An Unusual Fischer Indole Synthesis with 4-Keto Acids: An Indole Incorporating the Terminal Hydrazine Nitrogen

Article abstract of DOI:10.1021/jo00296a063

During preparation of a pharmaceutically active, N-benzylated indole derivative from 4-keto acid and N1-benzylated phenylhydrazine precursors, the N-unsubstituted indole analogue arose as a significant byproduct.The proportion of debenzylated indole was greater with α-alkylated rather than straight-chain keto acids and the byproduct was fully suppressed when a keto ester was substituted for the keto acid.The benzylic group was shown to have eliminated as the amine and 15N label incorporation demonstrated terminal phenylhydrazine nitrogen incorporation in the indole byproduct only, an exception to the usual course of the Fischer indolization reaction.A ring-chain equilibration in the ketimino acid intermediate is proposed to account for the competing pathway.