Lewis acid catalyzed reaction of cinnamanilides: Competition of intramolecular and intermolecular Friedel-Crafts reaction

Article abstract of DOI:10.1055/s-1997-1505

The first intermolecular Friedel-Crafts reaction of benzene leading to the formation of 3,3-diphenylpropionanilide 7 is described. 4-Methoxyaniline was reacted with cinnamoyl chloride to give 4-methoxycinnamanilide (5a), the treatment of which with aluminum (III) chloride in chlorobenzene at 120 °C or in benzene at 80 °C afforded exclusively 6-hydroxyquinolin-2(1H)-one (3a) or 4'-hydroxy-3,3-diphenylpropionanilide (7a), respectively. The formation of 7a rather than 3a in benzene indicated that an intermolecular Friedel-Crafts reaction occurred prior to the relatively more facile intramolecular ring cyclization. This intermolecular Friedel-Crafts reaction was observed during the attempted ring cyclization of cinnamanilide and its methoxy derivatives in aluminum (III) chloride/benzene. Preparation of 3a can also be achieved in 17% overall yield via the N-oxidation of 6-hydroxyquinoline followed by acetylation and hydrolysis.