The Cryptands

8 Lehn, J. -M. Supramolecular Chemistry Concepts and Perspectives, VCH Weinheim, 1995. 

building up two linear chains possessing suitable reactive groups at each chain end  

cyclisation reaction of these two chains leading to a corand (crown ether-like macrocycle)  

addition of a third chain to the corand to give a macrobicyclic compound. 

The synthetic versatility of azacrowns (crown ethers with some oxygen atoms replaced with NH fnnctionalities), such as 3.18, has made possible the synthesis of an enormous range of 

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The match between crown cavity diameter and cation diameter is obvious from Table 3 showing that, eg, and 12-crown-4 (la) or, respectively and 18-crown-6 (Ic) correspond. Similar are the cryptands of gradually increasing cavity size [2.1.1], [2.2.1] and [2.2.2] for and... 

As with the crowns, the situation becomes more complicated when there are other heteroatoms or substituents in one of the cryptand bridges. The symbol B is used to designate a benzo- or catechol unit in the bridge and subscripts are used to designate heteroatoms when non-oxygen heteroatoms are present. Examples of this are shown in structures 12 and 13 above. 

A number of bridged crown ethers have been prepared. Although the Simmons-Park in-out bicyclic amines (see Sect. 1.3.3) are the prototype, Lehn s cryptands (see Chap. 8) are probably better known. Intermediates between the cryptands (which Pedersen referred to as lanterns ) and the simple monoazacrowns are monoazacrowns bridged by a single hydrocarbon strand. Pedersen reports the synthesis of such a structure (see 7, below) which he referred to as a clam compound for the obvious reason . Although Pedersen appears not to have explored the binding properties of his clam in any detail, he did attempt to complex Na and Cs ions. A 0.0001 molar solution of the clam compound is prepared in ethanol. The metal ions Na and Cs are added to the clam-ethanol solutions as salts. Ultraviolet spectra of these solutions indicate that a small amount of the Na is complexed by the clam compound but none of the Cs . 

Although the cryptands are powerful cation complexing agents, there has been a need felt for increasing the lipophilicity of these materials. In particular, Montanari and his coworkers have utilized the lipophilic cryptands in phase transfer catalytic proces-sesi5,40 Lehn and his group. In all of this work, the principal structural varia-... 

If a bridged bis-crown is used instead of diaza-18-crown-6, the cryptand contains two macrorings facing each other (see Table 8.5). Note also that the 2,2 -binaphthyl unit has been used extensively by Cram and his coworkers to provide chirality to mono-cyclic systems as well (see Sect. 3.13). 

The similarity between the cryptands and the first of these molecules is obvious. Compound 7 7 is a urethane equivalent of [2.2.2]-cryptand. The synthesis of 7 7 was accomplished using a diacyl halide and l,10-diaza-18-crown-6 (shown in Eq. 8.13). Since amidic nitrogen inverts less rapidly than a tertiary amine nitrogen, Vogtle and his coworkers who prepared 7 7, analyzed the proton and carbon magnetic resonance spectra to discern differences in conformational preferences. Compound 7 7 was found to form a lithium perchlorate complex. 

The in-out bicyclic amines prepared by Simmons and Park bear a remarkable semblance to the cryptands but lack the binding sites in the bridges. As a result, these molecules interact with electrophiles in a fashion similar to other tertiary amines and generally do not exhibit strong interactions with alkali or alkaline earth metal ions. The in-out bicyclic amines are prepared by reaction of the appropriate acid chlorides and amines in two stages to yield the macrobicyclic amine after reduction of the amidic linkages. A typical amine is shown above as compound 18. 

Figure 7.7. X-ray structure of anion 10 and the cryptand encapsulated lithium ion (Newman projection of the carbanion is shown in the box). (Adapted from reference 47.)...

The cryptands (490) coordinate by three sulfur and three nitrogen donors only, forming distorted octahedral Ni11 complexes.1336... 

There are many examples of platinum(II) interacting with metals such as lead(II) or thallium(I) but few where the same metals interact with platinum(O). Catalano et al. have reported a series of metallocryptands such as the one shown in (11) that act as hosts for thallium(I)72 and lead(II).73 They have also reported an unsupported thallium(I) interaction with the platinum in [Pt(PR3)3] (R = Ph or R3 = Ph2py).74 The Pt Tl separations in the cryptands (2.791-2.795 A) are slightly shorter than those in the unsupported complexes (2.865-2.889 A).72,74... 

The imidazolate bridged Cu/Zn bimetallic complex of the cryptand (13) was structurally characterized and shown to have a Cu-Zn distance of 5.93 A (native Cu, Zn-SOD 6.2 A).146 The complex shows some activity in the dismutation of superoxide at biological pH that is retained in the presence of bovine serum albumin. 

