Supramolecular Packing of a Series of <i>N</i>‑Phenylamides and the Role of NH···OC Interactions

A series of seven N-phenylamides [R–C­(O)­NHPh, in which R: CH3, C­(CH3)3, Ph, CF3, CCl3, CBr3, and H] were used as models in this study. Molecular packing and intermolecular interactions were evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent 1H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···OC interactions promoted the first stages. The study in solution provided different values of association constant (Kass) governed by the hydrogen bond NH···OC, showing that the stronger interactions are directly influenced by the substituent steric hindrance. A correlation between Kass(NH···OC) from the solution and the NH···OC interaction energy in the crystal showed a good trend.本研究以7种N-苯基酰胺（N-phenylamide）为模型化合物，其通式为R–C(O)NHPh，其中R分别为CH3、C(CH3)3、Ph、CF3、CCl3、CBr3及H。本研究通过理论计算、溶液核磁共振及量子原子分子理论（quantum theory of atoms in molecules）分析，对目标化合物的分子堆积与分子间相互作用进行了表征。本研究以超分子簇（supramolecular cluster）为界定依据，结合能量参数与拓扑参数，提出了此类化合物的结晶机制。浓度依赖性1H核磁共振实验佐证了所提出的分子间相互作用。除R为H的化合物初始会形成四聚体外，其余所有化合物在所提出结晶机制的第一阶段均会形成二维层状结构或一维链状结构。强分子间NH···O=C相互作用是该初始结晶阶段的核心驱动力。溶液态研究得到了由NH···O=C氢键主导的不同结合常数（association constant, Kass），结果表明相互作用强度直接受取代基空间位阻的调控。溶液态测得的Kass(NH···O=C)与晶体中NH···O=C相互作用能之间呈现出良好的相关趋势。