CONTRlHUTIONS TO THE CHEMISTRY OF THE AMIDIWES. 59 IX.-Contrib;z.ctions to the Chemistry of the Arniclines. 2- Aminothiaxoles and 2-lrnin 0-2 3 -d i7z yd?*othiuzoles. 2-~~~~inotetrahydrot~~iaxoles and 2-Amino-4 : 5- cliJhydrothiazoles. By GEORGE YOUNG and SAMUEL IRWIN CROOKES. THIS investigation was undertaken with the purpose of studying the constitutions of the derivatives of such amidines as have one of the nitrogen atoms and the carbon atom of the group -N:C*Nz forming part of a closed chain, whilst the second nitrogen atom lies outside of the cyclic nucleus; these are referred to in the following pages as '( partially cyclic " amidines. In the present paper, we describe the alkylation of some amidines belonging to the thiazole group, and the determination of the constitutions of the alkyl bases formed.Traumann (Annalen, 1888, 249, 31) found that the base formed by the action of chloroacetone on thiocarbamide, and to which he ascribed the constitution EHAS>C*NH2, yielded on methylation Cll/le*N >C:NH, and that similarly the base, the derivative @FhT:>C*NH2, obtained by heating thiocarbamide with phenacyl bromide, yielded the methyl derivative, CH--S 8Me-NMe EH-- '>CXH. CPh XMe We have methylated the bases obtained by heating methylthio carbamide, allylthiocarbamide, and phenylthiocarbamide with chloro acetone. Traumann (Zoc. cit.) has shown that the bases formed in this manner from monosubstituted thiocarbamides, have the constitution EH-S>C*NHR. The position of the hydrogen atom, which is CMe*N substituted on alkylation, is discussed later.The methyl derivative, obtained from the base with R-CH,, is identical with 2-methylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole, CH--S >C:NMe, formed by the action of chloroacetone on s-cli- 8Me*NMe methylthiocarbamide. To determine the constitution of the alkyl derivatives of the bases with R = C3H5 and C,H,, we heated the methyl bases with concentrated hydrochloric acid at 250' in the expectation of obtairling a primary or secondary amine and the oxydihydrothiazole,60 YOUKG AND CROOKES: CONTRIBUTIONS TO THE CH- s NH2R + 8Me.N&Te >CO or GH--S >C:NR CMe-NMe >co. EH--S CMe*NH FH-'>C-NRMe -+ NHRMe + CMe*N' The high pressure in the tube after cooling, the evolution of hydrogen sulphide on evaporation of the mixture, and the separation of methylamine together with a less volatile primary amine (allyl- amine (1) and aniline respectively) from the products showed that the methyl bases had the constitutions >C:NPh, CH-- I I S>C:N*C,H, and CH--S CMe-NMe 8Me-NNe and that the hydrolysis had proceeded beyond the forination of the oxydihydrothiazole to, a t least, partial disruption of the thiazole nucleus. I n confirmation of this, it was found that 2-phenylaminothiazole, GH-S >C*NHPh, when hydrolysed with concentrated hydrochloric CMe*N acid at 350°, yielded aniline and small quantities of ammonia, hydrogen sulphide, and carbon dioxide. The methylation of the '( partially cyclic " amidines, VHR-S >C:NR', A' F H R ' S > ~ * ~ ~ ~ r CH,-N or CH,*NH has been studied by Gabriel, who methylated the bases with R=H arid CH,, and R=H, and obtained the derivatives (Ber., 1889, 22, 1142, 2984), whilst Prager, who methylated the bases of this type with R=CH, and R'=C,H, and o-C6H4Me (Ber., 1889, 22, 2998), obtained the derivatives YHMe-S $? HMe*S CH,- CH,-N N>C*NMePh and >C*NMe*C,H,Me.We have repeated Prager's preparations, have confirmed his results, and have extended the investigation to the metbylation and ethylstion of three bases in all, with R=CH, and R'=C,H,, o-C,H,Me, and p-C6H,3fe. On successive oxidation and hydrolysis of the alkylated bases, we obtained in each case p-methyltaurine and the secondary base : methyl- or ethyl-aniline, o-toluidine, and p-toluidine respectively, from which follows the constitution of the alkylated bases : CHMe*SO,H B.?Hn'e'S>C*NR'Alk --+ NHR'Alk + I CH,-N CH,*NH,CHEMISTRY OF THE AMIDINES. 