Macrocyclic complex demetallation

Among complexes of the first row transition metals most often used as templates, copper(II) macrocyclic complexes demetallate least readily as the energy of vacant d-orbitals decreases along the d, d , d, d, d ion series [4, 44], In this case, reductive transmetallation may be used [4,44]. Thus, by treatment of the copper] II) complexes with metallic zinc or zinc amalgam, it is possible to replace Cu by Zn [52] (Scheme 1.4). 

Two interlocked macrocyclic ligands as in (15) are topologically related to the catenanes, whence the name catenand derives.34,186 187 These macrocycles complex a variety of metals, presumably in a tetrahedral geometry.34,186 The stabilizing effect of the catenand topology is evident in the observed redox stability of the nickel(I) complex186 as well as the reluctance toward demetallation, observed for the copper(I) complexes.187... 

One of the more interesting hole size effects arises when the metal ion successfully acts as a template, but is labilised in the macrocyclic complex that is formed. The consequence of this is that the metal ion acts as a transient template. The metal ion may be viewed as pre-organising the reactants to form the macrocyclic products, but then finding itself in an unfavourable environment after the cyclisation. The effect is best observed when a small metal ion is used as a template for a reaction that can only give one product (or at least, only one likely product). What happens to the metal ion when it finds itself in an environment that does not match up to its co-ordination requirements The most useful consequence would be labilisation of the metal ion, with resultant demetallation and formation of the metal-free macrocycle. This would overcome one of the major disad-... 

Wild and co-workers have obtained the trans-P2S2-donor macrocycle XIII via a template reaction on Ptn. Demetallation is achieved by treatment of the macrocyclic complexes with aqueous hydroxide and then aqueous potassium cyanide. Separation of the stereoisomers uses chromatography on silica gel, however, the yields of the P2S2-donor rings are very low. The 7-membered P,S-donor ring, XIV, is obtained as a by-product in 6% yield, while the BBr3 adduct of XIII is the dominant product, isolated in 76% yield.40... 

A major disadvantage of employing the template effect is the need to remove the template once the macrocycle has been formed, without destroying the product. This is not necessarily an easy task and is, in some cases, impossible. There are a number of effective demetallation strategies, depending on the stability of the metal-macrocycle complex (or more generally of the template-host complex). 

The in situ or template method, where the intervention of a metal ion directs the course of reaction towards cyclic rather than polymeric products. The product is usually a macrocyclic complex of the template metal used, and the macrocyclic cavity is normally of a size commensurate with the metal s ionic radius. While this technique has resulted in the isolation of many macrocycles which are not available by other means its main drawback is that demetallation to produce free ligand is not always possible often the macrocycles prove unstable in the unco-ordinated state. 

Generation of free macrocycles from their metal complexes The removal of a macrocycle from its coordinated metal ion is a frequent procedure in macrocyclic ligand synthesis - conditions for inducing such demetallations are now briefly discussed ... 

Synthesis. These macrocycles are prepared from seven-membered ring dinitrile complexes, 84a-84c (Scheme 17), which contain either methylene, sulfur or oxygen in the five position (129). These cyclic dinitriles are synthesized by alkylating maleonitrile dithiolate or derivatives thereof with the corresponding dihalide. The dinitriles 84a-84c can be cyclized in magnesium propoxide to form porphyrazines 85a (33%), 85b (19%), and 85c (27%) (Scheme 17), which can be demetalated with trifluoroacetic to form 86a-86c. Additionally, 86a has been remetalated with nickel (87a, 92%), copper (88a, 95%), and zinc (89a, 94%). The sulfur and oxygen derivatives 85b, 85c, 86b, and 86c are of low solubility and are not suitable for further manipulation. 

Analogously, complex 218 was prepared by mixed macrocyclization of 2,5-diiminopyrrolidine (213) with ferf-butylphenylpyrroline (68) in 19% yield. The free base (219) (95%) was obtained by demetalation of magnesium complex 218 with trifluoroacetic acid and subsequent remetalation of 219 with Ni(OAc)2 gave the corresponding nickel complex 220 in 98% yield. 

These electrodes modified with metal complexes could have been substitutes for expensive platinum if they had been usable under conditions compatible with requirements for efficient fuel cells. However, they are not stable, particularly in contact with acidic media, which results from demetallation. This is known since the early works with N4 macrocycles and heat treatment has been proposed to enhance the durability of the carbon... 

Before we obtained the X-ray structure determinations of both the knotted and unknotted dicopper(I) complexes, we could identify them after careful comparative H NMR and mass spectroscopy studies performed not only on the dinuclear complexes but also on their respective free ligands afforded by demetalation. Treatment of Cii2(m-43) + by a large excess of potassium cyanide led indeed quantitatively to a plain 43-membered macrocycle whereas an analogous treatment of Cii2(K-86r+ led to the free knot K-86 whose topological chirality could be demonstrated by NMR and mass spectroscopy (Figure 20). 

Rich and co-workers employed the intramolecular SNAr reaction of arene-ruthenium n-complexes in their total syntheses of K-13 (9) and OF4949-III (7). Treatment of tripeptide complex 27 with potassium ferf-butoxide gave 17-membered macrocycle 28, which was demetalated in acetonitrile to give cycloisodityrosine 29, a precursor to OF4949-III (7) (Scheme 8). 34 ... 

A logical extension of the condensation reactions which yield multidentate nitrogen donors is the formation of macrocyclic ligands. The preference of palladium for square planar coordination makes it an ideal metal for the formation of complexes of these ligands. Thus palladium porphyrins are very stable and resistant to demetallation.281 Both 14- and 16-atom macrocycles have been used to form complexes. The ligand l,8-dihydro-5,7,12,14-tetramethyl-dibenzo[b,i][l,4,8,ll]tetraaza[14]annulene reacts with [PdCl2(PhCN)2] to yield the complex (46). 

The original Jager-type complexes can be deacylated by treatment with acid demetallation follows and the free macrocycles can be isolated (Scheme 20).134 These can be converted into iron(II) complexes with acetonitrile coordinated in the axial positions. However, these are unstable in the example with 15- and 16-membered rings and undergo cyclization as a result of carbanion attack on the coordinated acetonitrile (Scheme 21).134 136 A similar reaction occurs with the cobalt... 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

Model compound studies have shown the importance of porphyrin macrocycle basicity, resulting from electron-withdrawing substituents and metal ligands, on the reducibility and susceptibility of the central metal to reaction. Similar insight into the differences in relative basicity of vanadium- and nickel-containing complexes found in petroleum may therefore be valuable in rationalizing the observed effects and predicting demetallation activity. 

Nickel furochlorophin can be demetallated by treatment with concentrated sulfuric acid giving in good yield (60%) the free base the structure of which has also been resolved by X-ray crystallography (Fig. 35c). The macrocycle is more planar than its nickel complex (maximum deviation about 1 A) and can be easily converted into its Cu2 + and Zn2 + derivatives. 

These complexes of catenands are remarkably stable. However, treatment of the complex with cyanide results in demetallation and the formation of the free catenane, in which the two macrocyclic ligands are still interlocked. There is a conformational change upon demetallation and in the solid state the rings have slipped . It is not trivial to estab-... 

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