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Synthesis, Conformational Studies, X-ray Structures, and Complexation Properties of Semirigid Macrocyclic Phosphonamides

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journal contribution
posted on 13.12.1996, 00:00 by Pascale Delangle, Jean-Pierre Dutasta, Luc Van Oostenryck, Bernard Tinant, Jean-Paul Declercq
The semirigid phosphonamide ligands 15 have been synthesized from the macrocyclic precursors 69 by reaction with 1,3-propanediol ditosylate or 1,2-dichloroethane. For the thiophosphoryl compounds 1 and 2, and the phosphoryl derivative 5, the reactions were carried out in biphasic aqueous NaOH solutions. The phosphoryl derivatives 3 and 4 were better obtained from NaH in anhydrous tetrahydrofuran. The conformations of the hosts in solution were deduced from low-temperature NMR and NOE difference experiments. Conformational equilibria between exo and endo forms are observed for the 18-membered macrocycles 1 and 3. The exo conformer predominates in solution for the 21-membered macrocycle 2, whereas 4 exists as rapidly exchanging conformers. The X-ray crystal structures of macrocycles 1, 2, and 5 have been determined as well as the complexes 1·Hg(SCN)2 and 5·LiNO3. In the Hg2+ complex the metal ion is located out of the macrocyclic cavity and is coordinated to the thiophosphoryl unit. In 5·LiNO3the Li+ cation is located inside the macrocyclic cavity and is coordinated to a tetrahedral array of oxygen donors. Free energies of complexation (ΔG°) of the phosphorylated ligands 35 with alkali metal and ammonium cations were determined in CHCl3 saturated with H2O by picrate extraction experiments. The −ΔG° values are greatest for 4 complexing K+ and NH4+ (7.3 and 8.0 kcal/mol, respectively). The relationships between structure and binding are discussed.