Thiadiazoles and dihydrothiadiazoles. Part 5. Synthesis of 2,3-dihydro-1,3,4-thiadiazoles by reaction of aldehydes or ketones with thioaroylhydrazines

Abstract

A general method for the synthesis of 2,5- and 2,2,5-substituted 2,3-dihydro-1,3,4-thiadiazoles is described, involving the condensation of aldehydes or ketones with thioaroylhydrazines. Evidence for the cyclic nature of the products is discussed. The reaction of 4-methoxythiobenzoylhydrazine with β-chloropropiophenone gives 1-(4-methoxythiobenzoyl)-3-phenyl-4,5-dihydro-1H-pyrazole, whereas the corresponding reaction with α-chloroacetophenone gives the known compound 2-(4-methoxyphenyl)-5-phenyl-6H-1,3,4-thiadiazine. 4-Methoxybenzoylhydrazine also reacts with pentane-2,4-dione to give a mixture of 5-hydroxy-1-(4-methoxythiobenzoyl)-3,5-dimethyl-4,5-dihydro-1H-pyrazole and 2-acetonyl-5-(4-methoxyphenyl)-2-methyl-2,3-dihydro-1,3,4-thiadiazole, and with 4-oxo- and 5-oxo-alkanoic acids to give 2-(2-carboxyethyl)- and 2-(3-carboxypropyl)-5-(4-methoxyphenyl)-2-methyl-2,3-dihydro-1,3,4-thiadiazoles which are readily cyclized to 3-(4-methoxyphenyl)-5-methyl-4-thia-1,2-diazabicyclo[3.3.0]oct-2-en-8-one and 8-(4-methoxyphenyl)-6-methyl-7-thia-1,9-diazabicyclo[4.3.0]non-8-en-2-one.