Acceptor-substituted ferrocenium salts as strong, single-electron oxidants: synthesis, electrochemistry, theoretical investigations, and initial synthetic application

A series of mono- and 1,1'-diheteroatom-substituted ferrocene derivatives as well as acylated ferrocenes was prepared efficiently by a unified strategy that consists of selective mono- and 1,1'-dilithiation reactions and subsequent coupling with carbon, phosphorus, sulfur and halogen electrophiles. Chemical oxidation of the ferrocene derivatives by benzoquinone, 2,3-dichloro-5,6-dicyanobenzoquinone, AgPF(6) , or 2,2,6,6-tetramethyl-1-oxopiperidinium hexafluorophosphate provided the corresponding ferrocenium salts. The redox potentials of the synthesized ferrocenes were determined by cyclic voltammetry, and it was observed that all new ferrocenium salts have stronger oxidizing properties than standard ferrocenium hexafluorophosphate. An initial application of selected derivatives in an oxidative bicyclization revealed that they mediate the transformation under considerably milder conditions than ferrocenium hexafluorophosphate. Quantum chemical calculations of the reduction potentials of the substituted ferrocenium ions were carried out by using a standard thermodynamic cycle that involved the gas-phase energetics and solvation energies of the contributing species. A remarkable agreement between theory and experiment was found: the mean average deviation amounted to only 0.030?V and the maximum deviation to 0.1?V. This enabled the analysis of various physical contributions to the computed reduction potentials of these ferrocene derivatives, thereby providing insight into their electronic structure and physicochemical properties.     

Synthesis and structural studies of 1,1'-bis-amino-functionalized ferrocenes, ferrocene salts, and ferrocenium salts

Having isolated and characterized a series of sodium cyclopentadienide salts, we have synthesized a number of 1,1'-bis-amino-functionalized ferrocenes, 1,1'-bis-amino-functionalized ferrocene salts, and 1,1'-bis-amino-functionalized ferrocenium salts. Among these are the first crystallographically characterized examples of cyclopentadienyl units containing (piperidin-N-ylethyl)- and (pyrid-2-ylmethyl)cyclopentadienyl side chains. In the cases of some of the ferrocenes, ferrocene salts, and ferrocenium salts, there are some interesting structural features in the solid state. These include C-H...N and C-H...pi cloud interactions as well as N-H...O and N-H...F hydrogen bonds.     

Ferrocenderivate LX. Rationelle synthesen der ferrocen-1,1′-dicarbonsäure sowie von isomeren methyl-, phenyl-ferrocen- und [3]ferrocenophan-mono- und -1,1′-di-carbonsäuren

Mono- or 1,1′-bis-acylation of ferrocene, its mono and 1,1′-dimethyl and phenyl derivatives and of [3]ferrocenophane with o-chlorobenzoyl chloride/AlCl₃ affords the corresponding (isomeric) chlorobenzoyl ferrocenes in high yields which can be separated by column, layer or high pressure liquid chromatography and in the case of the monomethylferrocene monoketones also by crystallization. The cleavage of the (o-chlorobenzoyl)ferrocenes by potassium-t-butoxide (and traces of water) yields the corresponding ferrocene carboxylic acids except for the α-phenyl derivatives in almost quantitative yields, thus offering a very convenient access to these acids. In all cases the isomer distribution and thereby the relative site reactivities were determined.     

Nickel(I)‐Komplexe mit 1,1′‐Bis(phosphino)ferrocenen als Liganden

Nickel(I) Complexes with 1,1′‐Bis(phosphino)ferrocenes as Ligands The thermically stable monomeric Nickel(I) complexes [(d^tbpf)Ni(acac)] ( 1 ) and [(dⁱppf)NiCl] ( 2 ) were synthesized and characterized by elemental analyses, EPR spectroscopy, and by X‐ray crystal structure analyses of single crystals (d^tbpf: 1,1′‐bis(di‐tertbutylphosphino)ferrocene; dⁱppf: 1,1′‐bis(diisopropylphosphino)ferrocene). 1 is formed by reduction of Ni(acac)₂ with triethylaluminium in the presence of d^tbpf, together with the nickel(0) complex [(d^tbpf)Ni(C₂H₄)]. 1 contains a Ni^I atom surrounded of two O‐ and two P donor atoms in a distorted tetrahedral coordination. 2 was obtained by reduction of [(dⁱppf)NiCl₂] with NaBH₄. In 2 the nickel(I) atom adopts trigonal planar coordination.     

