Template thermodynamic coordination

In contrast, the thermodynamic template effect involves a particular template species (usually a transition-metal ion) binding to a ligand that is complementary to itself, within an equilibrating mixture of products that are formed without the involvement of the template. The binding of the template thermodynamically stabilises the most complementary product (usually a macrocyclic compound). An excellent example is the preparation of phthalocyanine (2.8). Treatment of 1,2-dicyanobenzene with either boron trichloride or uranyl chloride results in two different-sized macrocycles (2.6 and 2.7, respectively) (Scheme 2.4). Macrocycles 2.6 and 2.7 are themselves only stable when the template is still present. On the removal of the template, the normal phthalocyanine (2.8) is formed, which is highly stable and forms many coordination complexes with a range of transition-metal ions. This is also a very attractive synthetic procedure for the preparation of unsymmetrical phthalocyanines. 

The following reactions provide examples of the thermodynamic coordination template effect. 

Thus, when we say that, for instance, a kinetic coordination template effect is responsible for the production of some product, it does not mean that a possible contribution from the thermodynamic coordination template effect is ruled out. The role of the matrix does not depend on one or other of the two coordination template effects prevailing. It consists not only in the strict suppression of side effects, but also in directing the process to its most favourable pathway [2, 4]. 

So, when assessing the possibility of achieving either template process, the reactivity of the interacting groups, the conditions for displaying kinetic (the possibility of coordination and activation of the ligsons participating in the reaction, by 1/2 data) and thermodynamic coordination template effects, as well as the factors enumerated earlier in Chapter 1, must all be taken into account. 

By heating a mixture of solutions of o-phda in dimethylformamide and propargyl aldehyde in methanol the Schiff base H2L3OI was obtained in 27% yield [336]. In the presence of Cu +, Co or Ni + ions, macrocyclic complexes are produced in about 70% yield, thanks mainly to the thermodynamic coordination template effect. 

Dziomko and coworkers have utilized the nucleophilic aromatic substitution of aryl amines to chloropyrazoles or chloropyridines in the template step of their macrocycle syntheses.174 175 The nature of the template process is unclear and it could simply be thermodynamic. However, a kinetic effect is a distinct possibility and would require attack of a coordinated aryl amine (Scheme 52). 

One of the most spectacular and useful template reactions is the Curtis reaction , in which a new chelate ring is formed as the result of an aldol condensation between a methylene ketone or inline and an imine salt. The initial example of this reaction was the formation of a macrocyclic nickel(II) complex from tris(l,2-diaminoethane)nickel(II) perchlorate and acetone (equation 53).182 The reaction has been developed by Curtis and numerous other workers and has been reviewed.183 In mechanistic terms there is some circumstantial evidence to suggest that the nucleophile is an uncoordinated aoetonyl carbanion which adds to a coordinated imine to yield a coordinated amino ketone (equation 54). If such a mechanism operates then the template effect is largely, if not wholly, thermodynamic in nature, as described for imine formation. Such a view is supported by the fact that the free macrocycle salts can be produced by acid catalysis alone. However, this fact does not... 

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. 

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). 

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." ... 

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... 

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. 

---