Template condensation reaction, nickel macrocyclic complexes

Another series of macrocydic complexes has been prepared by Busch and co-workers by the condensation reaction of either pyridine-2,6-dicarboxaldehyde or 2,6-diacetylpyridine with various polyamines (Scheme 38). 24,2628,2640 2645 Other examples of template reactions leading to different types of macrocydic complexes are reported in Schemes 39-44.2628 2646 2650 The selfcondensation of l-amino-2-carboxaldehyde in the presence of nickel(II) gives two types of macrocycle (Scheme 45), M51... 

Neutral nickel(II) complexes with a number of deprotonated porphyrins have been prepared in most cases by the direct reaction of a nickel salt, usually Ni(ac)2-4H20, with the preformed diacid macrocycle, using media such as DMF, MeC02H or PhCl at refluxing temperature. Recently, the template synthesis of the complex with tetraalkylporphyrins has been reported (Scheme 61).2883 On the other hand the condensation reaction of 1,3,4,7-tetraalkylisoindole and nickel acetate tetrahydrate gives the [Ni(omtbp)] complex (omtbp = octamethyltetrabenzoporphyrinate dianion), 2884... 

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... 

A great variety of aza macrocycle complexes have been formed by condensation reactions in the presence of a metal ion, often termed template reactions . The majority of such reactions have inline formation as the ring-closing step. Fourteen- and, to a lesser extent, sixteen-membered tetraaza macrocycles predominate, and nickel(II) and copper(II) are the most widely active metal ions. Only a selection of the more general types of reaction can be described here, and some closely related, but non metal-ion-promoted, reactions will be included for convenience. The reactions are classified according to the nature of the carbonyl and amine reactants. 

Metal template syntheses of complexes incorporating the p-amino imine fragment have been introduced by Curtis as a result of his discovery that tris(l,2-diaminoethane)nickel(II) perchlorate reacted slowly with acetone to yield the macrocyclic complexes (40) and (41) (equation 8).81-83 In this macrocyclic structure the bridging group is diacetone amine imine, arising from the aldol condensation of two acetone molecules. This reaction is widely general, in the same way that the aldol reaction is, and can be applied to many types of amine complexes. The subject has been reviewed in detail with respect to macrocyclic complexes by Curtis.84... 

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-... 

In some cases a whole series of dehydrogenation reactions may proceed sequentially to yield aromatic or highly conjugated products. An example of this is seen in the aerial oxidation of the nickel(n) complex of the macrocycle formed by the template condensation of biacetyl bishydrazone with formaldehyde. The product of the oxidation is the fully aromatic dianionic macrocyclic complex (Fig. 9-24). 

The standard synthesis for cyclam was developed by Barefield and Wagner in 1976.29 They used similar starting materials to the van Alphen procedure but the cyclisation yield is improved through the use of a nickel (II) template. Glyoxal completes the macrocycle by a Schiff base condensation reaction. The resulting imine functionalities are reduced with sodium borohydride to leave the complexed macrocycle. The metal ion is then removed by reaction with cyanide and the free ligand extracted with chloroform (Scheme 3.19). Yields are typically in the region of 60%. 

Most of the template syntheses of nonbenzenoid macrocycles originated with Curtis (39) and involve the condensation of metal-amine complexes with aliphatic carbonyl compounds, e.g., the reaction of acetone with tris(diaminoethane)nickel(II) perchlorate at ambient temperature leads to the isolation of three products, two of which may be represented as cts-XLIX and trans-L and the other is formed by a further interconversion of complex L in solution (39,143). With Cu(II) diaminoperchlorates, a mixture of cis and trans complexes analogous to XLIX and L is formed, but with Co(II) only the trans analog of L has been isolated. When ketones containing bulky groups are used, the reaction is much slower, e.g., there is only a small yield of LI from... 

Examples of template procedures in which the ring-closing condensation involves reaction at a centre other than a donor atom have been documented. In an early synthesis of this type, the reaction of bis-(dimethylglyoximato)nickel(n) (62) with boron trifluoride was demonstrated to yield the corresponding complex of the N4-donor macrocycle (63) (Schrauzer, 1962 Umland Thierig, 1962). In this reaction the proton of each bridging oxime linkage is replaced by a BF2+ moiety. X-ray... 

The formation of macrocyclic ligands by template reactions frequently involves the reaction of two difunctionalised precursors, and we have tacitly assumed that they react in a 1 1 stoichiometry to form cyclic products, or other stoichiometries to yield polymeric open-chain products. This is certainly the case in the reactions that we have presented in Figs 6-8, 6-9, 6-10, 6-12 and 6-13. However, it is also possible for the difunctionalised species to react in other stoichiometries to yield discrete cyclic products, and it is not necessary to limit the cyclisation to the formal reaction of just one or two components. This is represented schematically in Fig. 6-19 and we have already observed chemical examples in Figs 6-4, 6-11 and 6-18. We have already noted the condensation of two molecules of 1,2-diaminoethane with four molecules of acetone in the presence of nickel(n) to give a tetraaza-macrocycle. Why does this particular combination of reagents work Again, why are cyclic products obtained in relatively good yield from these multi-component reactions, rather than the (perhaps) expected acyclic complexes We will try to answer these questions shortly. 

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