Reactions of Co-ordinated Amines

Such equilibria as Fig. 5-25 allow the generation of small but controlled amounts of a free amine in solution. This effective reduction in the nucleophilicity of the co-ordinated amine may be used to good advantage. For example, the alkylation of co-ordinated amines rarely proceeds beyond the monoalkylated stage. In contrast, the reactions of the free amines usually proceed further to give a mixture of polyalkylated products (Fig. 5-26). 

In many cases it is not known unambiguously which of these two mechanisms is operative. The pathway involving ligand deprotonation is most favoured by high oxidation state metal ions, and is relatively well-established for complexes of metal ions such as pla-tinum(iv), where appropriate intermediates may be isolated, and for cobalt(m), where there is very convincing kinetic evidence for the involvement of such deprotonated intermediates. The careful design of experiments and the selection of the correct complexes is crucial in this area of study. 

Perhaps the simplest reaction to envisage is the alkylation of a co-ordinated amine. These reactions are well-known and usually occur under strongly basic conditions. It is most likely that these reactions involve deprotonated amido intermediates, and are considered in that context. As we have seen in Chapter 2, the acidity of an amine proton should increase upon co-ordination to a metal centre, and with the charge on that metal. As a consequence, we might expect to see new types of reaction products derived from the amido ligand, particularly with high oxidation state metal complexes. The former effect is indeed the case, and dramatic reduction of the pKa of ammonia and amines is observed upon co-ordination to a metal ion (Table 5-1). 

The enhancement of the acidity of the amine is not limited to sites which are directly co-ordinated to the metal, but may also be transmitted for considerable distances through the molecule. For example, the complex bis(di-2-pyridylamine)palladium(ii) undergoes a facile deprotonation (Fig. 5-28). This reaction also serves to exemplify the importance of charge control over the level of protonation. The deprotonation yields the neutral doubly deprotonated complex. 

A direct consequence of the enhanced acidity of co-ordinated amines is seen in the reactions with chlorine in aqueous solution of some platinum(iv) complexes. In these reactions the nucleophilic attack of an intermediate amido complex upon chlorine leads to the formation of dichloroamido complexes (Fig. 5-29). 

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Charge effects may also play an extremely important role in controlling the reactions of co-ordinated amines with electrophilic reagents. This is very clearly seen in the alkylation reactions of nucleophilic sites remote from the metal. On electrostatic grounds we would expect the reaction of positively charged complexes with electrophiles to be less favoured than the reaction of neutral or anionic complexes, and this is indeed the case. Consider the attempted alkylation of the non-co-ordinated isoquinoline rings in the cop-per(n) complexes 5.14 and 5.15. Compound 5.14 is derived from salicylaldehyde and... 

In the case of complexes containing macrocyclic amines, it is often possible to isolate the intermediate deprotonated amido complexes. In the next section, we will consider some very important aspects of co-ordination chemistry, in which reactions of co-ordinated amine and/or amide play a crucial role. 

Perhaps of more synthetic utility is the alkylation of co-ordinated amines. As we illustrated in Fig. 5-26, the attempted alkylation of free amines usually results in the formation of numerous products. This is ascribed to the greater nucleophilicity of the alkylated amines with respect to the starting material. As an example, the reaction of 1,2-diamino-ethane with iodomethane yields three major products (Fig. 5-30). 

It is not usually possible to form mixed JVO-donor ligands by direct reaction of co-ordinated 1,3-diketonates with amines. In part, this is due to the delocalised charge of the formally anionic ligand rendering the diketonate less prone to attack by a nucleophile. This deactivation towards attack by nucleophiles should be contrasted with the facile reactions with electrophiles which have been discussed in Section 5.3. It is possible, however, to form complexes of conjugated /VO-donor ligands by direct reaction of the metal-free, 1,3-dicarbonyl with amine, followed by co-ordination (Fig. 5-48). 

