Types of Template Effect

Macrocycles formed by reactions that are described as proceeding by the thermodynamic template effect can take place in the absence 

The equilibrium template effect, so named by Thompson and Busch (137), is a combination of the two previous effects. In this case the 

Mixture of products including thiazoles, thiazolines, and mercaptals 

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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." ... 

The gel solution mixtures were packed in ampoules and crystallized at 100°C for various periods from 0.25 to 131 days. The solid products were washed with water to pH = 9 and dried overnight at 100°C, then calcined under passage of air at 540°C for 3 5 h. The molar ratio of Si/Al, (Na + K)/A1, K/(Na + K), and choline/0H were fixed at 9-3, 7.3 0.17, and 0.67, respectively. Based on the analysis of the slow crystallization rate process, the hydrothermal treatment was properly shortened by a temperature-programmed crystallization. Furthermore, the effects of seed materials, type of template, hydrothermal temperature, and Si/Al ratio of the gel mixture on the crystallization were investigated. 

Two primary types of template reaction have been identified and these demonstrate equilibrium template (see Box 5.4) and kinetic template effects. An example of an equilibrium template effect is provided by the reaction between butane-2,3-dione and 2-aminoethanethiol which produces, as its major product, a heterocycle in equilibrium with smaller amounts of the acyclic imine (Scheme 5.3). However, in the presence of Ni " ions the acyclic product forms in high yield as its nickel complex. 

The simplest type of template directed cyclization is metal cation induced macrocycliza-tion, as discussed in Section 1.1. Mandolin and co-workers [37] have made a detailed study of the influence of alkali and alkaline earth metal cations on the cyclization of 2-hydroxyphenyl-3,6,9,12-tetraoxa-14-bromotetradecyl ether 28 in methanol and in dimethyl sulfoxide (Scheme 1-8). They studied different sizes of macrocycle and metal cation to determine the most effective combination for cyclization the results from this study will be summarized in Section 1.4.2.3. 

A template is usually associated with favoring the formation of a determined product, but the way in which it does so is by favoring one product, disfavoring another, or both (since one can result in the other). The realization of this situation led to the classification of templates as either positive or negative. The principles are applicable in all types of templated systems, where one product is favored over others. It is useful to consider the effects of these... 

Two distinct classes of template effect have been distinguished since 1964 [39]. Both types of effect are, chemically, manifestations of molecular organisation by means of coordination to the template centre [14], This is their common feature. 

Chemical reactions in general can be accelerated to go in a forward direction using catalysts which do not participate directly in the reaction. Ihe type of catalyst used depends on the nature of reactants in the reaction and the different materials used are Pd, Pt, Ag, Ni, TiO, ZnO and Fe-Oxides. The inherent catalytic property of these materials can be further enhanced by increasing their specific surface area available for reactions, i.e., by reducing the particle size to nanodimensions. However, agglomeration of the nanoscale materials in their innate state is a serious limitation which reduces the effective surface area available for reaction. The aggregates are easy to recover and recycle. These limitations can be overcome mainly in two separate ways (i) immobilization of the nanoparticles in a porous support or carrier, and (ii) synthesis of the catalytic material as a nanoporous network-like structiu e using different types of templates. Bacterial cellulose has been used extensively as a support material to host the catalytic nanoparticles, while in some cases it has also been used as a template to synthesize catalyst network structure. Some typical studies wherein BC has been used as a support to hold PdCu, Pd, TiO and CdS nanoparticles are discussed first, followed by template structure based composites. 

It is not clear exactly when the association illustrated above actually takes place. It is certainly involved by the final ring closure stage, but it seems reasonable to assume that there is some cation-glyme type interaction taking place from the instant of solution. The fact that wrapping occurs in such a way that the two ends of the molecule are held in proximity, allows the reaction to be conducted at much higher concentrations than might otherwise be practical. Tlie evidence for the operation of such a template effect is presented and considered below. 

In the reaction of unprotected uridine with tri(imidazolyl-l)phosphine (ratio 1 1.5) under mild conditions (THF, — 78° to 0 °C, 10 min) and subsequent oxidation with iodide, two types of polymers [(Up)n (n = 2-6) and (Up)nU (n = 2—5)] are formed. Additives such as metal cations or polynucleotides (poly U and poly A) acting as templates in the oxidation process showed a significant effect on the ratio of the 3, 5 -linked to 2, 5 -linked oligomer 17 177 ... 

As described in this chapter, the sonochemical reduction technique appears to be a promising method for the preparation of various types of metal nanoparticles in an aqueous solution. By choosing more efficient organic additives, easily-reducible metal precursors, supports and templates with an appropriate role, more advanced functional nanoparticles could be synthesized successfully using the sonochemical reduction technique. In future, it is also possible to develop effective synthetic methods by combining the sonochemical method with other chemical methods. 

Examples of the operation of both types of effect have been documented. Nevertheless, while these effects are useful concepts, as mentioned previously, very often the role of the metal ion in a given in situ reaction may be quite complex and, for instance, involve aspects of both effects. As well, the metal may play less obvious roles in such processes. For example, it may mask or activate individual functional groups or influence the reaction in other ways not directly related to the more readily defined steric influences inherent in both template effects. 

Whereas Gold and Sghibartz showed that cation complexation depressed the rate of crown-ether disrupture, there is convincing evidence that crown ether formation is facilitated by the presence of cations. The template effect, presumably due to complexation of the open-chain precursor and formation of a crown-type conformation, clearly emerged from studies in which the yield of crown ethers was related to the type of cations present (Reinhoudt et al., 1976). Kinetic evidence for the template effect was presented by Mandolini and Masci (1977), who showed that the rate of cyclization of the precursor of benzo-18-crown-6 [2061 decreased in the order Ba2+ > SrJ+ > K+ > Na+ > Li+. This sequence is the same as the one found for the stability constants of the 1 1 complexes of these cations with 18-crown-6 in water (Table 3). 

Until now syntheses along path d) of Figure 3 are known only for small bicyclic systems, for instance N(CH2CH20)3B from triethanolamine and B(OH)3 (87), N(CH2CH2CH2)3B from triallylamine and BH3 (88). However, macrobicyclic structures may be obtained in this way from a tripod type structure by making use of the template effect of a complexed transition metal cation, which remains included in the product (89-91). 

This simple scheme can help us to understand unusual selectivity and high efficiency of such template reactions. The specific character of the enzyme effectiveness towards a particular substrate becomes obvious. The effect of macromolecular template on the reaction rate and particularly on its selectivity suggests that this type of reaction can be regarded as a catalyzed reaction. The template plays a role of a polymeric catalyst. On the other hand, the template polymerization is a particular case of a more general... 

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