3,4-Dimethoxypyridine-2-carbaldehyde in the synthesis of quinazolin-4(3H)-ones: partial demethylation at the dehydrogenation step

Abstract

The cyclocondensation of 2-aminobenzamide with 3,4-dimethoxypyridine-2-carbaldehyde affords a mixture of 2-(3,4-dimethoxypyridin-2-yl)-2,3-dihydroquinazolin-4(1H)-one and its open-chain tautomer. The dehydrogenation of these compounds with benzoquinones (DDQ, chloranil) as oxidants, giving 2-(pyridin-2-yl)quinazolin-4(3H)-ones, is accompanied by the demethylation of the methoxy group at the C(3) position of the 2-pyridyl moiety. When using 2-methoxy- or 2,3,4-trimethoxybenzaldehydes as deaza analogs of this aldehyde, the demethylation does not occur in the last step regardless of the nature of the oxidant.