| |||
| |||
| Names | |||
|---|---|---|---|
| Preferred IUPAC name Ferrocene[1] | |||
Other names
| |||
| Identifiers | |||
| |||
| ChEBI | |||
| ChemSpider |
| ||
| ECHA InfoCard | 100.002.764 | ||
| UNII | |||
| |||
| |||
| Properties | |||
| C10H10Fe | |||
| Molar mass | 186.04 g/mol | ||
| Appearance | light orange powder | ||
| Odor | camphor-like | ||
| Density | 1.107 g/cm3 (0 °C) 1.490 g/cm3 (20 °C)[2] | ||
| Melting point | 172.5 °C (342.5 °F; 445.6 K)[4] | ||
| Boiling point | 249 °C (480 °F; 522 K) | ||
| Insoluble in water, soluble in most organic solvents | |||
| logP | 2.04050[3] | ||
| Structure | |||
| D5h (eclipsed) D5d (staggered) | |||
| Sandwich structure with iron centre | |||
| Hazards | |||
| NFPA 704 (fire diamond) | |||
| NIOSH (US health exposure limits): | |||
PEL (Permissible) | TWA 15 mg/m3 (total) TWA 5 mg/m3 (resp)[5] | ||
REL (Recommended) | TWA 10 mg/m3 (total) TWA 5 mg/m3 (resp)[5] | ||
IDLH (Immediate danger) | N.D.[5] | ||
| Related compounds | |||
Related compounds | |||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Ferrocene is anorganometallic compound with the formulaFe(C5H5)2. The molecule is acomplex consisting of twocyclopentadienyl rings sandwiching a centraliron atom. It is an orange solid with a camphor-like odor thatsublimes above room temperature, and is soluble in most organic solvents. It is remarkable for its stability: it is unaffected by air, water, strong bases, and can be heated to 400 °C without decomposition. In oxidizing conditions it can reversibly react with strong acids to form the ferroceniumcationFe(C5H5)+2.[7]
The first reported synthesis of ferrocene was in 1951. Its unusual stability puzzled chemists, and required the development of new theory to explain its formation and bonding. The discovery of ferrocene and its manyanalogues, known asmetallocenes, sparked excitement and led to a rapid growth in the discipline oforganometallic chemistry.Geoffrey Wilkinson andErnst Otto Fischer, both of whom worked on elucidating the structure of ferrocene, later shared the 1973Nobel Prize in Chemistry for their work on organometallic sandwich compounds. Ferrocene itself has no large-scale applications, but has found more niche uses in catalysis, as a fuel additive, and as a tool in undergraduate education.
Ferrocene wasdiscovered by accident twice. The first known synthesis may have been made in the late 1940s by unknown researchers atUnion Carbide, who tried to pass hot cyclopentadiene vapor through an iron pipe. The vapor reacted with the pipe wall, creating a "yellow sludge" that clogged the pipe. Years later, a sample of the sludge that had been saved was obtained and analyzed by Eugene O. Brimm, shortly after reading Kealy and Pauson's article, and was found to consist of ferrocene.[7][8]
The second time was around 1950, when Samuel A. Miller, John A. Tebboth, and John F. Tremaine, researchers atBritish Oxygen, were attempting to synthesize amines from hydrocarbons andnitrogen in a modification of theHaber process. When they tried to react cyclopentadiene with nitrogen at 300 °C, at atmospheric pressure, they were disappointed to see the hydrocarbon react with some source of iron, yielding ferrocene. While they too observed its remarkable stability, they put the observation aside and did not publish it until after Pauson reported his findings.[7][9][10] Kealy and Pauson were later provided with a sample by Milleret al., who confirmed that the products were the same compound.[8]
In 1951,Peter L. Pauson andThomas J. Kealy atDuquesne University attempted to preparefulvalene ((C5H4)2) by oxidative dimerization ofcyclopentadiene (C5H6). To that end, they reacted theGrignard compoundcyclopentadienyl magnesium bromide indiethyl ether withferric chloride as an oxidizer.[7] However, instead of the expected fulvalene, they obtained a light orange powder of "remarkable stability", with the formulaC10H10Fe.[8][11]
Pauson and Kealy conjectured that the compound had two cyclopentadienyl groups, each with a single covalent bond from the saturated carbon atom to the iron atom.[7] However, that structure was inconsistent with then-existing bonding models and did not explain the unexpected stability of the compound, and chemists struggled to find the correct structure.[10][12]
