Microwave assisted synthesis of 3-aminoindole-2-carbonitriles from anthranilonitriles via N-unprotected 2-(cyanomethylamino)benzonitriles

Abstract

Anthranilonitrile 3a, 4,5-dimethoxyanthranilonitrile 3b and 5-nitroanthranilonitrile 3c, react with paraformaldehyde, KCN and ZnCl2 in acetic acid under acid catalysis (H2SO4) in a sealed tube at ca. 55 °C to give the corresponding 2-(cyanomethylamino)benzonitriles 4a-c in 96, 86 and 57% yields, respectively. Thorpe-Ziegler cyclisation of the N-unprotected 2-(cyanomethylamino)benzonitriles 4a-c with K2CO3 in EtOH at elevated temperatures and pressures using either microwave heating or conventional heating in a sealed tube gives 3-amino, 3-amino-5,6-dimethoxy, and 3-amino-5-nitroindole-2-carbonitriles 2a-c in moderate to good yields. All new compounds are fully characterised. © 2009 Elsevier Ltd. All rights reserved.