Structure determination of 6,6′-bis(trifluoromethyl)-thiazine-indigo from laboratory powder data and lattice-energy minimisation

Abstract

6,6 0 -bis(trifluoromethyl)-thiazine-indigo, C 18 H 8 F 6 N 2 O 2 S 2 , is a yellow derivative of the thiazine-indigo pigments. Due to its insolubility single crystals could not be grown; the structure had to be determined from powder diffraction data. The X-ray powder pattern -measured on a laboratory diffractometer in routine manner -could be indexed, although the crystallite size was only about 20 nm. The crystal structure was solved by lattice-energy minimisation using the program CRYSCA. Subsequently, the structure was refined by the Rietveld method using restraints. The compound crystallises in space group P2 1 /c with a ¼ 15.4136(12), b ¼ 7.8384(5), c ¼ 7.7102(6) A, b ¼ 112.736(6) , Z ¼ 2, with molecules on inversion centres. The molecules are connected by double hydrogen bonds, resulting in planar chains. These chains form stacks in [001] direction. The density is unusually high (r ¼ 1.7875 g/cm 3 ), this explains the observed insolubility of the compound.

Can the Formation of Pharmaceutical Cocrystals Be Computationally Predicted? 2. Crystal Structure Prediction

“…80,81 The proposed methodology allows the efficient identification of stable minima on complex lattice energy surfaces due to the presence of multiple, flexible molecules (or ions) in the asymmetric unit. This knowledge of the lattice energy landscape may prove useful in solving the crystal structures from powder X-ray data, 88,89 which is often necessary as many cocrystals are synthesized by solid-state grinding. Moreover, the lattice energy landscape can enhance the understanding of the range of possible crystal structures and help to anticipate possible crystallization problems such as disorder and polymorphism.…”