Synthesis of doryanine and related isoquinolones and isocoumarins

Abstract

4,5-Methylenedioxyhomophthalic acid, which was synthesised in two steps from 2-bromopiperonylic acid, on treatment with dimethylformamide–phosphoric trichloride at 100 °C furnished doryanine-4-carboxylic acid. Decarboxylation afforded doryanine[2-methyl-6,7-methylenedioxy-1 (2H)-isoquinolone]. The same reaction at 0 °C gave an intermediate isochromandione (8a), an alcoholic solution of which on treatment with hydrogen chloride gas furnished a 6,7-methylenedioxyisocoumarin-4-carboxylate acid ester; this also gave doryanine-4-carboxylic acid on heating with aqueous methylamine. The same series of reactions with 4-methoxyhomophthalic acid furnished the corresponding 7-methoxyisoquinolones and isocoumarins.