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.

本研究通过亚铁离子(Fe²+)作用于苯甲醛与2-吡啶甲胺经原位缩合反应生成的亚胺动态库(dynamic library of imines)，意外得到了咪唑并[1,5-a]吡啶衍生物(imidazo[1,5-a]pyridine derivative)。该反应产物可便捷分离，是唯一从色谱柱(chromatographic column)中洗脱得到的含氮产物。本研究提出了该反应的机理，并探讨了亚铁离子对这一复杂反应序列各步骤所产生的协同动力学与热力学效应。研究发现，所添加的金属阳离子为亚铁离子这一属性，对咪唑并[1,5-a]吡啶衍生物的生成及其在反应混合物中的占比均起到关键作用。在评估电子效应(electronic effects)时发现，仅当醛类反应物上带有适度给电子基团或适度吸电子基团时，方可获得令人满意的反应收率。针对对甲氧基苯甲醛(p-OCH3 benzaldehyde)与对硝基苯甲醛(p-NO2 benzaldehyde)，未检测到任何咪唑并[1,5-a]吡啶衍生物生成。