61 Our results, together with those of Traumann, Gabriel, and Prager, show that “ partially cyclic ” amidines of the thiazole series, having a hydrogen atom which may be substituted directly by an alkyl group, yield on alkylation derivatives in which the alkyl is attached to the nitrogen atom of t h e nucleus, except when the ring is already partially reduced and R’ in the formula A is an aryl group, the alkyl group in this case going to the side-chain nitrogen atom, as in B. This rule is probably of general application to the alkylation of “ partially cyclic ’’ arnidines of any carbo-nitrogen heterocyclic series. The results of alkylating ‘‘ partially cyclic ” amidines are in accord with those obtained by von Pechmann on methylating “mixed” amidines, if the rule of alkylation be stated in the following form :- on alkylation of an amidine, the alkyl group goes t o the more negative nitrogen atom.Von Pechmann (Ber., 1895, 28, 3362 ; 1897, 30, 1780) found that NHR on metbylation of a “mixed” amidine, which might be -CGNK, NR or -CeNHX, with an R, an alkyl group, or a hydrogen atom, and R’, an aryl group, and in which the two nitrogen atoms must vary widely in basicity, there is obtained only one methyl derivative : in which the methyl is attached to the same nitrogen atom as in the aryl group, that is to say, to the less basic or more negative nitrogen atom, but on methylation of a ‘‘ mixed ” amidine with R and R’, two similar groups, as phenyl and o-tolyl (Ber., 1895, 88, 869) or phenyl and P-naphthyl (Ber., 1897, 30, 1783), in which the difference of the basicity of the two nitrogen atoms can be only small, a mixture of the two possible methyl derivatives is obtained.The negative nature of a nitrogen atom in an unsaturated hetero- cyclic nucleus, as exemplified by the ease with which the hydrogen atom of the group -NH- is substituted by metals, is well known, as is also the increase of the basicity of cyclic compounds on reduction. To quote one example of this : diphenyltriazole, CPh<sg>CPh (Pinner, Annalen, 1897, 299, 255), has hardly any basic properties, being soluble in dilute alkali hydroxides, but insoluble in dilute acids ; whereas diphenyldihydrotriazole, CPh<-NH-->CHPh N*NH (Pinner, Eoc. cit., p.266), is a strong base, forming with hydrochloric, nitric, and acetic acids stable salts which are not decomposed by water. Of the two possible “ partially cyclic ” amidines,62 YOUNG AND CROOKES: CONTRlBUTIONS TO THE '>C:NR, I. 8H-S>C*NR*Alk and J I . tRlemNAlk CH-- CMe*N the alkyl group is in the more negative position in 11, and there- fore, 2-phenylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole is obtained on metbylation of the base >C:NK, CH-S or IV. 8Me-NH III. 8 H - S > ~ * ~ ~ ~ CMe *N which has R=C,H,. On the other hand, of the alkyl derivatives, '>C : NR , yHMe-- v. YHMe CH,--N ">C*NR*Alk or TI. CH, *NAlk derived from Gabriel and Prager's bases, FHMe-S >C:NR, CH,*NH >C*PU'HR or VIII.$!HMe*S VIT' CH,--N the alkyl is probably in the more negative position in V if R = a n aryl group, but in VI if R is a hydrogen atom or an alkyl group; hence Gabriel's methylated bases are of the latter, but Prager's of the former type. The constitution of the derivative obtained on alkylation of an amidine having been determined, it is assumed usually that the constitution of the amidine is to be represented by placing a hydrogen atom in the position taken up by the alkyl. Thus, according to von Pechmann (.Bey., 1897, 30, 1781), benzphenylamidine must be C6H5*C<NHph, because on methylation it yields the derivative NH N H C6H5'CeNMePh. I f , however, methylation of an amidine takes place not by direct substitution, but by addition of methyl iodide and subsequent elimination of hydrogen iodide, the intermediate additive product in the formation of the methyl derivative of benzphenyl- Beckmann and Fellrath, Annulen, 1893, 273, 24), which could be formed by addition of methyl iodide t o an amidine only of t b e constitution C6H,*CGNph. NH, This view of the mechanism of the alkylation of amidines is in agreement with the behaviour of ethylene-+-thiocarbamide and of propylene-+thiocarbamide. Gabriel, having determined the constitu- tion of their methyl derivatives (see p.60), represented these bases by the formulaeCHEMISTRY OF THE AMIDINES. 63 >C:NH. $: H Me* S CH,*NH '>C:NH and CH,- ~H,-NH Later, Gabriel and Leupold (Be?.., 1898, 31, 2832) treated these two bases with nitrous acid in benzene solution and obtained the derivatives >C*NO,, YHMe-S CH,--N ? HMe '> C C6H5 and CH2--X i.espectively, probably owing to the intermediate formation of diazo- compounds, pointing to the constitutions XE;i>C*N€€, and >C*NH, for the two bases.These constitutions are in agree- 7 HMe*S CH,--N ment with the imino-formulae for the methyl derivatives methylation takes place through the intermediate formation additive products if the of the YHMe-S >CI*NH, CH,*Nble ">CI *NII, and 7H2-- CH,-NMe or CH,-- '>C*NH, and yHMe--'>C*NH2. b H, N (MeI) CH,*N( MeI) Bamberger and Lorenzen (Annalen, 1893, 273, 274) have pointed out that the addition of methyl iodide takes place t o a tertiary, i n preference to a primary or