3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: A fascinating molecular framework to study the enantioseparation ability of the amylose (3,5-dimethylphenylcarbamate) chiral stationary phase. Part II. Solvophobic effects in enantiorecognition process

Abstract

The enantiomers of five chiral compounds incorporating the 3-(phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole scaffold and differing only in the linear alkyl chain (varying in length from 1 to 5 carbon atoms) linked to the oxygen atom were directly separated on the amylose (3,5-dimethylphenylcarbamate) based Chiralpak AD-3 chiral stationary phase. The effects of the mobile phase composition, the structure of the analytes and temperature on the retention and enantioselectivity were investigated. It was found that the enantiomeric separations were in all cases enthalpy-driven and disfavored by entropic term. U-shape curves obtained by plotting the chromatographic data versus the alcoholic percentage in n-pentane-methanol and n-hexane-ethanol mobile phases highlighted that, at higher alcohol concentrations, solvophobic interactions were operative in the retention mechanism. The unusual trend of such curves was linked to the nature of alkyl chain of the pyrazolines and it was indicative of the solvophobic contribution to the achievement of a high degree of enantioseparation.

Keywords: Chiral stationary phase; Chiralpak AD-3; Enantiomer separation; Receptorial-like enantioselectivity; Solvophobic interaction; Structure-enantioselectivity relationships.