Stereoselective homonucleophilic substitution of 3-O-methyl and 3-O-ethyloxazepam enantiomers by chiral stationary phase high-performance liquid chromatography.
Enantiomers of 3-O-methyloxazepam and 3-O-ethyloxazepam were resolved by chiral stationary phase high-performance liquid chromatography (CSP-HPLC). Temperature-dependent and acid-catalysed racemization of 3-O-methyloxazepam enantiomers in methanol and 3-O-ethyloxazepam enantiomers in ethanol were studied by quenching reaction products at various times by neutralization. Enantiomeric contents of reaction product were determined by CSP-HPLC. Thermodynamic parameters in the formation of the activated complex (Eact, delta H++, delta S++ and delta G++) were consistent with those determined by a spectropolarimetric method. A nucleophilically solvated and transient C3 carbocation intermediate resulting from an N4-protonated enantiomer is proposed to be an intermediate and responsible for the acid-catalysed stereoselective homonucleophilic substitution and the resulting racemization.
Yang
S K
SK
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Lu
X L
XL
D000143:Acids; D002851:Chromatography, High Pressure Liquid; D012984:Software; D013237:Stereoisomerism; D013693:Temazepam / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
D000143:Acids; C086273:3-O-ethyloxazepam; D013693:Temazepam