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Direct enantiomeric separation of β‐blockers on ChyRoSine‐a by supercritical fluid chromatography: Supercritical carbon dioxide as transient in situ derivatizing agent
Author(s) -
Siret L.,
Bargmann N.,
Tambuté A.,
Caude M.
Publication year - 1992
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.530040409
Subject(s) - chemistry , supercritical fluid chromatography , enantiomer , amine gas treating , chiral derivatizing agent , asymmetric carbon , chromatography , supercritical carbon dioxide , methanol , organic chemistry , supercritical fluid , high performance liquid chromatography , chiral column chromatography , optically active
The direct enantiomeric separation of a series of β‐blockers has been carried out on two chiral stationary phases (CSPs) derived from 3,5‐dinitrobenzoyl tyrosine: the commercially available ChyRoSine‐A and a recent improved version of this CSP. Using supercritical fluid chromatography (SFC), facile separations are achieved (1.1 < R s <7) within short analysis times. The parameters affecting the enantioselectivity (temperature, pressure, mobile phase nature, solute structure) have been investigated. The optimal mobile phase consists in a mixture of carbon dioxide‐methanol‐propylamine at 25°C. The solute structure has a great influence on the enantioselectivity. For instance, both amine and hydroxyl protons are necessary for chiral discrimination to occur. Furthermore, the steroselectivity value is directly connected to the amine substituent steric bulkiness. Surprisingly, these solutes are poorly resolved using normal phase liquid chromatography (NPLC). Accordingly, the specific influence of carbon dioxide on the enantiomeric separation of 1,2‐amino‐alcohols has been investigated using various techniques such as nuclear magnetic resonance (NMR) or molecular modelisation. It has been shown that carbon dioxide acts as a complexing agent toward the amino‐alcohol by setting up of a bridge with the hydroxyl and the amine protons of the solute. In that way, the resulting complex possesses lower acido‐basic properties and a higher conformational rigidity, responsible for chiral discrimination.