Cyanophenyloximes: Reliable and Versatile Tools for Hydrogen-Bond Directed Supramolecular Synthesis of Cocrystals

A systematic structural and spectroscopic examination of the products resulting from cocrystallization reactions between
three types of phenyloximes R−CN−OH (where R = H, Me, or CN) and a series of N-heterocyclic hydrogen-bond acceptors
demonstrates that the acidity of the oxime -OH hydrogen-bond donor is crucial to the efficacy of the supramolecular assembly
process. Cyanophenyloximes are comparable to carboxylic acids, in terms of success rate, whereas the significantly less acidic CH3-
and H-substituted analogues are not effective at generating cocrystals despite close similarities in steric and geometric parameters.
The importance and validity of using experimental pKa values and calculated electrostatic potential surfaces as a basis for predicting
the supramolecular yield of an O−H···N interaction for driving the formation of cocrystals (within a functional group class) is
unambiguously established, and six new crystal structures of cocrystals assembled using oxime···heterocycle-based hydrogen bonds
are presented.

本研究针对三种苯肟类化合物（R−CN−OH，其中R分别为H、Me或CN）与一系列氮杂环氢键受体之间的共结晶反应产物开展了系统性结构与光谱表征，结果表明：肟基-OH氢键给体（hydrogen-bond donor）的酸性对超分子组装（supramolecular assembly）过程的效率至关重要。氰基取代苯肟的共结晶成功率可与羧酸类化合物相媲美；而尽管甲基取代（CH3-）与氢取代（H）的类似物在空间位阻与几何参数上极为相近，但其酸性显著更低，无法有效生成共晶体（cocrystals）。本研究明确证实了以实验测得的pKa值与计算得到的静电势表面（electrostatic potential surfaces）为基础，预测某一官能团类别下驱动共晶体形成的O−H···N氢键相互作用的超分子产率的合理性与重要性；同时报道了6种基于肟基-杂环氢键组装而成的共晶体全新晶体结构。