Kinetic investigation of the effect of the amino acid side chains in the selective acidolysis of N-acyl-N,alfa,alfa-trialkyl glycine amides

Abstract

Accurate kinetic measurements of the rate constants for the acidolysis of five N-acetyl-N-(4-methoxybenzyl)-alfa,alfa-trialkyl glycine cyclohexyl amides in TFA were performed at 25.00 ºC and the reactions monitored by HPLC. The results were in all cases consistent with a first order behaviour with respect to the substrate. No direct correlation was obtained with this data between rate constant values and structure, but a good correlation coefficient was obtained when a multiple regression analysis was applied by taking advantage of a Taft equation using appropriate polar and steric substituent parameters. In a plot of the values observed for log k against those calculated by this equation all five points fell very close to the line of perfect correlation. The calculated sensitivity coefficients to polar and steric contributions were used to discuss the experimental results and showed that the acidolyses are comparatively less affected by steric effects than what one would expect.