Synthesis of 1,3,4-oxadiazole-2-thione derivatives

Oxadiazole derivatives as heterocyclic compounds have shown a broad range of biological activities.Seven 1,3,4-oxadiazole-2-thione derivatives were designed and synthesized,and all of them were characterized and confirmed by 1HNMR and mass spectrometry.Benzoyl hydrazine(2)was obtained by the reaction of benzoate methyl ester(1)and hydrazine hydrate under refluxing,then 5-phenyl-1,3,4-oxadiazole-2-thione(3)was obtained by the reaction of benzoyl hydrazine(2)and CS2in alkaline condition under reflux.Finally target compounds were obtained by Mannich reaction consisting of(3)condensation with amine in the presence of formaldehyde.In the process,the technology is optimized based on some parameters:reaction time,molar ratio of 80%hydrazine hydrate and benzoate methyl ester(1), molar ratio of CS2and benzoyl hydrazine(2)in reaction(a)and(b)respectively,the use of solvent in reaction(c).Pure target compounds were obtained by recrystallization from suitable solvent,the yields of which were between 20%-80%.Most of the compounds haven't been reported yet,and their bioactivities as tyrosinase inhibitors remain further study.