 1 Fabr. Heyden, D.R.-P., 254421, 261825, 268451, 269205, 269206. 
 
 297 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section 1. Aryl Derivatives containing One Aromatic Group 
 attached to One Antimony Atom. 
 
 i. Primary Phenylantimony Compounds. 
 
 The starting point in the preparation of these primary anti- 
 monials is the tertiary stibine, which is heated with antimony 
 chloride and xylene in a sealed tube for 48 hours at 240. 
 
 By fractionating the products of this reaction Hasenbaumer * 
 isolated phenylstibine dichloride, whereas Michaelis and Giinther 2 
 obtained from this process only diphenylstibine chloride in 
 small yield. Morgan and Micklethwait 3 showed that both 
 compounds are produced so that this method serves as a starting 
 point for both primary and secondary aromatic antimonials. 
 The simultaneous production of these two compounds has more 
 recently been confirmed by Griittner and Wiernik. 4 
 
 The best yield of phenylstibine dichloride is obtained when 
 triphenylstibine (30 grams) and antimony trichloride (40 grams) 
 are heated with xylene (18 c.c.) for 75 hours at 240-245, 
 when about 70 per cent, of the organic product consists of the 
 dichloride, the remainder consisting of diphenylstibine chloride. 
 A larger excess of antimony chloride does not increase the yield 
 of the phenyl compound. The reactions occurring are to be 
 represented as follows, the former being the more rapid and 
 effective. 
 
 i. Sb(C 6 H 5 ) 3 4-SbCl 3 ==Sb(C 6 H 5 )Cl 2 + Sb(C 6 H 6 ) 2 Cl. 
 ii. Sb(C 6 H 6 ) 2 Cl + SbCl 3 =2Sb(C 6 H 5 )Cl 2 . 
 
 Phenylstibine dichloride? C 6 H 5 -SbCl 2 , colourless crystals ; m.p. 
 58 ; b.p. 290, is very soluble in cold alcohol, benzene, ether, 
 or light petroleum. In the cold it has only a faint odour, but 
 on warming this becomes very pungent and attacks the mucous 
 membrane 
 
 Phenyldimethylstibine, C 6 H 6 -Sb(CH 3 ) 2 , colourless, mobile liquid ; 
 b.p. H2/i6-i8 mm. in C0 2 ; Df 1-4490, w^ 93 1-5983, is 
 prepared by the Grignard reaction with magnesium methyl 
 bromide in ethereal solution on crude phenylstibine dichloride. 
 It forms methiodide and ethiodide, colourless needles, decomposing 
 at 235 and 150, and dihalogen compounds, dichloride, dibromide, 
 and di-iodide, m.p.'s 128, 112-113, 98-5-99. 
 
 1 Ber., 1898, 31, 2910. 2 Ber., 1911, 44, 2316. 
 
 3 Chem. Soc. Trans., 1911, 99, 2288. 4 Ber., 1915, 48, 1749, 1759- 
 5 Hasenbaumer, Ber., 1898, 31, 2912. 
 
 298 
 
AROMATIC ANTIMONIALS 
 
 Phenyldiethylstibine, C 6 H 5 -Sb(C 2 H 5 )2, colourless liquid ; b.p. 
 !28/i6-i8 mm. in CO 2 , Df 1-3487, n 2 1-5903, fuming 
 and sometimes taking fire in air, prepared as above by the 
 Grignard reaction. Methiodide formed less readily than in the 
 preceding example; no ethiodide; dichloride and dibromide 
 both oily ; di-iodide (m.p. 88-5-89). 1 
 
 Phenylstibine oxide, C 6 H 5 -SbO, crystalline, m.p. 150, disagree- 
 able odour, prepared by the action of aqueous sodium carbonate 
 on the foregoing chloride. 
 
 Phenylstibine sulphide, C 6 H 5 -SbS, crystalline, m.p. 65, pro- 
 duced by dissolving the oxide or chloride in alcoholic ammonia 
 and passing in sulphuretted hydrogen, the liquid being then 
 acidified. 
 
 Phenylstibinic Acid, < \Sb'=O 
 
 Phenylstibinic chloride, C 6 H 5 -SbCl 4 , hygroscopic, crystalline 
 mass, obtained by saturating with chlorine an ethereal solution 
 of phenylstibine chloride. Hydrolysed by water into phenyl- 
 stibinic acid, C 6 H 5 -SbO(OH) 2 , white, amorphous powder, decom- 
 posing above 200, insoluble in water, but dissolving in ammonia, 
 caustic and carbonated alkalis, and in glacial acetic acid. The 
 alkali salts are easily soluble, crystalline substances ; the am- 
 monium salt is somewhat unstable ; the barium salt, 
 
 [C 6 H 6 -SbO(OH)-0] a Ba, 
 is a white precipitate. 
 
 Salts of the Arylstibinic Acids with Neutral Reaction. 
 
 The alkali salts of the arylstibinic acids were described by 
 Hasenbaumer (loc. cit.) as easily hydroly sable substances ; 
 the ammonium salts he assumed to be incapable of existence. 
 This matter was examined further by the Chemische Fabrik 
 von Heyden, 2 which succeeded in preparing soluble neutral alkali 
 salts and also the corresponding ammonium compounds. 
 
 The alkali salts having the composition Ar-SbO(OH)-OM or 
 ArSbO(OM) a give an alkaline reaction in aqueous solution, 
 but stable soluble salts with neutral reaction can be prepared 
 containing less than one molecular proportion of alkali to a 
 
 1 Griittner and Wiernik, Ber., 1915, 48, 1759. 
 
 2 D.R.-P., 267083. 
 
 2 99 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 molecular proportion of stibinic acid. A similar sparingly soluble 
 ammonium salt can be obtained by heating an ammoniacal 
 solution of the aromatic stibinic acid. 
 
 Phenylstibinic acid (2-5 grams) suspended in 25 c.c. of 
 water is dissolved by the addition of AT-sodium hydroxide 
 (lo'c.c.). The alkali salt is precipitated from the filtered solution 
 on the addition of 20 per cent, sodium hydroxide and washed 
 with salt solution until a neutral reaction is obtained. The resi- 
 due dissolves to a stable neutral solution. A similar quantity 
 of phenylstibinic acid is dissolved in 30 c.c. of Af-sodium hydroxide 
 and the excess of alkali neutralised with Af-sulphuric acid (litmus 
 indicator) . The turbid solution is heated on the water-bath, fil- 
 tered, and the filtrate evaporated to dryness. The residue is freed 
 from sodium sulphate by extraction with methyl alcohol. This 
 alcoholic extract when evaporated to dryness gives a soluble 
 neutral salt containing one atomic proportion of sodium to 
 three molecular proportions of phenylstibinic acid. 
 
 Acetyl-p-aminophenylstibinic acid (v. p. 315) gives a soluble 
 neutral sodium salt containing the same atomic proportion of 
 sodium obtained by dissolving the free acid in aqueous sodium 
 hydroxide, saturating the solution with carbon dioxide, filtering, 
 neutralising with acetic acid, filtering again, and precipitating 
 the alkali salt with sodium sulphate. The alkali salt, freed 
 from inorganic impurities by dissolving in methyl alcohol, is 
 obtained by concentrating the alcoholic extract. The product 
 contains water of crystallisation. 
 
 A soluble neutral salt of ^-aminophenylstibinic acid is prepared 
 by dissolving the acid in excess of aqueous sodium hydroxide, 
 neutralising with acetic acid, and precipitating the product 
 with alcohol. 
 
 The existence of these neutral soluble alkali salts containing 
 less than one atomic proportion of alkali metal to each molecular 
 proportion of acid has been observed in the case of the aryl- 
 stibinic acids but not in that of the arylphosphinic or arylarsinic 
 acids. These alkali salts are suitable for therapeutic injections. 
 
 m-Nitrophenylstibinic acid (I.). 
 
 ,OH 
 
 \SbO(OH) 2 ---> / \SbO. 
 
 NH- NUT' 
 
 II. III. 
 
 300 
 
AROMATIC ANTIMONIALS 
 
 Phenylstibinic acid is nitrated with a mixture of 12 parts 
 of nitric acid(D 1-5) and 4 parts of concentrated sulphuric acid, 
 the temperature ranging from 40 to 55. The solution poured 
 on to ice gives a yellow precipitate consisting in part of basic 
 nitrates. This product is dissolved in N-sodium hydroxide 
 and the nitro-acid precipitated with acetic or hydrochloric 
 acid. The compound, which is not very crystallisable, has no 
 melting point below 290. When heated with phosphorus 
 pentabromide and chloroform at 100-110 it is decomposed, 
 yielding i-bromo-3-nitrobenzene (70 per cent, of theory). 1 
 
 When reduced with zinc and ammonium chloride in alcohol 
 and with stannous chloride w-nitrophenylstibinic acid yields 
 successively w-aminophenylstibinic acid (II.) and w-amino- 
 phenylstibine oxide (III.). The hydrochloride of the former 
 amine has the following composition : 
 
 HCl,NH a -C 6 H 4 -SbOCl 2 . 2 
 
 2. Tolyl Series. 
 
 p-Tolylstibine chloride* CH 3 -C 6 H 8 -SbCl 2 , crystalline, m.p. 93'5> 
 b.p. above 360, is obtained by heating tri-^-tolylstibine (10 
 grams) and antimony trichloride (12 grams) with xylene at 
 245 for 48 hours. It is very soluble in the ordinary organic 
 solvents and is best obtained crystalline by distillation. 
 
 This dichloride forms the oxide, sulphide, and tetrachloride, 
 the last of these hydrolysing readily to p-tolylstibinic acid, 
 
 CH 3 -C 6 H 4 -SbO(OH) 2 , 
 a white, amorphous powder. 
 
 Section II. Diarylantimony Derivatives. 
 i. Phenyl Series. 
 
 Diphenylstibine chloride, (CH 5 ) 2 SbCl, is the by-product 
 obtained by heating together at 240-250 triphenylstibine and 
 antimony trichloride in the presence of dry xylene. The oily 
 product, after drying and removing the xylene, is fractionated 
 
 1 Morgan and Micklethwait, Chem. Soc. Trans., 1911, 99, 2296; cf. 
 Fabr. Heyden, D.R.-P., 287709. 
 
 2 Morgan and Micklethwait, Chem. Soc. Proc., 1912, 28, 20; cf. P. May, 
 ibid., p. 5, and Chem. Soc. Trans., 1912, 101, 1033. 
 
 3 Hasenbaumer, Ber., 1898, 31, 2914. 
 
 301 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 under 5-7 mm. pressure into two portions, the lower boiling 
 at 160-200 and the higher at 200-240. The higher fraction 
 solidifies on cooling and gives colourless crystals of diphenyl- 
 stibine chloride (m.p. 68). When treated with chlorine in dry 
 ether this substance yields diphenylstibine trichloride, which, 
 after crystallisation from hydrochloric acid, melts at IJ6 . 1 
 
 Diphenylmethylstibine* (C 6 H 5 ) 2 Sb-CH 3 , colourless, viscous oil, 
 b.p. !74-i77/i6-i8 mm. in CO 2 ; D? 1-2134 ; ri$ 1-6021, 
 oxidising in air but not fuming. Prepared from crude diphenyl- 
 stibine chloride and magnesium methyl bromide. Chloride, 
 (C 6 H 6 )2Sb(CH 3 )Cl 2 , colourless prisms, m.p. 144 ; bromide, 
 m.p. 148. 
 
 Diphenylethylstibine* (C 6 H 5 ) 2 Sb-C 2 H5, colourless, viscous oil, 
 b.p. 1 90-1 92 /i 6-1 8 mm. in CO 2 ; Df 5 1-3541, ng' 5 1-6309 ; 
 crystalline dichloride and dibromide, m.p.'s 163-164 and 158. 
 
 Diphenylstibine trichloride? (C 6 H 5 ) 2 SbCl 3 , lustrous, colourless 
 needles containing iH 2 O, m.p. 180. This substance is a by- 
 product in the interaction of antimony trichloride (48 grams), 
 chlorobenzene (48 grams), and sodium (20 grams). The two 
 chloro-compounds are dissolved in 150-200 c.c. of dry benzene 
 and added to the sodium previously granulated by melting and 
 shaking under boiling toluene. If the reaction does not occur 
 spontaneously, it is started by cautiously warming the mixture. 
 After 24 hours the filtered solution is evaporated, the oily residue 
 mixed with alcoholic hydrochloric acid, and dissolved in the 
 minimum amount of boiling alcohol. On cooling the greater 
 part of the triphenylstibine dichloride separates, and the mother 
 liquor, concentrated, yields impure diphenylstibine trichloride, 
 which is purified by extraction with hot dilute hydrochloric acid, 
 leaving undissolved triphenylstibine dichloride ; the yield of 
 diphenylstibine trichloride is about n to 16 per cent, of the 
 weight of antimony trichloride. On treatment with alcoholic 
 silver nitrate the trichloride yields a basic nitrate, crystallising 
 in lustrous, colourless needles, decomposing at 2o6. 5 
 
 Diphenylstibine trichloride is a by-product of the interaction 
 of antimony trichloride and mercury diphenyl in xylene at 130, 
 the main product being triphenylstibine dichloride. 6 
 
 1 Morgan and Micklethwait, Chem. Soc. Trans., 1911, 99, 2295. 
 
 2 Griittner and Wiernik, Ber., 1915, 48, i?59; Lettermann, Inaug. 
 Diss., Rostock, 1911. 3 Ibid. 
 
 4 Michaelis and Reese, Annalen, 1886, 233, 58; Morgan and Mickle- 
 thwait, Chem. Soc. Trans., 1911, 99, 2293. 5 Ibid. 
 6 Hasenbaumer, Ber., 1898, 31, 2911. 
 
 302 
 
AROMATIC ANTIMONIALS 
 
 Diphenylstibinic acid, (C 6 H 6 ) 2 SbOOH, white powder decom- 
 posing above 250. Its behaviour towards alkalis depends on 
 the mode of preparation from diphenylstibine trichloride. 
 
 1. When dissolved in alcohol and treated with dilute ammonia, 
 the trichloride gives a granular precipitate of diphenylstibinic 
 acid insoluble in ammonia or sodium carbonate. 1 
 
 2. The trichloride dissolved in aqueous sodium hydroxide and 
 the solution acidified with acetic acid gives a diphenylstibinic 
 acid readily soluble in ammonia or sodium carbonate. The 
 two preparations are probably differently hydrated forms of 
 diphenylstibinic acid, the less soluble form being possibly the 
 meta-compound, (C 6 H 6 ) 2 SbO -OH, whilst the more soluble product 
 may be an ortho- or a pyro-compound. 2 
 
 With hydrochloric acid, diphenylstibinic acid is reconverted 
 into diphenylstibinic chloride. 
 
 Di-m-nitrodiphenylstibinic acid (I.). 
 
 \] 
 
 Sb-OH. 
 
 SbOOH 
 
 This dinitro-compound is obtainable by the nitration of diphenyl- 
 stibinic acid, but it is preferably prepared by nitrating the 
 basic nitrate of this acid, produced by treating diphenylstibine 
 trichloride in alcoholic solution with silver nitrate. This basic 
 nitrate, crystallising in clusters of lustrous, colourless needles 
 (decomposing at 200), is added to nitric acid (D 1-5) mixed with 
 4 volumes of concentrated sulphuric acid, the temperature being 
 maintained at 40 and then raised to 55. The clear solution 
 poured on to ice gives a pale yellow product, which is dissolved 
 in .ZV-sodium hydroxide, reprecipitated by acetic or hydrochloric 
 acid, and crystallised from glacial acetic acid. The dinitrostibinic 
 acid separates in radiating clusters of flattened needles, de- 
 composing indefinitely at 212. It is insoluble in water, alcohol, 
 or benzene ; its alkali salts are soluble to an orange-yellow 
 solution. The other metallic salts are very sparingly soluble. 
 When heated at 130-160 with phosphorus pentabromide alone 
 or with bromine, this dinitrostibinic acid loses antimony and 
 i-bromo-3-nitrobenzene is produced. 3 
 
 Di-m-aminodiphenylhydroxystibine (II.), a colourless, caseous 
 
 1 Michaelis and Reese, Annalen, 1886, 233, 59.- 
 
 2 Morgan and Micklethwait, Chem. Soc. Trans., 1911, 99, 2296. 
 
 3 Ibid., 2294. 
 
 303 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 mass melting indefinitely at 76-80, is precipitated from acid 
 solution by ammonia and turns brown on exposure to air. 
 It is produced from the preceding compound by reduction 
 with tin and hydrochloric acid or zinc and ammonium chloride. 
 The hydrochloride, ClSb(C 6 H 4 -NH 2 ) 2 ,2HCl, crystallises from 
 acidified water in very soluble, colourless needles. This base 
 and its salts have an irritating action on the mucous membrane 
 of the throat and nose which is even more intense than that 
 noticed with tri-w-aminophenylstibine and its hydrochloride. 1 
 
 Section III. Triarylantimony Derivatives. 
 i. Phenyl Series. 
 
 Triphenylstibine, (C 6 H 5 ) 3 Sb, colourless, triclinic plates, m.p. 48 
 (51), b.p. 23i-232/i6-i8 mm., above 36o/76o mm. (with 
 partial decomposition) ; D I -4998/12. 2 
 
 Preparation i. Sodium method. 3 Redistilled antimony tri- 
 chloride (40 grams) and chlorobenzene (40 grams) are dissolved 
 in about 4 volumes of dry benzene and treated with sodium 
 (50 grams) in a reflux apparatus. A vigorous reaction sets in, 
 after which the mixture is heated to boiling and filtered from 
 unattacked sodium, the filtrate being then distilled to remove 
 benzene. The residue, which speedily solidifies, consists mainly of 
 triphenylstibine together with diphenylstibine trichloride and tri- 
 phenylstibine dichloride and some triphenylstibine oxide produced 
 by the action of moisture. The triphenylstibine is best purified 
 through its dichloride. The mixture of antimony compounds is 
 treated with alcoholic hydrochloric acid in which diphenyl- 
 stibine trichloride dissolves. The residue, freed from alcohol, is 
 treated with sufficient light petroleum to dissolve the stibine, and 
 chlorine is introduced so long as a precipitate is produced. The 
 triphenylstibine dichloride is recrystallised from alcohol dissolved 
 in alcoholic ammonia and reduced with a rapid stream of 
 sulphuretted hydrogen ; heat is generated, and the liquid 
 becomes dark red from the formation of ammonium polysulphide. 
 On cooling, triphenylstibine separates and is recrystallised from 
 light petroleum. 
 
 2. Grignard reaction. A 10 per cent, benzene solution con- 
 taining 18 grams of antimony trichloride is added slowly to the 
 
 1 Morgan and Micklethwait, Chem. Soc. Proc., 1912, 28, 20. 
 
 2 Ghira, Gazzetta, 1894, 24, [i], 317. 
 
 3 Michaelis and Reese, Annalen, 1886, 233, 45. 
 
 304 
 
AROMATIC ANTIMONIALS 
 
 Grignard reagent prepared from 50 grams of bromobenzene and 
 7-2 grams of powdered magnesium suspended in dry ether ; 
 the mixture is then boiled for six hours and distilled in steam 
 to remove benzene and bromobenzene. The fusible organic 
 residue is freed from diphenyl by extraction with small 
 quantities of cold alcohol, and the undissolved triphenylstibine 
 crystallised from hot alcohol. Yield nearly quantitative. 1 
 
 The condensation can be carried out entirely in ethereal 
 solution, but the yield is less. 2 
 
 Triphenylstibine can be purified through its sulphide (p. 306) . 
 One hundred grams of triphenylstibine sulphide dissolved in 
 450 c.c. of absolute alcohol and 50 c.c. of benzene are heated on 
 the water-bath with finely-divided copper (" Naturkupfer C ") 
 or with iron powder ; the filtered solution yields from 80 to 90 
 per cent, of pure triphenylstibine (m.p. 51). 3 
 
 Unlike triethylstibine, this aromatic stibine does not decompose 
 strong hydrochloric acid ; it removes chlorine from cupric and 
 ferric chlorides, however, becoming triphenylstibine dichloride 
 and forming the lower chlorides of the metals. It differs 
 from triphenyl-phosphine and -arsine in not combining 
 with mercuric chloride. On the contrary, it is decomposed 
 by this salt, yielding phenyl-mercuric chloride and antimony 
 trichloride. With chlorine and bromine it combines additively 
 to form triphenylstibine dichloride and dibromide. Triphenyl- 
 stibine dissolves in fuming nitric acid with a vigorous 
 reaction, and triphenylstibine nitrate crystallises out on 
 cooling. 
 
 Methyl iodide decomposes triphenylstibine, giving trimethyl- 
 stibine di-iodide, iodobenzene, and ethane. Zinc dimethyl de- 
 composes the stibine, giving toluene, antimony, and zinc. 
 
 When heated with arsenic, antimony is eliminated with the 
 production of triphenylarsine. 
 
 Triphenylstibine dichloride, (C 6 H 6 ) 3 SbCl 2 , colourless needles, m.p. 
 143, a by-product of the interaction between antimony chloride, 
 chlorobenzene, and sodium, is also prepared by chlorinating 
 triphenylstibine or by the interaction of antimony trichloride 
 and mercury diphenyl in dry xylene at 130.* It is not affected 
 by water, differing in this respect from the easily hydrolysed 
 
 1 Morgan and Micklethwait, Chem. Soc. Trans., 1911, 99, 2290. 
 
 2 Pfeiffer, Ber., 1904, 37, 4621 ; cf. Carre, Bull. Soc. chim., 1913, [iv], 
 13, 102. 3 Kaufmann, Ber., 1908, 41, 2762; D.R.-P., 240316. 
 
 4 Hasenbaumer, Ber., 1898, 31, 2911. 
 
 305 * 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 triphenylarsine dichloride. It is slowly attacked by aqueous 
 alkalis, and more readily hydrolysed by alcoholic alkalis. 
 
 Triphenylstibine dibromide, 1 (C 6 H 5 ) 3 SbBr 2 , colourless, flattened 
 needles from glacial acetic acid, m.p. 216 ; it is sparingly 
 soluble in the volatile organic solvents. 
 
 Triphenylstibine di-iodide, (C 6 H 6 ) 3 SbI 2 , lustrous, yellowish- 
 white plates from petroleum-benzene, m.p. 153. 
 
 Triphenylstibine dihydroxide, (C 6 H 5 ) 3 Sb(OH) 2 , white powder, 
 m.p. 212, insoluble in ether or petroleum, dissolving readily 
 in alcohol or glacial acetic acid ; prepared by adding triphenyl- 
 stibine dibromide to warm alcoholic potash. 
 
 Triphenylstibine dinitrate, 2 (C 6 H 5 ) 3 Sb(ON0 2 )2, colourless leaflets 
 from nitric acid, insoluble in water, m.p. 156 (with decomposi- 
 tion). 
 
 Triphenylstibine hydroxynitrate, 8 (C 6 H 6 ) 3 Sb(OH)-NO 3 , lustrous, 
 colourless leaflets from boiling water, softening at 220, m.p. 
 224-225 ; prepared by treating triphenylstibine dichloride with 
 alcoholic silver nitrate. This hydro xynitrate is reduced com- 
 pletely into triphenylstibine and ammonia on treatment with 
 Devarda's alloy in presence of alkali. 
 
 Triphenylstibine hydroxysulphate, [(C 6 H 5 ) 3 Sb(OH)] 2 -S0 4 , m.p. 
 252, colourless, nodular crystals, obtained by using aqueous 
 silver sulphate in the foregoing preparation. 
 
 Triphenylstibine hydroxychloride, (C 6 H 6 ) 3 Sb(OH) -Cl, transparent, 
 colourless spicules from benzene, m.p. 218, produced by adding 
 an alcoholic solution of triphenylstibine dichloride to a large 
 volume of boiling water, and evaporating the solution to the crystal- 
 lising point. This compound and the preceding hydroxysulphate 
 when sulphonated with about 10 parts of fuming sulphuric acid 
 (20 per cent. S0 3 ) at 100 yield a trisulphonic acid which, when 
 isolated from its barium salt by sulphuric acid, is obtained on 
 evaporation as a brittle, yellow mass resembling amber and 
 approximating in composition to the formula 
 (HO) a Sb(C 6 H 4 -S0 3 H) 3 , 3 H 2 0. 4 
 
 Triphenylstibine sulphide, " Sulphoform," (C 6 H 5 ) 3 SbS, white 
 needles, m.p. 119-120, is obtained by passing sulphuretted 
 hydrogen cautiously into a solution of triphenylstibine chloride 
 or bromide in alcoholic ammonia. When a faint yellow colora- 
 tion is produced, which disappears on shaking, the sulphide separ- 
 
 1 Michaelis and Reese, Annalen, 1886, 233, 49, 50. 2 Ibid. 
 
 3 Morgan, Micklethwait, and Whitby, Chem. Soc. Trans,, 1910, 97, 36. 
 
 4 Morgan and Micklethwait, ibid., 1911, 99, 2297. 
 
 306 
 
AROMATIC ANTIMONIALS 
 
 ates in colourless crystals (yield 80 per cent.). For triphenylstibine 
 chloride the solution needs to be boiling, but for the bromide 
 the reaction takes place at the ordinary temperature. Prolonged 
 treatment with hydrogen sulphide leads to an intense yellowish- 
 red solution from which only triphenylstibine and sulphur can 
 be obtained. The sulphide dissolves readily in benzene, chloro- 
 form, or glacial acetic acid, less easily in alcohol, and is very 
 slightly soluble in ether. It is insoluble in alcoholic sulphuretted 
 hydrogen or ammonia, but in alcoholic ammonium sulphide it 
 dissolves to a red solution which on prolonged heating gives 
 sulphur and triphenylstibine. This sulphide, introduced into 
 pharmacy as " Sulphoform," has a curative action in eczema, 
 seborrhoea, and similar skin troubles. Triphenylstibine sulphide 
 can be used as a convenient source of triphenylstibine, for when 
 dissolved in alcohol-benzene and boiled for one to four hours in a 
 reflux apparatus with " Naturkupfer C " or with iron powder 
 and a little ferric chloride the sulphur is removed by the metal, 
 and the yield of triphenylstibine is 80-90 per cent. 1 
 Tri-m-nitrotriphenylstibinic acid (I.), 
 
 J 3 L NH 2 
 
 I. II. 
 
 This trinitro-acid is produced by the nitration of triphenyl- 
 stibine hydro xy nit rate (p. 306), 3 grams of this nitrate being 
 added to 25 c.c. of nitric acid (D 1*5) and 6 c.c. of concen- 
 trated sulphuric acid maintained at 40 and afterwards at 
 55. After two hours the cooled solution is poured on to ice, 
 the precipitated nitro-compound dissolved in Af-sodium hydroxide, 
 reprecipitated by acid, and crystallised from glacial acetic acid. 
 The trinitro-compound separates in pale yellow leaflets, decom- 
 posing indefinitely from 170 to 191. Its alkali salts are soluble 
 to brownish-orange solutions ; the other metallic salts dissolve 
 only sparingly in water. Dry sodium tri-w-nitrotriphenyl- 
 stibinate, heated with phosphorus pentabromide, bromine, and 
 triethylamine in chloroform solution at 130-150, yields 
 i-bromo-3-nit robenzene . 
 
 Tri-m-aminotriphenylstibine (II.), colourless crystals from 
 glacial acetic acid, decomposing indefinitely at 80, sparingly 
 
 1 Kaufmann, D.R.-P., 223694, 240316; Ber., 1908, 41, 2762; Michaelis 
 and Reese, Annalen, 1886, 233, 44. 
 
 307 X 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 soluble in water or the volatile organic solvents, is prepared by 
 adding the preceding trinitro-compound to a suspension of zinc 
 dust in alcohol containing ammonium chloride. After half an 
 hour the solution is filtered into ice-cold water. The pre- 
 cipitated base dissolved in dilute hydrochloric acid is set free 
 by ammonia. The crystalline hydrochloride, Sb(C 6 H 4 -NH 2 ,HCl) 3 , 
 is readily soluble in alcohol or water, but is precipitated from 
 the latter by strong hydrochloric acid. 
 
