Calixarene-Type Macrocycles

Calixarenes are cyclophane-type molecules, in which at least four aromatic units are joined via methylene or related groups [9]. It is known that calix[4]arenes with hydroxy groups in the 2-position normally prefer a conelike conformation, however, depending on the substituents a more or less rapid dynamic interconversion with three possible partial cone conformations is possible (Fig. 1) [9, 10]. 

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- 

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Figure 14 A furan-derived, calixarene-type macrocycle [25]...

Calixarene-A Versatile Host Calixarenes are macrocyclic host molecules made from phenol units finked through methylene bridges. The great freedom to structurally modify calixarenes allows us to create various types of host structures. 

Calixarenes are macrocyclic molecules synthesized with high yield by condensation of appropriate arenes and aldehyde derivatives. Calix means bowF in Latin and Greek, and this phrase reflects the shape of the tetramer, which usually adopts a bowl or beaker-like conformation. Gutsche first introduced the name calixarene for this class of compounds [38]. Several authors have exhaustively reviewed the chemistry and synthetic procedures, which lead to different structural modifications of calixarenes [39-42]. In general, three types of calixarenes derivatives are known first, metacyclophanes (type 1) second, those obtained by condensation of formaldehyde with phenol (type 11), and third, those obtained by reaction with resorcinol (type III) (Scheme 6). The latter modifications are also called resorcarenes to distinguish calixarenes of type III from those of type II. 

A new type of calixarene-capped calixpyrrole (9) has been generated (32 %) in one-step from p-fe/t-butylcalix[4]arene tetramethylketone as the template <96TL7881>. A cylindrical calix[4]-fois-cryptand, in which the central calix[4]arene possesses two 1,3-altemating diaza-tetraoxa macrocycles on each face, has been synthesized <96TL8747>. A series of substituted l,4-(2,6-pyridino)-bridged calix[6]arenes has prepared and studied <96LA1367>. 

Metalated container molecules can be viewed as a class of compounds that have one or more active metal coordination sites anchored within or next to a molecular cavity (Fig. 2). A range of host systems is capable of forming such structures. The majority of these compounds represent macrocyclic molecules and steri-cally demanding tripod ligands, as for instance calixarenes (42), cyclodextrins (43,44), and trispyrazolylborates (45-48), respectively. In the following, selected types of metalated container molecules and their properties are briefly discussed and where appropriate the foundation papers from relevant earlier work are included. Porphyrin-based hosts and coordination cages with encapsulated metal complexes have been reviewed previously (49-53) and, therefore, only the most recent examples will be described. Thereafter, our work in this field is reported. 

Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors in host—guest chemistry, have been prepared by multiple (double, triple or quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes containing unsaturated ester or alkene moieties (453). This one-pot synthetic method has been readily extended to the preparation of different types of macrocycles such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring size of macrocycles can be controlled by appropriate choices of the nitrile oxide precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocy-clization is a potentially useful method for the synthesis of macrocycles. 

Cascade-type binding [3.24] of anionic species occurs when a ligand first binds metal ions, which then serve as interaction sites for an anion. Such processes occur for instance in lipophilic cation-anion pairs [1.31] and with Cu(ll) complexes of bis-tren 33, of macrocyclic polyamines [3.25, 3.26] and of calixarenes [3.27]. 

Again at the beginning of the 1970 s, other classes of synthetic macrocycles were being investigated, not necessarily in connection with biological problems. For instance, the rich chemistry of Schiff base derivatives (Fig. 4.8) was being developed and yielded the first macrocyclic complexes in 1979 (Fig. 4.9). Another type of interesting macrocyclic molecules are the calixarenes (Fig. 4.8) the history of which can be traced back to the first experiments, in Berlin in 1872, of Adolf von Baeyer (Nobel prize in chemistry in 1905) who treated p-substituted phenols with formaldehyde in the presence of acid or base. 

Further examples of related multi redox-active macrocycles 89 — 91 have also been synthesised and their electrochemistry examined [108 — 110], Calix-4-arenes have also been derived from ferrocene to form monomeric macrocycles of type 92 or 93 together with dimeric compounds of type 94 [102] and crystal structures of the latter two compounds were reported. Solution HNMR and electrochemical studies in CH3CN, CHCI3, or CH2CI2 showed, however, that there was no complex formation between these calixarenes and either aliphatic or aromatic amines. 

The facile condensation reaction between formaldehyde and phenols or their derivatives provides a major route into rigid macrocycles used in supramolecular chemistry. Calixarenes, the best-known class of phenol-derived macrocycles, are prepared this way, as are spherands and their relatives. Cyclotriveratrylene, however, is an excellent exemplar of the molecular basket type of ligand and has been known for the best part of a century. The basic cyclotriveratrylene synthesis is shown in Figure 3.1. The original procedure by Mrs. Gertrude Maud Robinson [1] has since been refined by others and many variations are known [2,3]. 

Yamato. T. Yasumatsu, M. Samw atari. Y. Doamekpor, L.K. Synthesis and ion selectivity of macrocyclic metacyclophanes analogous to spherand-type calixarenes. J. Inclusion Phenom. Molec. Reeognit. Chem. 1994. 79,... 

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