On the mechanism of the reaction between aryl acetates and hydroxylamine

Abstract

The reaction of aryl acetates and hydroxylamine produces O-acylhydroxylamine and Nacylhydroxylamine, the latter being essentially observed for good leaving group esters and the former for poor leaving esters. For both acylation reactions, kinetics studies suggested a tetrahedral intermediate intervention for nucleofuges in a pKa range of 1 to 9. Esters having leaving groups with a pKa value less than 7 react by a rate-determining step inferred to be the tetrahedral intermediate formation, while for esters having leaving groups with a pKa value equal to or higher than 7, the rate-limiting step has been proposed to be the tetrahedral intermediate decomposition. General bifunctional acid-base catalysis by a second hydroxylamine molecule was identified as one of the components of the reaction for the intermediate collapse to products in the poor leaving group ester

The role of ammonia oxide in the reaction of hydroxylamine with carboxylic esters

“…More recently, Mazera et al have reported kinetic studies on the reaction of hydroxylamine with five different derivatives of phenylacetate. 4 For phenylacetate, p-chlorophenylacetate and p-nitrophenylacetate, first and second order kinetics in hydroxylamine (second and third order global, respectively) were observed. These results point out that both bimolecular (one hydroxylamine) and termolecular (two hydroxylamines) mechanisms play a role in this reaction.…”

“…Unexpected results from previous investigations were the discovery of the catalyzed mechanisms. Mazera et al 4,5 have found that hydroxylamine can act as a bifunctional catalyst involving the oxygen and nitrogen atoms simultaneously. The nitrogen atom acts as a base, receiving a proton of the attacking nucleophilic atom, whereas the oxygen atom acts as an acid, forming a hydrogen bond with the carbonyl oxygen and transferring the proton.…”

“…Some recent papers have emphasized the role of the zwitterionic form of hydroxylamine in the reactions with phosphate esters 12 and sulfonamides. 13 The previous studies by Mazera et al 4,5 related to reactions with carboxylic esters have not included a bimolecular mechanism involving the zwitterionic form of hydroxylamine. In fact, any reliable theoretical study should make use of a solvation model able to predict correctly the stability of the zwitterionic form.…”

Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies

“…Hydroxylamine is a neutral a-nucleophile and shows remarkably high reactivity in nucleophilic substitutions at carboxylic acyl and phosphoryl centers. 18 The presence of a lone pair of electrons on the atom adjacent to the nucleophilic center makes hydroxylamine a unique ambident a-nucleophile. 18 Tabun is one of the most dangerous nerve agents, originally developed in Germany before World War II.…”

“…18 The presence of a lone pair of electrons on the atom adjacent to the nucleophilic center makes hydroxylamine a unique ambident a-nucleophile. 18 Tabun is one of the most dangerous nerve agents, originally developed in Germany before World War II. 4 Tabun shows deleterious effects due to the extraordinarily resistant nature of tabun-AChE conjugates toward most oxime reactivators.…”