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Updated: Aug 11, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Electron-Deficient Fluoroarene-Mediated Synthesis of Trifluoromethyl Ketones from Carboxylic Acids
Madhukar S Said1,2, Nilesh S Khonde1,2, Pradeep Kumar1,2
1Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
Abstract:
Fluoroarene-mediated trifluoromethylation of carboxylic acids for the synthesis of trifluoromethyl ketones is disclosed. The fluoroarene activates the acid group and generates the fluoride source in situ for the trifluoromethylation reaction. The present protocol is safe and metal-free, operates under mild reaction conditions, and does not require any external additives to generate trifluoromethyl anion. The current transformation provides good functional group tolerance and also delivers 92% and 88% yields of trifluoromethyl ketones in batch and continuous flow, respectively.
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