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Updated: Sep 28, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Trifluoromethylated Pyrazoles via Sequential (3 + 2)-Cycloaddition of Fluorinated Nitrile Imines with Chalcones and
Anna Kowalczyk1,2, Greta Utecht-Jarzyńska1, Grzegorz Mlostoń1
1Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91403 Łódź, Poland.
Abstract:
A general approach for preparation of two types of polyfunctionalized 3-trifluoromethylpyrazoles is reported. The protocol comprises (3 + 2)-cycloaddition of the in situ generated trifluoroacetonitrile imines with enones leading to trans-configured 5-acyl-pyrazolines in a fully regio- and diastereoselective manner. Initially formed cycloadducts were aromatized by treatment with manganese dioxide. Depending on the solvent used, the oxidation step either led to fully substituted pyrazoles (DMSO) or proceeded via a deacylative pathway to afford 1,3,4-trisubstituted derivatives (hexane) with excellent selectivity.
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