Kinetic and Thermodynamic Template Effects

As the equilibria are frequently complex, it is often difficult to recognize a thermodynamic template effect unequivocally. The best indication is the formation of a product in unexpectedly high yield. The principle of complementarity must be emphasized here If a ligand (host) in a product mixture is complementary to an available metal ion or neutral (guest) molecule, then this will be bound selectively, and the equilibrium shifted in its favor. 

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Diels-Alder reactions have also been accelerated inside the cavities of cyclic porphyrin trimers [45]. For example, diene 52 and dienophile 53 react selectively to give the exo adduct 54 (Scheme 1-14) inside the cavity of 39 [45a,b], Cyclic porphyrin trimer 39 is an effective kinetic and thermodynamic template for this reversible Diels-Alder reaction, of which the stereochemical outcome may be reversed to give mainly the endo adduct if a smaller porphyrin trimer is used [45 c]. 

Two possible roles for the metal ion in a template reaction have been delineated (Thompson Busch, 1964). First, the metal ion may sequester the cyclic product from an equilibrium mixture such as, for example, between products and reactants. In this manner the formation of the macrocycle is promoted as its metal complex. The metal ion is thus instrumental in shifting the position of an equilibrium - such a process has been termed a thermodynamic template effect. Secondly, the metal ion may direct the steric course of a condensation such that formation of the required cyclic product is facilitated. This process has been called the kinetic template effect. 

DMA) binds reversibly to Cjq. A similar effect was observed for 2,6-dimethoxy-anthracene [60], Use of, for example, a ten-fold excess of DMA results in an equilibrium between the various Cgg DMA adducts, with e,e,e-C5oDMA3 as the main component. Hence, synergetic combination of kinetic and thermodynamic control results in the generation of templates such as with incomplete... 

Many reactions in this section probably owe a thermodynamic template effect for part of their success, but it is the kinetic effect which is most clearly illustrated. Reactions have been chosen to display a range of geometrical features and also various types of bond formation. The coverage will be selective and many topics will be developed more fully in Chapter 61.1 The present section will be subdivided according to the involvement or otherwise of donor atoms. 

Myriad polydentate aza-macrocycles have been reported 41. The extent of the subject forces limitation of this discussion to only macrocycles containing a pyridine or dipyridine subunit. Most of these coronands have been synthesized by a SchifF base condensation of an aldehyde or ketone with a hfc-primary amine in the presence of a metal ion. The metal ion acts as a template, resulting in dramatic increases in yield of the desired cyclic product over linear polymerization products42 46. Lindoy and Busch45 have described this effect in two ways, kinetic and thermodynamic. If the metal ion controls the steric course of a series of stepwise reactions, the template effect is considered to be kinetic. If the metal ion influences an equilibrium in an organic reaction sequence by coordination with one of the reactants, the template effect is termed thermodynamic. It is the kinetic effect that is believed to be operative in most metal ion-assisted (in situ) syntheses of... 

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." ... 

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... 

Some believe that there are two main template effects kinetic and thermodynamic [8]. The latter is responsible for an increase in the yield of the complex with ligands formed in situ in the presence of metal ions, which bind products that result from ordinary reactions and to withdraw them from the reaction medium. These procedures are not true template reactions since they do not satisfy the above-mentioned conditions, and the metal ion causes equilibrium shift only. It is impossible to distinguish between kinetic and thermodynamic contributions to the template effect, since the coordination to the metal ion simultaneously causes both steric... 

Most of the templates diseussed in this chapter are kinetic templates. Some of the early examples of metal cation templated macrocyclization studied by Curtis and Busch [7,9] (Schemes 1-1 and 1-2) are thought to operate under thermodynamie eontrol. The clearest evidence for a thermodynamic template effect comes when the template-free product is not stable under the reaction conditions. For example, treatment of 1,2-dicyanoben-zene 11 with boron trichloride or uranyl chloride results in the formation of subphthalo-... 

Fluorescence Sensing of Anions, p. 566 Guanidium-Based Anion Receptors, p. (575 Halogen Bonding, p. 628 Macrocyclic Synthesis, p. 830 Molecular Squares, Boxes, and Cubes, p. 909 Naked Anion Effect, p. 939 Organometallic Anion Receptors, p. 1006 Rotaxanes and Pseudorotaxanes, p. 1194 Self-Assembly Definition and Kinetic and Thermodynamic Considerations, p. 1248 The Template Effect, p. 1493... 

Different roles for the metal ion in a template reaction have been dehneated and termed thermodynamic template effect and kinetic template effect In the first case, the metal ion picks out the macrocyclic ligand from an equilibrating mixture of products, thus driving the reaction equilibrium... 

In the cases considered thus far in this review, the templates have acted in a kinetic way once the product of the template-directed reaction is formed, the equilibrium processes regarding the product distribution are limited. In all these systems, kinetic and thermodynamic effects can play roles of varying importance. This fact was recognized long ago by Busch, who discerned between kinetic templates —in which transition states to products... 

An essential feature of template reactions of both the thermodynamic and kinetic type is the formation of a new chelate ring. One of the main difficulties in a discussion of mechanistic aspects of template reactions is the inevitable mixture and overlap of mechanistic effects. Those reactions which clearly exhibit a kinetic template effect could also depend to some extent on a thermodynamic one. Also, in some multistep macrocyclization processes, for example, both effects could be involved. Despite the inherent difficulties, the following discussion in this section will be subdivided into two, to cope predominantly with the thermodynamic and kinetic template effects. A further subdivision of thermodynamic and equilibrium effects will not be made. 

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