Ferrocene electrophilic substitution

The most notable chemistry of the biscylopen-tadienyls results from the aromaticity of the cyclopentadienyl rings. This is now far too extensively documented to be described in full but an outline of some of its manifestations is in Fig. 25.14. Ferrocene resists catalytic hydrogenation and does not undergo the typical reactions of conjugated dienes, such as the Diels-Alder reaction. Nor are direct nitration and halogenation possible because of oxidation to the ferricinium ion. However, Friedel-Crafts acylation as well as alkylation and metallation reactions, are readily effected. Indeed, electrophilic substitution of ferrocene occurs with such facility compared to, say, benzene (3 x 10 faster) that some explanation is called for. It has been suggested that. 

Phospholes and analogs offer a wide variety of coordination modes and reactivity patterns, from the ti E) (E = P, As, Sb, Bi) through ri -dienic to ri -donor function, including numerous and different mixed coordination modes. Electrophilic substitution at the carbon atoms and nucleophilic properties of the phosphorus atom are well documented. In the ri -coordinated species, group V heteroles nearly acquire planarity and features of the ir-delocalized moieties (heterocymantrenes and -ferrocenes). 

Due to the aromatic character of Cp2Ee predicted by Woodward and confirmed by the reactivity toward electrophilic substitutions, which proceed with rates comparable to anisole, the name ferrocene was coined in analogy to simple aromatic systems [6]. 

As mentioned above, ferrocene is amenable to electrophilic substitution reactions and acts like a typical activated electron-rich aromatic system such as anisole, with the limitation that the electrophile must not be a strong oxidizing agent, which would lead to the formation of ferrocenium cations instead. Formation of the CT-complex intermediate 2 usually occurs by exo-attack of the electrophile (from the direction remote to the Fe center. Fig. 3) [14], but in certain cases can also proceed by precoordination of the electrophile to the Fe center (endo attack) [15]. 

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. 

Its aromaticity cannot, of course, be tested by attempted electrophilic substitution, for attack by X would merely lead to direct combination with the anion. True aromatic character (e.g. a Friedel-Crafts reaction) is, however, demonstrable in the remarkable series of extremely stable, neutral compounds obtainable from (15), and called metallocenes, e.g. ferrocene (16), in which the metal is held by n bonds in a kind of molecular sandwich between the two cyclopentadienyl structures ... 

The behavior of ferrocene, bis(cyclopentadienyl)iron(II), as an aromatic molecule under conditions for electrophilic substitution has received much attention by both organic and inorganic chemists (59, 63). The Friedel-Crafts acylation may illustrate the reactivity of this very stable compound. 

The major product is the heteroannular disubstituted derivative, l,l -diacetyl-ferrocene (I), while a very small amount of a homoannular isomer, 1,2-diacetylfer-rocene (II), is also obtained. The first acetyl group therefore appears to deactivate the substituted ring toward further electrophilic substitution, and the second acetyl group preferentially enters the opposite ring. 

The dicyclopentadienyl metal compounds undergo Friedel-Crafts alkylation and acylation, sulfonation, metalation, arylation, and formyla-tion in the case of ferrocene, dicyclopentadienyl ruthenium, and dicyclopentadienyl osmium, whereas the others are unstable to such reactions ( ). Competition experiments (128) gave the order of electrophilic reactivity as ferrocene > ruthenocene > osmocene and the reverse for nucleophilic substitution of the first two by n-butyl lithium. A similar rate sequence applies to the acid-catalysed cleavage of the cyclopentadienyl silicon bonds in trimethylsilylferrocene and related compounds (129), a process known to occur by electrophilic substitution for aryl-silicon bonds (130). 

Diarene metals generally decompose under conditions of normal electrophilic substitution, but dibenzene chromium can be metalated with amyl sodium in alkanes, and subsequent reaction with carbon dioxide and dimethyl sulfate results in a complex mixture of mono-, di-, and poly-substituted dibenzene chromium methyl esters. It is interesting that these polysubstituted compounds are homoannular in contrast to the corresponding ferrocene compounds. In view of the scanty evidence and ease of oxidation, it is impossible to conclude whether the diarene metals are less aromatic than the dicyclopentadienyl metals as predicted by simple theory (Sec. III.A). 

Although dibenzenechromium is thermally quite stable, it is less so than ferrocene and melts with decomposition at 285° to give benzene and metallic chromium. Furthermore, it appears to lack the aromatic character of either benzene or ferrocene as judged by the fact that it is destroyed by reagents used for electrophilic substitution reactions. 

Ferrocenes, heterocyclic, 13, 1 Five-membered rings, electrophilic substitutions... 

The reactions of electrophilic substitution in metallocene structures of the type 3 (Sec. 1.1) are numerous and various [423 133]. The reaction capacity of coordinated cyclopentadienyl ligands in ferrocene 749 is especially studied in detail (3.197) [423-426,433]. It is significant that already in 1968 more than 300 such transformations had been reported [424], for example (3.197) ... 

Volume 13 of this serial publication comprises six chapters of which four deal with general accounts of compound classes 1-azirines (F. W. Fowler), phenanthridines (B. R. T. Keene and P. Tissington), tri-thiapentalenes (N. Lozac h), and heterocyclic ferrocenes (F. D. Popp and E. B. Moynahan). The other two chapters are concerned with particular aspects of the chemistry of groups of heterocyeles the tautomerism of purines (B. Pullman and A. Pullman) and quantitative aspects of the electrophilic substitution reactions of five-membered rings (G. Marino). 

The mechanism of electrophilic substitution reactions in ferrocene is illustrated below... 

This mechanism explains why the rate of electrophilic substitution in ferrocene derivatives is proportional to the ease of oxidation of Fe atom. 

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