5 4 YOUNG AND EYRE: OXIDATION OF 111.-Oxidation of Benxalthiosemicarbaxone. By GEORGE YOUNG, Ph.D., and WILLIAM EYRE, B.Sc. IT has been shown by Marckwald (Bey., 1892, 25, 3098; 1899, 32, 1081) that certain thiosemicarbazides, for example, C,H,*NH*N:C(SH) *NIT,, exist in two forms, of which the labile modification when treated with phosgene yields a mercaptotriazole, whilst the stable form with the same reagent yields an aminothiodiazolone. This difference, Marck- wald ascribes to stereoisomerism, thus : Young and Witham having found that benzalsemicarbazone could be oxidised by ferric chloride to phenylhydroxytriazole (Trans., 1900, 77, 224), C,H,*CH:N*NH*CO*NH, - C,H5*C< N>C*OH, we thought it might be of interest to apply the same reaction to benzalthiosemicarbazone in order t o determine, if possible, whether this compound would act as a mixture, or as one or the other of the two possible stereoisomeric forms : N*NH The substance represented by formula I would yield a n amino- phenylthiodiazole, 111, whilst that represented by I1 would yield a phenylmercaptotriazole, IT.The oxidation of benzalthiosemicarbazone . by ferric chloride takes place much more easily than that of benzalsemicarbazone ; the latter requires to be heated with an alcoholic solution of ferric chloride in sealed tubes a t 130-140°, whereas the thio-compound is oxidised by aqueous ferric chloride between 70" and 80°. The product consists almost entirely of the hydrochloride of a base which has the properties to be expected of an aminothiodiazole. I n one or two ex- periments, there was also obtained a trace of R substance of high melting point and soluble in alkali, which may have been the mer-BENZALTHIOSEMICARBAZONE. 55 captotriazole, but the quantity obtained was too small to admit of purification.Benzalthiosemicarbazone reacts, therefore, with ferric chloride almost, if not entirely, as if i t had the constitution represented by formula I. Changes in the conditions under which the oxidation took place produced no effect on the nature of the product. We endeavoured, but without success, to obtain a second form of benzalthiosemicarbazone. Our results being negative do not preclude the possibility of a second form, but, on the other hand, the substance may be tautomeric, and might, with another oxidising agent, yield the mercaptotriazole in the same manner as, according to Marckwald and Bott (Bey., 1896, 29, 2 9 14), benzoyl-4-phenylthiosemicarbazide yields phenylamino- phenylthiodiazole when treated with acetyl chloride, but diphenylmer- captotriazole when acted on by excess of benzoyl chloride, or when heated above its melting point, C,H, c<,>c N*N NH*C6H5.C,H,* C0.NH.N: C( SH)*NH* C,H, < C,H,*U<zFH$>C*SH. Benzal-4-phenylthiosemicarbazone and benzal-4-methylthiosemicarb- azone undergo oxidation by ferric chloride to the corresponding phenyl- amino- and methylamino-phenylthiodiazole : Traumann (Annulen, 1889, 249, 53) showed that the aminothiazoles can be equally well represented as iminothiazolines : HE-N HR*NH HC-S HC-S >C:NH. >C*NH, or Gabriel (Ber., 1889, 22, 1144; 1898, 31, 2832) found the amino- H,C*N thiazolines, H$+s>C*NH2, to react sometimes as such, sometimes as the tautomeric form, H2Y*NH H,C--S >C:NH.The aminothiodiazoles discussed in this paper are very similar in structure to the above compounds, and although we make use, as far as possible, of the " amino " nomenclature and constitutional formulze, the reactions and properties of our substances might be represented just as well by the '' imino " constitution. The structure of the methyl and acetyl derivatives of aminophenyl- thiodiazole is of some interest in connection with the work of Pulver- macher and of Freund on the aminothiodiazoles. Pulvermacher (Ber., 1894, 27, 61 3) found that phenylaminothiodi-56 YOUNG AND EYRE: OXIDATION OF azole on methylation aDd subsequent decomposition yielded aniline and methylamine, and he therefore gave to the base, the methyl deri- vative, and the acetyl derivative the respective formulae : Freund and Meinecke (Ber., 1896, 29, 251 1) methylated aminothio- diazole and aminomethylthiodiazole, and by comparison with the cor- responding synthetical bases prepared by Pulvermacher, determined the constitution of the methyl derivatives to be CHq8 N N(CH .3>C:NH ) and CH3*C<N"(CHs1>C:NH, S- and, following Pulvermacher's example, assumed that the acetyl derivatives were similarly constituted : Ami-nophenylthiodiazole yields with methyl iodide a methyl deriva- tive which is isomeric, and not identical with the methylaminophenyl- thiodiazole which we have prepared by the oxidation of