secondary, nitrogen atom, Owing t o these considerations, we have ascribed formulae of the type 111 to the amidines which yield the alkyl derivatives 11, VII to those which form the alkyl derivatives VI, and VIII to the parent bases of the compounds V.The foregoing remarks apply only to the direct alkylation of amidines by the action of alkyl haloids a t the laboratory or higher temperature with or without a solvent, and not to indirect alkylation by the action of alkyl haloids on a metallic derivative of the amidine With the idea that methylation by the latter method might lead to the formation of the isomeric series of alkyl derivatives, we digeste the silver derivatives of the 2-arylimino-5-methyltetrahydrothiazoles VIII with one molecule of methyl iodide, but without obtaining more than traces of oily products which might be the alkylated amidines, the original base being recovered almost entirely in each case.Similarly, Bamberger and Lorenzen (Zoc. cit., p. 282) found that only very small amounts of 1 : 2 : 5-trimethylbenzimidazole were64 YOUNG AND CROOKES: CONTRIBUTIONS TO THE formed by the action of methyl iodide on the silver derivative of 2 : 5-dimethylbenzimidazole, whilst Meldola, Eyre, and Lane (Trans., 1903, 83, 1185) obtained the same alkyl derivatives from ethenyldi- aminonaphthalenes by the direct and the indirect methods of alkyla- tion, but in much the poorer yields by the latter process. We suggest that in reality no alkylation of these amidines takes place by the indirect method, the small amounts of alkyl derivatives formed being due to interaction of the alkyl iodide with the liberated amidine, especially as the best yields by the indirect method appear to be obtained when, as in the experiments of Meldola, Eyre, and Lane (Zoc.cit., p. li93), an excess of the alkyl haloid is employed. On the other hand, 2-acetylimino-3 : 4-dimethyl-2 : S-dihydrothi- azole, >C:NAc, is formed in good yield by the indirect method from the acetyl derivative of 2-amino-4-methylthiazole, as was 2-acety limino-5-phenyl-3-methyl-2 : 3-dihydrothiodiazole, fH-S CMe*NMe from 2-amino 5-phenylthiodiazole, studied by Young and Eyre (Trans., 1901, 79, 54), whereas attempts to methylate the last substance by the direct method met with no success. It may be that the greatly diminished basicity of the nitrogen atom of the side-chain consequent on the introduction of the acetyl group causes isomeric change to take place : the hydrogen atom being less labile when attached to the less negative atom, the subsequent direct substitution, on treatment of the silver derivative with methyl iodide, >C: NAc, CH--Is '>C:NAc --+ fCIMe*NMe CH- CMe NAg I I being due to the increased acidity of the molecule.E x P E R I BI E N T A L. 2-Aminothiaxoles a n d 2-lmino-2 : 3-dihyclrotT~iaxoZes. 2-Anilino-4 methylthiazole mas prepared by Hantzsch and Weber (Ber., 1887, 20, 3130) by the action of aniline on 2-hydroxy-4-methyl- thiazole, and was found by these authors to melt a t 117". Traumann (Eoc. cit.), who prepared the base by acting on phenylthiocarbamide with chloroacetone, found it to melt at 115".On repeating theCHEMISTRY OF THE AMIDINES. 65 preparation by Traumann's method, we obtained a substance which crystallised from dilute alcohol in long needles and melted at 11 7-1 18'. When boiled with acetic anhydride and sodium acetate, the base formed an acetyl derivative, which was readily soluble in alcohol or benzene, but only moderately so in light petroleum; from the last solvent it crystallised, on slow evaporation, in clusters of soft, white, silky, matted needles which melted a t 1 1 4 ~ 5 ~ . 0.1655 gave 17.0 C.C. moist nitrogen a t 1 6 O and 755 mm. C,,H,N,S*C,H,O requires N = 12.07 per cent. N = 11.95. 2- Phen ylimino- 3 : 4-dime th y Z - 2 : 3-dih ydr ot 7kixo Ze, El- '>C : NPh. CMe*NMe 2-Anilino-4-methylthiazole was heated with methyl iodide and methyl alcohol in a closed vessel for one hour in the water-bath, and the product, after being diluted with water and boiled to expel the methyl alcohol, made alkaline and extracted with benzene; the oily residue obtained on drying and distilling the benzene residue was allowed to solidify slowly in a desiccator over soda-lime. The base prepared in this manner was moderately soluble in warm light petroleum, frolri its solution in which it separated in small, white crystals melting at 65-66".0.1458 gave 17.4 C.C. moist nitrogen a t 14.5" and 755 mm. N = 13.93. The plutinicldoi-ide, formed by adding platinic chloride to the solution of the base in warm dilute