Synthesis, X-ray Crystal Structures, and Cation-Binding Properties of Alkyl Calixaryl Esters and Ketones, a New Family of Macrocyclic Molecular Receptors

Calix[N]arenes (N = 4, 6, 8) have been converted into polyfunctional esters and ketones in a search for new macrocycles capable of showing ionophoric activity. Treatment with alkyl bromoacetates furnished the calixaryl acetate series, whereas chloroacetone-potassium iodide, phenacyl chloride, 1-adamantyl bromomethyl ketone, and bromopinacolone were used to make the calixaryl ketones series. The crystal structures of ethyl calix[4]aryl acetate (7), methyl calix[4]aryl acetate (13), ethyl calix[6]aryl acetate (11), and calix[4]aryl methyl ketone (20) have been determined. The crystals of 7 are triclinic, space group P1 with two molecules in the unit cell of dimensions a = 12.434 (2) Å, b = 15.033 (3) Å, c = 17.286 (4) Å, α = 103.01 (2)°, β = 102.97 (1)° and γ = 94.68 (1)°. The crystals of 13 are monoclinic, space group C2/c, with eight molecules in the unit cell of dimensions a = 27.066 (6) Å, b = 21.392 (6) Å, c = 21.348 (7) Å, and β = 119.32 (2)°. The crystals of 11 are monoclinic, space group C2/c, with four molecules in the unit cell of dimensions a = 21.906 (4) Å, b = 11.805 (2) Å, c = 23.534 (4) Å, and β = 91.79 (2)°. The crystals of 20 are orthorhombic, space group Pbcn, with four molecules in the unit cell of dimensions a = 19.644 (7) Å, b = 12.712 (3) Å, and c = 22.115 (7) Å. Both 11 and 20 have crystallographically imposed 2-fold molecular axes. The analysis establishes that all three tetramer derivatives possess the cone conformation in the solid state where the pendant-functionalized side chains are mutually syn with respect to the calixarene substructure and are thus preorganized for ion reception. NMR measurements confirm the existence of the cone conformation for these tetramers in solution at room temperature. In contrast, the centrosymmetric hexamer ester 11 has three adjacent groups syn, but the inversion symmetry places the other three ester groups in the anti position on the opposite side of the macrocycle. Extraction studies with alkali metal picrates from aqueous solution into dichloromethane, transport studies with alkali metal thiocyanates through a dichloromethane membrane, and stability constant measurements with alkali metal salts by UV absorption spectroscopy in methanol and acetonitrile were used to assess the ionophoric activity of these calixarene derivatives. The tetramer esters and ketones display peak selectivity for the sodium ion, the tetraketones being generally more efficient binders than the tetraesters. The hexaester extracts K⁺better than Na⁺and displays a plateau selectivity after K⁺. The octamers are the least effective ionophores. The selectivities shown by the picrate extraction technique are broadly mirrored in the transport studies. Stability constants range from 2 to 6, with a clear maximum for Na⁺with most of the tetramers and for K⁺with the hexamer; the values are of the same order of magnitude as for dibenzo-18-crown-6. The thermodynamic results are in fairly good agreement with the extraction and transport rate data. They enable a comparison of these new calixarene receptors with respect to crowns and cryptands: they are looser binders than cryptands 221 and 222; most tetramers offer in methanol a better Na⁺/K⁺selectivity than cryptand 221, and in acetonitrile, the hexamer is at least as selective for K⁺as cryptand 222.