Di Valentin C, Freccero M, Zanaletti R, Sarzi-Amadè M
Dipartimento di Chimica Organica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy.
J Am Chem Soc. 2001 Aug 29;123(34):8366-77. doi: 10.1021/ja010433h.
The reactivity of the alkylating agent o-quinone methide (o-QM) toward NH(3), H(2)O, and H(2)S, prototypes of nitrogen-, oxygen-, and sulfur-centered nucleophiles, has been studied by quantum chemical methods in the frame of DF theory (B3LYP) in reactions modeling its reactivity in water with biological nucleophiles. The computational analysis explores the reaction of NH(3), H(2)O, and H(2)S with o-QM, both free and H-bonded to a discrete water molecule, with the aim to rationalize the specific and general effect of the solvent on o-QM reactivity. Optimizations of stationary points were done at the B3LYP level using several basis sets [6-31G(d), 6-311+G(d,p), adding d and f functions to the S atom, 6-311+G(d,p),S(2df), and AUG-cc-pVTZ]. The activation energies calculated for the addition reactions were found to be reduced by the assistance of a water molecule, which makes easier the proton-transfer process in these alkylation reactions by at least 12.9, 10.5, and 6.0 kcal mol(-1) [at the B3LYP/AUG-cc-pVTZ//B3LYP/6-311+G(d,p) level], for ammonia, water, and hydrogen sulfide, respectively. A proper comparison of an uncatalyzed with a water-catalyzed reaction mechanism has been made on the basis of activation Gibbs free energies. In gas-phase alkylation of ammonia and water by o-QM, reactions assisted by an additional water molecule H-bonded to o-QM (water-catalyzed mechanism) are favored over their uncatalyzed counterparts by 5.6 and 4.0 kcal mol(-1) [at the B3LYP/6-311+G(d,p) level], respectively. In contrast, the hydrogen sulfide alkylation reaction in the gas phase shows a slight preference for a direct alkylation without water assistance, even though the free energy difference (DeltaDeltaG(#)) between the two reaction mechanisms is very small (by 1.0 kcal mol(-1) at the B3LYP/6-311+G(d,p),S(2df) level of theory). The bulk solvent effect, evaluated by the C-PCM model, significantly modifies the relative importance of the uncatalyzed and water-assisted alkylation mechanism by o-QM in comparison to the case in the gas phase. Unexpectedly, the uncatalyzed mechanism becomes highly favored over the catalyzed one in the alkylation reaction of ammonia (by 7.0 kcal mol(-1)) and hydrogen sulfide (by 4.0 kcal mol(-1)). In contrast, activation induced by water complexation still plays an important role in the o-QM hydration reaction in water as solvent.
在密度泛函理论（B3LYP）框架下，采用量子化学方法研究了邻醌甲基化物（o-QM）与氮、氧、硫中心亲核试剂的原型NH₃、H₂O和H₂S的反应活性，这些反应模拟了o-QM在水中与生物亲核试剂的反应活性。计算分析探究了NH₃、H₂O和H₂S与游离的以及与离散水分子形成氢键的o-QM的反应，目的是阐明溶剂对o-QM反应活性的特定和一般影响。使用多个基组[6-31G(d)、6-311+G(d,p)，对S原子添加d和f函数、6-311+G(d,p)、S(2df)以及AUG-cc-pVTZ]在B3LYP水平上对驻点进行了优化。发现对于加成反应计算得到的活化能在水分子的协助下降低，这使得这些烷基化反应中的质子转移过程至少分别降低了12.9、10.5和6.0 kcal mol⁻¹[在B3LYP/AUG-cc-pVTZ//B3LYP/6-311+G(d,p)水平]，分别对应氨、水和硫化氢。基于活化吉布斯自由能对未催化反应机制与水催化反应机制进行了恰当比较。在气相中o-QM对氨和水的烷基化反应中，与未催化反应相比，由与o-QM形成氢键的额外水分子协助的反应（水催化机制）分别更有利5.6和4.0 kcal mol⁻¹[在B3LYP/6-311+G(d,p)水平]。相比之下，气相中的硫化氢烷基化反应即使两种反应机制之间的自由能差（ΔΔG⁽#⁾）非常小（在B3LYP/6-311+G(d,p)、S(2df)理论水平下为1.0 kcal mol⁻¹），仍略微倾向于无水协助的直接烷基化。通过C-PCM模型评估的本体溶剂效应与气相情况相比，显著改变了o-QM未催化和水协助烷基化机制的相对重要性。出乎意料的是，在氨（相差7.0 kcal mol⁻¹）和硫化氢（相差4.0 kcal mol⁻¹）的烷基化反应中，未催化机制比催化机制更受青睐。相比之下，在以水为溶剂的o-QM水合反应中，水络合诱导的活化仍然起着重要作用。
