Reactions of harmaline (4,9-dihydro-7-methoxy-1-methyl-3H-pyrido[3,4-b]indole) and its derivatives. Part I. Reactions of harmaline with methyl acrylate

Abstract

The existence of an imine–enamine equilibrium in harmaline has been demonstrated by deuteriation studies; thus treatment with electrophilic olefins could bring about either N- or C-alkylation. At elevated temperatures, harmaline reacts with methyl acrylate to give 3,4,6,7-tetrahydro-10-methoxy-2H,12H-indolo[2,3-a]quinolizin-2-one (III). At room temperature, the major product is methyl 4-(3,4-dihydro-7-methoxy-β-carbolin-1-yl)butyrate (XI), which can be cyclized to 2,3,6,7-tetrahydro-10-methoxy-4H,12H-indolo[2,3-a]quinolizine-4-one (IV). With a large excess of methyl acrylate, the major product is methyl 3-(2,3,6,7-tetrahydro-10-methoxy-4-oxo-4H,12H-indolo[2,3-a]quinolizine-1-yl)propionate (XIV), formed along with a minor product resulting from the attack of three molecules of methyl acrylate on harmaline.