The ions having five tin or lead atoms are prepared by the reaction of a solution containing sodium and the cryptand reacting with alloys of sodium and tin or lead, respectively. It should also be mentioned that numerous derivatives of these materials have been prepared that contain alkyl and other groups. 

It should be noted that the three-dimensional polyether cages (the cryptands) are usually most effective at producing naked anions . With these, the metal ion is completely encapsulated by the polyether network and thus better charge separation is achieved. In the case of the crowns, such complete encapsulation does not normally occur and hence the counter anion is more readily able to associate directly with the com-plexed metal cation. In such cases, the use of the term naked is somewhat of a misnomer. 

Complexes of the cryptands having 2 1 stoichiometries are also known for example, with Pb(n), 2.1.1 forms a species of type [Pb2(2.1.1)]4+ in which both Pb(n) ions appear to lie outside the macrocyclic cavity (Arnaud-Neu, Spiess Schwing-Weill, 1982). 

The stability of cryptate complexes. The cage topology of the cryptands results in them yielding complexes with considerably enhanced stabilities relative to the corresponding crown species. Thus the K+ complex of 2.2.2 is 105 times more stable than the complex of the corresponding diaza-crown derivative - such enhancement has been designated by Lehn to reflect the operation of the cryptate effect this effect may be considered to be a special case of the macrocyclic effect mentioned previously. 

For those applications involving the activation of an inorganic anion (that is, generation of a naked anion), the cryptands, rather than the crowns, tend to be the reagents of choice. Such reagents are thus also ideal for applications involving phase-transfer catalysis of the type discussed previously. 

As discussed in Chapter 4, the selectivity of cage ligands (such as the cryptands) for particular guests tends to be more readily controlled by structural modification than is the case for the crowns. This is usually a reflection of the cavities being inherently better defined in the three-dimensional cage structures. 

In general, the cryptands (213) show a stronger correlation between thermodynamic stability and match of the metal ion for the cavity. Thermodynamic data for complexation of the alkali metal ions with a number of cryptands is summarized in Table 6.2. The data for the smaller (less flexible) cryptands 2.1.1, 2.2.1, and 2.2.2 illustrate well the occurrence of peak selectivity. 

In contrast to the peak selectivity just discussed, there is evidence that the larger, more flexible, ligands tend to exhibit plateau selectivity - a reflection that a number of the larger metal ions are accommodated by the cryptand without major variation in binding energy. 

In summary, although the metal-ion selectivity of the cryptands is normally largely enthalpy-controlled, entropic terms may also be quite important. Once again, the factors underlying these respective terms may be quite variable and, as a consequence, a criterion for preferred complexation based solely on a match of the cavity for the cation radius may not always be appropriate. 

An investigation of the kinetics of formation of the Li+ and Ca2+ complexes of cryptand 2.1.1 using stopped-flow calorimetry suggests that complexation occurs initially at one face of the cryptand such that the metal is only partially enclosed (to yield an exclusive complex). Then follows rearrangement of this species to yield the more stable product, containing the metal ion inside the cryptand (the inclusive product) (Liesegang, 1981). X-ray diffraction studies have indeed demonstrated that exclusive complexes are able to be isolated for systems in which the metal is too large to readily occupy the cryptand cavity (Lincoln et al., 1986). 

Table 7.1. Formation (kf) and dissociation (kd) rate constants for the alkali metal complexes of the cryptands of type (213) in methanol at 25 °C (Cox, Schneider Stroka, 1978).

Linking the macrocyclic receptor l,7-diaza-15-crown-5 to the fluorophore 7-nitrobenzofurazane leads to the Hg(ll) selective fluorescence probe NBO-crown <1997JFL231S>. The cryptand was functionalized with an electron-withdrawing fluorophore (NBD) which behaves as a fluorescence on/off signaling system by translocating Cd(ll) inside and outside the cryptand cavity <2004IC4626>. 

Rate constants for reaction of Ca2+aq with macrocycles and with cryptands (281,282,291) reflect the need for conformational changes, considerably more difficult for cryptands than for crown ethers, which may be considerably slower than formation of the first Ca2+-ligand bond. Ca2+aq reacts with crown ethers such as 18-crown-6 with rate constants of the order of 5 x 107M 1 s, with diaza crown ethers more slowly (286,326). The more demanding cryptands complex Ca2+ more slowly than crown ethers (kfslow reaction for cryptands with benzene rings fused to the macrocycle. The dominance of kA over kt in determining stability constants is well illustrated by the cryptates included in Table X. Whereas for formation of the [2,1,1], [2,2,1], and [2,2,2] cryptates kf values increase in order smoothly and gently, the k( sequence Ca[2,l,l]2+ Ca[2,2,l]2+ Ca[2,2,2]2+ determines the very marked preference of Ca2+ for the cryptand [2,2,1] (290). 

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