The experimentally observed effects of water, and the effects of silanol groups, on the liquid-phase amine–catalyzed aldol reaction of acetone with 4-nitrobenzaldehyde have been elucidated with a comprehensive theoretical model describing the reaction kinetics. The CBS-QB3 model chemistry is used, with bulk solvent effects accounted for according to COSMO–RS theory, and water molecules explicitly considered.. Two promoting water molecules were found to be optimal in reducing the Gibbs free energy barriers for reactions involving a proton transfer, i.e., the carbinolamine and enamine formation steps, and the aldol product liberation step. The presence of one water molecule in the carbon-carbon coupling step was already sufficient to prevent the formation of a site-blocking enamine species, which would otherwise lead to deactivation of the amine. Compared to a single water molecule, isolated silanol groups were found to assist the amine in a similar and slightly more pronounced manner, resulting in overall lower barriers for all transition states. Promotion by two vicinal silanols resulted in even lower barriers. The effect of water was found to be more pronounced in apolar hexane as compared to DMSO, i.e., resulting in a less pronounced deactivation of the amine, and lower barriers for reactions where water is assisting in the transition state.

通过描述反应动力学的综合理论模型，阐明了实验观察到的水和硅烷醇基团对丙酮与4-硝基苯甲醛在液相胺催化的醛醇缩合反应中的影响。使用了CBS-QB3模型化学，根据COSMO-RS理论考虑了本体溶剂效应，并明确考虑了水分子。发现两个促进水分子在减少涉及质子的反应的吉布斯自由能垒方面是最佳的转移，即甲醇胺和烯胺的形成步骤，以及醛醇产物释放步骤。在碳-碳偶联步骤中一个水分子的存在已经足以防止形成位点封闭的烯胺类，否则会导致胺失活。与单个水分子相比，发现分离的硅烷醇基团以相似且更明显的方式辅助胺，从而导致所有过渡态的整体势垒降低。两种邻位硅烷醇的促进作用导致更低的屏障。与DMSO相比，发现水的影响在非极性己烷中更为明显，即，导致胺的失活程度不那么明显，并且在水协助过渡态的反应中，势垒降低。