Cyclic polyaza

In their quest for large molecular cavities capable of binding molecules or ionic guests, Vogtle and coworkers 1 synthesized non-cyclic polyaza compounds via a repetitive stepwise process (one-directional case Scheme 4.2). The use of two-directional cores (Scheme 4.5), e.g., ethylenediamine, 2,6-di(aminomethyl)pyridine (8) or l,3-di(amino-methyl)benzene, with acrylonitrile afforded the tetranitrile 9, which was reduced with Co(n)-catalyzed borohydride to produce hexaamine 10. This terminal tetraamine was subsequently treated with excess acrylonitrile to generate the octanitrile 11 although the process was terminated at this stage, a foundation of dendrimer construction was established. 

Interest in developing new lanthanide and actinide reagents has led to the synthesis of many new maeroeyclics derived from cyclic polyaza and mixed polyaza-polyoxa ligands (Biinzli and Wessner 1984, Bombieri 1987, Vallarino 1989), and from cyclic and open-chain polycatecholates (Raymond et al. 1984). 

Small-ring cyclic diamines have already been discussed in Chapter 1.20. The azamacrocycles offer the possibility for functionalization at the nitrogen donor groups and many examples will be presented from triazamacrocycles up to much larger polyaza macrocycles that will bind more than one zinc ion. Particular mention must be made of the large contribution of Kimura and co-workers to this area. 

The alternative regiochemical disposition of the diazo and tether of indole 260 failed to deliver any product upon addition of catalyst. Friedrichsen and co-workers (136) also applied this method to amine substituted tethers to generate polyaza-cyclic compounds (Scheme 4.70). The presence of the amino substituted furan subsequent to diazo-decomposition made it possible to cleave the ether bridge through the facility of the amino group formed to produce adduct 263. 

Coronands (1) and (2) are macrocyclic species which contain various heteroatoms as binding sites. The term coronates refers to the complexes. The polyaza macrocycles were the first macro-cyclic ligands to be studied. 

In 1978, we reported the repetitive synthesis of noncyclic and cyclic (so called nonskid chainlike ) polyaza compounds, which were the first examples of cascade molecules (Scheme 1). Since that time, dendrimers have gained widespread attention in organic, as well as in inorganic2,3 and physical chemistry.4 In 1992, De Gennes received the Nobel prize in physics for his studies on chaos and fractals. His results are relevant for the molecular design of cascade polymers especially in their three-dimensional growth. 

The 1 1 cyclization process has been used extensively for the synthesis of the polyaza-crowns. A typical example of the first type of 1 1 cycloaddition is the reactions of an a,w-diacid chloride with an a,o)-diamine to form a cyclic diamide. A second molecule of the diamine is generally used to trap the released hydrogen chloride (Dietrich et al., 1973). The preparation of N,N -... 

The simultaneous addition of the two starting materials over an extended time period is not convenient. Tabushi and coworkers found that high-dilution techniques were not required for the reaction of diesters (including malonates) with diamines to form the cyclic bis-amides (Tabushi et al., 1976, 1977). The cyclic diamides were reduced to form the polyaza-crowns. This method, along with the yV-tosyl method for ring closure, are the most common procedures for the preparation of peraza-crowns. The yields for these ester plus amine... 

The diester (or methylacrylate) cyclization reactions give the cyclic mono-, di-, or tetraamides. These materials must be reduced to provide the polyaza-crown compounds. The reduction process is usually carried out using diborane-THF or lithium aluminum hydride. The best results were obtained with a large excess of borane, however, a stable boron complex with the macrocycle often results. It is difficult to separate the macrocycle from the complex. Reduction of [12]N3 diamide with borane-THF always gave the stable complex. This problem was avoided by first forming N-tosyl[12]N,-diamide using the ester cyclization method followed by reduction with borane-THF and detosylation with HBr/phenol (Helps et al., 1989b). 

Tabushi and coworkers reported a general synthetic procedure to prepare the polyaza-crown compounds by treating a polyamine with the dimethyl ester of an oligoglycolic acid followed by reduction of the resulting cyclic diamide (method M-2) (Tabushi et al., 1976, 1977a, 1977b). This method uses readily... 

Terminal bis secondary amines can be cyclized with dihaloalkanes. There could be some template affect by alkali metal cations in the cyclization step even though the log K for the association of the alkali metal ions (except lithium) with a cyclic amine is low. In the building-block method to form the polyaza-crowns (methods 0-1 and 0-2), sodium, or potassium carbonate... 

A useful crab-like cyclization has been used to synthesize a variety of polyaza- and peraza-crowns. The crab-like reactants are bis-a-chloroamides, which are more reactive than a regular alkyl chloride but are not as dangerous as the nitrogen mustards. The starting bis-a-chloroamide was reacted with a primary amine in acetonitrile in the presence of sodium carbonate followed by reduction of the cyclic diamide to form the polyaza-crown (method 0-6) (Bradshaw et al., 1989b Krakowiak et al., 1989b). Good yields of the cyclic diamides were observed. 

Template-catalyzed syntheses of peraza-cyclophanes via the cyclic oligo Schiff bases are common (Mandal et al., 1987). The reaction of a dialdehyde and a diamine to form a cyclic oligo Schiff base is usually successful, but only a few of the di or tetra Schiff bases have been reduced to the cyclic amines. Some examples of these cyclic Schiff base-forming reactions have been reported, but this subject will not be reviewed extensively because this book covers the saturated polyaza-crowns and cyclophanes. Reducing the Schiff... 

Despite more than 20 years of research in macrocyclic chemistry, there are many cyclic systems that have not been prepared. In thinking about methods to prepare these new systems, one should be aware of the many unexpected reactions that can take place during the preparation of the polyaza-crown macrocycles. The most aggravating side reaction is the formation of unwanted five- or six-membered rings from linear starting materials. A -[2-(2-Chloro-ethoxy)ethyl]acetamide, for example, was developed to elongate polyamine chains (Bradshaw et al., 1990 Krakowiak and Bradshaw, 1991 Krakowiak et al., 1989b). The shorter A -(2-chloroethyl)acetamide, on the other hand. 

The past year has seen the publication of Comprehensive Organic Chemistry, one volume of which contains much information on the six-membered ring systems to be reviewed in this article a monograph on the chemistry of condensed pyrazines has also appeared. Reviews on 1,4-thiazines, l,3-benzothiazines," pyridazines, benzo[c]cinnolines, quinazolines, purines, pyrrolo[3,2-c]quino-lines, 1,10-phenanthroline and its complexes, polyaza-phenanthrenes, and 1,9- and 1,10-diaza-anthracenes have been published. Other specialist reviews are devoted to catalytic methods of obtaining pyridine bases pyridine N-oxides the stereochemistry of quinolizines, indolizines, and pyrrolizines benzothiazinone dioxides 2-quinazolones and their cyclic homologues (e.g. 

Beer, P.D. Cadman, J. Lloris. J.M. Martinez-Miner. R. Soto, J. Pardo, T. Marcos. M.D. Anion interaction with ferrocene-functionalised cyclic and open-chain polyaza and aza-oxa cycloalkanes. J. Chem. Soc.. Dalton Trans. 

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