General Papers ARKIVOC 2007 (xv) 199-214 ISSN 1551-7012 Page 199 © ARKAT USA, Inc. On the mechanism of the reaction between aryl acetates and hydroxylamine Deise J. Mazera, José C. Gesser,* and Josefredo R. Pliego Universidade Federal de Santa Catarina, Departamento de Quimica, Campus Universitario, Trindade, Florianopolis, SC 88040-900, Brasil E-mail: gesserjc@yahoo.com.br Abstract The reaction of aryl acetates and hydroxylamine produces O-acylhydroxylamine and N- acylhydroxylamine, 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 Keywords: Aryl acetates, hydroxylaminolysis, hydroxamic acid, hydroxylamine Introduction Its biological importance as well as its synthetic applications have driven numerous mechanistic investigations of the acyl transfer reaction. 1-9 Besides describing the structural relationships which lead to the reactivity of carboxylic acid derivatives, the search for nucleophiles able to cleave selectively peptide and ester bonds is still a challenge in many areas of chemistry and biochemistry. 10-12 The development of such stable and highly reactive nucleophiles has a wide range of applications in chemical detoxification, e.g., where quantitative phosphate bond cleavage is the target. 13 Some researchers in this field have noted that α-nucleophiles, such as hydroxylamine, represent a new perspective, but a better understanding of the attacking nucleophilic atom is still to be gained and this has prompted extensive mechanistic studies of the reactions of α-nucleophiles with activated acyl derivatives 14-20 , phosphate esters 21-29 and amides 30-33 . Hydroxylamine is a single α-nucleophile, the neutral and anionic forms of which