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

Kalleshappa Sharath; Chikkappaiahnayaka Santhosh; Kalleshappa Sheela; R. Nandini; Manoj V. Mane; Krishna Ravi Singh; Maralinganadoddi P. Sadashiva

doi:10.1055/a-2743-3444

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2743-3444

Paper

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

Authors

Kalleshappa Sharath

¹Department of Studies in Chemistry, University of Mysore, Mysuru, India (Ringgold ID: RIN29243)
Chikkappaiahnayaka Santhosh

¹Department of Studies in Chemistry, University of Mysore, Mysuru, India (Ringgold ID: RIN29243)
Kalleshappa Sheela

¹Department of Studies in Chemistry, University of Mysore, Mysuru, India (Ringgold ID: RIN29243)
R. Nandini

²Centre for Nano and Material Science, Jain University, Bengaluru, India (Ringgold ID: RIN250161)
Manoj V. Mane

²Centre for Nano and Material Science, Jain University, Bengaluru, India (Ringgold ID: RIN250161)
Krishna Ravi Singh

¹Department of Studies in Chemistry, University of Mysore, Mysuru, India (Ringgold ID: RIN29243)
Maralinganadoddi P. Sadashiva

¹Department of Studies in Chemistry, University of Mysore, Mysuru, India (Ringgold ID: RIN29243)

Abstract

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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.

Keywords

α-Ketodithioesters - 1,3,4-Thiadiazoles - 1,3,4-Oxadiazoles - Acyl hydrazides - DFT-mechanistic studies - Regioselectivity

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