Resolution of enantiomeric amides on a cellulose-based chiral stationary phase. Steric and electronic effects

A series of enantiomeric amides were resolved on a commercially available chiral stationary phase (CSP) consisting of cellulose tribenzoate coated on macroporous silica. The amides were synthesized from several homologous series of aliphatic and aromatic chiral amines and a series of aliphatic chiral acids. The results of the study indicate that the formation of the solute-CSP diastereomeric complex is based on a combination of hydrogen bonding, pi-pi and amide dipole interactions. These interactions not only form the diastereomeric complex but also appear to position the solute and CSP within the complex. This is suggested by the fact that the enantiomeric elution order for a series of amides formed from aliphatic amines is R, S, whereas the enantiomeric elution order for the corresponding series of amides formed from aliphatic acids is S, R. The effects of steric bulk at the chiral center were also investigated; the results indicate that for the homologous series of aliphatic amides, an increase in the length of the alkyl chain attached to the chiral center results in an increase in the chiral resolution (alpha). This is not the case, however, for the homologous series of aromatic amides; the results suggest that chiral recognition is a function of the fit of the asymmetric portion of the solute in a chiral cavity (or channel) of the CSP and that this fit has rigid steric requirements.