CHARACTERIZATION AND CRYSTAL-STRUCTURE OF 2 POLYMORPHIC FORMS OF RACEMIC THALIDOMIDE

There are two polymorphic forms of racemic thalidomide. The alpha-poly morph was formed by crystallization from 2-ethoxyethanol, methanol or dichloromethane, while the beta-polymorph was formed by crystallizatio n from a supersaturated solution in refluxing 2-ethoxyethanol. The two polymorphs were characterized by IR spectra, differential scanning ca lorimetry (DSC). melting points, powder X-ray diffraction patterns, an d X-ray crystallography. They were easily differentiated by IR (KBr) i n which the alpha polymorph absorbed at 3196, 3098 and 859 cm(-1) and the beta at 3276 and 755 cm(-1). DSC scans of the alpha and beta forms showed endothermic peaks at 272.3 and 275.7 degrees C, respectively. During this measurement the alpha form was partially or fully converte d into the beta form if the rate of temperature change was slow or if the alpha form contained some beta which provided seed crystals for th e interconversion. Upon remelting both forms gave one peak correspondi ng to the beta polymorph. The powder X-ray diffraction patterns for th e two forms differ significantly. The crystal structures of the two po lymorphs differ primarily in their mode of hydrogen bonding. In the al pha polymorph the molecules form dimers, while in the beta the dimers form infinite linear strings linked by bifurcated hydrogen bonds along the b-axis.