Metal-free synthesis of 3-trifluoromethyl-1,2,4-triazoles via multi-component reaction of trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate

Binjie Wang; Yue Sun; An Cheng; Yeanlun Zhu; Jiye Wang; Zhengkai Chen; Xiao-Feng Wu

doi:10.3389/fchem.2022.1013977

Metal-free synthesis of 3-trifluoromethyl-1,2,4-triazoles via multi-component reaction of trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate

Front Chem. 2022 Sep 20:10:1013977. doi: 10.3389/fchem.2022.1013977. eCollection 2022.

Authors

Binjie Wang¹, Yue Sun², An Cheng¹, Yeanlun Zhu¹, Jiye Wang¹, Zhengkai Chen², Xiao-Feng Wu^{3

4}

Affiliations

¹ Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province, The Department of Criminal Science and Technology, Zhejiang Police College, Hangzhou, China.
² Key Laboratory of Surface & Interface Science of Polymer Materials of Zhejiang Province, Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, China.
³ Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
⁴ Leibniz-Institut für Katalyse e. V, Rostock, Germany.

Abstract

A convenient approach for the construction of pharmaceutically valuable 3-trifluoromethyl-1,2,4-triazoles has been developed, which employs the readily available trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate (TFBen) as starting materials. The multi-component reaction features broad substrate scope, high efficiency, and scalability, providing a facile and straightforward route to the biologically important 3-trifluoromethyl-1,2,4-triazole scaffolds in moderate to good yields. Considering its broad-spectrum pharmaceutical activity, the method offers the opportunity for the further study towards the toxicity risk assessment and structure-activity relationship of the pharmaceuticals containing trifluoromethyl-1,2,4-triazole cores.

Keywords: benzene-1,3,5-triyl triformate; metal-free; multi-component reaction; trifluoroacetimidoyl chloride; trifluoromethyl-1,2,4-triazole.