Kinetic study of Pd-catalyzed hydrogenation of N-benzyl-4-fluoroaniline

In multi-step organic syntheses, the protection of functional groups such as amines, alcohols, and carbonyl groups is frequently necessary to avoid undesired side reactions. For example, amines can be protected by benzyl groups, which form toluene after removal by hydrogenation. In the present study, the kinetics of Pd-catalyzed hydrogenation of N-benzyl-4-fluoroaniline, NB4FA, a compound that can undergo both debenzylation and defluorination, were investigated in a semi-batch reactor. The effects of various operating parameters (temperature, H-2 pressure, solvent type, buffer) were examined to identify factors that influence the reaction pathways. Mechanistic Langmuir-Hinshelwood models were evaluated by regressing the experimental data to determine the appropriate reaction expression for NB4FA debenzylation. Separate experiments to determine the hydrogenation kinetics of the main product, 4-fluoroaniline, 4FA, were also conducted. Finally, the complete transient reaction behavior of NB4FA hydrogenation was predicted well by combining the kinetics of NB4FA debenzylation and of 4FA hydrogenation to aniline, which was observed to be the main by-product. (C) 2015 Elsevier B.V. All rights reserved.