The electrochemistry of some ferrocene derivatives: redox potential and substituent effects

Fifteen ferrocene derivatives I–IX (four of which have been prepared for the first time: II, IIIf, V and VIII) have been prepared by Friedel–Crafts acetylation, Claisen condensation, Michael reaction, and ring closure by hydrazine hydrate. The anodic behaviour of these compounds has been studied by cyclic voltammetry at a platinum electrode in an aprotic solvent. All these substituted ferrocenes exhibit a reversible one‐electron oxidation reduction centred at each iron centre, and the effect of substituents on the half‐wave oxidation potential is discussed in terms of their electronic properties. Linear correlations have been observed between these potentials and the Hammett σ_x constant for the substituents. Cyclic voltammetry has been carried out for ferrocene derivatives IIIa, V and IX. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of Nonsymmetrically N,N′‐Diaryl‐Substituted 4,4′‐Bipyridinium Salts with Redox‐Tunable and Titanium Dioxide (TiO2)‐Anchoring Properties

A general method for the synthesis of so far unknown nonsymmetrically substituted N‐aryl‐N′‐aryl′‐4,4′‐bipyridinium salts is presented (Scheme 1). The common intermediate in all procedures is N‐(2,4‐dinitrophenyl)‐4,4′‐bipyridinium hexafluorophosphate ( 1 ⋅ ). For the synthesis of nonsymmetric arylviologens, 1 ⋅ was arenamine‐exchanged by the Zincke reaction, and then activated at the second bipyridine N‐atom with 2,4‐dinitrophenyl 4‐methylbenzenesulfonate. The detailed preparation of the six N‐aryl‐N′‐aryl′‐viologens 21 – 26 is discussed (Scheme 2). The generality of the procedure is further exemplified by the synthesis of two nonsymmetrically substituted N‐aryl‐N′‐benzyl‐ (see 11 and 12 ), and seven N‐aryl‐N′‐alkyl‐4,4′‐bipyridinium salts (see 28 – 34 ) including substituents with metal oxide anchoring and redox tuning properties. The need for these compounds and their usage as electrochromic materials, in dendrimer synthesis, in molecular electronics, and in tunable‐redox mediators is briefly discussed. The latter adjustable property is demonstrated by the reduction potential measured by cyclic voltammetry on selected compounds (Table).     

Solution‐Processable n‐Type Organic Field‐Effect Transistor (OFET) Materials Based on Carbonyl‐Bridged Bithiazole and Dioxocyclopentene‐Annelated Thiophenes

A series of electronegative π‐conjugated compounds composed of carbonyl‐bridged bithiazole and alkyl‐substituted dioxocyclopenta[b]thiophene were synthesized as a candidate for solution‐processable n‐type organic semiconductor materials and characterized on the basis of photophysical and electrochemical properties. Cyclic voltammetry measurements showed that the first half‐wave reduction potentials of these compounds are between −0.97 and −1.14 V versus ferrocene/ferrocenium, which corresponds to lowest unoccupied molecular orbital energy levels between −3.83 and −3.66 eV. Thanks to hexyl or dodecyl groups in the molecules, the compounds are sufficiently soluble to realize the fabrication of their thin films through a spin‐coating method. As a result, the prepared organic field‐effect transistors based on these newly developed compounds exhibited n‐channel characteristics not only under vacuum but also in air, and the best field‐effect electron mobility observed under vacuum was 0.011 cm² V⁻¹ s⁻¹ with an on/off ratio of 10⁸ and a threshold voltage of 16 V.     

Synthesis and biological evaluations of mono‐ and bis‐ferrocene uracil derivatives

Mono‐ ( 3a – 3e and 4a – 4e ) and bis‐ferrocene ( 5a – 5e and 6a – 6e ) conjugated 5‐substituted uracil derivatives that are bridged by 1,2,3‐triazole linker were synthesized. The impact of ferrocene unit and spacer between ferrocene and triazole on radical scavenging potency was observed. Bis‐ferrocenyl uracil derivatives exhibited better antiproliferative activities than their mono‐ferrocenyl analogs. Bis‐ferrocenyl methyl‐ ( 5b ) and halogen‐substituted ( 5e , 6c , and 6d ) uracil derivatives showed pronounced and selective cytostatic activities on colon adenocarcinoma (CaCo‐2) and Burkitt lymphoma (Raji) cells, with higher potency and selectivity than the reference drug 5‐fluorouracil. Generation of reactive oxygen species (ROS) in CaCo‐2 and Raji cells when treated with compounds 5b , 5e , and 6d was observed. Bis‐ferrocenyl 5‐chlorouracil 6c induced significant disruption in mitochondrial membrane potential that is accompanied by activation of apoptosis in CaCo‐2, Raji, and acute lymphoblastic leukemia (CCRF‐CEM) cells, while 6d caused mitochondrial dysfunction and apoptosis induction in CaCo‐2 and Raji cells. Potent antiproliferative activity of 6c and 6d could be associated with mitochondrial membrane potential disruption accompanied by apoptosis induction. Our findings highlighted 6c and 6d with potent and selective antiproliferative activity on CaCo‐2, Raji, and CCRF‐CEM cells that may be associated with targeting cancer cell mitochondria, as a molecular target.     

