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 center dot center dot center dot 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 center dot center dot center dot 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 center dot center dot center dot 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 center dot center dot center dot pyridine and the hydroxyl center dot center dot center dot 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 center dot center dot center dot pyridine heterosynthon.