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Updated: May 7, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
S-, N-, and Se-difluoromethylation using sodium chlorodifluoroacetate
Vaibhav P Mehta1, Michael F Greaney
1School of Chemistry, University of Manchester , Oxford Road, Manchester M13 9PL, U.K.
Abstract:
A simple protocol for the difluoromethylation of thiols is reported using chlorodifluoroacetate as the difluoromethylating agent. This cheap reagent undergoes smooth decarboxylation at 95 °C to afford difluorocarbene, which can be trapped with a variety of aromatic and heteroaromatic thiols. The reaction is also effective for the difluoromethylation of heterocyclic nitrogen compounds and phenylselenol.
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