hydrochloric acid, crystallised from the solution on cooling, and after being dried at 105" melted at 189-1 90°.CIIHl2N2S requires N = 13.72 per cent. 0.3446 gave 0.0584 Pt. Pt = 23-88. (C,,H,,N,S),,H,PtCI, requires Pt = 23.83 per cent. Hydrolysis of 3-Phenylimino- 3 : 4-dimethyl-2 : 3-diJqd~otJ~iaxole. The methylated base was heated with concentrated hydrochloric acid in a sealed tube at 245-250" for four and a half hours. After concentration on the water-bath, during which operation considerable quantities of hydrogen sulphide were evolved, an excess of potassium hydroxide was added and the product distilled in a current of steam, any alkaline vapours which passed through the receiver being retained by an acid trap. The distillate, after acidification and concentration, was again made alkaline and boiled in a reflux apparatus until no alkaline vapours could be detected on removal of the hydrochloric acid trap.The residual liquid in the boiling flask gave the isonitrile VOL. LXXXIX.66 YOUNG AND CROOKES: CONTRIBUTIONS TO THE reaction for primary amines and the bleaching powder reaction for aniline, whilst the solution from the hydrochloric acid trap gave only the first of these two reactions, but when made alkaline smolt strongly of methylamine. I n one experiment, a small amount of a white, solid substance separated from the distillate; it melted a t 78" and wits possibly 2-oxy-3 : 4-dimethyl-2 : 3-dihydrotliiazole. %Allylamino- 4-methylthiaxole, @Ec!>C? *NH * C,H,. The hydrochloride of this base was formed by gradually adding 1 mol. of chloroacetone to 1 mol. of allylthiocarbamide; as the re- action takes place with considerable development of heat, it was necessary t o cool the mixture with water.The cold product was treated with aqueous potassium hydroxide, and the solid thus obtained recrystallised from light petroleum, when it formed locg, white, silky needles. The base, which was observed to have a slight odour resembling that of thyme, melted at 40-41". N = 18.44, 0.2572 gave 40.9 C.C. moist nitrogen at 15O and 753 mm. 0*1780 ,, 0.2640 BaSO,. S = 20.66. C7H1,N,S requires N = 18-18 ; S = 20.78 per cent. The acetyl derivative, formed by boiling 2-allylamino-4-methyl- thiazole with acetic anhydride, was obtained as an oil which solidified slowly to a crystalline mass; it was readily soluble in benzene, but only moderately so in light petroleum, from which it orystallised in thin, square plates, It melted at 36-37" and had, especially before recrystallisation, an odour resembling that of impure aoe tamide, 0.2590 gave 0.3040 BaS04.S = 16.12. C7H,N,S*C2H,0 requires S = 16.33 per cent. '>C: N*C,H,. CH-- CMe*NMe 2-Allylimino-3 : 4-dimethyl-2 : 3-di?~ydi*othiaxole, I I The hydriodide formed by heating 2-allylamino-kmethylthiazole with methyl iodide and methyl alcohol in a closed vessel at 100" separated from the mixture after some days in almost colourless, large, prismatic plates. When dissolved in a small quantity of alcohol, in which it was readily soluble, and precipitated by addition of ether, the salt was obtained as a white, crystalline meal, which melted a t 1 1 6-1 17". 0.2035 gave 0.1616 AgT. 1=42.94.C,H,,N,S,HI requires I = 42.89 per cent.CHEMISTRY OF THE AMIDINES. 67 On treatment of the hydriodide with potassium hydroxide in con- centrated aqueous solution, extraction of the product with benzene, and evaporation of the extract, the free base was obtained as a slightly red, viscid oil possessing a characteristic odour ; it was readily soluble in dilute acids, and formed a crystalline platinichloride, which dissolved to only a slight extent in hot dilute hydrochloric acid. Hydyolysis of 2-Allylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole, The methylated base was heated with concentrated hydrochloric acid in 5 sealed tube a t 230-240" for five hours. The product was concentrated, made alkaline, and distilled in a current of steam; the distillate was treated in the same manner as that obtained by the hydrolysis of 2-phenylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole.Both the residual liquid from the reflux apparatus and the solution from the hydrochloric acid trap gave the isonitrile reaction, showing that the hydrolysis had resulted in the formation of two primary amines. 