Lewis Acid Catalyzed Reaction of Cinnamanilides: Competition of Intramolecular and Intermolecular Friedel-Crafts Reaction

Abstract

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-hyddroxyquinolin-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.