| Part I. A new way to cure chiral purity analysis headaches. Chiral alcohols and amines are widely used intermediates and pharmaceutically active ingredients. Methods for establishing the chiral purity of these compounds are of great interest to chemists. While state-of-art analysis is focused on direct analysis of these chiral molecules by chiral GC, HPLC and spectroscopic techniques, it is still interesting to develop chiral auxiliaries for traditional diastereomeric analyses. The over-the-counter, non-steroidal anti-inflammatory agent Naproxen is a readily available, inexpensive, enantiomerically pure carboxylic acid.*;We have developed this compound as an alternative to the more expensive Mosher's acid for chiral analysis. In this study, the use of (S)-Naproxen as a chiral auxiliary (See above reaction scheme) for the analysis of chiral of alcohols will be reported. We proved that the S,S diastereomeric product forms at a faster rate (ca. 4 times faster) than the S,R diastereomeric product. Initial attempts at quantitative analysis of enantiomeric mixtures of sec-phenethanol were unsuccessful due to these kinetic differences. However, we show that flooding the reaction with a large excess of (S)-Naproxen results in reproducible analysis of enantiomeric mixtures of sec-phenethanol by HPLC. Also, the diastereomeric separation of S-Naproxen esters by HPLC was thoroughly studied. The NMR measurements of S-Naproxen ester provided a complimentary method for the chiral analysis of chiral alcohols.;Part II. Kinetic studies for on-column isomerization interconversion. Investigations into dynamic molecular processes and determination of their kinetic parameters are frequently performed through the utilization of dynamic spectroscopic techniques (NMR, ESR, IR). These kinetic parameters can also be determined chromatographically, specifically for two species that can interconvert on a chromatographic time scale and can be separated chromatographically. This chemical interconversion can occur during sample preparation or on-column and may be influenced by the mobile phase or the stationary phase. Peak distortion might be observed when the conversion occurs during the chromatographic process.;The epimerization of trityloxymethyl butyrolactol has been investigated using dynamic chromatography and an approximation function introduced by Trapp and Schurig that is based on stochastic and theoretical plate models. The epimerization rate constants and Gibbs activation energies of epimerization are directly calculated from chromatographic peak parameters, i.e., retention times of the inter-converting species, peak width at half height and the relative plateau height by using the approximation function. The relationships between peak shape and chromatographic conditions, such as flow-rate, temperature and pH are investigated.*;*Please refer to dissertation for diagrams. |
