Synthesis of some substituted α-carbolines

Abstract

α-Carboline-1-oxide (I) with acetic anhydride gives 2-acetoxy-9-acetyl-α-carboline; with dimethyl sulphate it gives the salt (II; R = H). The latter salt is converted by alkali into the anhydronium base (III; R = OMe). The salt (II; R = H) and the base (III; R = OMe) are converted by sufficiently basic nucleophilic reagents into 2-substituted α-carbolines; the salt (II; R = Me) reacts even more readily with basic nucleophilic compounds.

Diethyl malonate and ethyl acetoacetate with (III; R = OMe) give the ester (V; R = CH₂CO₂Et). The acid (V; R = CH₂CO₂H) is readily decarboxylated to 2-methyl-α-carboline.

The benzotriazole (IV; R¹= NO₂, R²= H) in hot phosphoric acid does not give 3-nitro-α-carboline, but gives instead 2-nitropyrido[1,2-a]benzimidazole (VIII); the latter compound is also obtained by treating the amine (VII) with hydrochloric acid. However the benzotriazole (IV; R¹= NH₂, R²= H) is converted by phosphoric acid into 3-amino-α-carboline; the benzotriazole (IV; R¹= H, R²= CO₂H) is similarly converted into α-carboline-4-carboxylic acid. The preparation and proof of orientation of some 6-substituted α-carbolines are described.

The ¹H n.m.r. spectra of 2-, 3-, and 4-substituted α-carbolines are discussed.