Neutral and zwitterionic polymorphs of 2-(p-tolylamino)nicotinic acid

Abstract

2-(p-Tolylamino)nicotinic acid (TNA) was crystallized in three polymorphic forms. The crystal structures of forms I and II are sustained by the neutral O-H•••N hydrogen bond from the COOH donor to the pyridine N acceptor, whereas proton transfer occurred in form III to give a zwitterionic structure of N-H+•••O- hydrogen bond. Form III could be obtained only in the presence of pyridine-type coformers. The trimorphs were characterized by IR, Raman, and ss-NMR spectroscopy, DSC, and single crystal X-ray diffraction. The neutral form I and zwitterionic form III are 2D isostructural, whereas form II has a different crystal packing and molecular conformation. XPac analysis showed the 2D supramolecular construct and similarity in crystal structures of forms I and III. The difference in hydrogen bonding between the neutral and zwitterionic polymorph is analyzed by Hirshfeld surfaces. The isolation of zwitterionic TNA as a complex with m-nitrobenzoic acid and a TNA salt with o-aminopyridine provides a mechanistic rationale for the crystallization of the rare zwitterionic structure of amphoteric TNA molecule. © 2011 American Chemical Society.