2-*4 cetylinzino- 4 -naetlq I- 2 : 3 -dihydrothiaxole, '>c: N AC. CH- EMe*NH 2-Amino-4-methylthiazole hydrochloride was prepared by the action of chloroacetone on thiocarbamide (Traumann, loc. cit.), and the base liberated by addition of concentrated aqueous potassium hydroxide and extracted with benzene. On evaporationof the extract, there was obtained a slightly pink oil, which, when cooled over calcium chloride in a desiccator, solidified t o a white, slightly hygroscopic solid melting a t 4 2 O .The acetyl derivative, formed by boiling the anhydrous base with 1 mol. of acetic anhydride in a reflux apparatus, is moderately soluble in warm water, from which it separates on cooling in shining, colourless crystals. The melting point was found to be 134O, as given by Traumann. On addition of 1 mol. of silver nitrate and 1 mol. of ammonia in aqueous solution to its solution in alcohol, the acetyl compound formed a silver derivative as a dense, white precipitate, which, after being well washed and dried a t loo", was fairly stable to light. 0.1962 gave 0.0809 Ag. Ag=41-23. C,H,N,SAg*C,H30 requires Ag = 41 *03 per cent. When heated with 1 mol. of methyl iodide in methyl-alcoholic solution in a closed vessel at looo, the silver derivative forms 2 -acet y Zimino - 3 ; 4dimeth y I - 2 : 3 -dihydrothiazole, '> c: N A ~ , CH--- k.!Me*NMe68 YOUNG AND CROOKES: CONTRIBUTIONS TO THE which, on evaporation of the methyl-alcoholic solution and re- crystallisation of the residue, was obtained in wbite, nodular, crystalline aggregates which melted at about SOo, or sharply at 1 1 3 O , after being dried over sulphuric acid in a vacuum (Hantzsch and Weber, Ber., 1887, 20, 3124).Methylation of 2-MethyZamino-4-methyZthiazole. The hydrochloride of 2-methylamino-4-methylthiazole was prepared by slowly mixing chloroacetone and methylthiocarbamide in molecular proportions; it was found necessary to keep the reacting mixture cooled by means of ice-water. The base was liberated by treatment of its hydrochloride with aqueous potassium hydroxide, and recrystal- lised from benzene, from which it separated as a slightly pink oil; this solidified slowly, forming long, white needles, which melted at 6 4 O and dissolved readily in methyl alcohol or light petroleum.Traumann (Zoc. cit.) gives the melting point of this base as 42'. The result obtained from the sulphur determination, together with the formation of 2-methylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole, is sufficient proof of the constitution of our base. 0,1962 gave 0.3642 BaSO,. When heated with 1 mol. of methyl iodide in methyl-alcoholic solution in a closed vessel at 1 OOO, 2-methylamino-4-methylthiazole yielded 3-methylimino-3 : 4-dimethyl-2 : 3-dihydrothiazole hydriodide, CH-S >C:NMe,HI, which separated in stellate aggregates of 8Me-NMe crystals melting at 5 4 O , or at 164" after drying at 105O.Hantzsch and Weber, who prepared this salt by heating 2-amino- thiazole with 2 mols. of methyl iodide (Ber., 1887, 20, 3123), found it to melt at 54", or when anhydrous at 155O, whilst Traumann (Zoc. cit.), who obtained the base by treating s-dimethylthiocarbamide with chloroacetone, gives the melting point of the anhydrous hydriodide as 164". S = 25.52. C,H,N,S requires S = 25.06 per cent. 2-Im i 9% o t e t r u h y d r o t hi ax o 1 e s a n d %A mi n 0-4 : 5-d i h y d r o t h ia x o 2 e 8. 2 - Phsn~Zimino-5-methyZtetra~~ydi.ot~iazole, The hydrochloride, prepared by heating s-phenylallylthiocarbamide with concentrated hydrochloric acid in a closed vessel at looo, was treated with concentrated aqueous potassium hydroxide, and theCHEMISTRY OF THE AMIDINES.69 product recrystallised from hot dilute alcohol. The base obtained in this manner crystallised in needles and melted at 117' (Prager, zoc. cit.). 0.1673 gave 0-2044 BaSO,. 0.1577 ,, S = 16-79. 19.6 C.C. moist nitrogen at 11*5°and 755 mm. N = 14.71. The base formed a picrate, which crystallised from dilute alcohol in C,,H,,N,S requires S = 16.67 ; N = 14.58 per cent. rough, yellow needles and melted a t 154O. 0.1378 gave 20.7 C.C. moist nitrogen at 19' and 735 mm. N = 16.46. C,,H,,N,S,C6H30,N3 requires N = 16-63 per cent. When shaken with acetic anhydride, the base dissolved with slight development of heat, forming a clear solution; after some time, the mixture was dissolved in ether, and the ethereal solution was washed with aqueous potassium carbonate, dried, and distilled on the water- bath.The residual oil gradually solidified to a crystalline mass which melted at 47O. 0.1 808 gave 0,4069 CO, and 0.0993 H20. 