Metal-free and green synthesis of a series of new bis(2-alkylsulfanyl-[1,3,4]thiadiazolyl)-5,5′-disulfides and 2,2′-Dibenzothiazyl disulfide via oxidative self-coupling using hydrogen peroxide

Abstract

Many disulfide and 1,3,4-thiadiazole-1,2-dithiol compounds have been extensively investigated in the pharmaceutical industry due to their unique biological properties. A series of new bis(2-alkylsulfanyl-[1,3,4]thiadiazolyl)-5,5′-disulfide derivatives containing two 1,3,4-thiadiazole rings linked by SS bond spacer were synthesized via the oxidative self-coupling of 5-alkylsulfanyl-[1,3,4]thiadiazole-2-thiol using hydrogen peroxide and ethanol as green oxidant and solvent, respectively. The excellent yields of 93–97% with 100% conversion were achieved with a simple one-pot synthesis. There is no over-oxidation of 5-alkylsulfanyl-[1,3,4]thiadiazole-2-thiol and 2-mercaptobenzothiadiazole that leads to the formation of by-products such as thiosulfinate, thiosulfonate, and sulfonic acid. In this process, a straightforward, short reaction time, metal-free, reusable solvent, and mild reaction conditions are applied to produce bis(2-alkylsulfanyl-[1,3,4]thiadiazolyl)-5,5′-disulfides and 2,2′-dibenzothiazyl disulfide. Therefore, the oxidative self-coupling is potential for other disulfide compounds.