Polymorphs of 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid (Diclofenac): Differences from crystallography, Hirshfeld surface, QTAIM and NCIPlots

In this work, an experimental and theoretical comparison of the crystal structure of both polymorphs of the title compound was achieved. Hirshfeld surface analysis ( dnorm surface and two-dimensional fingerprint plots) which reveal the nature of intermolecular interactions for the title compounds were performed and discussed. The H∙∙∙H contacts were the major contributors to the Hirschfeld surface with 32.5% and 32.8% for Diclofenac (I) and Diclofenac (II), respectively. The contributions of the O∙∙∙H/H∙∙∙O (15.2%) and O∙∙∙H/H∙∙∙O (13.9%) interactions are smaller, but significant for the crystal architecture of Diclofenac (I) and Diclofenac (II), respectively. The quantum theory of atoms in molecules, reduced density gradient and natural bonds orbital studies was performed. The analysis showed the Cl∙∙∙π, H∙∙∙π, arene-CH∙∙∙Cl, and Cl∙∙∙Cl interactions as the main stabilizing forces of the crystal structure of polymorphs. The strength of the intermolecular hydrogen bond in Diclofenac (I) is greater than Diclofenac (II). The orbital origin of the hydrogen bond is attributed to the electron density transfer from the lone-pair of carbonyl oxygen in the carboxylic group to both, the intermolecular σ*(OH) from the carboxylic group and the intramolecular σ*(NH).