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Updated: Jul 28, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of 2-Difluoroethylated 2
Kohei Fuchibe1, Taro Matsuo1, Junji Ichikawa1
1Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan.
Abstract:
2-(1,1-Difluoroethyl)-2H-1,3-benzoxazines were synthesized by (i) the regioselective ring opening of 1,1-difluorocyclopropanes bearing an aryloxy group and (ii) the Ritter reaction followed by a Friedel-Crafts-type ring closure. When 2-aryloxy-1,1-difluorocyclopropanes were treated with triflic acid, the C-C bond distal to the CF2 moiety was cleaved regioselectively via protonation to generate the corresponding oxocarbenium ions. These intermediates readily underwent nucleophilic attack by nitriles, followed by a carbocationic cyclization to afford the 2-difluoroethylated benzoxazines.
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