Ferrocene Carboxaldehyde Research Articles

Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones

The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.

A Ferrocene Derivative Redox Sensor for Mercuric Ion: Synthesis and Electrochemical Study

The sensitive detection of mercuric ion is currently a task of prime importance for environmental or biological concerns. To develop sensitive mercuric ion sensors, various receptors consisting of a mercuric ion recognition unit and a probe exhibiting physical responses upon the coordination of mercuric ion have been reported. Among them, ferrocene derivatives are often applied to redox sensors due to the unique electrochemical property. In the presence of mercuric ions, the ion-recognition event induces the significant electrochemical changes at the redox active ferrocenyl moiety. In addition, the ease of functionalization of ferrocene leads to the synthesis of assorted ferrocene derivatives possessing the metal ion binding unit. Recently, our research has focused on the development of new ferrocene complexes as redox sensors for the mercuric ion detection. In this account, we report the synthesis and electrochemical analysis of 2-(ethylthiomethyl)-N-ferrocenylmethyl aniline in the presence of various metal ions, illustrating this ferrocene complex as a sensitive and selective redox sensor for the detection of mercuric ion. As shown in Scheme 1, 1-(bromomethyl)-2-nitrobenzene 1 was treated with ethanthiol with sodium metal to afford ethyl(2-nitrobenzyl)sulfide 2 in 72% yield. Subsequent reduction of compound 2 provided 2-(ethylthiomethyl)aniline 3 which reacted with ferrocene carboxaldehyde 4, forming imine 5. Due to the instability of compound 5 on the silica gel, compound 5 was not isolated and subject to the reduction conditions using NaB(OAc)3H to give 2-(ethylthiomethyl)-N-ferrocenylmethyl aniline 6 in 80% yield. With compound 6 in hand, electrochemical properties of compound 6 were evaluated in the absence of any metal ion via cyclic voltammetry (CV). In the range of 0.0 to 2.0 V, two oxidation peaks appear at 0.41 V and 1.04 V during the anodic scan, and no reduction peak was observed in the reverse scan, shown in Figure 1. When the anodic scan was reversed at 0.80 V subsequent to the 1 oxidation at 0.41 V, the reversible reduction peak at 0.30 V was detected, with the peak separation of ca. 0.11 V. Accordingly, the first oxidation peak at 0.41 V was speculated to be the oxidation of the ferrocene entity of compound 6. The second oxidation

Thermal Immobilization of Ferrocene Derivatives on (111) Surface of n-Type Silicon: Parallel between Vinylferrocene and Ferrocenecarboxaldehyde

Monolayers attached to a Si(111) surface through Si-C-C or Si-O-C covalent bonds were prepared by the thermally activated reaction (150 degrees C) of vinylferrocene (VFC) or ferrocenecarboxaldehyde (FCA) molecules with hydrogen-terminated Si(111) substrate in order to compare their reactivities. The resulting monolayers gave a couple of redox waves on voltammograms due to ferrocenyl moieties tethered at the surface. The voltammetric quantification revealed that the growth of electrochemically active layers was terminated within 5 h and the final surface coverages of the active ferrocenyl moieties were 58% and 16% for VFC- and FCA-based monolayers, respectively, indicating that the aldehyde molecule is less reactive. X-ray photoelectron spectroscopy and ellipsometry, however, gave an indication that the growth of the VFC layer did not self-terminate and proceeded beyond a monolayer, while this overgrown part of the layer was not electrochemically active.

1-[Ferrocenyl(hydroxy)methyl]-1,7-dicarba-closo-dodecaborane: Synthesis and X-ray crystal structure

