Formation of imidazo[1,5-a]pyridine derivatives due to the action of Fe2+ on dynamic libraries of imines

An imidazo[1,5-a]pyridine derivative was unexpectedly obtained through the action of Fe2+ on a dynamic library of imines generated in situ via condensation of benzaldehyde and 2-picolylamine. The reaction product was easily isolated as the only nitrogen-containing product eluted from the chromatographic column. A reaction mechanism is proposed, in which combined kinetic and thermodynamic effects exerted by Fe2+ on the various steps of the complex reaction sequence are discussed. The Fe2+ nature of the added metal cation was found to be pivotal for the achievement of the imidazo[1,5-a]pyridine derivative as well as its amount in the reaction mixture. When the electronic effects were evaluated, gratifying yields were obtained only in the presence of moderately electron-releasing or moderately electron-withdrawing groups on the aldehyde reactant. No traces of imidazo[1,5-a]pyridine derivatives were obtained for p-OCH3 and p-NO2 benzaldehyde.