One-pot thermo-induced radical-radical oxidative cross-coupling for symmetrical dimeric thiadiazole monosulfide formation

Abstract

The production of heterocyclic sulfide is the key building block in various applications, especially in the field of medicinal chemistry. Currently, heterocyclic sulfide was synthesized via deoxygenation of sulfoxide or cross coupling between sulfur sources and halogen compounds. However, these conventional methods suffer from drawbacks such as the use of toxic solvents, harsh reaction conditions, the requirement for transition metal catalysts, inert conditions, and the generation of toxic and corrosive halide-containing waste. In this study, a milder approach using hydrogen peroxide-mediated oxidative cross-coupling of 5-alkylsulfanyl-[1,3,4]thiadiazole-2-thiol successfully produces symmetrical dimeric thiadiazole monosulfide with an isolated yield of 73‒87 %. The molecular structure of bis(2-octylsulfanyl-[1,3,4]thiadiazolyl)-5,5′-sulfide was confirmed by X-ray crystal structure analysis. Interestingly, the formation of dimeric thiadiazole monosulfide undergoes a one-pot thermo-induced pathway. Density functional theory (DFT) indicates the formation of thiadiazole monosulfide is thermodynamically favorable through the cross-coupling reaction between thiadiazole thiyl radical and thiadiazole carbon-centered radical.