An Experimental and Theoretical Approach to Control Salt vs Cocrystal vs Hybrid Formation—Crystal Engineering of an E/Z-Butenedioic Acid/Phthalazine System

The understanding and control of proton transfer reactions between acid–base pairs in the solid state are two of the main challenges for the crystal engineering community. The ability to control proton transfer reactions in the solid state enables a more selective preparation of cocrystals and salts, which facilitates the design of solid materials with specific physicochemical properties. In this study, an approach to control proton transfer reactions of an E-butenedioic acid/phthalazine cocrystal–salt (hybrid) system is presented, which allows the selective formation of its cocrystal and salt. In this approach the dominant intermolecular interactions between acid–base pairs are identified. Such interactions appear to be crucial for the inhibition or promotion of proton transfers in the solid state. For this, the relationship between these interactions and the so-called ΔpKa rule has been investigated.