PARENT 5(7)-AZACHROMONES AND THEIR PARTIALLY HYDROGENATED DERIVATIVES: SYNTHESIS AND PHYSICOCHEMICAL PROPERTIES

Abstract

An approach to the preparation of hereto unknown parent 5- and 7-azachromones was developed. The key step relied on the NaHmediated condensation of isomeric 2(4)-acetyl-3-hydroxypyridines (obtained from isomeric 3-hydroxypyridine carboxylic acids) with ethyl formate. Physicochemical studies revealed that no significant changes in lipophilicity and slightly higher basicity values were observed upon introduction of the nitrogen atom into the parent chromone; therefore, 5- and 7-azachromones can be used as direct analogs of this classical heterocyclic fragment. The synthetic utility of azachromones was demonstrated by the preparation of a series of 3,4-dihydro-2H-pyrano[3,2-b]pyridines and -[2,3-c]pyridines. The catalytic hydrogenation of the pyranone ring of azachromones was performed for the selective preparation of isomeric azachromanols, which could be oxidized with MnO2 (to azachromanones) or involved into Barton–McCombie deoxygenation (for the synthesis of the non-substituted derivatives).