The structure was deduced and reported independently by three groups in 1952.[13]Robert Burns Woodward,Geoffrey Wilkinson, et al. observed that the compound was diamagnetic and nonpolar.[14] A few months later they described its reactions as being typical of aromatic compounds such asbenzene.[15] The name ferrocene was coined by Mark Whiting, a postdoc with Woodward.[16]Ernst Otto Fischer and Wolfgang Pfab also noted ferrocene's diamagneticity and high symmetry. They also synthesizednickelocene andcobaltocene and confirmed they had the same structure.[17] Fischer described the structure asDoppelkegelstruktur ("double-cone structure"), although the term "sandwich" came to be preferred by British and American chemists.[18] Philip Frank Eiland and Raymond Pepinsky confirmed the structure throughX-ray crystallography and later byNMR spectroscopy.[10][19][20][21]
The "sandwich" structure of ferrocene was shockingly novel and led to intensive theoretical studies. Application ofmolecular orbital theory with the assumption of a Fe2+ centre between twocyclopentadienide anionsC5H−5 resulted in the successfulDewar–Chatt–Duncanson model, allowing correct prediction of the geometry of the molecule as well as explaining its remarkable stability.[22][23]
The discovery of ferrocene was considered so significant that Wilkinson and Fischer shared the 1973Nobel Prize in Chemistry "for their pioneering work, performed independently, on the chemistry of the organometallic, calledsandwich compounds".[24]
Mössbauer spectroscopy indicates that the iron center in ferrocene should be assigned the +2 oxidation state. Each cyclopentadienyl (Cp) ring should then be allocated a single negative charge. Thus ferrocene could be described as iron(II) bis(cyclopentadienide),Fe2+[C5H−5]2.
Each ring has six π-electrons, which makes themaromatic according toHückel's rule. These π-electrons are then shared with the metal via covalent bonding. Since Fe2+ has sixd-electrons, the complex attains an18-electron configuration, which accounts for its stability. In modern notation, this sandwich structural model of the ferrocene molecule is denoted asFe(η5-C5H5)2, whereη denoteshapticity, the number of atoms through which each ring binds.
The carbon–carbon bond distances around each five-membered ring are all 1.40 Å, and all Fe–C bond distances are 2.04 Å. The Cp rings rotate with a low barrier about the Cp(centroid)–Fe–Cp(centroid) axis, as observed by measurements on substituted derivatives of ferrocene using1H and13Cnuclear magnetic resonance spectroscopy. For example, methylferrocene (CH3C5H4FeC5H5) exhibits a singlet for the C5H5 ring.[25]
From room temperature down to 164 K,X-ray crystallography yields the monoclinic space group; the cyclopentadienide rings are a staggered conformation, resulting in a centrosymmetric molecule, withsymmetry group D5d.[19] However, below 110 K, ferrocene crystallizes in an orthorhombic crystal lattice in which the Cp rings are ordered and eclipsed, so that the molecule has symmetry group D5h.[26] In the gas phase,electron diffraction[27] and computational studies[28] show that the Cp rings are eclipsed. While ferrocene has no permanent dipole moment at room temperature, between 172.8 and 163.5 K the molecule exhibits an "incommensurate modulation", breaking the D5 symmetry and acquiring an electric dipole.[29]
In solution, eclipsed D5h ferrocene was determined to dominate over the staggered D5d conformer, as suggested by bothFourier-transform infrared spectroscopy andDFT calculations.[30]
The first reported syntheses of ferrocene were nearly simultaneous. Pauson and Kealy synthesised ferrocene using iron(III) chloride and cyclopentadienyl magnesium bromide.[11] Aredox reaction produces iron(II) chloride. The formation of fulvalene (the intended outcome), does not occur.[8]
Another early synthesis of ferrocene was by Milleret al.,[9] who treated metallic iron withgaseous cyclopentadiene at elevated temperature.[31] An approach usingiron pentacarbonyl was also reported.[32]
More efficient preparative methods are generally a modification of the originaltransmetalation sequence using either commercially availablesodium cyclopentadienide[33] or freshlycracked cyclopentadiene deprotonated withpotassium hydroxide[34] and reacted with anhydrous iron(II) chloride in ethereal solvents.