0.1552 ,, 0.1557 BaSO,. S= 13.79. C,,H,,N2S~C2H,0 requires C = 61.54 ; H = 5-98 ; S = 13.68 per cent, The acetyl derivative was readily soluble in alcohol, ether, or benzene, less so in light petroleum, and separated from its solutions as an oil, which rapidly solidified on addition of a small quantity of the crystalline substance. When dissolved in alcohol and poured into an alcoholic solution of silver nitrate, the base formed the silver derivative, CloHI,N,SAg, which was obtained as a white precipitate.After being washed with dilute alcohol and dried at 904 the silver derivative detonated when heated on a piece of porcelain over the Bunsen flame, whilst when heated in a capillary tube it blackened and commenced to melt at 1 30°. C = 61.38 ; H = 6.10. 0,2473 gave 0.0890 Ag. CloH,,N2SAg requires Ag =I 36-08 per cent. With the object of obtaining possibly a methyl base isomeric with that prepared by Prager, the silver derivative was warmed with 1 mol. of methyl iodide in methyl-alcoholic solution and the product evaporated and shaken with benzene. The base obtained on evapora tion of the benzene solution was converted into its picrate, which crystallised in rough, yellow needles, melted at 154O, and gave analytical results agreeing with those required by the picrate of 2-phenylimino-5-methyltetrahydrothiazole. Ag = 35.99.70 YOUNG AND CROOKES: CONTKIBUTIONS TO THE 0.1279 gave 18.7 C.C.moist nitrogen at 17" and 756 mm. N = 16-86, CloH12N,S,C,K,07N, requires N = 16.63 per cent. C1,H,,N,SMe,CGH,O7N3 ,, N = 16.09 ,, ,, 2- P?LenyZ.nzet~hyZamino-5-met~LyZ-~ : 5 -dihydrothiaxoZe, YHMe.8 >C*NMePh. CH,-N As the action of methyl iodide on the silver derivative did not lead to the formation of a methyl base, 2-phenylimino-5-methyltetrahydro- thiazole was heated with 1 mol. of methyl iodide in methyl-alcoholic solution in a closed vessel at 100'. The base mas mixed also with an excess of methyl iodide, and the mixture was allowed to stand over- night in a flask cooled by ice-water (Prager, Zoc. cit., p.2997). By these two methods, the same methyl base was obtained as an oil, readily soluble in alcohol, ether, benzene, or dilute acids. The pZatinichZoride of the methyl base crystallised in salmon- coloured, nodular aggregates of plates and melted a t 184O. A,* 0.4758 gave 0*1132 Pt. Pt=23'79. B. 0.3254 ,, 0*0775 P t . Pt=23*81. (C,,Hl,N,S),,H,PtC16 requires Pt = 23.69 per cent, The yicrate of the methyl base melted under boiling water, in which it was slightly soluble, crystallising on cooling in soft, yellow needles ; it dissolved readily in alcohol, from which, on dilution, i t crgstallised in clusters of yellow needles. It melted at 114-1 15' ; Prager gives its melting point as 125". A. 0*1180 gave 17.1 C.C. moist nitrogen at 18" and 740 mm. N = 16.28, B. 0.1525 ,, 21.8 ,, ,, ,, 19' ,, 751 mm.N=16.23. C,,H,,N,S,C,H307N, requires N = 16.09 per cent. ? HMe's>C NEt Ph . CH,-N 2-Phenylirnino-5-methyltetrahydrothiazole was heated with 1 mol. of ethyl iodide in ethyl-alcoholic solution in a closed vessel at 100" and the product boiled with a small quantity of water, made alkaline, and extracted with benzene. On evaporation of the benzene, the ethyZ base was obtained as an oil, which was readily soluble in alcohol or ether, less so in light petroleum, and only sparinglyso in water, and had the peculiar odour characteristic of the group of compounds, On addition * The analyses A and B given for the platinichloride and piarate are for the salts sf the base prepared by the first and second methods of methylation respectively.CHEMISTRY OF THE AMIDINES.71 of platinic chloride to its solution in dilute hydrochloric acid, the base formed the platinichloride, which separated as a reddish-yellow, crystalline powder and melted and decomposed a t 156'. 0.6488, dried at 1 0 5 O , gave 0.1488 Pt. Pt = 82-93. (C,,H,,N,S),,H,PtCl, requires Pt = 22.94 per cent. Formation of P-Methyltauurine from 2-Phen~Zetl~~lc6mino-5-me~hyl-4 : 5 dih y h o t hiaxo Ze. The ethyl base was oxidised with potassium chlorate in slightly warm hydrocliloric acid, and the product evaporated to dryness and extracted with a mixture of alcohol and ether. The residue from this extract was heated with concentrated hydrochloric acid in a sealed tube at 150-200', and the solution filtered from tarry matters and evaporated to dryness.On extracting the dried product with absolute alcohol, a white residue was obtained, which, aftrer recrystallisation from 90 per cent. alcohol, separated from a small quantity of warm water in transparent, rhombic plates and agreed in its other properties with those of P-methyltaurine as described by Gabriel (Ber., 1889, 22, 2984). When powdered and heated in a capillary tube, P-methyltaurine melts a t 284-285'. 0.1732 gave 0.1638 (30, and 0.1015 H,O. 0.1845 ,, 0.3143 BaSO,. S= 23.39. 