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Amination of Heteroaryl Chlorides: Palladium Catalysis or SNAr in Green Solvents?

Authors

  • Katie Walsh,

    1. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK), Fax: (+44) 115 951 3564
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  • Dr. Helen F. Sneddon,

    1. Green Chemistry Performance Unit, GlaxoSmithKline R&D Ltd, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY (UK)
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  • Prof. Dr. Christopher J. Moody

    Corresponding author
    1. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK), Fax: (+44) 115 951 3564
    • School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK), Fax: (+44) 115 951 3564

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Abstract

The reaction of heteroaryl chlorides in the pyrimidine, pyrazine and quinazoline series with amines in water in the presence of KF results in a facile SNAr reaction and N-arylation. The reaction is less satisfactory with pyridines unless an additional electron-withdrawing group is present. The results showed that the transition-metal-free SNAr reaction not only compares favourably to palladium-catalysed coupling reactions but also operates under environmentally acceptable (“green”) conditions in terms of the base and solvent.

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