Host-guest chemistry cyclophanes

Since the seminal work of Cram on cyclophanes and resorci-narenes (1) the host-guest chemistry of container molecules has been extensively investigated and more sophisticated examples with other forms and larger cavities have been reported. Thus a large number of host-guest complexes containing neutral,... 

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. 

Most of the cycles which have been formed in this way belong to the field of host/guest chemistry, e.g., the azacrown ethers 31 [38] and 32 [39], tropocoronands such as 33 [40], or even cyclophanes such as the host compound 34 synthesized by Koga [41]. In the cavity formed by the two diphenylmethane units, 34 encloses naphthalene as a guest [42]. 

The first practical application for cyclophanes was found in host-guest chemistry [4]. Molecular recognition of ions and neutral molecules in functionalized cavities of cyclophanes has been demonstrated for numerous examples. Here, special interest has been attracted by complexes in water since it can directly model molecular recognition events in biological systems. The development of suitable water soluble hosts with high binding selectivity is an active field of research [5] that has recently been reviewed [6]. 

Why do we call them by this name It is because they are hybrids of both structural features, and consequently not only show the ionophoric properties of crown ethers but also the characteristic behavior of cyclophanes, especially the structural advantage to orient several moieties in desired directions. These interesting hybrids steadily growing in number, have thus been given this specific family name which may not be confused with any other families in host-guest chemistry. 

There are a great variety of examples in the crownophane family. All these compounds were made by using displacement reactions. This review deals mostly with their properties, but does not refer to their detailed synthetic methods. In this section, compounds are classified by the type of aromatic nuclei, and at the same time, it is emphasized how they work in the host-guest chemistry, taking advantage of the cyclophane skeleton. 

A hallmark in supramolecular chemistry came in 1967, when Pedersen created the first crown ethers. These were entirely synthetic, macrocyclic, and capable of recognizing and binding small ions. Crowns opened the door to many possibilities. Most importantly, new ideas began to flood, and a new field was created, called host-guest chemistry. Donald J. Cram was among the first to recognize the potential of crowns, and he assimilated his knowledge of cyclophanes, crowns, cyclo-... 

The main supramolecular self-assembled species involved in analytical chemistry are micelles (direct and reversed), microemulsions (oil/water and water/oil), liposomes, and vesicles, Langmuir-Blodgett films composed of diphilic surfactant molecules or ions. They can form in aqueous, nonaqueous liquid media and on the surface. The other species involved in supramolecular analytical chemistry are molecules-receptors such as calixarenes, cyclodextrins, cyclophanes, cyclopeptides, crown ethers etc. Furthermore, new supramolecular host-guest systems arise due to analytical reaction or process. 

Macrocycles are a highly topical subject. They constitute a large spectrum of compounds involving both artifical substances and natural products such as crowns, cryptands, cyclophanes, porphyrins, or macrolides. The former initiated the exiting area of host-guest supramolecular chemistry, which was highlighted by the award of the Nobel Prize for Chemistry to D. J. Cram, J.-M. Lehn, and C. J. Pedersen in 1987 but is still developing enormously. Porphyrins and macrolides are important active substances. No wonder that macrocycles are of immediate interest and everyone wants to know how they can be synthesized efficiently. 

Perhaps the most efficient stimulus in cyclophane chemistry goes back to the discovery of crown ethers by C. J. Pedersen in 1967 [(1967) J Am Chem Soc 89 7017] being the starting signal for a very promising field of research called Host-Guest or Supramolecular Chemistry. Actually the first crown ether that was synthesized, dibenzo-18-crown-6, was a cyclophane. 

The present book provides a state-of-the-art view on some of these topics including topological, conformational and host-guest problems written by five recognized experts. Because of this, the book lays no claim to being a quantitative overview of cyclophane chemistry. However, in this latter respect, the reader is referred to the excellent monographs produced by F. Diederich [(1991)... 

Another attempt to use the host-guest complexation of simple cyclophanes has been reported by Schneider They take the easily accessible host 7, an analogue of which had been demonstrated by Koga to bind aromatic guest molecules by inclusion into its molecular cavity, and study its rate effects on nucleophilic aliphatic substitutions of ambident anions (NOf, CN, SCN ) on 2-bromomethylnaphthalene 8 and benzylbromide. Similar bimolecular reactions are well known in cyclodextrin chemistry and other artificial host systems . In addition to the rather poor accelerations observed (see Table 3) the product ratio is changed in the case of nitrite favouring attack of the ambident nucleophile via its nitrogen atom. 

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