On the mechanism of the reaction between aryl acetates and hydroxylamine

Deise J Mazera,Josefredo R Pliego,José C Gesser

doi:10.3998/ark.5550190.0008.f20

Deise J Mazera, Josefredo R Pliego + Show 1 more

Open Access

https://doi.org/10.3998/ark.5550190.0008.f20

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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

Highlights

Its biological importance as well as its synthetic applications have driven numerous mechanistic investigations of the acyl transfer reaction.[1,2,3,4,5,6,7,8,9] 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.[10,11,12] 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]
Distribution of products In our studies, the reaction of aryl acetates 1–5 and hydroxylamine may be described by two distinct processes: (i) an initial fast reaction of aryl ester and hydroxylamine to produce a mixture of N- and O-acylated compounds, the composition of which is dependent on the substrate structure, Scheme 1
The relative extent of N-acylation observed from an analysis of the data in Table 1 was found to change widely with the nature of the acylating agent, ranging from 53% for 2,4-dinitrophenyl acetate (DNPA) to a only small amount (1.5%) for p- chlorophenyl acetate (PCPA)

Summary

Introduction

Its biological importance as well as its synthetic applications have driven numerous mechanistic investigations of the acyl transfer reaction.[1,2,3,4,5,6,7,8,9] 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.[10,11,12] 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].

Results

Conclusion