Hetero‐Seeding and Solid Mixture to Obtain New Crystalline Forms

Para-methyl benzyl alcohol (p-MeBA II) and para-chloro benzyl alcohol (p-ClBA) are quasi-isostructural and share the same hydrogen-bond patterns, but their crystals are not isomorphous. No new polymorphs could be obtained by conventional polymorph screening based on different solvents and different crystallization conditions. Formation of a new polymorph of p-MeBA named p-MeBA I, isomorphous with the crystal of p-ClBA, was induced by hetero-seeding with a small quantity of powdered p-ClBA added to a supersaturated solution of p-MeBA in hexane, while seeding of p-ClBA with p-MeBA II failed to give a new phase of p-ClBA isomorphous with known crystalline p-MeBA II. Mixed crystals of p-MeBA and p-ClBA were also prepared with different p-MeBA/p-ClBA ratios to understand the role of the different functional groups in the crystal structure. Crystal phases were characterized by combined use of single-crystal and powder X-ray diffraction, differential scanning calorimetry, and solid-state NMR spectroscopy.