Substitution on Ferrocene

The reaction is carried out under argon in a 2-liter three-necked flask fitted with a mechanical stirrer, reflux condenser, 250-ml pressure-equalizing addition funnel, and gas inlet and outlet. After purging with argon, the flask is charged with a solution of 89 g (0.48 mole) of ferrocene in 1 liter of dry tetrahydrofuran. The solution is next heated to 45°, and there is added dropwise with stirring, 155 ml (0.29 mole) of an -butyllithium solution (15% in heptane-pentane, 2 1, Foote Mineral Co.) during a period of 75 minutes. The resultant solution is maintained at 45° for an additional 2 hours, then is cooled to —77° by means of an external Dry Ice-chloroform bath. 

To the cooled solution is added dropwise with stirring, a solution of 64 g (0.48 mole) of -amyl nitrate in 100 ml of dry tetrahydrofuran during a period of 1 hour. The solution is finally allowed to warm to room temperature overnight. Work-up is carried out by adding an excess of ice-acetic acid, diluting with water, and extracting the aqueous solution several times with ether. The ether extracts are washed thoroughly 

Chromatography of the mixture on Activity I basic alumina yields, successively, ferrocene nitroferrocene (11.6g, 17%), mp 129.5-130.5° (recrystallized from pentane) and 1, T-dinitroferrocene (0.130 g), mp 207-209° (dec). 

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It should be noted that Lay and coworkers [12] have made a comparative study of the electrochemical behavior of ferrocene, 1,2,3,4,5-pentamethylferrocene and decamethylferrocene in 29 solvents and have concluded that increasing substitution on ferrocene reduces the solvent dependence of the ferrocene potential. Accordingly, they recommend that decamethylferrocene be adopted as a preferred reference standard for electrochemical measurements in nonaqueous... 

However, electrophilic aromatic substitution on ferrocene presents two complications (1) its susceptibility to one-electron oxidation, which precludes halogenation, nitration, or direct (H SO ) sulfonation and (2) competition between the Fe and the ring as the initial site of electrophilic attack. It is now clear from H NMR spectroscopy of the product of the protonation of ferrocene with a superacid at -122 °C that protonation of ferrocene initially occurs endo. The detailed structure of the protonation product has not been unambiguously established, but calculations imply that the proton is associated at least as much with the cyclopentadienyl carbons as with the iron. ... 

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. 

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... 

Like all the other acidity functions, W0(H) equals pH in dilute aqueous solution. In strong acids, this function should be a logarithmic measure of the proton activity as long as the normal potential of the redox system, ferrocene-ferricinium, is constant. This was, however, not the case in very strong acid solutions because ferrocene underwent protonation. Other electrochemical pH indicators have been proposed, such as quinine-hydroquinone or semiquinone-hydroquinone, the basicity of which can be modified by substitution on the aromatic ring. These electrochemical indicators have been used with success by Tremillon and co-workers48 for acidity measurements in anhydrous HF and HF containing superacids. 

Ferrocenylphosphines, chiral. Hayashi et al.1 have prepared a large number of chiral ferrocenylophosphines, which have planar chirality owing to 1,2-unsymmetrical substitution on the ferrocene group. In addition, one of the substituents contains a chiral carbon atom. The most interesting phosphines have amino or hydroxyl groups in the side chain. These phosphines, in combination with transition metals, can promote highly efficient enantioselective reactions. 

Fig. 23. Effect of successive ethyl group substitution in ferrocene on the >7Fe Mossbauer quadrupolar splitting values.184...

Continuing advances in the theoretical treatment of metallocenes and substituted derivatives can be anticipated. Despite the historical difficulties with molecular orbital calculations on ferrocene, the problems are now recognized to stem from failure to account for electron correlation effects. New approaches to addressing this issue, coupled with inevitable increases in computing power, should make more metallocenes with substituted groups systems amenable to accurate calculation. More realistic predictions of donor ability, and thus better estimates of their effects in nonlinear optical (NLO) systems, will be possible. 

The possibility of carrying out typical aromatic electrophilic substitution chemistry, such as Friedel-Crafts acylation, on ferrocene led to the synthesis of decaethylferrocene (Scheme 20) (88) as well as perethylated Cp-man-ganese tricarbonyls (59). A metallation/Me2S2 reaction sequence of a perchloro Cp ligand was also employed in the preparation of functionally... 

Togni s synthetic route to a planar chiral (trimethylsilyl group on ferrocene) and central chiral (asymmetric carbon in the NHC-Cp alkyl linker) carbene ligand starts from a central chiral aminomethyl ferrocene (see Figure 5.29) [9]. Lithiation and subsequent reaction with trimethylsilyl chloride introduces planar chirality on ferrocene. Quartemisation of the dimethylamino group with methyl iodide enables reaction with imidazole to the double Fc substituted imidazolium salt which can then be deprotonated to the free carbene with potassium rerf-butylate. 

There are a number of examples of chiral ferrocene derivatives prepared by reaction of substituted cyclopenta-diene anions with FeCl2 or a monocyclopentadienyl iron species rather than using the strategy of introduction and modification of a side chain on ferrocene itself. Addition... 

From the microwave studies of different substituted ferrocene compounds, correlations between properties of the substituents and structural changes were established. It was noted that the carbon-iron bond distance in -qS CsHs-Fe is much more sensitive to substitution on the cyclopentadienyl ligand than the C-C bond distances of the C5H5 ring. This is summarized in Table 2. A linear correlation of the gas phase structural parameter r(Fe-Cp) and the electronegativity of the... 

The ratio of ferrocene-modified siloxane subunits to unsubstituted siloxane subunits rrv.n ratio) was varied as was the length (a ) of the alkyl side chain onto which the ferrocene moiety was attached as shown in Fig. 3.3. The electrode containing co-polymer with m n ratio of 1 1 or 1 2 was the more efficient electron relay systems. The ferrocene-modified homopolymer on the other hand loses flexibility due to steric hindrance caused by the side chain substitution by ferrocene, preventing efficient electron transfer from the enzyme to the electrode. The length of the alkyl side chain onto which the ferrocene moiety is attached was also found to influence the electron transfer efficiency of the electron relay system. Maximal current density was measured... 

Figure 5-12 Electrophilic Substitution with Acylium Ion on Ferrocene 116...

Since the original observation (443) of the oxidation of ferrocene to the ferrocenium ion ( ° = 0.31 V, 0.2 M LiC104 in MeCN) (444), the formal potentials of well over 100 derivatives have been determined. Numerous studies assessing the effect of substitution on E° have been reported tabulated data and a discussion of the significance of the observed trends are available elsewhere (445, 446). As expected, donor substituents render the compound more easily oxidized so that, for example, [Fe(M-CsMe )2] has an ° value of -0.12 V in MeCN (447). 

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