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−1 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.

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Published in RSC Advances, v. 8, issue 28, p. 15459-15470.

This journal is © The Royal Society of Chemistry 2018

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

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RH and SL thanks Natural Science Foundation of Hubei Province (2014CFB787) and the President's Fund of Wuhan Institute of Technology (CX2016075) for financial support. PPZ acknowledges the financial support by the National Natural Science Foundation of China (Grant No. 21403097) and the Fundamental Research Funds for the Central Universities (lzujbky-2016-45).

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Electronic supplementary information (ESI) available: CCDC 1590160 and 1590161. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7ra13353g

c7ra13353g1.cif (33 kB)
Crystal structure data.