Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, California 94132, United States.
J Org Chem. 2012 Nov 2;77(21):9535-40. doi: 10.1021/jo301134q. Epub 2012 Oct 17.
The "element effect" in nucleophilic aromatic substitution reactions (S(N)Ar) is characterized by the leaving group order, F > NO(2) > Cl ≈ Br > I, in activated aryl halides. Multiple causes for this result have been proposed. Experimental evidence shows that the element effect order in the reaction of piperidine with 2,4-dinitrophenyl halides in methanol is governed by the differences in enthalpies of activation. Computational studies of the reaction of piperidine and dimethylamine with the same aryl halides using the polarizable continuum model (PCM) for solvation indicate that polar, polarizability, solvation, and negative hyperconjugative effects are all of some importance in producing the element effect in methanol. In addition, a reversal of polarity of the C-X bond from reactant to transition state in the case of ArCl and ArBr compared to ArF also contributes to their differences in reactivity. The polarity reversal and hyperconjugative influences have received little or no attention in the past. Nor has differential solvation of the different transition states been strongly emphasized. An anionic nucleophile, thiolate, gives very early transition states and negative activation enthalpies with activated aryl halides. The element effect is not established for these reactions. We suggest that the leaving group order in the gas phase will be dependent on the exact combination of nucleophile, leaving group, and substrate framework. The geometry of the S(N)Ar transition state permits useful, qualitative conceptual distinctions to be made between this reaction and other modes of nucleophilic attack.
亲核芳香取代反应（S(N)Ar）中的“元素效应”的特征是离去基团的顺序，在活化的芳基卤化物中，F > NO(2) > Cl ≈ Br > I。对于这一结果，已经提出了多种原因。实验证据表明，在哌啶与 2,4-二硝基苯基卤化物在甲醇中的反应中，元素效应顺序受活化能差的影响。使用极化连续体模型（PCM）对溶剂化进行计算研究，研究哌啶和二甲胺与相同芳基卤化物的反应，表明极性、极化率、溶剂化和负超共轭效应在甲醇中产生元素效应方面都具有一定的重要性。此外，与 ArF 相比，ArCl 和 ArBr 中 C-X 键的极性从反应物到过渡态发生反转，这也导致它们的反应性存在差异。过去，极性反转和超共轭影响几乎没有受到关注。不同过渡态的不同溶剂化也没有得到强烈强调。亲核试剂硫醇盐给出了非常早期的过渡态和与活化的芳基卤化物的负活化焓，对于这些反应，不存在元素效应。我们认为，在气相中，离去基团的顺序将取决于亲核试剂、离去基团和底物框架的精确组合。S(N)Ar 过渡态的几何形状允许对这种反应和其他亲核进攻模式进行有用的、定性的概念区分。
