Regioselective Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles and 1,3,4-Oxadiazoles via Alkyl 2-(Methylthio)-2-thioxoacetates and Alkyl 2-Amino-2-thioxoacetates

An acid-catalyzed regioselectivecyclization reactionof 2,5-disubstituted-1,3,4-thiadiazolesand 1,3,4-oxadiazoles has been developed. The synthetic precursorsalkyl 2-(methylthio)-2-thioxoacetates/alkyl 2-amino-2-thioxoacetatesreact efficiently with acyl hydrazides, which transformed into a seriesof dehydrative and desulfurative products with employment of p-TSA and AcOH through a regioselective cyclization process.The alkyl 2-amino-2-thioxoacetate pathway generates excellent yieldamong the mentioned procedures. The reported methods are operationallysimplistic and highly efficient with metal-free conditions and demonstratesignificant functional group compatibility. Regioselective cyclizedproducts were confirmed by single-crystal X-ray diffraction studies.

Automated summary

An acid-catalyzed regioselective cyclization reaction of 2,5-disubstituted-1,3,4-thiadiazoles and 1,3,4-oxadiazoles has been developed. The precursors alkyl 2-(methylthio)-2-thioxoacetates/alkyl 2-amino-2-thioxoacetates react efficiently with acyl hydrazides, leading to a series of dehydrative and desulfurative products. Among the mentioned procedures, the alkyl 2-amino-2-thioxoacetate pathway shows excellent yield. The reported methods are operationally simplistic and highly efficient with metal-free conditions, demonstrating significant functional group compatibility. Regioselective cyclized products were confirmed by single-crystal X-ray diffraction studies.