The synthesis and molecular structure of the novel 1-[ferrocenyl(hydroxy)methyl]-1,7-dicarba-closo-dodecaborane (1) is described. Compound 1 was synthesized from reaction of m-carborane and ferrocene carboxaldehyde using n-butyllithium (n-BuLi) or tetrabutylammonium fluoride (TBAF) in THF in 45% and 36% yield, respectively. Compound 1 consists of a ferrocene molecule tethered to m-carborane through a methylhydroxy bridge. The crystal structure of 1 was determined by single crystal X-ray diffraction analysis. Crystal data: 1 [Fe(C5H5)(C5H4-CH2O-1,7-C2B10H12)], formula weight = 359.17, crystallized in orthorhombic system, space group Pna2 1 with a=19.698(4) A, b=10.709(2) A, c=8.520(2) A, and V=1797.3(7) A3 and Z=4. Refined to R 1=0.043 for 4124 observed reflections with I/σ>2σ(I). The compound was crystallized as racemic twins in a ratio of 73(2)/27(2). The unsubstituted Cp ring was disordered and modeled as two conformations in a 53(3)/47(3) ratio. Intermolecular hydrogen bonding was observed from the hydrogen of the meta-carbon on the carborane cluster towards the hydroxyl oxygen.

Marcus theory of outer-sphere heterogeneous electron transfer reactions: High precision steady-state measurements of the standard electrochemical rate constant for ferrocene derivatives in alkyl cyanide solvents

The High Speed Channel Electrode is used to precisely measure the standard electrochemical rate constants under steady state conditions for the oxidation of substituted ferrocenes in alkyl cyanide solvents. First, the oxidation of ferrocene itself is kinetically analysed in the solvents: acetonitrile, propionitrile, butyronitrile and valeronitrile. Second, the oxidation kinetics of the ferrocene derivatives: ferrocene carboxylic acid, decamethyl ferrocene, bis(diphenylphosphino) ferrocene, ferrocene carboxaldehyde, α-hydroxyethyl ferrocene, t-butyl ferrocene, dimethyl aminomethyl ferrocene, dimethyl ferrocene and n-butyl ferrocene are measured in acetonitrile for comparison to ferrocene. The rate of electron transfer in the different alkyl cyanides is shown to depend on the longitudinal dielectric relaxation times of the solvents in accordance with solvent dynamic theory, whilst the electron transfer rates of the different ferrocene derivatives in acetonitrile are shown to depend on the hydrodynamic radii of the molecules. In both cases, a measured k 0 = 1.0 ± 0.2 cm s −1 for ferrocene oxidation in acetonitrile shows an excellent fit to the theoretical dependences.

XPS and electrochemical studies of ferrocene derivatives anchored on n- and p-Si(1 0 0) by Si–O or Si–C bonds

High-coverage functionalization of H-terminated n- and p-Si(1 0 0) with vinylferrocene ( VFC) and ferrocenecarboxaldehyde ( FCA) has been obtained by wet chemistry methods, via the formation of a covalent bond between silicon atoms and the carbon ( VFC) or the oxygen ( FCA) termination of the molecules. The resulting functionalized electrodes have been analyzed by XPS, before and after cyclic voltammetry and capacitance–voltage measurements in an electrochemical cell. The very high quality of the hybrid species Si–CH 2–CH 2–C 5H 4–Fe 2+–C 5H 5, resulting from VFC, has been certified by the negligible presence of silicon oxide and ferrocenium ions, and by the correct carbon/iron atomic ratio, accounting for the molecular species. The hybrid produced from FCA, Si–O–CH 2–C 5H 4–Fe 2+–C 5H 5, presents a higher amount of silica, carbon and ferrocenium, as a consequence of the higher temperature of the functionalization procedure and of the higher reactivity of FCA. The use of two closely similar redox molecules has allowed to compare the behaviour of the Si–C–Y vs. Si–O–Y bond (Y being the redox moiety), with respect to their electrochemical reactivity in an organic solution. Both hybrids behave similarly on n- and p-Si substrates, in terms of redox potentials, stability to more than 1000 voltammetric cycles, linearity of the current intensity with the scan rate. The vinyl derivative, however, showed a faster and more reversible electron transfer kinetics than the carboxaldehyde derivative and an enhanced stability to long-term electrochemical experiments. VFC/p-Si is the first reported ferrocene derivative anchored to monocrystalline silicon via a C–Si bond. It is also the only large-area hybrid capacitor, to date, to be frequency-independent up to several hundred Hz, having a redox capacitance of 10 −4 F cm −2, the highest reported so far for a monolayer on a Si(1 0 0) face.

