Phase Transition from Two Z′ = 1 Forms to a Z′ = 2 Form of a Concomitant Conformational Polymorphic System

Differential scanning calorimetry and hot-stage microscopy revealed two solid−solid phase transitions from two Z′ = 1 polymorphs to a Z′ = 2 form in a concomitant conformational polymorphic system of 2-(mesitylamino)nicotinic acid. Neat grinding and solvent-drop grinding experiments also confirmed that the high Z′ form is thermodynamically stable. The finding adds to a few cases where a high Z′ form is the most thermodynamically stable, apparently running contrary to a common notion that incomplete crystallization tends to produce metastable high Z′ structures. The high Z′ form of 2-(mesitylamino)nicotinic acid may be due to the combination of iso-energetic conformations and better packing. Lattice and conformational energy calculations were performed to provide further information about the intermolecular interactions of the polymorphs. Conformational search is in agreement with the conformers found in the three forms.