 The base and its salts, either in the solid state or in hot solution, 
 have a curious pungent odour and cause violent fits of sneezing. 
 The hydrochloride has a certain degree of trypanocidal power, 
 but when injected subcutaneously it is very irritant, causing 
 ulceration at the point of injection. 1 
 
 Tri-p-anisylstibine, 2 Sb(C 6 H 4 -OCH 3 )3, well-defined, colourless 
 rhombohedra, m.p. i8o-5-i$i, dissolving readily in chloroform, 
 benzene, or toluene, but less soluble in alcohol, ether, ethyl 
 acetate, glacial acetic acid, or carbon bisulphide, is prepared by 
 the following methods : 
 
 1. Sodium antimonide (150 grams), obtained by adding 
 40 grams of sodium gradually to antimony (360 grams) heated 
 to redness in a Hessian crucible, is powdered and treated with 
 ^>-bromoanisole (100 grams) in a reflux apparatus heated for one 
 hour at 217 and then 24 hours at 150-160. The warm product, 
 extracted at 70 with a mixture of benzene and chloroform, 
 is filtered from finely-divided antimony, and distilled first alone 
 and then in steam. The residue extracted with chloroform 
 yields a solution from which the stibine crystallises on adding 
 benzene. About 10 per cent, of this product is obtained, calcu- 
 lated on the weight of ^>-bromoanisole. This method can be 
 employed for other aromatic stibines, but it offers no advantages 
 over the sodium method. 
 
 2. Sodium (thrice the calculated quantity) is added in thin 
 slices to freshly distilled antimony trichloride (80-8 grams) 
 and ^-bromoanisole (200 grams) in 800 c.c. of benzene. A 
 vigorous reaction sets in, and after 24 hours the mixture is 
 heated to boiling with addition of 10-15 grams of sodium. The 
 benzene solution is distilled in steam to remove ^-bromoanisole. 
 The residue dissolved in benzene-chloroform yields iii-p- 
 anisyl stibine, 68 grams being obtained from 200 grams 
 of />-bromoanisole. This stibine is decomposed by boiling 
 
 1 Morgan and Micklethwait, Chem. Soc. Trans., 1911, 99, 2292. 
 z Loloff, Ber., 1897, 30, 2834. 
 
 308 
 
AROMATIC ANTIMONIALS 
 
 concentrated hydrochloric acid into anisole and antimony 
 trichloride. 
 
 The mercurichloride, (CH 3 -O-C 6 H 4 ) 3 Sb,HgCl 2 , white, crystalline 
 precipitate from alcohol, sintering at 235-240, decomposing at 
 285. Prolonged boiling with alcohol gives rise to ^>-anisyl- 
 mercuric chloride, CH 3 -OC 6 H 4 -HgCl (m.p. 239). 
 
 Tri-p-anisylstibine dichloride, (CH 3 -O-C 6 H 4 ) 3 SbCl 2 , is best 
 prepared by adding alcoholic cupric chloride to a chloroform- 
 alcohol solution of tri-/>-anisylstibine so long as cuprous chloride 
 is precipitated. The nitrate yields the dichloride, which separates 
 from chloroform-petroleum in white crystals, m.p. 116-117. 
 The dibromide, a white, crystalline product, m.p. 123, is obtained 
 by mixing bromine and the stibine in chloroform. This com- 
 pound and the chloride combine with benzene to form 
 derivatives (CH 3 -O-C 8 H 4 ) 3 SbX 2 ,C 6 H 8 , which lose benzene at 
 81-83. 
 
 Tri-p-anisylstibine di-iodide, yellow leaflets, m.p. 116, produced 
 from its generators in dry chloroform ; the dinitrate results from 
 the interaction of the dibromide and silver nitrate in alcoholic 
 solution ; it decomposes at 217. 
 
 Tri-p-anisylstibine oxide, (CH 3 -OC 6 H 4 ) 3 SbO, crystalline crusts 
 from alcohol, m.p. 191, produced by the action of alkalis on 
 the foregoing dihalides, preferably the bromide. 
 
 In this series the passage from tertiary to secondary aromatic 
 antimonials is effected in the following manner by means of 
 chlorine. 
 
 Tetrachlorodi-p-anisylstibine trichloride, 
 
 (CH 3 -0-C 6 H 2 Cl 2 ) 2 SbCl 3 , 
 
 colourless crystals, m.p. 184, is soluble in the organic media 
 excepting petroleum. It is produced by passing chlorine into 
 tri-^>-anisylstibine (i part) in 15 parts of dry chloroform. The 
 solution is allowed to evaporate in a dry atmosphere and the 
 residue is taken up with benzene, when the trichloride separates 
 on concentration. The mother liquor on treatment with light 
 petroleum yields a by-product, trichloro-/>-anisole (m.p. 60-61). 
 These compounds are produced by the chlorination of the three 
 />-anisyl groups, followed by the elimination of one of these in 
 the form of trichloro-^-anisole. 
 
 Tetrachlorodi-p-anisylstibine acid, (CH 3 -O-C 6 H 2 Cl 2 ) 2 SbO-OH, a 
 voluminous, white precipitate, m.p. 228-229, insoluble in the 
 ordinary organic media, soluble in dilute caustic soda to the 
 
 309 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 sodium salt and in alcoholic hydrochloric acid as the trichloride, 
 is produced by treating the preceding trichloride dissolved in 
 ether with aqueous alcohol. 
 
 Tri-p-phenetylstibine, (CaHg-O-CeH^Sb, warty aggregates of 
 acicular prisms, m.p. 82-83, is obtained by substituting ^-bromo- 
 phenetole for ^-bromoanisole in the preparation of tri-^>-anisyl- 
 stibine (p. 308), but, being more soluble than the latter in all 
 ordinary organic media, the yield is less. This stibine is 
 hydrolysed into phenetole and antimony trichloride by hot 
 concentrated hydrochloric acid. The mercuricMoride, softening 
 at 205-210 and decomposing at 225, the dichloride, m.p. 84, 
 the dibromide, a felted mass of needles, m.p. 110-111, the 
 di-iodide prismatic, crystals, m.p. 121-122, and the dinitrate, 
 crystalline crusts, m.p. 151-152, decomposing at 170, are all 
 prepared in accordance with methods already described above 
 for the tri-_-anisyl compounds. 
 
 2. Tolyl Series. 
 3CH 3 -C 6 H 4 Br + SbBr 3 + 6Na = (CH 3 -C 6 H 4 ) 3 Sb + 6NaBr. 
 
 Tri-o-tolylstibine, 1 (CH 3 -C 6 H 4 ) 3 Sb, colourless, transparent, 
 lustrous crystals from alcohol, m.p. 79-80, prepared by adding 
 sodium (50 grams) to antimony tribromide (36 grams) and 
 o-bromotoluene (51 grams) dissolved in about 200-300 c.c. of 
 benzene. The reaction proceeds spontaneously, and after 
 4-5 days the benzene is removed and the residue extracted 
 with light petroleum. If o-bromotoluene 2 containing a small 
 amount of ^-bromotoluene is employed, a small amount of 
 di-0-tolyl-^>-tolylstibine separates in tufts of colourless, acicular 
 crystals on concentrating the petroleum extract. The tri-o-tolyl- 
 isomeride remains in the mother liquor and is best obtained 
 through its dibromide produced by adding an ethereal solution 
 of bromine. Fractionation of this crude dibromide gives two 
 compounds, one melting at 185-186 (more soluble), and a less 
 soluble isomeride (m.p. 209) ; the latter when reduced with 
 sulphuretted hydrogen in alcoholic ammonia yields pure 
 tri-o-tolylstibine, which is very soluble in chloroform, benzene, 
 or ether, and less so in alcohol. 
 
 The mercurichloride, (CH 3 -C 6 H 4 ) 3 Sb,HgCl 2 , silky leaflets, 
 
 1 Michaelis and Genzken, Annalen, 1887, 242, 176. 
 
 2 Longuinine, Ber., 1871, 4, 516. 
 
 310 
 
AROMATIC ANTIMONIALS 
 
 softening at 125, decomposing at 135, obtained from alcoholic 
 solutions of its generators, is a very stable substance, and does 
 not yield o-tolylmercurichloride even at 250. 
 
 Tri-o-tolylstibine dichloride, (CH 3 -C 8 H 4 ) 3 SbCl 2 , colourless needles, 
 m.p. 178-179, is made by passing chlorine into an ethereal 
 solution of the stibine ; the dibromide, colourless, lustrous crystals, 
 m.p. 209-210, and the di-iodide, yellowish- white crystals, m.p. 
 174-175, are similarly prepared. 
 
 Tri-o-tolylstibine oxide, (CH 3 -C 6 H 4 ) 3 SbO, white, amorphous 
 powder, m.p. about 220, is prepared by the action of alcoholic 
 potash on the dichloride, the latter being regenerated on treating 
 the oxide with hydrochloric acid. 
 
 Di-o-tolyl-p-tolylstibine } (CH 3 -C 6 H 4 ) 3 Sb, acicular crystals, m.p. 
 112-113, the by-product found in the tri-o-tolylstibine con- 
 densation when ^-bromotoluene is present, yields a dibromide, 
 m.p. 185-186, and a mercurichloride, separating from alcohol 
 in colourless needles, m.p. 164-165. 
 
 Tri-m-tolylstibine, 1 (CH 3 -C 6 H 4 ) 3 Sb, fan-shaped clusters of 
 colourless crystals from alcohol, m.p. 67-68 (D I '3957/15*7), 
 is prepared by condensing antimony bromide and w-bromotoluene 2 
 with sodium in benzene as in the case of the ortho-isomeride, the 
 yield being 65 per cent, of the calculated amount. The mercuri- 
 chloride, (CH 3 -C 6 H 4 ) 3 Sb,HgCl 2 , softens at 100 and decomposes 
 at 140. When boiled with alcohol it is decomposed, yielding 
 w-tolylmercuric chloride. 
 
 Tri-m-tolylstibine dichloride, (CH 3 -C 6 H 4 ) 3 SbQ 2 , colourless 
 needles, m.p. 137-138, much more soluble in ether than its 
 o- and ^>-isomerides, is prepared by direct addition of its 
 generators ; the dibromide and 'di-iodide form colourless crystals 
 melting respectively at 113 and 138-139. 
 
 Tri-m-tolylstibine oxide, yellowish- white, amorphous powder, 
 softening at 186 and becoming transparent at 210, is obtained 
 by the action of alcoholic potash on the bromide ; dissolvedjn 
 glacial acetic acid, it yields a basic acetate, (C 7 H 7 ) 3 Sb(OH)Ac. 
 
 Tri-m-tolylstibine sulphide, lustrous, acicular crystals, m.p. 
 162-163, readily obtained from the dichloride by the action 
 of alcoholic ammonium sulphide. 
 
 Tri~p-tolylstibine, B (CH 3 -C 6 H 4 ) 3 Sb, well-defined, colourless, 
 
 1 Michaelis and Genzken, loc. cit., p. 184. 
 
 2 Wroblewski, Annalen, 1873, 168, 153. 
 
 3 Michaelis and Genzken, loc. cit., p. 167. 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 transparent rhombohedra from ether, m.p. 127-128, 
 D i -35448/15 -6, is prepared by adding sodium (50 grams, thrice 
 the calculated amount) to antimony tribromide (36 grams) 
 and />-bromotoluene (51 grams) in about 4 volumes of dry 
 benzene. After two to three days the filtered solution is con- 
 centrated, when the crude product crystallises (yield 63 percent.). 
 Unlike triphenylstibine, which is decomposed by mercuric 
 chloride into antimony trichloride and phenylmercuric chloride, 
 tri-^>-tolylstibine forms a mercurichloride, (CH 3 -C 6 H 4 ) 3 Sb,HgCl 2 , 
 a white precipitate from alcoholic solutions of its generators ; 
 it crystallises from ether in nacreous needles and leaflets, 
 softening at 165, decomposing at 175. When boiled with 
 alcohol, this additive compound decomposes, yielding ^-tolyl- 
 mercuric chloride. The tri-/-tolylstibine halides are produced 
 by combining their generators in ethereal solutions ; they form 
 colourless, lustrous crystals, the dichloride, dibromide, and di- 
 iodide melting respectively at 156-157, 233-234, and 182-183 ; 
 a hydroxy-iodide formed by partial hydrolysis of the di-iodide 
 melts at 218-219. 
 
 Tri-p-tolylstibine oxide, (CH 3 -C 6 H 4 ) 3 SbO, white, amorphous 
 powder, m.p. 220, produced by the action of alcoholic potash 
 on the preceding dihalides, is soluble in the ordinary organic 
 media, but insoluble in water. When dissolved in glacial acetic 
 acid it yields a crystalline basic acetate, (C 7 H 7 ) 3 Sb(OH)-Ac, 
 m.p. 168-169. 
 
 Tri-/>-tolylstibine x is readily obtained by the Grignard reaction ; 
 ^>-bromo toluene (20 grams), magnesium (3 grams), and antimony 
 tribromide (14 grams) being employed in ethereal solution. 
 The stibine separating from the ethereal solution is crystallised 
 from methyl alcohol. 
 
 Tribenzylstibine dichloride, 2 
 
 SbCl 3 , 
 $ 
 
 m.p. 105-108, lustrous, colourless crystals from alcohol, prepared 
 through the Grignard reaction with benzyl chloride and antimony 
 trichloride. When hydrolysed by weak alkalis, the dichloride 
 yields tribenzylstibine oxide, (C 6 H 5 CH 2 ) 3 SbO, which decomposes 
 indefinitely at 240. 
 
 1 Pfeiffer, Ber., 1904, 37, 4621. 
 
 2 Morgan and Micklethwait, Chem. Soc. Proc., 1912, 28, 69. 
 
 312 
 
AROMATIC ANTIMONIALS 
 
 PART II 
 
 The Diazo-synthesis of Arylantimony Derivatives. 
 Section IV. Aromatic StiUnic Acids. 
 
 The preparation of aromatic stibinic acids was greatly facili- 
 tated in 1911 when the Chemische Fabrik von Heyden made 
 the remarkable discovery that the stibinic group could be intro- 
 duced into aromatic nuclei through the agency of the diazo- 
 reaction. 1 
 
 Preparation of Phenylstibinic Acid from Aniline. The base 
 (i gram-mol.) dissolved in i litre of water containing sulphuric 
 acid (1-5 gram-mols.) is diazotised with a solution of sodium 
 nitrite (i mol.). A solution of 600 grams of sodium hydroxide 
 in 3 litres of water is added to aqueous antimony trichloride 
 prepared by dissolving antimony trioxide (0-5 mol.) in 764 grams 
 of hydrochloric acid (D 1-123). The solution, which is rapidly 
 cooled to o when a portion of the sodium antimonite separates, 
 is then treated with the diazonium solution, the mixture being 
 vigorously stirred. The evolution of nitrogen is favourably 
 influenced by the preliminary addition of copper paste. After 
 several hours the excess of sodium hydroxide is almost neutralised 
 with dilute sulphuric acid, and phenylstibinic acid is precipitated 
 from the nitrate by the addition of hydrochloric acid. The crude 
 product is purified from antimony trioxide by dissolving 100 grams 
 in 250 grams of hydrochloric acid (D 1-123) an d by saturating 
 the hot solution with dry ammonium chloride. Phenylstibinic 
 oxychloride separates in well-defined leaflets and is washed with 
 a saturated solution of ammonium chloride in hydrochloric acid 
 and dissolved in a slight excess of dilute aqueous sodium carbonate. 
 The purified phenylstibinic acid is precipitated by adding dilute 
 hydrochloric acid to the slightly alkaline filtrate. 
 
 Phenylstibinic acid thus obtained through the diaze-reaction 
 differs in a few particulars from the substance prepared by 
 Hasenbaumer. 2 
 
 1 Fabr. Heyden, D.R.-P., 254421. 
 
 2 Bey., 1898, 31, 2913 ; Inaug. Dissert., Rostock, 1898. 
 
 313 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Free Acid 
 
 Combination 
 Ammonia 
 
 Combination 
 Alkalis 
 
 with 
 
 with 
 
 Phenylstibinic Acid, 
 Hasenbaumer's Acid. 
 
 Amorphous, decom- 
 posed at 200. 
 
 Dissolving in am- 
 monia, but the com- 
 bination decom- 
 posed on heating. 
 No ammonium salt. 
 
 No well denned sodium 
 salt. 
 
 Chemische Fdbrik von 
 Hey den's Acid. 
 
 Amorphous, remaining 
 unchanged at 250. 
 
 Dissolving in ammo- 
 nia; crystalline am- 
 monium salt iso- 
 lated. 
 
 Easily soluble in aque- 
 ous sodium hy- 
 droxide or carbon- 
 ate. Sodium salt pre- 
 cipitated on addition 
 of sodium chloride. 
 
 Phenylstibinic acid, as was to be expected, is entirely different 
 in its properties from phenylphosphinic and phenylarsinic acids, 
 the latter being well crystallisable compounds, easily soluble in 
 water. These differences are similar to those between antimonic 
 acid and phosphoric and arsenic acids. 
 
 Phenylstibinic acid can also be prepared through the diazotisa- 
 tion of aniline antimonious chloride. Sodium nitrite (71 grams) 
 is added to a solution of aniline (93 grams) and antimony tri- 
 chloride (220 grams) in hydrochloric acid (850 grams, D 1-123) 
 and I litre of water. To the cooled solution are added, with 
 vigorous stirring, 400 grams of sodium hydroxide dissolved in 
 10 litres of water. After a short time nitrogen is evolved, and 
 phenylstibinic acid is extracted from the product as in the fore- 
 going process. 1 
 
 Antimony trichloride 2 forms, with diazonium chlorides, 
 additive compounds which are only very sparingly soluble in 
 the ordinary solvents. These products can be employed in the 
 diazo-synthesis of aromatic derivatives of antimony. 
 
 p-Hydroxyphenylstibinic Acid, HOC 6 H 4 -SbO(OH) 2 . The diazo- 
 solution from 109 grams of _/>-aminophenol, 147 grams of sulphuric 
 acid, i litre of water, and 71 grams of sodium nitrite is added, 
 with stirring, to the sodium antimonite mixture obtained as in 
 the foregoing condensation. The mixture is saturated with 
 carbon dioxide and filtered repeatedly to remove antimony 
 trioxide. The filtrate is saturated with sodium chloride and 
 
 1 Fabr. Heyden, D.R.-P., 261825; addition to D.R.-P., 254421. 
 
 2 P. May, Chem. Soc. Trans., 1912, 101, 1037. 
 
 314 
 
AROMATIC ANTIMONIALS 
 
 ^-hydroxyphenylstibinic acid precipitated by dilute sulphuric 
 acid. 
 
 ^-Hydroxyphenylstibinic acid, although sparingly soluble in 
 cold, dissolves more readily in hot water or in aqueous methyl 
 alcohol. It dissolves readily in ammonia solution, and the 
 ammonium salt is precipitated on adding ammonium chloride. 
 
 Preparation of p-Aminophenylstibinic Acid (p-Stibanilic Acid). 
 This substance, the antimony analogue of ^-arsanilic acid, is 
 obtained by the following reactions. Acetyl-^>-phenylenediamine 
 (i gram-mol.) added to well-cooled sulphuric acid (1-5 gram-mol.) 
 in i litre of water is diazotised with sodium nitrite (i mol.) 
 and the solution added to the cooled mixture of sodium anti- 
 monite. The decomposition being completed, the solution is 
 almost neutralised with dilute sulphuric acid and the remainder 
 of the caustic alkali removed by saturating with carbon dioxide. 
 The unaltered antimony trioxide is filtered off, the filtrate 
 saturated with sodium chloride, and the precipitated sodium 
 acetyl-^-aminophenylstibinate freed from sodium chloride by 
 dissolving in methyl alcohol and concentrating the solution. 
 This sodium salt is readily soluble in water to a neutral solution, 
 but is less soluble in excess of alkali. 
 
 Acetyl-p-aminophenylstibinic acid is sparingly soluble in water 
 or dilute acids ; it dissolves readily in ammonia or in alkali 
 hydroxides and carbonates. The acetyl group is readily removed 
 by hydrolytic agents. 
 
 4-Aminophenylstibinic Acid, * NH 2 <^ ^>SbO(OH) 2 . 
 
 Acetyl-4-aminobenzene-i-stibinic acid (50 parts) is heated for 
 some hours with 5 per cent, aqueous sodium hydroxide 
 (500 parts) until a diluted sample gives, with acid, a precipitate, 
 immediately re-dissolving in excess of this reagent. 4-Amino- 
 phenylstibinic acid is then precipitated from the alkaline 
 solution by dilute acetic acid. The sodium salt is deposited 
 on adding alcohol to a solution of the acid in aqueous sodium 
 hydroxide ; it is easily soluble in water. 
 
 4-Aminophenylstibinic acid is practically insoluble in the 
 ordinary organic media ; it is readily soluble in dilute acids or 
 alkalis. The acid itself tends to decompose, but its sodium 
 salt is more stable ; when, however, the latter is warmed with 
 potassium iodide and dilute sulphuric acid, antimony is eliminated 
 and ^-iodoaniline is produced. 
 
 1 Fabr. Heyden, D.R.-P., 270488. 
 315 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 4-Aminophenylstibinic acid is readily soluble in acids or alkalis ; 
 it condenses with aldehydes, and yields a red azo-derivative on 
 successive diazotisation and coupling with alkaline-/2-naphthol. 
 The o-hydroxybenzylidene derivative is obtained by its inter- 
 action with salicylaldehyde in presence of excess of acetic acid. 1 
 
 Sodium p-aminophenylstibinate (or p-stibanilate) is the anti- 
 monial analogue of the arsenical drug atoxyl (sodium ^>-arsani- 
 late) ; it has been recommended as a curative and protective 
 agent in diseases of protozoal origin. 
 
 NH 2 
 
 3-Aminophenyl-i-stibinic Acid, (^ \SbO(OH) 2 . 
 
 3-Nitrophenyl-i-stibinic acid (15 parts, cf. pp. 296 and 300) 
 is mixed with stannous chloride (48 parts) and added to 130 
 parts of alcoholic hydrochloric acid (37 per cent, hydrogen 
 chloride). The mixture becomes rapidly warm, the reagents 
 pass into solution, and colourless leaflets of m-aminophenyl- 
 stibinous chloride hydrochloride separate until the solution 
 sets to a stiff paste of crystals, which is washed with alcoholic 
 hydrochloric acid. The salt is purified by crystallisation from 
 dilute methyl alcohol containing hydrochloric acid ; it melts 
 and decomposes at 215 (v. p. 301). 
 
 3-Aminophenyl-i-stibinic acid is obtained by treating the 
 foregoing chloride hydrochloride successively with sodium 
 hydroxide, hydrogen peroxide, and a slight excess of acetic acid ; 
 it is a white powder decomposing on heating without definite 
 melting point and is insoluble in the ordinary organic media, 
 dissolving, however, readily in dilute alkalis and acids. The 
 addition to these solutions of excess of hydrochloric acid leads 
 to the precipitation of well-defined crystals of the oxychloride 
 hydrochloride, SbOCl 2 -C 6 H 4 -NH 2 ,HC1. 
 
 3-Nitro-4-acetylaminophenyl-i-stibinic acid 2 (I.). 
 
 SbO(OH) 2 SbO(OH) 2 
 
 v 
 
 JNO 2 
 
 [H-COCH 3 
 I. 
 
 1 Fabr. Heyden, D.R.-P., 254421. 
 
 2 Fabr. Heyden, D.R.-P., 259875, 287709. 
 
 316 
 
AROMATIC ANTIMONIALS 
 
 Anhydrous sodium 4-acetylaminophenylstibinate (113 grams), 
 obtained by drying the hydrated salt at 110, is dissolved in 
 glacial acetic acid (300 grams). To the cooled solution ( 10 
 to 2) are added successively 800 grams of concentrated sul- 
 phuric acid and a mixture of nitric acid (25-4 grams, D 1-515) 
 and sulphuric acid (100 grams) ; the mixture is stirred throughout 
 this operation and cooled below o. After stirring for several 
 hours the solution is poured into ice-water, the yellowish-brown 
 3-nitro-4-acetylaminophenyl-i-stibinic acid washed with water 
 and dried. This acid, which is readily soluble in ammonia and 
 in alkali hydroxides or carbonates, is reprecipitated from alkaline 
 solutions with acids, and decomposes on heating without definite 
 melting point. 
 
 S-Nitro-^-hydroxyphenyl-i-stibinic acid (II.) is produced by 
 boiling the preceding compound (35 grams) with aqueous 
 potassium hydroxide (300 grams, D 1-30) until all the ammonia 
 has been evolved ; it is precipitated by adding dilute sulphuric 
 acid to the alkaline solution. The dried acid, a brown powder, 
 insoluble in water and the ordinary organic solvents excepting 
 glacial acetic acid, has no melting point, but intumesces on 
 heating ; it is readily soluble in aqueous alkalis and ammonia. 
 This acid is also obtainable from ^-chloroaniline by the following 
 series of operations. 1 
 
 p-Chlorophenylstibinic acid (I.). 
 
 Cl/ SbOOH 2 Cl/ SbOOH 
 
 I. NO II. 
 
 \ 
 
 Clc SbOCl 2 OH SbO(OH) 2 
 
 NOT NOT 
 
 III. IV. 
 
 Antimony trichloride 2 (84 grams) dissolved in no grams of 
 hydrochloric acid (D 1-123) an d 5 grams of water is added to 
 a diazo-solution obtained by adding sodium nitrite (29 grams) 
 to ^>-chloroaniline (50 grams) dissolved in hydrochloric acid 
 (250 grams, D 1-123) an d water (150 grams). The bulky, yellow 
 precipitate is washed with dilute hydrochloric acid and 
 suspended in ij litres of water to which sodium hydroxide 
 
 1 Fabr. Heyden, D.R.-P., 261825; addition to D.R.-P., 254421. 
 
 2 P. May, Chem. Soc. Trans., 1912, 101, 1037. 
 
 317 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 solution (150 grams, D 1-47) is added. After the slow evolution 
 of nitrogen is ended the insoluble residue is extracted repeatedly 
 with warm dilute sodium hydroxide and the combined nitrates are 
 acidified. The precipitated ^-chlorophenylstibinic acid is dried 
 and dissolved in warm hydrochloric acid (no grams, D 1-123). 
 After adding animal charcoal the filtered solution is saturated 
 with solid ammonium chloride, when ^-chlorophenylstibinic 
 oxychloride, Cl-C 6 H 4 -SbOCl 2 , is precipitated, and washed with 
 hydrochloric acid (D 1-123) saturated with ammonium chloride 
 to remove inorganic antimony compounds. ^-Chlorophenyl- 
 stibinic acid is obtained in a state of purity by dissolving 
 the oxychloride in dilute sodium hydroxide and precipitating 
 the acid from the nitrate with dilute hydrochloric acid. 
 The dried, colourless acid dissolves in alcohol, benzene, 
 chloroform, or carbon bisulphide and is obtained therefrom 
 in a crystalline form which decomposes on heating without 
 melting. 
 
 ^-Chlorophenylstibinic acid when nitrated according to the 
 process outlined on p. 317 is converted into ^-chloro-^-nitrophenyl- 
 n-stibinic acid (II.), a slightly coloured powder which has no 
 definite melting point, but decomposes violently on heating ; it is 
 easily soluble in warm alcohol, but separates therefrom in an 
 amorphous condition on evaporation. On dissolving this com- 
 pound in concentrated hydrochloric acid and on adding 
 ammonium chloride there separates, on cooling, long needles 
 of the oxychloride (III.)* which are hydrolysed by water 
 regenerating 4-chloro-3-nitrophenyl-i-stibinic acid. Alkaline 
 hydrolysis of the chloronitro-compound leads to ^-nitro- 
 4-hydroxyphenyl-i-stibinic acid (IV., p. 317), which is obtained 
 in the form of the easily soluble potassium salt, a scarlet, 
 crystalline powder, by boiling for ten hours 4-chloro-3-nitro- 
 phenyl-i-stibinic acid (163 grams) with 300 grams of 50 per cent. 
 potassium hydroxide and concentrating the solution. The free 
 acid, a yellowish powder, is precipitated by acid from an 
 aqueous solution of the potassium salt. 1 
 
 3-^. mino-^-hydroxyphenyl-i-stibinic acid, 
 NH 2 
 
 \SbO(OH) 2 . 
 
 3-Nitro-4-hydroxyphenyl-i-stibinic acid (30-8 parts) 2 dis- 
 solved in 160 parts of water containing 4 parts of sodium hydroxide 
 1 Fabr. Heyden, D.R.-P., 262236. 2 D.R.-P., 259575, 262296. 
 
 318 
 
AROMATIC ANTIMONIALS 
 
 is reduced with anhydrous sodium hydrosulphite (65 parts) 
 in a solution of sodium hydroxide (2 parts) and in 200 parts 
 of water. As the red solution loses its colour a white precipitate 
 separates. The mixture being continually cooled, the excess 
 of sodium hydrosulphite is decomposed by a current of air and 
 the reduction product collected. 
 
 3-Amino-4-hydroxyphenyl-i-stibinic acid is unstable and 
 darkens even in a dried condition. On heating it decomposes 
 without melting. In water and the ordinary organic media 
 it is insoluble, but nevertheless it dissolves readily in alkalis, 
 ammonia, or acids. Its amino-group is diazotisable, and the 
 diazo-compound couples with alkaline resorcinol and other 
 phenols. The sodium salt, which is easily soluble in water, 
 is precipitated therefrom on the addition of alcohol. 
 
