The Template Effect

Nucleophile Relative rate Relative rate in protic media 

8 TT Gerbeleu, N. V., Arion, V. B. and Burgess, J., Template Synthesis in Macro cyclic Chemistry, John Wiley Sons, Ltd Chichester, 1999. 

In order to recognise a template effect two tests must be applied  

Accompanying chemical reactions must include significant spatial, topological or geometric control. 

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Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

The template effects of potassium and lithium ions are responsible for the efficiency of the synthesis of macrocyclic ligands in 18-CROWN-6 and2,2.7,7,12,12,17,l 7-OCTAMETHYL-21,22,23,24-TETRAOXAPER-HYDROQUATERENE. 

If the template effect of Endo and Kroto[9] does indeed exist and the growth of the tubule occurs outwards, a knowledge of the characteristics of the innermost tube is then of paramount importance in any attempt at modelizing the structure of a symmetric nanotube[ll]. By reversing eqn (17), possible values for Px and Qx can be obtained from... 

Numerous other methods exist for making the simple crowns. Many of these methods are compared in Sect. 3.1 which deals with variations in the synthesis of 18-crown-6. Further commentary on the influence of templating ions on the synthesis of crown ethers may be found in Chap. 2, which deals with various aspects of the template effect. 

One of the prime tenets of the template effect is that a cation of appropriate size coordinates with the heteroatom binding sites in the incipient ring system. Evidence to be discussed below indicates that there is a clear relationship between the size of the coordinating cation and the size of the ring formed. Before presenting this evidence, it is useful to note the approximate ring sizes of common crowns and the known ionic diameters of sundry metal cations. This is done in Table 2.1. 

Other indications of the template effect have been offered as well. Fenton, Cook and Nowell reported that the condensation of pyridine-2,6-dicarbaldehyde with 1,11-diamino-3,6,9-trioxaundecane in 1 1 molar ratio in butanol leads only to resinous gums . In the presence of equimolar amounts of Pb(SCN)2, the macrocycle illustrated in Eq. (2.5) was obtained in good yield . 

The addition of various alkali and alkaline earth cations to the cyclooligomerization of ethylene oxide by Dale and Daasvatn also provides strong presumptive evidence for the template effect. Recently, Reinhoudt, de Jong and Tomassen utilized several metal fluorides to effect crown formations . The reaction rates were found to be in the order Cs > Rb > > Na LE. Such an order would be expected on the basis of binding... 

The template effect has long been accepted prima facie by workers in the crown field because of the obvious relationship between ring size and complexation constant. In fact, Cram stated in 1975 that the templating properties of for preparing crown ethers is well established.. . In fact, the template effect was widely acknowledged and has always received overwhelming support. Nevertheless, few direct comparisons are available in the literature and we have restricted ourselves m this discussion only to direct rather than the large body of presumptive evidence which is currently available. 

The one-pot synthesis of 9 described above appears to afford only modest yields of azacrowns. One might wonder why any crown at all would be formed under non-high dilution conditions intended to yield only open-chained material. Vogtle suggests that this can be explained in terms of template, steric and entropy effects . These factors are of doubtless significance, but it is interesting to note that in the synthesis of poly-azamacrocycles, Richman and Atkins found that there was no significant template effect observed. The question of the template effect in Ihe syntheses of 9 has recently been addressed by Kulstad and Malmsten They conclude that the formation of 9 is assisted by the presence of alkali metal cations. 

Fig. 7. Ball and stick representations of (a) Na C Fee[N(CH2CH20)3]6 i and (b) Cs C Fe8[N(CH2CH20)3lg +, showing the template effect of the alkaline cation.

The particle size was below 50 nm (as determined by TEM image analysis), considerably smaller than that of the starting nanoemulsion, and showed a slight mean particle size increase and a broader size distribution with increasing O/S ratio, supporting the template effect of the nanoemulsion. The authors showed that these nanoparticles are interesting not only from a basic viewpoint but also for applications where safety and environmental concerns are important issues. 

Toward a better understanding of the templating effect in the formation of porous frameworks AlP04-5 a case of study... 

It is interesting to note that the size of the cluster cage, as reflected by their Ag-Ag and Ag-X distances, follows a trend with 82a < 82b < 82c, which is in line with the increasing size of the halide ion and demonstrates clearly the template effect of the halide ion in the cluster formation process. Analogous reactions using AgOTs or AgNC>3 as... 

In a 1 2 ratio these compounds yield a mixture of (Z/Z), (EIE) and (E/Z) isomers plus a substantial amount of the (E) and (Z) isomers of the monohydrazone monoketone. The complexity of the mixture (due to several equilibria that are established between its components) was illustrated by its complex H NMR spectrum. However, addition of one equivalent of barbiturate to the mixture led to a dramatic simplification of the NMR spectrum with the disappearance of the different products and the emergence of a single new species. This remarkable simplification of the spectrum is a consequence of the templating effect played by the barbiturate that amplifies the formation of only one of the receptors - in this case the ZyZ isomer. Interestingly, the addition of other species to the mixture such as acetate or 1-benzyluracil (with similar pKa values to barbiturate but different hydrogen bonding patterns) did not lead to the amplification of any specific species. 

Whereas Gold and Sghibartz showed that cation complexation depressed the rate of crown-ether disrupture, there is convincing evidence that crown ether formation is facilitated by the presence of cations. The template effect, presumably due to complexation of the open-chain precursor and formation of a crown-type conformation, clearly emerged from studies in which the yield of crown ethers was related to the type of cations present (Reinhoudt et al., 1976). Kinetic evidence for the template effect was presented by Mandolini and Masci (1977), who showed that the rate of cyclization of the precursor of benzo-18-crown-6 [2061 decreased in the order Ba2+ > SrJ+ > K+ > Na+ > Li+. This sequence is the same as the one found for the stability constants of the 1 1 complexes of these cations with 18-crown-6 in water (Table 3). 

For the synthesis of MgPz (2), the alkylated maleonitrile was treated with Mg butanolate. Because of the template effect of magnesium, maleonitrile molecules cyclotetramerize to form magnesium porphyrazine. MgPz is soluble in number of common solvents like chloroform, acetone etc. and little soluble in ethanol and methanol. The absence of CN peaks in IR spectram can easily be attributed to the cyclotetramerization, and the only strong peak was observed at 2,922 cm for C-H stretching vibration of 3-metylbutane groups. 

G. A. Melson, ed. Coordination Chemistry of Macrocyclic Compounds, Plenum, NY 1979 contains several chapters in which the template effect is utilised J. F. Lindoy, The Chemistry of Macrocyclic Ligand Complexes, Cambridge 1989. 

Until now syntheses along path d) of Figure 3 are known only for small bicyclic systems, for instance N(CH2CH20)3B from triethanolamine and B(OH)3 (87), N(CH2CH2CH2)3B from triallylamine and BH3 (88). However, macrobicyclic structures may be obtained in this way from a tripod type structure by making use of the template effect of a complexed transition metal cation, which remains included in the product (89-91). 

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