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Updated: Dec 29, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Nucleophilic trifluoromethoxylation of alkyl halides without silver
Yan Li1, Yang Yang1, Jinrui Xin1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Abstract:
The biological properties of molecules containing the trifluoromethoxy group have made these compounds important targets in pharmaceuticals and agrochemicals, yet their preparation is still a substantial challenge. Herein, we present a practical nucleophilic trifluoromethoxylation of alkyl halides with (E)-O-trifluoromethyl-benzaldoximes (TFBO) as a trifluoromethoxylation reagent in the absence of silver under mild reaction conditions. The trifluoromethoxylation reagent TFBO is easily prepared and thermally stable, and can release CF3O- species in the presence of a base. Furthermore, broad scope and good functional group compatibility are demonstrated by application of the method to the late-stage trifluoromethoxylation of alkyl halides in complex small molecules.
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