 3-Amino-4-hydroxyphenyl-i-stibinic acid is also obtained 
 from 3-nitro-4-hydroxyphenyl-i-stibinic acid by reduction in 
 aqueous solution with sodium amalgam. 1 
 
 m-A minodiphenylstibinic acid, 
 
 NH 2 
 /~ ~\ 
 
 - ^SbQ-OH. 
 
 w-Aminophenylstibinous chloride hydrochloride (320 parts, 
 v. page 316) is dissolved in water (1500 parts) containing 280 
 parts of sodium hydroxide and mixed in the cold with the 
 diazo-solution obtained in the usual way from aniline (93 parts), 
 hydrochloric acid (660 parts, D 1-085), water (400 parts), and 
 sodium nitrite (71 parts). After the vigorous evolution of 
 nitrogen has subsided w-aminodiphenylstibinic acid is precipi- 
 tated by adding acetic acid. The slightly coloured product 
 is readily soluble either in aqueous alkalis or acids ; it is purified 
 by dissolving in alkali and by adding to the solution excess 
 of strong hydrochloric acid when w-aminodiphenylstibinic acid 
 hydrochloride is precipitated. The dried hydrochloride (43 
 parts) is dissolved in warm methyl alcohol (300 parts) and the 
 solution saturated with sulphur dioxide at a temperature not 
 exceeding 26. After some hours hydrochloric acid (20 parts 
 D 1-123) an d water (100 parts) are successively added and the 
 precipitated by-products removed by nitration. 
 
 1 Fabr. Heyden, D.R.-P., 270488. 
 319 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Bis-m-aminodiphenylstibinous oxide, 
 NH a 
 
 /~ 
 
 \ 
 
 /' "\/ 
 
 The filtrate from the reduction is cooled with ice and cautiously 
 rendered alkaline, when bis-w-aminodiphenylstibinous oxide is 
 obtained as a caseous, slightly coloured precipitate sintering at 
 about 70, reducing Fehling's solution, and having a powerful 
 irritating action on the mucous membrane of the nose. This 
 oxide is insoluble in aqueous alkalis. 1 
 
 Phenyl-m-phenylenestibinic acid. 2 
 
 w-Aminodiphenylstibinous oxide (6 parts) is dissolved in 
 methyl alcohol containing 21-7 parts of hydrochloric acid 
 (D 1-084) diluted with water and treated with sodium nitrite 
 (1-42 parts) in aqueous solution. On neutralising the acid 
 solution with aqueous sodium hydroxide, an evolution of nitrogen 
 sets in, and after the reaction is ended, the liquid is acidified 
 and the crude product collected, dissolved in warm alcoholic 
 hydrochloric acid, reprecipitated by water, and extracted with 
 ether. The organic stibinic acid is removed from the ethereal 
 extract by dilute aqueous sodium hydroxide and precipitated 
 from the alkaline solution by ammonium chloride. In the 
 dried condition this acid is a light brown powder decomposing 
 on heating without definite melting point ; it is only sparingly 
 soluble in aqueous alkalis, but dissolves readily in warm glacial 
 acetic acid. The constitution ascribed to this acid by the 
 Chemische Fabrik von Heyden is indicated by formula I., although 
 the properties and mode of preparation of the substance are not 
 inconsistent with the dimeric configuration II. 
 
 1 Fabr. Heyden, D.R.-P., 269206; addition to D.R.-P., 268451. 
 
 2 Fabr. Heyden, D.R.-P., 269205; addition to D.R.-P., 254421, 
 
 320 
 
AROMATIC ANTIMONIALS 
 
 HO x v 
 
 \_V\_X 
 
 IK 
 
 \ / v~.^\ \ OH 
 
 x / | \ 
 
 [O 
 
 / \/ I 
 
 \- 6n 
 n. 
 
 Chloro-m-phenylenestibinic acid, 
 
 Cl 
 
 or ~ 
 
 01 
 
 \ _ / \ 
 
 \Sb/ 
 
 O^ \OH 
 I. II. 
 
 w-Amino-^-chlorophenylstibinous chloride (32 parts), prepared 
 by the reduction of ^-chloro-w-nitrophenylstibinic acid, is dis- 
 solved in 400 parts of water containing 133 parts of hydrochloric 
 acid (D 1-084) and converted into its sparingly soluble diazo- 
 compound by the addition of 7-3 parts of sodium nitrite. Sodium 
 hydroxide solution (250 parts, D 1-19) is added to the mixture 
 after cooling the latter with ice and stirring is continued until 
 the evolution of nitrogen has subsided. The solution is then 
 filtered and the crude product precipitated by adding hydrochloric 
 acid. The dried precipitate is dissolved in warm alcoholic 
 hydrochloric acid with the addition of animal charcoal and 
 reprecipitated after cooling by dilution with water. Chloro- 
 w-phenylenestibinic acid is further purified by dissolving in 
 aqueous alkali and reprecipitating with acid ; it is thus obtained 
 as a brown powder having no reducing action on Tollens's silver 
 solution. The acid is insoluble in the majority of organic 
 media ; it dissolves in aqueous alkali slowly in the cold and more 
 rapidly on warming. On heating it decomposes without ex- 
 hibiting any definite melting point. 
 
 321 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Section V.Mono-aryl Derivatives containing Tervalent Antimony. 
 i. Aromatic Stibinoxides. 1 
 
 Previously to 1911 only two aromatic stibino-oxides were 
 known, namely, phenylstibinoxide and ^>-tolylstibinoxide (Hasen- 
 baumer, Ber., 1898, 31, 2912, 2914), obtained by hydrolysis from the 
 corresponding chlorides, R'SbCl 2 . But at this date the Chemische 
 Fabrik von Heyden discovered that under suitable reducing 
 conditions the aromatic stibinic acids can be converted either into 
 the corresponding stibinous oxides or into compounds containing 
 the stibino-group -Sb=Sb-. Stannous chloride is employed to 
 prepare the oxides, whereas sodium hydrosulphite is a con- 
 venient agent for reducing the stibine oxides or stibinic acids 
 to the stibino-compounds. If nitro-groups are present in the 
 aromatic stibinic acid, these can, by a suitable choice of reducing 
 agent, be either reduced or left unchanged. Although it was 
 previously known that the reduction of arsenic acids led to 
 arseno-oxides and arseno-derivatives containing the group 
 -As As- (Ber., 1911, 43, 917), yet it was not to be expected that 
 stibinic acids would behave similarly. In many instances 
 organic antimony compounds react differently from the corre- 
 sponding arsenic derivatives. Antimony is more readily removed 
 from the aromatic nucleus, thus benzoyl chloride withdraws anti- 
 mony from triaminotriphenylstibine, whereas triaminotriphenyl- 
 arsine readily yields the tribenzoyl derivative. 2 Michaelis 3 in his 
 comparative studies noted the difference between the aromatic 
 derivatives of antimony and those of phosphorus and 
 arsenic. 
 
 NH 2 
 
 m-Aminophenylstibine oxide, <^ ^>SbO. 
 
 w-Nitrophenylstibinic acid (15 parts) prepared by nitrating 
 phenylstibinic acid with nitric-sulphuric acids is thoroughly 
 mixed with stannous chloride (48 parts) and treated with 130 
 parts of alcoholic hydrochloric acid (37 per cent. HC1). The 
 mixture becomes considerably warmer, the reagents pass into 
 solution, and a separation of colourless leaflets sets in until a 
 
 1 Fabr. Heyden, D.R.-P., 268451. 
 
 2 Giinther, Inaug. Dissert., Rostock, 1904, p. 13; Annalen, 1902, 
 321, 184. 
 
 3 Annalen, 1886, 233, 39. 
 
 322 
 
AROMATIC ANTIMONIALS 
 
 solid crystalline magma is produced. These crystals, consisting 
 of m-aminophenylstibinous chloride hydrochloride, 
 
 HCl,NH 2 -C 6 H 4 -SbCl 2 , 
 
 are obtained in a yield of 90 per cent, of the calculated amount, 
 a similar proportion being furnished by the reduction carried out 
 in concentrated aqueous hydrochloric acid, but by this method 
 the product is contaminated with coloured impurities. This 
 salt is fairly soluble in water or methyl alcohol, less so in ethyl 
 alcohol, and insoluble in acetone, ether, or benzene. When 
 crystallised from aqueous methyl alcohol containing hydrochloric 
 acid it melts at 215. 
 
 w-Aminophenylstibine oxide is obtained as a gelatinous 
 precipitate by hydrolysing the hydrochloride with aqueous 
 sodium hydroxide (3 mols.) ; it is washed with salt solution and 
 methyl alcohol. The oxide is soluble in acids, and its crystalline 
 sulphate is precipitated by alcohol. Like phenylstibine oxide, 
 this compound has an intensely irritating action on the mucous 
 membrane. With neutral or alkaline hydrogen peroxide 
 w-aminophenylstibine oxide is oxidised to m-aminophenyl- 
 stibinic acid, a white, amphoteric substance soluble in alkalis 
 or in acids. The crystalline hydrochloride, 
 
 HCl,NH a 'C a H 4 -SbO(OH) 2 , 
 separates on the addition of excess of hydrochloric acid. 1 
 
 2. Stibinoaryl Derivatives. 
 
 ^> Sb Sb C / 
 
 An aqueous solution of sodium hydrosulphite (10 parts) is 
 added, with stirring, to the solution of phenylstibinic acid 
 (5 parts) in the calculated amount of aqueous sodium hydroxide, 
 and the mixture warmed to 30 and stirred for several hours. 
 A yellow precipitate, which rapidly forms, becomes by the end 
 of the reduction yellowish-brown. The dried crude product is 
 freed from less soluble impurities containing sulphur by boiling 
 in a reflux apparatus with a mixture of equal parts of alcohol 
 and benzene containing copper powder. After distilling off 
 these solvents from the filtered solution, the stibinobenzene 
 separates as a pale yellow powder, insoluble in water, but 
 readily soluble in glacial acetic acid and crystallising from 
 1 D.R.-P., 268451. 2 Fabr. Heyden, D.R.-P., 268451. 
 
 323 Y 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 chloroform. On treatment with oxidising agents, such as 
 hydrogen peroxide in glacial acetic acid, stibinobenzene is 
 reconverted into phenylstibinic acid. 
 
 NH a NH 2 
 
 / \ /' 
 
 3 : ^'-Diaminostibinobenzene, f ; Sb=Sb ^ 
 
 \__/ 
 
 A filtered solution of sodium hydrosulphite (100 parts), 
 magnesium chloride (50 parts), and 10 per cent, sodium hydroxide 
 (100 parts) in 1000 parts of water is added to m-aminophenyl- 
 stibinous chloride-hydrochloride dissolved in 2000 parts of water 
 containing 64 parts of sodium hydroxide. A yellow precipitate 
 slowly separates, and after several hours, or more rapidly by 
 gently warming, a stiff orange-yellow paste is obtained, which on 
 account of its insolubility can be washed with water or aqueous 
 alkalis. When dissolved in glacial acetic acid the clear solution 
 becomes rapidly brown ; mineral acids such as dilute hydro- 
 chloric acid produce a far-reaching decomposition, the yellow 
 compound becoming brown and finally black with partial separ- 
 ation of elemental antimony. The stibino-compound is purified 
 by dissolving in tartaric acid and precipitating with 
 alcohol. 
 
 3 : 3'-Diaminostibinobenzene can also be prepared by adding 
 a saturated solution of sodium hypophosphite (70 parts) to 32 
 parts of w-aminophenylstibinous chloride hydrochloride dis- 
 solved in 1000 parts of water ; the excess of reducing agent 
 serves to fix the mineral acid, which would otherwise decompose 
 the reduction product. The course of the reaction is manifested 
 by a yellow coloration changing to brown. The solution is 
 heated rapidly nearly to boiling, and the reduction product 
 precipitated in yellowish-brown flakes by the addition of ammo- 
 niacal ice-water. This reduction may also be effected in 
 methyl alcohol. 
 
 3 : s'-Diamino-^-^-dihydroxystibinobenzene}- 
 NH a _NH a 
 
 Ho<__>-sb=sb-/_\oH 
 
 3-Nitro-4-hydroxyphenylstibinic acid (31 parts) dissolved in 
 
 500 parts of water and 6 parts of sodium hydroxide is mixed 
 
 with a solution of anhydrous sodium hydrosulphite (200 parts) 
 
 1 Fabr. Heyden, D.R.-P, 268451. 
 
 324 
 
AROMATIC ANTIMONIALS 
 
 in water (400 parts) and sodium hydroxide (17 parts). The red 
 solution slowly becomes decolorised and a precipitate appears 
 which redissolves on adding more sodium hydroxide. After 
 several hours' warming at 40, 3 : 3'-diamino-4 : 4'-dihydroxy- 
 stibinobenzene begins to separate as a reddish-brown precipitate, 
 and when completely deposited is collected in the entire absence 
 of air. The product is easily soluble in aqueous alkalis or acids ; 
 the latter, especially hydrochloric acid, however, speedily produce 
 a further change. The hydroxyl group is identified by means of 
 ferric chloride and the ammo-group through the diazo-reaction 
 and subsequent coupling. 
 
 3 : 3 / -Diamino-4 : 4'-dihydroxystibinobenzene is easily acyl- 
 ated ; it readily condenses with aldehydes. Alkaline hydrogen 
 peroxide oxidises it with loss of colour to 3-amino-4-hydroxy- 
 stibinic acid. 
 
 This substance, in the form of its dihydrochloride, is of ex- 
 ceptional interest as being the antimonial analogue of the 
 important arsenical drug salvarsan. 
 
 Application of Organic Compounds of Antimony. 
 
 Reference has already been made to the use of antimony 
 compounds containing the antimonyl group, SbO, in the treat- 
 ment of trypanosomiasis and allied diseases. These compounds 
 are not truly organo-antimonials in the sense in which this 
 expression is used throughout this monograph. For although 
 they contain both antimony and carbon, these elements are 
 not directly attached to one another, but are united through 
 the intermediary of oxygen. 
 
 The promising results obtained by Plimmer, Fry, Ranken 
 and others 1 in the treatment of sleeping sickness and yaws 
 both with antimony salts, such as lithium antimonyl tartrate, 
 and even with the finely divided metalloid itself, have led to 
 trials of various organo-antimony derivatives. The effect of 
 these products is promising, but so far nothing of specific effect 
 has been discovered to equal the arsenical drugs of the salvarsan 
 and neosalvarsan types. 
 
 Sodium acetyl-^-aminophenylstibinate (Stibacetin) has been 
 tried with success in rendering mice immune against various 
 strains of trypanosomes ; the dose required to do this was T Vth 
 
 1 Proc. Roy. Soc., 1909, 81, B, 334 ; 1910, 83, B, 140; Nature, 1913, 90, 
 662. 
 
 325 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 the lethal amount. Smaller quantities of the drug led to strains 
 of trypanosomes resistant to antimony. 1 
 
 Uhlenhuth has reported on the effect of stibacetin on experi- 
 mental tumours of rats and mice, the results being comparable 
 with those obtained with the arsenical analogue, arsacetin. 2 
 
 Complete immunity to trypanosomes in rats, dogs, and rabbits 
 was obtained by injecting the animals at the time of inoculation 
 with sodium antimony dithioglycinate or the triamide of anti- 
 mony trithioglycine (v. p. 295). Protection was also afforded 
 by injecting with the dithioglycinate twenty-four hours after 
 inoculation. In these compounds the antimony is united to 
 carbon only through the intermediary of sulphur. Sulphoform, 
 the sulphide of triphenylstibine, is another sulphurised anti- 
 monial which has been employed medicinally ; this substance 
 being used as a remedy in various skin diseases (cf. p. 306.) 
 
 The amino-derivatives of triphenylstibine oxide and of 
 diphenylarsinic and monophenylarsinic acids are active against 
 trypanosomes, but they are irritant when introduced sub- 
 cutaneously. 
 
 1 Lange, Zeitsch. Immunitats Forschungen Referate, 1912, 4, 6; cf. 
 Hiigel, Deutsche Medizinische Wochenschrift, 1913, 50. 
 
 2 Medizinische Klinik, 1912, 37. 
 
 326 
 
CHAPTER X 
 
 MISCELLANEOUS ORGANIC DERIVATIVES OF ARSENIC AND 
 ANTIMONY 
 
 Section I. Hydroaromatic Derivatives of Arsenic and Antimony. 
 
 ALTHOUGH the aliphatic and aromatic derivatives of these 
 metalloids have been studied very extensively, scarcely any 
 attention has been directed to the possibilities of combining 
 arsenic and antimony with saturated cyclic radicals. 
 
 The condensation of camphor (in the form of its sodium 
 derivative) with the trichlorides of phosphorus, arsenic, and 
 antimony has been investigated by the writer in collaboration 
 with F. M. G. Micklethwait and W. R. Moore. Sodium camphor 1 
 suspended in toluene condenses vigorously with arsenious chloride, 
 and the mixture when added to water yields a mixture of two acidic 
 substances ; one is dicamphorylarsinic acid, and the other, an 
 uncrystallisable material, is tricamphorylarsinic acid. A third 
 substance having the composition of tribornylarsine was also 
 obtained, but in quantities too small for detailed exami- 
 nation. 2 
 
 With antimony trichloride the reaction goes somewhat differ- 
 ently ; only one main product is obtained, namely tricamphoryl- 
 stibinic chloride, which is slowly resolved by water into tri- 
 camphorylstibinic acid, a very unstable compound decomposed 
 by dilute aqueous sodium hydroxide or even by boiling water. 
 
 For purposes of comparison the condensation was repeated with 
 phosphorus trichloride, and in this instance also only one product 
 was isolated, dicamphorylphosphinic acid. 3 
 
 1 Haller, Compt. rend., 1891, 112, 1490 ; 1892, 113, 22 ; cf. Forster, 
 Chem. Soc. Trans., 1901, 79, 957. 
 
 2 Morgan and Micklethwait, Chem. Soc. Trans., 1908, 93, 2146; 1909, 
 95, 1476. 
 
 3 Morgan and Moore, Chem. Soc. Trans., 1910, 97, 1699. 
 
 327 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Condensation Products from Sodium Camphor and the Trichlorides 
 of the Phosphorus Group. 
 
 Products. 
 
 Phosphorus 
 trichloride. 
 
 Dicamphoryl (Ci H 16 O) 2 POOH, 
 derivatives. dicamphorylphos- 
 phinic acid, stable 
 in concentrated 
 aqueous alkali hy- 
 droxides; decom- 
 posed by fused 
 alkali hydroxides. 
 
 Tricamphoryl 
 derivatives. 
 
 Arsenic 
 trichloride. 
 
 (C 10 H 16 0) 2 AsOOH, 
 d i c am phorylarsi- 
 nic acid, stable 
 in hot dilute 
 aqueous alkali 
 hydroxides ; de- 
 composed by very 
 strong solutions 
 of these alkalis. 
 
 (C ]9 H 15 0) 3 As(OH) ? , 
 tricamphorylarsi- 
 nic acid, is as 
 stable towards al- 
 kalis as the above 
 dicamphoryl de- 
 rivative. 
 
 Antimony 
 trichloride. 
 
 (C 10 H 15 0) 3 SbCl 2 , 
 t r i camphorylsti- 
 binic chloride, 
 slowly resolved by 
 water into 
 
 (C ]0 H 15 0) s Sb(OH) 2 , 
 tricamphorylsti- 
 binic acid, very 
 unstable, decom- 
 posed by dilute 
 aqueous sodium 
 hydroxide and 
 even by boiling 
 water. 
 
 o 
 
 CH As CH X 
 
 Dicamphorylarsinic Acid, C 8 H 14 <f I I \C 8 H 14 . 
 
 \CO OH CO/ 
 
 Camphor (75 grams) dissolved in warm toluene (200 c.c.) 
 is converted into sodium camphor by adding 7-5 grams of sodium . 
 The precipitated sodium derivative suspended in 200 c.c. of fresh 
 toluene is treated slowly with arsenious chloride (38 grams) 
 diluted with twice its bulk of toluene. Considerable heat is 
 generated; the mixture acquires a jelly-like consistence and 
 gradually assumes a deep crimson hue. This colour slowly 
 fades and the mixture regains its fluidity until it consists of a 
 yellow mobile solution with a pulverulent precipitate of sodium 
 chloride. After one hour the mixture is heated at 90-100, 
 and then poured into water and extracted with hot aqueous 
 sodium hydroxide. The alkaline extract, acidified, gives a 
 brownish- white precipitate of crude dicamphorylarsinic acid, 
 the yield being about 10 per cent, on the weight of camphor 
 taken. Crystallisation from benzene gives colourless crystals. 
 Further purification gives highly refractive, obliquely truncated 
 
 328 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 prisms, melting with decomposition at 266, [a]f? -f- 186-6. 
 Dicamphorylarsinic acid is almost insoluble in water or petro- 
 leum ; it dissolves more readily in benzene and is freely soluble 
 in chloroform or alcohol. 
 
 The salts of the alkali metals and ammonium are extremely 
 soluble in water or alcohol. The calcium, strontium, barium, 
 nickel, and cobalt salts are not precipitated in aqueous solutions ; 
 the ferric, mercuric, and cupric salts are almost insoluble in 
 water. 
 
 Silver dicamphorylarsinate, (C 10 H 15 O) 2 AsOOAg, a white, 
 sparingly soluble precipitate from sodium dicamphorylarsinate 
 and silver nitrate, is amorphous at first, but slowly becomes 
 crystalline. 
 
 Cadmium dicamphorylarsinate, [(C 10 H 15 O) 2 AsO 2 ]2Cd, separates 
 as a sparingly soluble, white, crystalline compound on mixing 
 strong aqueous solutions of - cadmium chloride and potassium 
 dicamphorylarsinate . 
 
 From aqueous solutions of its salts, dicamphorylarsinic acid 
 is set free by acetic acid, but only a very slight precipitate is 
 produced by carbonic acid. Dicamphorylarsinic acid does not 
 yield an oxime on treatment with hydroxylamine in hot aqueous 
 or alcoholic solutions. 
 
 Dicamphorylarsinic oxy chloride, (C 10 H 15 0) 2 AsO-Cl, obtained by 
 the interaction of potassium dicamphorylarsinate and phos- 
 phorus pentachloride, separates from chloroform and benzene 
 in colourless crystals melting at 158 : it is very sensitive to 
 moisture, and is rapidly decomposed on exposure to the atmo- 
 sphere ; its specific rotation, taken in dry chloroform, gave 
 [o] D + 106. 
 
 r 
 
 Tricamphorylarsinic Acid, \ C 8 H 
 
 ^8 AA 14\ | 
 
 X CO J3 
 
 As 
 
 OH 
 
 Sodium camphor and arsenious chloride are condensed in dry 
 toluene in the manner indicated in the preceding experiment, 
 and the product extracted repeatedly with aqueous sodium 
 hydroxide. After precipitation with mineral acid, the acidic 
 products are extracted with small quantities of benzene until 
 a residue is obtained consisting of crude dicamphorylarsinic 
 acid ; the benzene extracts also yield small quantities of this 
 substance. The final brown mother liquors are evaporated to 
 dryness, the residue dissolved in dilute aqueous sodium hydroxide, 
 and the solution boiled with animal charcoal and concentrated 
 
 329 
 
t 
 
 ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 to the crystallising point. The crystals, which consist of sodium 
 dicamphorylarsinate, are removed, the solution acidified, and 
 the viscid precipitate again subjected to the treatment with 
 benzene and sodium hydroxide to remove further quantities of 
 dicamphorylarsinic acid. The precipitate finally obtained is 
 a brown uncrystallisable solid, softening at 110 and melting 
 indefinitely at 130. This acid dissolves in water containing a 
 small amount of alcohol ; it is extremely soluble in benzene, 
 alcohol, or acetic acid, separating in a viscid condition from its 
 concentrated solutions in these solvents. The silver salt, is a 
 greyish-white precipitate obtained by double decomposition 
 with ammonium tricamphorylarsinate and silver nitrate. 
 
 T /CHI XI 
 
 Tricamphorylstibinic Chloride, 1 I CH 14 < I Sb<f . 
 
 NioJ. \ci 
 
 On adding a toluene solution of antimony trichloride to sodium 
 camphor suspended in the same medium, considerable heat is 
 generated and a bulky precipitate is produced. The mixture 
 warmed on the water-bath and left for a few days is then treated 
 with water, when a white precipitate of antimony oxide separates. 
 The toluene filtrate is distilled in steam, and the residue extracted 
 with benzene. From the concentrated benzene extract the 
 chloride separates in colourless, ice-like crystals, this separation 
 being promoted by the addition of light petroleum. When 
 recrystallised from benzene, the product melts and decomposes 
 at 244, although when rapidly heated it sometimes remains 
 unchanged at 247-248: [a]D=367-3 (in chloroform). 
 
 Tricamphorylstibinic chloride dissolves only sparingly in alcohol 
 and is insoluble in water. In acid solutions it is fairly stable, 
 and may be boiled with 2AMiydrochloric acid without decom- 
 position. On warming with 2N-sodium hydroxide, the chloride 
 is readily hydrolysed into antimonic and hydrochloric acids and 
 camphor. Destructive hydrolysis occurs on warming the 
 chloride with aqueous sodium hydrogen carbonate or dilute 
 ammonia. A similar decomposition is effected by alcoholic 
 silver nitrate. 
 
 Section II. Heterocyclic Rings containing Arsenic and Antimony. 
 
 Although certain arsenostilbene derivatives are regarded by 
 
 Karrer as containing two doubly-linked arsenic atoms in an 
 
 1 Morgan, Micklethwait, and Whitby, Chem. Soc. Trans., 1910, 97, 35. 
 
 330 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 eight -membered ring (p. 240), it was not until 1915 that 
 analogues of piperidine were synthesised in which the 
 nitrogen is replaced by phosphorus, arsenic, antimony, and 
 bismuth. 
 
 In this year Griittner and Wiernik obtained phenylcyc/o- 
 pentamethylenearsine and phenylc3/c/opentamethylenestibine. 
 This discovery was followed in 1916 by the preparation of even 
 simpler cyclic derivatives of arsenic when Zappi obtained 
 methylcyc/opentamethylenearsine. The general formula for these 
 arsenical analogues (I.) of AT-substituted piperidines (II.) is as 
 follows : 
 
 rI;>\ /CH 2 'CH 2 v 
 
 >AsR CH 2 < >NR. 
 
 H/ X CH 2 -CH/ 
 
 I. II. 
 
 On account of the analogy exhibited by the foregoing formulae, 
 Zappi suggests that the names arsedine and arsepedine should 
 be employed for the arsenical analogues of pyridine and piper- 
 idine respectively. 
 
 The general method of preparation is through the agency of the 
 Grignard reaction. 
 
 i-Methylarsepedine (Methylcyclopentamethylenearsine) , 
 
 xCH 2 -CH 2 \ 
 
 CH 2 < >A S ' CH 3> 
 
 X CH 2 -OV 
 
 colourless liquid having an odour of mustard oil ; D 1-218/18 ; 
 b.p. i56/76o mm., 76/36 mm., 65/2o-22 mm. ; volatile in 
 steam. It is prepared by adding methylarsenious chloride to the 
 magnesium derivative of ae-dichloropentane. It behaves as 
 an unsaturated compound, becoming oxidised in air to a colour- 
 less oxide, C 6 H 10 AsCH 3 :0, soluble in alkaline solution. The 
 methiodide, C 5 H 10 As(CH 3 ) 2 I, white, crystalline solid, m.p. 290, 
 decomposes on heating into methyl iodide and i-methylarsepe- 
 dine. With moist silver oxide the methiodide gives the strongly 
 alkaline hydroxide, C 5 H 10 As(CH 3 ) 2 -OH. i-Methylarsepedine com- 
 bines additively with the halogens yielding dihalogen derivatives, 
 C 5 H 10 As(CH 3 )(Hal) 2 . The dichloro- and dibromo-compounds are 
 hygroscopic substances ; the di-iodo-derivative is a yellow 
 powder decomposing at 120. i-Methylarsepedine furnishes a 
 platinichloride and picrate (yellow compounds, m.p. 163 and 
 
 258) .1 
 
 1 Zappi, Bull. Soc. chim., 1916, [iv], 19, 151, 290. 
 331 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 i-Phenylarsepedine (Phenylcyclopentamethylenearsine, I.), 
 
 yCH a 'CH 2 \ xCH 2 -CH 2 v 
 
 CH 2 A s ' c eH5 CH 2 >Sb-C 6 H 5 , 
 
 / 
 
 2 'e5 2 
 
 X CH 2 -CH/ \CH 2 -CH 
 
 I. II. 
 
 colourless, viscous oil of unpleasant odour; Df 1*2480 ; w 2 ^ 4 1'5944 ; 
 b.p. !53-i54"/i8-20 mm. (in carbon dioxide). 
 
