An Efficient Synthesis of New Fused Oxazinocarbazoles

Background: Oxazinocarbazoles are molecules of particular interest as they possess a broad spectrum of pharmacological activities, such as antiproliferative, antibacterial, antimalarial and antiplasmodial activities. Despite few synthetic methods reported in the literature for their synthesis, there appear to be no reports on the synthesis for oxazinocarbazole fused from simple starting materials. Method: The Mannich condensation of 4-hydroxycarbazole, aldehyde and secondary cyclic amine was carried out to get the corresponding carbazole Mannich base and its subsequent copper(II)acetate catalyzed intramolecular oxidative α-functionaliation of tertiary amine to achieve 1,3-oxazine core. The structures of obtained carbazole Mannich bases and fused oxazinocarbazoles were confirmed by NMR, IR and mass spectra. Results: Various substituted carbazole Mannich bases such as fluoro-, nitro-, dimethoxy-, trimethoxyderivatives reacted smoothly in the presence of copper(II)acetate to give the corresponding fused oxazinocarbazoles in good yields. Conclusion: We have developed a two step method for the synthesis of new oxazino[5,6-c]carbazole derivatives in good yields. This protocol is simple, atom-economic and proceeds smoothly under mild reaction conditions.