Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, United States.
J Phys Chem A. 2019 Sep 5;123(35):7609-7618. doi: 10.1021/acs.jpca.9b04555. Epub 2019 Aug 26.
The conformational preferences of 28 sterically and electronically diverse -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° 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° aryl amides and 3° -alkyl--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° amides maintain a trans conformation, and the bound arene lies in the same plane as the amide unless it has ortho substituents; for 3° -alkyl--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° -alkyl--aryl amides in which the alkyl and aryl substituents are not connected in a small ring, allylic strain between the two 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 π 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 π system. The trans conformation is favored for 2° 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° amides.
使用密度泛函理论（DFT），使用 B3LYP 函数和 6-31G(d) 基组，确定了 28 种具有不同空间位阻和电子效应的 -芳基酰胺的构象偏好。对于每个化合物，都对顺式和反式构象进行了优化，并计算了基态能量的差异。对于其中的 6 种化合物，还确定了 N-芳基键旋转（每 5°递增）时的势能面，适用于顺式和反式构象。还采用自然键轨道（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之前报道的实验数据进行比较，提出了对 2°芳基酰胺和 3°-烷基--芳基酰胺不同构象偏好的解释。该解释说明了决定最佳构象几何形状的空间位阻和电子因素的关系，以及顺式和反式构象之间能量差异的大小：除了在最极端的情况下，2°酰胺保持反式构象，芳环位于酰胺所在平面内，除非芳环有邻位取代基；对于 3°-烷基--芳基酰胺，其中烷基和芳基取代基连接在一个小环中，对于大多数情况下的酰胺，反式构象也是有利的，芳环和酰胺保持共轭；对于 3°-烷基--芳基酰胺，其中烷基和芳基取代基不在一个小环中，两个结合取代基之间的烯丙基应变迫使芳基取代基从酰胺平面中旋转出来，由于芳环的π系统与羰基氧原子上的孤对电子之间的排斥，反式构象相对于顺式构象变得不稳定。随着芳环上的电子密度增加，顺式构象变得越来越稳定，因为富电子芳环采用更正交的排列，增加了与羰基氧的相互作用，同时由于π系统中的电子密度增加，增加了排斥的程度。在几乎所有情况下，即使芳环与酰胺正交，2°酰胺也倾向于反式构象，因为 C-N-C 键角可以扩展，而 C-N-H 键角则会减小，而这对于 3°酰胺则不利。
