18-Membered-Ring Spherands Containing Five Anisyl Groups

The syntheses, characterization, and binding properties of four new spherands are reported, each of which contains five meta-linked anisyl binding sites incorporated in an 18-membered macrocyclic ring. A sixth binding site was (CH₂)₂O, (CH₂)₂S, (CH₂)₂C(CO₂Et)₂, or (CH₂)₂CH(CO₂Et). A crystal structure of the first of the above compounds contains two independent and slightly different molecules per unit cell. In both molecules the five anisyl CH₃O groups and one CH₂OCH₂ group possess an up-down-up-down-up-down conformation in proceeding clockwise around the ring, and all six oxygens' unshared electron pairs line an elongated spherical cavity preorganized to bind the smaller alkali metal cations. The free energies for this system binding Li⁺, Na⁺, and K⁺ picrates at 25 °C in CDCl₃ saturated with D₂O were respectively 12.8,14.4, and 10.4 kcal mol⁻¹ (−ΔG° values). Its sulfur analog was less selective in its binding, which still peaked with the Na⁺ picrate (−ΔG° = 12.2 kcal mol⁻¹). A crystal structure of this sulfur-containing spherand showed the six binding sites were preorganized similar to those of its oxygen analog. The two ester-containing systems failed to extract Li⁺ and Na⁺ picrate rapidly on the human time scale but were shown by other equilibration experiments to strongly bind LiClO₄ and NaClO₄ in CDCl₃ solution.