 Phenylarsenious chloride is added to the magnesium com- 
 pound of ac-dibromo- (or dichloro-) pentane in ethereal solution. 
 A poorer yield of i-phenylarsepedine is obtained through 
 Michaelis's method by the interaction of phenylarsenious chloride, 
 dibromo- (or dichloro-) pentane, and sodium in ether. The 
 dichloride, C 5 H 10 As(C 6 H 5 )Cl 2 , hygroscopic leaflets, melts at 
 138-139 ; the following are characteristic derivatives : 
 mercurichloride, needles, m.p. 2or5~2O2 ; methiodide, colourless 
 leaflets, m.p. T-79'5 ; n-butiodide, m.p. 140. 
 
 T-p-Tolylarsepedine, C 5 H 10 -As-C6H 4 -CH3, prepared with 
 ^>-tolylarsenious chloride by the Grignard reaction, has the 
 following characteristics : colourless oil, Df 1-2174 ; H 1-5948 ; 
 b.p. i62-i63/2O mm. (in carbon dioxide) ; dichloride, m.p. 134 ; 
 mercurichloride, m.p. 175. 
 
 Phenylcyclopentamethylenestibine (II.), prepared by the general 
 method from phenylstibine chloride, has the following 
 characteristics : colourless, viscous oil, unpleasant odour, b.p. 
 169-171 /i8-2o mm. (in carbon dioxide) ; Df 1-4966 ; f 4 1-6203. 
 Exposed to air it slowly oxidises to phenylcyclopentamethylene- 
 stibine oxide, C 6 H 10 -Sb(C 6 H 5 ):0, colourless powder unfused at 
 280; dichloride, m.p. 141-142. 
 
 The pyrrolidine analogues containing arsenic and antimony 
 have also been prepared by the Grignard reaction, using 
 aS-dibromobutane. 
 
 Phenylcyclotetramethylenearsine (I . ) , 
 
 CH 2 -CH 2 \ CH 2 -CH 2 v 
 | >As-C 6 H 6 >Sb-C 6 H 5 , 
 
 CH 2 -CH/ CH 2 -CH/ 
 I. II. 
 
 colourless, mobile oil, odour not unpleasant; b.p. i28-5/i5-i6mm.; 
 Di 7 1-2824 ; w" 1-6768 : prepared by adding phenylarsenious 
 chloride to the magnesium compound of aS-dibromobutane in 
 ethereal solution. It is very unsaturated, giving the following 
 additive compounds : dichloride, hygroscopic crystals, m.p. 
 
 332 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 120-5 ; mercurichloride, leaflets, m.p. 160-162 ; methiodide, 
 m.p. 135-136 ; and higher alkyl iodides. 
 
 Phenylcyc\Qtetramethylenestibine (II.), prepared by the Grignard 
 reaction, using phenylstibine chloride ; colourless oil, un- 
 pleasant odour, b.p. i56-i58/20-22 mm. ; rig 1-6313 ; di- 
 chloride and dibromide, birefringent crystals, m.p. 150 and I49 . 1 
 
 Section III. Arsenical Derivatives containing Heterocyclic Nuclei. 
 Arsenic Compounds of the Quinoline Series.* 
 
 Quinoline, 8-hydroxyquinoline, and tetrahydroquinoline when 
 treated with arsenious chloride in ethyl acetate yielded respect- 
 ively the additive compounds C 9 H 7 N,AsCl 3 , m.p. 138; 
 C a H 7 NO,AsCl 3 , m.p. 168 ; and C 9 H n N,AsCl 3 , m.p. 134. 
 
 The introduction of arsenic into the ring was not effected either 
 by the action of aluminium chloride or by Bechamp's reaction. 
 Skraup's reaction carried out on ^-arsanilic acid led merely to 
 quinoline. Knorr's reaction with ethyl acetoacetate on ^-arsanilic 
 acid did not give an arsenical product. 
 
 The reaction of Dobner and Miller furnished quinaldinearsinic 
 acid, CH 3 -C 9 H 6 N-AsO 3 H 2 , although only in poor yield, by mixing 
 ^-arsanilic acid (6 grams) with 21 c.c. of acetaldehyde and 
 allowing the excess of the latter to evaporate over sulphuric acid. 
 Fuming hydrobromic acid (48 c.c. of D 1-49) was added to 
 the mixture, when a yellow, crystalline material separated which 
 was washed with water dissolved in alcohol and reprecipitated 
 with water. The yellow arsinic acid begins to decompose at 
 140 and chars at 170. Reduced with sodium and ethyl alcohol 
 it yields quinaldinearsenious oxide, CH^-CgHgN-AsO, a flocculent 
 precipitate from alcohol-acetic acid, decomposing at 120. 
 
 Arsinic Acids of Indole Series? 
 Methylindolearsinic Acid (Methylketolearsinic Acid), 
 
 OAsO(OH) a 
 
 colourless needles, m.p. 180-182, prepared by adding methyl- 
 
 1 Griittner, Wiernik, and Krause, Ber., 1915, 48, 1473 ; 1916, 49, 437 
 
 2 Frank el and Lowy, Ber., 1913, 46, 2546. 
 
 3 C. F. Boehringer and Sohne, D.R.-P., 240793. 
 
 333 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 ketole (13 parts) to anhydrous arsenic acid (28-4 parts) in 
 6 parts of hot water. The product freed from arsenic acid with 
 water was dissolved in aqueous caustic soda and reprecipitated 
 by hydrochloric acid. This arsinic acid is easily soluble in alcohol 
 or glacial acetic acid. 
 
 Sodium salt, C 9 H 9 O 3 NAsNa,2|H 2 O, readily soluble in water, 
 decomposing at 225-235 ; quinine salt, 
 
 C 20 H 24 O 2 N 2 ,C 9 H 10 3 NAs,2H 2 0, 
 
 m.p. 170-172, easily soluble in methyl or ethyl alcohol, pre- 
 cipitated therefrom by water in colourless needles ; insoluble in 
 ether or chloroform. Chloro-derivative, m.p. 185-186 (decom- 
 posed) . 
 
 a-Naphthindolearsinic acid, crystals. a-Naphthindole (4 
 parts) in 40 parts of toluene heated in a reflux apparatus with 
 anhydrous arsinic acid (6-4 parts) in 5 parts of absolute alcohol : 
 the toluene is removed by distillation, the residue, after extraction 
 with alcohol, dissolved in aqueous caustic soda and reprecipitated 
 by acid. 
 
 Arsenical Derivatives of Thiophen. 
 
 The general methods of Bechamp and Bart are not readily 
 applicable to the thiophen series, and the arsenical derivatives 
 of this heterocyclic sulphur compound are preferably prepared 
 from the mercury derivatives which are easily obtained from 
 thiophen and its homologues. 
 
 Thienylarsenious Chloride (I.), 
 
 CH CH CH GIF 
 
 CH C-AsCl 
 
 \Q/ 
 
 CH C- 
 
 \s/ 
 
 AsCl 
 
 I. II. 
 
 Arsenious chloride (130 grams) is added to powdered mercuri- 
 dithienyl, the mixture being cooled during addition. The dark 
 brown nitrate from mercuric chloride is fractionated in hydrogen 
 under a pressure of n mm. The fraction 116-130 on further 
 rectification gives the dichloride boiling at 118-122 (n mm.) 
 as a light brown liquid with unpleasant odour. 
 
 Dithienylarsenious chloride (II.) is obtained from fraction 
 1 50-1 94 /i i mm. by further rectification as a brown liquid, 
 b.p. 2i9-232/i3 mm. 
 
 334 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 r CH CH" 1 
 
 Trithienylarsine, 
 
 L 
 
 C- 
 
 As. 
 
 The portions of the foregoing distillations boiling over 190 
 were concentrated and finally distilled with the aid of a Gaede 
 pump. The arsine is a pale yellowish-green, viscous liquid, 
 almost inodorous, b.p. 199-200 -5 /o -5 mm. 1 
 
 When thiophene-2-mercurichloride and arsenious chloride are 
 heated in toluene for a prolonged period the chief product is 
 dithienylarsenious chloride. 
 
 This synthetic process based on the use of organo-mercurials, 
 which is an extension of one of Michaelis's general methods for 
 arylarsenicals, 2 was first employed by C. Finzi, who oxidised 
 the chloro-compounds directly to arsinic acids. 
 
 Thiophen-2-arsinic Acid (Thienyl-2-arsinic Acid, I.) 
 
 CH CH 
 
 r CH CH 
 
 AsO(OH), 
 
 I. 
 
 CH C- 
 
 II. 
 
 AsOOH . 
 
 Mercury 2 : 2 '-dithienyl or preferably thiophen-2-mercuri- 
 chloride (white plates, m.p. 183), prepared by adding a cold 
 saturated solution of mercuric chloride and 30 per cent, aqueous 
 sodium acetate to thiophen dissolved in alcohol, is treated with 
 freshly distilled arsenious chloride, the mixture being finally 
 warmed on the water-bath. The product filtered from mercuric 
 chloride is treated successively with aqueous caustic soda and 
 hydrogen peroxide. Inorganic arsenic is separated partly by 
 crystallising out sodium arsenate and partly by precipitation with 
 barium chloride. The filtrate freed from barium with sulphuric 
 acid is evaporated to dryness, sodium chloride rendered insoluble 
 by concentrated hydrochloric acid, and the final mother liquor 
 evaporated over quicklime. The residue, consisting of a mixture 
 of two arsinic acids, is dissolved in absolute alcohol, decolorised 
 with animal charcoal, and converted into sodium salts. Sodium 
 thiophen-2-arsinate, C 4 H 3 S-AsO 3 HNa, separates in transparent, 
 colourless, non-deliquescent, rhombic scales, very soluble in 
 water. 
 
 1 Steinkopf (with Bauermeister) , Annalen, 1917, 413, 331. 
 
 2 Michaelis, Annalen, 1880, 201, 196 ; 1902, 320, 272 ; cf. pp. 62, 72. 
 
 335 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Thiophen-2-arsinic acid l is fairly soluble in water or alcohol 
 and forms colourless needles, m.p. 135-5. At 105-108 it is con- 
 verted into thiophen-2-arsinic anhydride. 
 
 Sulphurous acid, in the presence of a trace of hydriodic acid , 
 reduces this arsinic acid to thienyl-2-arsenious oxide, a white 
 substance insoluble in water but dissolving in concentrated 
 aqueous caustic alkali. Further reduction with alkali hydro - 
 sulphite leads to arsenothiophene, C 4 H 3 S-As:As-C 4 H 3 S. Salts 
 of thiophene-2-arsinic acid : Magnesium salt, colourless mam- 
 millated crystals, on boiling a solution of the acid with magnesia 
 mixture ; barium salt, (CaHsS-AsOgH^Ba, white crystals, pre- 
 pared by treating the acid successively with -baryta water and 
 carbon dioxide; the filtered solution yields the salt on concen- 
 tration ; silver salt, C^S'As'OaAga, white, amorphous pre- 
 cipitate. 
 
 2 : 2'-Dithienylarsinic Acid (II.). The alcoholic mother liquor 
 from sodium thiophen-2-arsinate in the foregoing preparation 
 is distilled to dryness. The residue, taken up with water and 
 dilute hydrochloric acid, gives 2 : 2 '-dithienylarsinic acid, sparingly 
 soluble in cold water ; it dissolves in alcohol, but not in ether or 
 benzene, and separates from boiling water in minute needles, 
 m.p. 172. 
 
 With magnesia mixture it does not yield a precipitate either 
 in the cold or on boiling, a property distinguishing this 
 secondary arsinic acid from arsenic acid or from primary arsinic 
 acids. 
 
 2 : 2 '-Dithienylarsinic acid is obtained in better yield by heating 
 thiophen-2-arsenious chloride with thiophen-2-mercurichloride 
 in sealed tubes. 
 
 The following nitro-compounds are obtained from the two 
 thienylarsinic acids. Although the orientation of the nitro- 
 group is not determined with certainty, it is inferred from analogy 
 with other reactions in the thiophen series that the nitro- 
 group takes up the remaining ortho-position with respect to 
 sulphur. 
 
 ^-Nitrothienyl-2-arsinic acid (I), 
 
 CH CH CH CH 
 
 NO 2 -C C-AsO 3 H a > NH a -C C-AsO 3 H 2 
 
 ' \S/ \S/ 
 
 I. II. 
 
 1 Finzi, Gazzetta, 1915, 45, [ii], 286. 
 
 336 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 Thiophen-2-arsinic acid is added to a cooled mixture of fuming 
 nitric and concentrated sulphuric acids, the nitrous fumes being 
 removed by a current of air. The nitro-compound precipitated 
 by the cautious addition of cold water (40-50 per cent.) is crystal- 
 lised from boiling water ; it forms slightly yellow prisms melting 
 and passing into its anhydride at 194. 
 
 ^-Aminothienyl-2-arsinic acid (II.) is produced by reducing the 
 preceding nitro-compound in methyl-alcoholic solution with 
 sodium amalgam. The alcohol is removed by distillation, the 
 residue acidified with excess of hydrochloric acid, and filtered 
 from sodium chloride and tarry impurity. Sodium acetate 
 added to the filtrate precipitates the aminoarsinic acid, crystal- 
 lising in yellowish leaflets, m.p. 194, sparingly soluble in organic 
 solvents, water, or methyl alcohol ; its hydrochloride, 
 
 HCl,NH 2 -C 4 H 2 S-AsO 3 H 2 , 
 
 soluble in water or alcohol, separates in dendritic forms like ice 
 crystals on glass ; acetyl derivative, colourless prisms from water, 
 decomposing at 134. 
 4 : ^'-Dinitrodithienyl-2-arsinic Acid, 
 
 CH CH CH CH 
 
 II ii 9. ii ii 
 
 NO 2 -C C As C ON0 2 . 
 
 \ s / 1 \S/ 
 OH 
 
 This dinitro-acid (decomposing at 287), prepared by nitrating 
 dithienyl-2-arsinic acid, is precipitated by diluting the mixed 
 nitric-sulphuric acids with water and purified through its sodium 
 salt. 1 
 
 Section IV. Arsenical Esters and Arsenical Lipoid and Protein 
 
 Combinations. 
 
 i. Arsenical Esters, 
 Esters of Arsenious and Arsenic Acids. 
 
 Although the esters of arsenious and arsenic acids are not 
 organo-arsenical compounds in the sense implied in this treatise 
 they are of utility in organic synthesis. 
 
 Methyl and ethyl ar senate, 2 R 3 AsO 4 , are produced by heating 
 
 1 Finzi and Furlotti, Gazzetta, 1915, 45, [ii], 290. 
 
 2 J. M. Crafts, /. Pharm., 1871, [iv], 13, 242. 
 
 337 z 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 well-dried silver arsenate suspended in ether with methyl or 
 ethyl iodide at 100 : 
 
 Me ester, b.p. 128-1 3o/6o mm. D 1-5591/14-5. 
 
 Et ester, b.p. i48-i5o/6o mm. D 1-3264/0. 
 
 Ethyl arsenite. Three methods of preparation. 
 
 (1) Arsenious oxide with ethyl silicate at 200 in sealed tubes, 
 SiO a deposited. 
 
 (2) Ethyl iodide with Ag 2 HAsO 3 at 150, yields less than with 
 arsenate. 
 
 (3) Preferable method : 3NaOC 2 H 5 + AsBr 3 = 3NaBr + 
 As(O-C 2 H 5 ) 3 in alcoholic solution. Ammonia is introduced to 
 precipitate AsBr 3 %NH 3 , the ethereal nitrate fractionated. 
 
 Me ester, As(OCH 3 ) 3 , b.p. 128-129. D 1-428. 
 
 Et ester, As(O-C 2 H 6 ) 3 , b.p. 165-166. D 1-224/4. 
 
 Am ester, As (OC 5 H U ) 3 , b.p. 288 and i93-i94/6o mm. 
 
 The alkyl arsenites are produced by heating crystallised ar- 
 senious oxide with various alcohols in a reflux apparatus so that 
 the alcohol and water vapour circulate over calcium carbide. 
 The water is eliminated and the dried alcohol drops back on the 
 oxide. In this way good yields of the esters are obtained. The 
 method is available for the phenyl ester. * 
 
 An ingenious modification of this method is due to Lang, 
 Mackey, and Gortner, in which anhydrous copper sulphate is 
 used in the reflux apparatus as the dehydrant. Good yields 
 are obtained in most instances. 
 
 o/ o/ 
 
 /o /o 
 
 Me ester . . . . 33-8 Trimethylcarbinyl ester 54-27 
 
 Et ,, . . . . 4-5 Amyl ester 54 -oo 
 
 Pr ,, . . . . 56-75 ^soAmyl ester 58-62 
 
 f'so-Butyl ester . . 56-25 
 
 The phenyl ester made by this method is a yellow, viscous 
 liquid freezing at 31, b.p. 305/30 mm. ; D 1-59. The tolyl 
 and naphthyl esters are producible by this method : resorcinyl 
 arsenite, (C 6 H 4 O 2 ) 3 As 2 , is an amber liquid, m.p. 24, D 1-9, 
 decomposed by water, 2 soluble in alcohol. 
 
 Mixed anhydrides of arsenious oxide 3 : 
 
 Acetyl arsenite, As[OCOCH 3 ] 3 , colourless needles, m.p. 82 ; 
 b.p. i65-i7O/3i mm. ; soluble in chloroform or ethyl acetate, 
 
 1 Auger, Compt. rend., 1906, 143, 968. 
 
 2 Chem. Soc. Trans., 1908, 93, 1364; Chem. Soc. Proc., 1909, 25, 199. 
 
 3 Pictet and Bon, Bull. Soc. chim., 1905, [iii], 33, 1139. 
 
 338 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 decomposed by water or alcohols. When fused with benzole 
 acid it yields benzoyl arsenite. As[OCOC 6 H 5 ] 3 , white, crystalline 
 mass ; m.p. 155 ; soluble in anhydrous solvents except petroleum. 
 The complex monoiodo-arsenical ester 
 
 r _SO 3 Na-i 
 
 0:As O/ 
 
 OH I 
 
 is prepared by heating at 100 silver arsenate (10 parts) with 
 29 parts of sodium 2 : 6-di-iodophenol-4-sulphonate in 300 parts 
 of water. 1 
 The hexamethylenetetramine compound of arsenic acid, 
 
 (C 6 H 12 N 4 ) 3 (H 3 As0 4 ) 2 , 
 
 is precipitated on mixing saturated alcoholic solutions of its 
 generators. It is much less toxic than arsenic acid. 2 
 
 The iron salts of arsenitartaric and arsenicitric acid have been 
 recommended for use in therapeutics. 3 
 
 2. Arsenical Compounds of the Unsaturated (Acetylenoid) 
 Higher Fatty Acids Elarson. 
 
 Good clinical results have been obtained in anaemia with the 
 strontium salt of an arsenical additive compound of behenolic 
 acid containing As 13 and Cl 6 per cent. The salt 
 has been introduced into pharmacy under the name of 
 " Elarson."* 
 
 The acids of the acetylene series have the property of combining 
 with trihalides of phosphorus and arsenic, and when the 'more 
 complex acids are employed the products are fatty (lipoid) 
 materials absorbable in the alimentary canal ; they still possess 
 acidic properties, yielding soluble alkali salts and insoluble 
 calcium and strontium salts. 
 
 Stearolic acid and arsenious chloride (r| parts) are heated at 
 140, the product is dissolved in ether, shaken with water to 
 remove excess of arsenic compounds, the ethereal solution con- 
 centrated, rendered alkaline, and the clear solution acidified. 
 The precipitated fatty mass is redissolved in ether and the 
 solution dried with calcium chloride and evaporated. 
 
 Similar products are obtainable from behenolic acid and 
 
 1 Wolffenstein, D.R.-P., 239073. 
 
 2 Bossi, Giorn. Farm. Chim., 1911, 60, reprint. 3 D.R.-P., 208711. 
 4 E. Fischer and Klemperer, Therapie der Gegenwart, 1913. J an - 
 
 339 z 2 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 arsenious bromide, phosphorus trichloride and phosphorus 
 tribromide, and from stearolic acid and phosphorus trichloride. 1 
 
 Alternative methods of production consist in treating behenolic 
 acid with arsenious oxide, anhydrous copper, or magnesium 
 sulphate and leading in dry hydrogen chloride or bromide at 
 I40. 2 
 
 The acetylenoid acids can be mixed with arsenious oxide and 
 treated slowly with thionyl chloride or heated with arsenic or 
 phosphorus and sulphuryl chloride, the temperature being raised 
 to I40-I45 . 3 
 
 The esters of the chloroarsinosoacetylenoid acids are thera- 
 peutically valuable, being soluble in lipoid substances and devoid 
 of acid reaction. 
 
 Methyl behenolate reacts similarly with arsenious chloride at 
 135 and yields on ethereal extraction methyl chloroarsinoso- 
 behenolate as a brown oil ; the ethyl ester has similar properties. 
 Behenolic anhydride, from behenolic acid and phosgene in pyr- 
 idine, condenses with arsenious chloride at 140 and yields a 
 brown solid, chloroarsinosobehenolic anhydride. 
 
 Chloroarsinosobehenolic acid and thionyl chloride undergo 
 a vigorous interaction, and the product, a complex acid chloride, 
 condenses with aniline to yield chloroarsinosobehenolanilide. 4 
 
 The iron salts of these arsenical and phosphorus acids are of 
 utility and are made by adding alcoholic ferric chloride or basic 
 ferric acetate to alcoholic solutions of the arsinoso- compound. 5 
 
 The chemical nature of these substances was worked out by 
 Fischer 6 in the case of the behenolic acid derivatives, as this 
 material was more amenable than the products from stearolic 
 and phenylpropiolic acids. The unsaturated aliphatic acids 
 containing triple (acetylene) linkings combine with arsenious 
 chloride to give an additive compound containing the group I. 
 
 AsCl 2 Cl AsO Cl 
 
 I. II. 
 
 As the result of treatment with alkali during the process of 
 separation the chlorine atoms attached to arsenic are removed 
 
 1 Heinemann, D.R.-P., 257641. E. Fischer, U.S. P., 1082509, 1082510 ; 
 Eng. P., 18732/1912, 10378, 10379/1913 ; Fr. P., 449014. 
 
 2 Heinemann, D.R.-P., 268829. 8 Heinemann, D.R.-P., 271159. 
 * D.R.-P., 273219. 6 Heinemann, D.R.-P., 271158. 
 6 E. Fischer, Annalen, 1914, 403, 109. 
 
 340 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 and replaced by oxygen, giving rise to a compound containing 
 the group II. To these products Fischer gives the name of 
 chloroarsinoso-compound. 
 
 Chloroarsinosobehenolic acid, C 2 aH 4() O 8 AsCl, is prepared from 
 pure behenolic acid and arsenious chloride (1-25 parts) heated 
 at 140 for six hours, when the mixture is subsequently shaken 
 with water and ether. The ethereal solution is treated suc- 
 cessively with cold N-caustic potash and dilute hydrochloric 
 acid. The preparation still contains behenolic acid, which crys- 
 tallises out on cooling. The final product containing about 
 86 per cent, of the chloroarsinoso-compound is a light brownish- 
 red oil insoluble in water, but dissolving easily in alcohol, ether, 
 benzene, chloroform, or olive oil. The alkali salts are soluble, 
 and a carefully neutralised solution of the potassium salt has 
 been used in intravenous injections. 
 
 Strontium chloroarsinosobehenolate, ' ' Elarson, ' ' (C 22 H 3 9 O 3 AsCl) 2 Sr , 
 is an amorphous, colourless precipitate 'obtained by adding an 
 alcoholic solution of the chloroarsinoso-acid to a methyl- 
 alcoholic solution of strontium chloride saturated with gaseous 
 ammonia. It is very sparingly soluble in alcohol, ether, or 
 olive oil. 
 
 Methyl chlorobehenolarsinic acid ester, C 23 H 44 O 6 AsCl : Chloro- 
 arsinosobehenolic acid, is converted into its methyl ester by 
 heating with sulphuric acid and methyl alcohol. The methyl 
 ester is treated with bromine in carbon disulphide solution ; the 
 solution is diluted with ether and shaken with water. The 
 crude ester is converted into its strontium salt, (CgsH^OgAsCl^Sr, 
 and set free with acid. 
 
 This acid ester is hydrolysed by methyl-alcoholic potash to 
 the dibasic chlorobehenolarsinic acid, which is purified through 
 its strontium salt, C 23 H 40 O 5 AsClSr. 
 
 In these arsinic acid derivatives produced from chloroarsinoso- 
 behenolic acid by the oxidising action of bromine the following 
 arsenical group is probably present. 
 
 /^ 
 
 L 
 
 I /OH I 
 ):AsC Cl 
 
 \ 
 
 In these compounds the arsenic is much more firmly held 
 to the carbon than in the chloroarsinoso-derivatives which are 
 decomposed into arsenious and behenolic acids by warming on 
 the water-bath with dilute alkali. 
 
 341 
 
ORGANIC COMPOUNDS OF ARSENIC AND ANTIMONY 
 
 Arsenical Esters containing Complex Open Chain Radicals. 1 
 
 Dibromobehenic acid (12 grams), obtained by brominating 
 erucic acid, is heated gradually with 7-4 grams of silver ar- 
 senate; the reaction occurs between 125 and 170; 1-5 grams of 
 the arsenate are added and silver bromide is removed quan- 
 titatively. 
 
 Lecithin (50 grams) is converted into bromolecithin by 10 
 grams of bromine and the product heated in toluene with the 
 equivalent amount of silver arsenate. After filtering from silver 
 bromide, the toluene is distilled off in vacuo, and the residue 
 contains the organic arsenical ester. 
 
 3. Protein Combinations containing Arsenic. 
 
 Insoluble combinations containing firmly attached arsenic 
 are produced by dissolving albumin from white of egg 
 (100 grams) in acetic anhydride at 137, cooling the solution, 
 and adding phosphoric anhydride (200 grams). The mixture 
 is then treated with arsenious chloride (50 grams), the excess 
 of inorganic reagents subsequently decomposed by water, and 
 the resulting phosphoric and arsenious acids removed from the 
 protein precipitate by washing with water. The preliminary 
 solution in acetic anhydride may be omitted. The product, 
 an amorphous,, brown mass, contains 0-6 per cent, of arsenic 
 and 0-8 per cent, of phosphoric oxide ; it is insoluble in water, 
 dilute acids, or organic media, but is soluble in dilute aqueous 
 alkalis. It fails, to give the ordinary analytical reactions of 
 arsenic with sulphuretted hydrogen or ammonium phospho- 
 molybdate. A similar product is obtained by adding successively 
 sulphur trioxide (200 grams) and arsenious chloride (100 grams) 
 slowly to well-cooled white of egg (1200 grams). The mixture 
 is washed with water till free from sulphuric and arsenious 
 acids. 2 
 
 The product dried at 150 is a yellowish-brown powder in- 
 soluble in water or dilute acids, but dissolving in dilute aqueous 
 alkalis ; its alkaline solution is not coagulated on warming. 
 The percentages of arsenic and added sulphur trioxide are 
 0-6 and 0-3 per cent, respectively. Similar products are obtained 
 from casein, plant albumin, glue, peptones, and albumoses ; 
 
 1 Wolffenstein, D.R.-P., 239073. 2 Gnezda, D.R.-P., 201370. 
 
 342 
 
ORGANIC DERIVATIVES OF ARSENIC AND ANTIMONY 
 
 they all contain arsenic in a firmly combined form in which its 
 analytical reactions are masked. 1 
 
 An arsenical preparation insoluble in the gastric juices is 
 obtained by adding arsenious chloride diluted with alcohol to 
 gliadin or glutenin suspended in alcohol at the ordinary tempera- 
 ture and stirred for six hours. The alcohol is removed in vacua 
 and after polymerisation the product washed with absolute 
 alcohol. This arsenical albumin is soluble in hot water and 
 contains about 4-33 per cent, of arsenic. 2 
 
 Soluble stable combinations of salvarsan base and protein 
 substances have been produced by the interaction of salvarsan 
 and the alkali salts of lysalbic and protoalbic acids, nucleic acid 
 or casein. The insoluble additive product is dissolved in alkali 
 hydroxide and the alkali salt precipitated by alcohol-ether 
 or obtained solid by evaporating in vacuo? 
 
 Colloidal iron arsenate-albumose preparations 4 have been 
 suggested for use in therapeutics. 
 
 1 Cf. D.R.-P., 104496, 135306, 135307. 2 Kloffer, D.R.-P., 214717. 
 
 3 Bering, D.R.-P., 261542. 
 
 4 Kalle, D.R.-P., Anmeldung 23394/10 12 p. 
 
 343 
 
APPENDIX 
 
 Estimation of Arsenic in Organic Compounds. 
 