Ferrocenophanes with Interannular Nitrogen–Gallium Bridges. 1,3,2‐Diazagalla‐[3]Ferrocenophanes and an 1‐Aza‐3‐Azonia‐2‐Gallata‐[3]Ferrocenophane. Synthesis and Structure

1,1′‐Bis(trimethylsilylamino)ferrocene reacts with trimethyl‐ and triethylgallium to give the μ‐[ferrocene‐1,1′‐diyl‐bis(trimethylsilylamido)]tetraalkyldigallanes. These were converted into the 1,3‐bis(trimethylsilyl)‐2‐alkyl‐2‐pyridine‐1,3,2‐diazagalla‐[3]ferrocenophanes, of which the ethyl derivative was characterized by X‐ray structural analysis. Treatment of gallium trichloride with N,N′‐dilithio‐1,1′‐bis(trimethylsilylamino)ferrocene affords μ‐[ferrocene‐1,1′‐diyl‐bis(trimethylsilylamido)]tetrachlorodigallane along with bis(trimethylsilyl)‐2,2‐dichloro‐1‐aza‐3‐azonia‐2‐gallata‐[3]ferrocenophane as a side product, and both were structurally characterized by X‐ray analysis. The solution‐state structures of the new gallium compounds and aspects of their molecular dynamics in solution were studied by NMR spectroscopy (¹H, ¹³C, ²⁹Si NMR).     

Synthesis of mono-amino-functionalised ferrocene, ferrocene salts and ferrocenium salts

A number of mono-amino-functionalised ferrocenes, ferrocene salts and a mono-amino-functionalised ferrocenium salt have been synthesised and characterised. This represents a novel method of accessing these important classes of molecules. In the cases of some of the ferrocene salts, there are some interesting structural features in the solid state. These include N-H...O and N-H...F hydrogen bonds.     

Efficient Synthesis of 1,4‐Bis‐heteroatom‐substituted Tetraselanylbenzenes via 1,4‐Dilithiation of Hexaselanylbenzene and Investigation on Their Electronic Properties

We successfully synthesized mono‐ and bis‐substituted polyselanylbenzenes 3 and 5 via mono‐ and dilithiation of hexakis(phenylselanyl)benzene ( 1 ), respectively. Introduction of various heteroatom functionalities into hexaselanylbenzene changed the electronic properties dependent on the σ‐symmetric circular orbitals that were formed by the interactions between neighboring heteroatoms. In the cyclic voltammetry and theoretical studies on bis‐heteroatom‐substituted benzenes 5 , the extent of the interactions in the circular orbitals with σ‐symmetry affected the stability of the cationic species of 5 . This study would give insight into the molecular design for new σ‐delocalized systems and inspire the development of tuning electronic properties of benzene derivatives by σ‐type orbital interactions derived from heteroatom functionalities.     

CH‐Directed Anion–π Interactions in the Crystals of Pentafluorobenzyl‐Substituted Ammonium and Pyridinium Salts

Simple pentafluorobenzyl‐substituted ammonium and pyridinium salts with different anions can be easily obtained by treatment of the parent amine or pyridine with the respective pentafluorobenzyl halide. Hexafluorophosphate is introduced as the anion by salt metathesis. In the case of the ammonium salt 4 , water co‐crystallisation seems to suppress effective anion–π interactions of bromide with the electron‐deficient aromatic system, whereas with salts 5 and 6 such interactions are observed despite the presence of water. However, due to asymmetric hydrogen‐bonding interactions with ammonium side chains, the anion of 5 is located close to the rim of the pentafluorophenyl group (η¹ interaction). In 6 the CH–anion hydrogen bonding is more symmetric and fixes the anion on top of the ring (η⁶). A similar structure‐controlling effect is observed in case of the 1,4‐diazabicyclo[2.2.2]octane derivatives 7 . Here the position of the anion (Cl, Br, I) is shifted according to the length of the weak CH–halide interaction. The hexafluorophosphate 7 d reveals that this “non‐coordinating” anion can be located on top of an aromatic π system. In the methyl‐substituted pyridinium salts 9 and 10 different locations of the bromide anions with respect to the π system are observed. This is due to different conformations of the mono‐ versus disubstituted pyridine, which leads to different directions of the weak, but structurally important, H_Me? Br bonds.     

