Reactivity of some nucleophiles and amino-acid derivatives towards 4-dimethylamino-1-methoxycarbonylpyridinium chloride

Abstract

The kinetics of the reaction of 4-dimethylamino-1-methoxycarbonylpyridinium chloride (MeOCOPy⁺NMe₂) with water and nucleophiles have been examined as a model reaction of 1-acyl-4-dimethylaminopyridinium ions with amino-acid residues of proteins.

Second-order rate constants determined for a series of 11-L-amino-acids allow the calculation of the relative reactivity of the different functional groups as well as the prediction of the selectivity of the reagent at various pH values (thiol, phenol, and imidazole functions are much more reactive than primary amines).

The reagent MeOCOPy⁺NMe₂ is particularly insensitive to hydrolysis in the pH range 5–7, a region in which hydrolysis is often competitive with nucleophilic reactions. A Brönsted correlation is observed with primary amines; the slope is β= 1, a value which is usually interpreted as a rate-determining breakdown of the tetrahedral intermediate. For thiol and phenol functional groups, the attack is the rate-determining step.

A comparison with AclmH⁺ reactivity shows a similar behaviour for both substrates although MeOCOPy⁺NMe₂ is much less reactive.