Heterogeneous hydrogenation reactions using a continuous flow high pressure device.

Several hydrogenation reactions involving O-debenzylations, aromatic nitro group reductions and reductive dethionations were investigated under continuous flow conditions in a novel, laboratory scale hydrogenation device that combines endogeneous hydrogen generation and heterogeneous Pd/C or Raney-Ni catalyst cartridges. The hydrogenation of organic compounds through addition and/or hydrogenolysis, typically carried out in the presence of a suitable heterogeneous metal catalyst, is of great significance not only in research laboratories but also in the chemical and pharmaceutical industries. Functional group reductions (e.g. alkene, alkyne, nitro) and deprotections (e.g. benzyl) are very common in catalytic hydrogenations. Small scale batch hydrogenations pose an operational hazard in the use of hydrogen gas, requiring dedicated high-pressure resistant reactors or autoclave conditions. Alternative hydrogenation methodologies which are efficient, viable, avoiding the hazards of using exogenic hydrogen gas under high pressure conditions and with the feasibility to scale up key hydrogenation steps are sought after persistently. ∗ To whom correspondence should be addressed. E-mail: [email protected], Tel. +43-316-380 5351, Fax: +43-316-380 9840. 2 In recent years, the concept of carrying out laboratory scale organic chemical transformations under continuous flow conditions has received increased attention. Flow-through processes using cartridgebased reactors containing immobilized reagents or catalysts have the potential to deliver compounds in high intrinsic purities by automated, workup-free, solution-phase methods often without the need for subsequent chromatographic purification. As a consequence, flow-through reactors are increasingly being viewed attractive for implementing smaller laboratory-scale processes. In addition, microreactor technology based on microfluidic flow has found considerable current interest in organic and highthroughput synthesis. In this context, Kobayashi and co-workers recently described a microfluidic device for conducting hydrogenation reactions under continuous flow conditions. In these microreactor-type devices substrate solutions and external hydrogen gas are pumped through a palladium-immobilized microchannel (circa 100-200 μm in width and depth) at ambient temperature and atmospheric hydrogen pressure. This technology promises high compatibility with multiphase catalytic hydrogenations and an efficient interaction between hydrogen, substrates and a palladium catalyst to afford a smooth reaction. Alternatively, catalytic transfer hydrogenations in continuous flow format have been described by Kunz and co-workers, employing nanopalladium clusters in monolithic polymer/carrier materials. Gas-Liquid Mixer Hydrogen Generator Electrolytic Cell Heater Unit Product by Fraction Collection HPLC Pump 0.1-9 mL/min Catalyst Cartridge Pressure Control (1-100 bar H2) (rt 100 °C) Power Supply (substrates) Figure 1. Laboratory scale hydrogenation device H-cubeTM (schematic).