Combined NMR spectroscopy and molecular mechanics studies on the stable structures of calix[n]arenes

All possible conformations of unmodified calix[n]arenes (1_n: n = 4-7) were systematically generated by CONFLEX3 using corresponding model compounds 2_n: the numbers of the trial conformations and the final conformations are 110 and 5 for 2₄, 645 and 23 for 2₅, 4438 and 133 for 2₆ and 31620 and 809 for 2₇. These initial structures for 1_n, were optimized by MM3(92): the numbers of the energy minima are 4 for 1₄,10 for 1₅, 90 for 1 ₆ and 651 for 1₇. The most stable structures screened out of these conformational isomers were compared with those predicted by ¹H NMR spectroscopic studies and with those determined by X-ray crystallographic studies. It was shown that (i) the small-ring calix[n]arenes (1₄ and 1₅) keep the high molecular symmetry because stable intramolecular hydrogen bonds among the OH groups can be formed in the regular cone conformer whereas the large-ring calix[n]arenes (1₆ and 1₇) lose the molecular symmetry and tend to adopt a 'pinched' conformation because the formation of the stable intramolecular hydrogen bonds inevitably induces ring deformation, (ii) there exists no special torsional difference between even-numbered calix[n]arenes (1₄ and 1 ₆) and odd-numbered calix[n]arenes (1₅ and 1₇) and (iii) the structures obtained from X-ray analysis and NMR spectroscopic studies can be generated as the most stable structures in the computational studies. The results have enabled us to give reasonable rationales to several controversial problems that have been troubling calixarene chemists.