0,1936 C=25*79 ; El-6.51. ,, 1'7.5 C.C. moist nitrogen at 17' and 742 mm. N= 10.24, H = 6.48 ; N = 10.07 ; NH,=CH;CHMe*SO,H requires C = 25.90 ; S = 23.02 per cent, s-p- TolyZallylthiocarbmnide, C,H,Me:NH* C'S*NH*C,H,. This substance was prepared by boiling p-toluidine with a slight excess of allylthiocarbimide in alcoholic solution in a reflux apparatus. On removal of the alcohol and excess of the thiocarbimide by distillation in a current of steam, the product separated as a heavy oil, which solidified on cooling and, after purification by repeated crystallisation from dilute alcohol, was obtained in nodular aggregates of almost colourless needles which melted at 98'.09011 gave 0.2304 BaBO,. S= 16.75. CI1H1,N,S requires S = 15.53 per cent,72 YOUNG AND CROOKES: CONTRIBUTIONS TO THE YHMe* >c : N.C,H,. CH,*NH s-p-Tolylallylthioearbamide was converted into the corresponding tetrahydrothiazole by the action of concentrated hydrochloric acid at 100' under pressure. The clear solution thus obtained was evapor- ated to dryness, the residue treated with aqueous potassium hydroxide, and the liberated base purified by recrystallisation from alcohol.2 -p-Tolylimino-5-methylte trahydrot hiazole crys t allised from dilute alcohol in small, shining plates or broad needles, or from ether in diamond-shaped plates, and melted at 106". 0.1563 gave 0.3664 CO, and 0.0970 H,O. 0.1887 ,, 22.2 C.C. moist nitrogen at 16'and 750 mm. N = 13.49. 0.1759 ,, 0.2001 BaSO,. S= 15.64. C,,H,,N,S requires C = 64.08 ; H = 6.80 ; N = 13.59 ; S = 15.53 per The base dissolved readily in dilute hydrochloric acid, and on addition of platinic chloride formed the platiniddoride, which crystal- lised in small, rough, thick, yellow needles, and after being dried at 110" melted and decomposed a t 204'. C = 63.97 ; H = 6.90.cent, 0.5061 gave 0.1199 Yt. (C,,H,,N2S),,H,PtC1, requires Pt = 23.74 per cent. The acetyl derivative, C,,H,,N ,S*C,H,O, was formed by gently warming the base with acetic anhydride ; i t crystallised from light petroleum in white prisms and melted at 61'. Pt = 83.69. 0.1689 gave 0-1606 BaSO,. Cl3H1,ON2S requires S = 12-90 per cent. When boiled with dilute hydrochloric acid, the acetyl derivative gradually dissolved, and on addition of potassium hydroxide to the solution the parent base, melting at 106O, was precipitated. S = 13-08. 2-p- Tolylmethylarnino-5-methyl- 4 ; 5-dihydrothiaxole, ~HMe*s>C*NMe*C,H7. CH2--N On shaking 2-p-tolylimino-5-methyltetrahydrothiazolo with slightly more than one mol. of methyl iodide, the mixture became warm and changed to a clear liquid which gradually solidified.The product was boiled with a small quantity of water to free it from the excess OF methyl iodide, made alkaline, and extracted with ether. TheCHEMISTRY OF THE AMIDINES. 73 methyl base, which was obtained as an oil on evaporating the ethereal extract, dissolved readily in dilute hydrochloric acid, alcohol, ether, or benzene, and had the characteristic odour of the 2-amino-4 : B-dihydro- t hiazoles. The platinichloride melted and decomposed at 1104 0.2213 gave 0.0513 Pt. Pt=23.18. (C,,H,,N,S),,H,PtCI, requires Pt = 22.94 per cent. Oxidation of 2-p- Tolylmethykamino-5-metlr~yk-4 : 5-dihydrothiaxole. The p-tolylmethylamino-base was oxidised with potassium chlorate and hydrochloric acid, and the product treated as described under the oxidation of the phenylethylamino-base.The final residue, after extraction with absolute alcohol, crystallised from water in transparent plates, melted at 284--285O, and on analysis gave numbers agreeing with those required for P-methyltaurine. 0.1821 gave 0.3088 BaSO,. S = 23.32. C3H,03NS requires S = 23.02 per cent. The absolute alcoholic extract was evaporated with hydrochloric acid, treated with an excess of aqueous potassium hydroxide, and dis- tilled in a current of steam. On addition of hydrochloric acid and platinic chloride to the distillate, the platinichloride of methyl-p-tolui- dine separated as a red, crystalline powder, which was dried at 110'. 0.4109 gave 0,1222 Pt. Pt = 29-74. (C6H3[,MeoNHMe),,H~PtCls requires Pt = 29.91. 2-p-Tolylethylamino-5-methyl-4 : 5-dihydrothiclzole, CH,-N ~HMe*s>C*NEt*C,H7.2-p-Tolylimino-5-methyltetrahydrothiazole was heated with slightly more than one mol. of ethyl iodide in ethyl-alcoholic solution in a closed vessel for one hour a t looo, and the product boiled with water, made alkaline aud extracted with ether. The ethyl base was obtained, on evaporation of the ethereal solution, as an oil which was easily soluble in alcohol, benzene, or dilute acids. The plctinnichloride separated from its solution in warm dilute hydro- chloric acid in orange-coloured crystals, which melted and decomposed at 189-190'. 