Acid-catalyzed Cyclization of α-Ketodithioesters and Acyl Hydrazides: A Divergent and Regioselective Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles and 1,3,4-Oxadiazoles

Abstract Herein, we report an acid-catalyzed regioselective cyclization reaction for the synthesis of 2,5-disubstituted-1,3,4-thiadiazoles and 1,3,4-oxadiazoles. The transformation involves the dehydrative cyclization reaction between α-ketodithioesters and acyl hydrazides in p-TSA/EtOH and the desulfurative cyclization in AcOH/EtOH to form 1,3,4-thiadiazoles and 1,3,4-oxadiazoles, respectively, through a regioselective cyclization manner. Notably, cyclization occurs rapidly at mild reaction conditions under metal-free conditions, demonstrating the operational simplicity and practical applicability of the methodology. The reported procedures exhibit broad functional group compatibility accompanied by good to excellent yields providing a valuable alternative to existing synthetic approaches. Furthermore, the regioselective cyclizations of products were supported by DFT-based mechanistic studies, which provided insights into the selective cyclization pathways.