Abstract
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 (NaH2PO4 and H2SO4). 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.
Highlights
Our method[1] developed previously allows the efficient, industrially feasible, and selective, Pd-catalyzed heterogeneous catalytic hydrogenation of nitriles to the corresponding primary amines in liquid phase
The reduction of benzonitrile (BN) to benzylamine (BA) was carried out over palladium on different supports, in two immiscible solvents, applying a medium acidic additive (NaH2PO4), under mild conditions (30 °C, 6 bar), and a very pure product (>99%) was obtained without any purifying procedures.[1]. This method was applied in the hydrogenation of benzyl cyanide (BC) to 2-phenylethylamine (PEA), but the complete conversion of BC was accompanied by lower primary amine selectivity (45%) and isolated yield (40%).[2]
By adapting the aforementioned reduction process modified slightly, the liquid-phase catalytic hydrogenation of 3-phenylpropionitrile (PPN), which belongs to the homologous series of BN and BC, to 3-phenylpropylamine (PPA) was examined in detail
Summary
Our method[1] developed previously allows the efficient, industrially feasible, and selective, Pd-catalyzed heterogeneous catalytic hydrogenation of nitriles to the corresponding primary amines in liquid phase. The reduction of benzonitrile (BN) to benzylamine (BA) was carried out over palladium on different supports, in two immiscible solvents (dichloromethane/water), applying a medium acidic additive (NaH2PO4), under mild conditions (30 °C, 6 bar), and a very pure product (>99%) was obtained without any purifying procedures.[1] Later, this method was applied in the hydrogenation of benzyl cyanide (BC) to 2-phenylethylamine (PEA), but the complete conversion of BC was accompanied by lower primary amine selectivity (45%) and isolated yield (40%).[2]. By adapting the aforementioned reduction process modified slightly, the liquid-phase catalytic hydrogenation of 3-phenylpropionitrile (PPN), which belongs to the homologous series of BN and BC, to 3-phenylpropylamine (PPA) was examined in detail. It plays the most significant role in the pharmaceutical industry because it can be applied to produce carboxypeptidase B (CpB) enzyme inhibitors,[7] antimuscarinic drugs,[8] or potential anticancer agents.[9]
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