ALKANEDIYL BRIDGED CALIX[4]ARENES - SYNTHESIS, CONFORMATIONAL-ANALYSIS, AND ROTATIONAL BARRIERS

In calix[4]arenes when one methylene bridge carries an alkyl or aryl s ubstituent, two diastereomeric cone conformations are possible in whic h this substituent assumes the equatorial or axial position. Two diast ereomers with cir or trans arrangement of the substituents exist for t he corresponding compounds with two substituted bridges, and diastereo meric cone conformations have to be considered additionally in most ca ses. Molecular mechanics calculations predict an energetical preferenc e of the equatorial position of the substituents in both systems. This preference is markedly more pronounced for alkyl groups than for aryl groups. To test these predictions a series of calix[4]arenes in which one (4) or two opposite (5) methylene bridges are substituted by alky l or aryl groups was synthesized by fragment condensation. For these c alixarenes the solution conformations, the equatorial/axial conformati onal equilibria, and the energy barriers for the cone to cone ring inv ersion wore determined by H-1 NMR spectroscopy. The experimental energ y differences between the two cone conformations correlate well with t he calculated ones. Free energies of activation Delta G(t) for the con e to cone ring inversion of the monoalkyl substituted compounds 4 incr ease in the order methyl < tert-butyl < ethyl < isopropyl. For the bis alkyl substituted compounds (5b-d) only the cis-isomer could be isolat ed while cis- and trans-isomers were obtained for 5a and for the bisar yl compounds 5e-g. Among the cis-isomers 5a-d exist exclusively as the equatorial conformers. while the conformational equilibrium is strong ly solvent dependent for 5e-g. Single crystal X-ray structures were ob tained for several calixarenes with one (4b) or two substituted bridge s(5e-g). Here the substituents are found exclusively in the equatorial position. and the molecular conformation is similar to the calculated one.