Alkylation of Ethyl 3-quinolinecarboxylate, Ethyl 4-isoquinolinecarboxylate and Their Derivatives with Grignard Reagents

Abstract

The mechanism of reactions of Grignard reagents toward ethyl 3-quinolinecarboxylate (I), ethyl 4-isoquinolinecarboxylate (II) and their derivatives was estimated by HMO calculations.
Grignard reagents attack preferentially one of the heteroaromatic ring carbons as estimated by HMO calculations. Compounds I and II react with Grignard reagents, RMgX (R=methyl, ethyl, propyl, butyl, phenyl, benzyl), to give, respectively, ethyl 4-substituted-1, 4-dihydro-3-quinolinecarboxylates (III) and ethyl 1-substituted-1, 2-dihydro-4-isoquinolinecarboxylates (V) instead of corresponding alcohols. Oxydation of III and V with potassium permanganate gives ethyl 4-substituted-3-quinolinecarboxylates (VII) and ethyl 1-substituted-4-isoquinolinecarboxylates (VIII). Each of compounds VII further reacts with the Grignard reagent to give a mixture of the 4, 4-disubstituted-1, 4-dihydro-3-quinolinecarboxylate and 3-(α, α-disubstitutedhydroxymethyl)-4-substituted quinoline, while compounds VIII to give only 4-(α, α-disubstitutedhydroxymethyl)-1-isoquinolines.