The
N-arylacetylation of amino acid (2) by
N-succinimidyl arylacetates (1 a) to give the corresponding
N-arylacetyl amino acid was studied kinetically in an aqueous solution [pH = p
Ka, of the amino group in (2)] at 20°C. The reaction was competitive with the decomposition of (1 a) and the rate was expressed as
V = (
kd+
k2 [2]) [1a], where
kd and
K2 are the rate constants for the decomposition and
N-arylacetylation, respectively.
The second order rate constant,
k2, was correlated with the nucleophilicity (p
Ka) of (2), giving slopes of 0.70.8for log
vs. p
Ka Plots. The rate of ortho-substituted (1 a) was less than those of meta- and para-substituted (1 a), owing to the steric hindrance of the ortho-substituted (1 a). Hammett plots for meta- and para-substituted (1 a) showed a linear relationship with ρ=0. 530. 77. The rate of
N-arylacetylation predominated due to the inductive and steric effects of (1 a) and (2). The rate ratios, 10
-3 k2/
kd, exceeded unity except in some cases for (2). The reactivity of (1 a) was also compared with those of N-succinimidyl benzoates (1 b) and
N-acylsuccinimides (1 c).
A possible mechanism involving nucleophilic attack is proposed and discussed based on the above results.
View full abstract