Stereointegrity of thalidomide: gas-chromatographic determination of the enantiomerization barrier.
Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, two chromatographic methods, dynamic gas chromatography (DGC) and stopped-flow gas chromatography (SFGC) were used to determine the enantiomerization barrier of thalidomide. In the presence of a chiral stationary phase (CSP), the enantiomers of thalidomide produced characteristic elution profiles exhibiting plateaus and/or peak broadening which were observed between 190 and 220 degrees C in DGC. To obtain the enantiomerization barrier of thalidomide from experimental data, the fast and efficient simulation program ChromWin was used to simulate the elution profiles and obtain kinetic activation parameters. From temperature-dependent measurements the rate constants k(1) and k(-1) and the kinetic activation parameters DeltaG#, DeltaH# and DeltaS# of the enantiomerization of thalidomide were obtained by DGC. The enantiomerization barrier DeltaG# was determined to be 154+/-2 kJ/mol with DGC and 150+/-3 kJ/mol with the sfGC technique at 200 degrees C, respectively. The concept of the retention increment R' has been applied to separate the enantiomerization barrier of thalidomide in the dissolved and complexed state of the CSP.
Trapp
Oliver
O
Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.
Schoetz
Gabriele
G
Schurig
Volker
V
D002849:Chromatography, Gas / Q000379:methods; D003879:Dermatologic Agents / Q000032:analysis / Q000737:chemistry; D006993:Hypnotics and Sedatives / Q000032:analysis / Q000737:chemistry; D013237:Stereoisomerism; D013792:Thalidomide / Q000032:analysis* / Q000737:chemistry
D003879:Dermatologic Agents; D006993:Hypnotics and Sedatives; D013792:Thalidomide