Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a Polysilane/SiO₂‐Supported Palladium Catalyst under Continuous‐Flow Conditions

Abstract

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.

The production of tyramineviathe selective hydrogenation of 4-hydroxybenzyl cyanide over a carbon-supported palladium catalyst

“…19 Illustrating imaginative exploitation of this technology, Saito and co-workers have applied a supported Pd catalyst operating in a continuous ow regime to employ a selective nitrile reduction stage to synthesize the antidepressant drug venlafaxine. 20 In 2016 McMillan and co-workers reported on the hydrogenation of aromatic nitrile compounds over a carbon-supported Pd catalyst. 21 Hydrogenation of benzonitrile to form benzylamine was readily achieved but this was subsequently followed by a hydrogenolysis reaction to produce toluene.…”

Recent Progress in Continuous‐Flow Hydrogenation

“…Nitriles as important chemical materials are widely used in the organic synthesis, for example, as an important source of amino compounds. Newly developed polysilane/SiO 2 ‐supported Pd showed outstanding activity in the hydrogenation of nitriles 61 , as reported by Kobayashi and co‐workers . In their work, two new catalysts were prepared using two supports, that is, Al 2 O 3 and SiO 2 , from DMPSi‐supported Pd catalysts (DMPSi‐Pd).…”

“…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. In addition, Kobayashi and co‐workers applied this continuous‐flow reaction to the total synthesis of venlafaxine, which is a common antidepressant drug using DMPSi‐Pd/Al 2 O 3 as the catalyst . The hydrogenation step as the key reaction gave the desired compound in 92–93 % yield.…”

Facile synthesis of supported Ru–Triphos catalysts for continuous flow application in selective nitrile reduction

“…† For selectivity enhancement towards the primary amine, both homogeneous and heterogeneous catalysts oen require the use of base additives. 13,[18][19][20]67,68 Remarkably, mild and additive-free conditions can be applied for this highly selective heterogeneous Ru-Triphos system similar to the homogeneous system of Beller and co-workers. 31 When screening the whole supported catalyst library at 100 C and 1.0 mol% catalyst loading, JJ-supported C 2 and PS-bound C 4 performed analogously compared to C 1 (Table 1, entries 4 and 6).…”

“…13,17 Milder reaction conditions can be applied when utilizing supported Pd catalysts, however, these are still reliant on acidic conditions to produce the terminal amines selectively. [18][19][20] On the other hand, there has been a growing interest to develop highly selective homogeneous catalysts for applications in nitrile reduction under very mild conditions. Most transition-metal complexes are based on precious metals featuring well-dened ligand structures, 17,21,22 but more recently also base metals 23,24 have been employed.…”