Highly Selective Hydrogenative Conversion of Nitriles into Tertiary, Secondary, and Primary Amines under Flow Reaction Conditions

Abstract

Flow reaction methods have been developed to selectively synthesize tertiary, secondary, and primary amines depending on heterogeneous platinum-group metal species under catalytic hydrogenation conditions using nitriles as starting materials. A 10 % Pd/C-packed catalyst cartridge affords symmetrically substituted tertiary amines in good to excellent yields. A 10 % Rh/C-packed catalyst cartridge enables the divergent synthesis of secondary and primary amines, with either cyclohexane or acetic acid as a solvent, respectively. Reaction parameters, such as the metal catalyst, solvent, and reaction temperature, and continuous-flow conditions, such as flow direction and second support of the catalyst in a catalyst cartridge, are quite important for controlling the reaction between the hydrogenation of nitriles and nucleophilic attack of in situ-generated amines to imine intermediates. A wide variety of aliphatic and aromatic nitriles could be highly selectively transformed into the corresponding tertiary, secondary, and primary amines by simply changing the metal species of the catalyst or flow parameters. Furthermore, the selective continuous-flow methodologies are applied over at least 72 h to afford three different types of amines in 80-99 % yield without decrease in catalytic activities.

Continuous Hydrogenation of Nitriles to Primary Amines with High Selectivity in Flow by Using Raney Cobalt

“…For instance, Rebeka et al [15a] proposed a continuous process for the hydrogenation and reduction of deuterated nitriles with Raney Ni at 4 MPa and 80 °C. Valuable results on the synthesis of �, �-deuteramine were obtained with ease, safety, and sustainability; Yamada et al [22] developed a method for the selective synthesis of primary, secondary, and tertiary amines by changing the catalyst under flow conditions. The continuous flow method for amine synthesis took 72 hours and resulted in a yield of 80-99 % without loss of catalytic activity.…”

Recent Advancements in Continuous‐Flow Suzuki‐Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes

“…[10][11][12][13][14] In recent decades, switching the technologies of fine chemical synthesis from traditional batch reactors to flow systems, especially for the use of packed-bed reactors with heterogeneous catalysts, has surfaced as means to enhance the reaction efficiency, safety and environmental compatibility. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] This is mainly due to the continuous collection of the desired product from the reactor outlet, eliminating the need for catalyst separation from the reaction mixture. In addition, these technologies are anticipated to help bridge the gap between academic studies and industrial applications.…”

Microwave-assisted C–C bond formation of diarylacetylenes and aromatic hydrocarbons on carbon beads under continuous-flow conditions

“…We have focused on the development of heterogeneous metal-catalyzed organic transformations under flow conditions 48 , 49 . In these studies, platinum on beaded activated charcoal (Pt/CB, CB; carbon bead) efficiently catalyzed the hydrogen extraction reactions of methylcyclohexanes (MCH) 50 and 2-propanols (2-PrOH) 51 , the so-called liquid organic chemical hydrides (LOCHs) 52 , 53 , under single-mode MW irradiation conditions (Fig.…”