Ferrocene and its derivatives

Nesmeyanov et a/.545 used a mixture of ferrocene, deuterated trifluoroacetic acid and benzene in the molar ratios 1 2 20 in a preliminary investigation of the reactivity of ferrocene and its derivatives. At 25 °C, rate coefficients were 1,620 x 10-7 (ferrocene) and 19.3 xlO-7 (acetylferrocene). In a subsequent publication by Alikhanov and Shatenshtein543 these values were altered to 1,600 x 10-7 and 1.5 x 10 7, respectively, and a value of 0.77 x 10"7 added for 1,1-diacetylferrocene. Under the same conditions, toluene gave a value of 0.3 x 10-7 so that the activating effects of these compounds relative to benzene can be approximately determined. 

Nesmeyanov et a/.546 have also measured the effects of substituents in deuteration of ferrocene by deuterated trifluoroacetic acid in dichloromethane at 25 °C. Rate coefficients were measured for ferrocene and its derivative in a range of such acid mixtures, the composition of which was omitted, and in some cases the rate of exchange for ferrocene was calculated on the basis of a linear relationship between log and —H0. Results including the calculated knl values are given in Table 161. It should be noted that, in discussing those results, the authors quoted the incorrect partial rate factors for dedeuteration of toluene arising from the use of the incorrect data for benzene (see p. 199). This should be taken into account... 

Numerous chemical reactions have been carried out on ferrocene and its derivatives.317 The molecule behaves as an electron-rich aromatic system, and electrophilic substitution reactions occur readily. Reagents that are relatively strong oxidizing agents, such as the halogens, effect oxidation at iron and destroy the compound. 

The electroactive units in the dendrimers that we are going to discuss are the metal-based moieties. An important requirement for any kind of application is the chemical redox reversibility of such moieties. The most common metal complexes able to exhibit a chemically reversible redox behavior are ferrocene and its derivatives and the iron, ruthenium and osmium complexes of polypyridine ligands. Therefore it is not surprising that most of the investigated dendrimers contain such metal-based moieties. In the electrochemical window accessible in the usual solvents (around +2/-2V) ferrocene-type complexes undergo only one redox process, whereas iron, ruthenium and osmium polypyridine complexes undergo a metal-based oxidation process and at least three ligand-based reduction processes. 

Since the first report on the ferrocene mediated oxidation of glucose by GOx [69], extensive solution-phase studies have been undertaken in an attempt to elucidate the factors controlling the mediator-enzyme interaction. Although the use of solution-phase mediators is not compatible with a membraneless biocatalytic fuel cell, such studies can help elucidate the relationship between enzyme structure, mediator size, structure and mobility, and mediation thermodynamics and kinetics. For example, comprehensive studies on ferrocene and its derivatives [70] and polypy-ridyl complexes of ruthenium and osmium [71, 72] as mediators of GOx have been undertaken. Ferrocenes have come to the fore as mediators to GOx, surpassing many others, because of factors such as their mediation efficiency, stability in the reduced form, pH independent redox potentials, ease of synthesis, and substitutional versatility. Ferrocenes are also of sufficiently small size to diffuse easily to the active site of GOx. However, solution phase mediation can only be used if the future biocatalytic fuel cell... 

Apart from electron promoters a large number of electron mediators have long been investigated to make redox enzymes electrochemically active on the electrode surface. In the line of this research electron mediators such as ferrocene and its derivatives have successfully been incorporated into an enzyme sensor for glucose [3]. The mediator was easily accessible to both glucose oxidase and an electron tunnelling pathway could be formed within the enzyme molecule [4]. The present authors [5,6] and Lowe and Foulds [7] used a conducting polymer as a molecular wire to connect a redox enzyme molecule to the electrode surface. 

When I- is titrated with Cu(Cl04)2 in AN, it is oxidized in two steps, I ->If and If ->I2. The formal potentials of the two steps are +0.396V and -0.248V vs Ag/Ag+, respectively. Many organic compounds, such as hydroquinone, ascorbic acid, ferrocene and its derivatives, allylamine, hydroxylamine, phenylhydrazine, thiourea and SH compounds, can also be titrated with Cu(II) in AN. Figure 4.9 shows the titration curves of tetramethylbenzidine (TMB) in AN [12]. In dry AN, TMB is oxidized in two steps as follows ... 

