THE OXAZOLIDINE AND OXAZOLIDONE DERIVATIVES OF EPHEDRINE AND EPHEDRINELIKE COMPOUNDS: SYNTHESIS, STEREOCHEMISTRY, AND ENANTIOMERIC RESOLUTION ON CHIRAL HPLC STATIONARY PHASES

A series of (alpha)-(beta)-amino alcohols, structurally similar to ephedrine, were condensed with a variety of aromatic aldehydes. The results were the diasteriomeric rigid five-membered rings whose configuration has been determined by proton magnetic resonance and single-crystal x-ray diffraction. The results of the condensation of primary (alpha)-(beta)-amino alcohols with aldehydes were Schiff bases. Because of the inability of the chiral stationary phases (CSPs) to resolve Schiff bases, this group of compounds was condensed with phosgene to give the oxazolidones. The reaction of norephedrine and phosgene produces a rigid oxazolidone ring system. The cyclization proceeds without racemization. Chromatography of the enantiomeric oxazolidones on the CSP produced two prominent peaks with (alpha) = 1.04 and R(,s) of 0.96. Oxazolidines were also resolved on four different commercially available Pirkle-type HPLC chiral stationary phases using ionic and covalent bonds of the R-N(3,5-dinitrobenzoyl)-phenylglycine or S-N(3,5-dinitrobenzoyl)leucine as the CSPs. The oxazolidines derived from the condensation of ephedrine and aldehydes containing a (pi)-basic moiety, such as naphthaldehyde, were resolved as were those oxazolidines synthesized by using a (pi)-acid aldehyde such as P-nitrobenzaldehyde. Oxazolidines resulting from condensation of ephedrine and a (pi)-neutral aldehyde such as benzaldehyde and 4-bromobenzaldehyde were not resolved. The observed elution order varied with the identity of the introduced aryl group and was independent of the nature (ionic or covalent) of chiral stationary phases to stationary support, and was consistent but inverted when S-leucine analogue was substituted for R-phenylglycine CSP. The result of this study suggest a chiral recognition model based on the formation of diastereomeric solute-CSP complexes through a single attractive interaction and chiral discrimination resulting from the difference in steric fit.