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 CH 3 - 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 p K 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.