Natural cocrystallisation of two ferrocenyl compounds

In the reaction of H2N–NC(CH3)–C(CH3)N–OH (L) with ferrocenecarboxaldehyde (FCAL) in methanol, the 1∶1 condensate 1a of L and FCAL crystallises with the 2∶1 condensate 1b of FCAL and hydrazine to form the cocrystal 1. In 1, 1a∶1b = 2∶1. The cocrystal is characterised by single crystal X-ray crystallography, 1H NMR and cyclic voltammetry. 1 is centrosymmetric (spacegroup P21/c). While 1b can be prepared easily in pure form, it seems that 1a cannot crystallise in pure form.

Second harmonic generation in ferrocene based hydrogen bonded assemblies

Supramolecular assemblies formed by electron donors and acceptors might possess very large optical nonlinearity, even larger than the sum of the constituents if they form noncentrosymmetric networks. To probe this hypothesis we have functionalized barbituric acid, by condensing it with ferrocene carboxaldehyde to give 1, a hydrogen bond donor–acceptor–donor (H DAD). This molecule complements the hydrogen bond donor acceptor sites of 2,6-diaminopyridine ( 2) which is a hydrogen bond acceptor–donor–acceptor (H ADA). 2,6-Diaminopyridine was further functionalized with acetyl ferrocene to give 3, which forms complexes with 1. Complex formation was studied using nuclear magnetic resonance spectroscopy. The second order nonlinear optical (NLO) response of these hydrogen bonded assemblies has been probed by hyper Rayleigh scattering (HRS) measurements and was found to be maximum when 1 was mixed with five equivalents of 3. A plausible explanation for the formation of 1:5 complex was given on the basis of control experiments with 4, a methylated analog of 1, and the addition of a strong hydrogen bond acceptor solvent, methanol.

Organometallic dyes: Part 1. Synthesis of orange to cyan dyes based on donor–conjugated–acceptor chromogenes using ferrocene as the donor group

AbstractA novel series of organometallic donor–conjugated–acceptor dyes derived from ferrocene as the donor group have been synthesized via the Knoevenagel reaction of ferrocene carboxaldehyde and various active methylene compounds to give a range of dyes ranging from orange to blue–green in color. The most bathochromic dye is that derived from dialkyl thiobarbituric acid and the least is that derived from the tetralone. The dyes showed an unusual negative solvatochromism as the solvent polarity increased. All dyes synthesized are expected to have some non‐linear optical properties, as evidenced from the pronounced solvatochromism. Copyright © 2001 John Wiley & Sons, Ltd.

Synthesis and nonlinear optical properties of a range of 1-ferrocenyl(2 -(4-alkyl)pyridiniumyl)ethylene iodides

The preparation of a range of compounds of general formula FcCHCHC 5H 4N +X, where X=C n H 2 n+1 ( n=1–5, 10 or 18) and O −, was achieved via condensation of the relevant picolinium iodide with ferrocene carboxaldehyde. The spectroscopic properties of these materials were shown to be very similar, however the SHG, measured by the Kurtz powder technique, showed that increasing the alkyl chain above three carbons resulted in a dramatic loss of SHG efficiency. The O − compound also yielded very little SHG.

Novel conducting polyaniline bearing functional groups

A copolymer formed from aniline and o-aminobenzylamine (ABA) was electrochemically synthesized from a solution of ABA and aniline with a mole ratio of 85:15. Its properties were studied by cyclic voltammetry. Relative conductivity measurements have been carried out showing that the copolymer's conductivity can be switched in the same way as that of poly(aniline) (PANI); they also indicate the presence of primary amino groups that allow a later derivatization. Ferrocene carboxaldehyde (FeCp 2CHO) was coupled to the copolymer showing the presence of primary amino groups. This modified polymer also has switching conductivity properties.

