Surfactant Provided Control of Crystallization Polymorphic Outcome and Stabilization of Metastable Polymorphs of 2,6-Dimethoxyphenylboronic Acid

2,6-Dimethoxyphenylboronic acid was used as a model substance to investigate the additive crystallization approach for polymorph control in phenylboronic acids. It was crystallized under different conditions by performing evaporation and cooling crystallization from different solvents. Most of the crystallizations from pure solvents produced the thermodynamically stable Form I, but in evaporation crystallization from alcohols, Form II or even a new polymorph, Form III, could be obtained. Structurally related substances, polymers, and surfactants with diverse intermolecular interaction possibilities were tested as additives. Surfactants were found to facilitate the crystallization of the metastable forms and therefore were investigated more extensively. The surfactants Span 20 and n–octyl-β-D-glucopyranoside provided crystallization of the metastable forms in the evaporation crystallization and notably stabilized Form II. The lattice energy, energy frameworks, Hirshfeld surface analysis, full interaction maps, and morphology prediction were used to identify the structural differences between Forms I and II and rationalize the ability of the additives to provide formation of Form II in the crystallization and to stabilize it.