 RECENT developments in the investigation of organic deriv- 
 atives of arsenic have brought into prominence the problem of 
 estimating this element when directly combined with carbon. 
 The following methods have been adopted for destroying the 
 organic matter in these substances : 
 
 (1) Combustion of the substance mixed with soda-lime by 
 heating in a stream of air or oxygen ; the residue is dissolved in 
 hydrochloric or nitric acid, the arsenic then precipitated as 
 sulphide, and finally converted into magnesium pyroarsenate. 1 
 
 (2) Oxidation of the organic arsenic derivative by fusion with 
 sodium peroxide, the arsenic being estimated gravimetrically as 
 pyroarsenate. 2 
 
 (3) Destruction of the organic matter with nitric acid containing 
 magnesium nitrate, when a final ignition leads to the formation 
 of magnesium arsenate. 3 
 
 (4) The substance is carefully mixed with its own weight of 
 potassium nitrate, oxidised with nitric acid. The mixture 
 evaporated to dryness, extracted with acetic acid, and treated 
 successively with sodium acetate and standard uranium acetate 
 solution (i c.c. ~ 0-0053 As) 4 . 4 
 
 Exception has been taken to the sodium peroxide method on 
 the ground that at the high temperature produced by the 
 oxidation some loss of volatile arsenic compounds may result. 
 But with due care in mixing and heating the reagents the loss 
 becomes almost inappreciable, even when the oxidation is 
 violent and the substance employed somewhat volatile. 
 
 The chief difficulty arises at a later stage in the precipitation 
 of magnesium ammonium arsenate in the presence of the large 
 
 1 La Coste and Michaelis, Annalen, 1880, 201, 224. 
 
 2 Pringsheim, Amer. Chem. /., 1904, 31, 386. 
 
 3 Monthule, Ann. Chim. anal., 1904, 9, 308. 
 
 4 Martindale, Extra Pharmacopoeia, 1915, II. 27. 
 
 344 
 
APPENDIX 
 
 excess of alkali salt produced from the sodium peroxide. The, 
 results obtained are almost uniformly too high, even when 
 measured quantities of " magnesia mixture " and the other 
 reagents are employed. Satisfactory values are obtained by 
 redissolving the magnesium ammonium arsenate and reprecipi- 
 tating it with ammonia, but this procedure renders the analysis 
 very long and tedious, as the two precipitations each require 
 considerable time for their completion. 
 
 The arsenic may be removed by rendering acid with hydro- 
 chloric acid and distilling. But the process is lengthy owing 
 to the unavoidably large bulk of solution to be distilled with a 
 ferrous salt in a current of hydrogen chloride. 1 
 
 lodimetric method of Little, Cohen, and Morgan. 
 
 A quicker method giving satisfactory results is based on a 
 volumetric process due to Gooch and Browning. 2 
 
 The reaction involved may be sufficiently indicated by the 
 following equation : 
 
 As 2 O 6 + 4HI ^ As 2 O 3 -f 2H 2 O + 2l 2 , 
 
 these authors having shown that the change takes place quan- 
 titatively from left to right, when the liberated iodine is removed 
 by boiling. The arsenious oxide is then titrated with standard 
 iodine in the usual way. 
 
 Procedure? 
 
 The finely powdered substance (0-2 to 0-3 gram) is mixed in 
 a nickel crucible with 10 to 15 grams of sodium peroxide and 
 sodium carbonate in equal proportions, a portion of these re- 
 agents being spread over the mixture to prevent loss by projec- 
 tion. A gentle heat is applied for about fifteen minutes, and 
 the fusion completed by raising the temperature to dull redness 
 for five minutes. With careful mixing and heating, the oxidation 
 generally takes place without fuming or detonation. 
 
 The contents of the crucible are extracted with water and 
 rinsed into a 450 c.c. conical flask. From 25 to 31 c.c. of sul- 
 
 1 Morgan, Chem. Soc. Trans., 1904, 85, 1001. 
 
 2 Amer. J. Sci., 1890, [iii], 11, 66. 
 
 3 Little, Cahen, and Morgan, Chem. Soc. Trans., 1909, 95, 1478 ; cf. 
 Warunis, Chem. Zeit., 1912, 31, 1205; Bohrisch and Kiischner, Pharm. 
 Zentr.-h. 1911, 52, 1365. 
 
 345 
 
APPENDIX 
 
 phuric acid (i : i) are added cautiously, and, if necessary, the 
 solution is boiled down to 100 c.c., when i gram of potassium 
 iodide is introduced, and the liquid further concentrated to 40 c.c. 
 A few drops of dilute sulphurous acid are added to destroy 
 the last traces of iodine, and the bright green solution is diluted 
 considerably with hot water and saturated with hydrogen sul- 
 phide. The arsenious sulphide is collected, washed about 
 three times with hot water, dissolved off the filter with 20 c.c. 
 of JV/2-sodium hydroxide, and the filtrate returned to the 
 conical flask, where it is treated with 30 c.c. of hydrogen peroxide 
 (20 vols.) , the excess of this reagent being destroyed by heating 
 on the water-bath for ten minutes. After the frothing has 
 subsided, a few drops of phenolphthalein are added, followed 
 by ii c.c. of sulphuric acid (i : i), this quantity giving 10 c.c. 
 in excess. One gram of potassium iodide is now added to the 
 liquid, which should have a volume of 100 c.c., and the solution 
 concentrated to 40 c.c., when its pale yellow colour is removed 
 by a few drops of dilute sulphurous acid. Cold water is quickly 
 added, and the diluted solution neutralised with 2Af-sodium 
 hydroxide and just acidified with sulphuric acid. The requisite 
 amount of 11 per cent, sodium phosphate (see Note 3) is added, 
 and the arsenite solution titrated with standard iodine and 
 starch in the usual way. 
 
 Notes on the Method. 
 
 1. A gravimetric estimation may be effected by proceeding as 
 far as the oxidation of the sulphide with alkaline hydrogen 
 peroxide and then precipitating as magnesium ammonium arse- 
 nate by Austin's method. 1 
 
 2. The manipulation might be simplified by estimating 
 directly, by Gooch and Browning's method, the arsenate in 
 the filtered aqueous extract of the fused mass. The filtration of 
 nickel hydroxide and carbonate is, however, extremely tedious, 
 and this modification of the process does not lead to greater 
 rapidity or accuracy. The precipitate may be rendered more 
 amenable by oxidation to nickelic hydroxide with the aid of 
 bromine, but the results obtained in the titration are not satis- 
 factory. 
 
 3. The titration may be carried out in the presence of sodium 
 hydrogen carbonate, but the addition of disodium hydrogen 
 
 1 Zeitsch, anorg. Chem., 1900, 23, 146. 
 346 
 
APPENDIX 
 
 phosphate, which has been advocated by E. W. Washburn, 1 is 
 preferable. The volume of n per cent, sodium phosphate 
 added should be equal to the number of c.c. of N/io-iodine 
 required in the titration. 
 
 4. This method gives trustworthy results with all the commer- 
 cial arsenical derivatives, whether containing triadic or pentadic 
 arsenic. 
 
 lodimetric method of Ewins. 
 
 A method of estimating arsenic in organic tissues, devised by 
 Norton and Koch, 2 has been successfully utilised in the estimation 
 of the metalloid in its organic derivatives. 3 The principle is 
 essentially that of KjeldahFs method of the determination of 
 nitrogen adapted to the estimation of arsenic (or antimony) . 
 
 In a comparatively simple and rapid method of determining 
 arsenic in salvarsan and neosalvarsan described by Lehmann, 4 
 the substance is completely oxidised by means of permanganate 
 and concentrated sulphuric acid, the product further treated 
 with hydrogen peroxide, and the arsenic finally estimated volu- 
 metrically by the amount of iodine liberated from an acid 
 solution containing potassium iodide. The method is rapid 
 (one to one and a half hours for the estimation), and gives 
 accurate results with the compounds mentioned and certain 
 closely allied derivatives provided adequate precautions are 
 taken to ensure the complete elimination of excess of hydrogen 
 peroxide (merely boiling is insufficient). In certain cases, 
 however, the method entirely fails, owing to the fact that pre- 
 liminary treatment with potassium permanganate and sulphuric 
 acid does not bring about complete oxidation. Benzarsinic 
 acid and dimethyl- and diethyl-benzarsinic acids are especially 
 resistant to this treatment. The method of Norton and Koch 
 is applicable to such compounds, and quite satisfactory results 
 have been obtained with arsenic derivatives of widely differing 
 constitution. The method requires only the simplest apparatus 
 and materials, needs very little attention, and is applicable 
 to all but very volatile arsenic derivatives. Essentially it 
 consists in the moist combustion of the organic compounds 
 
 1 /. Amer. Chem. Soc., 1908, 30, 31. 
 
 2 Ibid., 1905, 27, 1247. 
 
 3 Ewins, Chem. Soc. Trans., 1916, 109, 1356. 
 
 4 Apoth. Zeit., 1912, 27, 545. 
 
 347 
 
APPENDIX 
 
 by means of concentrated sulphuric acid ; the arsenic present 
 is converted into arsenious acid, which is finally estimated 
 volumetrically by means of iodine in the usual manner. 
 
 Procedure. 
 
 A small quantity of the substance (o-i to 0-2 gram) is washed 
 into a long-necked Kjeldahl flask of about 300 c.c. capacity. 
 Ten grams of potassium sulphate and 0-2 to 0-3 gram of starch 
 are then added. Any solid adhering to the neck of the flask 
 is washed in with a little water. Twenty c.c. of concentrated 
 sulphuric acid are next cautiously added, and the flask is then 
 placed on a wire gauze over a Bunsen flame. As soon as the 
 contents of the flask begin to froth the flame is lowered somewhat 
 until the frothing diminishes, which generally happens within 
 about ten to fifteen minutes from the commencement of heating. 
 The flame is then again turned on full, and heating continued 
 until the liquid becomes colourless or of a very pale yellow tint. 
 The flask is shaken once or twice during the heating in order 
 to wash down any material adhering to the walls. The time 
 required for the complete combustion of the material is usually 
 about four hours, but during the greater part of this time the 
 flask may safely be left without attention. 
 
 The contents of the flask are next allowed to cool, and then 
 washed quantitatively into a flat-bottomed flask of about 350 
 c.c. capacity. A solution of sodium hydroxide (io-i2AT) is 
 then added from a burette until the solution is just distinctly 
 alkaline to litmus. 
 
 The flask and its contents are then cooled to about 30-40, 
 and a few drops of concentrated sulphuric acid added until 
 the solution is again distinctly acid. A saturated solution of 
 sodium hydrogen carbonate is next added from a burette until 
 the solution becomes distinctly alkaline and an excess of 5-10 
 c.c. of the reagent is present. 
 
 To this solution is now added 2 c.c. of a i per cent, solution 
 of starch, and the arsenious acid present is titrated by means 
 of a N/2O-solution of iodine. Towards the end of the titration 
 the solution usually develops a reddish-violet tint, which fades 
 perceptibly on keeping. The end-point, however, is only 
 reached when the solution acquires the characteristic deep blue 
 colour given by free iodine in the presence of starch. This 
 blue colour, moreover, shows no tendency to fade on keeping. 
 
 348 
 
APPENDIX 
 
 From the amount of iodine required, the percentage of arsenic 
 present is easily calculated. One c.c. of 2V/20-iodine = 0*001875 
 gram of arsenic. 
 
 The Pharmacopoeia Germanica oxidises 0-2 gram of the 
 arsenic compound with 10 c.c. of concentrated sulphuric acid 
 and i c.c. of fuming nitric acid in a long-necked 100 c.c. Jena 
 flask. After boiling for one hour the cooled mixture is treated 
 with 50 c.c. of water and evaporated, this procedure being 
 repeated. To the cold solution are added successively 10 c.c. 
 of water and 2 grams of potassium iodide in 5 c.c. of water, 
 sufficient' water being added to dissolve the precipitate. After 
 thirty minutes the iodine is titrated (without an indicator) with 
 N/io sodium thiosulphate : i c.c. = 0-003748 gram of arsenic. 
 
 Analysis of very Volatile Arsenicals. 
 
 Gaseous and very volatile arsenical compounds such as methyl- 
 arsine and phenylarsine are analysed as follows by Palmer and 
 Dehn. 1 
 
 The carbon and hydrogen are estimated by combustion in 
 a long tube packed with lead chromate and copper oxide, the 
 burning being conducted in a current of oxygen. For the 
 arsenic estimation a similar tube is employed packed with pure 
 zinc oxide. The contents are dissolved in acid, the arsenic 
 precipitated as arsenious sulphide, oxidised to arsenic acid, and 
 reprecipitated as magnesium ammonium arsenate and weighed 
 as pyroarsenate. 
 
 Separation of Arsenic Acid from p-Arsanilic Acid and its 
 Derivatives. 
 
 Sufficient hydrochloric acid is added to decompose the alkali 
 salt of the organic arsinic acid. The substituted arsanilic acids 
 are usually precipitated completely from the cooled acid solution, 
 and the arsenic acid remaining in the nitrate is then thrown 
 down as magnesium ammonium arsenate and weighed as pyro- 
 arsenate. 
 
 ^-Arsanilic acid itself is not, however, precipitated completely 
 in the foregoing circumstances. The soluble portion is converted 
 into its azo-resorcinol derivative, which is precipitated almost 
 completely, the last trace of colour being removed by animal 
 charcoal. 2 
 
 1 Ber., 1901, 34, 3597. 2 Schmitz, Ber., 1914, 47, 364. 
 
 349 
 
APPENDIX 
 
 Estimation of Antimony in Organic Compounds. 
 
 In the combustion of organic antimony derivatives Landolt 
 employed a mixture of warm copper oxide with 4-5 per cent, 
 of potassium chlorate which was kept dried over concentrated 
 sulphuric acid. The estimation of carbon and hydrogen in 
 an organic antimonial is effected satisfactorily with oxygen 
 in a lead chromate combustion tube when the antimony is fixed 
 as lead antimonate. 
 
 The antimony is estimated by heating with a mixture of sodium 
 peroxide and sodium carbonate as in the fusion method for 
 arsenic in its organic derivatives. The fused mass is rendered 
 slightly acid either with hydrochloric acid alone or mixed with 
 phosphoric acid, and the antimony is precipitated by sulphuretted 
 hydrogen from the boiling solution in the form of the black, 
 crystalline, anhydrous antimonious sulphide. This precipitate 
 is collected in a broad Soxhlet tube so arranged that it can be 
 heated to 280-300 by a ring burner. The Soxhlet tube is 
 fitted with a glass stopper carrying a thermometer and furnished 
 with a side tube through which carbon dioxide is passed during the 
 heating in order to exclude air from the sulphide. 1 By this 
 procedure the antimony can be determined gravimetrically 
 as trisulphide. 
 
 Antimony when present in aromatic stibines and their deriv- 
 atives is estimated by burning the substance with oxygen in a 
 narrow tube containing lime and soda-lime, dissolving out the 
 contents of the tube with hydrochloric acid, and precipitating 
 the antimony as trisulphide. This substance is oxidised and 
 weighed as Sb 2 O 4 . 2 
 
 1 Cahen and Morgan, Analyst, 1909, 34, 3, 
 
 2 Michaelis and Reese, Annalen, 1886, 233, 46; Loloff, Ber., 1897, 30, 
 2835- 
 
 350 
 
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 351 
 
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 W. R. LANG AND J. O. WOODHOUSE. Some Esters of Arsenious 
 
 Acid. Part II, Resorcinyl Arsenite. Chem. Soc. Prcc., 1909, 
 
 25, 199. 
 H. F. V. LITTLE, E. CAHEN, AND G. T. MORGAN. The Estimation 
 
 of Arsenic in Organic Compounds. Chem. Soc. Trans., 1909, 
 
 95, 1478. 
 LAVERAN. Antimonyl Anilintartrate (Aniline-emetic). Pharm. 
 
 Zeit, 1909, 54, 919. 
 E. MAMELI. Sull' acido i-amino-2-nitro-^-fenilarsinico. Boll. 
 
 chim farm., 1909, 48, 682. 
 AND PATTA. Sull' acido para-iodiofenilarsinico e sull' ioduro 
 
 di para-iodiofenilarsenico. Boll. Soc. Medico. Chir. Pa via, 
 
 1909. 
 W. H. MARTINDALE. Organic Arsenic Compounds. Seventh 
 
 International Congress of Applied Chemistry, 1909. 
 G. T. MORGAN AND F. M. G. MICKLETHWAIT. Organic Derivatives 
 
 of Arsenic. Part III. Triaminotriphenylarsine Oxide and Tri- 
 
 camphoryl-arsinic Acid. Chem. Soc. Trans., 1909, 95, 1476. 
 A. BERTHEIM. Vber halogenierte p-Aminophenylarsinsduren. 
 
 Ber., 1910, 43, 530. 
 
 356 
 
BIBLIOGRAPHY 
 
 G. T. MORGAN, F. M. G. MICKLETHWAIT, AND G. S. WHITBY. 
 
 Organic Derivatives of Antimony. Part I. Tricamphorylstibine 
 
 Chloride and Triphenylstibine Hydroxy nitrate and Hydroxy- 
 
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 AND MOORE. Dicamphorylphosphinic Acid. Chem. Soc. 
 
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 MROCZKOWSKI. Dialkylaminoarylarsinsduren. Dissert. Rostock, 
 
 1910. 
 
 L. BENDA. Uber die p-Nitmnilin-arsinsdure. Ber., 1911, 44, 3293. 
 . Uber p-Phenylendiamin-arsinsdure. Ber., 1911, 44, 3300. 
 . o-Aminophenyl-arsinsdure (o-Arsanilsdure) . Ber., 1911, 
 
 44, 3304. 
 
 . Uber Nitro-oxyphenylarsinsdure (AsO 3 H 2 : NO 2 : OH = 
 
 i 13:4)- Ber., 1911, 44, 3445. 
 . Ifber die ^-Amino-^-oxy-phenyl-i-arsinsdure und deren 
 
 Reduktionsprodukte. Ber., 1911, 44, 3578. 
 
 A. BERTHEIM. Nitro- und Amino-arsanilsdure. Ber., 1911, 44, 3093. 
 AND L. BENDA. Die Konstitution der isomeren Amino-phenyl- 
 
 arsinsdure und der Michaelischen Nitro-phenyl-arsinsdure. 
 
 Ber., 1911, 44, 3297. 
 P. EHRLICH AND S. HATA. The Experimental Chemotherapy of 
 
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 E. MAMELI AND PATTA. Dell' acido para-iodiofenilarsinico e di 
 
 alcuni suoi derivati. Arch. Farmacologia sper., 1911, xi 
 
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 W. H. MARTINDALE AND W. W. WESTCOTT. Salvarsan or " 606 " 
 
 (Dioxydiaminoarsenobenzol) . Its Chemistry, Pharmacy, and 
 
 Therapeutics. London, 1911. 
 
 P. MAY. The Chemistry of Synthetic Drugs. London, 1911, p. 186. 
 A. MICHAELIS AND A. GiJNTHER. Uber Diphenylstibin-Verbin- 
 
 dungen. Ber., 1911, 44, 2316. 
 G. T. MORGAN AND F. M. G. MICKLETHWAIT. Organic Derivatives 
 
 of Antimony. Part II. The Orienting Influence of Antimonic 
 
 Substituents in the Benzene Nucleus. Chem. Soc. Trans., 1911, 
 
 99, 2288. 
 P. EHRLICH AND A. BERTHEIM. Uber das Salzsdure 3 : ^'-diamino- 
 
 4 : ^'-dioxybenzolund seine ndchsten Verwandten. Ber., 1912, 
 
 45,756. ' 
 L. BENDA. Uber die Nitrierung der Arsanilsdure. Ber., 1912, 
 
 45, 53- 
 
 P. FRIEDLANDER. Fortschritte der Theerfarbenfabrikation: Berlin, 
 Vol. IX, 1908-10, 884 ; Vol. X, 1910-12, 1064 ; Vol. XI, 
 1912-14, 870. 
 
 FOURNEAU AND OECHSLIN. Chlorure de I'acide dichlorarsinoben- 
 zoique-T : 4. Ethers de I'acide benzarsinieux et de I'acide 
 benzarsinique. Bull. Soc. chim., 1912, [iv], 11, 909. 
 
 S. FRAENKEL. Die Arzneimittel Synthese. Berlin, 1912, p. 663. 
 
 P. KARRER. Zur Kenntnis aromatischer Arsinverbindungen, 
 I. tfber p-Nitrosophenylarsinsdure. Ber., 1912, 45, 2065. 
 
 357 
 
BIBLIOGRAPHY 
 
 P. MAY. Aromatic Antimony Compounds. Part III. Some 
 
 Primary Aryl Derivatives. Chem. Soc. Trans., 1912, 101, 1033. 
 
 . Aromatic Antimony Compounds. Part IV. Compounds of 
 
 Antimony Trichloride with Diazonium Chlorides. Ibid., 
 
 1912, 101, 1037. 
 
 L. MAURETONIO. L'Arsenico. Milan, 1912. 
 
 G. T. MORGAN AND F. M. G. MICKLETHWAIT. Organic Derivatives 
 
 of Arsenic and Antimony. (Preliminary Note.) Chem. Soc. 
 
 Proc., 1912, 28, 20. 
 . Aromatic Amino-derivatives containing Antimony. 
 
 (Preliminary Note.) Chem. Soc. Proc., 1912, 28, 69. 
 M. NIERENSTEIN. Organische Arsenverbindungen und ihre chemo- 
 
 therapeutische Bedeutung. Ahren's Sammlung Chemischer 
 
 und Chemisch-technischer Vortrage. Stuttgart, 1912. 
 H. SCHMIDT. Die aromatische Arsenverbindungen. Berlin, 1912. 
 WINMILL. Asymmetric Quaternary Arsonium Compounds and 
 
 their Attempted Resolution. Chem. Soc. Trans., 1912, 101, 
 
 718. 
 N. ANDREW. Derivatives of Naphthylarsinic Acid. J. Russ. 
 
 Phys. Chem. Soc., 1913, 45, 1980. 
 A. BERTHEIM. Handbuch der organischen Arsenverbindungen. 
 
 Stuttgart, 1913. 
 J. CH. BONGRAND. Sur la neutralisation des solutions de chlor- 
 
 hydrate de dioxydiamino-arsenobenzene. J. Pharm. Chim., 
 
 1913, [vii], 7, 49. 
 
 CARRE. Sur les phenylstibines. Bull. Soc. chim., 1913, [iv], 
 
 13, 102. 
 J. DANYSZ. De I'emploi de quelques combinaisons medicament- 
 
 euses nouvelles dans le traitement des trypanosomiases. 
 
 Compt. rend., 1913, 157, 644. 
 P. EHRLICH. Address in Pathology on Chemiotherapy. British 
 
 Medical Journal, August i6th, p. 353. 
 - AND P. KARRER. Uber Arseno-stibino- und Arseno- 
 
 bismuto-Verbindimgen. Ber. ,^1913, 46, 3564. 
 S. FRANK EL AND P. LOWY. Uber Arsen-Verbindungen der 
 
 Chinolingruppe. Ber., 1913, 46, 2546. 
 E. FISCHER AND G. KLEMPERER. Uber eine neue Klasse von 
 
 Lipoid Arsenoverbindungen. Therapie der Gegenwart, 1913. 
 L. HUGOUMENQ AND A. MOREL. Recherches sur les combinaisons 
 
 des acides carbo%y-arylarsiniques avec les amines derives des 
 
 albumines. Sur I'acide hippitrarsinique (AsO 3 H 2 -C 6 H 4 - 
 
 CONH-CH 2 -COOH). J. Pharm. Chim., 1913, [vii], 7, 383. 
 P. KARRER. Zur Kenntnis aromatischer Arsenverbindungen III. 
 
 Uber Diazimid-arylarsinsduren und einige ihrer Derivate. 
 
 Ber., 1913, 46, 249. 
 . Zur Kenntnis aromatischer Arsenverbindungen IV. Dar- 
 
 stellung der ^-Nitro-^-dimethylaminophenylarsinsaure und 
 
 der 3-Nitro-^-oxy-phenyl-arsinsdure. Ber., 1913, 46, 515. 
 A. MICHAELIS AND A. ScHAFER. Zur Kenntnis der Arseno- 
 
 Verbindungen. Ber., 1913, 46, 1742. 
 
 358 
 
BIBLIOGRAPHY 
 
 L. BENDA. Uber o-Anisidin-arsinsdure und einige ihrer Derivate. 
 
 Ber. 1914, 47, 995. 
 . Uber die Reduktion der 3 : $-Dinitro-4~aminophenyl-i- 
 
 arsinsdure. Ber., 1914, 47, 1316. 
 A. BERTHEIM. Methylierende Spaltung von Arsenoverbindungen. 
 
 Ber., 1914, 47, 274. 
 A. A. BOON. A Chapter in Applied Chemistry. Pharm. J., 1914, 
 
 39, 836. 
 J. DANYSZ. Composes de chlore de brome et de I'iode de dioxydiamido- 
 
 arsenobenzol et d l argent. Compt. rend., 1914, 158, 199. 
 P. EHRLICH. Eine Darstellung seines wissenschaftlichen Wirkens 
 
 (Festschrift zum 60 Geburtstage des Forschers 14 Mdrz, 
 
 1914). Jena, 1914. 
 E. FISCHER. Uber eine neue Klasse von aliphatischen Arsen- 
 
 verbindungen. Annalen, 1914, 403, 109. 
 P. KARRER. Zur Kenntnis aromatischer Arsen-VerbindungenV .Uber 
 
 p-Jodoso- und p-Jodo-phenyl-arsinsdure. Ber., 1914, 47, 96. 
 . Zur Kenntnis aromatischer Arsen-Verbindungen VI. Uber 
 
 einige Umsetzungen der 3 : $-Dichlor-^-diazo-phenylarsin- 
 
 sdure. Ber., 1914, 47, 1781. 
 . m Zur Kenntnis aromatischer Arsenverbindungen VIII. 
 
 Uber einige Reduktionsprodukte der 2 : ^-Dinitro-phenyl- 
 
 arsinsdure und eine grosse Klasse von neuen Carbaminsdure- 
 
 Derivativen. Ber., 1914, 47, 2275. 
 G. T. MORGAN. Organic Derivatives of Arsenic and Antimony. 
 
 Pharm. J., 1914, 38, 516, 537, 567. 
 K. OCHSLIN. Action du trichlorine d'arsenic sur les bases aro- 
 
 matiques monoalcoylees et sur les ethers des phenylalcoylglycines. 
 
 Ann. Chim., 1914, [ix], 1, 239. 
 ROEDER AND BLAST. Neue Arsenierung organischer Verbin- 
 
 dungen. Ber., 1914, 47, 2748. 
 SCHMITZ. Versuche uber die Haftfestigkeit der Arsensdure am 
 
 aromatischen Kern. Ber., 1.914, 47, 363. 
 BARTHE. Antipyrine Cacodylate, Antipyrine Methylarsinate. Bull. 
 
 Soc. Pharm. Bordeaux, 1914,348,353 ; Pharm. J., 1915,94,99. 
 H. BAUER. Uber Resorcin-arsinsdure und einige ihrer Derivate 
 
 und Reduktionsprodukte. Ber., 1915, 48, 509. 
 . Uber m-Aminophenol-arsinsduren und der en Reduktions- 
 produkte. Ber., 1915, 48, 1579. 
 A. BERTHEIM. Uber sekunddre aliphatisch-aromatische Arsin- 
 
 sduren und deren Reduktionsprodukte, speziell 3 : ^-Diamino- 
 
 4 : ^-dioxy-diphenyl-dimethylarsin. Ber., 1915, 48, 350. 
 P. EHRLICH AND P. KARRER. Arseno-Metallverbindungen. Ber., 
 
 1915, 48, 1634. 
 C. FINZI AND V. FURLOTTI. Acidi arsenicali derivati dal tiofene. 
 
 Gazzetta, 1915, [ii], 45, 290. 
 . Acidi arsenicali derivati dal tiofene. Gazzetta, 1915, 45, 
 
 [ii], 280. 
 G. GRI)TTNER AND M. WIERNIK. Neue heterocyclische Systeme. 
 
 I. Piperidin-Analoge in denen das Stickstoffatom durch 
 
 359 
 
BIBLIOGRAPHY 
 
 Phosphor, Arsen, Antimon oder Wismuth ersetzt ist. Ber., 
 1915, 48, 1473. 
 
 G. GRUTTNER AND M. WIERNIK. BeUrdge zur Kenntnis der 
 organischen Antimonverbindungen. I. Die Einwirkung von 
 Antimon-trichlorid auf Triphenylantimon. Ber., 1915, 48, 
 1749; //. Darstellung gemischter Alkyl-stibine. Ibid., 1759. 
 
