[102-54-5]  · C10H10Fe  · Ferrocene  · (MW 186.05)

(source of most substituted ferrocenes and hence precursor of substituted cyclopentadienes and cyclopentanes; the derived ferrocenium salts find use as mild oxidants; replacement of one ring by arenes yields cationic complexes which undergo nucleophilic addition and substitution at the arene ring, leading to substituted arenes)

Alternate Name: bis(cyclopentadienyl)iron.

Physical Data: mp 173-174 °C; sublimes slowly at room temperature, rapidly at 100 °C; bp 249 °C; d 1.49 g cm-3.

Solubility: sol all common organic solvents; insol water.

Form Supplied in: deep orange crystals; widely available.

Handling, Storage, and Precautions: stable up to 470 °C; stable to alkalis and, in the absence of air, to strong, non-oxidizing acids; oxidized by air in the presence of strong acids and by many oxidizing agents, including HNO3 and the halogens, reversibly forming the cation (C5H5)2Fe+.


Ferrocene1,2 is a typically aromatic system and as such has a wide-ranging chemistry based on its substitution reactions. As a synthetic reagent its primary use is as a source of useful ferrocene derivatives themselves. These include sensors, which make use of the readily reversible oxidation of ferrocene and its derivatives, monomers for the synthesis of redox active polymers, compounds with nonlinear optical properties, and antianaemic agents. Ferrocene also serves as the source of cationic complexes of benzene derivatives, which are thereby rendered reactive towards nucleophiles. Although ferrocene derivatives can be cleaved to yield cyclopentane or cyclopentadiene derivatives, it has only rarely found use for this purpose.

With only the limits imposed by their facile oxidation, ferrocene derivatives undergo all the common functional group transformations of arenes. It is appropriate here to review only the principal direct substitution processes with emphasis on differences from the chemistry of benzenoid aromatics. These arise chiefly from the impossibility of effecting direct halogenation or nitration since all potential reagents oxidize ferrocene to the unreactive ferrocenium cation [Fe(C5H5)2]+. This cation itself is a very mild one-electron oxidizing agent which has frequently been employed to oxidize other organometallic species.

The ferrocenyl group, C5H5FeC5H4, is commonly abbreviated as Fc.

Electrophilic Substitution Reactions.

Ferrocene shows very high reactivity towards electrophiles, making it more closely comparable to phenol than to benzene. Thus it undergoes facile Vilsmeier formylation to the aldehyde (eq 1)3 and Mannich-type aminomethylation (eq 2).4 The aminomethylated product is frequently utilized in the form of its quaternary ammonium salt, FcCH2NMe3+ I-, which is highly reactive towards nucleophiles, readily undergoing SN1-type reactions due to the high stability of a-ferrocenyl carbocations.5 This stability also accounts for the basicity of the aldehyde which keeps it in the protonated form during the reaction depicted in eq 1, thereby preventing further substitution. This and similar examples show that electronic effects are transmitted to a substantial degree from the substituted to the unsubstituted ring. In the case of eq 2, disubstitution to yield 1,1-bis(dimethylaminomethyl)ferrocene can be achieved under forcing conditions.6

Friedel-Crafts acylation [with acid chlorides/AlCl3 (eq 3) or acid anhydrides/BF3] is readily regulated by the choice of reaction conditions to give mono- or disubstitution; the latter includes a very small amount of 1,2-disubstitution.1 Column chromatography readily separates mixtures. Sulfonation, best done with Chlorosulfonic Acid,7 is more difficult to regulate (eq 4).

Arylation occurs when ferrocene is treated with arenediazonium salts and can likewise yield both mono- (eq 5) and 1,1-disubstituted products; it has been shown to proceed via an initial electron-transfer step.8

Most other simple ferrocene derivatives arise either by functional group transformations of the above products or via metallated compounds. Mercuration yields mixtures of mono- and bis(acetoxymercury) derivatives (eq 6), readily converted by Lithium Chloride or NaCl to the chloromercury derivatives and differing sufficiently in solubility to be fairly easily separated.9 The chloromercury compounds in turn react with halogens, copper halides, or N-halosuccinimide to provide a good source of mono- and dihaloferrocenes.10

Lithiation is of wider use as well as more controllable. Whereas n-Butyllithium yields mixtures of mono- and 1,1-dilithioferrocene (eq 7),11 addition of N,N,N,N-Tetramethylethylenediamine leads almost exclusively to the dilithio derivative,12 and replacement of n- by t-Butyllithium results in highly selective monolithiation.13 Lithioferrocene in turn can then serve as the source of the haloferrocenes by reaction with polyhalocarbons or p-toluenesulfonyl halides, etc.,10d,e of nitroferrocene by reaction with, for example, alkyl nitrates (eq 8)14a or N2O4,14b of aminoferrocene by reaction with O-alkylhydroxylamines, e.g. eq 9,15 and of ferroceneboronic acid by reaction with tributyl borate.16

The boronic acid is an alternative precursor of haloferrocenes and can similarly give acetoxyferrocene, both by reaction with copper salts (eq 10).17 The acetate reacts with Grignard reagents to give hydroxyferrocene, but both this phenolic compound and aminoferrocene are very sensitive to oxidation and relatively little is known of their chemistry.

