Phenyl-Perfluorophenyl Synthon Mediated Cocrystallization of Carboxylic Acids and Amides

The significance of face-to-face π−π stacking of phenyl and perfluorophenyl rings (Ph-PhF), a robust
supramolecular synthon in aromatic and perfluoroaromatic crystal structures, is studied in the cocrystallization of
simple aromatic carboxylic acids and amides. X-ray crystal structures of C6H5COOH·C6F5COOH 1, C6H5CONH2·C6F5CONH2 2, and C6H5CONH2·C6F5COOH 3 are analyzed to understand the role of Ph-PhF synthon in directing
self-assembly and hydrogen bonding in these cocrystals. The strong hydrogen bond donor acidity of C6F5COOH and
C6F5CONH2 together with mixed stacks of phenyl and perfluorophenyl rings steer acid···acid and amide···amide
hydrogen bonding in cocrystals 1 and 2. Acid···amide hydrogen bonding is sufficiently strengthened by donor acidity
and acceptor basicity in 3 that the role of the Ph-PhF synthon is weaker because the aromatic rings stack with
lateral offset. The complex C6H5COOH·C6F5CONH2 4 could not be obtained under similar crystallization conditions.
The crystal structure of C6F5CONH2 is determined to compare molecular conformation and hydrogen bonding with
motifs in the cocrystals. This study shows the viability of the Ph-PhF synthon in the presence of strong hydrogen
bonding COOH and CONH2 groups for crystal engineering.

本研究针对苯基与全氟苯基环（Ph-PhF）的面对面π-π堆积作用的重要性展开探讨，该相互作用是芳香族与全氟芳香族晶体结构中一类稳定的超分子合成子（supramolecular synthon），相关研究围绕简单芳香族羧酸与酰胺的共结晶（cocrystallization）过程开展。通过解析C₆H₅COOH·C₆F₅COOH（化合物1）、C₆H₅CONH₂·C₆F₅CONH₂（化合物2）以及C₆H₅CONH₂·C₆F₅COOH（化合物3）的X射线晶体结构（X-ray crystal structures），以明确Ph-PhF合成子在调控上述共晶体的自组装与氢键形成中的作用机制。C₆F₅COOH与C₆F₅CONH₂具备较强的氢键给体酸度，结合苯基与全氟苯基环的混合堆叠模式，主导了共晶体1与2中酸-酸、酰胺-酰胺的氢键相互作用。在化合物3中，酸-酰胺氢键因给体酸度与受体碱度的协同作用得到显著增强，使得Ph-PhF合成子的作用相对弱化，此时芳香环以侧向偏移的方式发生堆叠。在相同结晶条件下，未能获得C₆H₅COOH·C₆F₅CONH₂（化合物4）。为对比共晶体中的分子构象与氢键基元，本研究还解析了C₆F₅CONH₂的晶体结构。本研究证实，即便存在强氢键作用的COOH与CONH₂基团，Ph-PhF合成子仍可应用于晶体工程（crystal engineering）领域。