Template, metal ion

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

These authors suggest that the reaction may proceed through the formation of their mixed anhydrides , and illustrate a metal ion templated, mixed carboxylic-sulfonic anhydride. 

As mentioned previously, Schiff-base condensations between amines and aldehydes or ketones have played a prominent role in metal-ion template chemistry. A generalized Schiff-base condensation (to produce an imine linkage) is given by [2.15],... 

Polymeric pseudocrown ether networks have been generated in situ by the photopolymerization of poly(ethylene glycol) diacrylate transition metal complexes <00CM633>, and the effect of metal ion templation was evaluated. The 1,6,13,18-tetraoxa[6.6]paracyclophane-3,15-diyne (termed pyxophanes) was prepared from hydroquinone and l,4-dichlorobut-2-yne it forms size-selective 7i-complexes with alkali metal cations <00CC2377>. Dibenzo[ ]crown-m have been used in numerous elegant studies in which they were the needles that were threaded by diverse reagents the resultant... 

Brady, R. A. Sanders, J. K. M. Thermodynamically controlled cyclisation and interconversion of oligocholates Metal ion templated living macrolac-tonisation. J. Chem. Soc. Perkin 11997, 3237-3253. 

The application of Schiff base chemistry to the synthesis of heterophanes possessing diverse subunits has been reviewed in part (82MI52202, B-79MI52201). An example of this procedure is the treatment of (19) with 2,3-diaminopyridine, with or without metal ion templation, to give (20) as an isomeric mixture (75MI52200). 

The highest flexibility for a variation of the functional group and the chains X and Y (i.e. the size of the rim of the lamp shade) will be realiad when the synthesis of 3 is convergent and modular (Scheme 1). Amide bonds can easily be formed in macrocyclizations [13], therefore macrocyclic diamines 7 and diacyl dichlorides 8 had to be prepared. For the synthesis of macrocyclic diamines 7, also a large number of reactions are known. However, in this case a reduction of a macrocyclic diamide could not be achieved [11]. Therefore, another route was used the formation of macrocyclic diimines 6 (bis-Schiff bases) followed by NaBH4 reduction to the macrocyclic diamines 7. This approach has the advantage that for the construction of macrocyclic diimines 6, the metal ion template effect [14] may be exploited. 

The synthetic strategy used for the construction of concave pyridine bislactams 3 (Scheme 1) can also be applied to other concave bases. When instead of a pyridine-2,6-dialdehyde 4, l,10-phenanthroline-2,9-dicarbaldehyde (9) was used in a metal ion template directed synthesis of macrocyclic diimines, after reduction, also macrocyclic 1,10-phenanthroline diamines 10 could be obtained in good yields. Here too, the crude diamines 10 were used in the next reaction step. Bridging of 10 with diacyl dichlorides 8 gave concave 1,10-phenanthroline bislactams 11. Scheme 2 summarizes the synthesis and lists the synthesized bimacrocycles 11 [18]. 

The catenands are synthesized using the metal ion template effect, whereby a bis complex is formed from an a,a -disubstituted o-phenanthroline. This initial product is treated with a diiodoal-kane to effect the ring closures.34... 

Figure 6-5. A metal-ion-templated cyclisation of a compound containing two donor atoms (filled circles) and two reactive groups (open circles). The co-ordination of the open-chain ligand to the metal ion brings the reactive sites into close proximity and favours the intramolecular reaction.

The use of metal ions as kinetic synthetic templates is extremely widespread, and is an excellent way in which to bring about the organisation of a number of reacting components in order to direct the geometry of the product. Because some metal ions, such as the transition metals, often have preferred coordination geometries (e.g. tetrahedral, square planar, octahedral etc), changes in metal ion may have a profound effect on the nature of the templated product. Metal-ion-templated syntheses may be classified more generally as examples of self-assembly with covalent postmodification. For example, the synthesis of the artificial siderophore 10.2 is effected by the use of an octahedral Fe3+ template.8 In this case, the macrobicyclic product is obtained as the Fe3+ complex from which it is difficult to separate. 

In contrast, the thermodynamic template effect in macrocycle synthesis is a process by which the presence of a metal ion template stabilises thermodynamically, or removes (e.g. by precipitation) one particular (usually cyclic) product from an equilibrating mixture, driving the equilibrium towards this thermodynamic minimum. This leads us to the conclusion that any thermodynamically stabilising influence may drive an equilibrium mixture towards a particular product according to Le Chatalier s Principle (in an equilibrating situation, the system will react to diminish the effects of externally applied changes in conditions). 

Figure 15. Self assembly of a [2]catenane using a metal-ion template effect.

A requirement for a metal ion template has been established for the majority of reactions described in this section. Other reactions described are those in which metal ions, particularly Na +, are part of the stoichiometry of the reactions but for which a template function has not been identified. 

The variety of macrocycles that have already been prepared by template reactions (see Sections III and VI) suggest that, in designing a macrocycle synthesis to meet a future need, the use of a metal ion template should not be ignored. 

Quadridentate ligands such as (237) are prepared by what must be one of the first (1944) uses of metal ion template ligand synthesis (Figure 5). ... 

Metal ion template mediation in macrocyclic synthesis has been a part of the field since its inception, its importance having been realized early in the development of this area. Two specific roles for the metal ion in template reactions have been proposed. These are, in turn, kinetic and thermodynamic in origin." In the kinetic template effect, the arrangement of ligands already coordinated to the metal ion provides control in a subsequent condensation during which the macrocycle is formed. The thermodynamic effect serves to promote stabilization of a structure which would not be favored in the absence of a metal ion. Schiff base condensations tend to be dependent on this latter type of template effect. Some of the more routine and general synthetic procedures will be described here. A more in-depth treatment can be found in a review by Curtis, with particular emphasis on general methods as well as modifications of preformed macrocycles." ... 

As mentioned already, a further group of catenanes have been synthesised via metal-ion template procedures discussion of these species is presented in the next chapter as part of a wider treatment of the use of metals in self-assembly processes. 

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