Excited State Intramolecular Proton Transfer in Ethynyl‐Extended Regioisomers of 2‐(2′‐Hydroxyphenyl)benzothiazole: Effects of the Position and Electronic Nature of Substituent Groups

Although the organic dyes based on excited state intramolecular proton transfer (ESIPT) mechanism have attracted significant attention, the structure‐property relationship of ESIPT dyes needs to be further exploited. In this paper, three series of ethynyl‐extended regioisomers of 2‐(2′‐hydroxyphenyl)benzothiazole (HBT), at the 3′‐, 4′‐ and 6‐positions, respectively, have been synthesized. Changes in the absorption and emission spectra were correlated with the position and electronic nature of the substituent groups. Although 4′‐ and 6‐substituted HBT derivatives exhibited absorption bands at longer wavelengths, the keto‐emission of 3′‐substituted HBT derivatives was found at a substantially longer wavelength. The gradual red‐shifted fluorescence emission was found for 3′‐substituted HBT derivatives where the electron‐donating nature of substituent group increased, which was opposite to what was observed for 4′‐ and 6‐substituted HBT derivatives. The results derived from the theoretical calculations were in conformity with the experimental observations. Our study could potentially provide experimental and theoretical basis for designing novel ESIPT dyes that possess unique fluorescent properties.     

Unexpected formation of 1,2‐dihydro‐2‐azolyl‐and azinylisoquinolines by the reduction of the corresponding isoquinolinium salts with sodium borohydride in methanol

The reduction of different 2‐azolyl‐and azinylisoquinolinium salts with sodium borohydride in methanol was studied. Surprisingly, contrary to what is found in the literature 1,2‐dihydroisoquinoline derivatives were obtained. Their formation was attributed to the electron withdrawing character of the heterocyclic ring in position 2 of the isoquinolinium moiety. This was corroborated by synthesis and reduction of differently substituted 2‐phenyl‐ and 2‐methylisoquinolinium salts.     

N‐(4‐Biphenylmethyl)imidazoles as Potential Therapeutics for the Treatment of Prostate Cancer: Metabolic Robustness Due to Fluorine Substitution?

3,3′,5,5′‐ And 2,2′,6,6′‐tetrafluoro‐substituted 1‐[(1,1′‐biphenyl]‐4‐yl)methyl]‐1H‐imidazoles were synthesized as inhibitors of 17α‐hydroxylase‐C17,20‐lyase (P450 17, CYP 17). P450 17 is the key enzyme of androgen biosynthesis. Its inhibition is a novel therapeutic approach for treatment of prostate cancer. To increase the so‐far insufficient in vivo lifetime of such compounds, the metabolically sensitive positions were blocked by F‐substitution. The meta‐ and ortho‐F‐substituted compounds were prepared by selective metallation or halogen/metal permutation reactions performed on symmetrically substituted 1,1′‐biphenyls. Compared with the halogen‐free compounds, the ortho‐F‐substituted derivatives did not match the activity, whereas the meta‐F‐substituted isomers equaled or surpassed the latter.     

Bridged ferrocenes : VII. Synthesis of di- and tri-bridged ferrocenes with pentamethylne chains

Double or successive bridge-enlargement reactions were used on appropriate α-ketones followed by reduction to prepare 1,1′-pentamethyleneferrocene, VIII, 1,1′,3,3′-bis(pentamethylene)ferrocene, XX, and 1,1′,2,2t?,4,4′-tris(penta-methylene)ferrocane, XXX. The bridge-enlarging reactions are discussed, and the PMR spectral behavior of the polybridged ferrocenes is briefly discussed.     

