Cavitands structures

Functionalization of cavitand structure by solvent-drop grinding. 

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). 

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]... 

The flexibility and the different conformations adopted by the re-sorc[4]arene can be rigidified in the cone shape configuration by bridging the phenol functions with different substituents [38]. We will report here on the tetra-bridged phosphorus cavitands (phosphocavitand), whose general structure is presented in Scheme 2 [39]. 

The cavitands are essentially synthesized from their resorc[4]arene precursors which are readily obtained by resorcinol condensation with aldehydes. The main feature comes from the different configurations that are expected for this tetrameric species and the relative thermodynamical stability of each isomer, which has been widely investigated by several authors. In addition, the conformational mobility of the resorc[4]arene molecules will depend on substitution at the upper and lower rims [28, 36, 40, 41]. The first attempt to synthesize a phosphorus bridged cavitand was to treat resorc[4]arene la (1, R=CH3) with phenylphosphonic dichloride or phenylphosphonothioic dichloride. Only inseparable isomer mixtures were obtained and isolation of the desired cavitands was not possible [42]. The first isolated phosphorylated resorcinol-based cavitand was described in 1992 by Markovsky et al., who prepared compound D from la and four equivalents of o-phenylenechlorophos-phate in the presence of triethylamine [43, 44]. For this compound, a tautomeric temperature and solvent dependent equilibrium exists between the spirophosphorane structure and the cyclic phosphate form (Scheme 4). 

To underline the effect of the P-phenyl group in the iiio isomer, the X-ray structure of the iiio isomer of cavitand 12c was solved from single crystal X-ray analysis (Fig. 2). It is noteworthy that the inner space is almost entirely occupied by the inward oriented P-phenyl group, precluding less efficient complexation properties [68]. 

The reaction of amidophosphito cavitands with Cr, Mo, and W hexacar-bonyl, and C5H5Mn(CO)3 resulted in the formation of the binuclear complexes. The structure was elucidated by and NMR and X-ray diffraction analysis, and showed that the distal bi-nuclear structure was formed. The tetra-nuclear complex was only obtained with tetra-phosphitocavitand 14 and Cr or Mo hexacarbonyl (Scheme 19) [72]. 

The two-point interaction between POin cavitands and alcohol guest was exemplified by the solid state structure of the 16(f) C2H50H complex showing hydrogen bond to the P=0 group and CH interactions between the... 

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. 

As described above, cavitand 13 is able to extract efficiently silver(I) ion. For a guest to host ratio G/H>2 a new species was formed and recovered in quantitative yield and was identified as the 2 4 complex 132-(AgPic)4. The X-ray crystal structure of the 132-(AgPic)4 complex showed a supramolecular assembly made of two cavitands linked by their upper rim with four silver cations through P=S...Ag...S=P coordination (Fig. 9) [70]. 

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. 

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. 

Figure 3.10 Structures of water-soluble cavitand-type hosts Gibb s octaacid (host 5) and Rebek s cavitand (host 6).

Recent examples of this kind of methodology can be found, for example, in the work of Rebek et al. [10] The catalyst used is a cavitand armed with a Zn salen-type complex (Figure 1.2). The cavitand adopts a vase-like conformation that is stabilized by a seam of hydrogen bonds provided by the six secondary amides. The structure of the catalyst permits a slow dynamic exchange between free and bound guest (reactant) on the H NMR time-scale that is controlled by the folding and unfolding of the cavitand. 

When the guest used is p-nitrophenylcholine carbonate (PNPCC) the Lewis acid zinc(n) activates the well-positioned carbonyl group in the P PCC Zn-cavitand towards reactions with external nucleophiles. The energy minimized structure of the PNPCC Zn-cavitand complex shows that cation-n interactions and C —O -Zn coordination bond occurs simultaneously. 

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