POLYMORPHISM OF N-(2,6-DIOXO-3-PIPERIDYL)PHTHALIMIDE (THALIDOMIDE) - STRUCTURAL CHARACTERIZATION OF A 2ND MONOCLINIC RACEMIC MODIFICATION

The X-ray crystal structure of the drug N-(2,6-dioxo-3-piperidyl)pthalimide (thalidomide), C13H10N2O4, obtained from 1:1 dimethyformamide-ethanol solution, is reported. This species is monoclinic, space group C2/c, with a = 20.679(5), b = 8.042(2), c = 14.162(5)angstrom, beta = 102.86(3)degrees, 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 group P2(1)/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.