Microwave-Assisted Multicomponent Synthesis of Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives

Abstract

A microwave procedure was efficiently applied to the synthesis of a series of heteropolycyclic compounds with known or potential biological activities. Antitumor amide 3was obtained in a few minutes and with high yields through a solventless, one-pot cyclization, followed by treatment with the suitable amine. This method was also used to access tetracyclic aza-compounds 5/6, where their selective formation as N,N-syn and N,N-anti regioisomers was investigated under a solventless condition, or by changing the solvent, in the presence of solid supports and a catalytic amount of ecofriendly metal salts. Thermal access to similar polycyclic compounds recently reported under conventional heating by using the preformed pyridinium or isoquinolinium ylides was improved in this instance by microwave irradiation and extended to the synthesis of diaza-esters. In any case, the one-pot, three-component cyclization was more atom-efficient than the N-ylide sequence.

Keywords:

• Heterocyclic cyclization
• microwave-assisted synthesis
• one-pot synthesis
• regioselectivity

ACKNOWLEDGMENTS

The authors thank A. Sterni, M. Rossi, and D. Avi, University of Trento, for recording mass, UV/vis, and IR spectra, respectively.

Notes

^a For py/EAA sequence: 80 °C, 4 h, in EtOH when metal salts were used;^{[ 7 ]} for ylide sequence: in CH₃CN, 50 °C, 24 h.

^b In the presence of 0.05 g of solid support.

^c Using the dry metal chelate previously obtained by stirring 4 with the metal salt (0.3 equiv.) in EtOH, 1 h.

^d 4 (0.01 g, 1 mol. equiv.), EAA (1.3 equiv.), pyridine (6.2 equiv.), 540 W, 4–6 min, 110–140 °C.

^e 4 (0.01 g, 1 mol. equiv.), pyridinium salt 9 (1.1 equiv.), K₂CO₃ (3.5 equiv.), or the system otherwise specified, under heating^{[ 10 ]} or by irradiation at 230 W, 15 min.

^a–d As described in Table 1, with isoquinoline instead of pyridine.

^e 4 (0.01 g, 1 mol. equiv.), 11 (1.1 equiv.), K₂CO₃ (3.5 equiv.), 230 W, 15 min.