Liquid‐crystalline azobenzene‐containing ferrocene‐based polymers: study on synthesis and properties of main‐chain ferrocene‐based polyesters with azobenzene in the side chain

Ferrocene‐based polymers are characterized by their electrochemical activity, good redox properties, thermal, photochemical stability, and liquid crystallinity, and thus they have various applications in different fields. A comprehensive investigation on the synthesis and properties of three novel main‐chain ferrocene‐based polyesters with azobenzene in the side chain (MFPAS) was carried out. The main‐chain ferrocene‐based polyester, poly(N‐phenyldiethanolamine 1,1′‐ferrocene dicarboxylate (PPFD), was synthesized via the solution polycondensation reaction of 1,1′‐ferrocenedicarbonyl chloride with phenyldiethanolamine (PDE). The novel MFPAS were synthesized via the post‐polymerization azo‐coupling reaction of PPFD with three different 4‐substituted anilines including 4‐nitroaniline, 4‐aminobenzoic acid, and 4‐aminobenzonitrile to produce 4‐nitrophenylazo‐functionalized‐PPFD (PPFD‐NT), 4‐carboxyphenylazo‐functionalized‐PPFD (PPFD‐CA), and 4‐cyanophenylazo‐functionalized‐PPFD (PPFD‐CN), respectively. All the synthesized polymers were characterized by ¹H NMR spectroscopy, Fourier transform infrared spectroscopy, and UV–visible spectroscopy. In addition, powder X‐ray diffraction patterns were measured for the synthesized polymers. The photoisomerization of the MFPAS was studied. The thermal properties of the MFPAS were studied using thermogravimetric analysis and differential scanning calorimetry. PPFD‐CA and PPFD‐CN were found to be more thermally stable than PPFD‐NT. Finally, the liquid‐crystalline properties of PPFD and the MFPAS were examined using polarized optical microscope. It was found that all the polymers possessed nematic phases and exhibited textures with schlieren disclinations. Copyright © 2012 John Wiley & Sons, Ltd.     

Ferrocene Derivatives Bearing one and two Isocyanato,Isothiocyanato and Isoselenocyanato Substituents

Isocyanato‐ ( 1a ), 1,1′‐di(isocyanato)‐ ( 2a ), isothiocyanato‐ ( 1b ), 1,1′‐di(isothiocyanato)‐ ( 2b ), isoselenocyanato‐ ( 1c ) and 1,1′‐di(isoselenocyanato)ferrocene ( 2c ) were prepared and studied by ¹H, ¹³C and ¹⁴N NMR spectroscopy. Isocyanatoferrocene ( 1a ) trimerizes upon chromatography on alumina to give 3a . The molecular structures of 2c and 3a were determined by X‐ray analysis, and almost undistorted ferrocene‐like structures were found in both cases.     

A Highly Efficient Synthesis of Optically Active Ferrocenylethylamines via Hydride Reduction of Chiral Ferrocenylketimines

Due to using (R)‐ or (S)‐α‐methylbenzylamine as a chiral auxiliary, and low‐temperature regime for reduction of the intermediate ferrocenyl‐mono‐ or 1,1′‐bis‐ketimines, the corresponding secondary mono‐ or 1,1′‐bis‐amines were prepared with high diastereoselectivity. Removal of the α‐methylbenzyl group afforded the optically active primary mono‐ and bis‐ferrocenylethylamines in high yields. The absolute configuration of (R,R)‐ 3a and (S,S)‐ 3b was determined by X‐ray single crystal diffraction.     

Substituted 2,2′‐Bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyl Complexes of Zinc

The condensation reaction of 2,2′‐diamino‐4,4′‐dimethyl‐6,6'‐dibromo‐1,1′‐biphenyl with 2‐hydroxybenzaldehyde as well as 5‐methoxy‐, 4‐methoxy‐, and 3‐methoxy‐2‐hydroxybenzaldehyde yields 2,2′‐bis(salicylideneamino)‐4,4′‐dimethyl‐6,6′‐dibromo‐1,1′‐biphenyl ( 1a ) as well as the 5‐, 4‐, and 3‐methoxy‐substituted derivatives 1b , 1c , and 1d , respectively. Deprotonation of substituted 2,2′‐bis(salicylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyls with diethylzinc yields the corresponding substituted zinc 2,2′‐bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyls ( 2 ) or zinc 2,2′‐bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐6,6′‐dibromo‐1,1′‐biphenyls ( 3 ). Recrystallization from a mixture of CH₂Cl₂ and methanol can lead to the formation of methanol adducts. The methanol ligands can either bind as Lewis base to the central zinc atom or as Lewis acid via a weak O–H ··· O hydrogen bridge to a phenoxide moiety. Methanol‐free complexes precipitate as dimers with central Zn₂O₂ rings.