Theoretical study of base-catalyzed amide hydrolysis: Gas- and aqueous-phase hydrolysis of formamide
Theoretical study of base-catalyzed amide hydrolysis: Gas- and aqueous-phase hydrolysis of formamide
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DOI：
10.1021/ja9837349
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发表时间：
1999-06-23
影响因子：
15
通讯作者：
Kollman, PA
中科院分区：
文献类型：
--
作者：
Bakowies, D;Kollman, PA
采用量子化学和统计力学相结合的方法研究了甲酰胺在气相和水溶液中的碱催化水解反应。一个三步骤的程序已被应用，其中包括高层次的从头计算，校准的经验溶质-溶剂的潜力，和经典的Monte Carlo模拟的溶质浸泡在浴中的溶剂分子的气相反应路径的确定。这些模拟产生溶剂效应作为沿预定反应坐标沿着的平均力的势。碱催化水解的三个连续步骤中的每一个都进行了详细的分析：四面体中间体的形成，其构象异构化，以及随后的分解产物。该反应在气相中是非常放热的，并且对于后两个步骤仅涉及适度的障碍。然而，水性溶剂诱导朝向中间体形成的显著屏障。另一方面，它也有利于构象异构化，并产生一个更像产品的过渡态的分解步骤。溶剂效应，表示在溶剂化的自由能的差异，被发现反映在溶质的电荷分布的变化，并很容易解释的氢键模式的分析。计算的自由能分布是令人满意的协议与现有的实验数据的溶液相反应。
Base-catalyzed hydrolysis of formamide in the gas phase and in aqueous solution has been studied using a combination of quantum chemical and statistical mechanical methods. A three-step procedure has been applied which comprises the determination of a gas-phase reaction path by high-level ab initio calculations, the calibration of empirical solute-solvent potentials, and classical Monte Carlo simulations of the solute immersed in a bath of solvent molecules. These simulations yield the solvent effect as a potential of mean force along the predetermined reaction coordinate. Each of the three consecutive steps of base-catalyzed hydrolysis has been analyzed in detail: the formation of a tetrahedral intermediate, its conformational isomerization, and the subsequent breakdown to products. The reaction is very exothermic in the gas phase and involves only moderate barriers for the latter two steps. Aqueous solvent, however, induces a significant barrier toward formation of the intermediate. On the other hand, it also facilitates conformational isomerization and produces a more product-like transition state for the breakdown step. Solvent effects, as expressed by differences in free energy of solvation, are found to reflect variations in the solute's charge distribution and are readily explained by the analysis of hydrogen bond patterns. The calculated free energy profile is in satisfactory agreement with available experimental data for the solution-phase reaction.