Pleconaril Polymorphs: Crystal Structures of Form I and Form III, Evidence of the Enantiotropy, and Assessment of the Structural Purity

Form I (HT) and form III (LT) of pleconaril are enantiotropically related with a calculated temperature
of transition Tτ = 35.7 °C (supposing an ideal behavior). Structural data obtained from single crystal X-ray diffraction
at 100 K and room temperature show that (i) form I (HT) can be described as a network of dimers and form III can
be described as a three-dimensional weakly H-bonded network of monomers. (ii) These two varieties contradict the
density rule. (iii) The solid−solid transition (not observed) could only occur via a destructive−reconstructive
mechanism. Investigations on the pleconaril−ethanol binary system show that the conversion form I ⇔ form III at
Tτ = 31 ± 2 °C is only possible when mediated by a solvent. A favorable set of thermodynamical and kinetic conditions
allows quantification of form I in form III down to 0.1% by using differential scanning calorimetry. To assess the
structural purity, this method could be applied to other compounds fulfilling five restrictive conditions.