Hierarchy of supramolecular synthons: Persistent hydroxyl⋯pyridine hydrogen bonds in cocrystals that contain a cyano acceptor

An analysis of the Cambridge Structural Database reveals >99% occurrence of the hydroxyl⋯pyridine supramolecular heterosynthon in crystal structures that contain hydroxyl and pyridine moieties in the absence of other hydrogen-bonding moieties. The occurrence of the hydroxyl⋯cyano supramolecular heterosynthon in crystal structures that contain hydroxyl and cyano moieties is ca. 77%. Such high frequencies indicate that these heterosynthons are strongly favored over the competing hydroxyl⋯hydroxyl supramolecular homosynthon. However, the CSD does not contain enough information to evaluate which supramolecular heterosynthon prevails when only OH, pyridine, and CN moieties are present in a crystal structure. We have addressed the competition between the hydroxyl⋯pyridine and the hydroxyl⋯cyano supramolecular heterosynthons by characterizing a series of 17 cocrystals that are composed of cocrystal formers which contain a permutation of OH, pyridine, and CN functional groups. Structural analysis reveals that all cocrystals are sustained by the hydroxyl⋯pyridine heterosynthon.