Hydrogenation of nitriles to primary amines with heterogeneous catalysts under liquid-phase continuous-flow conditions is described. Newly developed polysilane/SiO2-supported Pd was found to be an effective catalyst and various nitriles were converted into primary amine salts in almost quantitative yields under mild reaction conditions. Interestingly, a complex mixture was obtained under batch conditions. Lifetime experiments showed that this catalyst remained active for more than 300 h (TON≥10 000) without loss of selectivity and no metal leaching from the catalyst occurred. By using this continuous-flow hydrogenation, synthesis of venlafaxine, an antidepressant drug, has been accomplished.
Keywords: continuous flow; fine chemical synthesis; heterogeneous catalysis; hydrogenation; nitriles.