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Acid‐catalyzed stereoselective heteronucleophilic substitution and racemization of 3‐ O ‐methyloxazepam and 3‐ O ‐ethyloxazepam
Author(s) -
Yang Shen K.
Publication year - 1994
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/chir.530060304
Subject(s) - racemization , chemistry , enantiomer , stereoselectivity , protonation , nucleophilic substitution , racemic mixture , methanol , catalysis , substitution reaction , medicinal chemistry , stereochemistry , organic chemistry , ion
Enantiomers of 3‐ O ‐methyloxazepam (MeOX) and 3‐ O ‐ethyloxazepam (EtOX) were resolved by chiral stationary phase high‐performance liquid chromatography (CSP‐HPLC). Reaction kinetics and deuterium isotope effects of acid‐catalyzed racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by spectropolarimetry. The acid‐catalyzed heteronucleophilic substitution reactions of racemic MeOX in ethanol and racemic EtOX in methanol were studied by reversed‐phase HPLC. Thermodynamic parameters involved in the reactions were obtained by temperature‐dependent reaction rates. The effects of solvent's dielectric constant on the heteronucleophilic substitution reactions were also determined. A nucleophilically solvated and transient C3 carbocation intermediate resulting from an N4‐protonated enantiomer, derived from a 1,4‐benzodiazcpine either in M (minus) or P (plus) conformation, is proposed to be an intermediate and responsible for the acid‐catalyzed stereoselective nucleophilic substitution and the resulting racemization. © 1994 Wiley‐Liss, Inc.