Lévay Krisztina, Tóth Kamilla Dóra, Kárpáti Tamás, Hegedűs László
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8, H-1111 Budapest, Hungary.
ACS Omega. 2020 Mar 4;5(10):5487-5497. doi: 10.1021/acsomega.0c00125. eCollection 2020 Mar 17.
A previously developed and industrially feasible process for selective, Pd-mediated, liquid-phase heterogeneous catalytic hydrogenation of nitriles to primary amines was extended to the reduction of 3-phenylpropionitrile (PPN) to 3-phenylpropylamine (PPA). PPN, which belongs to the homologous series of benzonitrile (BN) and benzyl cyanide (BC), was hydrogenated under mild reaction conditions (30-80 °C, 6 bar), over Pd/C, in two immiscible solvents (dichloromethane/water) and using acidic additives (NaHPO and HSO). Although relatively high conversion (76%) was achieved, the selectivity to PPA (26%) and its isolated yield (20%) were lesser than those in the case of the hydrogenation of BN or BC reported earlier. However, the purity of PPA was >99% without using any purification method. Quantum chemical calculations using a density functional theory (DFT) method were performed to compare the adsorption interactions of the different imine intermediates on palladium, as well as to clarify the differences observed in the primary amine selectivity. PPA is a valuable intermediate for the synthesis of carboxypeptidase B enzyme inhibitors, antimuscarinic drugs, or potential anticancer agents in the pharmaceutical industry.
一种先前开发的、具有工业可行性的、用于腈选择性、钯介导的液相加氢制伯胺的多相催化过程扩展至将3-苯基丙腈（PPN）还原为3-苯基丙胺（PPA）。PPN属于苯甲腈（BN）和苄基氰（BC）的同系物系列，在温和反应条件（30-80℃，6巴）下，于Pd/C上，在两种不互溶的溶剂（二氯甲烷/水）中并使用酸性添加剂（NaHPO和HSO）进行氢化反应。尽管实现了相对较高的转化率（76%），但PPA的选择性（26%）及其分离产率（20%）低于先前报道的BN或BC氢化反应中的情况。然而，PPA的纯度在未使用任何纯化方法的情况下大于99%。采用密度泛函理论（DFT）方法进行了量子化学计算，以比较不同亚胺中间体在钯上的吸附相互作用，并阐明在伯胺选择性方面观察到的差异。PPA是制药工业中合成羧肽酶B酶抑制剂、抗毒蕈碱药物或潜在抗癌剂的有价值中间体。
