Synthesis of 1,2,4-thiadiazole derivatives by oxidation of 2-cyanothioacrylamides with dioxane dibromide                  

Among five-membered S,N-heterocyclic compounds, 1,2,4-thiadiazoles are of particular interest due to their broad spectrum of biological activity. Derivatives of this class have been found to possess neuroprotective, anticholinesterase, and antioxidant properties. Functionally substituted 1,2,4-thiadiazole derivatives have also found applications in agrochemistry, with many compounds in this class acting as antidotes to the herbicide 2,4-D, as well as fungicides, insecticides, and plant growth regulators.

Previous studies have established that compounds containing a 1,2,4-thiadiazole moiety can be synthesized via the oxidation of primary thioamides. Among the previously reported systems that facilitate the oxidative dimerization of thioamides, notable examples include dimethyl sulfoxide activated by electrophilic reagents, as well as NaNO₂-AcOH, BrCH₂NO, and H₂O₂. In the present work, we investigated the reaction of dioxane dibromide with 2-cyanothioacrylamides. The products of this reaction were identified as 1,2,4-thiadiazole derivatives, which were obtained in moderate yields of 62-68% at room temperature.

Given the known biological activity of these compounds, it was deemed appropriate to evaluate their potential biological action profile. Accordingly, molecular docking was employed to predict potential ligand-protein targets. Ffurthermore, the antidote effect of the synthesized compounds against the herbicide 2,4-D was assessed under laboratory conditions. Analysis of the obtained data revealed that the synthesized compounds exhibit a moderate antidote effect.