A facile synthesis of 4-, 6- and 7-formyl-1H-indole-2-carboxylates: The CH₂SO₃H functionality as a masked formyl group

Abstract

The valuable new synthetic intermediates, ethyl 4-, 6-and 7-formyl-1H-indole-2-carboxylates (10, 11, 12) were prepared from 2-ethoxycarbonyl-1H-indole-4-, 6-and 7-methanesulfonic acids (1, 2, 3), respectively. The transformation of sulfomethyl group to formyl function was accomplished through elimination of SO 2 to yield ethyl 4-, 6-and 7-chloromethyl-1H-indole-2-carboxylates (4, 5, 6), hydrolysed to ethyl 4-, 6-and 7-hydroxymethyl-1H-indole-2-carboxylates (7, 8, 9), then oxidized to aldehydes (10, 11, 12). Protection at N1 of indole was not necessary. A marked increase in the rate of hydrolysis of 7-chloromethyl-indoles compared to that of 4-and 6-(chloromethyl)indoles was observed.