Thermodynamically Controlled Templated Synthesis

Although this concept was only recently articulated as a general approach to the synthesis of chemical species exhibiting molecular recognition capabilities, many of the principles and practices that characterize DCC had been in place for several decades. DCC may be viewed as the intersection of two pre-edsting approaches to synthesis thermodynamically controlled templated synthesis and combinatorial chemistry. 

Scheme 1.9 [3]Catenane 20 has been generated using thermodynamically controlled templated synthesis [37].

Thermodynamic control (Figure 1, right) is based on adsorption of substances until quasi-equilibrium stage. In this case, the surface ratio of the adsorbed species is defined by the ratio of products of their concentration and binding constant. This deposition is much less influenced by poorly controllable fluctuations of external conditions and provides much better reproducibility. The total coverage can be almost 100%. Because of these reasons, the thermodynamic control is advantageous for preparation of mixed nanostructured monolayers for electrochemical applications including a formation of spreader-bar structures for their application as molecular templates for synthesis of nanoparticles. 

Eurlan RLE, Otto S, Sanders JKM. Supramolecular templating in thermodynamically controlled synthesis. Ptoc Natl Acad Sci USA 2002 99 4801-4804. 

Most of the systems described in Chapter 5 contain small- or medium-sized or multinuclear benzenoid and non-benzenoid arenes. In Chapter 6, Hoger gives an overview over the mastery of the synthesis of macro- and megacycles. He shows different approaches towards shape-persistent macrocycles and carefully examines and discusses selected examples that display the advantages and disadvantages of macrocycle synthesis under kinetic and thermodynamic control. The template approach (both supramolecular and covalent) towards functionalized rings is also discussed and introduces a strong motif of supramolecular chemistry, which is much further developed but in a more polymer-oriented topic, in the next chapter. 

Following the introduction of MCM-41 type materials [1], the synthesis of surfactant templated nanostructured materials has attracted the attention of the scientific community because it provides the possibility of tailoring pore size, geometry and surface chemistry through control of the synthesis conditions. Potential applications of these materials range from separations and catalysis [2] to the production of biomimetic materials [3] and devices for optical and electronic applications [4]. Several synthesis protocols have been developed in the last ten years and are the focus of many recent reviews [5]. Despite the enormous experimental effort to develop methods to control the structure and composition of templated nanoporous materials, modeling the different processes has remained elusive, mainly due to the overlapping kinetic and thermodynamic effects. The characterization of... 

Figure 3-9 Metal-templated synthesis of the [2]catenane 36 under thermodynamic control.

Thermodynamic control in organic synthesis is very familiar, for example, in the synthesis of esters, acetals, or imines. Specific product formation can be favored by shifting the equilibrium position, through the removal or addition of water, the choice of solvent, the use of excess reagents, or by controlling the temperature and pressure of the reaction. Templates may be used in thermodynamically controlled synthesis to guide the system towards the production of a desired product that fits the template. 

Therefore, chloroform does not act as a template for particular pillar[n]ar-ene homologs, and pillar[6]arene is obtained under kinetic control. Yields of the pillar[ ]arene homologs under kinetic control were much lower than those obtained under thermodynamic control. Therefore, we investigated several reaction solvents that fit into the pillar[6]arene cavity to act as a template solvent for the synthesis of pillar[6]arenes under thermodynamic control. 

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." ... 

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