Cavitands cavity

The reaction of ferrocenecarbaldehyde (98) and resorcinol (99) under acidic conditions gave the phenolic macrocycle (100), which on addition of chlorobromomethane in the presence of a base produced the first redox-active cavitand (141,142) (101) (Scheme 31). An X-ray structural investigation on crystals of (101), obtained from a dichlorometh-ane-diethyl ether solvent mixture, revealed the inclusion of a dichloro-methane guest molecule within the cavitand host cavity (Fig. 23). Related redox-active cavitand host molecules ((102) and (103)) containing ferrocene moieties lining the wall of the cavitand cavity have also been prepared by our group (141, 142). 

Molecular mechanics calculations (142) performed on neutral inclusion complexes of cavitand (101) suggested that the cavitand cavity would allow inclusion of small organic guest species such as carbon... 

Fig 1. Stereographic projection of the crystal structure of the 2 1 inclusion compound between CS2 and cavitand 1. One CS2 ( guest ) molecule is encapsulated within the host cavity, the second CS2 ( solvent ) being located between the complexed entities (taken from Ref.27>)... 

Figure 1 shows the crystal structure of the 5,10 12,17 19,24 26,3-tetrakis (dimethyl-siladioxa)-l, 8,15,22-tetramethyl[l4]metacyclophane cavitand (7) which has an enforced cavity appropriately sized to include only slim linear guests 12b). This cavitand forms crystals of a 1 1 molecular inclusion complex with CS2, the guest species being almost entirely encapsulated within the host cavity 27). The crystal structure of the complexed... 

A further category of cavitands are the calixarenes (Gutsche, Dhawan, No Muthukrishnan, 1981 Gutsche Levine, 1982). Structure (255) illustrates an example of this type which is readily prepared by treatment of 4-f-butylphenol with formaldehyde and base. The compound may exist in other conformations besides the saucer-shaped one illustrated by (255). Similarly, f-butyl-calix[4]arene (256 R = CH2COOH) has an enforced hydrophilic cavity in the shape of a cone the alkali and ammonium salts of this host are soluble in water (Arduini, Pochini, Reverberi Ungaro, 1984). 

Further examples of cavitand-type structures include hw-cyclo-triveratrylene derivatives such as (257) (Gabard Collet, 1981 Canceill, Lacombe Collet, 1986) and the bowl-shaped hosts represented by (258) - the base of the bowl is formed by the four methyl groups. Once again, the shape of these molecules is maintained by conformational constraints. Cavitand (258) is able to accommodate simple solvent molecules such as dichloromethane and chloroform. Moreover, its cavity is large enough to form inclusion complexes with up to four molecules of water (Moran, Karbach Cram, 1982). 

Molecular models indicate that cavitand (259) has a tall, vase-shaped architecture in which the four benzene rings and four nine-membered rings combine to form a concave cavity to which is attached the four diazanaphthalenes (Moran, Karbach Cram, 1982). The latter groups resemble flaps which may occupy either equatorial or axial positions. In the former arrangement, the inner surface area of the cavity is quite reduced and hence a considerable decrease in the inclusion ability of this form is expected. 

Fig. 6 Wave-like ribbon structure of complex 18.p-xylene.l.5(DMF), where DMF=dimethyl-formamide. Guest p-xylene occupies the cavitand molecular cavity, while disordered DMF (only one position shown) occupies the cage created by pendant arms at the lower rim [39]... 

Alternative routes were used to prepare a series of tetra-bridged phospho-rus(III) cavitands with PNR2 (R=alkyl) or POMe groups and with various substituents at the lower rim of the cavity (Scheme 7). For instance, compounds 3a-3e were synthesized from P(NR2)s and the corresponding re-sorc[4]arene in benzene at room temperature [50], or in hot dioxane [51,... 

The two-steps synthesis of thiophosphorylated cavitands is by far the best method to control the stereoselectivity of the resultant products. As for the P=0 partners, it is important to obtain the all-inward oriented P=S donating groups in high yields to benefit from cooperative effects of the P=S donor groups and the aromatic cavity in the formation of host-guest complexes. 

