Reaction of 3-acetonyl-5-cyano-1,2,4-thiadiazole with phenylhydrazine hydrochlorides: Indolization and phenylpyrazolation

Treatment of 3-acetonyl-5-cyano-1,2,4-thiadiazole (1) with 4-methyl or 4-me thoxyphenylhydrazine 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-cyan o-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 ma nner, when 1 was treated with 4-chlorophenylhydrazine hydrochloride, indoli zation was suppressed by phenylpyrazolation giving rise to 5-cyano-3-(5-chl oro-2-methylindol-3-yl)-1,2,4-thiadiazole (6) and 5-cyano-3-[1-(4-chlorophe nyl)-3,5-dimethylpyrazol-4-yl]-1,2,4-thiadiazole (7), The reaction mechanis m is discussed. Compounds 4, 5 and 6 exhibited weak antimicrobial activity against Helicobacter pyroli.