 P. KARRER. Zur Kenntnis aromatischer Arsenverbindungen. 
 IX. Uber einige Stilben-arsinsduren und ihre Derivate. Ber., 
 
 1915, 48, 305. 
 
 . Zur Kenntnis aromatischer Arsenverbindungen. X. Uber 
 
 oiiho-carboxyliertes Diamino-dioxy-arsenobenzol. Ber., 1915, 
 48, 1058. 
 
 . Zur Kenntnis der aromatischen Arsenverbindungen. XI. 
 
 Uber gemischte Arsenoverbindungen. Ber., 1916, 49, 1648. 
 
 W. H. MARTINDALE AND W. W. WESTCOTT. The Extra Pharma- 
 copoeia. Vol. I, pp. 140, 160 ; Vol. II, pp. 20, 24. i6th 
 Edition, London, 1915. 
 
 A. MICHAELIS. Uber Arseno-benzolsduren. Ber., 1915, 48, 870. 
 
 A. RENAULT, L. FOURNIER AND L. GUENOT. Cinq cent cinquante 
 cas de syphilis traites par un compose organique d' arsenic, de bro- 
 mine d'argent et d'antimonyle. Compt. rend., 1915, 161, 685. 
 
 J. ABELIN. Uber die u-Methylsulfonsditre der p-Amino-phenyl- 
 arsinsdure. Bicchem. Zeitsch., 1916, 78, 191. 
 
 DALIMIER AND LEVY-FRANCHEL. Le 102 de Danysz dans le 
 traitement de la syphilis maligne ou grave. Compt. rend., 
 
 1916, 162, 440. 
 
 A. J. EWINS. The Estimation of Arsenic in Organic Compounds. 
 
 Chem. Soc. Trans., 1916, 109, 1356. 
 E. SIEBURG. Uber Ester aromatischer Arsenverbindungen (der 
 
 p-Benzarsinsdure] mit Aminosduren und hoheren Alkoholen. 
 
 Arch. Pharm., 1916, 254, 224. 
 . Zur Biologie aromatischer Arsenverbindungen. Zeitsch. 
 
 physiol. Chem., 1916, 97, 53. 
 E. V. ZAPPI. Note preliminaire sur une nouvelle chaine heterogene 
 
 contenant de I' arsenic dans le noyau : la cyclopentamethylene- 
 
 methylarsine. Bull. Soc. chim., 1916, [iv], 19, 151. 
 . Sur une nouvelle chaine heterogene contenant de V arsenic 
 
 dans le noyau : la methylarsepedine (cyclopentamethylene- 
 
 methylarsine. Ibid., 290. 
 G. GRUTTNER AND E. KRAUSE. Neue heterocyclische Systeme. 
 
 II. Pyrrolidin-Analoge in denen das Stickstoffatom durch 
 
 Phosphor, Arsen oder Antimon ersetzt ist. Ber., 1916, 49, 437. 
 L. BENDA. Uber Arsenverbindungen der Anthrachinonreihe. 
 
 J. pr. Chem., 1917, [ii], 95, 74. 
 J. DANYSZ. The Physico-chemical Properties of the Products of 
 
 the Group of the Arsenobenzenes. Their Transformation in the 
 
 Organism. Ann. Inst. Pasteur, 1917, 31, 114. 
 W. STEINKOPF (WITH M. BAUERMEISTER) . Studien in der 
 
 Thiophenreihe. Uber Quecksilber- und Arsen-Thiophenverbin- 
 
 dungen. Annalen, 1917, 413, 331. 
 
 360 
 
INDEX OF AUTHORS' NAMES 
 
 Abelin, 161. 
 
 Adler, K., 158. 
 
 Adler, O., 158, 171, 174, 176, 198. 
 
 Adler, R., 171, 174, 176, 198. 
 
 Adler, W., 174, 198. 
 
 Aktien-Gesellschaf t fur Anilin 
 
 Fabrikation, 179. 
 Allschul, 159. 
 Amort, 23. 
 Andrews, N., 239. 
 Auger, 28, 29, 34, 35, 40, 41, 47, 
 
 62, 338. 
 
 Baeyer, 10, 13, 17, 29, 33. 
 Barrowcliff, 158, 180, 182, 184. 
 Bart, 84, 85, 89, 106, 133, 145, 149, 
 
 I6O, 2OI, 2O2, 2O6, 211, 264. 
 
 Barthe, 16. 
 
 Bauer, 199, 204, 207, 234, 245. 
 
 Bauermeister, 335. 
 
 Bechamp, 64, 65, 153. 
 
 Benda, 144, 147, 156, 157, 167, 168, 
 170, 171, 173, 174, 176, 178, 
 182, 185, 187, 190, 196, 198, 
 200, 203, 205, 206, 233, 248. 
 
 Berle, 25, 58. 
 
 Bertheim, 84, 85, 88, 89, 93, 94, 
 130, 144, 154, 158, 160, 168, 
 176, 182, 187, 190, 195, 200, 
 205, 225, 229, 234, 242. 
 
 Berzelius, 6, 8, 59, 60, 61. 
 
 Biginelli, 46, 47. 
 
 Billy, 28, 34. 
 
 Blasi, 66, 79. 
 
 Blumenthal, 65. 
 
 Boehringer, C. F., and Sohne, 247, 
 249, 250, 333. 
 
 Bohrisch, 345. 
 
 Bon, 338. 
 
 Bongrand, 226. 
 
 Bossi, 339. 
 
 Breinl, 65. 
 
 Buckton, 27, 53, 54, 56, 57. 
 
 Bulecki, 277. 
 
 Bunsen, R. W., 5, 6, 7, 13, 14, 15, 
 
 18, 30, 40, 62. 
 
 Burroughs Wellcome & Co., 159. 
 Biischler, 125. 
 
 Cadet de Gassicourt, i, 2, 3, 4, 5, 64, 
 
 154- 
 
 Cahen, 345, 350. 
 Cahours, 10, 17, 21, 22, 23, 26, 27, 
 
 31, 32, 41, 42, 43, 44, 48, 50, 
 
 277. 
 Chemische Fabrik von Heyden, 84, 
 
 211, 293, 296, 297, 299, 301, 
 
 313-319, 323, 324- 
 Crafts, J. M., 337. 
 Cramer, 58. 
 
 Dalimier, 286. 
 
 Danysz, 279, 285, 286. 
 
 Davy, 59. 
 
 Dehn, 9, 19, 27, 34, 35, 37, 38, 39, 
 40, 41, 45, 47, 48, 49, 50, 51, 
 62, 63, 76, 83, 89, 90, 100, 118, 
 
 349- 
 
 Dering, 228, 343. 
 Dumas, J. B., 6, 7, 14, 15. 
 Durande, J. F., 3, 4. 
 
 Eisenlohr, 105. 
 
 Emmerling, 46. 
 
 Erdmann, 24. 
 
 Ehrlich, 87, 94, 154, 158, 160, 182, 
 
 224, 225, 229, 257, 273, 274, 
 
 276, 279, 281, 285. 
 Ewins, 226, 347. 
 
 Feitz, 92. 
 
 Finzi, C.,-335, 336, 337. 
 Fischer, E., 339, 340. 
 Forster, 327. 
 Fourneau, 261. 
 
 MORGAN'S ORGANIC COMPOUNDS. 
 
 361 
 
INDEX OF AUTHORS' NAMES 
 
 Fournier, 286. 
 Frankel, 333. 
 Frankland, 10, 20, 62. 
 Friedlander, 58. 
 Fromm, 81. 
 Fry, 296, 325. 
 Furlotti, 337. 
 
 Gal, 42, 277. 
 
 Gautier, 34. 
 
 Genzken, 310, 311. 
 
 Ghira, 304. 
 
 Gibbs, 19. 
 
 Giemsa, 250. 
 
 Gimborn, 103. 
 
 Gnezda, 342. 
 
 Gortner, 338. 
 
 Green, 15. 
 
 Grete, in. 
 
 Gronover, 23. 
 
 Griittner, 298, 299, 302, 331, 333. 
 
 Guenot, 286. 
 
 Giinther, 298, 322. 
 
 Halle, S., 224. 
 
 Haller, 327. 
 
 Hantzsch, 16. 
 
 Hasenbaumer, 298, 299, 301, 
 
 35, 314. 322. 
 Heinemann, 340. 
 Hellot, xii. 
 Henius, 65. 
 Hibbert, 27. 
 Hisinger, 59. 
 Hofmann, 27, 41, 52, 54. 
 Hiigel, 326. 
 Hugounenq, 261. 
 
 302, 
 
 Jorgensen, 43, 57. 
 Jowett, 184. 
 
 Kahn, 158, 171, 174, 198. 
 
 Kalle, 343. 
 
 Kantorowicz, 97, 101, no, 117. 
 
 Karrer, 85, 86, 146, 179, 181, 
 203, 231, 237, 240, 241, 
 250, 269, 273, 274, 279, 
 
 330- 
 
 Kaufmann, 305, 307. 
 Kay, 197. 
 Kelbe, 126. 
 Kionka, 65. 
 Klatt, 107. 
 Klemperer, 339. 
 Klinger, 29, 35, 62. 
 Kloffer, 343. 
 Koch, 347. 
 
 182, 
 243, 
 281, 
 
 Kolbe, 20. 
 Krause, 333. 
 Kreutz, 29, 35, 62 
 Kiirschner, 15. 
 Kuschner, 345. 
 
 La Coste, 27, 44, 66, 89, 90, 96, 
 100, 105, 108, no, 128, 132, 
 
 154. 344- 
 Landolt, 10, 17, 18, 21, 22, 41, 43, 
 
 53. 54> 35- 
 Lang, 338. 
 Lange, 326. 
 Lauterwald, 112. 
 Lavoisier, 59, 61. 
 Lehmann, 347. 
 Leprince, 35. 
 Lettermann, 302. 
 Levy-Franchel, 286. 
 Liebig, 61. 
 Link, 89, 91, 96, 98. 
 Little, 345. 
 Loesner, 84, 89, 100, 143, 145, 146, 
 
 I57 I 7- 
 Loloff, 308. 
 Longuinine, 310. 
 Lowig, 21, 25, 57, 61, 62. 
 Lowy, 333. 
 
 Mackey, 338. 
 
 Mameli, 85, 88, 190. 
 
 Mannheim, 23, 33, 43, 48, 49, 116. 
 
 Maret, H., 3, 4. 
 
 Marshall, 15. 
 
 Martindale, 16, 22, 36, 155, 163, 
 
 295, 344- 
 
 Maspmann, 46. 
 
 May, P., 296, 301, 314, 317. 
 
 McGarth, 29, 34, 48, 51, 118. 
 
 Meister, Lucius und Briining, 88,147, 
 I 55> I 59> I 6o, 161, 165, 169, 
 171, 176, 187-190, 195, 196, 
 I 97 199-207, 213-220, 224, 
 227-230, 233, 237, 244, 245, 
 250, 252-254, 257, 259, 262- 
 275, 281-284, 286, 287. 
 
 Merck, 56. 
 
 Meyer, 35, 62, 63, 192, 207. 
 
 Michaelis, 50, 65, 66 et seq., 87, 
 89-96, 97 et seq., 152, 154, 160, 
 164, 165, 169, 170, 220, 222, 
 223, 276, 293, 298, 302, 304, 
 306, 307, 310, 311, 322, 335, 
 344, 350. 
 
 Micklethwait, 187, 295, 298, 301, 
 et seq., 308, 312, 327, 330. 
 
 Monthule, 344. 
 
 Moore, 34, 327, 
 
 Morel, 261. 
 
 362 
 
INDEX OF AUTHORS' NAMES 
 
 Morgan, 163, 187, 298, 301, et seq. 
 
 308, 312, 327, 330, 345, 350. 
 Morveau, Guyton de, 3, 4. 
 Mouneyrat, 155, 161, 163, 197, 255, 
 289. 
 
 Nierenstein, 34. 
 Noelting, 179. 
 Norton, 347. 
 
 Oechslin, K., 166, 167, 191, 192, 
 
 194, 201, 207, 258, 261. 
 Ostwald, 13. 
 
 Paetow, 50, 114. 
 
 Palmer, 36, 37, 39, 47, 62, 76, 83, 
 
 89, 349- 
 
 Parke Davis & Co., 218. 
 Partheil, 23, 49. 
 Patta, 85, 88. 
 Peachey, 92. 
 Pfeiffer, 101, 305, 312. 
 Philips, 100, 101, 102, 149. 
 Pictet, 338. 
 
 Plimmer, 295, 296, 325. 
 Pope, 93. 
 Poulenc, 131, 166, 167, 191, 193, 
 
 194, 201, 230, 258, 260. 
 Predari, 91, 108, 109. 
 Pringsheim, 344. 
 Pyman, 156, 158, 171, 172, 180, 182, 
 
 185- 
 
 Rabinerson, 220. 
 
 Ranken, 296, 325. 
 
 Ravaut, P., 290, 291. 
 
 Reese, 293, 302, 304, 306, 307, 350. 
 
 Reiset, 13. 
 
 Remfry, 158, 180, 182. 
 
 Renault, 286. 
 
 Reynolds, 156, 172, 185. 
 
 Riche, 17, 21, 22, 32, 43, 44, 50. 
 
 Roeder, 66, 79. 
 
 Rosenheim, 277. 
 
 Rostock (Dissertations), 103, 105, 
 107, 112, 114, 119, 125, 302, 
 313, 322. 
 
 Riidorff, 46. 
 
 Sachs, 97, 101, no, 117. 
 
 Schafer, 276. 
 
 Schering, 155, 160. 
 
 Schild, 65. 
 
 Schmitz, 159, 349. 
 
 Schulte, 82, 87, 97, 125. 
 
 Schwarz, 143. 
 
 Schweitzer, 21, 25, 54, 61, 62. 
 
 Seemann, 119. 
 
 Sieburg, 130, 131, 138, 261. 
 
 Steinkopf, 335. 
 
 Strzyzowski, 46. 
 
 Thenard, L. J., 4, 5, 154. 
 Thomas, 65. 
 Todd, 34. 
 
 Uhlenhuth, 326. 
 
 Valentiner, 143. 
 Valerio, 46. 
 Van Haaren, 23. 
 Vitali, 34, 35- 
 
 Washburn, E. W:, 347. 
 
 Warunis, 345. 
 
 Weitz, 99, 105. 
 
 Wellcome, H. S., 171, 172, 184. 
 
 Werner, 42. 
 
 Whitby, 306, 330. 
 
 Wiernik, 298, 299, 302, 331, 333. 
 
 Wilcox, 41, 49, 50, loo. 
 
 Winmill, 91, 92. 
 
 Witt, 86. 
 
 Wohler, 19, 61. 
 
 Wolfifenstein, 339, 342. 
 
 Wroblewski, in, 311. 
 
 Zappi, 331. 
 
 363 
 
INDEX OF SUBJECTS 
 
 2-Acetylamino-i : 5 - benzarsenious 
 oxide, 218. 
 
 2 - Acetylamino -1:5- benzarsinic 
 
 acid, 175. 
 
 3 - Acetylamino -1:5- benzarsinic 
 
 acid, 175. 
 3-Acetylamino-i-methyl-4 : 6-benz- 
 
 arsinic acid, 175. 
 Acetyl-^-aminophenylarsenic ses- 
 
 quisulphide, 177. 
 4- Acetylaminopheny larsenoanti- 
 
 monious bromide, 275. 
 ^-Acetylaminophenylarsenobismuth 
 
 bromide, 275. 
 
 4-Acetylaminophenylarsine, 275. 
 Acetyl - p - aminophenylstibinic 
 
 acid, 300. 
 4 - Acetylaminophenylstibinoarseno - 
 
 4-phenylglycine, 274. 
 Acetyl - 5 - aininotolyl - 2 - arsinic 
 
 acid, 172. 
 2 - Acetylaminoterephthal - 6 - 
 
 arsinic acid, 176. 
 Acetyl - p - arsanilic acid and 
 
 sodium salt, 160. 
 Acetyl arsenite, 338. 
 Acetylatoxyl, 160. 
 Aliphatic antimony compounds, 53 
 
 et seq. 
 Aliphatic arsenic compounds, 32 
 
 et seq. 
 
 Alkargen, 9. 
 Alkarsin, 5. 
 p - Alkylaminophenylarsinic acids, 
 
 167. 
 Alkylation of arsenical oxy-com- 
 
 pounds, 28. 
 Alkyl halides, interaction of, with 
 
 arsenic or antimony and their 
 
 alloys, 21, 22. 
 
 Alkyl organo-metalloidal com- 
 pounds, syntheses of, 20. 
 Alloys of arsenic and antimony, 
 
 interaction of, with alkyl hal- 
 ides, 21. 
 
 Allylthiocarbamino-^-arsanilicacid, 
 161. 
 
 3-Amino-o-cresol-5-arsinic acid, 206. 
 
 5 - Amino -2:4- dihydroxyphenyl- 
 arsinic acid and acetyl deriv- 
 ative, 245. 
 
 m-Aminodiphenylstibinic acid, 319. 
 
 3 - Amino - 4 - hydroxyarseno - 4' - 
 acetylaminostibinobenzene hy- 
 drochloride, 274. 
 
 3 - Amino - 4 - hydroxyarsenobenz- 
 ene, 266. 
 
 3 - Amino - 4 - hydroxyarsenobenz- 
 
 ene hydrochloride, 265. 
 
 4 - Amino - 4' - hydroxyarsenobenz- 
 
 ene, 265. 
 
 3 - Amino - 4 - hydroxybenzene- 
 arsenomethane, 268. 
 
 3 - Amino - 4 - hydroxyarseno- 
 phenyl - 4" - glycine, 265, 267. 
 
 3 - Amino - 4 - hydroxyarsenosti- 
 binobenzene, 273. 
 
 3 - Amino - 4 - hydroxyphenylarsine 
 and urethane derivative, 264. 
 
 3 - Amino - 4 - hydroxyphenyl - 
 arsine, urethane derivative, co- 
 ordination compound of, 264. 
 
 3 - Amino - 4 - hydroxyphenylar- 
 
 senious oxide, 228. 
 
 4 - Amino - 3 - hydroxyphenyl- 
 
 arsenious oxide, 233. 
 
 3 - Amino - 4 - hydroxyphenyl - 
 
 arsinic acid and urethane de- 
 rivative, 205, 245. 
 
 4 - Amino - 3 - hydroxyphenyl - 
 
 arsinic acid, 206. 
 
 3 - Amino - 4 - hydroxyphenyl - 
 arsenoantimonious acetate hy- 
 drochloride, 275. 
 
 3 - Amino - 4 - hydroxyphenyl - i - 
 stibinic acid, 318, 319. 
 
 3 - Amino - 2 - hydroxytolyl - 5 - 
 arsinic acid, 206. 
 
 5 - Amino - 2 - methoxy - 4 - hy - 
 
 droxyphenylarsinic acid, 247. 
 
 364 
 
INDEX OF SUBJECTS 
 
 4 - Amino - 3 - methoxyphenyl - 
 
 arsinic acid, 173, 174. 
 3-Aminophenol-6-arsinic acid, 206. 
 
 2 - Aminophenol - 4 - arsinic acid 
 
 and methane derivative, 205. 
 p - Aminophenylarsenious oxide, 
 
 217. 
 p - Aminophenylarsenious oxide, 
 
 acyl derivatives of, 218. 
 m - Aminophenylarsenious sulphide, 
 
 170. 
 p - Aminophenylarsenious sulphide, 
 
 177. 
 p - Aminophenylarseno-selenide and 
 
 -telluride hydrochloride, 271. 
 4 - Aminophenylarsine, 263. 
 o - Aminophenylarsinic acid, 170. 
 w-Aminophenylarsinic acid, 167, 
 
 168, 169. 
 w-Aminophenylarsinic acid, ure- 
 
 thane derivative of, 189. 
 4 - Aminophenyl - i - arsinic acid 
 
 and salts, 158, 159. 
 p - Aminophenylmethylarsinic acid 
 
 and acetyl derivative, 186. 
 w-Aminophenylstibine oxide, 322, 
 
 323- 
 
 3 - Aminophenyl - i - stibinic acid, 
 
 316. 
 
 m-Aminophenylstibinic acid, 323. 
 ^-Aminophenylstibinic acid, acetyl 
 
 derivative and sodium salt, 300, 
 
 3!5> 3i6. 
 m-Aminophenylstibinous chloride, 
 
 hydrochloride, 316, 323. 
 
 1 - Aminonaphthyl - 4 - arsinic acid, 
 
 174. 
 
 2 - Aminoresorcinol - 5 - methyl 
 
 ether, 204. 
 
 4 - Aminothienyl - 2 - arsinic acid 
 
 and acetyl derivative, 337. 
 2 - Aminotolyl - 5 - arsenious oxide, 
 218. 
 
 2 - Aminotolyl - 5 - arsinic acid and 
 
 sodium salt, 171, 172. 
 
 3 - Aminotolyl - 4 - arsinic acid, 150. 
 4-Aminotolyl-3-arsinic acid, 178. 
 
 5 -Aminotolyl- 2 -arsinic acid, 172. 
 2 - Amino - p - xylyl - 5 - arsinic acid 
 and acetyl derivative, 173. 
 
 4 - Amino -1:3- xylyl - 5 - arsinic 
 
 acid, 178. 
 
 iso-Amylarsine disulphide, 51. 
 o-Anisidine-4-arsinic acid, 173, 174. 
 ^>-Anisylarsenic chloride, 93. 
 ^-Anisylarsinic acid, 93. 
 p-Anisylarsinic anhydride, 93. 
 />-Anisyltrimethylarsonium iodide, 
 
 94- 
 
 Antimony analogues of atoxyl and 
 salvarsan, 295, 296, 297. 
 
 Application of organic compounds 
 
 of antimony, 325, 326. 
 Aromatic - aliphatic arsines, syn- 
 thesis of, 76, 77. 
 
 Aromatic aliphatic arsinic acids, 94. 
 
 Aromatic arseno-bismuth halides, 
 275, 276. 
 
 Aromatic polyarsenides, co-ordina- 
 tion compounds of, with 
 cupric chloride, 287. 
 cuprous chloride, 286. 
 mercuric chloride, 287. 
 silver nitrate, 287. 
 
 Aromatic stibines and their deriv- 
 atives, 293 et seq. 
 
 Aromatic stibinoxides, 322. 
 
 Arrhenal, 34. 
 
 Arsacetin, 155, 160. 
 
 o-Arsanilic acid, 157, 170. 
 
 m-Arsanilic acid, 167, 168, 169. 
 
 /?-Arsanilic acid and salts, 158, 159. 
 
 ^-Arsanilic acid, organo-mercurial 
 compounds of, 183 et seq, 
 
 ^-Arsanilic acid, thio-derivatives of, 
 176 et seq. 
 
 ^-Arsanilic acid, urethane derivative 
 of, 190. 
 
 Arsenic acid, action on aniliner, 154. 
 
 Arsenicalderivatives of naphthalene, 
 125. 
 
 Arsenical esters, 337, 338. 
 
 Arsenical esters containing complex 
 open chain radicals, 342. 
 
 Arsenoarylglycines, 2 5 7-261 . 
 
 Arsenobenzene and its analogues, 
 24, 68, 87, 224, 276. 
 
 Arsenobenzene and its derivatives, 
 co-ordination compounds of, 
 281, 282. 
 
 Arsenobenzene, co-ordination com- 
 pound of, with cupric chloride, 
 88. 
 
 Arsenobenzene, co-ordination com- 
 pounds, gold derivatives, 281. 
 
 Arsenobenzene, co-ordination com- 
 pound of, and silver nitrate, 
 281. 
 
 Arsenobenzene derivatives, syn- 
 thesis of dissymmetric, 262. 
 
 Arsenobenzene - bis - 4 - oxymethyl- 
 enecarboxylic acid, 215, 216. 
 
 Arsenobenzenes, synthesis of dis- 
 symmetric 'by intermolecular 
 rearrangement, 269. 
 
 Arsenobenzene - bis - 4 - thio- 
 methylenecarboxylic acid, 216. 
 
 o-Arsenobenzoic acid, 137. 
 
 />-Arsenobenzoic acid, 137. 
 
 Arsenobillon, 224. * 
 
 4-Arseno-o-cresol, 214. 
 
 Arsenohippuric acid, 260, 261. 
 
 365 
 
INDEX OF SUBJECTS 
 
 Arsenomethane, 40, 47. 
 
 Arseno-a-naphthalene, 125. 
 
 Arseno--naphthalene, 126. 
 
 Arsenonaphthalene derivatives, 239. 
 
 Arseno-^>-phenetole, 94. 
 
 Arsenophenols, 213 et seq. 
 
 />-Arsenophenol, 213. 
 
 Arsenophenyl-^>-glycine and sodium 
 salt, 257. 
 
 Arsenophenylglycine, co-ordination 
 compound of, and gold chloride, 
 281. 
 
 Arsenophenyl-^>-glycine, formalde- 
 hyde derivatives of, 260. 
 
 Arsenophenylmethane, 1 1 8 . 
 
 Arsenophenyl-^>-methylglycine, 258. 
 
 Arsenothiophene, 336. 
 
 Arseno-m-toluene, 106. 
 
 Arseno-^>-toluene, 107. 
 
 ^-Arseno-o-tolylglycine, 258. 
 
 5-Arsenotolyl-2-glycine, 259. 
 
 Arseno-w-xylene, 119. 
 
 Arseno--xylene, 120. 
 
 Arsines (primary aromatic), 76. 
 
 Arseno-/>-anisole, 93. 
 
 Arsinotribenzoic acid and salts, 133. 
 
 Arylarsenic chlorides, 73. 
 
 Arylarsenious acids and esters, 73. 
 
 Arylarsenious chlorides, 72. 
 
 Arylarsenious oxides, 73. 
 
 Arylarsenious sulphides, 75. 
 
 Arylarseno-derivatives, 75. 
 
 Aryl arseno-phospnides and anti- 
 monides, co-ordination com- 
 pounds of, 272. 
 
 Arylarsine oxide carboxylates, 71. 
 
 Arylarsines and their immediate 
 derivatives, 64 et seq. 
 
 Arylarsinic acids, 74. 
 
 Arylarsinic anhydrides, 74. 
 
 Arylcacodyls, 77. 
 
 Arylmercurichlorides, use of, in 
 syntheses, 66. 
 
 Asymmetric arsenic atom, 91, 92. 
 
 Asyphil, 159. 
 
 Atoxyl, 153 etseq., 158, 159. 
 
 Atoxyl, acetylation of, 155. 
 
 Atoxyl, aldehyde condensation pro- 
 ducts of, 164. 
 
 Atoxyl, constitution of, 154. 
 
 Atoxyl, reactions of, 163. 
 
 Atoxyl, toxicity of, 288. 
 
 Azobenzene-4-arsinic acid, 181. 
 
 A.zobenzene -4:4'- diarsinic acid, 
 181. 
 
 Azo-compounds containing an ar- 
 senobenzene residue, 220. 
 
 Azo derivatives of ^-arsanilic acid, 
 179. . 
 
 Azo dyes from ^-arsanilic acid, 179, 
 1 80 et seq. 
 
 Bechamp reaction, 153 et seq. 
 Benzarsenious acid, 129. 
 jfr-Benzarsenious acid, anhydride and 
 
 salts, 131. 
 
 ^-Benzarsenious chloride, 131. 
 ^-Benzarsenious iodide, 130. 
 Benzarsinic acid, 106, 128. 
 Benzarsinic acids and their deriv- 
 atives, 128. 
 
 o-Benzarsinic acid and salts, 133. 
 m-Benzarsinic acid, anhydride and 
 
 salts, 133. 
 ^-Benzarsinic acid and salts, 129, 
 
 130. 
 Benzeneazo -2:4- tolylenediamino- 
 
 4'-arsinic acid, 181. 
 Benzene derivatives with three 
 
 aromatic nuclei attached to one 
 
 arsenic atom, 100 et seq. 
 Benzenediazonium-4-arsinate, 1 79. 
 Benzene - w-3 13'- disulphamino - 
 
 bis- 3- amino- 4:4'- dihydroxy- 
 
 arsenobenzene, 256. 
 Benzenesulphonyl - p - arsanilic 
 
 acid, 163. 
 
 Benzenesulphonylatoxyl, 155. 
 Benzoyl arsenite, 339. 
 Benzylarsenious chloride, 117. 
 Benzylarsine, 118. 
 Benzylarsinic acid and disulphide, 
 
 118. 
 Betaines of aromatic arsenicals, 
 
 138 et seq. 
 Bis - p - alkylaminophenylarsinic 
 
 acids, 167. 
 Bis - m - aminodiphenylstibinous 
 
 oxide, 320. 
 Bis - 3 - amino - 4 - hydroxyphenyl- 
 
 arsenoantimonide, 272. 
 2 -Bromo- 1 -aminophenylarsinic acid, 
 
 176. 
 Butyryl-^-arsanilic acid, 160. 
 
 Carboxymethyleneoxyphenyl - 4 - 
 arsinic acid, 216. 
 
