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Racemization and stereoselective alcoholysis of temazepam
Author(s) -
Yang Shen K.
Publication year - 1999
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(1999)11:3<179::aid-chir2>3.0.co;2-g
Subject(s) - racemization , chemistry , enantiomer , stereoselectivity , circular dichroism , high performance liquid chromatography , methanol , chirality (physics) , chiral column chromatography , stereochemistry , protonation , chromatography , medicinal chemistry , organic chemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark , ion
Enantiomers of temazepam (TMZ), an anxiolytic drug in clinical use, were resolved and stabilized by the use of aprotic solvents in chiral stationary phase high‐performance liquid chromatography (CSP‐HPLC). The enantiomers were used to study racemization and heteronucleophilic substitution (alcoholysis) reactions in anhydrous acidic methanol and ethanol. Kinetics of spontaneous racemization and stereoselective conversions to 3‐O‐methyltemazepam (MeTMZ) and 3‐O‐ethyltemazepam (EtTMZ) were determined by circular dichroism (CD) spectropolarimetry and CSP‐HPLC. The rates of conversion of rac‐TMZ to rac‐MeTMZ (or rac‐EtTMZ) were determined by ultraviolet‐visible spectrophotometry. The results indicated that, for example, both N4‐protonated and unprotonated forms of (S)‐TMZ underwent spontaneous racemization and its 3S‐hydroxyl group was highly stereoselectively substituted at C3 position by the ethoxy group of ethanol to form EtTMZ enriched in ( S )‐EtTMZ. Similar stereoselective reactions occurred for TMZ enantiomers in acidic methanol. Chirality 11:179–186, 1999. Published 1999 Wiley‐Liss, Inc.