Mild and Simple Conversion of Primary Amines to N-Substituted Glycines

04 April 2008

During an attempted imidazolidinone synthesis researchers at the University of Cardiff discovered a simple way to prepare N-substituted glycine derivatives. Treatment of a primary amine, such as benzylamine, with two equivalents of glyoxylic acid produces N-formyl-Nbenzylglycine
in 79% yield. The reaction works best in water or dichloromethane, but the advantage of using water in this case is that addition of 2M HCl after formation of the initial product allows for the direct one-pot conversion to N-benzylglycine hydrochloride.

Secondary amines and tertiary amines do not react and so this method also allows selective conversion of a primary amine to the glycine derivative in the presence of a secondary amine. Yields are typically 40-60% for this conversion.

T.K. Gibbs, M. Boomhoff, and N.C.O. Tomkinson,* Synlett, 2007, 1573.