Polymorphism of N-(2,6-dioxo-3-piperidyl)pthalimide (thalidomide): Structural characterization of a second monoclinic racemic modification

The X-ray crystal structure of the drug N-(2,6-dioxo-3-piperidyl)pthalimide (thalidomide), C₁₃H₁₀N₂O₄, obtained from 11 dimethyformamide-ethanol solution, is reported. This species is monoclinic, space groupC2/c, witha=20.679(5),b=8.042(2),c=14.162(5) , =102.86(3)°,Z=8,R=0.051 for 1674 unique reflections. crystal packing is determined by intermolecular N–H... O hydrogen bonding which is more extensive than that reported in the literature for a racemate of thalidomide crystallizing in space groupP2₁/n. Comparison of the melting behavior and X-ray powder diffractograms of the two racemic polymorphs shows that they are distinctly different, allowing easy identification of these species. By comparing experimental X-ray powder patterns with those calculated from single crystal data, it was concluded that neither of these polymorphs undergoes a phase change on trituration.