Conformational color polymorphism and control of crystallization of 5-methyl-2-[(4-methy1-2-nitrophenyl)amino]-3-thiophenecarbonitrile

5-Methyl-2-[(4-methyl-2-nitrophenyl)amino]-3-thiophenecarbonitrile is an ex ample of conformational and color polymorphism. The compound crystalizes in red (R), dark red (DR), light red (LR), and orange (O) modifications. Ther e are two specific goals for this study. One is to characterize the complex thermodynamic relationship among these four known forms, and the other is to use the knowledge of the thermodynamic relationship to control the cryst allization of these forms. The different forms were characterized by X-ray powder diffractometry as well as Fourier-transform infrared (FT-IR) and Ram an spectroscopy; their complex thermodynamic relationships were determined by thermal analysis, solubility measurements, and slurry conversion studies . According to the solubility results, all forms are enantiotropically rela ted: R is the thermodynamically most stable form above 60 degreesC, O is th e most stable form between room temperature and 60 degreesC, LR is the most stable form below - 15 degreesC, and DR is metastable throughout the entir e temperature range. DR, LR, and O have very similar free energy at ambient temperature, which is the reason for the complex transition behavior. Fina lly, a schematic energy-temperature diagram was constructed that combines a ll experimental data in a comprehensive thermodynamic picture and provides insights into how to control the crystallization of the individual forms. ( C) 2001 Wiley-Liss, Inc.