The Reactivity of Ambident Nucleophiles: Marcus Theory or Hard and Soft Acids and Bases Principle?

The model reactions CH₃X + (NH—CH=O)M ➔ CH₃—NH—NH═O or NH═CH—O—CH₃ + MX (M = none, Li, Na, K, Ag, Cu; X = F, Cl, Br) are investigated to demonstrate the feasibility of Marcus theory and the hard and soft acids and bases (HSAB) principle in predicting the reactivity of ambident nucleophiles. The delocalization indices (DI) are defined in the framework of the quantum theory of atoms in molecules (QT-AIM), and are used as the scale of softness in the HSAB principle. To react with the ambident nucleophile NH═CH—O⁻, the carbocation H₃C⁺ from CH₃X (F, Cl, Br) is actually a borderline acid according to the DI values of the forming C…N and C…O bonds in the transition states (between 0.25 and 0.49), while the counter ions are divided into three groups according to the DI values of weak interactions involving M (M…X, M…N, and M…O): group I (M = none, and Me₄N) basically show zero DI values; group II species (M = Li, Na, and K) have noticeable DI values but the magnitudes are usually less than 0.15; and group III species (M = Ag and Cu(I)) have significant DI values (0.30–0.61). On a relative basis, H₃C⁺ is a soft acid with respect to group I and group II counter ions, and a hard acid with respect to group III counter ions. Therefore, N-regioselectivity is found in the presence of group I and group II counter ions (M = Me₄N, Li, Na, K), while O-regioselectivity is observed in the presence of the group III counter ions (M = Ag, and Cu(I)). The hardness of atoms, groups, and molecules is also calculated with new functions that depend on ionization potential (I) and electron affinity (A) and use the atomic charges obtained from localization indices (LI), so that the regioselectivity is explained by the atomic hardness of reactive nitrogen atoms in the transition states according to the maximum hardness principle (MHP). The exact Marcus equation is derived from the simple harmonic potential energy parabola, so that the concepts of activation free energy, intrinsic activation barrier, and reaction energy are completely connected. The required intrinsic activation barriers can be either estimated from ab initio calculations on reactant, transition state, and product of the model reactions, or calculated from identity reactions. The counter ions stabilize the reactant through bridging N- and O-site of reactant of identity reactions, so that the intrinsic barriers for the salts are higher than those for free ambident anions, which is explained by the increased reorganization parameter Δr. The proper application of Marcus theory should quantitatively consider all three terms of Marcus equation, and reliably represent the results with potential energy parabolas for reactants and all products. For the model reactions, both Marcus theory and HSAB principle/MHP principle predict the N-regioselectivity when M = none, Me₄N, Li, Na, K, and the O-regioselectivity when M = Ag and Cu(I). © 2019 Wiley Periodicals, Inc.     

Is There a Minimum Electrophilicity Principle in Chemical Reactions？

For 25 simple reactions, the changes of the hardness （△η）, polarizability （△α） and electrophilicity index （△ω） and their cube-roots （△η^1/3, △α^1/3, △ω^1/3） were calculated. It is shown that although the Maximum Hardness and Minimum Polarizability Principles are not valid for all reactions, but in most cases △ω^1/3〈0, whereas we always find △ω〈0. Our observation implies to this fact that for those chemical reactions in which the number of moles decreases or at least remains constant, the most stable species （reactants or products） have the lowest sum of electrophilicities. In other words ＂the natural direction of a chemical reaction is toward a state of minimum electrophilicity＂. This fact may be called Minimum Electrophilicity Principle （MEP）.     

HSAB-driven chemoselective N-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives

The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1H)-pyrimidinones 1-3 undergo highly chemoselective N¹-methylation or ethylation when treated with methyl- or ethylsulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O²-alkylation. Potassium salts of the same bases in DMF undergo prevalent O²-attack. Under the same conditions, a similar but less chemoselective behaviour is observed in alkylation of thymine and uracil, where some N³-attack occurs. This can be rationalised in terms of the HSAB principle.     

异构现象与最大硬度原理

利用原子-键电负性均衡方法计算了700多个异构体的硬度, 通过与标准生成焓所确定的相对稳定性比较后发现, 多数异构体并不遵守最大硬度原理.     

Fukui函数和局域软度应用于亲电加成反应的区位选择性的研究

Fukui函数、局域软度、广义Fukui函数以及广义软度通常被称为反应描述符。使用它们研究和探讨了HCl与不对称烯烃以及溴苯硒与不对称苯乙烯的亲电加成反应的区位选择性。在MP2/6-311++G(d, p)理论水平下,采用有限差分方法计算这些反应描述符,同时也使用ABEEMσπ方法进行了计算。ABEEMσπ模型下的局域软度和广义局域软度,分别结合局域硬-软酸碱(HSAB)原理,得出亲电试剂氯化氢与溴苯硒,更容易进攻不对称乙烯和苯乙烯中的马氏碳原子,符合马氏规则。而有限差分方法不能完全地解释该系列反应的区位选择性。此外,主要产物所对应的马氏碳原子的广义局域软度值,就能够预测出此类反应的活性序列,所得结果与速率常数有很好的关联。     

An Electrostatic Bond Energy Model for Enthalpies of Formation of Chloroalkanes in Gaseous States

An electrostatic bond energy model is formulated to fit the enthalpies of formation and dipole moments of the alkanes and chloroalkanes. In this model, the charge distributions are calculated by an electrostatic approach similar to the "MSE" method, and the enthalpy of formation of a molecule is the sum of the bond energy terms plus the electrostatic energy of the interactions between the charges on all atoms. All parameters of this model are obtained by parameterization. The calculated dipole moments for 13 chloroalkanes and enthalpies of formation for 19 alkanes and non-geminal chloroalkanes agree with the determined values very well. To calculate the enthalpies of formation of geminal chloroalkanes, a correction mainly attributed to the van der Waals interactions in the geminal substituted group, about 24 kJ/mol per pair of geminal chlorine atoms, is introduced.     

DFT-HSAB prediction of regioselectivity in 1,3-dipolar cycloadditions: behavior of (4-substituted)benzonitrile oxides towards methyl propiolate

The regioselectivity of 1,3-dipolar cycloadditions between (4-substituted)benzonitrile oxides and methyl propiolate cannot be rationalized on the basis of the electron demand of the reactants or frontier molecular-orbital theory. To this problem, we have applied a quantitative formulation of the hard-soft acid-base principle developed within the density functional theory. Global and local reactivity indices were computed at B3LYP/6-311+G(d,p) level. The details of charge transfer upon the reactive encounter have been elucidated, and the computed regioselectivity has been shown to be in good agreement with experimental data.