Über neue und über verbesserte Wege zum Aufbau von pharmakologisch wichtigen Aminen. VII. Über die Synthese von sekundären und tertiären Aminen durch Hydrierung von Nitrilen

The Reductive Amination of Aldehydes and Ketones and the Hydrogenation of Nitriles: Mechanistic Aspects and Selectivity Control

“…[24] However, it was also postulated that NH 3 is first eliminated from the gem-diamine to form an enamine intermediate that is subsequently hydrogenated to the tertiary amine. [25] A study of the hydrogenation of lauronitrile over a Co catalyst furnished evidence that the secondary amine is not formed in the Co-catalysed hydrogenolysis of the gem-diamine, since the secondary imine accumulates in the reaction mixture (as shown by chromatography and spectroscopy) and the secondary amine is formed only at the end of the reaction by hydrogenation of the imine.…”

“…[28] This would be in agreement with the mechanism proposed by Kindler and Hesse for the hydrogenation of nitriles. [24] According to them, tribenzylamine could be obtained in the reduction of benzonitrile via hydrogenolysis of the gem-diamine intermediate formed from the addition of dibenzylamine to benzylimine (Scheme 8).…”

The Reductive Amination of Aldehydes and Ketones and the Hydrogenation of Nitriles: Mechanistic Aspects and Selectivity Control

“…[24] However, it was also postulated that NH 3 is first eliminated from the gem-diamine to form an enamine intermediate that is subsequently hydrogenated to the tertiary amine. [24] However, it was also postulated that NH 3 is first eliminated from the gem-diamine to form an enamine intermediate that is subsequently hydrogenated to the tertiary amine.…”

“…The fact that the reduction of benzonitrile, over Pd and Pt catalysts, did not yield tribenzylamine served as an argument in favour of the enamine mechanism. [24] According to them, tribenzylamine could be obtained in the reduction of benzonitrile via hydrogenolysis of the gem-diamine intermediate formed from the addition of dibenzylamine to benzylimine (Scheme 8). As the enamine is not possible because of the absence of hydrogen atoms in the a-position of the cyano group, the tertiary amine can not be formed (Scheme 8).…”

Synthesis by Reduction

“…The crucial step is the transimination of the intermediate imine 35 with dimethylamine to give an iminium ion, which is reduced to give the amine 55 (Scheme 13). [85][86][87] Scheme 13 Selective Syntheses of Primary and Tertiary Amines [78,82,85] (49): [71] 10% Pd/C (2.0 g) was added to a soln of nitrile 48 (10.0 g, 61.3 mmol) in 95% EtOH (150 mL) and concd HCl (10 mL), and the mixture was hydrogenated at 2.7 atm in a Parr shaker apparatus for 10 h at rt. The catalyst was removed by filtration and the solvent was evaporated under reduced pressure.…”