Amidoalkylation reactions of anilines. A direct synthesis of benzodiazepines
Intermolecular amidoalkylation reactions on aromatic rings constitute an effective strategy for the construction of heterocyclic c0mpounds.l A variety of substituents, including nitro groups, can be accommodated on the aromatic ring. However, anilines or acetanilides react with acyl iminium ions to afford mixtures of products in only modest yields.2 Moreover, the reactions with both o- and p-toluidine yield products wherein the position of substitution of the electrophile is directed by the methyl groupq3 This reactivity profile is due to deactivation by the iminium salt that is produced either by protonation in an acid-catalyzed reaction or by complexation with the Lewis acid catalyst.
Reprinted (adapted) with permission from The Journal of Organic Chemistry, 48(17); 2936-2937. Doi: 10.1021/jo00165a034. Copyright 1983 American Chemical Society.