Modern modifications of Pauson and Kealy's original Grignard approach are known:
Even someamine bases (such asdiethylamine) can be used for the deprotonation, though the reaction proceeds more slowly than when using stronger bases:[33]
Direct transmetalation can also be used to prepare ferrocene from some other metallocenes, such asmanganocene:[35]
Ferrocene is anair-stable orange solid with a camphor-like odor.[36] As expected for a symmetric, uncharged species, ferrocene is soluble in normal organic solvents, such as benzene, but is insoluble in water. It is stable to temperatures as high as 400 °C.[36]
Ferrocene readilysublimes, especially upon heating in a vacuum. Its vapor pressure is about 1Pa at 25 °C, 10 Pa at 50 °C, 100 Pa at 80 °C, 1000 Pa at 116 °C, and 10,000 Pa (nearly 0.1atm) at 162 °C.[37][38]
Ferrocene is anaromatic substance.Electrophiles typicallysubstitute onto, rather thanadd to, the cyclopentadienyl ligands. For example, a common undergraduate experiment performsFriedel-Crafts acylation withacetic anhydride and aphosphoric acid catalyst. Just as this reagent mixture convertsbenzene toacetophenone, it converts ferrocene toacetylferrocene.[39]
In the presence ofaluminium chloride, Me2NPCl2 and ferrocene react to give ferrocenyl dichlorophosphine,[40] whereas treatment withphenyldichlorophosphine under similar conditions formsP,P-diferrocenyl-P-phenyl phosphine.[41]Vilsmeier-Haack formylation usingformylanilide andphosphorus oxychloride givesferrocenecarboxaldehyde.[42]
Unsubstituted ferrocene undergoes aromatic substitution more easily than benzene, because electrophiles can attack the metal ion before rearranging to theWheland intermediate.[43] Thus ferrocene reacts with the weak electrophileP4S10 to form a diferrocenyl-dithiadiphosphetane disulfide.[44]Mannich conditions suffice to iminylate ferrocene untoN,N-dimethylaminomethylferrocene.[citation needed]
Superacidic protonation does not complete aromatic substitution, but rather traps the unrearrangedbent intermediatehydrido salt, [Cp2FeH]PF6.[45] Strongly oxidizing electrophiles, such ashalogens andnitric acid, neither rearrange to a Wheland intermediate nor coordinate to iron, instead generating ferrocenium salts (see§ Redox chemistry).[43]
In accordance withcluster compound theory, ferrocene's rings behave as a single delocalized π system. Electronic perturbations to one ring propagate to the other. For example, introduction of adeactivating aldehyde group on one ring inhibits formylation of the other ring as well.[42]
Ferrocene readily metallates. Ferrocene reacts withbutyllithium to give1,1′-dilithioferrocene, which is a versatilenucleophile. In combination with butyllithiium,tert-butyllithium produces monolithioferrocene.[46] Likewise ferrocenemercurates to give ferrocendiyl dimercuriacetate.[47]
Further reaction gives thenitro, halo-, and borono derivatives.[47]
Ferrocene undergoes a one-electron oxidation at around 0.4 V versus asaturated calomel electrode (SCE), becomingferrocenium.[12] Although the nomenclature is not internally consistent, ferrocenium is abbreviatedFc+.[48] This reversible oxidation has been used as standard in electrochemistry as Fc+/Fc = 0.64 V versus thestandard hydrogen electrode,[49] however other values have been reported.[50][51]Ferrocenium tetrafluoroborate is a common reagent.[52] The remarkably reversible oxidation-reduction behaviour has been extensively used to control electron-transfer processes in electrochemical[53][54] and photochemical[55][56] systems.
