Neutral and Zwitterionic Polymorphs of 2-(p-Tolylamino)nicotinic Acid

作者：Nath Naba K; Kumar S Su*****; Nangia Ashwini^*

来源：Crystal Growth & Design, 2011, 11(10): 4594-4605.

DOI：10.1021/cg200853u

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 center dot center dot center dot 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+center dot center dot center dot 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 1 and zwitterionic form III are 2D isostructural whereas form II has a different crystal packing and molecular conformation. XPac analysis showed the 2D supromolecular 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 and a TNA salt with o-aminopyridine provides a mechanistic rationale for the crystlization of the rare zwitterionic structure of amphoteric molecule.

• 出版日期2011-10