Formation of 15-membered azalactone by double reductive amination was analyzed using molecular mechanics and density functional theory calculations for simplified model compounds. As a result, the following aspects were clarified. When methylamine attacks a linear bis-aldehyde in the first step, there are possibilities that two regioisomers are formed. However, one of them exhibited remarkably stable energy level compared with the other. The stable isomer indicated a short distance between a methylamine moiety and an unreacted aldehyde. This short distance, about 2.3 Å, could be explained by hydrogen bonding, which implied relatively easy cyclization in the second step. Moreover, this cyclization process was supposed to be exothermic according to comparison of energy levels before and after cyclization.

中文翻译：

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使用分子力学和密度泛函理论计算通过双还原胺化形成15元氮杂内酯的计算研究。

使用简化的模型化合物的分子力学和密度泛函理论计算，分析了通过双重还原胺化形成的15元氮杂内酯。结果，阐明了以下方面。当第一步中甲胺攻击线性双醛时，有可能会形成两种区域异构体。但是，其中一个与另一个相比表现出了非常稳定的能级。稳定的异构体表明甲胺部分和未反应的醛之间的距离很短。这种短的距离（约2.3Å）可以用氢键解释，这意味着在第二步中相对容易环化。此外，根据环化前后能量水平的比较，该环化过程被认为是放热的。