Solution growth and thermal treatment of crystals lead to two new forms of 2-((2,6-dimethylphenyl)amino)benzoic acid

We report the discovery of two new forms (II and III) of a potential non-steroidal anti-inflammatory and thyroid drug, 2-((2,6-dimethylphenyl)amino)benzoic acid (HDMPA) through solution growth and thermal treatment of crystals. Form II has been discovered through crystal growth in a variety of solvents, and characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), FT-IR, and Raman spectroscopy. Form II converts into form III upon thermal treatment, as indicated by the phase behavior study of form II with differential scanning calorimetry (DSC). Form III has been characterized by IR, Raman and PXRD. Conformational flexibility of the molecule seems to lead to the polymorphism of the system. A conformational scan shows the conformational minima correspond to the conformers in the polymorphs. Lattice energy calculations show energies of -48.14 and -50.31 kcal mol for forms I and II, providing information on the relative stability for each form. Hirshfeld analysis revealed that intermolecular interactions such as C⋯C, H⋯H, C⋯H, and H⋯O contribute to the stability of the crystal forms.