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Updated: Aug 7, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Traceless N-Polyfluoroalkylation of Weakly Nucleophilic Nitrogen Containing Compounds
Laura Santos1, Florian Audet1, Morgan Donnard1
1Laboratoire d'Innovation Moléculaire et Applications (UMR7042), Université de Strasbourg, Université de Haute-Alsace, CNRS, 25 rue Becquerel, 67000, Strasbourg, France.
Abstract:
Here we report an efficient access to high-value N-polyfluoroalkyl anilines, primary polyfluoroalkylamines and N,N-bis(polyfluoroalkyl)amines, via N-polyfluoroalkylation of sulfonamides and phthalimide derivatives using sulfuryl fluoride (SO2 F2 ). The in situ formation of polyfluoroalkyl fluorosulfonates from commercially available fluorinated alcohols and economical sulfuryl fluoride is highly advantageous given that some polyfluoroalkyl halides are ozone-depleting substances (ODS) regulated by the Montreal protocol. This general method is applied to the polyfluoroalkylation of a variety of sulfonamides, N-sulfonyl carbamates and phthalimide with a wide tolerance of functional groups. The process thus provides viable access for industry to N-(polyfluoroalkyl)anilines as well as primary and secondary N-(polyfluoroalkyl)amines, which are very valuable but not easily accessible building blocks for life science applications.
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