Acylation of ferrocene

This experiment examines the effect of reaction time, temperature, and mole ratio of reactants on the synthetic yield of acetylferrocene by a Eriedel-Crafts acylation of ferrocene. A central composite experimental design is used to find the optimum conditions, but the experiment could be modified to use a factorial design. 

The successful acylation of ferrocene set off a vigorous research effort that has resulted in the establishment of the present field of metallocene chemistry, ir- Cyclopentadienyl compounds of ruthenium, osmium, manganese, vanadium, and chromium also exhibit certain aromatic-type reactions in varying degrees. These metallocenes thus represent a new class of heterocyclic compounds in which transition metals, akin to nitrogen, oxygen, and sulfur in classical heterocycles, not only are an integral part of the structure but actually participate directly in many reactions. 

A useful synthetic technique involves the acylation of ferrocene with di-phenylcarbamyl chloride and aluminum chloride (50). The product, diphenyl-carbamylferrocene (X), is readily hydrolyzed to ferrocenecarboxylic acid (XI). Acylation of X followed by hydrolysis produces good yields of l -acylferrocene-carboxylic acids. 

Friedel-Crafts acylation of ferrocene gave the ketone (193) which was oxidized rapidly on alumina columns to the diketone.63 The action of phosphorus oxychloride-dimethylformamide on 193 gave 194 and then 195, which could then be converted into the ferrocenyl-acetylene (196).63... 

Figure 7.26 Selectivity in Friedel-Crafts acylation of ferrocene...

The first example of a Friedel-Crafts type reaction in an ionic liquid medium dates back to 1976 when the electrochemical oxidation of hexamethylbenzene in [C2py]Br-AlCl3 afforded a mixture of alkylated polyphenyl compounds.[69] Other early examples include the alkylation of benzene in C2Ciim C1-A1C137 and the acylation of ferrocene in [C2Ciim]I-AlClJ71 There are now numerous examples of Lewis- or Bronsted acid-catalysed Friedel-Crafts type reactions in ionic liquids. These include alkylation,[72 76] acylation,[71,77"83] arylation,[77 841 sulfonylation,[851 sulfoamylation[86] and O-acetylation of alcohols.[87,881... 

Our first ferrocene papers described one more reaction the synthesis of bis(tetrahydroindenyl)iron through the acylation of ferrocene with succinic anhydride, reduction, then closure of the six-membered ring followed by reduction again. The compound was identical with that obtained by... 

Li J, Su W, Lin J et al (2005) Friedel-Crafts acylation of ferrocene catalyzed by immobilized ytterbium (III) tiiflate in ionic liquid. Syn Commun 35 1929-1937... 

Acylation. Zinc oxide is found to be a good catalyst for acylation of ferrocene. 

Good synthetic results have been achieved in the acylation of ferrocene with acetic anhydride (AAN) in EtMeimCl-AlClg/toluene mixture. The monoacetylated product can be obtained in 80%-96% yield, ft is significant that no acetylation of toluene is observed under these conditions. 

Surette,J.K. D., Green, L., and Singer, R. D.1996. l-Ethyl-3-methylimidazolium hologenoaluminate melts as reaction media for the Friedel-Crafts acylation of ferrocene. Chem. Commun. 2753-2754. 

An efficient and ecofriendly procedure for the small-scale acylation of ferrocene with carboxylic acids is based on the in situ production of the mixed carboxylic-triflic anhydride (Table 4.15 see also Chapter 3). The reaction is simply performed by adsorbing ferrocene on the surface of activated alumina (preheated at 150°C for 3 h) and adding a mixture of carboxylic acid and trifluoroacetic anhydride (TFAA) at room temperature for a selected time. Products 40 are recovered in 55%-98% yield simply by elution with diethyl ether. 

The bentonite-supported polytrifluoromethanesulfosiloxane (B-PTF-MSS) shows good catalytic activity in the electrophilic acylation of ferrocene with different acyl chlorides to afford products 66 (Scheme 4.40). The catalyst B-PTFMSS can be prepared by refluxing a stirred suspension of bentonite and trifle acid in ethanol and calcining at 200°C for 4 h. The maximum efficiency achieved is -80% ferrocene conversion. The catalyst can be reused with similar activity for two further cycles. Similar good results are achieved with aliphatic acyl chlorides ( 60%-75% yield of product 66), whereas poor yields are obtained with chlorobutyryl chloride (18%), ferrocenoyl chloride (8%), and BC (8%). 

Hu, R.-J. and Li, B.-G. 2004. Novel solid acid catalyst, bentonite-supported polytrifluoromethanesulfosiloxane for Friedel-Crafts acylation of ferrocene. Catal. Lett. 98 43 7. 

Use of thienyl chloride in the Friedel-Crafts acylation of ferrocene gave the expected ketone as well as the diketone... 

Many reports have focused on the functionalization and derivatization of cyclo-pentadienyl groups bound to iron in ferrocene complexes. As an example, a series of ferrocenyl esters have been prepared via solvent-free reactions of ferrocenoyl fluoride with substituted phenols after microwave heating for just 1 min. " In the case of 4-bromophenol, the YIF was 1.2, but most substrates gave somewhat lower yields than the conventional method. However, the microwave approach did not require the addition of A, A -dimethylaminopyridine that was necessary conventionally. Other reports include a green approach to the acylation of ferrocene using the polymeric sulfonic acid Nation as an acid catalyst " and a one-pot approach to the synthesis of l,5-dioxo-3-substituted[5]ferrocenophanes from l,T-diacetylferrocene and aldehydes via a Claisen-Schmidt reaction. " " ... 

Very recently, Cui, Wu, and co-workers reported the first catalytic asymmetric direct G—H bond acylation of ferrocene derivatives (Scheme 5.25). After systematically screening of N-protected amino acids, the commercially available Ac-L-Phe-OH proved to be the optimal ligand. Additionally, a variety of carbonyl sources were initially tested, which indicated that the diphenyl... 

Scheme 5.25 Pd-catalyzed asymmetric C—H bond acylation of ferrocene derivatives reported by Cui and Wu.

Some interesting results are observed in the study of bentonite-supported polytrifluoromethane-sulfosiloxane (B-PTMSS) as a catalyst in the acylation of ferrocene with different acyl chlorides [73] (ferrocene/acyl chloride ratio=0.5) (Scheme 3.13). 

The conversions of acyl chlorides increase in the following order aromatic acyl chlorides (-20%) < chlorobut3Tyl chloride (-30%) < long chain acyl chlorides (70-80%). The catalyst can be utilized for at least three cycles in the acylation of ferrocene with butyiyl chloride, showing similar activity (81,73, and 86% ferrocene conversion, respectively). 

Hf(OTf)4 was also reported for Friedel-Crafts acylation of ferrocenes and heteroarenes as well as in Friedel-Crafts acylations in the biphasic medium of an ionic liquid and supercritical carbon dioxide. ... 

The Friedel-Crafts acylation of ferrocene, which was mentioned above, has been studied in considerable detail. Substitution can be effected under very mild conditions, for instance with acetic anhydride containing phosphoric add as catalyst, to give mono-acetylferrocene. With aluminium chloride as catalyst, good yields of either mono- or l,l -diacetylferrocene can be obtained according to the proportions of reagents taken. 

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