Synthetic Applications of Chelated Ligand Reactions

By reducing the rate of reaction, metal chelation can be used in the synthesis of reaction intermediates. By involving a sensitive functional group in chelation, protection of this group during various synthetic procedures can be achieved. By altering the pathway of a reaction with chelation, products not otherwise obtainable can be formed. 

The following example illustrates the manner in which changes that occur in the rate of a ligand reaction upon metal chelate formation can be used for synthetic purposes. Two halogen atoms are introduced into a molecule of 8-hydroxyquinoline rapidly and almost simultaneously to give the 5,7-dihalo derivative (118). Studies on the rate of bromination of the Cr(III) or Cu(II) chelates of 8-hydroxyquinoline showed that mono-bromination in the 5-position occurred extremely rapidly, whereas the subsequent introduction of another bromine atom in the 7-position was quite slow. Advantage was taken of this difference in reaction rates to prepare the 5-bromo-, 5-chloro-, and 5-iodo-substituted compounds of 8-hydroxyquinoline and its 2-methyl and 4-methyl derivatives in good yields (169). 

Tropolone usually undergoes electrophilic attack in the 7-position, but is brominated in the a-position. The bromination of the Cu(II) chelate of tropolone, however, takes place in the 7-position and is therefore a route for the preparation of 7-bromotropolone (60). Similar changes in the 

A reactive group in a ligand can be protected by metal chelate formation. For example, in the compound (XCV) one of the amino groups is protected and the terminal amino group is free to react (124, 126). The reactive nitroso group in o-nitrosophenol can be protected by the formation of a stable and water-insoluble copper(II) chelate (159). It is possible that other reactive groups, such as the mercapto group in 8-mercaptoquinoline, could be protected by metal chelation in the course of a synthetic procedure. 

Another approach to the synthesis of these Schiff base type of chelates is to use a metal ion-induced rearrangement reaction. The compound 

---