benzal-ri-methyl- thiosemicarbazone : C,H,*CH:N*N:C(SH)*NH*CH, - C,H,*C<,->C*NH*CR,. N=EJ To the methyl base prepared by methylation and to its acetyl deri- vative, we must ascribe the constitutional formulze : Aminophenylthiodiazole yields with acetic anhFdride an acetyl derivative which has distinctly acid properties.It is easily soluble in dilute alkalis, and forms stable sodium and silver derivatives. The action of methyl iodide on the silver acetyl compound yields a methyl acetyl derivative which is identical with the above acetyl derivative of the methylated aminophenylthiodiazole. The acetyl derivative of aminophenylthiodiazole must therefore have the constitution We consider that there is no ground for the assumption that the methyl and acetyl groups take up the same position when an amino- thiodiazole is methylated or acetylated, and as our acetylaminophenyl- thiodiazole closely resembles the acetyl derivatives described by FreundBENZALTHIOSEMICARBAZONE.57 and Meinecke, we are of opinion that the constitution which they ascribe to theseacetyl compounds is open to doubt, and that their substances would be better represented by the formulae : HC<i>C*NH-CO*CH,, N N and CH,*C<~~>C*NH-CO*CH,. The acetyl derivative of methylaminophenylthiodiazole has probably the constitution : EX P ERI M ENT AL. Benxalt~~ioseinicurbaxons, C,H,* CH : N* N C( SH) *NH,.-T h iosemi- carbazide, prepared according to the method described by Freund and Imgart (Ber., 1895, 28, 948), was dissolved in warm alcohol and benzaldehyde added.On cooling, part of the benzalthiosemicarbazone crystallised ont in hair-like needles, and the remainder was precipitated by the addition of water. Benzalthiosemicarbazone is easily soluble in warm alcohol, and slightly so in boiling water, from which it crystallised, on cooling, in long, thin, shining plates which melted at 156'. After recrystal- lisstion from alcohol, the substance melted at 159-160'. Benzalthiosemicarbazone has slightly acid properties, as it is fairly soluble in caustic soda, and is reprecipitated by dilute hydrochloric acid. 0.2140 gave 0.2716 BaSO,. S = 17.41. C,H,N,S requires S = 17.87 per cent. Benzalthiosemicarbazone is easily oxidised by aqueous ferric chloride. The oxidation commences at about 70'.The best results were obtained by suspending the benzalthiosemicarbazone in water, adding rather more than one molecular proportion of ferric chloride, and warming for half an hour in a water-bath at 80-90°. After filtering from a small amount of solid matter A, the filtrate was slightly ccncentrated, if necessary, and and allowed to cool. The hydrochloride of the oxidation product crystallised out in white needles which, after recrystallisation, melted at 213 -214". Further quantities of less pure hydrochloride were obtained by concentrating the mother liquors. The hydrochloride contains one molecular proportion of water of crystallisation, which is given off at 90'. 0.2904 gave 0*1810 AgC1. HC1 e 15-86. 0.51'72, at 90°, lost 0.0420 H,O.0.3312, dried at 90°, gave 0.2182 AgC1. H,O = 8-12. HC1= 16-76. C,H?N,S,HCl requires HC1= 17.10 per cent. C,H,N,S,HCl,H,O requires HC1= 18-76 ; H,O = 7.77 per cent.58 YOUNG AND EYBE: OXIDATION OF The solid matter, .A, consisted principally of unchanged benzalthio- semicarbazone, but in some experiments contained also a very small amount of a , substance of higher melting point which was soluble in alkalis. This substance, which was not further investigated, may have been the mercaptotriazole isomeric with the base which formed the chief product. Aminophenylthiodiccxole, C,H,* C<!3C NH, .-T he hydrochloride obtained by the oxidation of benzalthiosemicarbazone was dissolved in water and excess of ammonia added. The precipitated base on re- crystallisation from 50 per cent.alcohol, formed colourless, micro- scopic hexagonal plates which melted a t 222-2233. 0.2148 gave 0.4294 CO, and 0*0800 H,O. 0.2570 ,, 55 C.C. moist nitrogen at 23' and 755.2 mm. N = 23.96. 0.2456 ,, 0,3194 BaSO,. S=17.83. C,H,N,S requires C = 54.24 ; H = 3.95 ; N = 23.72 ; S = 18.08 per cent. The base is easily soluble in dilute acids. On addition of concen- trated hydrochloric acid to the solution in dilute acid, the hydrochloride described above is obtained. C = 54-52 ; H= 4.14. Acetykaminophenylthiodiazole, C6H5* C<s>C*NH* N*N CO* CH,.