Chemistry of 8-chloroberberine

8-Chloroberberine (V), obtained by treatment of oxyberberine (I) with phosphorus oxychloride, is a reactive intermediate. Treatment with ammonia, methylamine, n-propylamine, aniline, and p-toluidine furnished the 8-berberinylidene derivatives IV and VII-X. Reaction of V with malononitrile, ethyl acetoacetate, and ethyl malonate anions yielded the 8-berberinylidene derivatives XII-XIV. Acid hydrolysis of XIV gave 8-berberinylacetic acid (XV) whose reduction provided 8-canadinylacetic acid (XVI). Grignard reagents react readily with V. Methylmagnesium iodide, ethylmagnesium iodide, and benzylmagnesium iodide led to 8,8-dimethyldihydroberberine (XVII), 8,8-diethyldihydroberberine (XIX), and the benzyl derivative XX, respectively. Sodium borohydride reduction of XX gave rise to 8-benzylcanadine (XXI).