Premium
Stereoselective nucleophilic substitution of oxazepam and racemization in acidic methanol and ethanol
Author(s) -
Yang Shen K.,
Bao Ziping,
Shou Magang
Publication year - 1996
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1996)8:2<214::aid-chir7>3.0.co;2-i
Subject(s) - racemization , chemistry , enantiomer , methanol , stereoselectivity , nucleophilic substitution , chromatography , high performance liquid chromatography , stereochemistry , organic chemistry , catalysis
Enantiomeric and racemic oxazepam (OX), 3‐ O ‐methyloxazepam (MeOX), and 3‐ O ‐ethyloxazepam (EtOX) were used to study racemization, heteronucleophilic, and homonucleophilic substitution reactions in anhydrous acidic methanol and ethanol. Kinetics of racemization and nucleophilic substitution reactions in nondeuterated and deuterated solvents were determined by circular dichroism spectropolarimetry, chiral stationary phase high‐performance liquid chromatography (HPLC), reversed‐phase HPLC, and mass spectrometry. Several reactions occurred when ( S )‐OX, for example, was dissolved in acidic methanol: (1) ( S )‐OX itself underwent spontaneous racemization, (2) the 3‐hydroxyl group of ( S )‐OX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in ( S )‐MeOX, (3) the 3‐methoxy group of ( S )‐MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in ( S )‐MeOX, and (4) the 3‐methoxy group of ( R )‐MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in ( R )‐MeOX. Repetitive reactions 3 and 4 eventually resulted in a racemic MeOX. Similar reactions occurred for an enantiomeric OX in acidic ethanol. © 1996 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.