Methylation of indazoles and related reactions

Abstract

When methylated under neutral conditions, 4-, 6- and 7-nitroindazole gave the 2-methyl derivatives as the main products, whereas 5-nitroindazole formed mainly the 1-methyl derivative. On methylation under acidic conditions, 6-nitroindazole yielded only the 1-methyl derivative and 5-nitroindazole solely the 2-methyl derivative. 6-Hydroxyindazole was methylated to give 6-methoxyindazole and 6-hydroxy-2-methylindazole. 1,2-Dimethylindazoline was conveniently synthesised in high yield from 3-chloroindazole. Treatment of 6-nitroindazole with formalin in methanolic hydrochloric acid at 60° gave solely 1-methoxymethyl-6-nitroindazole.