Heterocyclic synthesis from o-halogeno-acids. Part III. Synthesis of 2-methylindole-4-carboxylic acid and related compounds and of some derivatives of 3-phenylisoquinolin-1(2H)-one

Abstract

Condensation of 2-bromo-3-nitrobenzoic acid with acetylacetone in the presence of copper(II) acetate and ethanolic sodium ethoxide gives 2-acetylacetonyl-3-nitrobenzoic acid. Deacetylation with water–dimethyl sulphoxide at 170 °C yields 3-methyl-5-nitroisocoumarin, which is converted by catalytic hydrogenation and alkaline hydrolysis into 2-methylindole-4-carboxylic acid. Similar condensation and reduction reactions yield related compounds including dimethyl 2-methylindole-3,4-dicarboxylate. Tricyclic products are obtained by heating o-phenacylbenzoic acid with 2-amino-1-phenylethanol, ethane-1,2-diamine, and o-phenylenediamine. o-Phenacylbenzoic acid is also converted into 2-substituted 3-phenylisoquinolin-1(2H)-ones, which are cyclised to form dibenzo[a,g]-quinolizin-8-one derivatives and/or oxazolo[2,3-a]isoquinolinylium salts.