Co-ordinated hydroxide

Figure 3-6. Two competing mechanisms for the formation of [Co(en)2(H2NCH2C02)]2+ from co-ordinated glycinate ester. Pathway 1 involves the attack of a co-ordinated hydroxide upon a monodentate -bonded glycinate, whilst pathway 2 involves external hydroxide attacking a didentate chelating glycinate.

Figure 4-10. The initially proposed, but incorrect, mechanism for the nickel(n)-assisted hydrolysis of 4.1 involving nucleophilic attack by a co-ordinated hydroxide.

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). 

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. 

How may we distinguish between pathways that involve external attack by hydroxide and those that involve co-ordinated hydroxide There is a considerable accumulation of data that suggest the two latter pathways are the most important (i.e., attack of external hydroxide upon monodentate amino acid ester is not greatly accelerated). The attack by external hydroxide may be studied independently and accurate rate constants may be determined for insertion in the composite rate equation with the two competing processes. In some cases it is possible to detect the five-co-ordinate and the other intermediates. Finally, some elegant labelling studies have provided very strong evidence for the exi-... 

Figure 5-68. The labelling experiment that distinguished between the various pathways for hydrolysis of amino acid esters. The site of the label may be determined by IR spectroscopy or other methods. Pathway A involves co-ordinated hydroxide nucleophile and pathway B, external hydroxide. Both pathways are found to be important for cobalt(m).

Figure 5-70. The hydrolysis of the ester 5.32 is accelerated by copper(n) salts. The initial step is the formation of the chelated copper(n) complex, followed by intramolecular attack of co-ordinated hydroxide upon the co-ordinated ester group.

Figure 5-71. The hydrolysis of the tridentate ligand 5.33 is accelerated by co-ordination to a metal ion. The two reaction involves intramolecular attack by co-ordinated hydroxide.

In the preceding section we discussed the use of co-ordinated hydroxide as an intramolecular nucleophile. It could also act as a nucleophile to an external electrophile. Over the past few decades, there has been considerable interest in the nucleophilic properties of metal-bound hydroxide ligands. One of the principal reasons for this relates to the widespread occurrence of Lewis acidic metals at the active site of hydrolytic enzymes. There has been a lively discussion over the past thirty years on the relative merits of mechanisms involving nucleophilic attack by metal-co-ordinated hydroxide upon a substrate or attack by external hydroxide upon metal-co-ordinated substrate. As we have shown above, both of these mechanisms are possible with non-labile model systems. 

However, we may also design model systems to study the reactions of co-ordinated hydroxide with external electrophiles. The simplest models utilise non-labile complexes with a single hydroxide ligand, such as [M(NH3)5(OH)]2+ (M = Co or Rh). Various electrophiles have been shown to react with such metal-bound hydroxide ligands, and some of these reactions are indicated in Fig. 5-73. 

Co-ordinated water is more reactive than co-ordinated hydroxide in the intra-... 

Gels of yttrium hydroxide are powerful catalysts for the hydrolysis of (76), and it was suggested that the hydroxide acts as a bifunctional general acid and nucleophile. The fact that gels of transition-metal hydroxides do not show comparable activity was attributed to their fixed co-ordination number, resulting in more rigid stereochemistry. 

Pd(H20)4] at 40°C [73]. A kinetic study indicated that internal attack on the Pd-co-ordinated nitrile ligand by the aqua (not hydroxide) ligand and external attack on the nitrile ligand by solvent water occur at a similar rate. 

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. 

The following relative second-order rate constants have been obtained for hydroxide ion-catalysed hydrolysis glycine ethyl ester, 1 protonated glycine ethyl ester, 41 and the cupric ion complex of glycine ethyl ester, F3 x 10 (Conley and Martin, 1965). The large effect of the cupric ion cannot be due entirely to electrostatic effects, but rather to catalysis by direct co-ordination with the ester function. 

Hydroxylamine plays the same part in the molecule as ammonia in ammino-platinum compounds, but the substances differ somewhat in chemical behaviour, for hydroxylamine is more readily eliminated than ammonia from the complex. Also, m-dihydroxylamino-dichloro-platinum is not obtained by the interaction of free hydroxylamine and potassium chloroplatinite, the method used for the preparation of cis-dichloro-diammino-platinum. Again, tetrammino-platinous hydroxide, [Pt(NH3)4](OH)2, is a very strong base and easily soluble in water, whilst tetrahydroxylamino-platinous hydroxide, [Pt(NH2OH)4](OH)2, is almost insoluble in water and a comparatively weak base.2 For this reason Werner 3 suggested a different formula for the two substances, and indicated that possibly in the tetrahydroxylamino-com-pound the co-ordination number of the metal is six and not four, as in the tetrammino-compounds thus ... 

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. 

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). 

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. 

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. 

The second mechanism requires a preliminary displacement of chloride by the oxygen of the ester to give a chelated complex which may be attacked by external hydroxide as seen in Chapter 3. In practice, the displacement of chloride from cobalt(m) is very slow and this mechanism proceeds by the SNlcb mechanism, in which loss of chloride ion is aided by deprotonation of the amine. The first step involves deprotonation of the en ligand followed by chloride loss to give a five co-ordinate intermediate (Fig. 5-63). 

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