-The base was added to an equal weight of acetic anhydride. The mixture rapidly became hot and soon solidified. The product on recrystal- lisation from boiling alcohol formed small needles which melted at 276'.0.3052 gave 0.3214 BaSO,. The acetyl compound is very slightly soluble in water, moderately so in boiling alcohol, and easily so in aqueous alkalis. A sodium derivative is precipitated by the addition of concentrated aqueous caustic soda to the solution in the dilute alkali. The silver derivative was prepared by dissolving the acetyl com- pound in dilute ammonia and running the solution into aqueous silver nitrate. S = 14.44. C,,H,ON,S requires S = 14.6 1 ;per cent. The white precipitate was washed with water and alcohol. 0.1742 gave 0.0576 Ag. Ag = 33.07. CloH80N,SAg requires Ag = 33.13 per cent. -The silver acetyl derivative was treated with methyl iodide and methyl alcohol, and after standing overnight was heated for half anBENZALTHIOSEMICARB AZONE. 59 hour a t 100' in a sealed tube.ing alcohol, formed prismatic needles melting a t 144'. The product, recrystallised from boil- 0.2378 gave 37.7 C.C. moist nitrogen at 14" and 751.2 mm. N = 18.43. 0,2578 ,, 0.2534 BaSO,. S= 13.48. Iminometl~yl~~en?lZthiodicczoline, C,H,* C<E*N(cH3)>C:NH.- Aminophenylthiodiazole was heated with methyl iodide and methyl alcohol in a sealed tube f o r 1 hour a t 100'. On cooling, the hydr- iodide of the new base crystallised out in large, Ant prisms which melted a t 245-246'. On addition of aqueous caustic potash to the hydriodide, the base separated as an oil. The hydrochloride melts at 218-219', and the platinichloride at 217-218'. On analysis of the latter : C11Hl,0N3S requires N = 18.03 ; S = 13.73 per cent. 0.3134 gave 0.0776 Pt.Pt=24.76 On adding the base to acetic anhydride heat was developed and on cooling the acetyl derivative crystallised out. This compound has the same melting point (144O) and crystalline appearance as the acetylimino- met hylphenylthiodiazoline described above. It was analysed with the following result : 0.1410 gave 22.4 C.C. moist nitrogen at 16.5'and 744.2 mm. N = 18.08. (CgH,N3S)2,H2PtCI, requires Pt = 24.62 per cent. C,,H,,ON,S requires N = 18.03 per cent. Benzal-4-methylthiosemicarbazone, C,H,*CH:N*N: C( S H) *NH* CH,, was prepared according to Pulvermacher's directions (Be?.. , 1894, 27, 623) and its properties agreed with his description. 0.1368 gave 26.2 C.C. moist nitrogen a t 16'and 740.0 mm. N = 21.72, This compound was oxidised with ferric chloride in exactly the same way as benzalthiosemicarbazone.The hydrochloride which separated was treated with aqueous caustic potash and the base thus obtained was crystallised from alcohol. C,HgN3S requires N = 21 *76 per cent. moderately soluble in hot alcohol, from which it separates in shining plates melting at 183-184'; it is fairly soluble in benzene, from which it crystallises in flat needles, and very slightly soluble in hot water from which i t is deposited in microscopic, rough needles. 0-0950 gave 18.3 C.C. moist nitrogen at 15' and 744.2 mm. N= 22.07. C9H,N3S requires N = 21.99 per cent,60 OXIDATION OF BENZALTHIOSEMICARBAZONE. From the hydrochloride a platinichloride was prepared which melted a t 208-209*. 0.5526 gave 0.1352 Pt. Pt = 24.46.(C,H,N3S),,H,PtC16 requires Pt = 24.62 per cent. Meth ylccce t y Zaminophen y Zthiodiazole, C,E,* C@iy>C *N<' CO*CH,'- H3 Methylaminothiodiazole was added to an excess of acetic anhydride. The acetyl compound crystallised from alcohol in long needles which melted at 1959 0.1314 gave 20.6 C.C. moist nitrogen at 15' and 744.2 mm. N = 17.99. CllHIION,S requires N = 18.03 per cent. Benzal-4-phen ylt hiosemicarbazone, C,H,*CH : N-N : C( SH)*NH* C,H,, mas made by the action of benzaldehyde on 4-phenylthiosemicarbazide. It melted a t 190' and agreed in its properties with those described by Pulvermacher (Zoc. cit.). It was boiled for half an hour with an alcoholic solution of ferric chloride. The product, which separated on dilution and evaporation of the alcohol, was treated with caustic soda. The resulting base, which melted a t 199-200°, was easily soluble in boiling alcohol, It formed a hydrochloride insoluble in water but soluble in alcoholic hydrochloric acid. With acetic anhydride, it formed an acetyl derivative melting a t 140'. The properties of the base agree fully with Marckwald and Bott's (Zoc. cit.) description of phenylaminophen ylthiodiazole, C,H,*C<!L!>C NH- C,H,. 0.3464 gave 3.3266 BaSO,. When an alcoholic solution of the base is poured into alcoholic S= 12.35. Cl,HIlN3S requires S = 12.65 per cent. silver nitrate, a white precipitate is formed. On analysis : 0.6860 gave 0.2070 Ag. Ag= 30.17. Cl,HloN,SAg requires Ag = 30.00 per cent. This silver derivative when air-dried is stable at the ordinary tem- perature ; when suddenly heated, i t decomposes with explosive vio- lence and with the evolution of phenylisonitrile. UNIVERSITY COLLEGE, SHEFFIELD.