Separation of enantiomers of Baclofen
type: CreativeWork
description: (3-(Aminomethyl)-4-chlorobenzenepropanoic acid (Baclofen), 3-(p-chlorophenyl)pyrrolidone (Baclofen lactam) and 3-(p-Chlorophenyl)glutaramide (baclofen's synthetic precursor) were individually used as substrates in co-crystallisation experiments with several resolving agents. Experiments were conducted in the solid state and in solution. The (-) enantiomer of the lactam and the ( +) enantiomer of the glutaramide were found to cocrystallise selectively with (2R,3R)-( +)-tartaric acid and (S)-(-)-a.-Methylbenzylamine respectively. Both these dissociable diastereomers Vere analysed by X-ray crystallography. HPLC analysis of the lactam retrieved from the former co-crystals indicated only partial separation of its (+) and (-) enantiomers. X-ray crystallographic, thermal, and polarimetric analyses were perfom1ed on the ( + )- and (-)-salts of the latter co-crystals. The solubilities of these salts in methanol were found to differ by a factor of 4. A solubility diagram was established showing the phase equilibria of various ratios of these two salts in methanol. The(+) enantiomer of the glutaramide was separated from the methylbenzylamine in the (+) salt by treatment with HCI. This enantiomer was converted to (R)-(-)-Baclofen by means of a Hofinann Rearrangement with an overall yield of 40%. The enantiomeric excess of (R)-(".")-Baclofen was 99.7%.
abstract: (3-(Aminomethyl)-4-chlorobenzenepropanoic acid (Baclofen), 3-(p-chlorophenyl)pyrrolidone (Baclofen lactam) and 3-(p-Chlorophenyl)glutaramide (baclofen's synthetic precursor) were individually used as substrates in co-crystallisation experiments with several resolving agents. Experiments were conducted in the solid state and in solution. The (-) enantiomer of the lactam and the ( +) enantiomer of the glutaramide were found to cocrystallise selectively with (2R,3R)-( +)-tartaric acid and (S)-(-)-a.-Methylbenzylamine respectively. Both these dissociable diastereomers Vere analysed by X-ray crystallography. HPLC analysis of the lactam retrieved from the former co-crystals indicated only partial separation of its (+) and (-) enantiomers. X-ray crystallographic, thermal, and polarimetric analyses were perfom1ed on the ( + )- and (-)-salts of the latter co-crystals. The solubilities of these salts in methanol were found to differ by a factor of 4. A solubility diagram was established showing the phase equilibria of various ratios of these two salts in methanol. The(+) enantiomer of the glutaramide was separated from the methylbenzylamine in the (+) salt by treatment with HCI. This enantiomer was converted to (R)-(-)-Baclofen by means of a Hofinann Rearrangement with an overall yield of 40%. The enantiomeric excess of (R)-(".")-Baclofen was 99.7%.
author: Wildervanck, Alexander Franciscus
language: eng
date published: 1996
date modified: 2026-07-22T22:23:30Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Chemistry

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property ID: Handle
value: http://hdl.handle.net/11427/20462