We have already seen that imines may be formed by the oxidative dehydrogenation of co-ordinated amines and that this is a commonly observed process, particularly in macrocyclic systems. Likely mechanisms for these dehydrogenations were suggested in Chapter 5, which emphasised the role of the variable oxidation state metal ions in the process. These reactions are quite general and many examples involving iron or ruthenium complexes have been studied in detail. 

Examples of reactions of co-ordinated ligands in square-planar complexes include hydrolysis of /rfl j-[PtCl(CO)(PR3)2], the reaction of platinum(ii)-alkene complexes with ethylamine, and of palladium(ii)-alkene complexes with n-butylamine. In the last case there is evidence that the amine co-ordinates to the palladium before attack at the coordinated alkene occurs. 

Cobalt(ni) Complexes.—The xlcb mechanism originally proposed by Garrick in 1937 is now widely accepted as the most likely mechanism for the base hydrolysis of cobalt(m) complexes. The use of Co n.m.r. shows some promise for determination of the pXa s of co-ordinated amines. An equilibrium constant of 0.39 0.051 mol has been established in this way for reaction (51). ... 

The reactions of co-ordinated isocyanide in Pt(CNEt)2(PMeaPh)a with ethanol, aniline, benzyl mercaptan, or similar compounds occur by 1,2-m-addition to the carbon-nitrogen bond, to give carbene compounds of the type (12). Addition of methylamine to co-ordinated methyl isocyanide in [Fe(CNMe)e] is thought to occur by attack of methyl-amine-N at isocyanide-C, to give initially (13). ... 

Initial explanations in terms of an associative SN2-type reaction proved untenable, and the reaction is now thought to involve deprotonation of a co-ordinated amine (Fig. 2-17). This is the SN1 cb or Deb mechanism. The key step is the formation of the amide intermediate, [Co(NFl3)4(NH2)Cl]+, which undergoes halide loss to generate the reactive five-co-ordinate intermediate [Co(NH3)4(NH2)]2+ (2.2) (Fig. 2-18). 

The metal ion does, however, introduce a new subtlety into these reductions. The reduction of the two imine groups in the nickel(n) complex 4.10 is readily achieved with Na[BH4], The free tetraamine ligand would be expected to exhibit a facile pyramidal inversion at each nitrogen atom, whereas in the nickel(n) complex this inversion is not possible without significant weakening (or breaking) of the Ni-N bonds. In macrocyclic complexes it is very often found that the complex obtained by the reduction of a co-ordinated imine does not possess the same stereochemistry as that obtained by the direct reaction of the free amine with metal ion. 

In the case of amine nucleophiles, the products from the reaction with co-ordinated cyanates are carbamates or ureas (Fig. 4-34), and this provides a particularly convenient method for the preparation of carbamate complexes. An example of this behaviour is seen in the reaction of 3,5-dimethylpyrazole with cyanate in the presence of copper(n) salts (Fig. 4-35). Similar reactions are observed with co-ordinated thiocyanates and other heterocumulene s. 

Figure 5-27. The deprotonation of a co-ordinated amine provides another way of rendering the amine nucleophilic. The spz hybridised nitrogen atom bears a lone pair which may be used in reactions with electrophiles.

Although this was at first thought to indicate that an associative mechanism was indeed operative in these reactions, over the years a body of further data accumulated to suggest that this was not the case. It is now clear that the deprotonation of a co-ordinated amine is the key step in this mechanism, which is based upon dissociative ligand loss from an amido intermediate. This process is known as the SN1 cZ mechanism, and was mentioned briefly in Chapter 2, and illustrated in Fig. 2-13. The first step involves the deprotonation of the co-ordinated amine (Fig. 5-40). 

The design of polydentate ligands containing imines has exercised many minds over many years, and imine formation is probably one of the commonest reactions in the synthetic co-ordination chemist s arsenal. Once again, the chelate effect plays an important role in stabilising the co-ordinated products and the majority of imine ligands contain other donor atoms that are also co-ordinated to the metal centre. The above brief discussion of imine formation will have shown that the formation of the imine from amine and carbonyl may be an intra- or intermolecular process. In many cases, the detailed mechanism of the imine formation reaction is not fully understood. In particular, it is not always clear whether the nucleophile is metal-co-ordinated amine or amide. Some intramolecular imine formation reactions at cobalt(m) are known to proceed through amido intermediates. A particularly useful intermediate (5.24) in metal-directed amino acid chemistry is... 

