Reactions of Co-ordinated Water or Hydroxide

We saw in Chapter 2 that co-ordination of a water molecule to a metal ion modifies the pK and can make the water considerably more acidic. This stabilisation of the hydroxide anion is rationalised in terms of transfer of charge from the oxygen to the metal in the coordinate bond. Some typical pKa values of co-ordinated water molecules are given in Table 5-2. 

A co-ordinated hydroxide ligand will still possess some of the nucleophilic properties of free hydroxide ion, and this observation proves to be the basis of a powerful catalytic method, and one which is at the basis of very many basic biological processes. In general, hydrolysis reactions proceed more rapidly if a water nucleophile is replaced by a charged hydroxide nucleophile. This is readily rationalised on the basis of the increased attraction of the charged ion for an electrophilic centre. However, in many cases the chemical properties of the substrate are not compatible with the properties of the strongly basic hydroxide ion. This is exactly the situation that biological systems find themselves in repeatedly. For example, the uncatalysed hydration of carbon dioxide is very slow at pH 7 (Fig. 5-61). 

In the laboratory the process would be accelerated by the addition of an alkali metal hydroxide this both accelerates the reaction by replacing the neutral nucleophile by an anionic one and also perturbs the equilibrium towards the right-hand side by Le Chate- 

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At first sight these reactions are simple examples of metal-activated nucleophilic attack upon the nitrile carbon atom. However, the geometry of the co-ordinated chelating ligand is such that the nitrile nitrogen atom is not co-ordinated to the metal ion (4.3 and 4.4) It was initially thought that this provided evidence for a mechanism involving intramolecular attack by co-ordinated water or hydroxide (Fig. 4-10). However, detailed mechanistic studies of the pH dependence of the reaction have demonstrated that the attack is by external non-co-ordinated water (or hydroxide) (Fig. 4-11). 

Another special example of the metal-promoted hydrolysis of an amide is seen with the lactam rings of cephalosporins or penicillins. The hydrolysis of penicillin, 3.5, is accelerated 100 million times in the presence of copper(n) salts. Unfortunately, the precise mechanism of the reaction, whether it involves intra- or intermolecular attack by hydroxide or water, or even the site of co-ordination, is not known with any certainty. 

It is very often extremely difficult to demonstrate that a metal-co-ordinated hydroxide ion is involved in a particular reaction. Studies of kinetic behaviour provide one of the most powerful tools for the determination of reaction mechanisms. It is not, however, always easy to distinguish between intra- and intermolecular attack of water or hydroxide. The most unambiguous studies have been made with non-labile cobalt(m) complexes, and we will open this discussion with these compounds. 

The reaction is highly exothermic as one might expect for an oxidation reaction. The mechanism is shown in Figure 15.1. Palladium chloride is the catalyst, which occurs as the tetrachloropalladate in solution, the resting state of the catalyst. Two chloride ions are replaced by water and ethene. Then the key-step occurs, the attack of a second water molecule (or hydroxide) to the ethene molecule activated towards a nucleophilic attack by co-ordination to the electrophilic palladium ion. The nucleophilic attack of a nucleophile on an alkene coordinated to palladium is typical of Wacker type reactions. 

We saw in Chapter 3 that the hydrolysis of chelated amino acid esters and amides was dramatically accelerated by the nucleophilic attack of external hydroxide ion or water and that cobalt(m) complexes provided an ideal framework for the mechanistic study of these reactions. Some of the earlier studies were concerned with the reactions of the cations [Co(en)2Cl(H2NCH2C02R)]2+, which contained a monodentate amino acid ester. In many respects these proved to be an unfortunate choice in that a number of mechanisms for their hydrolysis may be envisaged. The first involved attack by external hydroxide upon the monodentate A-bonded ester (Fig. 5-62). This process is little accelerated by co-ordination in a monodentate manner. 

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