Investigations on solid-solid phase transformation of 5-methyl-2-[(4- methyl-2-nitrophenyl)amino]-3-thiophenecarbonitrile

Abstract

Solid-solid transformation of 5-methyl-2-[(4-methyl-2-nitrophenyl)amino]-3- thiophenecarbonitrile from the dark-red to the red form was investigated. By controlled crystallization, the dark-red form was prepared and the crystals were sieved into fractions: coarse (>250 μm), medium (125-177 μm), and fine (<88 μm). The transformation rate order (fastest to slowest) of the different fractions is coarse > medium > fine. However, milling accelerates the transformation, that is, smaller particles generated by milling transforms faster. Furthermore, ethanol vapor annealing slows both the transformation of the coarse and medium fractions, especially the latter. Therefore, the mechanism of transformation is not directly related to the crystal-size and most likely related to the amount and activity of the defects in the crystals. The three-dimensional (3-D) Avrami-Erofe'ev model, know as "random nucleation and growth" model, fits the kinetics of coarse fraction best. Higher relative humidity accelerates the transformation dramatically even though the compound is highly-hydrophobic. With minimal hydrogen bonding interaction involved, it appears even small amounts of water can serve as a nucleation catalyst by binding to the crystal surface, especially at defect sites, thus increasing the molecular mobility of these sites, promoting the transformation to the second phase and thereby increasing the transformation rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.