CeO2-catalyzed one-pot selective synthesis of N-alkyl amides from nitriles, amines and water

Among 13 kinds of metal oxides, ceria (CeO2) shows the highest catalytic activity for one-pot selective synthesis of the secondary amide from 2-cyanopyridine and n-octylamine as a test reaction. CeO2 acts as a reusable heterogeneous catalyst, and it is effective for the secondary amide formation from various nitriles and amines in high yields (73% to >99%). Pharmacologically important products such as heteroaromatic N-alky amides and morpholine amide are effectively synthesized, indicating that CeO2 can be a practically useful catalyst. A proposed mechanism includes (1) hydration of nitrile to the primary amide and (2) transamidation of the primary amide with amine as the rate-limiting step. This reaction mechanism provides a reason why the present catalytic system gives high selectivity.

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► First example for one-pot N-alkyl amides synthesis from heteroaromatic nitriles and amines under neutral conditions.
► Commercial CeO2 as the most active catalyst among various metal oxides.
► Effective synthetic method of pharmaceutically important heteroaromatic amides.