Lithiation also provides the principal route to 1,2-disubstituted ferrocenes since functionally substituted ferrocenes generally lithiate to yield 2-lithio derivatives at least as the kinetically favored products, as illustrated for (dimethylaminomethyl)ferrocene (eq 11).11,18

Formation and Uses of (Arene)cyclopentadienyliron Cations.

Replacement of one ring in ferrocene is the route chiefly used to obtain arenecyclopentadienyliron salts (eq 12);19 they can also be obtained similarly from CpFe(CO)2Cl. The reaction succeeds with a wide range of arene substituents and with polycyclic arenes. Electron-withdrawing substituents are preferentially retained,19a,20 for example as in eq 13.20

The synthetic value of these complexes arises from their reactivity towards nucleophiles (significantly greater than that of (arene)Cr(CO)3, but less than that of [(arene)Mn(CO)3]+).21a Hydride and carbon nucleophiles add to give cyclohexadienyl complexes (eq 14),22 whereas fluoro and chloro or nitro substituents are substituted by softer nucleophiles (eq 15).23 Halogen substituents on the five-membered ring are much more difficult to replace.22f

Directive effects on the addition (eq 14) can be roughly summarized by stating that electron-withdrawing groups direct the incoming nucleophile to the 2-position while donating groups direct to the 3-position with some addition at the 4-position; these effects are weaker than in electrophilic aromatic substitution, so that a methyl substituent allows nearly random addition of hydride to carbons 2, 3, and 4.21

The cyclohexadienyl groups can generally be rearomatized by reaction with N-Bromosuccinimide (eq 16)24 or in some cases trityl salts,24b thus opening the way to further additions, but cyano, benzyl, malonyl, and similarly reactive exo substituents are cleaved by these reagents.

The acidity of a-hydrogens in (alkylbenzene)cyclopentadienyliron salts allows alkylation,25,26 as exemplified for the hexamethylbenzene complex (eq 17).25a The intermediate methylenecyclohexadienyl complexes in such reactions have sufficient carbanionic character to act as nucleophiles in Michael-type addition (eq 18).26

Side chains in these cations may also be oxidized, for example eq 1927 and eq 20.28

Cleavage of the complexes to recover substituted arenes has been achieved by thermolysis,23a,29 photolysis,30 electrochemical reduction,31 and rather inefficiently by oxidation (directly from cyclohexadienyl precursors).22 It is also known to occur by reaction with a wide variety of donor ligands including phosphines or phosphites (preferably with electron transfer catalysis or with photolysis),32 nitriles,33 and thioethers;34 these reactions are widely used to prepare the corresponding salts (eq 21), but yields of recovered arenes are rarely reported.33b

Heterocyclic syntheses employing this class of reaction are exemplified by eq 2235 and eq 23.29b

Cleavage of Ferrocenes.

Ferrocene resists hydrogenation under conditions which readily convert benzene to cyclohexane and has only been reduced (to metal and cyclopentane) at ca. 350 °C using a Raney Nickel catalyst.36a It is cleaved by an excess of Bromine to give pentabromocyclopentane;36 neither of these degradations has been applied to derivatives.

Cleavage to metal and cyclopentadienide anion is achieved smoothly with lithium and amines (ethylamine).37 A few substituted ferrocenes have been degraded by this method and the resultant lithium cyclopentadienides used to prepare new complexes. Thus the product of eq 2 was shown to yield 1,1-bis(dimethylaminomethyl)ferrocene by the sequence shown in eq 24,38a although a better route to this product was described at the same time.38b A low yield of 1,1-dimethoxyferrocene was obtained in similar fashion from methoxyferrocene.38c Tris- and tetrakis(cyclopentadienyl)methane have been generated via the tri- and tetralithium salts (LiC5H4)3CH and (LiC5H4)4C by Lithium-Ethylamine reduction of Fc3CH and Fc3C(C5H5), respectively.38d,e

Despite the considerable stabilization of a-ferrocenyl cations, allowing their facile formation and in suitable cases isolation as stable salts, they are relatively easily cleaved, particularly on irradiation. That a partial positive charge at the 2-position suffices is exemplified by (2-pyridyl)ferrocene. After quaternization with Iodomethane, this amine, which is readily obtained from ferrocenyllithium and pyridine,39 is photolyzed in good yield in aqueous alkaline solution (eq 25).40

This route has been applied to fused ferrocenodihydropyridines (generated in four steps from [FcCH2NMe3]I) (eq 26).41

In an attempt to extend the latter example to tricyclic systems, appropriately substituted (amidophenyl)ferrocenes were prepared as precursors via arylation (eq 5) of ferrocene with 2-nitro- and with 2-cyanobenzenediazonium salts. The final Bischler-Napieralski type cyclization step appeared to proceed smoothly, but instead of the expected fused ferrocenes (isolated in low yield when n = 1) the metal-free heterocycles were the main products (eq 27);42 i.e. cleavage had occured without quaternization even in the dark.

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Peter L. Pauson

University of Strathclyde, Glasgow, UK

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