Reaction of 3-Acetonyl-5-cyano-1, 2, 4-thiadiazole with Phenylhydrazine Hydrochlorides

Treatment of 3-acetonyl-5-cyano-1, 2, 4-thiadiazole (1) with 4-methyl or 4-methoxyphenylhydrazine hydrochloride provided 5-cyano-3-(2, 5-dimethylindol-3-yl)-1, 2, 4-thiadiazole (2) or 5-cyano-3-(5-methoxy-2-methylindol-3-yl)-1, 2, 4-thiadiazole (3) as the sole product, respectively. In contrast, treatment of 1 with phenylhydrazine hydrochloride resulted in the formation of 5-cyano-3-(2-methylindol-3-yl)-1, 2, 4-thiadiazole (4) and the unexpected 5-cyano-3-(3, 5-dimethyl-1-phenylpyrazol-4-yl)-1, 2, 4-thiadiazole (5). In a similar manner, when 1 was treated with 4-chiorophenylhydrazine hydrochloride, indolization was suppressed by phenylpyrazolation giving rise to 5-cyano-3-(5-chloro-2-methylindol-3-yl)-1, 2, 4-thiadiazole (6) and 5-cyano-3-[1-(4-chlorophenyl)-3, 5-dimethylpyrazol-4-yl]-1, 2, 4-thiadiazole (7). The reaction mechanism is discussed. Compounds 4, 5 and 6 exhibited weak antimicrobial activity against Helicobacter pylori.