Reaction of indigo malonic ester with dimethyl sulfate

Abstract

Indigo malonic ester (I), the product of indigo condensation with malonic ester, a representative of the class of 6,13-dioxopyrido[1,2-a;3,4-b]diindoles, has been known since the beginning of the previous century; it has been fi rst obtained in 1926 alongside the product of indigo condensation with phenylacetic acid and its N-acyl derivatives [1]. The chemical properties of these compounds were not practically further examined. Yet the pyrido[1,2-a;3,4-b]diindole system is the structural skeleton of a series of marine alkaloids of a high biological action, e.g., fascaplysin from the sponge Fascaplysinopsis sp. [2].We examined the reaction of indigo malonic ester (I) with dimethyl sulfate. The reaction was carried out in DMF in the presence of sodium hydride. It was initially presumed that the indigo malonic ester being an ambidente nucleophile would form a mixture of N-and O-methylation products. However unexpectedly alongside the product of the N-methylation II we isolated a substituted pyrido [3,4-b]indole III (Scheme 1).We failed to convert fully compound II into III, and increasing the reaction duration and the excess of dimethyl sulfate did not affect the yield of compound III.The sequence of transformations leading to compound III may be rationalize as follows. Evidently fi rst the ambidente anion originating from initial pyridodiindole I at the action of sodium hydride suffers the O-methylation. The product of the О-methylation in the presence of excess dimethyl sulfate is methylated again at the nitrogen Scheme 1.