Organostannoxanes and Cyclophosphazenes as Scaffolds for Multi-Ferrocene Assemblies

The reactions of n-butylstannonic acid and di n-butyltinoxide with ferrocene monocarboxylic acid have been studied. In the former reaction a hexameric compound, [n-BuSn(O)OC(O)C5H4FeC5H5]6 has been isolated in a quantitative yield. In the latter reaction a tetrameric compound [{n-Bu2SnO2C(C5H4FeC5H5}2O}]2 has been isolated. In contrast to the drum like structure of the former compound, the latter has a ladder like arrangement. Both [n-BuSn(O)OC(O)C5H4FeC5H5]6 and [{n-Bu2SnO2C(C5H4FeC5H5)}2O]2 are electro-chemically robust and show a single oxidation peak in the cyclic voltammetric experiment corresponding to the simultaneous oxidation of six and four ferrocene substituents respectively. The hydrazine substituted cyclophosphazenes, N3P3[N(Me)NH2]6, gem-N3P3Ph2[N(Me)NH2]4, and gem-N3P3(O2C12H8)2[N(Me)NH2]2, are readily condensed with ferrocene carboxaldehyde, C5H5FeC5H4CHO, to afford the corresponding cyclophosphazenes linked to the ferrocenyl moiety through the hydrazone linkage, N3P3[N(Me)N=CHC5H4FeC5H5]6, gem-N3P3Ph2[N(Me)N=CHC5H4FeC5H5]4, and gem-N3P3(O2C12H8)2]N(Me)N=CHC5H4FeC5H5]2.

Synthetic ferrocenic mefloquine and quinine analoguesas potential antimalarial agents

A few years ago we proposed a strategy for the synthesis of new ferrocene-chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic ferrocenyl moieties. Now, this strategy has been applied to the antimalarial amino-alcohols class to afford new potentially active analogues of mefloquine and quinine bearing a substituted ferrocenic group. The pathway used for the synthesis of the mefloquine analogues includes the coupling of an aminomethyl substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the other hand, the synthesis of quinine analogues was ensured by the ‘inverse’ reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The configurations of each diastereoisomer were unambiguously determined by spectroscopic data. The mechanistic interpretations were fully discussed. Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial activity than mefloquine and quinine themselves. Comparing optical isomers, those isomers dissimilar to ferrocenyl derivatives presented better antimalarial activities than those similar to ferrocenyl.

Ferrocenecarboxaldehyde labeled DNA probe for the study on DNA damage and protection.

A ferrocenecarboxaldehyde (FCA) labeled DNA probe is used for the first time in the study of DNA damage and protection. The electrochemically active reagent FCA was labeled successfully on to a denatured calf-thymus DNA by 1-ethyl-3- (3-dimethyl-aminopropyl) carbodiimide (EDC). The FCA labeled DNA probe was used to hybridize with the sample DNA sequence accumulated on the surface of a graphite electrode. The anodic peaks of the FCA bound to the double-stranded DNA (dsDNA) by differential pulse voltammetry (DPV) were used for the detection of DNA damage and protection. Thiourea, sodium benzoic acid and isopropanol can decrease DNA damage by hydroxyl radicals, and their protection efficiencies are discussed.

Electrochemical labeled DNA probe for the detection of sequence-specific DNA

An electrochemical labeled DNA probe for the detection of sequence-specific DNA is discussed. The denatured calf-thymus DNA was successfully labeled with the electrochemical active reagent ferrocenecarboxaldehyde (FCA) by 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC). This FCA labeled DNA probe is used to hybridize with the sample DNA sequence accumulated on the surface of a graphite electrode. Only the complementary sequence (cDNA) can form a double-stranded DNA (dsDNA) with the FCA labeled DNA probe. The anodic waves of the FCA bound to the double-stranded DNA (dsDNA) by differential pulse voltammetry (DPV) are used for the detection of cDNA. The anodic peak currents ( i pa) of FCA are related to the concentration of cDNA sequence between 1.0×10 −8 and 5.0×10 −6 mol l −1. The detection limit is 5×10 −9 mol l −1( S/ N=3). The probe showed high sensitivity and selectivity.

Studies on Ferrocene Immobilized Sol-Gel Glasses and Its Application in the Construction of a Novel Solid-State Ion Sensor

