Lewis acid promoted Friedländer condensation reactions between anthranilonitrile and ketones for the synthesis of tacrine and its analoques

Abstract

Nesse trabalho estudou-se a reação de ciclodesidratação entre antranilonitrila e várias cetonas na presença de diferentes ácidos de Lewis não reportados na literatura, para a obtenção de 9-amino-1,2,3,4-tetrahidroacridinas. As reações de ciclodesidratação foram realizadas em condições térmicas empregando-se diferentes solventes e também na ausência de solvente, seguidas de hidrólise alcalina, levando à obtenção dos produtos em bons a excelentes rendimentos após isolamento.

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 ~ BF3.Et2O > FeCl3 > BiCl3 ~ SbCl3 ~ SnCl2.2H2O. 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, CoCl2.2H2O and CsCl were not effective.