The present paper reports a study on the chiral discrimination at the solid state of methyl 2-(diphenylmethylsulfinyl)acetate (hereafter, DMSAM) as a key intermediate in the synthesis of an acetamide derivative (modafinil). A partial solid solution (i.e., stable “racemic conglomerate” with partial miscibility at the solid state) between enantiomers was characterized by X-ray single crystal analyses and high performance liquid chromatography (HPLC). Binary and ternary phase diagrams of DMSAM were investigated by HPLC measurements, differential scanning calorimetry (DSC), discontinuous isoperibolic thermal analysis (DITA), and Raman spectroscopy. Finally, the distribution of the two enantiomers inside single crystals was studied by dissolution and Raman microspectroscopy.

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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 S 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.