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-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-chlorophenylhydrazine 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-thia diazole (7). The reaction mechanism is discussed. Compounds 4, 5 and 6 exhibited weak antimicrobial activity against Helicobacter pylori.
Iwakawa
T
T
Aburahi Laboratories, Shionogi & Co., Ltd., Shiga, Japan.
Nakai
H
H
Sugimori
G
G
Murabayashi
A
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects; D007211:Indoles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D010659:Phenylhydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry; D013830:Thiadiazoles / Q000737:chemistry*
C406445:3-acetonyl-5-cyano-1,2,4-thiadiazole; D000900:Anti-Bacterial Agents; D007211:Indoles; D010659:Phenylhydrazines; D011720:Pyrazoles; D013830:Thiadiazoles