Conformationally Mobile Calixarenes

5 Conformational Properties of the Calixarenes 5.1 Conformationally Mobile Calixarenes 

The possibility of conformational isomerism in the calix[4]arenes, adumbrated by Megson112) and Ott and Zinkell3), was made explicit by Comforth et al.10) who 

Inversion Rate a Function of -Substituents Ring Size Solvent AG, keal/mole T c Ref. 

A number of calixarenes with various /7-substituents and ring sizes have now been studied by means of dynamic lH NMR, and the free energies of activation for the conformational inversion have been calculated, as shown in Fig. 21. 

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The preferred conformation of the unsubstituted calixarene shown in Fig. 1 (X = CH2) is 1,3-alternating, whereby two opposite rings are perpendicular to the plane formed by the four methylene groups and the other two are parallel to the same plane [11]. In the case of calix[6]arenes the conformational mobility is enhanced and 1,3,5-alternating or 1,4-alternating winged conformations have been identified as the preferred ones [9]. Very few heteratom-... 

Much of the attraction that supramolecular chemists have for calixarenes is due to their conformational mobility. The calix[4]arenes are particularly widely used as their conformers, illustrated in Fig. 1.10, interconvert until large groups are attached... 

The structures and abbreviations used for designating the calix[4]arenes are shown in (5). These calix[4]arenes, have both a wide (upper) and a narrow (lower) rim that can be chemically modified to produce complexants that are selective for particular metal ions. In the simple calixarene framework the wide rim has hydrocarbon functionalities, and the narrow rim phenolic groups. Calixarenes are conformationally mobile, and the extreme structures for the calix[4]arenes have been termed the cone, partial cone, 1,3-alternate, and 1,2-alternate conformations (6). Because of the conical geometry of the calix[4]arene structure, the cavity size of the wide rim is larger than that of the narrow rim. 

Since the calixarenes form complexes with a variety of guests (see Chapter 5) it is not surprising that their conformational mobility is influenced by cations. 

Conformational mobility of calixarenes with one or more hydroxyls replaced by other groups... 

Conformational Mobility of Calixarene Methyl Ethers, Ethyl Ethers, Deoxycalixarenes, Calixquinones, and Calixarenethiols... 

Calixarenes fully functionalized at the lower rim with ether groups show a weak affinity for alkali metal ions. The case of the tetramethyl ether of /7-T rT-butylcalix[4]arene (13) is quite interesting, since it is conformationally mobile, and can adapt its conformation to different metal ions. The Na+ ion is exclusively complexed by the cone isomer, while Cs is preferentially bound by the partial cone isomer. 

Extensive studies of the conformational preferences of calixarenes have established certain shape preferences, and a view of the cone-shaped form that has found the most use in molecular recognition studies is shown below. It should be remembered, though, that without additional structural constraints that favor this form, a simple calixarene is conformationally mobile and exists in several different forms. 

When a solution of 2,6-dimethyl-4-hydroxybenzyl alcohol 32 in nitrobenzene was treated with 0.5 equiv. of AICI3 at 90 °C, the expected macrocycle 33 was not observed, but isomeric calixarene 35 was isolated as the sole product in 28 % yield [14]. This remarkably simple preparation of octakis meto-substituted calixarene 35 probably involves the rearrangement of32-34 prior to the cyclization (Scheme 3.9). Indeed, when 34 was submitted to the same reaction conditions, 35 was obtained in 50 % yield. Dynamic behaviour of 35 was smdied using the combination of NMR study and molecular mechanics calculations. The NMR spectra are in agreement with a species that is conformationally mobile on the NMR time scale at room temperature. The increased flexibility of 35 compared to parent caUx[4]arene can be ascribed to the lower energy barrier for inversion due to the steric repulsions... 

To date the calix[n]arene family consists of 17 cyclooligomers, ranging from the tetramer to the eicosamer [1], Those constitued by 4, 6, and 8 phenolic units are called major" because they are obtainable in good yields with typical one-pot procedures, differently by the minor" calixarenes, with odd phenolic units (n = 5, 7), only obtainable in lower yields. Usually, the cyclic oligomers with a number of phenolic units >7 are termed large" [2] and they have in conunon a number of features, such as the high conformational mobility and the large variety of possible conformations. 

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