Ferrocene electrophilic aromatic substitution

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Attempted acetylation of 2,2, 5,5 -tetramethyl-l,l -distibaferrocene (29) or 3,3, 4,4 -tetramethyl-l,T-distibaferrocene (61) led to destruction of the ring system and the formation of intractable products. Acid-catalyzed H/D isotopic exchange (Scheme 14) is the simplest electrophilic aromatic substitution. Both l,T-diphosphaferrocene55 (7) and l,l -diarsa-ferrocene (8)13 undergo rapid exchange at the a positions when treated... 

Dibenzenechromium is less thermally stable than ferrocene. Furthermore, unlike ferrocene, (C6H6)2Cr is not subject to electrophilic aromatic substitution the electrophile oxidizes the chromium(O) to chromium instead of attacking the rings. 

However, electrophilic aromatic substitution on ferrocene presents two complications (1) its susceptibility to one-electron oxidation, which precludes halogenation, nitration, or direct (H SO ) sulfonation and (2) competition between the Fe and the ring as the initial site of electrophilic attack. It is now clear from H NMR spectroscopy of the product of the protonation of ferrocene with a superacid at -122 °C that protonation of ferrocene initially occurs endo. The detailed structure of the protonation product has not been unambiguously established, but calculations imply that the proton is associated at least as much with the cyclopentadienyl carbons as with the iron. ... 

Electrophilic attack on coordinated polyenyl ligands is uncommon, but electrophilic attack on the Ti -cyclopentadienyl ligands in certain complexes has become synthetically valuable. For example, the acetylation of ferrocene (Equation 12.75) is a reliable Friedel-Crafts process " and generates derivatives used to make many ferrocenyl ligands. Similar electrophilic aromatic substitution reactions of haloboranes on ferrocene (shown in Equation 12.76) and on the anion generated from deprotonation of tungstenocene dihydride (Equation 12.77) leads to borylcyclopentadienyl complexes. " ... 

Ferrocene cannot be nitrated using the conventional HNO3-H2SO4 mixed acid conditions, even though nitration is an electrophilic aromatic substitution reaction. Explain. 

Ferrocene is also called "dicyclopentadienyl iron" which accurately describes its sandwich structure. What may not be apparent is that the molecule is quite nonpolar it is soluble in hexane. The two cyclopentadienyl rings are formally aromatic, six-electron systems and as such are extremely electron rich. The ferrocene system can be functionalized by electrophilic aromatic substitution chemistry. The property of ferrocene most relevant to our efforts, however, is that an electron may be lost reversibly from iron [Fe(II) = e + Fe(ni)] so that the entire molecule becomes positively charged. The half wave potential for ferrocene is observed at about 400 mV (vs. calomel) in aqueous solution and the ferricinium species is stable in water for hours. This contrasts, for example with nitrobenzene or most quinones, which are generally less to much less stable than this upon reduction. These properties make ferrocene particularly attractive for applications in redox-altered chemisuy. 

Ferrocenes are aromatic compounds similar to benzene, as they have a high basicity, electrophilic substitution reactions such as Friedel-Crafts acylation (eq. (15.12)), metalation (eqs. (15.14) and (15.16), Scheme 15.1), Mannich reaction (aminomethylation, eq. (15.13)) and formylation (Scheme 15.1) are liable to proceed as described above. These products also have a high reactivity and they are used as raw materials for other ferrocene derivatives as shown in Schemes 15.1 and 15.2. For example, if one bridged ferrocene is obtained from Scheme 15.1 to form another bridge, lithium diisopropylamide (EDA) is reacted, oxidized with CuCl2, and reduced with LiAlH4 to afford a two bridged ferrocenophane as shown in eq. (15.23) [50,69]. 

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. 

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. 

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. 

The possibility of carrying out typical aromatic electrophilic substitution chemistry, such as Friedel-Crafts acylation, on ferrocene led to the synthesis of decaethylferrocene (Scheme 20) (88) as well as perethylated Cp-man-ganese tricarbonyls (59). A metallation/Me2S2 reaction sequence of a perchloro Cp ligand was also employed in the preparation of functionally... 

---