Intensified Hydrogenation in Flow Using a Poly(β-cyclodextrin) Network-Supported Catalyst

The intersection of heterogeneous catalysis and flow chemistry is of great importance for the emerging distributed manufacturing of specialty chemicals. Specifically, continuous production of aryl amines is an essential step for on-demand and on-site manufacturing of fine chemicals. This work presents a heterogeneous flow chemistry route for accelerated chemoselective hydrogenation of nitroarenes using a poly(β-cyclodextrin) network-supported palladium catalyst. The developed packed-bed flow reactor enables the selective hydrogenation of a rationally selected library of nitroarenes with >99% yield at room temperature and short residence times (1 min). Utilizing sodium borohydride as the hydrogen carrier in a pressurized packed-bed flow reactor allows safe and efficient delivery of hydrogen to nitroarene molecules. We demonstrate the robustness and versatility of the flow reactor packed with the network-supported catalyst through its consistently high reaction yield over a 3 day run and its reusability and stability in several solvent mixtures with a single-reactor aryl amine manufacturing throughput of up to 31.5 g/day. Furthermore, the catalytic packed-bed reactor is used in a case study for a two-step telescopic synthesis of a critical intermediate for the antibacterial drug linezolid, further supporting its utility as an industrially relevant catalyst for the broad application of catalytic hydrogenations in flow.