Substituents on the cyclopentadienyl ligands alters the redox potential in the expected way: electron-withdrawing groups such as acarboxylic acid shift the potential in theanodic direction (i.e. made more positive), whereas electron-releasing groups such asmethyl groups shift the potential in thecathodic direction (more negative). Thus,decamethylferrocene is much more easily oxidised than ferrocene and can even be oxidised to the corresponding dication.[57] Ferrocene is often used as aninternal standard for calibrating redox potentials in non-aqueouselectrochemistry.
Monosubstituted ferrocenes have the formula(C5H5)Fe(C5H4R). These derivatives are often referred to asferrocenyl (abbreviatedFc) compounds.[48] Examples includeferrocenyl aldehyde (FcCHO),ferrocenyl carboxylic acid (FcCO2H), and ferrocenyl methanol (FcCH2OH). When the substituent is chiral, then the entire molecule is chiral.
Disubstituted ferrocenes can exist as either 1,2-, 1,3- or 1,1′- isomers, none of which are interconvertible. Ferrocenes that are asymmetrically disubstituted on one ring are chiral – for example [CpFe(EtC5H3Me)]. Thisplanar chirality arises despite no single atom being astereogenic centre..[58]Several approaches have been developed to asymmetrically 1,1′-functionalise the ferrocene.[59]
Ferrocene and its numerous derivatives have no large-scale applications, but have many niche uses that exploit the unusual structure (ligand scaffolds,pharmaceutical candidates),robustness (anti-knock formulations,precursors to materials), and redox (reagents and redox standards).
Chiral ferrocenylphosphines are employed as ligands for transition-metal catalyzed reactions. Some of them have found industrial applications in the synthesis of pharmaceuticals and agrochemicals. For example, thediphosphine1,1′-bis(diphenylphosphino)ferrocene (dppf) is a valued ligand forpalladium-coupling reactions andJosiphos ligand is useful for hydrogenation catalysis.[60] They are named after the technician who made the first one, Josi Puleo.[61][62]
Ferrocene and its derivatives areantiknock agents used in the fuel forpetrol engines. They are safer than previously usedtetraethyllead.[63] Petrol additive solutions containing ferrocene can be added to unleaded petrol to enable its use in vintage cars designed to run on leaded petrol.[64] Theiron-containing deposits formed from ferrocene can form aconductive coating onspark plug surfaces. Ferrocene polyglycol copolymers, prepared by effecting a polycondensation reaction between a ferrocene derivative and a substituted dihydroxy alcohol, has promise as a component of rocket propellants. These copolymers provide rocket propellants with heat stability, serving as a propellant binder and controlling propellant burn rate.[65]
Ferrocene has been found to be effective at reducing smoke and sulfur trioxide produced when burning coal. The addition by any practical means, impregnating the coal or adding ferrocene to the combustion chamber, can significantly reduce the amount of these undesirable byproducts, even with a small amount of the metal cyclopentadienyl compound.[66]
Ferrocene derivatives have been investigated as drugs,[67] with one compoundferrocerone [ru] approved for use in the USSR in the 1970s as aniron supplement, though it is no longer marketed today.[68] Only one drug has entered clinical trials in recent years,Ferroquine (7-chloro-N-(2-((dimethylamino)methyl)ferrocenyl)quinolin-4-amine), anantimalarial,[69][70][71] which has reached Phase IIb trials.[72] Ferrocene-containing polymer-based drug delivery systems have been investigated.[73]
The anticancer activity of ferrocene derivatives was first investigated in the late 1970s, when derivatives bearingamine oramide groups were tested against lymphocyticleukemia.[74] Some ferrocenium salts exhibit anticancer activity, but no compound has seen evaluation in the clinic.[75] Ferrocene derivatives have strong inhibitory activity against human lung cancer cell line A549, colorectal cancer cell line HCT116, and breast cancer cell line MCF-7.[76] An experimental drug was reported which is a ferrocenyl version oftamoxifen.[77] The idea is that the tamoxifen will bind to theestrogen binding sites, resulting in cytotoxicity.[77][78]
Ferrocifens are exploited for cancer applications by a French biotech, Feroscan, founded by Pr. Gerard Jaouen.
