Structure-enantioselectivity relationship of hypnotic-sedative 1,4-disubstituted piperazine derivatives on cellulose tris(4-methylbenzoate) chiral stationary phase

Chromatographic behaviour of 19 chiral 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity has been examined on cellulose tris(4-methylbenzoate) with hexane-isopropanol mobile phases. The chiral resolution has been obtained for of 14 (out of 19) compounds. While three of the resolved compounds (5, 6 and 10) did not undergo enantiodifferentiation (α = 1) at relatively high isopropanol content (50-10%) in hexane, however, enantiodifferentiation was possible (α = 1.06-1.40) at lower isopropanol contents. Enantioselectivity changes induced by isopropanol content variations were discussed in terms of the concept of true and apparent separation factors. The retention factors of the compounds were described with the aid of modified Soczewiński-Snyder equation. Theoretical calculations were carried out for the chiral stationary phase model, which stressed the importance of a solute and the stationary phase aromatic ring interactions.