Template Synthesis of Macrocycles

A requirement for a metal ion template has been established for the majority of reactions described in this section. Other reactions described are those in which metal ions, particularly Na +, are part of the stoichiometry of the reactions but for which a template function has not been identified. 

Condensation of a series of diaminodialdehydes with ethylene-diamine, o-phenylenediamine, or 1,8-diaminonaphthalene in the presence of Ni(II), Co(II), and Cu(II) acetates has afforded a series of macrocyclic quadridentate complexes containing 14-, 15-, or 16-membered rings (10, 11, 16)  

The free ligand (XXVII) was first prepared by a template condensation of o-phenylenediamine with pentane-2,4-dione in the presence of Ni(II) ions (56), with removal of the metal ion by subsequent reaction with anhydrous HC1 in ethanol, and then isolated as the hydrochloride 

Ochai and Busch (101) briefly mention the synthesis of a macrocycle containing a pyridyl unit (XXXII) from the condensation of 2,6-diacetylpyridine with bis(3-aminopropyl)imine in the presence of Ni(II) ions. A similar condensation (38), using the same pyridyl source, with tetraethylaminetetramine in the presence of Fe(II) ions produces macrocycles XXXIII and XXXIV, containing five and six donor 

Other macrocycles containing pyridyl units (XXXV-XXXVIII) have been synthesized on Co (II) and Ni(II) templates by Lewis and Wainwright (84). In the case of Ni(II) the free macrocycle XXXVIII can be generated it reacts almost quantitatively with Fe(II) ions to give an air-stable high-spin complex. However, most macrocycles 

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N. V. Gerbeleu, V. B. An on, J. Burgess Template Synthesis of Macrocyclic Compounds 1999, ISBN 3-527-29559-3... 

Template reactions of dicarbonyl compounds and diamines have been extended recently to include the dialdehydes (3O)60>61 and (32)62-63 and a range of new diamines such as (31) and (33).64 Examples are shown in equations (6) and (7). The new diamines have also been used in the template synthesis of macrocyclic complexes based on 2,6-diacetylpyridine.60,65... 

Probably one of the commonest reactions encountered in the template synthesis of macrocycles is the formation of imine C=N bonds from amines and carbonyl compounds. We have seen in the preceding chapters that co-ordination to a metal ion may be used to control the reactivity of the amine, the carbonyl or the imine. If we now consider that the metal ion may also play a conformational role in arranging the reactants in the correct orientation for cyclisation, it is clear that a limitless range of ligands can be prepared by metal-directed reactions of dicarbonyls with diamines. The Tt-acceptor imine functionality is also attractive to the co-ordination chemist as it gives rise to strong-field ligands which may have novel properties. All of the above renders imine formation a particularly useful tool in the arsenal of preparative co-ordination chemists. Some typical examples of the templated formation of imine macrocycles are presented in Fig. 6-12. 

Gerbeleu, N.V. Arion, V.B. Burgess, J. Template Synthesis of Macrocyclic Compounds. John Wiley Weinheim, New York, Chichester, 1999, 565 pp. 

History of ligand substitution in Co111 complexes Coordination Chemistry of Macrocyclic Compounds (book) Template synthesis of macrocycles... 

The alternative route to phosphorus macrocycles uses the coordinating properties of phosphine ligands to assemble the macrocycle precursors in favorable conformations using a transition metal as a template. The general principles are illustrated in Scheme 4, developed by Cooper and coworkers. This template synthesis of macrocycles may occur fortuitously for example, Musker and coworkers fortuitously dimerized their ligand (41) to afford the macrocycle [16]aneP2S2 (44). 

The kinetics and mechanism of synthesis and decomposition of macrocyclic compounds are regarded as one of the most important aspects in the chemistry of these compounds. The majority of papers concern metal ions complexing with preliminarily synthesized macrocyclic ligands and metal ion substitutions by other metal ions in the preliminarily prepared complexes. Template synthesis, the most promising approach to the directed preparation of macrocyclic compounds with desired structures [17], plays a still more decisive role in the chemistry of macrobicyclic complexes with encapsulated metal ion. However, the literature contains only scarce data on the kinetics and the mechanism of the template synthesis of macrocyclic compounds because of the difficulties encountered in experimental determinations of kinetic and thermodynamic parameters, such as low product yields, nonaqueous media, high temperatures, and side reactions. 

The most common template synthesis of macrocycles containing both sulfur and nitrogen atoms is the condensation of a-diketones (or acetone), 3-mer-... 

The various aspects of template synthesis of macrocyclic compounds have been discussed in a series of monographs and reviews [1-21]. However, there is no strict definition of what can be called a template reaction. A synthetic chemist who takes advantage of the template effect in synthesis will have his own view of what constitutes a template process. It is therefore appropriate to conamence here with a general definition, which is that the template eflFect is the enhancement of chemical reaction by complementary surfaces [22, 23]. One of the first examples was connected with the discovery of the double helix structure of DNA (Figure 1-1) by Watson and Crick in 1953 [24]. The template effect is operative in its rephcation. Each chain of the DNA double helix serves as template, or mould, for the formation of the second chain. 

The template synthesis of macrocyclic complexes rra 5-[M(L9)]" (M"" = Ni, Co +, Fe +) from 1-phenyl-1,2-propanedione and 1,3-diaminopropane occurs [44] according to Scheme 1-2. Reaction (1) represents the organic reaction prior to addition of a metal salt. When a methanolic solution of the latter is added to the reaction mixture, the metal-directed condensation is realised, producing the carbi-nolamine and final products. It is obvious that reaction (2) is a consequence of shifting the position of tautomeric equilibrium under the influence of a metal ion exclusively towards [M(L9)] , the latter subsequently being transformed into [M(L10)]"+. That the condensation reaction actually takes place within the metal coordination sphere has been demonstrated by the isolation of the corresponding cobalt(III) macrocyclic complexes with L9. 

As has been noted [175], the nitroalkane/formaldehyde approach to the template synthesis of macrocyclic tetramine ligands has two notable advantages compared with conventional synthesis of comparable ligands ... 

Template synthesis of macrocyclic systems based on di- and polyamines and polyfunctional dicarbonyl compounds... 

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