 Carboxymethylenethiophenyl - 4 - 
 arsinic acid, 216. 
 
 Cacodyl, 6 et seq., 10. 
 
 Cacodyl, co-ordination compounds 
 of, 13, 16. 
 
 Cacodyl oxide, 6. 
 
 Cacodyl, salts of, 13, 14, 15. 
 
 Cacodyl superchloride, 117. 
 
 Cacodyl trichloride, 16. 
 
 Cacodylic acid, 9, 15. 
 
 Cacodylic acid, salts of, 16. 
 
 Camphor, sodium derivative, con- 
 densation product of, with 
 trichlorides of the phosphorus 
 group, 328. 
 
 366 
 
INDEX OF SUBJECTS 
 
 Carbamino-^-arsanilic acid, 161. 
 Carbethoxy - 3 - aminophenol - 6 - 
 
 arsinic acid, 206, 207. 
 2 - Carboxy - 4 - aminophenylarsinic 
 
 acid, 237. 
 2 - Carboxy - 4 - hydroxyphenyl- 
 
 arsinic acid, 238. 
 2 - Carboxy - 4 - nitrophenylarsinic 
 
 acid, 237. 
 
 Carboxyphenylarsenious acid, an- 
 hydride and salts, 131. 
 Carboxyphenylarsenious iodide, 
 
 130. 
 ^-Carboxyphenylarsinic acid and 
 
 salts, 129, 130. 
 
 Chloroacetyl-^>-arsanilic acid, 160. 
 2 - Chloro - i - aminophenyl - 4 - 
 
 arsinic acid, 176. 
 4-Chloro-o-arsanilic acid, 178. 
 Chloroarsines (primary), 72. 
 Chloroarsinosobehenolic acid, anilide 
 
 and salts, 340, 341. 
 Chloroarsinosobehenolic anhydride, 
 
 340. 
 
 Chlorobehenolarsinic acid, 341. 
 2 - Chloro - 4 - dimethylamino - 
 
 phenylarsenious oxide, 250. 
 2 - Chloro - 4 - dimethylamino - 
 
 phenyl - i - arsinic acid, 250. 
 4 - Chloro - 3 - nitrophenyl - i - 
 
 stibinic acid, 318. 
 C hloro - m - phenylenestibinic acid, 
 
 321. 
 ^-Chlorophenylstibinic acid, 317, 
 
 318. 
 5-Chlorotolyl-2-arsinic acid, 228, 
 
 241. 
 
 Chloro-m-xylylarsinic acid, 119. 
 Chromophors, 276. 
 " Cobolt," i, 2. 
 
 Compound radicals, theory of, 59. 
 Co-ordination compounds of aro- 
 matic arsenicals, 277 et seq. 
 Co-ordination compounds of aryl- 
 
 arsenical derivatives and 
 
 metals, 282. 
 Copper salvarsan, 228. 
 m-Cresol-4-arsinic acid, 198. 
 o-Cresol-4-arsinic acid, 197, 198. 
 ^-Cumylarsenious chloride, 120. 
 ^-Cumylarsinic acid, 120. 
 
 Dealkylation of tertiary arsines and 
 derivatives, 29, 30, 31. 
 
 2:2'- Diacetyldiamino - 5 - arseno - 
 benzoic acid, 259. 
 
 5:5'- Diacetyldiamino -2:4: 2' : 
 4' - tetrahydroxyarsenobenzene, 
 
 245- 
 
 Diacetyl -2:2'- diaminotolyl - 5 - 
 arsinic acid, 187. 
 
 Diacetylarseno - p - phenylglycine, 
 
 259- 
 
 4 : 4 / -Diaminoarsenobenzene, 219. 
 4:4'- Diamino -a-arsenonaphtha- 
 
 lene, 239. 
 5:5'- Diamino - i : i' - arseno - 2 : 
 
 2' - stilbene, 240, 241. 
 4:4'- Diaminodiarylarsinic acids, 
 
 183 et seq. 
 2:2'- Diamino - 3 : 3' - dihydroxy - 
 
 arsenobenzene, 202, 233. 
 2:2'- Diamino - 5 : 5' - dihydroxy- 
 
 arsenobenzene, 234. 
 3 : 3' - Diamino -4:4'- dihydroxy- 
 
 arsenobenzene, 224. 
 4:4'- Diamino -2:2'- dihydroxy- 
 
 arsenobenzene, 234. 
 4:4'- Diamino - 3 : 3' - dihydroxy - 
 
 arsenobenzene, 232. 
 5:5'- Diamino -2:2'- dihydroxy- 
 
 arsenobenzene, 233. 
 3:3'- Diamino -4:4'- dihydroxy - 
 
 arsenobenzene dihydrochloride, 
 
 226, 227. 
 3:3'- Diamino -4:4'- dihydroxy- 
 
 arsenobenzene-silver-bromide- 
 
 antimonyl sulphate, 285, 
 
 286. 
 
 5:5'- Diamino -4:4'- dihy- 
 droxy - i : i' - arseno -2:2'- 
 
 stilbene, 241, 242. 
 3:3'- Diamino - 2 : 2' - dihydroxy - 
 
 5:5"- arsenotoluene, 237. 
 4:4'- Diamino -5:5'- dihydroxy - 
 
 2:2'- arsenotoluene, 237. 
 
 5 :$' - Diamino -4:4'- dihydroxy - 
 
 2:2'- dicarboxyarsenobenzene, 
 
 238. 
 3:3'- Diamino -4:4'- dihydroxy- 
 
 diphenyldimethyldiarsine, 242. 
 3:3'- Diamino - 4 : 4' - dihydroxy - 
 
 o-arsenonaphthalene dihydro- 
 chloride, 239. 
 3:3'- Diamino - 4 : 4' - dihydroxy - 
 
 stibinobenzene, 324, 325. 
 5 15' - Diamino -2:2'- dimethoxy - 
 
 4 : 4'- dihydroxyarsenobenzene, 
 
 246. 
 5:5'- Diamino -2:2'- dimethoxy - 
 
 4:4'- dihydroxyarsenobenzene 
 
 hydrochloride, 204. 
 3:3'- Diaminodiphenylarsenious 
 
 sulphide and acetyl derivative, 
 
 222. 
 4:4'- Diaminodiphenylarsinic acid 
 
 and salts, 185, 186. 
 Di - m - aminodiphenylhydroxy - 
 
 stibine and hydrochloride, 303, 
 
 304- 
 2:2'- Diaminoditolyl - 5 - arsinic 
 
 acid, 186. 
 
 367 
 
INDEX OF SUBJECTS 
 
 3:4"- Diamino - 4 - hydroxyarseno- 
 
 benzene, 267. 
 3:5- Diamino - 4 - hydroxyphenyl- 
 
 arsinic acid, 207. 
 2:3- Diaminophenazine - 7 - ar - 
 
 sinic acid, 182. 
 2:3- Diaminophenylarsinic acid, 
 
 195- 
 3:4- Diaminophenylarsinic acid, 
 
 195, 196. 
 
 3:3'- Diaminostibinobenzene, 324. 
 5:5'- Diamino - 2 : 2'-stilbene-i : i'- 
 
 diarsinic acid, 240. 
 5:5'- Diamino - 2 : 4 : 2' : 4' - tetra- 
 
 hydroxyarsenobenzene, 204, 
 
 245- 
 
 Di--anisylarsenious chloride, 99. 
 
 Di-^J-anisylarsenious oxide, 99. 
 
 Diarylarsenic trichlorides, 78. 
 
 Diarylarsenious chlorides (second- 
 ary), 77. 
 
 Dibenzarsenious acid, 129. 
 
 Di-/>-benzarsenious acid, 132. 
 
 Di-/>-benzarsenious iodide, 132. 
 
 Dibenzarsinic acid, 128. 
 
 Di--benzarsinic acid, 132. 
 
 Dibenzylarsinic acid and salts, 114, 
 116, 117. 
 
 Dibenzylarsinic acid, hydrochloride 
 and other salts, 117. 
 
 Dibenzylthioarsinic acid, 117. 
 
 Dibromo--arsanilic acid, 176. 
 
 Dicamphorylarsinic acid and salts, 
 327, 328, 329. 
 
 Dicamphorylarsinic oxychlorides, 
 
 329- 
 
 Dicamphorylphosphinic acid, 327. 
 2:2'- Dicarboxy - 4 : 4' - dihydr- 
 
 oxyarsenobenzene, 237. 
 Di--carboxydiphenylarsinic acid, 
 
 132. 
 3' : 5' - Dichloro - 3 - amino -4:4'- 
 
 dihydroxyarsenobenzene, 268. 
 Dichloro--arsanilic acid, 176. 
 Dichloro--arsinobenzoyl chloride, 
 
 131- 
 
 5:5'- Dichloro -4:4'- diamino- 
 3:3'- dihydroxyarsenobenz- 
 ene, 238. 
 
 4:4'- Dichloro -5:5'- dinitro - 
 2:2'- stibene - i : i' - diarsinic 
 acid, 242. 
 
 3:5- Dichloro - 4 - iodophenylar- 
 sinic acid, 86. 
 
 3 : 5-Dichlorophenylarsinic acid, 86. 
 
 Diethylaminophenylarsenious ox- 
 ide and salts, 221, 222. 
 
 Diethylarsine, 45. 
 
 Diethylarsinic acid, 18. 
 
 Diethylarsinoxybenzoic acid hydro- 
 chloride, 133. 
 
 Diethylarsinobenzoic acid and salts 
 
 134- 
 Diethylarsinosulphidobenzoic acid, 
 
 I 34- 
 4:4'- Dihydroxyarsenobenzene - 
 
 3:3'- phosphamic acid, 255, 
 
 256. 
 
 4 : 4'-Dihydroxyarsenobenzene, co- 
 ordination compounds of, with 
 
 gold chloride, 282. 
 4:4'- Dihydroxydiphenylarsinic 
 
 acid, 200. 
 2:2'- Dihydroxyditolyl - 5 - arsinic 
 
 acid, 200. 
 2:4- Dihydroxyphenylarsinic acid, 
 
 245- 
 2:4- Dihydroxyphenylarsinic acid 
 
 and methoxy-derivatives, 199. 
 3:4- Dihydroxyphenylarsinic acid, 
 
 199, 200. 
 4 : 4 / -Dihydroxystibinoarsenobenz- 
 
 ene, 274. 
 
 Di-iodo--arsanilic acid, 176. 
 Di-iodoarsenobenzene, 88. 
 Di-iodomethylarsinic acid and salts, 
 
 36. 
 
 Dwsoamylarsine, 51. 
 Diisoamylarsine chloride (basic), 50. 
 Dh'soamylarsine chlorodibromide, 
 
 51. 
 
 Dwsoamylarsine sulphide, 51. 
 
 Dwsoamylarsinic acid, 51. 
 
 2:2'- Dimethoxy -4:4'- dihydr- 
 
 oxyarsenobenzene, 204. 
 2:4- Dimethoxyphenylarsinic acid, 
 
 247. 
 4 - Dimethylaminobenzene - 2' - 
 
 azotoluene-5'-arsinic acid, 181. 
 sym- 3:3'- Dimethylamino -4:4'- 
 
 dihydroxyarsenobenzene, 235. 
 4 - Dimethylaminodinitrophenylar- 
 
 sinic acids, 193. 
 
 3 - Dimethylamino - 4 - hydroxy- 
 
 phenylarsinic acid, 235. 
 
 4 - Dimethylamino - 2 - hydroxy- 
 
 phenylarsinic acid, 207. 
 4 - Dimethylamino - 3 - nitrophenyl- 
 
 arsinic acid, 192. 
 2 - Dimethylaminophenazine - 7 - 
 
 arsinic acid, 182. 
 p - Dimethylaminophenylarsenious 
 
 oxide and salts, 220, 221 
 p - Dimethylaminophenylarsinic 
 
 acid, 164. 
 
 Dimethylallylarsine, 49. 
 Dimethylanilinearsenious oxide and 
 
 salts, 220, 221. 
 Dimethylarsine, 36, 37. 
 Dimethylarsinetrichlorostannide, 3 8 . 
 Dimethylarsinic acid. See Caco- 
 
 dylic acid. 
 
 368 
 
INDEX OF SUBJECTS 
 
 Dimethylarsonium iodide, 43. 
 Dimethylarsonium sulphate, 38. 
 Dimethyldiethylarsonium salts, 44. 
 Dimethyldusoamylarsonium iodide, 
 
 50. 
 
 Dimethyldiisoamylcacodyl, 19. 
 Dimethylethylarsine, 43. 
 4:4'- Dimethyl - 3 : 4 : 5 : 3' : 4' : 5' - 
 
 hexaminoarsenobenzene, 248. 
 3:5- Dinitro -p - arsanilic acid, 191. 
 m-Dinitroarsenobenzene, 145. 
 3:3 / -Dinitroarseno--toluene, 150. 
 Dinitrodiarylarsinic acids, 78. 
 3:3'- Dinitro - 4 : 4' - dihydroxy- 
 
 arsenobenzene, 230. 
 3:5- Dinitro -2:4- dihydroxy- 
 
 phenylarsinic acid, 204, 245. 
 Di--nitrodiphenylarsenious acid, 
 
 148. 
 Dinitrodiphenylarsenious bromide, 
 
 chloride, sulphide, 148. 
 Dinitrodiphenylarsinic acid and 
 
 salts, 148. 
 Di - m - nitrodiphenylstibinic acid, 
 
 303- 
 4:4'- Dinitro - dithienyl - 2 - 
 
 arsinic acid, 337. 
 3:5- Dinitro - 2 - hydroxyphenyl - 
 
 arsinic acid, 203. 
 3:5- Dinitro - 4 - hydroxyphenyl - 
 
 arsinic acid, 203. 
 2:4- Dinitrophenylarsenious oxide, 
 
 243- 
 
 Di-^>-nitrodiphenylarsinic acid, 145. 
 
 2 : 4-Dinitrophenylarsinic acid, 147. 
 
 2 : 4-Dinitrophenylarsinic acid, re- 
 duction products of, 243, 244. 
 
 2 : 6-Dinitrophenol-4-arsinic acid, 
 203. 
 
 .3 : 4-Dinitrosophenylarsinic acid, 
 182. 
 
 5:5'- Dinitro - 2 12'- stilbene - 
 i : i '-arsinic acid, 240. 
 
 4:4"- Dioxalylaminoarsenobenzene, 
 219. 
 
 Diphenylarsine, 100. 
 
 Diphenylarsenic chloride, 96. 
 
 Diphenylarsenic oxychloride, 97. 
 
 Diphenylarsenious bromide, 96. 
 
 Diphenylarsenious chloride, 95. 
 
 Diphenylarsenious oxide, 97. 
 
 Diphenylarsenious sulphide, 99. 
 
 Diphenylarsinic acid and salts, 97. 
 
 Diphenylbenzarsinic acid and salts, 
 
 134- 
 
 Diphenyldiethylarsonium iodide, 98. 
 Diphenyldimethylarsonium iodide 
 
 and platinichloride, 98. 
 Diphenylethylarsine and dichloride, 
 
 98. 
 Diphenylethylstibine and salts, 302 . 
 
 Diphenylmethylarsine, 98. 
 Diphenylmethylethylarsoniumhydr- 
 
 oxide and salts, 98, 99. 
 Diphenylmethylstibine and salts 
 
 302. 
 
 Diphenylstibine chloride, 301, 302. 
 Diphenylstibine trichloride, 302. 
 Diphenylstibinic acid, 303. 
 Diphenylsulphidobenzarsinic acid, 
 
 135- 
 
 Diphenyl-jb-tolylarsine and double 
 salts, 112. 
 
 Diphenyl - p - tolylarsine dihydrox- 
 ide and salts, 112. 
 
 Diphenyl - p - tolylarsine-oxide - p - 
 carboxylic acid, 136. 
 
 Diphenyl - p - tolylethylarsonium 
 iodide and platinichloride, 113. 
 
 Diphenyl - p - tolylmethylarsonium 
 iodide and other salts, 113. 
 
 4:4'- Dipiperidino - 3 : 5 : 3' - 5' - 
 tetraminoarsenobenzene, 250. 
 
 Di-w-propylarsinic acid, 49. 
 
 Dipseudocumylphenylarsine and 
 salts, 123. 
 
 Dipseudo c umylphenylmethylarso- 
 nium hydroxide, 123. 
 
 Disazobenzene 4:4'- diarsinic acid, 
 181. 
 
 Disazobenzene - 4 : 2" : 4 '" - triar- 
 sinic acid, 181. 
 
 Displacement of arsenic from aro- 
 matic arsenicals, 218, 219. 
 
 Dissymmetric arsenobenzenes, syn- 
 thesis of, from two dissimilar 
 arylarsinic acid or arylarseni- 
 ous oxides, 266. 
 
 Dithienylarsenious chloride, 334. 
 
 2 : 2 / -Dithienylarsinic acid, 336. 
 
 Di-^-tolylarsenic chloride, 108. 
 
 Di-^?-tolylarsenious chloride, 108. 
 
 Di-^-tolylarsenious oxide, 108. 
 
 Di-_p-tolylarsinic acid, 108. 
 
 Di-0-tolyl--tolylstibine and salts, 
 
 311- 
 Di-m-xylylphenylarsine and salts, 
 
 122. 
 
 Drugs containing tervalent arsenic, 
 application of, 287 et seq. 
 
 " Ehrlich 606," 224. 
 
 " Ehrlich 914," 251. 
 
 Elarson, 339, 340, 341. 
 
 Enesol, 199. 
 
 Erythrarsine, 40. 
 
 Estimation of antimony in organic 
 compounds, 350. 
 
 Estimation of arsenic in organic 
 compounds, 344 et seq. 
 
 Estimation of arsenic in very vola- 
 tile compounds, 349. 
 
 MORGAN'S COMPOUNDS 
 
 369 
 
 B B 
 
INDEX OF SUBJECTS 
 
 Estimation of arsenic by iodimetric 
 
 method of Ewins, 347, 348. 
 Estimation of arsenic by iodimetric 
 
 method of Little, Cahen, and 
 
 Morgan, 345, 346. 
 Ethyl arsenate, 337, 338. 
 Ethylarsenious chloride, 44. 
 Ethylarsenious di-iodide, 44. 
 Ethylarsine, 47. 
 
 Ethylarsinic acid and salts, 44, 45. 
 Ethylarsinic disulphide, 45. 
 Ethyl arsenite, 338. 
 Ethylcacodyl, 17. 
 Ethylcacodylic acid, 18. 
 Ethyldiphenylbenzarsinate dichlor- 
 
 ide, 135. 
 Ethylenehexaethyldiarsonium di- 
 
 bromide, 52. 
 Ethylenehexaethylphospharsonium 
 
 dibromide, 52. 
 
 Ethylenetriethylarsammonium di- 
 bromide, 52. 
 Ethyl phenyldi-^-benzarsinate di- 
 
 chloride, 135. 
 C - Ethylphenylmethylglycine - 4 - 
 
 arsinic acid and propyl ester, 
 
 166. 
 Ethyl phenyl--tolyl--benzarsinate 
 
 dichloride, 136. 
 Ethyltmsoamylarsonium iodide, 50. 
 
 Hippurarsinic acid, 261. 
 
 Hydroaromatic derivatives of ar- 
 senic and antimony, 327. 
 
 2 - Hydroxy -1:5- benzarsinic acid 
 and salts, 198, 199. 
 
 4 - Hydroxybenzene - 2 - azotoluene- 
 5 -arsinic acid, 180. 
 
 p - Hydroxybenzylidine - p - arsan- 
 ilic acid, 164. 
 
 ^-Hydroxyphenylarsenious oxide, 
 212, 213. 
 
 4 - Hydroxyphenylarsenostibino- 
 benzene, 274. 
 
 4-Hydroxyphenylarsine, 263. 
 
 ^-Hydroxyphenylstibinic acid, 314. 
 
 Hydryl, 184. 
 
 Indole series, arsinic acids of, 333, 
 
 334- 
 Injections of arsenic drugs, statistics 
 
 of, 289 et seq. 
 Iodoacetyl-^>-arsanilic acid, 155, 
 
 160. 
 2 - lodo - i - aminophenylarsinic 
 
 acid, 176. 
 
 Iodoarseno--xylene, 120. 
 Iodopropionyl-^?-arsanilic acid, 160. 
 ^-lodosophenylarsinic acid, 85. 
 ^-lodoxyphenylarsinic acid, 86. 
 
 Fission of arsenobenzene and its 
 derivatives by alkyl iodides, 
 88. 
 
 Formyl-^-arsanilic acid, 160. 
 
 Galyl, 251, 255, 256. 
 
 Grignard reaction, 27. 
 
 Grignard reaction for preparation 
 
 of aryl antimony compounds, 
 
 294. 
 
 Halogenated arsenophenols, 214. 
 
 Hectine, 155, 163. 
 
 Heterocyclic rings containing ar- 
 senic and antimony, 330. 
 
 Hexaminoarsenobenzene and its 
 derivatives, 247 et seq. 
 
 3 : 4 : 5 : 3' : 4' : 5' ~ Hexaminoar- 
 senobenzene, 248. 
 
 3 : 3' - Hexamethyldiammonium - 
 4:4' - dihydroxyarsenobenz- 
 ene, 236. 
 
 Hexamethylenetetramine c o m - 
 pound of arsenic acid, 339. 
 
 Hexamethyl -4:4': 4"' - triamino - 
 triphenylarsine, 224. 
 
 Hexamethyltriaminotritolylmethyl- 
 arsonium iodide, 223. 
 
 Kharsin, 172, 183. 
 Kharsivan, 124. 
 
 Luargol, 277 et seq., 285, 286. 
 Ludyl, 251, 256, 257. 
 
 Malonyl-^-arsanilic acid, 161. 
 Mercury diaryls, use of, in synthesis 
 
 of arylarsines, 66, 67. 
 Metallic alkyls, interaction of, with 
 
 arsenic and antimony halides, 
 
 26. 
 2 - Methoxy - 4 - hydroxyphenyl- 
 
 arsinic acid, 246. 
 3-Methylamino - 4 - hydroxyphenyl- 
 
 arsinic acid, 234, 235. 
 Methylanthranilylarsine, 273. 
 Methyl arsenate, 337, 338. 
 Methylarsenic, 40. 
 Methylarsenious oxide and salts, 33. 
 i -Methy larsepidine, 331. 
 Methylarsine, 37, 39. 
 Methylarsinic acid and salts, 34, 35. 
 Methylated salvarsans, toxicity of, 
 
 236. 
 Methylcarbamino-^-arsanilic acid, 
 
 162. 
 
 370 
 
INDEX OF SUBJECTS 
 
 Methyl chloroarsinosobehenolate, 
 
 34- 
 Methyl chlorobehenolarsinic acid 
 
 ester, 341. 
 Methylcyclopentamethylenears i n e, 
 
 331- 
 
 Methyldiethylarsine, 43. 
 Methylindolearsinic acid, 333, 334. 
 Methylketolearsinic acid, 333, 334. 
 
 4 - Methylnitrosoaminophenylarsinic 
 
 acid, 192. 
 
 Methyl salvarsan, 228. 
 Methyltriethylstibonium iodide, 58. 
 
 o-Naphthindolearsinic acid, 334. 
 a-Naphthylarsenious chloride and 
 
 oxide, 125. 
 
 -Naphthylarsenious chloride, 126. 
 o-Naphthylarsinic acid, 126. 
 j8-Naphthylarsinic acid, 126. 
 Neokharsivan, 251. 
 Neosalvarsan, 251 et seq., 253. 
 Neosalvarsan, co-ordination com- 
 pounds of, with 
 cupric chloride, 284. 
 gold chloride, 285. 
 platinic chloride, 285. 
 silver nitrate, 284. 
 Neutral salts of arylstibinic acids, 
 
 299, 300. 
 New cacodyl, 34. 
 3 - Nitro - 4 - acetylaminophenyl - 1- 
 
 stibinic acid, 316, 317. 
 2 - Nitro - i - aminophenyl - 4 - 
 
 arsinic acid, 191. 
 
 2 - Nitro - 3 - aminophenylarsinic 
 acid, 189. 
 
 2 - Nitro - 4 - aminophenylarsinic 
 
 acid, 189. 
 
 3 - Nitro - 4 - aminophenylarsinic 
 
 acid, 190. 
 
 5 - Nitro - 2 - aminophenylarsinic 
 
 acid, 187, 188. 
 
 6 - Nitro - 3 aminophenylarsinic 
 
 acid, 188. 
 
 6-Nitro-w-arsanilic acid, 188. 
 3-Nitrobenzarsinic acid, 151. 
 5 - Nitro - 2 - carboxy - 4 - hydroxy - 
 
 phenylarsinic acid, 238. 
 3 -Nitro-4-chlorophenylarsinic acid, 
 
 228. 
 4-Nitro-5-chlorotolyl-2-arsinic acid, 
 
 242. 
 Nitro-derivatives of aromatic arseni- 
 
 cals, 142 et seq. 
 5 - Nitro -2:4- dihydroxyphenyl - 
 
 arsinic acid, 204, 245. 
 3 - Nitro - 4 - dimethylaminophenyl- 
 
 arsinic acid, 231. 
 3 - Nitro - 4 - hydroxyphenylarsenic 
 
 sesquisulphide, 215. 
 
 3 - Nitro - 4 - hydroxyphenylarseni- 
 ous oxide, 253. 
 
 2 - Nitro - 3 - hydroxyphenylarsinic 
 
 acid, 202. 
 
 3 - Nitro - 4 - hydroxyphenylarsinic 
 
 acid, 200, 201. 
 
 4 - Nitro - 2 - hydroxyphenylarsinic 
 
 acid, 202. 
 
 5 - Nitro - 2 - hydroxyphenylarsinic 
 
 acid, 202. 
 3 - Nitro - 4 - hydroxyphenylarsinic 
 
 acid, reduction of, 225. 
 3 - Nitro - 4 - hydroxyphenylmethyl- 
 
 arsinic acid, 242. 
 3 - Nitro - 4 - hydroxyphenyl - i 
 
 stibinic acid, 317, 318. 
 3 - Nitro - 2 - hydroxytolyl - 5 - 
 
 arsinic acid, 201. 
 
 5 - Nitro - 2 - methoxy - 4 - hydroxy- 
 phenylarsinic acid, 204, 246. 
 5 - Nitro - 2 - methylphenylarsinic 
 
 acid, 240. 
 i - Nitronaphthyl - 4 - arsinic acid, 
 
 239- 
 2-Nitrophenol-4-arsinic acid, 200, 
 
 201. 
 m - Nitrophenylarsenic . sesquisul - 
 
 phide, 146, 147. 
 
 m-Nitrophenylarsenic sulphide, 146. 
 m-Nitrophenylarsenious acid, 145. 
 ^-Nitrophenylarsenious acid, 145. 
 m-Nitrophenylarsenious bromide 
 
 and chloride, 146. 
 o-Nitrophenylarsinic acid, 145. 
 w-Nitrophenylarsinic acid and salts, 
 
 143. *44- 
 
 ^-Nitrophenylarsinic acid, 145. 
 
 Nitrophenylarsinic acid, constitu- 
 tion of, 156, 157. 
 
 w-Nitrophenylstibinic acid, 300, 
 301. 
 
 5-Nitroresorcinolarsinic acid, 
 
 204. 
 
 4-Nitrothienyl-2-arsinic acid, 336, 
 
 337- 
 3-Nitro-4-tolylarsenious dibromide 
 
 and sulphide, 150. 
 3-Nitro-4-tolylarsinic acid and salts, 
 
 149, 150. 
 3-Nitro-4-tolylarsinicacid, reduction 
 
 products of, 150 et seq. 
 3-Nitro-4-triazophenylarsinic acid, 
 
 182. 
 
 Nitro-m-xylylarsinic acid, 151, 152. 
 Nitro--xylylarsinic acid, 152. 
 />-Nitrosophenylarsinic acid, 179. 
 N - Nitrosophenylmethylglycine - 
 
 4-arsinic acid, amyl ester of, 
 
 194. 
 
 Novarsenobenzol, 251. 
 Novarsenobillon, 251. 
 
 371 B B 2 
 
INDEX OF SUBJECTS 
 
 Optically active arsenic compounds, 
 
 109. 
 Organic bismuth compounds, 275, 
 
 276. 
 
 Orsudan, 155, 172, 184, 288. 
 Orthoarsenious acid, derivatives of, 
 
 129. 
 Oxalyl--aminophenylarsinic acid, 
 
 161. 
 Oxalyl-^-arsanilic acid, 161. 
 
 Paracacodyl oxide, 30. 
 
 Pectine, 288. 
 
 Penicillium brevicaule (arsenical 
 mould), 45, 46. 
 
