A practical guide for estimating rates of heterolysis reactions.
A practical guide for estimating rates of heterolysis reactions.
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DOI：
10.1021/ar100091m
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发表时间：
2010-11
影响因子：
18.3
通讯作者：
Nicolas Streidl;B. Denegri;O. Kronja;H. Mayr
中科院分区：
文献类型：
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作者：
Nicolas Streidl;B. Denegri;O. Kronja;H. Mayr
化学家受过良好的训练，能识别出是什么控制着一系列化合物的相对反应性。因此，众所周知，R-X的电离速率如何受到碳正离子R（+）的稳定性、离去基X（-）的性质或溶剂的电离能力的影响。另一方面，当要求估计某种底物在某种溶剂中电离的半衰期时，大多数化学家都放弃了。然而，这个问题在日常实验室实践中是至关重要的。某种底物R-X能在酒精或水溶液中处理而不被溶解吗？具有生物活性的叔胺或唑能通过季铵离子电离释放吗？在本帐户中，我们描述了解决此类实验问题的直接方法。这些问题的半定量答案由相关方程logk(25°C) = s(f)(N（f) + E(f)）给出，其中碳正离子R（+）用电逸性参数E(f)来表征，在某种溶剂中的离去基X（-）用核逸性参数N(f)和核逸性特异性灵敏度参数s(f)来表征。由于s(f)通常约为1 (0.8 < s(f) < 1.2)，当E(f) + N(f) = -4时，25℃下电离半衰期约为1小时。这个相关方程在形式上类似于线性自由能关系，该关系被用来推导目前可用的最全面的亲核和亲电性尺度（Mayr， H.; Bug， T.; Gotta, m.f.; Hering， N.; Irrgang， B.; Janker， B.; Kempf， B.; Loos， R.; official， A. R.; Remennikov， G.; Schimmel， H.）。j。化学。社会科学学报，2001,23(3):9500-9512。在相关方程的基础上，对不同苯并羟基衍生物（芳基(2)CH-X）的628个溶剂溶解速率常数k（25°C）进行最小二乘最小化，我们得到了39个苯并羟基离子的电逸性参数E(f)和101个常见离去基和溶剂组合的核逸性参数N(f)和s(f)。我们表明，参考电离液的E(f)参数可以用于确定几乎任何离去基和溶剂组合的N(f)和s(f)。参考体系的核逸性参数可以类似地用于推导其他类型碳正离子的电逸性E(f)。虽然人们早就认识到好的亲核试剂不一定是不好的核试剂，但现在有报道称，在亲电性和电疏性之间也没有一般的反比关系。虽然亲电性较强的甲基和甲氧基取代苯并氢氧离子通常是较弱的电离合剂，但在氨基取代苯并氢氧离子系列中，亲电性和电离合性之间的反比关系被打破。由于这种处理既没有明确考虑碳阳离子的差异溶剂化，也没有明确考虑空间效应，因此对不属于苯并羟基系列的底物的预测仅在10因子内可靠。这对物理有机化学家来说是很难接受的，因为他们习惯于在狭窄的化合物群中进行高精度的研究。然而，在25个数量级的反应性范围内寻找方向的合成化学家可能会欣赏这种方法的简单性，它只需要考虑E(f) + N(f)的和或参考我们的总结图。
Chemists are well trained to recognize what controls relative reactivities within a series of compounds. Thus, it is well-known how the rate of ionization of R-X is affected by the stabilization of the carbocation R(+), the nature of the leaving group X(-), or the solvent ionizing power. On the other hand, when asked to estimate the half-life of the ionization of a certain substrate in a certain solvent, most chemists resign. This question, however, is crucial in daily laboratory practice. Can a certain substrate R-X be handled in alcoholic or aqueous solution without being solvolyzed? Can a biologically active tertiary amine or azole be released by ionization of a quaternary ammonium ion? In this Account, we describe a straightforward means of addressing such experimental concerns. A semiquantitative answer to these questions is given by the correlation equation log k(25 °C) = s(f)(N(f) + E(f)), in which carbocations R(+) are characterized by the electrofugality parameter E(f), and leaving groups X(-) in a certain solvent are characterized by the nucleofugality parameter N(f) and the nucleofuge-specific sensitivity parameter s(f). As s(f) is typically around 1 (0.8 < s(f) < 1.2), ionization half-lives of around 1 h at 25 °C can be expected when E(f) + N(f) = -4. This correlation equation is formally analogous to the linear free energy relationship that was used to derive the most comprehensive nucleophilicity and electrophilicity scales presently available (Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. Reference Scales for the Characterization of Cationic Electrophiles and Neutral Nucleophiles. J. Am. Chem. Soc. 2001, 123, 9500-9512). By subjecting 628 solvolysis rate constants k(25 °C) for different benzhydryl derivatives (aryl(2)CH-X) to a least-squares minimization on the basis of the correlation equation, we obtained and tabulate here (i) the electrofugality parameters E(f) for 39 benzhydrylium ions and (ii) the nucleofuge-specific parameters N(f) and s(f) for 101 combinations of common leaving groups and solvents. We show that the E(f) parameters of the reference electrofuges can be used to determine N(f) and s(f) for almost any combination of leaving group and solvent. The nucleofuge-specific parameters of the reference systems can analogously be used to derive the electrofugalities E(f) of other types of carbocations. While it has long been recognized that good nucleophiles are not necessarily poor nucleofuges, it is now reported that there is also no general inverse relationship between electrophilicity and electrofugality. Although more electrophilic methyl- and methoxy-substituted benzhydrylium ions are generally weaker electrofuges, the inverse relationship between electrophilicity and electrofugality breaks down in the series of amino-substituted benzhydrylium ions. Because neither differential solvation of the carbocations nor steric effects are explicitly considered by this treatment, predictions for substrates not belonging to the benzhydrylium series are only reliable within a factor of 10. This is hardly acceptable to physical organic chemists, who are used to high precision within narrow groups of compounds. The synthetic chemist, however, who is seeking orientation in a reactivity range of 25 orders of magnitude, might appreciate the simplicity of this approach, which only requires considering the sum E(f) + N(f) or consulting our summary graphs.