Continuous Flow Hydrogenation of Functionalized Pyridines

Authors

  • Muhammed Irfan,

    1. Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl Franzens University of Graz, Heinrichstrasse 28, 8010 Graz, Austria, Fax: +43-316-3809840
    Search for more papers by this author
  • Elena Petricci,

    1. Dipartimento Farmaco Chimico Tecnologico, Universitá degli Studi di Siena, Via A. Moro, 53100 Siena, Italy
    Search for more papers by this author
  • Toma N. Glasnov,

    1. Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl Franzens University of Graz, Heinrichstrasse 28, 8010 Graz, Austria, Fax: +43-316-3809840
    Search for more papers by this author
  • Maurizio Taddei,

    1. Dipartimento Farmaco Chimico Tecnologico, Universitá degli Studi di Siena, Via A. Moro, 53100 Siena, Italy
    Search for more papers by this author
  • C. Oliver Kappe

    1. Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl Franzens University of Graz, Heinrichstrasse 28, 8010 Graz, Austria, Fax: +43-316-3809840
    Search for more papers by this author

Abstract

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 °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. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Ancillary