Imines thermodynamic template reactions

Simple Imines Formed by Thermodynamic Template Reactions 156... 

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... 

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. 

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... 

An elegant example of thermodynamic templating has been reported by Lynn and co-workers [30]. The reversible reaction of amine 16 with aldehyde 17 to give hexanucleo-tide imine 19 is favored by a hexanucleotide template 18 (Scheme 1-5). The imine can then be reduced to the corresponding amine 20 to fix the new hexanucleotide and remove it from the thermodynamic cycle. The hexanucleotide template 18 has a catalytic role in this overall process because, amazingly, it binds 19 about 10 times more strongly than 20, so product inhibition is not a problem. (Systems of this type are described in detail in Chapter 5.)... 

The threading-followed-by-capping method has been recently employed by Stoddart to prepare a [2]rotaxane under thermodynamic control [60]. In this approach, the dibenzylammonium ion 28 - which is terminated by an aldehyde function - is mixed with the dibenzo[24]crown-8 ether (20) to form a threaded species. Upon addition of a bulky amine, the aldehyde-terminated template can be converted into an imine in a reversible reaction establishing a dynamic equilibrium (see 29 and 30 in Scheme 17). 

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. 

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