Template effect with metal ions

Figure 3.45 Kinetic studies of the template effects of metal ions on cyclisation to form benzo [18] crown-6. ( Wiley-VCH Verlag GmbH Co. Reproduced with permission).

The cyclization reaction of dihalogen or ditosylate compounds with bis primary or bis secondary amines is similar to the diacid dichloride reaction except that the diaza-crown is obtained in a single step. This is a convenient procedure particularly since the dihalide is usually readily available and inexpensive. This cyclization process does not need high-dilution techniques because of template effects by metal ions. It is important to note that when using a bis primary amine and a dihalide, many side products such as the cryptands and bis-crown ethers can be formed (Alfa et al., 1988 Krakowiak and Bradshaw, 1991). 

Polymeric pseudocrown ether networks have been generated in situ by the photopolymerization of poly(ethylene glycol) diacrylate transition metal complexes <00CM633>, and the effect of metal ion templation was evaluated. The 1,6,13,18-tetraoxa[6.6]paracyclophane-3,15-diyne (termed pyxophanes) was prepared from hydroquinone and l,4-dichlorobut-2-yne it forms size-selective 7i-complexes with alkali metal cations <00CC2377>. Dibenzo[ ]crown-m have been used in numerous elegant studies in which they were the needles that were threaded by diverse reagents the resultant... 

Higher yields of crown ethers are generally obtained if the cyclisation reaction can be templated by a metal ion of appropriate size. Thus, potassium ions are well known to enhance the yields of 18-crown-6 derivatives,1,3 while addition of the smaller lithium ion enhances the yields of reactions giving 13-and 14-membered tetraoxa rings.4b4c Such a reaction has been used to good effect in the synthesis of the chiral 14-crown-4 dibenzyl ether, L-ll, which can be prepared in a yield of 65% (Scheme 4.7) (cf. 11% for the untemplated 18-crown-6 analogue) by co-condensation of l-7 with the appropriate linear ditoluenesulfonate. 

Other Oxygen-containing Derivatives. Acetone and furan condense in an acidic medium to form (54). The yield is increased by the addition of metal salts, e.g. IiC104. The increase has been attributed to acidity (pH) effects rather than to effects of metal ion templates. This is the first demonstration of the importance of the effects of pH in metal-assisted cyclizations. Compound (54) is cleaved by m-chloroperoxybenzoic acid to form the novel octaketone (55), with a n s-enedione configuration. The endoperoxide (56) is converted into a bis-epoxide on treatment with catalytic amounts of cobalt(n) 5,10,15,20-tetraphenylporphine at — 10°C, and the epoxide rearranges to (57) at 20... 

The expression template reaction indicates mostly a reaction in which a complexed me) ion holds reactive groups in the correct orientation to allow selective multi-step reactions. T1 template effect of the metal is twofold (i) polymerization reactions are suppressed, since th local concentration of reactants around the metal ion is very high (ii) multi-step reactions are possible, since the metal holds the reactants together. In the following one-step synthesis eleven molecules (three ethylenediamine — en , six formaldehyde, and two ammonia molecules) react with each other to form one single compound in a reported yield of 95%. It is ob vious that such a reaction is dictated by the organizing power of the metal ion (I.I. Creasei 1977),... 

In terms of enzyme catalysis, the following factors are likely to influence the magnitude of the rate enhancement in enzymatic processes (a) proximity and orientation effects (b) electrostatic complementarity of the enzyme s active site with respect to the reactant s stabilized transition state configuration (c) enzyme-bound metal ions that serve as template, that alter pK s of catalytic groups, that facilitate nucleophilic attack, and that have... 

The kinetic template effect is observed in reactions in which the metal ion acts by coordinating the reactants. This effect has also been described as a coordination template effect. A more direct description of a kinetic template reaction is one which involves Combination of two Ligands Attached to the same. Metal ion. Such a description leads to the useful acronym CLAM reaction , which graphically portrays the key reaction step. The process can be generalized and compared with the non-template reaction in Scheme 30. 

The hexahydropyrimidine (58), formed from l-phenylpropane-l,2-dione and propane-1,3-diamine, is an excellent precursor for the a-diimine macrocyclic complexes (60), presumably via the amino ketone (59) (Scheme 36).126 In this case, intramolecular cyclization of (59) to (58) is reversible, so that the metal ion can exert a thermodynamic template effect in formation of the complex (60). This represents a further example of a long-known phenomenon in which a metal ion can stabilize an a-diimine structure by virtue of the formation of stable five-membered chelate rings. Many 2-hydroxy- or 2-mercapto-amines undergo reaction with a-dicarbonyl compounds to yield heterocyclic compounds rather than a-diimines. However, in the presence of suitable metal... 

The catenands are synthesized using the metal ion template effect, whereby a bis complex is formed from an a,a -disubstituted o-phenanthroline. This initial product is treated with a diiodoal-kane to effect the ring closures.34... 

The operation of the mismatch effects may be seen to best advantage when a range of products is possible from a single reactant or set of reactants. The reaction of ethylene oxide with metal salts results in the formation of crown ethers (Fig. 6-30). Obviously, a whole range of different cyclic oligomers and acyclic polymers could be formed from ethylene oxide. If we specifically wanted to obtain 18-crown-6, with a hole size of about 1.4 A, we would expect to use a potassium ion as template (r = 1.38 A). In fact, 18-crown-6 is obtained in good yield from the reaction of ethylene oxide with potassium tetra-fluoroboratc. In contrast, if we wanted 12-crown-4, with a hole size of about 0.8 A, it... 

In many cases it is possible to utilise the hole size effects for the synthesis of specific types of macrocycle. Thus, a tetradentate macrocycle (6.33) is expected to be obtained from a template condensation of 2,6-diacetylpyridine with 1,5,9-triazanonane in the presence of small, first-row transition metal dications. The hole size of 6.33 closely matches the size of these metal ions. This is indeed what happens when Ni2+ (r = 0.8 A) is used as a template for the condensation and the nickel(n) complex of 6.33 is obtained in good yield (Fig. 6-32). However, when Ag+ (r = 1.0 A) is used as a template, the metal ion... 

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