Lewis acid/acetic acid-catalysed electrophilic amidation of simple arenes with O-acetyl acetohydroxamic acid

Abstract

Electrophilic arene CH amination constitutes an intrinsically more atom- and step-economical pathway towards arylamines than CX → CN methods. However, most literature examples are restricted to arenes with extensive directing groups (DG) and/or nitrogen coupling partners with large leaving groups (LG). Moreover, only few cases of EAs using cheap metals (e.g., Fe) have been reported. Herein, we demonstrate the catalytic activity of various Lewis acids in the electrophilic amidation of simple arenes with O-acetyl acetohydroxamic acid in acetic acid. With 5 mol% FeIII(citrate)·H2O, up to 27 % yield was achieved, whereas 5 mol% BiCl3 gave up to 31 % yield. Instability of the amidation agent and product inhibition were identified as the yield-limiting factors. The observed regioselectivity, as well as kinetic and spectroscopic data suggest an electrophilic aromatic substitution mechanism, in which acetic acid and the Lewis acid generate a highly electrophilic species from AcNHOAc.