3-(Indolyl)-Phthalides and (2-Carboxybenzyl)-Indoles

New chemical and spectral evidence is presented concerning the structures of phthalides derived from fusion of indoles with phthalaldehydic or opianic acids. The phthalides derived from indole and 7-methylindole are assigned the 3-substituted indole structures Ia, If and Ib, Ig. The phthalides derived from skatole and its derivatives are reassigned the 1-substituted indole structures IIa–IIf. The phthalide derived from 2-methylindole and opianic acid, about which conflicting reports appear in the literature, is assigned the 3-substituted indole structure Ih, analogous to the phthalide (Ic) from 2-methylindole and phthalaldehydic acid. New phthalides are described from the reactions of phthalaldehydic acid with 1-methylindole (Id), 1,2-dimethylindole (Ie), 2,3-dimethylindole (IIg) and 1,3-dimethylindole (IIIg). The structures of all the products studied indicate that the tendency to form phthalides at available positions of the indole nucleus is in the order 3 > 1 > 2. Structures VIII and possibly IX are proposed for by-products from the reactions of phthalaldehydic acid with 1-methylindole and skatole, respectively. The (indolyl)-phthalides have been found to undergo hydrogenolysis under low pressure hydrogenation. This constitutes a general synthetic route to (2-carboxybenzyl)-indoles of all three types: 1-, 2- and 3-substituted indoles.