Continuous Flow Hydrogenation of Functionalized Pyridines

The heterogeneous hydrogenation of substituted pyridines has been accomplished by employing a continuous flow hydrogenation device that incorporates in situ hydrogen generation by electrolysis of H2O and pre-packed catalyst cartridges. In general, the hydrogenation reactions proceeded smoothly regardless of the supported precious metal catalyst (Pd/C, Pt/C, or Rh/C). By using 30-80 bar of hydrogen pressure at 60-80 degrees C full conversion was typically achieved in all cases at a flow rate of 0.5 mL min(-1), providing the corresponding piperidines in high yields. For disubstituted pyridines, variations in stereoselectivity were observed depending on both the metal catalyst and the temperature/pressure of the hydrogenation reaction. For ethyl nicotinate the selectivity between partial and full hydrogenation could be tuned depending on the hydrogen pressure, solvent, and the choice of supported metal catalyst. Changing the hydrogen source from H2O to D2O allowed the preparation of deuteriated derivatives. ((C) Wiley-VCH Verlag GmbH & Co. XGaA, 69451 Weinheim, Germany, 2009)