Tsang Wing Y, Ahmed Naveed, Hemming Karl, Page Michael I
Department of Chemical and Biological Sciences, The University of Huddersfield, Queensgate, Huddersfield, UK.
J Org Chem. 2008 Jun 20;73(12):4504-12. doi: 10.1021/jo800407x. Epub 2008 May 15.
Activated sulfonyl derivatives, similar to acyl ones, usually undergo aminolysis with amines in water as nucleophilic attack by the amine is preferred to hydrolysis. However, despite being active sulfonyl derivatives, four-membered heterocyclic sulfonamides, beta-sultams, do not undergo aminolysis in aqueous solution but preferentially react to give hydrolysis products only. The rate of the reaction of beta-sultams in buffered solutions of simple primary amines shows a first-order dependence on amine concentrations attributed to general base-catalyzed hydrolysis by the amine. Even N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, which is both a beta-sultam and a beta-lactam, undergoes hydrolysis at the sulfonyl center rather than aminolysis at either the sulfonyl or acyl center. The solvent kinetic isotope effects (SKIE, k(H(2)O)/k(D(2)O)) for the amine-catalyzed hydrolyses are 1.4 and 1.9 for the hydrolysis of N-benzoyl-beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, respectively, compatible with a general base-catalyzed mechanism. The amine-catalyzed hydrolysis gives a Bronsted beta value of +0.9 for both N-benzoyl beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, indicating that the general base amine is almost fully protonated in the transition state. A general base-catalyzed mechanism for hydrolysis rather than nucleophilic attack was also deduced for the reaction of N-benzyl-4,4-dimethyl-3-oxo-beta-sultam with carboxylate anions based on a SKIE of 1.7-1.9 and rate constants which fit the Bronsted plot for amines. In contrast to acyl transfer reactions, those for sulfonyl transfer appear to show an inverse reactivity-selectivity relationshipthe most active compounds being the most selective. The lack of reactivity of beta-sultams toward amine nucleophiles appears to be related to the mechanism of ring opening of beta-sultams with a decreased reactivity toward amines relative to hydroxide ion, probably related to the expulsion of the relatively poor leaving group amide anion.
与酰基衍生物类似，活化的磺酰基衍生物通常在水中与胺发生氨解反应，因为胺的亲核进攻比水解更占优势。然而，尽管是活性磺酰基衍生物，四元杂环磺酰胺（β-内磺酰胺）在水溶液中并不发生氨解反应，而是仅优先反应生成水解产物。β-内磺酰胺在简单伯胺缓冲溶液中的反应速率对胺浓度呈一级依赖性，这归因于胺的广义碱催化水解。即使是既是β-内磺酰胺又是β-内酰胺的N-苄基-4,4-二甲基-3-氧代-β-内磺酰胺，也在磺酰基中心发生水解，而不是在磺酰基或酰基中心发生氨解。对于N-苯甲酰基-β-内磺酰胺和N-苄基-4,4-二甲基-3-氧代-β-内磺酰胺的胺催化水解，溶剂动力学同位素效应（SKIE，k(H₂O)/k(D₂O)）分别为1.4和1.9，这与广义碱催化机制相符。对于N-苯甲酰基-β-内磺酰胺和N-苄基-4,4-二甲基-3-氧代-β-内磺酰胺，胺催化水解的布仑斯惕β值均为+0.9，表明广义碱胺在过渡态几乎完全质子化。基于1.7 - 1.9的SKIE和符合胺的布仑斯惕图的速率常数，对于N-苄基-4,4-二甲基-3-氧代-β-内磺酰胺与羧酸根阴离子的反应，也推导出水解的广义碱催化机制而非亲核进攻。与酰基转移反应相反，磺酰基转移反应似乎呈现出相反的反应性-选择性关系——活性最高的化合物选择性最强。β-内磺酰胺对胺亲核试剂缺乏反应性似乎与β-内磺酰胺的开环机制有关，其对胺的反应性相对于氢氧根离子降低，这可能与相对较差的离去基团酰胺阴离子的离去有关。
