Reactivity and mechanism in the hydrolysis of β-Sultams

Nicholas J. Baxter, Laurent J.M. Rigoreau, Andrew P. Laws, Michael I. Page

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

β-Sultams show extraordinary rate enhancements of 109- and 107-fold, respectively, compared with the acid- and base-catalyzed hydrolysis of corresponding acyclic sulfonamides. They are about 103-fold more reactive than analogous β-lactams. The alkaline hydrolysis of some β-sultams shows a rate term that is second-order in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a trigonal bipyramidal intermediate (TBPI). The Bronsted β(Ig) value for the alkaline hydrolysis of N-aryl-β-sultams is -0.58 and the kinetic solvent isotope effect k(OH)/(H2O)/k(OD)/(D2O) is 0.60 compatible with rate-limiting formation of the TBPI. Conversely, k(OH)/(H2O)/k(OD)/(D2O) for N-alkyl-β-sultams is 1.55, indicative of rate-limiting breakdown of the TBPI. The acid-catalyzed hydrolysis of β-sultams is strongly retarded by electron-withdrawing groups α to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Bronsted β(Ig) value for the acid-catalyzed hydrolysis of N-benzyl-β-sultams is 0.32. The general-acid-catalyzed hydrolysis of N-benzyl-β-sultam by carboxylic acids shows a Bronsted α value of 0.67 and is attributed to a specific acid- nucleophilic mechanism with the formation of a mixed-anhydride intermediate.

LanguageEnglish
Pages3375-3385
Number of pages11
JournalJournal of the American Chemical Society
Volume122
Issue number14
Early online date25 Mar 2000
DOIs
Publication statusPublished - 12 Apr 2000

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Hydrolysis
Acids
Ions
Anhydrides
Carboxylic acids
Sulfonamides
beta-Lactams
Isotopes
Carboxylic Acids
beta-sultam
Electrons
Kinetics

Cite this

Baxter, Nicholas J. ; Rigoreau, Laurent J.M. ; Laws, Andrew P. ; Page, Michael I. / Reactivity and mechanism in the hydrolysis of β-Sultams. In: Journal of the American Chemical Society. 2000 ; Vol. 122, No. 14. pp. 3375-3385.
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Reactivity and mechanism in the hydrolysis of β-Sultams. / Baxter, Nicholas J.; Rigoreau, Laurent J.M.; Laws, Andrew P.; Page, Michael I.

In: Journal of the American Chemical Society, Vol. 122, No. 14, 12.04.2000, p. 3375-3385.

Research output: Contribution to journalArticle

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N2 - β-Sultams show extraordinary rate enhancements of 109- and 107-fold, respectively, compared with the acid- and base-catalyzed hydrolysis of corresponding acyclic sulfonamides. They are about 103-fold more reactive than analogous β-lactams. The alkaline hydrolysis of some β-sultams shows a rate term that is second-order in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a trigonal bipyramidal intermediate (TBPI). The Bronsted β(Ig) value for the alkaline hydrolysis of N-aryl-β-sultams is -0.58 and the kinetic solvent isotope effect k(OH)/(H2O)/k(OD)/(D2O) is 0.60 compatible with rate-limiting formation of the TBPI. Conversely, k(OH)/(H2O)/k(OD)/(D2O) for N-alkyl-β-sultams is 1.55, indicative of rate-limiting breakdown of the TBPI. The acid-catalyzed hydrolysis of β-sultams is strongly retarded by electron-withdrawing groups α to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Bronsted β(Ig) value for the acid-catalyzed hydrolysis of N-benzyl-β-sultams is 0.32. The general-acid-catalyzed hydrolysis of N-benzyl-β-sultam by carboxylic acids shows a Bronsted α value of 0.67 and is attributed to a specific acid- nucleophilic mechanism with the formation of a mixed-anhydride intermediate.

AB - β-Sultams show extraordinary rate enhancements of 109- and 107-fold, respectively, compared with the acid- and base-catalyzed hydrolysis of corresponding acyclic sulfonamides. They are about 103-fold more reactive than analogous β-lactams. The alkaline hydrolysis of some β-sultams shows a rate term that is second-order in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a trigonal bipyramidal intermediate (TBPI). The Bronsted β(Ig) value for the alkaline hydrolysis of N-aryl-β-sultams is -0.58 and the kinetic solvent isotope effect k(OH)/(H2O)/k(OD)/(D2O) is 0.60 compatible with rate-limiting formation of the TBPI. Conversely, k(OH)/(H2O)/k(OD)/(D2O) for N-alkyl-β-sultams is 1.55, indicative of rate-limiting breakdown of the TBPI. The acid-catalyzed hydrolysis of β-sultams is strongly retarded by electron-withdrawing groups α to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Bronsted β(Ig) value for the acid-catalyzed hydrolysis of N-benzyl-β-sultams is 0.32. The general-acid-catalyzed hydrolysis of N-benzyl-β-sultam by carboxylic acids shows a Bronsted α value of 0.67 and is attributed to a specific acid- nucleophilic mechanism with the formation of a mixed-anhydride intermediate.

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