Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil.
J Org Chem. 2010 Nov 5;75(21):7186-93. doi: 10.1021/jo101366m.
Hydrolysis of closely related compounds show how subtle structural differences markedly change reaction mechanisms. While in the hydrolysis of 3-acetoxy-2-naphthoic acid (3AC2NA) the reacting groups rotate freely, favoring intramolecular general base catalysis, the 1-acetoxy-2-naphthoic acid (1AC2NA) isomer is caged in an energy wall that freezes a conformation suitable for intramolecular nucleophilic attack, in contrast to the results expected for reactions governed largely by electronic effects. The results highlight the importance of the dynamics of equilibrium fluctuations between most stable conformers in the control of the reaction mechanism, (i) promoting the nucleophilic attack in 1AC2NA by allowing the most stable conformers to equilibrate only via rotation in a direction that intercepts the reaction coordinate and (ii) favoring a general base-catalyzed water attack in 3AC2NA by favoring equilibration via rotation that allows inclusion of a water molecule in a proper position for reaction.
水解密切相关的化合物可以揭示出结构上的细微差异如何显著改变反应机制。在 3-乙酰氧基-2-萘甲酸（3AC2NA）的水解中，反应基团可以自由旋转，有利于分子内的广义碱催化；而 1-乙酰氧基-2-萘甲酸（1AC2NA）异构体则被束缚在能量壁中，冻结了适合分子内亲核攻击的构象，这与主要由电子效应控制的反应的预期结果形成对比。这些结果强调了在反应机制控制中，最稳定构象之间的平衡波动动力学的重要性，（i）通过允许最稳定构象仅通过在截获反应坐标的方向上旋转来平衡，从而促进 1AC2NA 中的亲核攻击，（ii）通过有利于通过允许水分子进入适当位置进行反应的旋转来平衡，从而有利于 3AC2NA 中的广义碱催化的水攻击。