Ferrocene and related derivatives are used as powerful burn rate catalysts inammonium perchlorate composite propellant.[79]
Ferrocene analogues can be prepared with variants of cyclopentadienyl. For example, bisindenyliron and bisfluorenyliron.[62]
Carbon atoms can be replaced by heteroatoms as illustrated by Fe(η5-C5Me5)(η5-P5) and Fe(η5-C5H5)(η5-C4H4N) ("azaferrocene"). Azaferrocene arises from decarbonylation of Fe(η5-C5H5)(CO)2(η1-pyrrole) incyclohexane.[80] This compound on boiling underreflux inbenzene is converted to ferrocene.[81]
Iron arene complexes are possible, but bis(arene)s are difficult to stabilize. The bis(benzene)iron(II) cation, isoelectronic withbis(benzene)chromium, is unstable against nucleophilic attack, and decomposes "instantaneously" inacetonitrile. It can be observed, however, in metastablenitromethane solution.[82]
Because of the ease of substitution, many structurally unusual ferrocene derivatives have been prepared. For example, the penta(ferrocenyl)cyclopentadienyl ligand,[83] features a cyclopentadienyl anion derivatized with five ferrocene substituents.
cyclopentadienyl.png)
Inhexaferrocenylbenzene, C6[(η5-C5H4)Fe(η5-C5H5)]6, all six positions on abenzene molecule have ferrocenyl substituents (R).[84]X-ray diffraction analysis of this compound confirms that the cyclopentadienyl ligands are not co-planar with the benzene core but have alternatingdihedral angles of +30° and −80°. Due to steric crowding the ferrocenyls are slightly bent with angles of 177° and have elongated C-Fe bonds. The quaternary cyclopentadienyl carbon atoms are alsopyramidalized. Also, the benzene core has achair conformation with dihedral angles of 14° and displaysbond length alternation between 142.7 pm and 141.1 pm, both indications of steric crowding of the substituents.
The synthesis of hexaferrocenylbenzene has been reported usingNegishi coupling ofhexaiodobenzene and diferrocenylzinc, usingtris(dibenzylideneacetone)dipalladium(0) ascatalyst, intetrahydrofuran:[84]
Theyield is only 4%, which is further evidence consistent with substantialsteric crowding around the arene core.
Ferrocene, a precursor to iron nanoparticles, can be used as a catalyst for the production of carbon nanotubes.[86]Vinylferrocene can be converted to (polyvinylferrocene, PVFc), a ferrocenyl version ofpolystyrene (the phenyl groups are replaced with ferrocenyl groups). Anotherpolyferrocene which can be formed is poly(2-(methacryloyloxy)ethyl ferrocenecarboxylate), PFcMA. In addition to using organic polymer backbones, these pendant ferrocene units have been attached to inorganic backbones such aspolysiloxanes,polyphosphazenes, and polyphosphinoboranes, (–PH(R)–BH2–)n, and the resulting materials exhibit unusual physical and electronic properties relating to the ferrocene / ferrocinium redox couple.[85] Both PVFc and PFcMA have been tethered ontosilica wafers and thewettability measured when the polymer chains are uncharged and when the ferrocene moieties are oxidised to produce positively charged groups. Thecontact angle with water on the PFcMA-coated wafers was 70° smaller following oxidation, while in the case of PVFc the decrease was 30°, and the switching of wettability is reversible. In the PFcMA case, the effect of lengthening the chains and hence introducing more ferrocene groups is significantly larger reductions in the contact angle upon oxidation.[85][87]
.JPG)
{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link){{cite book}}:ISBN / Date incompatibility (help)
| International | |
|---|---|
| National | |
| Other | |