Reactivity and Mechanism in the Hydrolysis of β-Sultams

Abstract

β-Sultams show extraordinary rate enhancements of 10 9 -and 10 7 -fold, respectively, compared with the acid-and base-catalyzed hydrolysis of corresponding acyclic sulfonamides. They are about 10 3 -fold more reactive than analogous β-lactams. The alkaline hydrolysis of some β-sultams shows a rate term that is secondorder in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a trigonal bipyramidal intermediate (TBPI). The Brønsted β lg value for the alkaline hydrolysis of N-aryl-β-sultams is -0.58 and the kinetic solvent isotope effect k OHfor 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 R to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Brønsted β lg value for the acid-catalyzed hydrolysis of N-benzyl-β-sultams is 0.32. The generalacid-catalyzed hydrolysis of N-benzyl-β-sultam by carboxylic acids shows a Brønsted R value of 0.67 and is attributed to a specific acid-nucleophilic mechanism with the formation of a mixed-anhydride intermediate.

Theoretical Study for Alcoholysis of N-Benzyl 3-Oxo-?-Sultam

“…They are potential sulfonylating agents of a variety of nucleophiles [3]. β-Sultams also have the potential to act as peptide mimics and as transition state analogues of the tetrahedral intermediates formed in many acyl transfer reactions [4]. The mechanism of its action has been studied with experimental [2][3][4][5][6][7][8] and theoretical [9][10][11] methods.…”

Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNALeu(UUR) and tRNALys

“…The storage of 3 ′ isomers 12a/12b in methanol for a longer period of time resulted in their partial isomerization, enabling improvement of the overall yield of 2 ′ -TBDMS derivatives 11a/11b. Separated 5-aminomethyl(-2-thio)uridine 11a/11b was then used as a donor in a Michaeltype addition to 4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl ethenesulfonate (13) (Baxter et al 2000;Ogata and FIGURE 2. Protecting groups selected for sulfonic acid residue of taurine; TBDPS, tert-butyldiphenylsilyl; TBDMS, tert-butyldimethylsilyl; TMS, trimethylsilyl.…”

Acid‐Catalyzed Reactions of Twisted Amides in Water Solution: Competition between Hydration and Hydrolysis

“…This rate acceleration arises mainly from the increase in exothermicity in the first step; the second step of the nucleophilic attack is less affected by the twisting of the amide bond. Presumably, the current strategy should be applicable for various acid-catalyzed processes of both organic and enzymatic reactions, such as the hydrolysis of b-lactam antibiotics [3] and b-sultams, [98,99] and the decarboxylation of carboxylic acids. [100] The present results therefore have useful implications for the theoretical treatment of protontransfer reactions in chemistry and biology.…”