Regioselective N-Trideuteromethylation of Tautomeric Polyaza Heterocycles

Jianxin Zhang; Bowen Lei; Mingrui Qin; Tao Lei; Ge Yang; Junjie Liu; Qianhui Liu; Da-Jin Yang; Shu-Feng Song; Yudong Yang

doi:10.1021/acs.joc.4c00448

Regioselective N-Trideuteromethylation of Tautomeric Polyaza Heterocycles

J Org Chem. 2024 May 16. doi: 10.1021/acs.joc.4c00448. Online ahead of print.

Authors

Affiliations

¹ Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.
² China National Center for Food Safety Risk Assessment (CFSA), Building 2, No. 37 Guangqu Road, Chaoyang District, Beijing 100022, P. R. China.

PMID: 38752832
DOI: 10.1021/acs.joc.4c00448

Abstract

Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF₃SO₃CD₃ as the -CD₃ source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d₃, ipronidazole-d₃, hydroxy dimetridazole-d₃, and ronidazole-d₃.