Studies on the syntheses of heterocyclic compounds. Part 865. A novel synthesis of indole derivatives by intramolecular nucleophilic aromatic substitution

Abstract

Cyclisation of N-(2-bromo-4,5-dimethoxyphenethyl)acetamide (6) afforded 1-acetyl-2,3-dihydro-5,6-dimethoxy-1H-indole (13) by intramolecular nucleophilic aromatic substitution using sodium hydride and cuprous halide in dimethylformamide. The dihydroindoles (14), (15), and (16) were also synthesised from the corresponding amides (8) and (10) and the carbamate (12) in a similar manner. The dihydroindoles (13), (14), and (16) were converted into the indoles (20) and (21) in excellent yield by oxidation and subsequent alkaline hydrolysis. The 2-oxindoles (26) and (27) were also prepared under similar reaction conditions from the phenylacetamide (24) and (25).