Lewis Acid Promoted Friedlander Condensation Reactions between Anthranilonitrile and Ketones for the Synthesis of Tacrine and its Analogues

The scope of Lewis acid-promoted cyclodehydratation reactions between anthranilonitrile and several ketones, to afford tacrine and its derivatives, was expanded to include the use of various metal chloride salts not reported in the literature. The ability of the Lewis acids to effectively promote the cyclodehydratation between anthranilonitrile and cyclohexanone as the ketone was found to be the following order: InCl3 > AlCl3 similar to BF3 center dot Et2O > FeCl3 > BiCl3 similar to SbCl3 similar to SnCl2 center dot 2H(2)O. The reactions were performed under both solvent and solvent-free conditions in good to excellent yields. Other Lewis acids screened, such as RuCl3, CeCl3, NiCl2, CoCl2 center dot 2H(2)O and CsCl were not effective.