Journal of the American Chemical Society 2008-02-13

Glycine enolates: the effect of formation of iminium ions to simple ketones on alpha-amino carbon acidity and a comparison with pyridoxal iminium ions.

Juan Crugeiras, Ana Rios, Enrique Riveiros, Tina L Amyes, John P Richard

Index: J. Am. Chem. Soc. 130(6) , 2041-50, (2008)

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Abstract

Equilibrium constants in D2O were determined by 1H NMR analyses for formation of imines/iminium ions from addition of glycine methyl ester to acetone and from addition of glycine to phenylglyoxylate. First-order rate constants, also determined by 1H NMR, are reported for deuterium exchange between solvent D2O and the alpha-amino carbon of glycine methyl ester and glycine in the presence of increasing concentrations of ketone and Brønsted bases. These rate and equilibrium data were used to calculate second-order rate constants for deprotonation by DO- and by Brønsted bases of the alpha-imino carbon of the ketone adducts. Formation of the iminium ion between acetone and glycine methyl ester and between phenylglyoxylate and glycine is estimated to cause 7 unit and 15 unit decreases, respectively, in the pKa's of 21 and 29 for deprotonation of the parent carbon acids. The effect of formation of iminium ions to phenylglyoxylate and to 5'-deoxypyridoxal (DPL) [Toth, K.; Richard, J. P. J. Am. Chem. Soc. 2007, 129, 3013-3021] on the carbon acidity of glycine is similar. However, DPL is a much better catalyst than phenylglyoxylate of deprotonation of glycine, because of the exceptionally large thermodynamic driving force for conversion of the amino acid and DPL to the reactive iminium ion.