Solvent-Mediated and Interface-Engineered Ni/NiO@CN Catalysis for the Conversion of Vanillin into Drug Intermediates Vanillonitrile

Vanillonitrile (VN), a valuable pharmaceutical intermediate, is traditionally synthesized through toxic cyanide-based routes. Herein, we report a green, two-step approach for VN synthesis starting from vanillin (VL), a lignin-derived platform molecule. The process integrates solvent-assisted condensation and catalytic pyrolysis, supported by mechanistic insights from density functional theory (DFT). In the first step, vanillin azine (VA) is selectively synthesized in ethanol, with solvent polarity and noncovalent interactions governing reaction kinetics and selectivity. Pyrolysis experiments and quantum chemical calculations reveal that hydrogen-transfer-induced N–N bond cleavage is the dominant route for VA conversion. A heterostructured Ni/NiO@CN catalyst featuring interfacial Ni–N sites was developed to lower activation energy and promote electron redistribution, enhancing VN selectivity to 57.2%. Surface potential and spin polarization analysis further confirmed efficient electron transfer pathways. This work provides a sustainable and efficient route to nitrogen-containing fine chemicals from renewable lignin and offers mechanistic guidance for future biomass-based catalytic designs.