High‐performance liquid chromatographic enantioseparation of naphthol‐substituted tetrahydroisoquinolines on polysaccharide‐based chiral stationary phases

Abstract

The stereoisomers of 15 naphthol-substituted tetrahydroisoquinoline analogs were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl carbamate) (Cellulose 1), cellulose tris-(3-chloro-4-methylphenyl carbamate) (Cellulose 2), cellulose tris-(4-methylbenzoate) (Cellulose 3) and cellulose tris-(4-chloro-3-methylphenyl carbamate) (Cellulose 4). Experiments were performed in normal-phase mode with n-heptane(n-hexane)-alcohol-diethylamine mobile phases in the temperature range 5-40 °C. Thermodynamic parameters were calculated from plots of lnk or lnα vs 1/T. On the Cellulose 1 column, Δ(ΔH°) ranged from -6.8 to 5.9 kJ/mol, Δ(ΔS°) from -16.7 to 21.0 J/mol/K and the Gibbs energy, -Δ(ΔG°) from 0.2 to 1.5 kJ/mol; on the Cellulose 2 column, Δ(ΔH°) ranged from -7.8 to 2.5 kJ/mol, Δ(ΔS°) from -16.1 to 13.2 J/mol/K and - Δ(ΔG°) from 0.7 to 3.0 kJ/mol. Both enthalpy- and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature.

Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors

“…Consequently, the Q values ( Q = Δ(Δ H °)/ T × Δ(Δ S °) 298 K ), which are used for visualizing the relative contribution of enthalpic and entropic terms to the free energy of adsorption, are smaller than 1 for Chiralpak AS, using 100% MeOH as mobile phase, which confirms an unusual entropy controlled enantioseparations. In other cases, Q values were higher than 1, indicated that mainly the enthalpy controls the enantioseparation, as usual . The highest Q value was observed on Chiralpak AD column using IPA with a corresponding extremely high T iso value (3951°C).…”

Enantioseparation and thermodynamic study of naphthalene derivatives, new melatoninergic agonists, on coated amylose [tris(S)‐1‐phenylethylcarbamate] stationary phase. Transposition to preparative scale

“…For the other compounds (1, 2, 4 and 5), ∆∆ H° and ∆∆ S° values were both positive, suggesting an entropically driven enantioseparation. The selectivity increases with increasing temperature (Ilisz et al ., ) and once again this behavior can be seen in Fig. .…”

“…The second‐eluted enantiomer forms a more stable complex with the selector (it has fewer degrees of freedom on the CSP) than does the first‐eluted enantiomer, with more unfavorable entropy for enantiosparation. The selectivity decreases with increasing temperature (Ilisz et al ., ) and this behavior is observed in Fig. .…”

“…() for the separation of naproxen. More recently, Péter's group reported two studies describing naphthol derivative separation involving either amylose and cellulose tris ‐3,5‐dimethylphenylcarbamate CSPs (Ilisz et al ., ) or cellulose tris ‐3,5‐dimethylphenylcarbamate, cellulose tris ‐4‐methylbenzoate, cellulose tris ‐3‐chloro‐3‐methylphenylcarbamate and cellulose tris ‐4‐chloro‐3‐methylphenylcarbamate (Ilisz et al ., ). Thus, literature focusing on the chiral separation of new naphthalenic derivatives is not very abundant and, above all, does not mention the use of amylose tris ‐( S )‐1‐phenylethylcarbamate CSP (Chiralpak AS).…”

High‐performance liquid chromatographic enantioseparation of amino alcohol analogues possessing 1,2,3,4‐tetrahydroisoquinoline skeleton on polysaccharide‐based chiral stationary phases

“…The HPLC separation of salsolinol enantiomers has been achieved through the application of various CSPs (Deng et al ., ; Baum and Rommelspacher, ; Rommelspacher et al ., ; Stammel and Thomas, ; Stammel et al ., ; Zhang et al ., , ; de los Angeles Juricic et al ., ). The normal‐phase HPLC separation of phenyl‐ and naphthol‐substituted Tiq analogues has been accomplished using polysaccharide‐based CSPs (Kazoka et al ., ; Ilisz et al ., ).…”