Thermodynamic template synthesis

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

The subject matter of this chapter will be subdivided into sections concerning template synthesis of the complexes structural and thermodynamic properties of the complexes with synthetic cyclic polyamines complexes with mixed-donor macrocycles reactivity of the complexes cryptates and complexes with phthalocyanines and porphyrins. 

SYNTHESIS AND REACTIONS OF IMINE CHELATES 61.1.2.1 Simple Imines Formed by Thermodynamic Template Reactions... 

The synthesis of quadridentate imine chelates usually requires the combination of two equivalents of the carbonyl compound and a diamine, as in the formation of complexes of ligands (6),17 18 (7)19 and (8).20,21 In similar fashion, thermodynamic template reactions allow the very effective synthesis of quinquedentate and sexadentate metal complexes of ligands such as (9),22 (10),23 (ll),24 (12)25 and (13).26 Condensation of 1,1,1-tris(aminomethyl)ethane with pyridine-2-carbaldehyde alone yields... 

Template reactions between a-diketones and diamines have been used for the synthesis of complexes of macrocyclic ligands such as (38)78 and (39).79 Some insight into the mechanism of the formation of these macrocycles has been provided by some recent work which shows the value of the thermodynamic template effect (Scheme 6).80... 

Thermodynamic template reactions allow the formation of hydrazones from hydrazines and carbonyl compounds, in the same manner as simple imines are formed. However, in many cases it is more convenient to form hydrazones in non-template reactions, as they are generally easier carbonyl derivatives to isolate than are simple imines. Hydrazone complexes often are capable of further manipulation and both aspects of synthesis and reactivity will be combined in this section. 

Such complexes form a precursor to a full discussion of the vast and highly topical field of self-assembly (Chapter 10). We consider them here since they resemble structurally the types of compounds discussed in Section 4.7, but unlike metal-based anion receptors the simple thermodynamic equilibrium between host, anion and complex is not the only process occurring in solution. In fact multiple equilibria are occurring covering all possible combinations of interaction between anions, cations and ligands. These systems have the appeal that the formation of particular metal coordination complexes are thus subject to thermodynamic anion templating (cf. the thermodynamic template effect in macrocycle synthesis, Section 3.9.1) and vice versa. 

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). 

At the same time, this method has a series of disadvantages. Among them, we note the possibiity of contamination of the final product not only by the excess of one of the reactants [2], but also by complexes of the components of the ligand system. So, to carry out strictly template synthesis experiments, it is necessary to take into account a comparative stability of coordination compounds, obtained on the basis of initial components-precursors and the ligand itself. Not only the thermodynamic characteristics of complex-formation processes should be taken into consideration [326,327], but also the influence of solvolysis processes (especially hydrolysis) and the type of atmosphere (air oxygen). 

Template-directed synthesis has also been exploited for combinatorial purposes in which a reversible reaction and the use of thermodynamic templates have been used. Two different processes have been envisaged and validated, both of which consider the dynamic optimization of a receptor-ligand interaction where one of the partners is the template that drives the self-assembly of a reversible library of other partners from which the best binder for the template is selected (Fig. 8.53). If the receptor is a template, a library made using a reversible reaction is incubated with the receptor and... 

The kinetics and mechanism of synthesis and decomposition of macrocyclic compounds are regarded as one of the most important aspects in the chemistry of these compounds. The majority of papers concern metal ions complexing with preliminarily synthesized macrocyclic ligands and metal ion substitutions by other metal ions in the preliminarily prepared complexes. Template synthesis, the most promising approach to the directed preparation of macrocyclic compounds with desired structures [17], plays a still more decisive role in the chemistry of macrobicyclic complexes with encapsulated metal ion. However, the literature contains only scarce data on the kinetics and the mechanism of the template synthesis of macrocyclic compounds because of the difficulties encountered in experimental determinations of kinetic and thermodynamic parameters, such as low product yields, nonaqueous media, high temperatures, and side reactions. 

The precatenate intermediate can be regarded as a threaded complex, which is thermodynamically stabilized by coordination bonds, from this simple consideration, a transition metal-templated synthesis of rotaxanes was devised, the principle of which is shown in Figure 28 [117]. The threading step (i) is a complexation reaction. 

Scheme 12 Template synthesis of the first-formed bis (P-N-NH ) complex and thermodynamic P-N-N-P product complex...

The most general definition of a template is as a structure-directing agent. In surfactant solutions the final templated polymers can be either discrete nanoparticles or mesostructured bulk materials as a consequence of polymerization, respectively, in the non-continuous or continuous domains of the template. Thermodynamically stable media, such as microemulsions, equilibrium vesicles, or lyotropic mesophases are especially useful as templates because of their structural definition and reproducible morphologies. The mesostructure of a thermodynamically stable template is defined by composition and temperature, but this same feature makes the structure unstable to changes in temperature, pH, or concentration. The aim of template synthesis is to transfer the self-organized template structure into a mechanically and chemically stable, durable, and processable material. 

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

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