Polymorphism and Phase Behaviors of 2-(Phenylamino)nicotinic Acid

Abstract

ABSTRACT:The discovery and phase transition studies of four polymorphs of 2-(phenylamino)nicotinic acid are described in this report. The four polymorphs were crystallized from solution under different conditions. All polymorphs differ in the degree of conjugation of the two aromatic rings and thus are of conformational polymorphism. Three of the four modifications have more than one conformer in the asymmetric unit. Due to the difference in conformation, all polymorphs display distinctive colors as well as different hydrogen-bonding arrangements. Phase behaviors of the four forms were studied by differential scanning calorimetry and hot-stage microscopy, indicating that metastable forms underwent phase transition to the stable one initiated by mechanical perturbation in solution or assisted by heating in the solid state. As such, this polymorphic system exhibits polychromism, conformational isomorphism, thermochromism, and mechanochromism. It may be valuable for further solid-state structure-property relationship studies.

Crystal packing and crystallization tendency from the melt of 2-((2-ethylphenyl)amino)nicotinic acid

“…The substitution of an -ethyl group on the phenyl ring leads to formation of crystals with acid-pyridine synthons by preventing planar conformation due to steric hindrance. This relationship between synthon and conformation has been observed for other compounds examined in previous studies [13][14][15][16]. Furthermore, the hydrogen-bonding motif was also present in the amorphous state, which likely impedes the recrystallization from the amorphous state.…”

“…Samples were packed in a 5 mm zirconia rotor and 13 C spectra were obtained with cross-polarization/magicangle spinning (CP/MAS) and total sideband suppression (TOSS) at ambient temperature. Operating conditions included a spinning speed of 6 kHz, acquisition time of 16 ms, TPPM high-power proton decoupling, and a 1 H pulse width of 5 μs (90°).…”

“…Figure 7 shows the 13 C SSNMR spectra of solution state, crystalline Form I, and amorphous samples of 2EPNA. Peak assignment was based on solution-phase spectra and quantum chemical calculations (Table 2).…”

“…By covalently linking bulky alkyl or electron-withdrawing groups to the phenyl ring of diarylamine compounds, we investigated how the molecular structure influences the hydrogen bonding motif in the crystal [13][14][15][16]. It was observed that bulky alkyl groups lead to crystal structures with the acid-pyridine synthon because of the groups' ability to destabilize the planar conformation by steric repulsion and expose the pyridine nitrogen [15].…”

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association

“…Recent efforts have been devoted to the development of consistent and reliable crystallization processes for producing desirable polymorphs, including on-line, spectroscopy-based monitoring designs of crystal growth in solution (3)(4)(5). Polymorphic formation is known to be affected by a wide variety of growth conditions, such as type of solvent (6)(7)(8), supersaturation (4,9), temperature (10), and use of additives (11,12). Despite considerable efforts studying crystallization mechanism, understanding of kinetic factors that govern polymorphic formation in solution largely remains limited (13).…”