As mentioned above, reactions of this type have been widely used in the synthesis of macrocyclic ligands. Indeed, some of the earliest examples of templated ligand synthesis involve thiolate alkylations. Many of the most important uses of metal thiolate complexes in these syntheses utilise the reduced nucleophilicity of a co-ordinated thiolate ligand. The lower reactivity results in increased selectivity and more controllable reactions. This is exemplified in the formation of an A -donor ligand by the condensation of biacetyl with the nickel(n) complex of 2-aminoethanethiol (Fig. 5-78). The electrophilic carbonyl reacts specifically with the co-ordinated amine, to give a complex of a new diimine ligand. The beauty of this reaction is that the free ligand cannot be prepared in a metal-free reac-... 

Sometimes this deactivation is so great that co-ordinated amines are non-nucleophilic. This is particularly likely when the ligand is co-ordinated to a non-labile metal centre. However, even in these cases, all is not lost. We may also use the enhanced acidity of ligands co-ordinated to a metal centre to generate reactive nucleophiles which would not otherwise be readily accessible. For example, nickel(n) complexes of deprotonated diamines may be prepared, and react with dialkylating agents to yield macrocyclic complexes (Fig. 6-10). To clarify this, consider the reaction in Fig. 6-10 in a little more detail. The amine 6.14 is reactive and unselective, and does not give the desired macrocycle upon reaction with the ditosylate. Deprotonation of the amine under mild conditions is not pos-... 

Figure 6-14. The reduction of co-ordinated macrocyclic imines provides a method for the preparation of macrocyclic amines. The reaction above illustrates one of the standard methods for the preparation of cyclam. The metal ion may be removed from the nickel(n) complex by prolonged reaction with cyanide.

New kinetic data on the reactions of chlorocyclophosphazenes with amines have appeared. The reactions of both N3P3CI6 and N3P3Cl5-NMe2 with dimethylamine in THF were shown by conductivity measurements to follow a second-order rate law, which was first order in dimethylamine. The formation of both mono- and bis-dimethylamino-derivatives was visualized as proceeding by the rapid formation of a five-co-ordinated intermediate, followed by a relatively slow entropy-controlled THF-catalysed dehydrochlorination. It was suggested that the entropy of... 

Formation of ruthenium(m) complexes by attack at co-ordinated amines promises to be a useful synthetic method. Recent examples include the reactions of the [Ru(NH3)e] + ion with aldehydes (RCHO) to give the corresponding co-ordinated nitrile, [Ru(NH8)6(NCR)] + (R = Me or Ph, and the oxidant is unknown), or the reaction with glyoxal, MeCOCOMe, in the presence of hydroxide ion to give the ion (45). From kinetic studies of the latter reaction, a mechanism is proposed in which the [Ru(NH3)sNH2] ion attacks at one carbonyl centre of MeCOCOMe, followed by further deprotonation of the cis ammonia molecule, cyclization, and elimi-... 

Several other useful reviews of reactions involving metal ions have also been published. Redox reactions of chromium(m)-amine species have been described and a survey has been made of the solution chemistry together with reaction paths involved in the redox reactions of various plutonium species. Oxidation reactions of thallium(m) have also been described. Developments in the redox chemistry of peroxides have been reviewed, the nature of the reactions which involve iron(iii) in various complexed forms providing a fascinating example of the manner in which geometry and co-ordination to the metal centre greatly affect the reactivity of the system. Redox properties of cobalt chelates, with delocalized... 

Reactions between the lighter second group dialkyls, which are A type acceptors, and bases such as ethers and tertiary amines may be complicated both by steric factors and by heats of co-ordination sometimes being similar to heats of depolymerization of electron-deficient polymers. 

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