Kinetics and Pathway Analysis Reveals the Mechanism of a Homogeneous PNP-Iron-Catalyzed Nitrile Hydrogenation

Nitrile hydrogenation via the in situ-generated PNP-Fe^II(H)₂CO (1) catalyst leads to a previously inexplicable loss of mass balance. Reaction kinetics, reaction progress analysis, in situ pressure nuclear magnetic resonance, and X-ray diffraction analyses reveal a mechanism comprising reversible imine self-condensation and amine–imine condensation cascades that yield >95% primary amine. Imine self-condensation has never been reported in a nitrile hydrogenation mechanism. The reaction is first order in catalyst and hydrogen and zero order in benzonitrile when using 2-propanol as the solvent. Variable-temperature analysis revealed values for ΔG_298 K^⧧ (79.6 ± 26.8 kJ mol^–1), ΔH^⧧ (90.7 ± 9.7 kJ mol^–1), and ΔS^⧧ (37 ± 28 J mol^–1 K^–1), consistent with a solvent-mediated proton-shuttled dissociative transition state. This work provides a basis for future catalyst optimization and essential data for the design of continuous reactors with earth-abundant catalysts.