Chiral Porous Organic Cages Used As Stationary Phases For High Performance Liquid Chromatography

Porous organic cages（POCs）are a class of porous molecular materials which self-assembled by discrete,small cage-like molecules through weak intermolecular forces,and their porosity are composed of the internal cavity of the cage molecule and the accumulation pores outside the cage molecule.POCs have good solubility in common organic solvents that gives them advantages in synthetic modification,preparation of composite materials and coating to prepare porous membranes in solution state,so they have attracted extensive attention in many fields.To date,many chiral POCs have been explored as chiral stationary phases（CSPs）for resolution of enantiomers by gas chromatography（GC）,however,to the best of our knowledge,there have been no reports on the use of chiral POCs as CSPs for HPLC enantioseparation.Therefore,it is necessary to explore the application potential of POCs in HPLC.In this thesis,three kinds of hydroxyl functionalized chiral POCs were synthesized and immobilized on the surface of thiol-functionalized silica gel by thiol-ene click reaction to prepare CSPs for HPLC,and their chiral separation capability was evaluated.The main research contents are as follows:（1）In the introduction section,the basic concept of chirality,the significance of chiral separation,the main methods of chiral separation,HPLC and its CSPs were introduced.Moreover,the main synthetic methods and applications of POCs were briefly reviewed.（2）A [3+6] prismatic homochiral POC NC1-R with hydroxyl functional group was synthesized by Schiff condensation reaction of3,3’,5,5’-tetraformyl-4,4’-biphenyldiol with（1R,2R）-cyclohexanediamine,and it was immobilized on the surface of thiol-functionalized silica gel by thiol-ene click reaction to prepare novel CSPs（CSP-1 and CSP-2）for HPLC.The chiral separation capability of the CSPs were evaluated and compared with commercial Chiralpak AD-H and chiralcel OD-H columns.The experimental results showed that twenty-three and fifteen chiral compounds were resolved on CSP-1 and CSP-2 under normal-phase mode,respectively.CSP-1 with cationic imidazolium spacer has better resolution capability than CSP-2.Furthermore,CSP-1 has good chiral resolution complementarity to commercial Chiralpak AD-H and chiralcel OD-H columns.In addition,CSP-1 also exhibits good enantioselectivity under reversed-phase mode.（3）A [4+6] chiral POC with hydroxyl functional group was synthesized by condensation of 2-hydroxy-1,3,5-triformylbenzene with（1R,2R）-1,2-diphenylethylenediamine and immobilized on the surface of thiol-functionalized silica gel by thiol-ene click reaction to prepare CSP for HPLC.The separation capability of the CSP were evaluated.Thirteen racemates were resolved on the CSP indicate that it has good chiral recognition capability.In addition,ten positional isomers were also separated on the CSP with different degrees of separation.（4）A [4+8] chiral POC with hydroxyl functional group was synthesized by condensation reaction of 5,5’-（propane-2,2-diyl）bis（2-hydroxyisophthalaldehyde）with（1R,2R）-cyclohexanediamine and immobilized on the surface of thiol-functionalized silica gel by thiol-ene click reaction to prepare CSP for HPLC.The chiral resolution performance of the CSP in normal phase HPLC（NP-HPLC）and reversed phase HPLC（RP-HPLC）modes was investigated.The experimental results showed that the CSP has good chiral separation performance not only in NP-HPLC mode but also in RP-HPLC mode.In addition,the chiral resolution performances of the CSP in the two modes are complementary to each other.Some chiral compounds cannot be resolved in NP-HPLC mode but can be well resolved in RP-HPLC mode,thus broadening the enantiomers separation scope and applicability.