The complexation of anionic species by tetra-bridged phosphorylated cavitands concerns mainly the work of Puddephatt et al. who described the selective complexation of halides by the tetra-copper and tetra-silver complexes of 2 (see Scheme 17). The complexes are size selective hosts for halide anions and it was demonstrated that in the copper complex, iodide is preferred over chloride. Iodide is large enough to bridge the four copper atoms but chloride is too small and can coordinate only to three of them to form the [2-Cu4(yU-Cl)4(yU3-Cl)] complex so that in a mixed iodide-chloride complex, iodide is preferentially encapsulated inside the cavity. In the [2-Ag4(//-Cl)4(yU4-Cl)] silver complex, the larger size of the Ag(I) atom allowed the inner chloride atom to bind with the four silver atoms. The X-ray crystal structure of the complexes revealed that one Y halide ion is encapsulated in the center of the cavity and bound to 3 copper atoms in [2-Cu4(//-Cl)4(//3-Cl)] (Y=C1) [45] or to 4 copper atoms in [2-Cu4(/U-Cl)4(/U4-I)] (Y=I) and to 4 silver atoms in [2-Ag4(/i-Cl)4(/i4-Cl)] [47]. NMR studies in solution of the inclusion process showed that multiple coordination types take place in the supramolecular complexes. 

The main feature for cation recognition by tetra-bridged phosphorylated cavitands arises from the cooperative effect of the four phosphorus groups and the aromatic molecular cavity. In the phosphorus(IV) cavitands guest binding will be achieved through O (P=0) or S (P=S) coordination with different affinity for hard or soft metal ions. On the other hand, transition metal rim complexes described above can act as host for metal cation. 

The Ag cations are coordinated to two sulfur atoms of different cavitands with Ag-S distances in the range 2.47-2.50 A. In the solid, efficient r-stack-ing of the P-phenyl groups with the picrate anions stabilizes the supramolecular complex (Fig. 10). The two cavitands are aligned along their common C4 axis and offset by about 45°, leading to a helical structure. The inner space is reduced by the occupancy of the sulfur atoms, and there is probably not enough room to accommodate small guests inside the cavity. 

As stated above, systematic names of macrocyclic host molecules were absurdly complicated for routine discussions [22]. Therefore Vogtle proposed the name coronand for crown ethers, and that of coronates for their complexes while cryptand complexes were called cryptates . The corresponding noncyclic analogues are podands such as 64 [23] and podates, respectively. The cumbersome name podando-coronands (and correspondingly podando-coronates ) was proposed for lariat ethers [24] having at least one sidearm like 65. Examples of hemispherands 66 [25], cavitands 25 [26] and those of some other hosts are discussed in Chapter 7 in some detail, whilst the exceptional stability of fragile guests 4 [2a] and 67 [27] in the hemicarcerand 5 cavity are discussed in Chapters 1 and Section 7.3. 

Cavitands are hosts formed in acidic condensation reactions between resorcinol derivatives and aldehydes.46 The resulting cyclic octol compounds are usually tetrameric and contain four aromatic units that form a relatively shallow bowl in the preferred C4v conformation. Further synthetic elaboration on the structure of the octols allows us to fix the conformation of these compounds in C4v symmetry with a well defined, albeit small cavity. 

For quite some time most synthetic efforts to prepare cavitand-type hosts led to compounds that were only soluble in low polarity solvents. Because of their potential biological relevance, interest on the synthesis of water-soluble cavitands developed quickly, but only recently a number of accessible hosts has become available. We will describe here recent work done by us on Gibb s octaacid, deep-cavity cavitand58 and Rebek s water-soluble cavitand.59 The structures of these compounds are shown in Fig. 3.10. 

Cavitands refer to synthetic organic compounds containing rigid cavities at least equal in size to smaller alkali metal ions such as Li+. 

Methylene-bridged resorcin[4]arenes or cavitands, of the general structure shown in Scheme 8, are suitable as templates for the organization of peptide structure because of their rigidity, enforced cavities and synthetic availability.132 59 ... 

The spherically shaped cryptophanes are of much interest in particular for their ability to bind derivatives of methane, achieving for instance chiral discrimination of CHFClBr they allow the study of recognition between neutral receptors and substrates, namely the effect of molecular shape and volume complementarity on selectivity [4.39]. The efficient protection of included molecules by the carcerands [4.40] makes possible the generation of highly reactive species such as cyclobutadiene [4.41a] or orthoquinones [4.41b] inside the cavity. Numerous container molecules [A.38] capable of including a variety of guests have been described. A few representative examples of these various types of compounds are shown in structures 59 (cyclophane) 60 (cubic azacyclophane [4.34]), 61a, 61b ([4]- and [6]-calixa-renes), 62 (cavitand), 63 (cryptophane), 64 (carcerand). 

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