Exploring chiral separation of 3-carboxamido-5-aryl isoxazole derivatives by supercritical fluid chromatography on amylose and cellulose tris dimethyl- and chloromethyl phenylcarbamate polysaccharide based stationary phases☆

Abstract Four polysaccharide based chiral stationary phases were chosen, two chlorinated: Lux™ Amylose-2 (tris-5-chloro-2-methylphenylcarbamate of amylose) and Lux™ Cellulose-2 (tris-3-chloro-4-methylphenylcarbamate of cellulose) and two methylated: Chiralpak ® AD-H (tris-3,5-dimethylphenylcarbamate of amylose) and Chiralcel ® OD-H (tris-3,5-dimethylphenylcarbamate of cellulose) to separate four 3-carboxamido-5-aryl isoxazole derivatives by supercritical fluid chromatography. The effect of chiral stationary phase, co-solvent nature (MeOH, EtOH, 2-PrOH and ACN) and percentage (10–20%), temperature (20–45 °C) and chemical structure of the compounds on retention, resolution and elution order were thoroughly studied. In addition, thermodynamic parameters were determined from the linear portion of the Van’t Hoff plots. For all the derivatives, the Lux™ Cellulose-2 and Chiralpak ® AD-H provided excellent resolutions ( R s  = 9.78) in short run time (under 6 min). The preparation of about 10 mg of each of the eight enantiomers was achieved successfully on a Chiralpak ® AD-H with various percentages of ethanol as a co-solvent. Lastly, the enantiomeric purity of each of the eight individual enantiomer generated was determined and found higher than 98%.