Kinetics and mechanism of decomposition of N-chloro-α-amino acids

Abstract

The kinetics of decomposition of N-chloro derivatives of the following amino acids have been studied in phosphate buffer solution in the pH range 6-1 3: glycine, alanine, 2-aminoisobutyric acid, N-methylglycine, N-methylalanine, 2-(methylamino)isobutyric acid, proline, N-methylvaline, valine, isoleucine, and L-tert-leucine. The rates of decomposition of N-chloro-a-amino acids were found to be independent of the initial concentrations, ionic strengths, buffer concentrations and pH in the studied range. The first-order rate constants were found to increase as the relative permittivity decreased. The decomposition of N-chloroamino acids was followed by either a spectrophotometric method or an iodometric method, and in some cases the reaction was monitored by determining the rate of CO, evolution. The three methods gave results that were in good agreement. The effects of both a-carbon substitution and N-substitution on the rate of decomposition were investigated. All the kinetic data obtained appear to be consistent with a concerted mechanism in which dechlorination and decarboxylation take place concomitantly, resulting in the formation of an imine intermediate via an imine-like transition state. The imine may then be hydrolysed to the corresponding aldehyde or ketone, and amine. The kinetic data suggest that factors which influence the stability of the imine-like transition state affect the rate of decomposition of the N-chloro amino acid. The data from the decomposition of N-chloro amino acids may be useful in designing chemically stable, biodegradable germicidal agents.N-Chloro-a-amino acids are not generally stable in solution but readily decompose to ammonia, carbon dioxide, chloride ion, and carboxyl products. Several studies have focused on the mechanism of decomposition of N-chloro-a-amino acids.'-6 Fox and Bullock' have put forward a mechanism which involves initial loss of the a-proton followed by dechlorination of the intermediate carbanion, while Becker and Grob suggest that decomposition occurs with concomitant decarboxylation and N-dechlorination via an E,-like mechanism. Recent studies by Hand and Margerum4 appear to support this latter mechanism. We now describe some detailed structure-activity studies carried out on N-and C-a-substituted N-chloro-a-amino acids which were designed to determine in more detail the nature of mechanism of decomposition of N-chloro-a-amino acids.

Decomposition of N-Chloroglycine in Alkaline Aqueous Solution: Kinetics and Mechanism

“…41 Systematic studies on the kinetics and mechanism of the decomposition of N-chlorinated amino acids postulate the formation of imines which undergo further reactions. 20,21,23,[44][45][46][47][48][49][50] Some of these investigations suggests that decarboxylation and the loss of chloride ion occurs via a concerted Grob fragmentation mechanism. [51][52][53] Earlier results on the decomposition kinetics are somewhat controversial.…”

Chloramine-T in Radiolabeling Techniques

“…These compounds are very unstable. Their decomposition is associated with the loss of chlorine titer (11,12). To determine if a similar reaction would occur between amino acids and NCMGE, we used 1-aminocyclohexane carboxylic acid as a model amino acid.…”

Pressure and pH dependence of the kinetics of decarboxylative dechlorination of N-chloro-l-alanine

“…For N-chloroalanine written as X-CHMe-COOH, the parent compound (X=Me) is isobutyric acid, and p* is estimated to be 0. 8 …”

“…This might be a kinetic (primary) salt effect or an equilibrium (secondary) salt effect, the latter possibility arising from the existence of two ionization equilibria in this pH range [8], [22], and [26]. The smooth line was drawn with eq.…”

“…In order to investigate the applicability of the theory to reaction rates we sought a reaction whose kinetic solvent effects would not be confounded by secondary influences, such as solvent effects on pH. The decomposition of N-chloro-aamino acids in the neutral solution range possesses the following features, very attractive for our purposes: ( I ) the kinetics are first-order, and the reaction is unimolecular; (2) the reaction rate is independent of pH over the approximate range 4 to 13 [5,7,8]; (3) the rate-determining step of the process is not a solvolysis; and (4) the reaction is known to display a sensitivity to solvent composition [8]. In support of the solvent effect work, we have conducted further mechanistic studies, which we report here.…”