A theoretical comparison of conformational features of calix [4] aromatics

Although there are tremendous studies about the conformational feature of calix[4]arenes and its analogies, no theoretical study has been done systematically about why some structural modifications could completely lead to a change of conformational preference. For example, calix[4]arene 1 adopts a cone conformation while its analogue calix[4]pyrrole 7 only adopts a 1,3-alternate conformation. So if this is only because of the effect of OH-OH hydrogen bonds, then why does O-methyl substituted calix[4]arene 2 still has cone conformation? In this paper, the conformational features of a series of seven calix[4]axomatics, calix[4]arene and calix[4]pyrrole related structures, have been investigated at BLYP/6-31G{*} level both in the gas phase and in CH2Cl2 solution. The calculations demonstrated that three main factors influence the conformational preference of these calix[4] aromatics, i.e. the intramolecular hydrogen bond, the adjacent ring-ring electrostatic interaction and the intrinsic flexibility of the [1(4)] metacyclophane framework. Calix[4]benzene 3 and calix[4]pyridine 4 have little conformational preferences due to their flexible [1(4)] metacyclophane framework, the lack of hydrogen-bonding interactions and weak ring-ring electrostatic interactions. In contrast, calix[4] aromatics 1 and 5-7 have either intramolecular hydrogen bonds (1) or ring-ring electrostatic interactions (5-7). Consequently, calix[4]arene 1 has the cone preference and calix[4]pyrrole, calix[4]furan, and calixthiophene (5-7) have the 1,3-alternate preference. Methoxy calix[4]arene prefers a cone or partial cone conformation, because the 1,3-alternate and 1,2-alternate conformations are destabilized by electrostatic repulsions involving the methoxy group and the adjacent phenyl ring.