Studies on Models for Tetrahydrofolic Acid. I. The Condensation of Formaldehyde with Tetrahydroquinoxaline Analogs

To investigate the mechanisms of tetrahydrofolic acid catalyzed one carbon unit transfers, we have synthesized several tetrahydroquinoxaline analogs. A kinetic investigation of the condensation with formaldehyde of one of these models reveals the intermediacy of the iminium cation as a steady-state species and the importance of general catalysis in formation of the imidazolidine ring, the latter a model for 5,10-methylenetetra-hydrofolic acid. The relevance of these results to the mechanism of one carbon unit transfers and the importance of certain structural and electronic features in the actual cofactor are discussed.