 " Phenarsenylammonium," 153. 
 
 Phenazine-2 : 7-bisarsinic acid, 182. 
 
 ^-Phenetylarsenious chloride, 94. 
 
 p-Phenetylarsinic acid, 94. 
 
 Phenol-^>-arsinic acid and salts, 197. 
 
 Phenylalkylglycinearsinic acids and 
 their reduction products, ortho- 
 and meta-nitro-derivatives of, 
 
 I94> 195- 
 Phenylarsenic chloride and oxy- 
 
 chloride, 79, 80. 
 
 Phenylarsenic sesquisulphide, 82. 
 Phenylarsenious acid, esters of, 81, 
 
 82. 
 Phenylarsenious oxide and salts, 
 
 78, 80. 
 
 Phenylarsenious sulphide, 82. 
 Phenylarsenimide, 82. 
 i-Phenylarsepidine and salts, 332. 
 Phenylarsine, 89. 
 
 Phenylarsine-/>-carboxylic acid, 137. 
 Phenylarsinic acid, 83. 
 Phenylarsinic acid, esters of, 84, 
 
 85- 
 Phenylarsinic acid ^-iodochloride, 
 
 85- 
 
 Phenylarsinic acids, salts of, 84. 
 Phenylarsinic anhydride, 83. 
 Phenylbenzylarsinic acid, 95. 
 Phenylbenzylmethylallylars o n iu m 
 
 iodide, 92. 
 Phenylcacodyl, 97. 
 Phenylcarbamino-^-arsanilic acid, 
 
 162. 
 Phenylcy c/opentamethylene a r s i n e 
 
 and salts, 332. 
 Phenylcyc/opentamethylenestib i n e, 
 
 oxide and dichloride, 332. 
 Phenylc^c/otetramethyle nearsine 
 
 and salts, 332. 
 Phenylcyc/otetramethylenes t i b i n e 
 
 and salts, 333. 
 Phenyldi-^>-benzarsinic acid and 
 
 salts, 135. 
 Phenyldiethylarsine, 90. 
 
 Phenyldiethylarsinibetaine and 
 
 salts, 138. 
 
 Phenyldiethylarsinic chloride, 90. 
 Phenyldiethylstibine and salts, 299. 
 Phenyldimethylarsine, 90. 
 Phenyldimethylarsine dibromide 
 
 and tetrabromide, 91. 
 Phenyldimethylstibine and salts, 
 
 298. 
 
 Phenyl diphenylarsenite and brom- 
 ide, 98. 
 
 Phenyldi-/-tolylarsine, 113. 
 Phenyldi-p-tolylarsine oxide and 
 
 salts, 113. 
 Phenylditolylarsinoxidedicarboxylic 
 
 acid, 136. 
 Phenylditolylarsinoxidetet r a c a r b- 
 
 oxylic acid, 136. 
 Phenyldi - p - tolylethylarsonium 
 
 iodide, 113. 
 Phenyldi - p - tolylmethylarsonium 
 
 iodide, 113. 
 Phenyldixylylarsineox idedicarb- 
 
 oxylic acid, 137. 
 ^-Phenylenearsinic acid, 89. 
 ^>-Phenylenediaminearsinic acid, 
 
 196. 
 
 Phenylethylarsenious bromide, 92. 
 Phenylethylarsinic acid, 95. 
 Phenylethyl - n - propylallylarson- 
 ium d - o - bromocamphor - TT - 
 sulphonate, 92. 
 Phenylethyl - n - propylallylarson- 
 
 ium iodide, 92. 
 
 Phenylethyl-w-propylarsine, 92. 
 Phenylglycine-^>-arsine, 263. 
 Phenylglycine-^?-arsenic disulphide, 
 
 177, 178. 
 Phenylglycine - ^-arsenious chloride 
 
 hydrochloride, 266. 
 Phenylglycine-/>-arsinic acid and 
 
 nitrile, 165. 
 Phenyliodomethyldiethylarso n i u m 
 
 iodide, 91. 
 
 PhenyHsoamylarsinic acid, 95. 
 Phenylmethylallylarsine, 92. 
 Phenylmethylarsenious bromide, 91. 
 Phenylmethylarsinic acid, 94. 
 Phenylmethyldiethylarsonium iod- 
 ide, 91. 
 Phenylmethylglycine - 4 - arsinic 
 
 acid, 166. 
 Phenyl -m- phenylenestibinic acid, 
 
 320. 
 
 Phenyl - p - tolylarsenious chloride, 
 and oxide, 108, 109. 
 oxychloride, 108, 109. 
 sulphide, 109. 
 
 Phenyl - p - tolylarsinic acid, 109. 
 Phenyl -p- tolylbenzarsinic acid, 
 136 
 
 372 
 
INDEX OF SUBJECTS 
 
 Phenyl - p - tolyldiethylarsonium 
 
 iodide and derivatives, log. 
 Phenyl-^?-tolylethylarsine and di- 
 
 chloride, 109. 
 Phenyl - p - tolylmethylethylarso- 
 
 nium iodide, 109. 
 chloride, 109. 
 Phenyltriethylarsonium dichloro- 
 
 iodide, 91 
 
 Phenyltriethylarsonium iodide, 90. 
 Phenyltmsoamylarsonium iodide, 
 
 91. 
 
 Phenylstibine dichloride, 298. 
 Phenylstibine oxide and salts, 299. 
 Phenylstibinic acid, preparation of, 
 
 from aniline, 313. 
 Phenylstibinic acid, properties of, 
 
 3*4- 
 
 Phenylstibinic oxychloride, 313. 
 fsoPhthaloarsinic acid, 120. 
 Phthalyl--arsanilic acid, 163. 
 Polyarsenical compounds containing 
 
 aromatic groups, synthesis of, 
 
 270, 271. 
 Polyarsmes, 52. 
 w-Propylarsine, 48. 
 w-Propylarsinic acid and salts, 48. 
 C-Propylphenylmethylglycine - 4 - 
 
 arsinic acid, 166. 
 Protein combinations containing 
 
 arsenic, 342, 343. 
 
 Pseudocumylarsenious chloride, 120. 
 Pyrobismethylarsinic acid, 35. 
 
 euinaldinearsinic acid, 333. 
 uinoline series, arsenic compounds 
 of, 333- 
 
 Reduction of aromatic compounds 
 containing quinquevalent ar- 
 senic, 211, 212. 
 
 Report on intravenous injection of. 
 arsenic drugs, by P. Ravaut, 
 290, 291, 292. 
 
 Resorcinolarsinic acid and methyl 
 derivatives, 199. 
 
 Resorcinyl arsenite, 338. 
 
 Salicyl-4-arsinic acid and salts, 
 198, 199. 
 
 Salvarsan, 208, 209, 210, 211 and 
 following, 224 et seq. 
 
 Salvarsan, carboxylated derivatives 
 of, 237. 
 
 Salvarsan, chloro-derivatives of, 
 238. 
 
 Salvarsan co - ordination com- 
 pounds, copper derivatives, 
 280. 
 
 mercury derivatives, 281. 
 silver derivatives, 280. 
 
 Salvarsan, co-ordination com- 
 pounds of, with 
 auric chloride, 282, 284. 
 auric chloride and silver nitrate, 
 
 283. 
 
 cupric chloride, 284. 
 cupric chloride and cuprous chlor- 
 ide, 283. 
 
 mercuric chloride, 283. 
 platinic chloride, 282, 284. 
 silver nitrate, 283. 
 silver nitrate and auric chloride, 
 
 283. 
 Salvarsan from dimethylaniline, 
 
 231. 
 Salvarsan, glycine derivatives of, 
 
 254. 255. 
 
 Salvarsan, isomerides of, 232. 
 Salvarsan, C-methyl derivatives 
 
 of, 237. 
 Salvarsan, AT-methyl derivatives of, 
 
 234- 
 Salvarsan, stilbene analogues of, 
 
 240. 
 Secondary aliphatic derivatives of 
 
 arsenic, synthesis of, 50. 
 Separation of arsenic acid from p - 
 
 arsanilic acid, 349. 
 Soamin, 159. 
 Sodium acetyl - 2 - aminotolyl - 5 - 
 
 arsinate, 172. 
 Sodium 3:3'- diamino - 4 : 4' - di - 
 
 hydroxyarsenobenzene - N - 
 
 methylenesulphinate, 251. 
 Sodium 3:5- dihydroxymercuri - 
 
 4-aminophenylarsinate, 183. 
 Sodium 3 - hydroxymercuri - 4 - 
 
 aminophenylarsinate, 183. 
 Sodium method of preparing arom- 
 atic stibines, 294. 
 Sodium phenyltrithioarsinate, 83. 
 Sodium salvarsan, 227. 
 Sodium, use of, in synthesis of 
 
 arylarsines, 67, 68, 69. 
 Spirarsyl, 208, 251, 257. 
 Stibacetin, 325. 
 ^-Stibanilic acid, acetyl derivative 
 
 and sodium salt, 315, 316. 
 Stibinobenzene, 323. 
 Sulphoform, 294, 306, 307, 326. 
 p - Sulphomethylaminophenylar- 
 
 sinic acid, 163. 
 
 Tertiary arsines, 69, 70. 
 
 Tertiary arsines containing a tolyl 
 residue, 107 et seq, 
 
 Tertiary butylphenylarsenious chlor- 
 ide, 121. 
 
 Tertiary butylphenylarsinic acid, 
 121. 
 
 373 
 
INDEX OF SUBJECTS 
 
 Tetra-allylarsonium mercuri-iodide , 
 
 49. 
 Tetrabenzylarsonium hydroxide and 
 
 salts, 1 1 6. 
 Tetra-w-butylarsonium iodide^ and 
 
 double salts, 49. 
 
 Tetrachloroarsenophenol, 214, 215. 
 Tetrachlorodi - p - anisylstibinic 
 
 acid, 309. 
 
 Tetradichlorodi-^-anisylstibine tri- 
 chloride, 309. 
 Tetraethylarsonium hydroxide and 
 
 salts, 43. 
 Tetraethyldiaminoarsenob e n z e n e, 
 
 222. 
 
 Tetraethyldiarsine, 17 et seq. 
 Tetraethylstibonium hydroxide and 
 
 salts, 57. 
 
 Tetraiodocacodylic acid, 36. 
 Tetraisopropylarsonium iodide, 48. 
 Tetramethylarsonium hydroxide 
 
 and salts, 32, 33. 
 Tetramethyldiaminoarsenobenzene, 
 
 221. 
 3:3'- Tetramethyldiamino -4:4'- 
 
 hydroxyarsenobenzene, 236. 
 Tetramethyldiarsine, 12. 
 4 : 4 / -Tetramethyl-3 : 4 : 5 : 3' : 4' : 5'- 
 
 hexaminoarsenobenzene,25o. 
 Tetramethylstibonium hydroxide 
 
 and salts, 54. 
 4:4'- Tetramethyl - 3 : 4 : 3' : 4' - 
 
 tetraminoarsenobenzene, 231. 
 
 2 : 4 : 2' : 4' - Tetraminoarsenobenz- 
 
 ene, 244. 
 
 3 : 4 : 3' : 4' - Tetraminoarsenobenz- 
 
 ene-iV-methylene sulphinate, 
 
 co-ordination compound of, 
 
 and cupric chloride, 282. 
 3 : 5 : 3' : 5' - Tetramino - 4' : 4' - 
 
 dihydroxyarsenobenzene, 244. 
 3 : 5 : 3' : 5 / -Tetramino-2 : 4 : 2' : 4'- 
 
 tetrahy droxyar senobenzene, 
 
 246. 
 
 Tetraminotetraphenyldiarsine, 222. 
 2 : 4 : 2' : 4' - Tetranitroarsenobenz- 
 
 ene, 244. 
 
 Tetranitrotetraphenyldiarsine, 148. 
 Tetranitrotetraphenyldiar s e n i o u s 
 
 sulphide, 148. 
 
 Tetraphenylarsenic disulphide, 99. 
 Tetraphenylarseniketobetaine and 
 
 salts, 141. 
 
 Tetraphenyldiarsine, 97. 
 Tetra-tt-propylarsonium iodide, 48. 
 Thienylarsenious chloride, 334. 
 Thienyl - 2 - arsenious oxide, 336. 
 Thienyl - 2 - arsinic acid and salts, 
 
 335. 336. 
 
 Tmocarbamino-^j-arsanilic acid, 
 16.2. 
 
 Thio-derivatives of arylarsinic acids 
 Thiophene, arsenical derivatives of, 
 
 Thiophene-2-arsinic acid and salts, 
 . 335. 336. 
 
 Thiophene-2-arsinic anhydride, 336. 
 
 m-Toluarsinic acid, 119. 
 
 ^-Toluarsinic acid, 120. 
 
 Toluene derivatives with one arom- 
 atic nucleus attached to one 
 arsenic atom, 105. 
 
 Toluene derivatives with two or 
 three aromatic nuclei attached 
 to one arsenic atom, 108 and 
 following. 
 
 Toluene-^-sulphonylarsanilic acid, 
 
 155- 
 p - Toluenesulphonyl - p - arsanilic 
 
 acid, 163. 
 
 o-Tolylarsenic chloride, 105, 
 ^-Tolylarsenic chloride, 106. 
 p - Tolylarsenic sesquisulphide, 
 
 107. 
 o-Tolylarsenious chloride and oxide, 
 
 105. 
 
 m-Tolylarsenious chloride, 105. 
 w-Tolylarsenious oxide, 106. 
 ^-Tolylarsenious oxide and chloride, 
 
 106. 
 
 ^?-Tolylarsenious sulphide, 107. 
 i-^-Tolylarsepidine and salts, 332. 
 o-Tolylarsinic acid and salts, 105, 
 
 241. 
 ^-Tolylarsinic acid and salts, 106, 
 
 107, 128. 
 m-Tolylarsinic anhydride, acid and 
 
 salts, 106. 
 
 ^-Tolyldiethylarsine, 107. 
 ^-Tolyldimethylarsine, 107. 
 o-Tolylglycine--arsinic acid, 166. 
 o-Tolylglycine-5-arsinic acid, 258. 
 ^-Tolylmethyldiethylarsonium iod- 
 ide, 107. 
 />-Tolyltriethylarsonium iodide, etc., 
 
 107. 
 ^-Tolyltrimethylarsonium iodide, 
 
 107. 
 
 ^-Tolylstibine chloride, 301. 
 ^-Tolylstibinic acid, 301. 
 Triarylalkylarsonium hydroxides 
 
 and salts, 71, 
 3:4:5- Triaminophenylarsinic 
 
 acid, 248, 249. 
 
 Triaminotriarylarsine oxides, 187. 
 Tri-3-aminotriphenylarsine, salts and 
 
 derivatives, 222, 223. 
 Tri-w-aminotriphenylstibine, 307, 
 
 308. 
 Tri-3-amino-tri-4-tolylarsine, salts 
 
 and derivatives, 223. 
 
 374 
 
INDEX OF SUBJECTS 
 
 Triamylstibine, dinitrate, and oxide, 
 
 58. 
 
 Tri-^-anisylarsine, 105. 
 Tri-J>-anisylstibine and salts, 308, 
 
 309. 
 4-Triazo-3 : 5-dichlorophenylarsinic 
 
 acid, 87. 
 
 4-Triazophenylarsinic acid, 181. 
 Tribenzarsenious acid, 129. 
 Tri-^-benzarsenious acid and salts, 
 
 133- 
 
 Tribenzarsinic acid, 128. 
 Tri-^?-benzarsinic acid and salts, 
 
 132. 
 Tribenzylarsine, oxide and salts, 
 
 114, 115. 
 
 Tribenzylethylarsonium iodide, 115. 
 TribenzyHsopropylarsonium iodide, 
 
 I I 5- 
 
 Tribenzylmethylarsonium hydrox- 
 ide and iodide, 115. 
 Tribenzylpropylarsonium iodide, 
 
 115- 
 
 Tribenzylstibine oxide and dichlor- 
 ide, 312. 
 
 Tricamphorylarsinic acid, 327, 329. 
 
 Tricamphorylstibinic chloride, 327, 
 330. 
 
 Tri-^-cumylarsine and salts, 124. 
 
 Triethylarsine and salts, 41. 
 
 Triethylarsenibenzobetaine and 
 salts, 139. 
 
 Triethylarsine, co-ordination com- 
 pounds of, 42. 
 
 Triethylarsine oxide, 42. 
 
 Triethylbromoethylarsonium brom- 
 ide, 44. 
 
 Tri-/>-ethylphenylarsine and salts, 
 122. 
 
 Triethylstibine, 54. 
 
 Triethylstibine oxide and salts, 55, 
 
 56, 57- 
 Trusopropylethylarsonium iodide, 
 
 48. 
 
 Trimesitylarsine and salts, 124. 
 3 - Trimethylammonium-4-hydroxy- 
 
 phenylarsinic acid, 236. 
 Trimethylarsine and salts, 32. 
 Trimethylarsenibenzobetaine and 
 
 salts, 138. 
 
 Trimethylethylarsonium iodide, 44. 
 Trimethylstibine, oxide and salts, 
 
 Tri - a - naphthylarsine and salts, 
 
 127. 
 Tri - ft - naphthylarsine and salts, 
 
 127, 128. 
 Trinitrodipseudocumylphenylarsine 
 
 oxide, 124. 
 Trinitrotricumylarsine oxide and 
 
 salts, 124. 
 
 Trinitrotrichlorotri-^-tolylarsine di- 
 
 chloride, 151. 
 
 Tri-3-nitrotriphenylarsine, 149. 
 Tri-p -nitrotripheny larsinic acid , 
 
 148, 149. 
 Tri-3-nitrotriphenylarsine oxide, 
 
 salts and halogen derivatives, 
 
 149. 
 Tri- w-nitrotriphenylstibinic acid , 
 
 37- 
 Tri-3-nitrotri-4-tolylarsine, oxide 
 
 and salt, 151. 
 Tri-^J-phenetylarsine, 105. 
 Tri--phenetylstibine and salts, 310. 
 Triphenylarsenibetaine and salts, 
 
 139, 140. 
 Triphenylarseniketobetaines , 140 
 
 and following. 
 Triphenylarsine and salts, 68, 100, 
 
 101, 102. 
 Triphenylarsineoxide-c arboxylic 
 
 acid and salts, 134. 
 Triphenylarsineoxide - di -p - carb - 
 
 oxylic acid and salts, 135. 
 Triphenylarsineoxide hexacarb- 
 
 oxylic acid, 137. 
 Triphenylarsineoxide - tetracarb - 
 
 oxylic acid, 136. 
 Triphenylarsineoxide trisulphonic 
 
 acid, 102. 
 
 Triphenylarsinocholine chloride, 104. 
 Triphenylarsinomethylcholine chlor- 
 ide, 104. 
 Triphenylethylarsonium iodide and 
 
 platinichloride, 104. 
 Triphenylhydroxyethyl arsonium 
 
 chloride, 104. 
 
 Triphenyliodomethylarsonium iod- 
 ide and chloride, 104. 
 Triphenylmethylarseniketobet a i n e 
 
 and salts, 140. 
 
 Triphenylmethylarsonium hydrox- 
 ide and salts, 103, 104. 
 Triphenylstibine and salts, 304, 305, 
 
 306. 
 
 Tri-w-propylarsine, 48. 
 Tri-M-propylethylarsonium iodide, 
 
 48. 
 Tripseudocumylarsine and salts, 
 
 123. 
 Tris - 3 - amino - 4 - hydroxy - 
 
 phenylarsenodibismuth dichlor- 
 
 ide, 276. 
 Tri-tertiary-butylphenylarsine and 
 
 salts, 125. 
 Tri - tertiary - butylphenylmethylar- 
 
 sonium hydroxide, 125. 
 Trithienylarsine, 335. 
 Tri--tolylallylarsonium bromide 
 
 and other salts, 1 1 1 . 
 Tri--tolyla.rsine, 1 1 Q t 
 
 375 
 
INDEX OF SUBJECTS 
 
 Tri-^-tolylarsine dihydroxide and 
 
 salts, no. 
 
 Tri-m-tolylarsine and salts, in. 
 Tri-m-tolylbenzylarsonium chloride, 
 
 112. 
 Tri - p - tolyldibromoallylarsonium 
 
 bromide, in. 
 Tri-w-tolylethylarsonium iodide, 
 
 112. 
 
 Tri--tolyliodomethylarsonium iod- 
 ide, no. 
 
 Tri-m-tolyh'sopropylarsonium iod- 
 ide, 112. 
 
 Tri-_/>-tolylmethylarsenibetaine and 
 salts, 141. 
 
 Tri - />-tolylmethylarseniketobetaine 
 and salts, 141. 
 
 Tri-w-tolylmethylarsonium iodide 
 and other salts, 112. 
 
 Tri-^>-tolylmethylarsonium iodide 
 and other salts, in. 
 
 Tri - />-tolylphenylarseniketobetaine 
 and salts, 142. 
 
 Tri-w-tolyl-n-propylarsonium iod- 
 ide, 112. 
 
 Tri-o-tolylstibine and salts, 310, 
 
 Tri-m-tolylstibine and salts, 311. 
 Tri--tolylstibine and salts, 311, 
 
 312. 
 
 Tri-m-xylylarsine and salts, 121. 
 Tri-^-xylylarsine and salts, 121, 
 
 122. 
 Trypanosomes, effect of atoxyl upon, 
 
 212. 
 
 Unsaturated higher fatty acids, 
 arsenical compounds of, 339, 
 34. 34 1 - 
 
 Vinyltriethylarsonium hydroxide 
 and salts, 44. 
 
 m-Xylylarsenic chloride, 119. 
 m-Xylylarsenious oxide and salts, 
 
 119. 
 ^-Xylylarsenious oxide and salts, 
 
 120. 
 
 m-Xylylarsinic acid, 119. 
 ^-Xylylarsinic acid, 120. 
 
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MONOGRAPHS ON INDUSTRIAL 
 CHEMISTRY 
 
 Edited by Sir EDWARD THORPE, C.B., LL.D., F.R.S. 
 
 Emeritus Professor of General Chemistry in the Imperial College of Science and Technology, 
 South Kensington ; and formerly Principal of the Government Laboratory, London. 
 
 INTRODUCTION 
 
 TOURING the last four or five decades the Appli- 
 ^^^ cations of Chemistry have experienced an extra- 
 ordinary development, and there is scarcely an industry 
 that has not benefited, directly or indirectly, from this 
 expansion. Indeed, the Science trenches in greater 
 or less degree upon all departments of human activity. 
 Practically every division of Natural Science has now 
 been linked up with it in the common service of man- 
 kind. So ceaseless and rapid is this expansion that 
 the recondite knowledge of one generation becomes a 
 part of the technology of the next. Thus the conceptions 
 of chemical dynamics of one decade become translated 
 into the current practice of its successor ; the doctrines 
 concerning chemical structure and constitution of one 
 period form the basis of large-scale synthetical processes 
 of another ; an obscure phenomenon like Catalysis is 
 found to be capable of widespread application in 
 manufacturing operations of the most diverse character. 
 This series of Monographs will afford illustrations of 
 these and similar facts, and incidentally indicate their 
 bearing on the trend of industrial chemistry in the near 
 future. They will serve to show how fundamental and 
 essential is the relation of principle to practice. They 
 
will afford examples of the application of recent know- 
 ledge to modern manufacturing procedure. As regards 
 their scope, it should be stated the books are not intended 
 to cover the whole ground of the technology of the matters 
 to which they relate. They are not concerned with the 
 technical minutia of manufacture except in so far as these 
 may be necessary to elucidate some point of principle. In 
 some cases, where the subjects touch the actual frontiers of 
 progress, knowledge is so very recent and its application 
 so very tentative that both are almost certain to ex- 
 perience profound modification sooner or later. This, 
 of course, is inevitable. But even so such books have 
 more than an ephemeral interest. They are valuable as 
 indicating new and only partially occupied territory ; and 
 as illustrating the vast potentiality of fruitful conceptions 
 and the worth of general principles which have shown 
 themselves capable of useful service. 
 
 The following Volumes have already been arranged for : - 
 
 The Scientific Use of Coal. By W. A. BONE, D.Sc., F.R.S., 
 Imperial College of Science and Technology, South Kensington. 
 
 Catalysis in Industrial Chemistry. By G. G. HENDERSON, M.A., 
 D.Sc., LL.D., F.R.S., The Royal Technical College, Glasgow. 
 
 Synthetic Colouring Matters: Sulphur Dyes. By G. T. 
 
 MORGAN, D.Sc., F.R.S., F.I.C., Finsbury Technical College, 
 London. 
 
 Organic Compounds of Arsenic and Antimony. By G. T. 
 
 MORC.AN, D.Sc., F.R.S., F.I.C., Finsbury Technical College, 
 London. 
 
 Synthetic Colouring Matters : Vat Colours. By JOCELYN F. 
 THORPE, C.B.E., D.Sc., F.R.S., Imperial College of Science and 
 Technology, South Kensington. 
 
 Naphthalene. By W. P. WYNNE, D.Sc., F.R.S., The University, 
 Sheffield. 
 
 Synthetic Colouring Matters: Azo-Dyes. By FRANCIS W, KAY, 
 D.Sc., The University, Liverpool. 
 
 Utilisation of Atmospheric Nitrogen : Synthetical Production 
 of Ammonia and Nitric Acid. By A. W. CROSSLEY, C.M.G., 
 D.Sc., F.R.S., F.I C. ( King's College, Strand. 
 
Cement. By BERTRAM BLOUNT, F.I.C. 
 
 Edible Oils and Fats. By C. A. MITCHELL, B.A., F.I.C 
 
 The Principles and Practice of Q as -purification. By EDWARD 
 V. EVANS, F.I.C., Chief Chemist, South Metropolitan Gas Company. 
 
 Refractories. By J. W. MELLOR, D.Sc. 
 
 The Applications of Electrolysis in Chemical Industry By 
 
 ARTHUR J. HALE, B.Sc., F.I.C., Finsbury Technical College, 
 London. 
 
 Ozone and Hydrogen Peroxide: their Properties, Technical 
 Production and Applications. By H. VINCENT A. BRISCOE, 
 D.Sc., A.R.C.S., Imperial College of Science and Technology, 
 South Kensington. 
 
 The Natural Organic Colouring Matters. By A. G. PERKIN, 
 F.R.S., The Dyeing Department, The University, Leeds ; and 
 A. E. EVEREST, D.Sc., PH.D., Technical College, Huddersfield. 
 
 Industrial Applications of the Rarer Metals. By WILLIAM G. 
 WAGNER and W. E F. POWNEY, A.I.C. 
 
 Liquid Fuel for Internal Combustion Engines. By Sir BOVER- 
 TON REDWOOD, Bart., D.Sc., F.R.S.E., and J. S. S. BRAME, Royal 
 Naval College, Greenwich. 
 
 Cellulose- Silk. By C. F. CROSS, B.Sc., F.R.S., F.I.C. 
 
 The Zinc Industry. By ERNEST A. SMITH, The Assay Office, 
 Sheffield. 
 
 The Electric Arc in Chemical Industry. By J. N. PRING, D.Sc., 
 The University, Manchester. 
 
 By- Product Coking Practice. By ERNEST BURY, M.Sc. 
 
 Organic Synthetic Reactions : their Application to Chemical 
 Industry. By JULIUS B. COHEN, B.Sc., Ph.D., F.R.S. 
 
 Colour in Relation to Chemical Constitution. By E. R. 
 
 WATSON, M.A., D.Sc., The University, Leeds. 
 
 Synthetic Colouring Matters: Triphenylmethane Dyes. By 
 
 R. ROBINSON, D.Sc., Professor of Organic Chemistry in the 
 University of Liverpool. 
 
 Synthetic Colouring Matters: Anthracene and Allied Dye- 
 stuffs. By F. W. ATACK, M.Sc. Tech., B.Sc. (Lond.), F.I.C. 
 of the Municipal School of Technology, Manchester. 
 
 Synthetic Colouring Matters: Acridine and Xanthene Dye- 
 stuffs. By JOHN T. HEWITT, M.A., D.Sc., F.R.S., University of 
 London (East London College). 
 
 Synthetic Colouring Matters: Azine and Oxazine Dye-stuffs. 
 
 By JOHN T. HEWITT, M.A., D.Sc., F.R.S., University of London 
 (East London College). 
 
 Synthetic Drugs: Local Anaesthetics. By W. H. HURTLEY, 
 D.Sc., St. Bartholomew's Hospital ; and M. A. WHITELEY, D.Sc., 
 Imperial College of Science and Technology, South Kensington. 
 
MONOGRAPHS ON BIOCHEMISTRY 
 
 Edited by R. H. A. PLIMMER, D.Sc., and F. G. HOPKINS, 
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 The Nature of Enzyme Action. By W. M. BAYLISS, M.A., D.Sc, 
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