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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Metal-free electrochemical C4-H arylation of 5-aminopyrazoles with gentisate derivatives
Yan Tang1, Yirui Chen1, Chao Xiong1
1Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China. lingfei@zjut.edu.cn.
Abstract:
We report a metal-free electrochemical C4-H arylation of 5-aminopyrazoles with readily available gentisate derivatives under constant current at room temperature, without the need for bases, chemical oxidants, or transition-metal catalysts. A variety of 1,3,4-trisubstituted pyrazoles bearing a free 5-amino group were obtained in good to excellent yields with complete C4 regioselectivity. The use of gentisate esters as arylating agents circumvents the need for preoxidation to quinones, streamlining the synthetic sequence. Mechanistic studies support a radical-radical cross-coupling pathway involving proton transfer, electron transfer, and cathode reduction. This protocol offers a practical and sustainable approach to synthesize functionalized pyrazoles, which are privileged scaffolds in pharmaceuticals and agrochemicals.
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