Regioselective Friedel—Crafts Alkylation of Anilines and Amino-Substituted Heteroarenes with Hexafluoroacetone Sesquihydrate.

A variety of arenes, including anilines, pyrroles, indoles, aminooxazoles, aminothiazoles, aminoquinolines, and aminopyridines, underwent regioselective Friedel−Crafts alkylation in neat hexafluoroacetone sesquihydrate in a broad range of temperatures, reaction times, and yields (2%−94%) depending strongly on the electron density of the substrate. Prior N,N-dibenzylation of aniline and 2-aminopyridine strongly promoted substrate reactivity and resulted in higher yields (> 80%). The described Friedel−Crafts alkylations in hexafluoroacetone sesquihydrate occurred regioselectively at the para-positions of anilines or at the positions β to the sp2-hybridized nitrogen atom in heteroarenes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)