Type C Syntheses

Type C Syntheses (C—C—N—C + S).—The reaction of a-aminobenzyl cyanide, PhCH(NHa)CN, with aldehydes and sulphur in the presence of an organic base results in good yields of anils (9), which are hydrolysed by acids to 2-substituted 

Type C Syntheses (N—C H4—S—C).—The thiocyanation of para-substi-tuted alkanolanilines (24) by sodium thiocyanate and bromine in glacial acetic acid at room temperature results in the immediate cyclization of the primary substitution products (25) to 2-imino-3-hydroxyethyl-2,3-dihydro-benzothiazoles (26). The assigned structures, supported by the spectral evidence, were confirmed by the alternative synthesis of (26) from appropriately substituted thioureas by Hugershoff s method.  

Hisano and Y. Yabuta, Chem. and Pharm. Bull. (Japan), 1973, 21, 511. 

Aminothiocyanogen may take the place of the more commonly employed dithiocyanogen in introducing the thiocyanato-group into aromatic nuclei. p-Toluidine is converted by this reaction into 2 amino-6-methylbenzothia-zole in 94% yield. l-Aminocyclohex-l-en-3-one (27) similarly affords the substituted 4,5,6,7-tetrahydrobenzothiazole (28). 

The interaction of azobenzene-2-sulphenyl bromide and methyl alkyl ketones in aqueous ethanol yields benzothiazol-2-yl alkyl ketones (33), by way of intermediate sulphides.  

Numerous benzothiazoles are being produced from the pre-formed ring-system by replacement reactions, and by standard modifications of existing substituents. Compounds so formed are listed in Table 

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Type C syntheses are typified by the oxidative cyclization of amidinothiono groups, and this has become the basis of a versatile synthesis of 1,2,4-thiadiazoles. This type of reaction is known for its speed and absence of side reactions. The synthesis of unsymmetrical 3,5-disubstituted-l,2,4-thiadiazoles of unambiguous structure in high yields is possible by this method. 

Type C Syntheses of Thiazoles (C-C-N-C S). A -(Cyanomethyl)imines R COCH(CN)N=CR OEt (R = EtO, R = Me R = NH2, R = Me or Ph), when treated with H2S, give thiazoles (87) and imidazoles (88). Of the same type, the substituted 2-azabutadiene Me2NCH=C(C02Me)N=C(SMe)2, with H2S, gives 2-methylthiothiazole-4-carboxylic acid methyl ester (89). Treatment of the imine Me2C=NMe at 400-500 with SO2 and a Zr02/ CaO/NaOH catalyst gives 4-methylthiazole. ... 

Type C Syntheses (C-C-W-C + S). in 75 yield from C13CCH(0H)NHCH0 with S0C12 and SQ in... 

Synthesis. - Type C Syntheses (C-C-H-C + S). Imines prepared from aldehydes and t NCR CR R X (X=leaving group,R1,R, R3,R =H, alkyl,Ar) react with S donors such as Na2S to form the corresponding thiazolidines (152)1. ... 

Type C Syntheses (N—C6H4—S—C).—Conversion of o-nitroarylthio-acetic acids, prepared from a-mercaptoacetic acid and the appropriate derivative of < -nitro-chlorobenzene, into the corresponding benzothiazolin-2-one (9) can be brought about by treatment with acetic anhydride followed by hydrolysis with base or acid" (see Vol. 3, p. 622). 

Type C Syntheses [N—C—N—C—S]. From amidino-thiono-compounds. The general synthesis of 1,2,4-thiadiazoles by the oxidative cyclization of compounds incorporating the amidino-thiono-grouping [—C(=NH)NHCS—] has been extended by the synthesis of l-acyl(and -sulphonyl)-3-thioacyl-guanidines (41) from acyl- or sulphonyl-guanidines (40) with thioacid O-esters in the presence of sodium hydride, followed by their oxidation with hydrogen peroxide in pyridine. 

Type C Syntheses [NCNCS].—The oxidative cyclization of compounds incorporating the amidinothiono-group [C( NH)NHCS] continues to provide the most versatile route to 1,2,4-thiadiazoles. 

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