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 rnoxdecular 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 (?G =11.1 kcal/mol) and 315 K (?C = 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 1H-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) Å). 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.