Synthesis of Some Novel Heteroannelated Chromones by Basic Rearrangement of 6-Methylchromone-3-Carbonitrile

Abstract

A new series of chromeno(2,3-b)pyridines was efficiently synthesized via chemical transformations of 6-methylchromone-3-carbonitrile with some methylene-active compounds bearing -CH2-CN and -CH2-CO- moieties. Some heteroannelated chromeno(2,3-b)pyridines were also synthesized. The structures of the new synthesized products were deduced on the basis of their analytical and spectral data. including anticancer (2-4), antitumor (5), antiproliferative (6), neuroprotective (7), HIV-inhibitory (8, 9), antimicrobial (10, 11), antioxidant (12), anti-inflammatory (13), and antibiotic (14). Heteroannelated chromones showed significant biological activities including pharmacological (15), antiplatelet (16), antiallergic (17), antiangiogenic (18), antirheumatic (19), antibacterial (20), anti-inflammatory, and analgesic (21). 3-Substituted chromones have been reported to be used as a very good building blocks for the synthesis of various heterocycles (22-26). Introduction of an electron-withdrawing cyano group at position 3 of the chromone system changes crucially the reactivity of the pyrone ring with respect to nucleophiles and provides a broad synthetic potential of 3-cyanochromones (27-31). The present work was aiming at studying the chemical reactivity of 6-methylchromone-3-carbonitrile (1) towards some carbon nucleophiles under basic conditions using 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as a basic catalyst, with the hope of constructing a novel series of heteroannelated chromeno(2,3-b)pyridines. In our previous work (23), 6-methylchromone-3-carbonitrile (1) showed a different behavior than chromone-3-carbonitrile in reactions with benzimidazol-2-ylacetonitrile, as methylene-active nitrile. Thus, the present work was aimed at studying the chemical transformations of 6-methylchromone-3-carbonitrile (1) with a variety of methylene-active compounds bearing -CH2-CN and -CH2-CO- groups. The reaction of 6-methyl- chromone-3-carbonitrile (1) with malononitrile in absolute ethanol containing DBU as a basic catalyst afforded 2-amino-7-methyl-5-oxo-5H-chromeno(2,3-b)pyridine-3-carbonitrile (2) as yellow crystals. Compound 2 may be synthesized via deprotonation of malononitrile followed by Michael addition at the C-2 position of the