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 center dot center dot center dot 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 center dot center dot center dot heterocycle-based hydrogen bonds are presented.