P-tert-butylcalix[6]arene Symmetrically Tetrasubstituted With Pyridine Pendant Groups - Synthesis, X-ray Crystal-structure, and Conformational-analysis By Dynamic Nmr-spectroscopy and Molecular Mechanics Calculations

The synthesis and conformational analysis of the title compound 1 by dynamic NMR spectroscopy and MM2 molecular mechanics calculations are presented. Complete assignments of both proton and carbon NMR spectra were achieved by a combination of COSY, HMQC, and HMBC experiments at 280 K. From VT-NMR analysis in the range 220-345 K, two coalescence temperatures at 227 (DELTA-G = 11.1 kcal/mol) and 315 K (DELTA-G = 14.2 kcal/mol) were ascertained in CDCl3. MM2 energies of the 14 possible conformers of 1 (grouped into five families A-E, depending on the relative orientations of the four pyridinyl pendant moieties) showed conformer A as the most stable. The symmetry of NMR signals and NOESY data restricted the possible conformations of 1 in solution, at temperatures below 315 K, to those designated as A and C. Whereas conformers of type C could be ruled out on the basis of MM2 results, conclusive evidence in favor of the existence of conformer A in solution was provided by H-1-NMR and ROESY spectra of 1 in CD2Cl2 at 183 K. Consistent with the above results, a probable mechanism for the conformational interconversion of 1 is proposed. Compound 1 in the solid-state structure, determined by X-ray crystallography, adopts the 1,2,4,5 alternate conformation (A1), which has crystallographic two-fold symmetry. The major features determining the conformation are a pair of intramolecular O-H...O hydrogen bonds, (O...O 2.78 (1) angstrom). The molecular cavity is rendered inaccessible by the four CH2PY pendant groups (two on either side of the calixarene annulus), which prevent possible enclathration of solvent molecules