Two new sol-gel glass systems with immobilized ferrocene are developed using two different types of sol-gel precursors. System (1) is developed using ferrocene carboxaldehyde and a mixture of two silanes (3-aminopropyltriethoxy silane and 2-(3,4-epoxycyclohexyl)-ethyltrimethoxy silane). System (2) is developed using ferrocene monocarboxylic acid and a mixture of 3-glycidoxypropyltrimethoxysilane and trimethoxysilane. The surfaces of the sol-gel glasses are analyzed based on scanning electron microscopy (SEM). The electrochemistry of ferrocene in system 1 and system 2 is characterized based on cyclic voltammetry. System 1 shows capacitive CV at slow scan rate whereas system 2 shows good reversible electrochemistry of ferrocene. The potentiometric response of the ferrocene immobilized sol-gel glass (system 1) is studied in 10 mM Tris-HCl buffer pH 7.0. A reproducible potential difference of system 1 to the order of –30 mV is recorded for 2 months with respect to a double junction SCE reference electrode. An ion sensing membrane is assembled over the ferrocene immobilized sol-gel glass using plasticized PVC matrix membrane containing dibenzo-18-crown-6. A typical potentiometric response of the ion sensor is reported. The response of the ion-sensor shows better response time, high reproducibility and relatively better slope for potassium analysis as compared to earlier reported solid-state K+ ion-sensor based on dibenzo-18-crown-6 neutral carrier. The reproducibility, detection limit and relative response of the ion sensor to Na+ and NH4+ ions are reported.

Synthesis and electrochemistry of ferrocenemethylamine and its conjugated acid. Crystal structure of ferrocenemethylammonium chloride

Ferrocenemethylamine ( 2) is conveniently synthesized by reductive ammination of ferrocene carboxaldehyde ( 1) in methanolic solution. The crystal structure of ferrocenemethylamine hydrochloride ( 3) is reported. In the solid state, 3 possesses a layered N–H⋯Cl–H-bonded network, resulting in the formation of 4- and 8-membered rings of alternating nitrogen and chlorine atoms, with an interlayer separation of 9.17 Å. The one-electron oxidation potentials of 2 and 3 in nine solvents are reported (CHCl 3, MeCN, MeOH, acetone, DMF, THF, nitrobenzene, EtOH, iPrOH). The present results have been used to evaluate the effects of different solvent parameters, such as the solvent polarizability and the solvent dielectric constant, on the redox properties of 2 and 3. The redox properties of 3 depend on the dielectric constant ε of the solvent.

Synthesis of ferrocene derivatives with π-extended conjugation

Synthesis of ( E)-1-ferrocenyl-2-( p-iodophenyl)ethene was carried out by means of the Wittig reaction between the p-iodobenzyl triphenylphosphonium ylid and the ferrocene carboxaldehyde, satisfactory as a mixture of E/Z isomers. Isomerization Z → E was induced by iodine—NBS in quantitative yield. The X-ray molecular structure of this ( E)-isomer indicates that the molecules are linked by charge transfer complexation between the iodine atom and the cyclopentadiene ring. The conjugation of the molecule of l-ferrocenyl-2-( p-iodophenyl)ethene was expanded to the ( Z,Z)- and ( E, E)-1,4-di[1-ferrocenyl-2( p-iodophenyl)ethenyl]biphenyl and to the ( Z,Z)- and ( E,E)-1,4-di(l-ferrocenyl-2-( p-phenylethenyl)-1,3-butadiyne, both as centrosymmetric structures.

A practical synthesis of ethynylferrocene from ferrocene carboxaldehyde: structure of 1,4-diferrocenyl-1,3-butadiyne

Ethynylferrocene was satisfactoryly obtained by a Wittig reaction between ferrocene carboxaldehyde and chloromethylentriph-enylphosphonium ylid to give an E/ Z mixture of 2-chloro-1-ferrocenylethene. Both isomers were isolated pure by chemical methods. Reaction of the isomers mixture with n-butyllithium allowed ethynylferrocene to be obtained in good yield. The method was applied in one pot giving the ethynylferrocene and ( E/ Z)-1,4-diferrocenyl-but-1-en-3-yne as a secondary product. Oxidative coupling to 1,4-difeerrocenyl-1,3-butadiyne has been carried out in quantitative yields. A single-crystal analysis of t he diyne was carried out, but the compound is unreactive in solid state.

Enantiospecific conversion of ( S)-alanine to ( R)-α-methyl phenylalanine

Based on the strategy of self-reproduction of chirality, a practical enantiospecific conversion of ( S)-alanine to ( R)-α-methyl phenylalanine via the N-pivaloyl 1,3-oxazolidin-5-one derived from ferrocene carboxaldehyde and sodium alaninate is described.