Abstract

4,9-Dihydro-3H-β-carboline and 6-methoxy-4,9-dihydro-3H-β-carboline were subjected to catalyst-free one-pot α-arylation with 1- or 2-naphthol, 6-hydroxyquinoline or 5-hydroxyisoquinoline as N-containing analogues via direct aza-Friedel-Crafts reactions. The procedure was then extended to other electron-rich aromatic compounds, such as indole or indole-2-carboxylic acid, to yield new indole γ-amino acid derivatives containing -β carboline skeleton. All the reactions were performed both under neat conditions and with microwave irradiation. The reaction of 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole and benzaldehyde with 1-naphthol as nucleophile led to the formation of the N-alkylated compound as a single product, whereas the reaction with 2-naphtol resulted in the two possible α-arylated/N-alkylated products, in a ratio depending on the reaction conditions.

Keywords: β-Carboline, Indole, Naphthol, Aza-Friedel-Crafts alkylation, modified Mannich reaction, Microwave reaction.

Graphical Abstract