No abstract

Single crystals of (()-modafinil have been grown in gel medium obtained from the hydrolysis and condensation of tetramethoxysilane (TMOS). Three different crystal morphologies have been highlighted, corresponding to two modifications and a twin. The first polymorphic form was found to match with the known monoclinic form I (P2 1 /a, Z′ ) 2, a ) 14.502 Å, b ) 9.678 Å, c ) 20.844 Å, and β ) 110.17°). The determination of the second form allowed us to validate the previously predicted form III (orthorhombic Pna2 1 , Z′ ) 2, a ) 14.510 Å, b ) 9.710 Å, c ) 19.569 Å). The analysis of the twinned bodies and the structural similarities between form I and form III allowed us to identify the twin law: a stacking fault of (001) form I leading to a form III like interface. The analysis of the structures also suggested possible multitwinning.

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.