Optimization of the HPLC enantioseparation of 3,3′-dibromo-5, 5′-disubstituted-4,4′-bipyridines using immobilized polysaccharide-based chiral stationary phases

摘要

The HPLC enantioseparation of nine atropisomeric 3,3′,5,5′- tetrasubstituted-4,4′-bipyridines was performed in normal and polar organic (PO) phase modes using two immobilized polysaccharide-based chiral columns, namely, Chiralpak IA and Chiralpak IC. The separation of all racemic analytes, the effect of the chiral selector, and mobile phase (MP) composition on enantioseparation and the enantiomer elution order (EEO) were studied. The beneficial effect of nonstandard solvents, such as tetrahydrofuran (THF), dichloromethane (DCM), and methyl t-butyl ether on enantioseparation was investigated. All selected 4,4′-bipyridines were successfully enantioseparated on Chiralpak IA under normal or PO MPs with separation factors from 1.14 to 1.70 and resolutions from 1.3 to 6.5. Two bipyridines were enantioseparated at the multimilligram level on Chiralpak IA. Differently, Chiralpak IC was less versatile toward the considered class of compounds and only five bipyridines out of nine could be efficiently separated. In particular, on these columns, the ternary mixture n-heptane/THF/DCM (90:5:5) as MP had a positive effect on enantioseparation. An interesting phenomenon of reversal of the EEO depending on the composition of the MP for the 3,3′-dibromo-5, 5′-bis-(E)-phenylethenyl-4,4′-bipyridine along with an exceptional enantioseparation for the 3,3′-dibromo-5,5′-bis-ferrocenylethynyl-4, 4′-bipyridine (α = 8.33, R_s = 30.6) were observed on Chiralpak IC.