Original uses of the pH-zone refining principle: Adaptation to synthesis imperatives and to ionic compounds

Countercurrent chromatography is a powerful separation technique based on t he partition of solutes between two immiscible liquid phases. The first one , maintained in the column by a centrifugal force, acts as the stationary p hase; the second phase, circulating through the apparatus, elutes compounds according to their partition coefficients. The total liquid nature of this process allows the addition of auxiliary components in both phases, increa sing the separation power of countercurrent chromatography. In 1991, Y. Ito introduced pH-Zone refining systems in which the stationary phase contains a retainer and the mobile one an eluter. The acid-base system that acts as the retainer-eluter pair interacts with s olutes and enables a separation based on acidic constant (pKa) base. First, this method was successfully used to separate and purify two poly-aza hete rocyclic isomers, obtained by hetarynic dimerization and which are precurso rs of antitumor agents. Because of several imperatives, a new system, adapted from the classical on e (eluter-retainer), was developed to respect our limitations. Secondly, io nic solutes such as sulfonic acid compounds cannot be studied by such a sys tem, based on the influence of the acidic constant. Therefore, the retainer is replaced by a cationic liquid resin with very strong hydrophobic proper ties. Added to the organic stationary phase, this resin gives the stationar y phase an ion-exchange behavior, guided by the eluter contained in the mob ile phase. Applied to ionic solutes, the study of this new system highlight s the main parameters of the separation.