Why Do N-Alkylated Anilides Bend Over? The Factors Dictating the Divergent Conformational Preferences of 2° and 3° N-Aryl Amides
Why Do N-Alkylated Anilides Bend Over? The Factors Dictating the Divergent Conformational Preferences of 2° and 3° N-Aryl Amides
复制标题
DOI：
10.1021/acs.jpca.9b04555
复制
发表时间：
2019-09-05
影响因子：
2.9
通讯作者：
Bloomfield, Aaron J.
中科院分区：
文献类型：
--
作者：
Pros, Gabrielle J.;Bloomfield, Aaron J.
采用密度泛函理论（DFT），利用B3LYP泛函和6-31G(d)基集确定了28种立体和电子结构不同的n -芳基酰胺的构象偏好。对于每种化合物，顺式和反式构象都进行了优化，并计算了基态能量差。其中6种化合物的势能面是顺式和反式构象围绕n -芳基键旋转的函数（旋转幅度为5度）。采用自然键轨道（NBO）删除策略来确定共轭对每个构象能量的贡献程度。通过将这些计算结果与先前报道的实验数据进行比较，给出了2度n -芳基酰胺和3度n -烷基- n -芳基酰胺不同构象偏好的解释。这一解释解释了所观察到的决定最佳构象几何形状的空间和电子因素之间的关系，以及顺式和反式构象之间的能量差异的大小：除了在最极端的情况下，2度酰胺保持反式构象，n键芳烃与酰胺位于同一平面，除非它有邻位取代基；对于3度n -烷基- n -芳基酰胺，其中烷基和芳基取代基连接在一个小环中，除甲酰胺外，大多数情况下也倾向于反式构象，并且芳烃和酰胺保持共轭；对于3度n -烷基- n -芳基酰胺，其中烷基和芳基取代基没有连接在一个小环中，两个n键取代基之间的烯丙基张力迫使芳基取代基旋转出酰胺的平面，并且由于芳烃的π系统和羰基氧原子上的孤对之间的排斥力，反式构象相对于顺式构象不稳定。随着芳烃上电子密度的增加，顺式构象比反式构象越来越稳定，因为越富电子的芳烃采用更正交的排列，增加了与羰基氧的相互作用，同时由于pi系统中电子密度的增加而增加了排斥力的大小。在几乎所有的情况下，即使芳烃与酰胺正交，2度酰胺也有利于反式构象，因为C-N-C键角的扩展会以C-N-H键角为代价，而这对3度酰胺则不利。
The conformational preferences of 28 sterically and electronically diverse N-aryl amides were determined using density functional theory (DFT), using the B3LYP functional and 6-31G(d) basis set. For each compound, both the cis and trans conformers were optimized, and the difference in ground state energy calculated. For six of the compounds, the potential energy surface was determined as a function of rotation about the N-aryl bond (by 5 degrees increments) for both cis and trans conformers. A natural bond orbital (NBO) deletion strategy was also employed to determine the extent of the contribution of conjugation to the energies of each of the conformers. By comparing these computational results with previously reported experimental data, an explanation for the divergent conformational preferences of 2 degrees N-aryl amides and 3 degrees N-alkyl-N-aryl amides was formulated. This explanation accounts for the observed relationships of both steric and electronic factors determining the geometry of the optimum conformation, and the magnitude of the energetic difference between cis and trans conformers: except under the most extreme scenarios, 2 degrees amides maintain a trans conformation, and the N-bound arene lies in the same plane as the amide unless it has ortho substituents; for 3 degrees N-alkyl-N-aryl amides in which the alkyl and aryl substituents are connected in a small ring, trans conformations are also favored, for most cases other than formamides, and the arene and amide remain in conjugation; and for 3 degrees N-alkyl-N-aryl amides in which the alkyl and aryl substituents are not connected in a small ring, allylic strain between the two N-bound substituents forces the aryl substituent to rotate out of the plane of the amide, and the trans conformation is destabilized with respect to the cis conformation due to repulsion between the pi system of the arene and the lone pairs on the oxygen atom of the carbonyl. The cis conformation is increasingly more stable than the trans conformation as electron density is increased on the arene because the more electron-rich arenes adopt a more orthogonal arrangement, increasing the interaction with the carbonyl oxygen, while simultaneously increasing the magnitude of the repulsion due to the increased electron density in the pi system. The trans conformation is favored for 2 degrees amides even when the arene is orthogonal to the amide, in nearly all cases, because the C-N-C bond angle can expend at the expense of the C-N-H bond angles, while this is not favorable for 3 degrees amides.