Aluminium chloride-catalyzed intermolecular vs intramolecular friedel-crafts reaction of acrylanilides and 3-chloropropanamides

Article abstract of DOI:10.1002/jccs.200000018

3-Phenylpropionanilide (4a) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl₃/ benzene, compared with a yield of 39% by the 1,4-conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel-Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3-phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N-phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl₃-catalyzed demethylation to form the ArOAlCl₂ complex which decreased the availability of the π-electron in the N-phenyl aromatic system.