EXPERIMENTAL AND QUANTUM-CHEMICAL STUDY OF NUCLEOPHILIC SUBSTITUTION MECHANISM IN BERBERINE
Keywords:berberine, berberrubine, alkylamination, catalytic hydrolysis, DFT calculations
Principal differences in the interaction mechanisms of alkaloid berberine with primary and secondary amines were investigated experimentally and by quantum-chemical calculations according to density functional theory (DFT/B3LYP) with 6-31G** basis set. The nucleophilic substitution of 9-metoxy group with primary amine was shown to proceed through a stage of σ-complex formation and led to 9-alkylamino derivatives of berberine. Analogous substitution with a secondary amine did not occur due to unfavorable thermodynamic parameters. The secondary amine participated in this reaction not as the attacking nucleophile, but rather as a bifunctional catalyst of berberine hydrolysis to berberrubine. The driving force for all these rocesses was the stabilization of products by hydrogen bonding. Based on the obtained results, we developed a new effective method for the preparation of berberrubine, one of the key intermediates in synthetic transformations of berberine. New 9-monoalkylamino derivatives of berberine containing indole moieties were synthesized.
How to Cite
Burov, O. N.; Kletskii, M. E.; Fedik, N. S.; Kurbatov, S. V.; Lisovin, A. V. Chem. Heterocycl. Compd. 2015, 51, 997. [Khim. Geterotsikl. Soedin. 2015, 51, 997.]
For this article in the English edition see DOI 10.1007/s10593-016-1810-1