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 pK_a 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.