摘要/Abstract

采用密度泛函理论（DFT）方法研究了在酸性条件下对带有氮杂原子的伯胺与醛的缩合反应机理.研究结果表明，在酸性条件下，碱性更强的杂环氮比羰基氧更容易被质子化，杂环氮作为氢质子桥使缩合反应能垒大大降低，计算得到的反应能量跨度为13.08 kcal/mol.同时，将伯胺上含氮杂环上的N原子调变为P，As原子及改变N原子的位置后缩合反应能垒升高，证实了杂环氮原子协助氢转移的重要性，此理论研究为揭示含氮杂环伯胺与醛的缩合反应机理提供了新的思路与理论依据.
关键词: 含氮杂环, 伯胺, 胺醛缩合, 密度泛函理论, 氢转移
Imines and the intermediate methylamine by the aldimine condensation of primary amines with aldehydes have a potential application in the field of pharmacy, life science, catalysis, material science, etc. In this reaction, the hydrogen transfer in the dehydration step normally prefers the pathway via a water bridge in aqueous solution or a directly dehydration in organic solvent. It is a different mechanism for the aldimine condensation of amine owning neighbouring nitrogenous heterocycle. Herein we investigated the mechanism of aldimine condensation of primary amine containing nitrogenous heterocycle with aldehyde in dichloromethane under acidic conditions using density functional theory (DFT) at ωB97X-D/6-31++G(d,p) level, the calculated results show that compared with specific acid catalysis, the heterocyclic nitrogen with stronger basicity is easier to be protonated than the oxygen of carbonyl group. The whole reaction proceeds two hydrogen transfer steps via nitrogen bridge owning an energy span of 13.08 kcal/mol. The rate-determing step is the second hydrogen transfer step. In each step the heterocyclic nitrogen is a bridge to assist the hydrogen transfer, which could reduce the free energy barrier of the aldimine condensation. It is unfavorable for the reaction pathway via directly hydrogen transfer with a four-membered ring transition state owning a free energy barrier of 32.73 kcal/mol, and the reaction pathway via a water bridge is not located. Meanwhile, the energy barriers increased for systems in which the N atom in heterocycle of primary amine is replaced by P/As atoms. The rate-determining step changes from the second hydrogen transfer step for N system to the first hydrogen transfer step for As system. The position effect of adjacent nitrogen atom is also investigated. The γ position owns the highest reactivity of the aldimine condensation, which implies that the ring strain plays an important role in the aldimine condensation of primary amine containing nitrogenous heterocycle with aldehyde. This theoretical study may provide insights to unveil the nature of aldimine condensation of aldehyde and primary amine owning nitrogeneous heterocycle.
Key words: nitrogenous heterocycle, primary amine, aldimine condensation, DFT, hydrogen transfer


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