Macrocyclization metal cation templated

Early work involved the use of metal cations as templates in macrocyclization reactions. Seidel [6] reacted 2-aminobenzaldehyde 1 with anhydrous zinc chloride (Scheme 1-1), but did not recognize that he had prepared the macrocycle 2, and it was not until 40 years later that Busch [7] and co-workers elucidated the structure of this type of macrocycle and investigated how metal cations template its formation. 

Most of the templates diseussed in this chapter are kinetic templates. Some of the early examples of metal cation templated macrocyclization studied by Curtis and Busch [7,9] (Schemes 1-1 and 1-2) are thought to operate under thermodynamie eontrol. The clearest evidence for a thermodynamic template effect comes when the template-free product is not stable under the reaction conditions. For example, treatment of 1,2-dicyanoben-zene 11 with boron trichloride or uranyl chloride results in the formation of subphthalo-... 

Aza macrocycles have also been used as templating agents in the formation of zinc and other metal cation-containing aluminophosphates via hydrothermal synthesis.705 The zeolite-like structures have been formed in the presence of cyclam- and hexaaza-based macrocycles. 

Since Pedersen s original work on the use of cations to template the formation of crown ethers [18-20], a large number of different templating agents for macro-cyclization reactions have been reported. While the initial work concentrated on the use of metal cations, further developments demonstrated that species with hydrogen bonding donor or acceptor properties could be equally useful to template the synthesis of macrocyclic molecules. 

Reinhoudt and co-workers (101-105) have reported a series of Schiff base macrocyclic polyether ligand complexes prepared via barium cation-templated Schiff base condensation of the appropriate polyether dialdehyde with a diamine, in the presence of a transition metal or uranyl acetate, followed by removal of the Ba2+ template cation on subsequent addition of guanidinium sulfate (Scheme 19). The copperdl) and nickeldl) complexes (62) and (63) exhibit reversible redox couples... 

Template effects play an important role in most of the cyclizations leading to alloxygen macrocycles. Usually, alkali or alkaline earth metal cations serve as a template ion. Transition metal cations are useful in the syntheses of macrocyclic polyamines. The template effect is less pronounced in the case when formation of mixed nitrogen/ oxygen macrocycles are formed in comparison with their all-oxygen analogues. 

Figure 2.24. Schematic representation of the principle of transition-metal-templated synthesis of [2]-rotaxanes from macrocyclic chelate (A), metal cation (black disk) and open chelate (B). The latter bears functions X at its extremities, which will be used for anchoring or constructing the stoppers (represented as diamonds). (/) Threading step (//) stoppering step (in) removal of the metal template.

Since the free SBs are not always stable, many SB complexes are prepared by template synthesis which implies carrying out the condensation reaction in the presence of a metal ion. This is a very common method for the preparation of macrocyclic SB complexes.2,3 In this case large alkaline earth metal cations (i.e., Ba11, lanthanoids, or Pb11) have proved to be efficient templates. The size... 

Barefield and coworkers employed a template process in multi-steps using autoclaves and perchlorate salt intermediates. Even with the many steps, a yield of 52% for the A, A, A "-trimethylcyclam was realized. These procedures, however, are good only for certain ring systems and macrocycle sizes. Each ring size with differing numbers of nitrogen atoms requires a particular tern-plating metal cation. 

In 1932, a dark blue by-product was isolated during the industrial production of phthalimide from phthalic anhydride and ammonia in an iron vessel. This unexpected by-product was eventually identified as iron(II)phthalocyanine Now we know that the iron had templated the formation of this macrocycle [8]. Curtis investigated the condensation of acetone 4 and 1,2-diaminoethane 3 in the presence of metal cations and showed that the macrocycles 5 and 6 could be prepared both by templated and untemplated processes (Scheme 1-2) [9, 10],... 

The simplest type of template directed cyclization is metal cation induced macrocycliza-tion, as discussed in Section 1.1. Mandolin and co-workers [37] have made a detailed study of the influence of alkali and alkaline earth metal cations on the cyclization of 2-hydroxyphenyl-3,6,9,12-tetraoxa-14-bromotetradecyl ether 28 in methanol and in dimethyl sulfoxide (Scheme 1-8). They studied different sizes of macrocycle and metal cation to determine the most effective combination for cyclization the results from this study will be summarized in Section 1.4.2.3. 

Macrocyclization templates are not restricted to metal cations but also include hydro-phobic organic units, such as the adamantanecarboxylate templated formation of cage 24 described by Fujita (Scheme 1-6) [31]. Other examples, which will be described in later chapters, include Cram and co-workers use of solvents to template formation of carce-plexes solvents such as dimethylacetamide were found to stabilize the charged intermediate formed during carceplex synthesis. The empty carcerands were never formed... 

Fig. 11 Principle of transition metal-templated synthesis of a [2]rotaxane. A thick line represents a dpp chelate, a black dot represents a metal cation, a hatched diamond represents a Au(III) porphyrin and an empty diamond represents a Zn(II) porphyrin. The transition metal controls the threading of Au(III) porphyrin-pendant macrocycle (A) onto chelate (B), to form prerotaxane (C). Construction of the porphyrin stoppers at the X functions leads to the metal complex [2]rotaxane (D). Removal of the template cation forms the free rotaxane (E)...

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