Some Items of Interest to Process R&D Chemists and Engineers

The direct synthesis of nitriles from abundant, stable, and inexpensive carboxylic acids remains highly challenging due to significant thermodynamic and kinetic barriers.Inspired by enzymatic nitrile synthase activity, Liu, Jiao, and co-workers developed a practical methodology using urea as a nitrogen source and Mg/Pd cocatalysis (Nat.Catal., DOI: 10.1038/ s41929-025-01446-y).This approach exhibits broad functional group tolerance�including alkenyl, alkynyl, alcohol, ether, epoxy, carbonyl, ester, amide, and heterocycles�demonstrated across more than 70 examples, including bioactive molecules.The process is scalable to 10 g with reduced Pd loading (3 mol %) and enables additive recycling (p-hydroxybenzoic acid).Using 15 N-labeled urea, late-stage isotopic labeling was achieved.Mechanistic studies suggest initial Mg-catalyzed coupling of urea and carboxylic acid to form a carbamic carboxylic anhydride followed by 1,3 O→N acyl transfer and decarboxylation to afford an amide intermediate.Subsequent Pd-mediated activation and nucleophilic attack lead to nitrile formation alongside acetamide.