Secondary Amines from Catalytic Amination of Bio-Derived Phenolics over Pd/C and Rh/C: Effect of Operation Parameters

Abstract

The production of renewable chemicals using lignocellulosic biomass has gained significant attention in green chemistry. Among biomass-derived chemicals, secondary amines have emerged as promising intermediates for synthetic applications. Here, we report a systematic study on the reductive amination of phenolics with cyclohexylamine using Pd/C and Rh/C as catalysts. The catalytic tests were performed in batch reactors under different reaction conditions (various: amine concentration (0.1–0.4 mol/L), hydrogen pressure (0–2.5 bar), temperature (80–160 °C), and substituted phenols (phenol, o-cresol, p-cresol, and methoxyphenol)) and using tert-amyl alcohol as a solvent. The experimental observations were consistent with a multi-step mechanism, where hydrogenation of phenol to cyclohexanone is followed by condensation of the ketone with cyclohexylamine to form an imine, which is finally hydrogenated to produce secondary amines. In addition, there was evidence of parallel self-condensation of the cyclohexylamine. The study also supported a limited dehydrogenation capacity of Rh/C, unlike Pd/C, which increases this capacity at higher temperatures generating a higher yield of cyclohexylaniline (up to 15%). The study of the alkylated phenols demonstrated that the nature and propensity of hydrogenation of the phenolic controls their amination. Kinetic analysis revealed reaction orders between 0.4 and 0.7 for H2, indicating its dissociative adsorption. Meanwhile, phenol’s order (between 1–1.8) suggests a single participation of this compound in the hydrogenation step. The order of 0.4 for cyclohexylamine suggests its participation as a surface-abundant species. The apparent activation energies derived from a power law approximation were of 37 kJ/mol and 10 kJ/mol on Pd/C and Rh/C, respectively.

Microwave-Assisted Reductive Amination under Heterogeneous Catalysis for the Synthesis of β-Adrenergic Agonist and Related Structures

“…Many of these reduction steps require the presence of a catalyst to activate the reducing agent [4], and transition-metals (such as Ru, Rh, Pd, Ag, Ir, Pt, and Au) have also been used extensively [5] in the preparation of active pharmaceutical ingredients (APIs) [6,7]. Despite its cost, Rh shows remarkable activity for such a reaction, as shown in the recent literature [8][9][10][11], and has the potential to be employed in robust hydrogenation catalysts with low metal loading. A Rh/Al 2 O 3 -catalyzed reductive amination of furfural and other aldehydes, especially those associated with biomass, was recently reported by Chatterjee, Kawanami, and coworkers using an aqueous solution of NH 3 [12].…”

Improved Synthesis of β-Adrenergic Agonist and Related Structures by Microwave-Assisted Metal-Catalysed Reductive Amination

“…Many of these reduction steps require the presence of a catalyst to activate the reducing agent [4], and transition-metals (such as Ru, Rh, Pd, Ag, Ir, Pt, and Au) have also been used extensively [5] in the preparation of active pharmaceutical ingredients (APIs) [6,7]. Despite its cost, Rh shows remarkable activity for such a reaction, as shown in the recent literature [8][9][10][11], and has the potential to be employed in robust hydrogenation catalysts with low metal loading. A Rh/Al 2 O 3 -catalyzed reductive amination of furfural and other aldehydes, especially those associated with biomass, was recently reported by Chatterjee, Kawanami, and coworkers using an aqueous solution of NH 3 [12].…”