Enantiomeric Recognition of Racemic 4‐Aryl‐1,4‐dihydropyridine Derivatives via Chiralpak AD‐H Stationary Phases

Abstract

The chromatographic chiral resolution of two new series of racemic 4-substituted-1,4-dihydropyridine derivatives was studied on a commercial Chiralpak AD-H column. Analytes without 5,5-dimethyl substituents (1-15) are more efficiently resolved than analytes with 5,5-dimethyl groups (16-30). The AD-H column discriminated between enantiomers through both hydrogen bonding attractions and π-π interactions. This interpretation is in accord with plots of the logarithm of separation factors, log(α), versus σ (Hammett-Swain substituent parameter) and σ(+) (Brown substituent constant) plots. By elucidating the effects of the remote substituents on these chiral separations, it was shown that the influence of π-π interaction forces increase when steric bulk effects act to decrease the hydrogen bonding attractive forces on the AD-H column.

Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair Analysis

“…Investigating aromatic substituent effects has long been used as a means to better understand chiral molecular recognition, particularly for the π-acidic and π-basic CSPs where π-π interaction is believed to be important. Hammet-type analysis has often been used to gain an appreciation of the relative contribution of these electronic effects, although the results are often only roughly directional in nature [3,[66][67][68]. Figure 8 shows several MMP clusters where the effects of ortho aromatic substitution on chiral recognition can be observed.…”

Novel Stereoselective High‐Performance Liquid Chromatographic Method for Simultaneous Determination of Guaifenesin and Ketorolac Enantiomers in Human Plasma

“…During the chiral resolution, the enantiomers fit stereogenically in different fashions into the chiral grooves of the CSP, which is stabilized by various types of bonding of different magnitudes, and thus chiral discrimination between enantiomeric solutes is then determined by differences in steric fit in the chiral cavity …”

“…For phenylcarbamate derivatized polysaccharides, the main chiral adsorption sites are probably the polar carbamate groups, which are able to interact with a racemate through hydrogen bonding and dipole–dipole interaction (carbonyl and carboxylic groups present in KET molecule, hydroxyl group in GUA molecules). Moreover, the π–π interactions between the phenyl groups of the phenylcarbamates and hydrophobic aromatic group of a racemate (phenyl ring in both GUA and KET molecules) may also play an important role in their recognitions …”

“…The benefit of these substituents in different positions has led to the development of new polysaccharide‐based chiral stationary phases . The enantioselectivity of those CSPs was evaluated with different chromatographic and electromigration techniques such as normal‐phase liquid chromatography (NPLC), reversed‐phase liquid chromatography (RPLC), polar organic solvent chromatography (POSC), superficial fluid chromatography (SFC), and capillary electrochromatography (CEC) …”

Liquid Chromatography Enantioseparations of Halogenated Compounds on Polysaccharide‐Based Chiral Stationary Phases: Role of Halogen Substituents in Molecular Recognition

“…44 Caccamese et al reported the direct HPLC enantioseparation of venlafaxine and 11 analogs, among which were the halogenated β-aminoalcohols 9-11 (Table 9). Pittman and colleagues reported the enantioseparations of a series of 4-haloaryl-1,4-dihydropyridines using Chiralpak AD-H with n-hexane-containing MPs.…”