Enantiomer Separation Of Chiral Triazole Fungicides By Supercritical Fluid Chromatography

Enantiomeric separation of chiral triazole fungicides provides pure enantiomers for activity or toxicity investigation and is the guidance for single-or enriched-enantiomer triazole fungicide production. Fourteen chiral triazole fungicides were separated by supercritical fluid chromatography (SFC) with supercritical CO2modified with different alcohols (methanol, ethanol or2-propanol) as the mobile phase. The effect of different chiral stationary phase (CSP), type and concentration of modifier, column temperature and back pressure on the separation was investigated.With the results of chiral separation of14triazole fungicides on three different chiral columns, the optimal separation condition of each compounds was selected.12triazole fungicides were baseline separated except Etaconazole and Difenoconazole. Flutriafol, Penconazole, Paclobutrazol, Diclobutrazol, Etaconazole and Difenoconazoleon obtained optimal separation on Chiralcel OD column; Prothioconazole, Epoxiconazole, Diniconazole and Bitertanol got optimal separation on Sino-Chiral OJ column; Simeconazole, Uniconazole and Metconazole achieved optimal separation on Chiralpak IB column. By comprehensive comparison of separation results on14triazole fungicides we can conclude that Chiralcel OD-H column has advantages of chiral recognition over Chiralpak IB column and Sino-Chiral OJ column. But Chiralpak IB or Sino-Chiral OJ column has better performance in separation speed, especially Sino-Chiral OJ column. The change of the chiral stationary phase may cause inversion and shape change of chromatography peaks.In order to obtain reasonable elution time, it is inevitable to add different polarity and suitable concentration of the alcohol modifier to the mobile phase, or the compounds are very difficult to be eluted. On three different chiral columns, when using different modifier of the same concentration, the eluted speed of fungicide enantiomers decreased in order of methanol, ethanol,2-propanol. Separation factor and resolution had complicated change depending on the change of modifier type and we could not conclude a law. Every compounds had its own best modifier conditions. When using the same modifier, as the concentration increased, the capacity factor gradually reduced, the separation factor stabilized in relative range, resolution basically reduced, but unusual results accasionally occursed.On Chiralcel OD column, the capacity factor, separation factor and resolution presented complicated change depending on temperature and it’s difficult to find a unified rule. The isoenantioselective temperature of Simeconazole, Uniconazole, two enantiomers of Bitertanol (corresponding the3rd and4th chromatography peaks) and two enantiomers of Bromuconazole (corresponding the3rd and4th chromatography peaks) were365.6K,341.5K,545.4and365.3K, which were above the range of temperature assayed. The enantiomeric separation was an "enthalpy driven" process and the separation factor decreased as the temperature increased. The isoenantioselective temperature of two enantiomers of Metconazole (corresponding the1st and2nd chromatography peaks) was287.8K, which was below the range of temperature assayed. The enantiomeric separation was an "entropy driven" process and the separation factor increased as the temperature the increase.On Chiralcel OD column, as the pressure increased, the capacity factor of fungicide enantiomers decreased gradually, but unconspicuous. the separation factor basical kept within a certain range; the change of the resolution was complicated.