Chen Xin, Brauman John I
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2008 Nov 12;130(45):15038-46. doi: 10.1021/ja802814a. Epub 2008 Oct 18.
The relationship between nucleophilicity and the structure/environment of the nucleophile is of fundamental importance in organic chemistry. In this work, we have measured nucleophilicities of a series of substituted alkoxides in the gas phase. The functional group substitutions affect the nucleophiles through ion-dipole, ion-induced dipole interactions and through hydrogen bonding whenever structurally possible. This set of alkoxides serves as an ideal model system for studying nucleophiles under microsolvation settings. Marcus theory was applied to analyze the results. Using Marcus theory, we separate nucleophilicity into two independent components, an intrinsic nucleophilicity and a thermodynamic driving force determined solely by the overall reaction exothermicity. It is found that the apparent nucleophilicities of the substituted alkoxides are always much lower than those of the unsubstituted ones. However, ion-dipole, ion-induced dipole interactions, by themselves, do not significantly affect the intrinsic nucleophilicity; the decrease in the apparent nucleophilicity results from a weaker thermodynamic driving force. On the other hand, hydrogen bonding not only stabilizes the nucleophile but also increases the intrinsic barrier height by 3 to approximately 4 kcal mol (-1). In this regard, the hydrogen bond is not acting as a perturbation in the sense of an external dipole but more directly affects the electronic structure and reactivity of the nucleophilic alkoxide. This finding offers a deeper insight into the solvation effect on nucleophilicity, such as the remarkably lower reactivities in nucleophilic substitution reactions in protic solvents than in aprotic solvents.
在有机化学中，亲核性与亲核试剂的结构/环境之间的关系至关重要。在这项工作中，我们测量了一系列取代醇盐在气相中的亲核性。官能团取代通过离子 - 偶极、离子诱导偶极相互作用以及在结构允许时通过氢键作用来影响亲核试剂。这组醇盐作为研究微溶剂化环境下亲核试剂的理想模型体系。我们应用马库斯理论来分析结果。利用马库斯理论，我们将亲核性分为两个独立的组分，一个是固有亲核性，另一个是仅由总反应放热决定的热力学驱动力。结果发现，取代醇盐的表观亲核性总是远低于未取代的醇盐。然而，离子 - 偶极、离子诱导偶极相互作用本身并不会显著影响固有亲核性；表观亲核性的降低是由较弱的热力学驱动力导致的。另一方面，氢键不仅稳定了亲核试剂，还使固有势垒高度增加了3至约4千卡摩尔⁻¹。在这方面，氢键并非像外部偶极那样作为一种微扰起作用，而是更直接地影响亲核醇盐的电子结构和反应性。这一发现为溶剂化对亲核性的影响提供了更深入的见解，例如在质子溶剂中亲核取代反应的反应活性明显低于非质子溶剂中的反应活性。
