The Hydrolysis of Azetidinyl Amidinium Salts. Part 1. The Unimportance of Strain Release in the Four-membered Ring

Michael I. Page, Philip Webster, Leon Ghosez

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The alkaline hydrolysis of azetidin-2-ylideneammonium salts gives a mixture of β-lactams, by exocyclic C-N bond fission, and β-amino amides, by opening the four-membered ring. Despite the anticipated release of strain energy in opening the four-membered ring the β-lactam is usually the major product i.e. exocyclic C-N fission is favoured over endocyclic C-N fission. This occurs even when the basicities of the endo- and exo-cyclic nitrogens are similar. The apparent reluctance of the four-membered ring to open is also not the result of entropic or stereoelectronic factors. The kinetics of the reaction indicate the presence of a neutral tetrahedral intermediate because there are two changes in the rate dependence upon hydroxide ion with increasing base concentration. There is also a term in the rate law for the carbonate-catalysed reaction which is both first order in carbonate ion and first order in hydroxide ion. The neutral tetrahedral intermediate must be formed reversibly and undergo deprotonation of its hydroxy group at high pH. By assuming that this deprotonation by hydroxide ion is rate limiting and diffusion controlled, the equilibrium constants for the formation of the neutral tetrahedral intermediate can be calculated. These are reported together with the calculated microscopic rate constants for the formation and breakdown of the intermediate.

LanguageEnglish
Pages805-811
Number of pages7
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number5
DOIs
Publication statusPublished - May 1990

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Hydrolysis
Deprotonation
Salts
Carbonates
beta-Lactams
Equilibrium constants
Alkalinity
Strain energy
Amides
Rate constants
Nitrogen
Ions
Kinetics
hydroxide ion

Cite this

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abstract = "The alkaline hydrolysis of azetidin-2-ylideneammonium salts gives a mixture of β-lactams, by exocyclic C-N bond fission, and β-amino amides, by opening the four-membered ring. Despite the anticipated release of strain energy in opening the four-membered ring the β-lactam is usually the major product i.e. exocyclic C-N fission is favoured over endocyclic C-N fission. This occurs even when the basicities of the endo- and exo-cyclic nitrogens are similar. The apparent reluctance of the four-membered ring to open is also not the result of entropic or stereoelectronic factors. The kinetics of the reaction indicate the presence of a neutral tetrahedral intermediate because there are two changes in the rate dependence upon hydroxide ion with increasing base concentration. There is also a term in the rate law for the carbonate-catalysed reaction which is both first order in carbonate ion and first order in hydroxide ion. The neutral tetrahedral intermediate must be formed reversibly and undergo deprotonation of its hydroxy group at high pH. By assuming that this deprotonation by hydroxide ion is rate limiting and diffusion controlled, the equilibrium constants for the formation of the neutral tetrahedral intermediate can be calculated. These are reported together with the calculated microscopic rate constants for the formation and breakdown of the intermediate.",
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The Hydrolysis of Azetidinyl Amidinium Salts. Part 1. The Unimportance of Strain Release in the Four-membered Ring. / Page, Michael I.; Webster, Philip; Ghosez, Leon.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 5, 05.1990, p. 805-811.

Research output: Contribution to journalArticle

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AB - The alkaline hydrolysis of azetidin-2-ylideneammonium salts gives a mixture of β-lactams, by exocyclic C-N bond fission, and β-amino amides, by opening the four-membered ring. Despite the anticipated release of strain energy in opening the four-membered ring the β-lactam is usually the major product i.e. exocyclic C-N fission is favoured over endocyclic C-N fission. This occurs even when the basicities of the endo- and exo-cyclic nitrogens are similar. The apparent reluctance of the four-membered ring to open is also not the result of entropic or stereoelectronic factors. The kinetics of the reaction indicate the presence of a neutral tetrahedral intermediate because there are two changes in the rate dependence upon hydroxide ion with increasing base concentration. There is also a term in the rate law for the carbonate-catalysed reaction which is both first order in carbonate ion and first order in hydroxide ion. The neutral tetrahedral intermediate must be formed reversibly and undergo deprotonation of its hydroxy group at high pH. By assuming that this deprotonation by hydroxide ion is rate limiting and diffusion controlled, the equilibrium constants for the formation of the neutral tetrahedral intermediate can be calculated. These are reported together with the calculated microscopic rate constants for the formation and breakdown of the intermediate.

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