Synthesis and Characterization of Novel 1,3-Thiazole and 2-Amino-1,3,4-Thiadiazole Derivatives

Thiosemicarbazone derivatives 3a–e were synthesized by the reaction of various aldehydes 1a–e with 4-methyl thiosemicarbazide 2 in 78% to 90% yield. Then, the thiazole moieties of the target materials 5a–e were obtained in high yields (71–93%) using the Hantzsch reaction utilizing thiosemicarbazone derivatives 3a–e with ethyl-2-chloroacetoacetic ester. The substituted nitrile derivatives 7a–e were obtained in moderate to high yield (58–84%) from the reaction of compounds 5a–e with chloroacetonitrile by the nucleophilic aliphatic substitution reaction in the presence of anhydrous potassium carbonate. Finally, substituted 2-amino-1,3,4-thiadiazole compounds 9a–e were obtained in moderate to good yields (51–62%) from the reaction of thiosemicarbazide with substituted nitrile derivatives 7a–e. As a result, compounds that all share a high disposition for biological activities were obtained. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, elemental analysis, and mass spectrometric techniques.