Polymorphism in Xaliproden (SR57746A): An X‑ray Diffraction, Calorimetric, and Solid-State NMR Investigation

Three polymorphic phases of xaliproden
are evidenced through thermal
analysis: Form II has an orthorhombic symmetry, while Forms I and
III have monoclinic unit cells. Structural characterizations of xaliproden
are carried out by means of single-crystal and synchrotron powder
X-ray diffraction (XRD), as well as high-resolution solid-state 13C cross-polarization at magic angle spinning (CPMAS) nuclear
magnetic resonance (NMR) spectroscopy. Diffraction crystallography
indicates that the structures of two of the polymorphs are highly
similar despite different thermal events observed by thermal analysis.
Further X-13C (X = 1H or 19F) CPMAS
NMR spectra, recorded under either 1H or double-resonance 1H/19F decoupling, provide evidence for the occurrence
of 19F self-decoupling in Form III, indicating that the
structural disorder observed in the X-ray diagram is dynamic, with
rotation of the CF3 group around the C–C single
bond. The results show that polymorphism between xaliproden Forms
I and III mostly deals with the degree of freedom of the CF3 group, higher in Form III than in Form I and clarifies the status
of Form III that can therefore be assigned to a well-defined polymorph
of xaliproden.