Host-Guest Complexation. 30. Quinquaryl and Bis(urea) Binders

Article abstract of DOI:10.1021/ja00329a058

Six new types of macrocycles and one open- chain analogue are described, along with their conformational behavior and binding free energies toward alkali metal, ammonium, and alkylammonium picrates.The cycles are 20-membered and are composed by attaching aryloxy, cyclic urea, pyridyl, ethylene, methylene, and oxygen units to one another.The structures and points of attachment of all but the latter two units are drawn and are symbolized by capital letters. A, A', U, D, F, G, Py, E.The structures of the hosts and the synthetic intermediates are indicated by line formulas consisting of sequences of letters which represent the sequences of units bonded to one another in the hosts.The key intermediate in the synthesis of A'(A'DE)2O (5) and A'(A'DCH2)2Py (6) was bis(phenol) A'(A'DH)2 (18).Ring closure of this compound with O(CH2CH2OTs)2 and base gave A'(A'DE)2O (5, 49percent) and with BrCH2PyCH2Br and base gave A'(A'OCH2)2Py (6, 11percent).Treatment of the second key intermediate, bis(phenol) A(UDH)2 (32) with O(CH2CH2OTs)2 and base gave A(UDE)2O (7, 56percent) and with BrCH2PyCH2Br and base gave A(UDCH2)2Py (8, 29percent).A mixture of the third key intermediate, bis(hydroxymethylphenol) A(UFH)2 (33), with BrCH2PyCH2Br and base gave bis(hydroxymethylene) compound A(UFCH2)2Py (9, 47percent), methylation of which produced A(UGCH2)2Py (10, 82percent).Methylation of A(UFH)2 (33) directly gave open-chain reference compound A(UFMe)2 (11, 38percent).Spectral experiments (1H NMR and 13C NMR) demontsrated that free cycles A(UDCH2)2Py (8), A(UFCH2)2Py (9), and A(UDCH2)2Py (10) exist in solution as two conformers, one that binds guests (binding or B' conformer) and one that is nonbinding (N' conformer).In solution, the two conformers equilibrate observably on the human and slowly on the 1H NMR time scales.When treated with guest, each host gives a single complex formed instantaneously with B, but over a period of hours with N'.Interestingly, A(UDCH2)2Py (8) crystallizes in the free state and as its NaClO4 complex as its binding (B') conformer, which is disfavored in CdCl3 solution at equilibrium (/ = 3 at 28 deg C).In the absence of polar or ionic catalysts, the B' conformer goes to the N' conformer at 28 deg C with ΔG^<*> ca. 22 kcal mol^-1.In contrast, A(UFCH2)2Py (9) crystallizes as its nonbinding (N') conformer, which also predominates in the free state in CDCl3-DCON(CD3)2 solution (/ = 2.2 at 28 deg C).Molecular models and NMR spectral comparisons suggest that the N' conformations of A(UDCH2)2Py (8), A(UFCH2)2Py (9), and A(UGCH2)2Py (10) either have their single methyl groups or their two methylene groups turned inward to fill their cavities.The binding free energies (-ΔG^deg) at 25 deg C in CDCl3 saturated with D2O were determined by the extraction technique for hosts 5-11 binding the picrate salts of Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, NH4⁺, CH3NH3⁺, and t-BuNH3⁺.Maximum binding by the six cycles of the guests was observed for Na⁺ or K⁺ ions, with -ΔG^deg values in the 13.3-10.0 kcal mol^-1 range.Quinquaryl systems, A'(A'DE)2O...