Azamacrocycles

The macrocycles are generally characterized by their extreme resistance to dissociation, (see however Prob. 6). The kinetics of acid-promoted dissociation of an extensive series of Ni(II) and Cu(II) complexes, (ML) have been reported,The general rate law is (see Prob. 2, Chap. 2)  

Alternatively, they can arise as a result of the rate-determining reaction of H+ with a reactive form of ML (ML ) which might be an isomer originating, for example, from the chiral NH centers (Sec. 7.9.). 

The formation of Cu(cyclam) by reaction of cyclam with a large variety of copper complexes (CuL +) is interesting  

Provided that the stability of the CuL + is not very high (log A 10), the value of k is similar to that for. There is an inverse relationship of log k with log K (CuL +) with more stable complexes (Fig. 8.7). It is also worthy of note that although the main cyclam species at the pH of the study (4-9) is cyclamHj, the reactive species is cyclamH. Ref. 130. 

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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. 

Synthesis and metal complexes of azamacrocycles with pendant arms having additional ligating groups. T. A. Kaden, Top. Curr. Chem., 1984,121,157-179 (54). 

Because acid-base properties on the inside of molecules will be discussed, those macrocycles (and related compounds) which possess functional groups hanging on the outside of the ring, e.g. lariat ethers or substituted polyazamacrocyles (Kaden, 1984 Gokel, 1991, 1992), will be mentioned only briefly. From the large group of azamacrocycles only a small fraction will be discussed in detail because the basic functionality rarely is located in a defined i/j-position. 

Countless macrocycles containing basic functionalities have been synthesized and, for a large number of compounds, values have been determined (Patai, 1980 Gokel and Korzenowski, 1982 Kaden, 1984 Kimura, 1985 Lindoy, 1989 Vogtle, 1989, 1991 Gokel, 1991, 1992 Izatt et al., 1991, 1992 Dietrich et al., 1993). Usually, the basic function in these macrocycles is a nitrogen atom the compounds are (poly)azamacrocycles. But in azacrowns like [1] or cyclams [2] the /n-orientation of the lone pair at the nitrogen atom is not assured. Murakami et al. (1991) synthesized the... 

Many azamacrocycles, like cyclam [2] for instance, contain more than one nitrogen atom and therefore possess more than one pK. Therefore, in the discussion of the basicity of these compounds, it is not only the in- and OMt-orientation of the lone pair or the proton, respectively, that has to be considered. There is also an influence of the first on the second, third, etc. protonation. The developing Coulomb repulsions are very sensitive to the charge separation. In 15-membered rings this phenomenon has been investigated in detail (Arnaud-Neu et al., 1979). 

Catalysis ferrocene [13], Ni-azamacrocyclic complex [14], metal-porphyrin [15]... 

C-functionalization of azamacrocycles is in general more difficult to achieve than N-functional-ization. The latter has been developed to an extent that macrocycles carrying side chains with various ligating groups are accessible, and Ni11 complexes can be prepared with high selectivity and predisposition for high thermodynamic and kinetic stability. 

Kimura and co-workers have made a major contribution to this area with dizinc azamacrocycle complexes characterized including phosphate ester X-ray structures.445,446 They have also studied ligands with pendent alcohol groups.44... 

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. 

Electrocatalytic dehalogenation of organohalides has also been performed in heterogeneous conditions, at a graphite electrode coated by a poly(acrylic acid) film grafted with the nickel(II) tetra-azamacrocyclic complex (20).292... 

Fig. 28. Mannosylated clusters built around the azamacrocycle cyclam.196 197...

B. Konig, T. Fricke, A. Wa/imann, U. Krallmann-Wenzel, and T. K. Lindhorst, y-Mannosvl clusters scaffolded on azamacrocycles Synthesis and inhibitory properties in the adhesion of type 1 fimbriated Escherichia coli to guinea pig erythrocytes, Tetrahedron Lett., 39 (1998) 2307-2310. 

Fig. 18. 3-Hydroxy,2-pyridinone siderophore mimics based on an azamacrocycle central ring structure.

It is well-established that the molecular and electronic structures of metal complexes of azamacrocycles are greatly affected upon N-alkylation (197). This is mainly due to two factors (a) the decrease of the ligand field strength and (b) the increase in the steric requirements upon going from a secondary to a tertiary amine donor function (251). To examine whether the properties of the dinuclear amine-thiophenolate complexes are affected by the N-alkyl substituents, analogous complexes of the... 

This kind of argument may also be invoked for some Cr(III)-azamacrocyclic complexes. In this regard, it is noted that the macrocycle effect (which is essentially an enhanced chelate effect) stabilizes metal ions entrapped in the cavity formed by macrocyclic organic ligands... 

Another important class of iron compounds is that of the tetra-azamacrocycle ligands. As a typical example we can cite the Fe(II) complexes of the 14-membered macrocycles illustrated in Scheme 10, which have different degrees of unsaturation. 

Figure 3.8. Titration of the fluorescence of anthrylazamacrocydes 5c and 5e (10 and 100 fiM, respectively) by added metal ions. The three experiments shown are ( ) titration of 5c in pH 12 buffer with Zn(Cl04)2. (o) titration of 5c in pH 12 buffer withZnfClO and 1 M NaC104 (a) titration of 5c in pH 6 buffer with HgfClOah. The chelation-enhanced quenching (CHEQ) of 5e by Hg(ll) ion was accomplished at pH 6 because, while the azamacrocycle is sufficiently deprotonated at this pH to bind...

The study of the complexing of macrocycle ligands should be considered for its intrinsic importance rather than for its value in illuminating the mechanism of substitution. Kinetic (but much more thermodynamic °) data are available for the reactions of the different macrocycle ligand types, shown in Fig. 4.5, including azamacrocycles,crown ethers and cryp-tands, and porphyrins. ... 

Appropriately placed groups on the porphyrin periphery can aid considerably the incorporation of metal ions into the ring. The porphyrin shown, Hjtmpp, 13 reacts rapidly with Co(II), Ni(II), Cu(II) in dmf/H20. The rate data indicate that an initial adduct is formed which allows the metal to more easily transfer into the porphine ring. See also Ref. 129 for a similar behavior with an azamacrocycle. 

Imine metathesis has continued to be a popular exchange reaction for DCLs. Various groups have found novel systems in which the reaction can be applied, as well as interesting ways to halt the equilibration. For example, Wessjohann and coworkers have demonstrated that Ugi reactions can efficiently halt equilibration of an imine DCL, combining an irreversible diversification process with areversible library selection [24]. Xu and Giusep-pone have integrated reversible imine formation with a self-duplication process [25], and Ziach and Jurczak have examined the ability of ions to template the synthesis of complex azamacrocycles [26]. The mechanistically related reactions of hydrazone [27] and oxime [28] exchange have also been explored as suitable foundations for DCL experiments. 

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