Theoretical and experimental studies of the isomeric protonation in solution for a prototype aliphatic ring containing two nitrogens.
Theoretical and experimental studies of the isomeric protonation in solution for a prototype aliphatic ring containing two nitrogens.
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含两个氮原子的原型脂肪环溶液中异构质子化的理论和实验研究。
DOI：
10.1021/jp9082085
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
MesserJr,WilliamS
中科院分区：
文献类型：
--
作者：
Nagy,PeterI;Maheshwari,Aditya;Kim,Yong-Wah;MesserJr,WilliamS
对N-甲基哌嗪作为一个含仲、叔氮原子的六元脂肪环的互变异构质子化反应进行了理论计算。在三种溶剂，水，乙腈，和二氯甲烷中的质子化进行了研究。采用IEF-PCM极化连续介质溶剂模型，在B3 LYP/aug-cc-pvtz和QCISD（T）/CBS水平上进行了计算.相对溶剂化自由能也计算上明确的溶剂模型，利用自由能微扰理论，在Monte Carlo模拟中实现。计算了N-甲基哌嗪互变异构体在无限稀释水溶液中以47/53的比例在仲氮质子化（NMps）而不是在叔氮质子化（NMpt）的相对自由能。该比率在低极性溶剂中进一步降低。与此相反，NMR实验表明，质子化主要发生在仲氮在0.37摩尔的水溶液与NMps/NMpt = 80/20。NMps互变异构体在相同浓度的二氯甲烷中是唯一的。理论和实验之间的差异解决了考虑并行的溶质质子化的缔合平衡。其结果是，理论预测的互变异构体的比例与实验值接近一致。NMps互变异构体可以形成一个优选的二聚体结构，其中一个或两个氯离子与缔合单体的质子形成氢键。计算结果表明，质子迁移可能发生在水溶剂的帮助下或沿着分子内质子跳跃的扭曲船构象。在DCM中的变温NMR实验的基础上，预测的活化自由能为约10千卡/摩尔。
Theoretical calculations were carried out for studying the tautomeric protonation ofN-methylpiperazine as a prototype six-member aliphatic ring containing a secondary and a tertiary nitrogen atom. The protonation was investigated in three solvents, water, acetonitrile, and dichloromethane. Calculations were performed up to the B3LYP/aug-cc-pvtz and QCISD(T)/CBS levels by applying the IEF-PCM polarizable continuum dielectric solvent model. Relative solvation free energies also were calculated upon explicit solvent models by utilizing the free-energy perturbation theory as implemented in Monte Carlo simulations. The relative free energy for theN-methylpiperazine tautomer protonated at the secondary (NMps) rather than at the tertiary (NMpt) nitrogen was calculated at a ratio of 47/53 in infinitely dilute aqueous solution. The ratio further decreased in lower-polarity solvents. In contrast, NMR experiments suggested that the protonation takes place primarily at the secondary nitrogen in 0.37 molar aqueous solution withNMps/NMpt = 80/20. TheNMps tautomer was exclusive in dichloromethane at the same concentration. The discrepancy between theory and experiment was resolved by considering association equilibria in parallel with the protonation for the solute. As a result, the theoretically predicted tautomer ratios were obtained in close agreement with the experimental values. TheNMps tautomer could form a preferable dimeric structure, where one or two chloride anion(s) was/were in hydrogen bonds with protons of the associating monomers. The calculations suggest that the proton relocation may take place by solvent assistance in water or along an intramolecular proton jump in the twist-boat conformation. The predicted activation free energy was about 10 kcal/mol on the basis of variable-temperature NMR experiments in DCM.