Continuous hydrogenation of nitriles to primary amines with high selectivity in flow

Hydrogenation of nitriles is considered to be an atom-economic route in the pharmaceutical industry to synthesize amines, crucial building blocks in the fine chemical industry. However, high selectivity of primary amines and high efficiency are difficult to achieve in conventional batch reactors due to that severe back mixing and poor mass transfer performance producing a mixture of secondary, tertiary amines and hydrogenolysis byproducts. In this study, a continuous flow system based on a micro-packed bed is developed for the hydrogenation of nitriles to primary amines and the hydrogenation of benzonitrile (BN) is selected as the model reaction. With the optimal reaction conditions, maximal conversion of BN (100%) and selectivity to benzylamine (99.1%) are obtained. The reaction kinetics is also determined after the internal and external diffusion limitations are eliminated. Moreover, the continuous flow system based on the micro-packed bed exhibited remarkable substrate suitability in other nitrile hydrogenation systems.