Reversible one-electron oxidation of ferrocene and its derivatives to cation radicals (so-called ferricenium cations) is a well-known reaction. The cation radical center is localized at the iron atom. In contrast to this statement, the hole transfers though conjugated systems were proven for the bis(ferrocenyl) ethylene cation radical (Delgado-Pena et al. 1983) and the cation radical of bis(fulvaleneiron) (LeVanda et al. 1976). Scheme 1-53 depicts these structures. 

Low-voltage mass spectrometry has been used to identify ferrocene and its derivatives, for by using an ionizing voltage of 8 eV only the molecular ion peaks are observed (44,189). Reed and Tabrizi studied the mass spectra... 

For the sake of completeness we have included in this section other reports concerning ferrocene and its derivatives, whether or not a heterocyclic system is involved. 

The chemistry of ferrocene and its derivatives form a significant subset of iron organometallic chemistry. Ferrocene is commercially available its chemistry will be discussed in Section 7. 

Now let me come back to primary substitutions at the ferrocene nucleus. Together with Vil chevskaya, we phosphorylated ferrocene and its derivatives to triferrocenylphosphine oxides [263, 264). An unusual reaction, discovered in collaboration with Perevalova and Yur eva, was the direct cyanation of ferrocene with hydrocyanic acid in the presence of ferric chloride [265,272). Initially, cyanide attacks the iron atom of the ferricinium cation, then the cyanide group transfers to the ring while the iron is simultaneously reduced. The reaction was termed by us as the ricochet (from the metal to the nucleus) substitution it may be applied to many substituted ferrocenes and to the ruthenocenium cation [273), and it is now the simplest route to ferrocene carboxylic acids through their nitriles. Further, ferrocene was studied in acid-medium reactions with oxo compounds. With aldehydes [274), the reaction was complicated by the transformation of ferro-cenylalkyl carbinol formed Initially via the carbonium ion, followed by transformation to a radical which, in its turn, was coupled to 1,2-bis-(ferrocenylalkyl)ethane (27.5). The reaction with acetone led to 2,2-di-ferrocenylpropane (276). 

How does ferrocene and its derivatives meet these constraints First, from a geometric point of view and as opposed to most known organic donors (or acceptors),... 

Ferrocene modified flexible polymeric electron transfer systems Ferrocene and its derivatives are readily available and commonly used organometalUc redox mediators, so it is quite natural that they were selected first to synthesize mediator modified polymeric electron transfer systems. Siloxane pol5uners are flexible but aqueous insoluble pol3nmers. As previously indicated, a flexible polymer backbone allows close contact between the redox center(s) of the enzyme and the mediator, and the water insoluble property of the polymer prevents not only redox polymer from leaching into bulk media but also prevents enzyme diffusion away fi-om the electrode surface by entrapping it in the polymer/carbon paste matrix. Therefore, ferrocene and... 

A.N. Nesmeyanov, N.A. Volkenau, and I.N. Bolesova, The interaction of ferrocene and its derivatives with aromatic compounds. Tetrahedron Lett. 1963, 25, 1725-1729. 

A particular feature of the mesogens of group 8 elements is the extensive liquid-crystal chemistry of ferrocene and its derivatives, and as such this subject is given its own subsection below. 

First examples of second-sphere coordination adduct between a CD and such organometallic complexes were observed with the ferrocene and its derivatives. Thus, Breslow was the first to report in 1975 that ferrocene forms a 1 1 adduct with the /3-CD in both A/T-dimethylformamide and dimethyl sulfoxide. Nevertheless, the first crystalline inclusion complexes of ferrocene and its derivatives were prepared by Harada and Takahashi in 1984. The inclusion complexes were obtained by direct addition of crystals of ferrocene or its derivatives into aqueous solutions of CD. The stoichiometry of the inclusion complexes was found to be dependent on the sizes of the CD. The /3-CD and y-CD formed 1 1 stoichiometric inclusion complexes whereas a-CD formed a 2 1 (CD guest) complex with ferrocene. From induced circular dichroism experiments, three structures were proposed for these adducts as shown in Figure... 

Ferrocene and its derivatives even mediate the enzymatic redox reactions of PQQ-dependent enzymes. As an example, the mediation of the enzymatic glucose dehydrogenation by PQQ-glucose dehydrogenase has been reported [140] the same enzyme also can use phenazines as electron acceptors [141]. 

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