Metal ions as templates

The result of condensation of (3-dicarbonyl compounds with 3,4-diaminofurazan depends on the reaction conditions. With metal ions as templates, 14-membered rings 188 were formed exclusively (91MI2), whereas in the absence of these ions, only fused diazepines 189 were formed (Scheme 122) (89UKZ1064). 

The use of metal ions as templates for macrocycle synthesis has an obvious relevance to the understanding of how biological molecules are formed in vivo. The early synthesis of phthalocyanins from phthalonitrile in the presence of metal salts (89) has been followed by the use of Cu(II) salts as templates in the synthesis of copper complexes of etioporphyrin-I (32), tetraethoxycarbonylporphyrin (26), etioporphyrin-II (78), and coproporphyrin-II (81). Metal ions have also been used as templates in the synthesis of corrins, e.g., nickel and cobalt ions in the synthesis of tetradehydrocorrin complexes (64) and nickel ions to hold the two halves of a corrin ring system while cycliza-tion was effected (51), and other biological molecules (67, 76, 77). 

Although there has been some activity using metal ions as templates the overwhelming majority of studies have used low molecular weight organic molecules as templates. Metal ions which has been exploited are those which form a variety of well-defined coordination complexes, i.e. the transition metal... 

As a typical example of Method 1, Nishide el al. cross-linked poly(4-vinyl-pyridine) (PVP) with 1,4-dibromobutane (DB) in the presence of metal ions as templates [2-4], The adsorption behaviour of Cu(II), Co(II), Zn(II), Ni(II), Hg(II) and Cd(II) on the obtained resins was studied. The resins preferentially adsorbed the metal ion which had been used as template. PVP was cross-linked by alkylation of pyridine groups in PVP with DB to yield insoluble PVP resins, of which free pyridines were utilised to coordinate metal ions (Scheme 9.2). The stability constant of the Cu(II) complex of the resin was largest for the resin prepared with Cu(II) as template, being due to its large entropy change for the complexation. 

The macrocyclic ligands (33) and (34) were made by Brooker and co-workers using metal ions as template reagents (Scheme 8).66-68... 

The MIPs are particularly versatile materials, especially as the number and types of templates that have been successfully imprinted increase. For example, imprinted polymers have been prepared using metal ions as templates. ° Potential applications for these polymeric ionophores include the remediation of toxic metals from the environment, recognition elements for ion sensors for medical diagnostics, catalysis, and... 

Goodman et al. [89] used metal ions as template for two-armed receptor libraries, and showed that octahedral Ru(II)-complexes with two terpyridine ligands could discriminate between two different ammonium derivatives. 

The macrocycle L1 [structure (1)] having an inner ring of 18-member atoms has been synthesized (as its metal complexes) by the use of large metal ions as templates for the [2 + 2] Schiff base condensation of two molecules of 2,6-pyridinedicarboxaldehyde with two molecules of 1,2-benzenediamine.2 The template action of the metal ion is evidenced by the observation that only oils or gums are obtained in metal-free reactions. When the Ba2+ ion (ionic diameter 2.84 A)2 is employed as template, the product complex has a 2 1 ligand metal stoichiometry (Part A), whereas, for the Ca2+, Sr2 or Pb2+ ions (ionic diameter 2.24, 2.52, and 2.58 A, respectively), the products have a 1 1 metal-to-ligand stoichiometry. Smaller metal ions are ineffective as templates for the synthesis of L1. 

The fundamental step in the preparation of polyazamacrocycles is the cyclization reaction. The classical synthesis, using metal ions as templates <75MI 928-01 >, cyclizations at high dilution <61CB1410>, or the tosylate method of Richman and Atkins <74JA2268>, have been reviewed extensively. Several newer approaches have been developed in the 1980s and 1990s. 

Synthesis of azomethyne macrocycles by condensation of dicarbonyl compounds with diamines without the use of metal ions as template agents 07UK843. 

Route B Several examples are also known where a ligand/chelate precursor is reacted with a polymer ligand or in another case in the presence of a metal ion as template directly under construction of a polymeric metal complex. Difficulties can arise from side-reactions which mean that other reaction products can also be formed. The disadvantage is that such side-products are also covalently incorporated into the polymer, and no purification is possible. Therefore detailed design of the synthesis and then careful analysis is necessary. 

Fig. 2 Efficient syntheses of macrocycles for concave reagents using thermodynamic control for macrocyclizations (a) Formation of concave 1,10-phenanthrolines 2 by ring-closing metathesis (b) selection of niacrocyclic diimines 7 from a dynamic combinatorial library with the help of transition metal ions as templates and subsequent reduction to 8. here formation of an 18-membered macrocycle by using Ca. ...

Nishide, H. Deguchi, J. Tsuchida, E. Adsorption of metal ions on crosslinked poly (4-vinylpyridine) resins prepared with a metal ion as template. J. Polym. Sci. 1977,15,... 

For the ring closure of macrocycles, the use of templates is a common tool to enhance the yield and selectivity. Substrates using metal ions as templates were successfully converted to the macrocyclic product. The templating metal center remains in the product. The nickel complex 20 is oxidized on platinum, undergoes hydrogen shift, and is trapped by water providing nickel secocorrinate 21 [36] (Scheme 8). 

This can easily be explained by taking into account the weaker donor properties of thioether sulphur atoms as compared to thiol or thione sulphurs [62]. This mode of coordination of isothiosemicarbazones was later used for carrying out similar condensation reactions in the presence of other metal ions as templates. Thus by interaction of equimolar amounts of 2-hydroxybenzaldehyde 5-methyl-isothiosemicarbazone, anhydrous iron( III) chloride, and 2-hydroxybenzaldehyde in a mixture of absolute ethanol and DMF the template reaction became possible, giving rise to the formation of [Fe(L62)Cl] (Eq. 2.27) [63]. The synthesis of dimers [Fe(L62)]20 (R = CH3, C2H5, n-C3H7, n-C4H9) was performed by reaction of 2-hydroxybenzaldehyde 5-alkylisothiosemicarbazone and 2-hydroxybenzaldehyde with anhydrous FeCl3 in absolute ethanol or -butanol, followed by addition of triethylamine as base [64]. For these complexes the possibility was established of mutual transformations (Eq. 2.28). 

This aspect of the fascinating chemistry of bis-isothiosemicarbazones is also connected with using redox-active metal ions as templates. It results in a change of... 

The properties of non-innocent ligands (redox-activity) for the open-chain and macrocyclic ligand products have not been revealed yet, but the research is only in its infancy. Employment of redox-active metal ions as templates should create conditions for displaying this special behaviour. 

In contrast to dap, 2,6-dfp undergoes 2 + 2 cyclocondensation reactions with 3,3-triamines in the absence of metal ions as template. Using bis(3-aminopropyl)-methylamine or lV,lV-bis(3-aminopropyl)-A, iV -dimethyl-l,2-diaminoethane as ligsons is supposed to give the 28-membered ring-expanded macrocycles L708 and L709, respectively (Eq. 3.34) [82]. 

Recently, a biomimetic ion imprinted technique (that is, using metal ion as template) has become a potential tool for the preparation of robust materials that have the ability to specifically bind a metal ion species with high selectivity. However, most of these traditional imprinting techniques suffer from low binding capacity, poor site accessibility, and slow binding kinetics because of most imprinted sites were embedded in high rigid polymer matrix interior. 

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