Synthesis of 2,3-dihydro-1H-pyrrolo[1,2-a]indoles by intramolecular nucleophilic aromatic substitution

Abstract

Condensation of 2-methoxy-Δ¹-pyrroline (3) with 2-bromo-5-methoxy-4-methylphenylacetonitrile (6)[prepared from 3-hydroxy-4-methylbenzaldehyde (17) in four steps] gave α-(2-bromo-5-methoxy-4-methylphenyl)-α-pyrrolidin-2-ylideneacetonitrile (10). Several other α-aryl-α-pyrrolidin-2-ylideneacetonitriles [(8), (9), and (11)] were also synthesised from the corresponding phenylacetonitriles [(4), (5), and (7)]. (Z)-α-Aryl-α-pyrrolidin-2-ylideneacetates [(14)–(16)] were prepared by similar condensation reactions or by ethanolysis of the nitriles (8) and (10). Treatment of compounds (9), (10), and (16) with sodium hydride and copper(I) bromide in dimethylformamide gave quantitatively the 2,3-dihydro-1H-pyrrolo[1,2-a]indole-9-carbonitriles (21)–(23). Heating the nitriles (21) and (22) with nickel–aluminium alloy in aqueous acetic acid yielded the corresponding aldehydes (24) and (25). 2,3-Dihydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole-9-carbaldehyde (25) was further converted via the 8-nitro-compound (26) into the 5,8-quinone (28).