The aminolysis of penicillin derivatives. Rate constants for the formation and breakdown of the tetrahedral addition intermediate

Nigel P. Gensmantel, Michael I. Page

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

There is a non-linear dependence of the rate of aminolysis of benzylpenicillin and 6-β-aminopenicillanic acid upon hydroxide ion concentration which is interpreted in terms of formation of a tetrahedral addition intermediate. At high concentrations of hydroxide ion the rate-limiting step is formation of the tetrahedral intermediate but at low concentrations it is the diffusion-controlled encounter of the intermediate and hydroxide ion. Rate constants for the formation of the intermediate and its breakdown to reactants are reported for a variety of amines. The dependence of these rate constants upon the pKa of the conjugate acid of the amine yield Brønsted β values of ca. 0.3 and -0.6 for the formation and breakdown of the intermediate, respectively. There is thus quite a large dependence of the rate of expulsion of the amine from the intermediate upon the basicity of the amine despite the rate constants for this step being ca. 10 9-1010 s-1. Possible stereoelectronic control in the breakdown of the tetrahedral intermediate is discussed. There is no evidence for intramolecular general base catalysis in the formation of the tetrahedral intermediate from 6-β-aminopenicillanic acid.

Original languageEnglish
Pages (from-to)137-142
Number of pages6
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number2
DOIs
Publication statusPublished - 1 Jan 1979
EventAnnual Research Conference of the Royal Institution of Chartered Surveyors, COBRA 2006 - London, United Kingdom
Duration: 7 Sep 20068 Sep 2006

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Penicillins
Amines
Rate constants
Derivatives
Acids
Ions
Penicillin G
Alkalinity
Catalysis
hydroxide ion
aminopenicillanic acid

Cite this

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abstract = "There is a non-linear dependence of the rate of aminolysis of benzylpenicillin and 6-β-aminopenicillanic acid upon hydroxide ion concentration which is interpreted in terms of formation of a tetrahedral addition intermediate. At high concentrations of hydroxide ion the rate-limiting step is formation of the tetrahedral intermediate but at low concentrations it is the diffusion-controlled encounter of the intermediate and hydroxide ion. Rate constants for the formation of the intermediate and its breakdown to reactants are reported for a variety of amines. The dependence of these rate constants upon the pKa of the conjugate acid of the amine yield Br{\o}nsted β values of ca. 0.3 and -0.6 for the formation and breakdown of the intermediate, respectively. There is thus quite a large dependence of the rate of expulsion of the amine from the intermediate upon the basicity of the amine despite the rate constants for this step being ca. 10 9-1010 s-1. Possible stereoelectronic control in the breakdown of the tetrahedral intermediate is discussed. There is no evidence for intramolecular general base catalysis in the formation of the tetrahedral intermediate from 6-β-aminopenicillanic acid.",
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The aminolysis of penicillin derivatives. Rate constants for the formation and breakdown of the tetrahedral addition intermediate. / Gensmantel, Nigel P.; Page, Michael I.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 2, 01.01.1979, p. 137-142.

Research output: Contribution to journalArticle

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N2 - There is a non-linear dependence of the rate of aminolysis of benzylpenicillin and 6-β-aminopenicillanic acid upon hydroxide ion concentration which is interpreted in terms of formation of a tetrahedral addition intermediate. At high concentrations of hydroxide ion the rate-limiting step is formation of the tetrahedral intermediate but at low concentrations it is the diffusion-controlled encounter of the intermediate and hydroxide ion. Rate constants for the formation of the intermediate and its breakdown to reactants are reported for a variety of amines. The dependence of these rate constants upon the pKa of the conjugate acid of the amine yield Brønsted β values of ca. 0.3 and -0.6 for the formation and breakdown of the intermediate, respectively. There is thus quite a large dependence of the rate of expulsion of the amine from the intermediate upon the basicity of the amine despite the rate constants for this step being ca. 10 9-1010 s-1. Possible stereoelectronic control in the breakdown of the tetrahedral intermediate is discussed. There is no evidence for intramolecular general base catalysis in the formation of the tetrahedral intermediate from 6-β-aminopenicillanic acid.

AB - There is a non-linear dependence of the rate of aminolysis of benzylpenicillin and 6-β-aminopenicillanic acid upon hydroxide ion concentration which is interpreted in terms of formation of a tetrahedral addition intermediate. At high concentrations of hydroxide ion the rate-limiting step is formation of the tetrahedral intermediate but at low concentrations it is the diffusion-controlled encounter of the intermediate and hydroxide ion. Rate constants for the formation of the intermediate and its breakdown to reactants are reported for a variety of amines. The dependence of these rate constants upon the pKa of the conjugate acid of the amine yield Brønsted β values of ca. 0.3 and -0.6 for the formation and breakdown of the intermediate, respectively. There is thus quite a large dependence of the rate of expulsion of the amine from the intermediate upon the basicity of the amine despite the rate constants for this step being ca. 10 9-1010 s-1. Possible stereoelectronic control in the breakdown of the tetrahedral intermediate is discussed. There is no evidence for intramolecular general base catalysis in the formation of the tetrahedral intermediate from 6-β-aminopenicillanic acid.

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