0.6832 gave 0.1505 Pt. Pt = 22.03. (C,,H,,N2S),,H2PtCI6 requires Pt = 22.21 per cent.74 YOUNG AND CROOKES: CONTRIBUTIONS TO THE Oxidation of 2-p-~olyZethyZ~mino-5-meth~Z-4 : 6-dihydrothiuxole. The p-tolylethylamino- base was oxidised with potassium chlorate and dilute hydrochloric acid, and the product hydrolysed with con- centrated hydrochloric acid a t 160-200'.The residue obtained on evaporation was extracted with absolute alcohol and recrystallised from waterl when it formed transparent plates and melted a t 284-285' (@-met h yltaurine). 0.1932 gave 0.3286 BaSO,. The alcoholic extract yielded the platinichloride of ethyl-p-toluidine, 0.8336 gave 0,0666 Pt. S = 23-38. C,H,O,NS requires S = 23.02 per cent. Pt = 28.51. (C,H,Me*NH Et),,H,PtC1, requires Pt = 28.68 per cent. YHMe S >C:N* C,H,. CH,*NH %o-~olyhino-5 -methyltetra~ydrothiaxob, This base mas prepared according to Prager's directions (Zoc. cit., p.2999) from s-o-tolylallylthiocarbamide ; i t crystallised in small plates and melted a t 126'. 0-1699 gave 0.1941 BaSO,. C,,H,,N,S requires S = 15-53 per cent. On addition of silver nitrate to its solution in alcohol, the base formed the silver derivative as a white precipitate, which was washed and dried a t 105'. S= 15.71. 0.9561 gave 0.3289 Ag. C,,H,,N,SAg requires Ag = 34.49 per cent. The acetyl derivative, C,,H1,N,S*C2H,0, was prepared by boiling the base with acetic anhydride and shaking the product with water ; it crystallised from light petroleum in stout prisms, melted a t 58", and was easily soluble in benzene, alcohol, ether, or acetone, but only sparingly so in light petroleum. Ag= 34-40. 0,1529 gave 0.3522 CO, and 0.0897 H,O. C = 62.82 ; H= 6.52.0.2137 ,, 0.2029 BaSO,. S= 13.05. C,,H,,ON,S requires C = 62-90 ; H = 6.45 ; S = 12.90 per cent. The acetyl derivative dissolved unchanged in cold dilute hydro- chloric acid from its solution, in which it was precipitated unchanged on addition of aqueous sodium hydroxide, but when boiled with the dilute acid it was hydrolysed, and the precipitate obtained on addition of the alkali hydroxide consisted of the parent base melting at 126".CHEMISTRY OF THE AMIDINES. 75 2 -0- To ZyZmet?ylamino- 5 -methyZ-4 : 5 -di?bydrot?&zoZe, \!HMe*S CH,-N >C*NMe* O,H,. This substance was obtained as an oil by shaking 2-o-tolylimino-5- methylte trahydrot hiazole with methyl iodide and liberating the methyl base with aqueous potassium hydroxide. The platinichloride melted and decomposed at about 200". Pt = 22.S8. 0.5318 gave 0.1217 Pt. (C,,H,,N,S),,H,PtCl, requires Pt = 22.94 per cent. On oxidising the base with potassium chlorate and hydrochloric acid and hydrolysing the product with concentrated hydrochloric acid at 150-200°, we obtained, as did Prizger, P-methyltaurine melting a t 2 84-285'. 0.3044 gave 0.5106 BaSO,. S = 23.31. C,H90,NS requires S = 23.02 per cent. 2-0- To Zyleth ylnrnino-5-meth y Z-4 ; 5 -dihydrot?hiaxole, YHMe* S>C*NEt*C7H,. CH,-N The hydriodide of this base was formed by heating 2-o-tolylimino-5- methyltetrahydrothiazole with ethyl iodide and ethyl alcohol in a closed vessel at 100". When liberated by means of potassium hydroxide, the base was obtained as an oil which had the characteristic odoiir and dissolved readily in alcohol, ether, benzene, or dilute acids. The plutinicldoride formed orange-red crystals which melted and decomposed at 203O. 0.7959 gave 0.1764 Pt. Pt=22*17. (Cl,H18N2S),,H2PtC1, requires P t = 22.21 per cent, The base was oxidised with potassium chlorate and hydrochloric acid, the oxidation product hydroly sed with concentrated hydrochloric acid, and the residue obtained by evaporation extracted with absolute alcohol. The part insoluble in absolute alcohol was P-methyltaurine, as after recrystallisation from 90 per cent. alcohol it melted at 284-2 85'. 001587 gave 0.1499 CO, and 0.0945 H20. 0.2173 ,, C-25-76; H=6.62. 19.2 C.C. moist nitrogen at 16' and 754 mm. N = 10.22. C,H,O,NS requires C = 25.90 ; H = 6-48 ; N = 10.07 per cent.76 FORD AND GUTHRIE: THE INFLUENCE OF CERTAIN The absolute alcoholic extract yielded the platinichloride of ethyl-o- toluidine. 0.2786 gave 0.0800 Pt. Pt = 28.70. (C,H,Me*NHEt),,H,PtCI, requires Pt = 28.68 per cent. We take this opportunity of thanking the Research Fund Com- mittee of the Chemical Society for a grant by which the expenses of this investigation were partly defrayed.