Friedel-Crafts acylation reactions metal halides

Friedel-Crafts acylation reactions of aromatics are promoted by Tilv complexes.104 In some cases, a catalytic amount of the titanium compound works well (Scheme 28). In addition to acyl halides or acid anhydrides, aldehydes, ketones, and acetals can serve as electrophile equivalents for this reaction.105 The formylation of aromatic substrates in the presence of TiCl4 is known as the Rieche-Gross formylation metalated aromatics or olefins are also formylated under these conditions.106... 

The Friedel-Crafts acylation reaction, rapid under the influence of a powerful metal halide catalyst, is very selective. The data gathered in recent studies of the acetylation reaction in ethylene dichloride are presented graphically in Fig. 13. The p-phenyl substituent again deviates from the correlation line. Certain apparently real accelerations exist for the large ra-alkyl groups in this reaction. 

A considerable amount of research has been concerned with the nature of the electrophiles that are involved in Friedel-Crafts acylation reactions. We will summarize the main points. Acyl halides and carboxylic acid anhydrides have been known, for many years, to form stable complexes with a variety of acid catalysts. A well-defined product is formed between acetyl fluoride and boron trifluoride at low temperatures. Analytical and conductivity data characterized the material as acetylium tetrafluoroborate, and this was further confirmed by IR measurements. In the system acetyl chloride-aluminum chloride the acetylium ion can be differentiated from the donor-acceptor complex involving the carbonyl group by means of their IR carbonyl stetching frequencies. A number of other acyl fluorides have been shown to form well-defined acylium salts by interaction with a number of metal fluorides. Acylium salts can also be prepared from acyl chlorides by means of metathetical reactions involving anhydrous salts such as silver hexafluoroantimonate. As well as characterization by means of IR spectroscopy, acylium salts have been studied in non-nucleophilic solvents by NMR spectroscopy. The NMR data for the ben-... 

In Friedel-Crafts acylation reactions, benzene is reacted with acyl chlorides or acid anhydrides in the presence of metal halides (Lewis acids). The importance of acylation is that there is no rearrangement, unlike alkylation where there is a possibility of rearrangement of the cation intermediates. 

Acidic chloroaluminate ionic liquids have already been described as both solvents and catalysts for reactions conventionally catalyzed by AICI3, such as catalytic Friedel-Crafts alkylation [35] or stoichiometric Friedel-Crafts acylation [36], in Section 5.1. In a very similar manner, Lewis-acidic transition metal complexes can form complex anions by reaction with organic halide salts. Seddon and co-workers, for example, patented a Friedel-Crafts acylation process based on an acidic chloro-ferrate ionic liquid catalyst [37]. 

In the case of the tricarbonylarene metals, enhancement of nucleophilic substitution relative to the free arene is reported 106), In contrast to earlier reports 106) Friedel-Crafts acylation of tricarbonylbenzene chromium occurs under mild conditions 18), Molecular-orbital calculations of the 7r-electron activation energies for these reactions 63) confirm enhanced nucleophilic reactivity and suggest electrophilic activity similar to that of the free arene. The nucleophilic displacement of halide by methoxide ion... 

All lation. Thiophenes can be alkylated in the 2-position using alkyl halides, alcohols, and olefins. Choice of catalyst is important the weaker Friedel-Crafts catalysts, eg, ZnCl2 and SnCl, are preferred. It is often preferable to use the more readily accompHshed acylation reactions of thiophene to give the required alkyl derivatives on reduction. Alternatively, metalation or Grignard reactions, on halothiophenes or halomethylthiophenes, can be utilized. 

A 1 2 mixture of l-methyl-3-ethylimidazolium chloride and aluminum trichloride, an ionic liquid that melts below room temperature, has been recommended recently as solvent and catalyst for Friedel-Crafts alkylation and acylation reactions of aromatics (Boon et al., 1986), and as solvent for UV/Vis- and IR-spectroscopic investigations of transition metal halide complexes (Appleby et al., 1986). The corresponding 1-methyl-3-ethylimidazolium tetrachloroborate (as well as -butylpyridinium tetrachlo-roborate) represent new molten salt solvent systems, stable and liquid at room temperature (Williams et al., 1986). 

Reaction XX. (6) Action of certain Anhydrous Metallic Halides (Aluminium Chloride, Aluminium Bromide, Aluminium and Hydrogen Chloride, Ferric Chloride) on a mixture of an Aromatic Hydrocarbon or certain Derivatives, and an Acyl Halide. (Friedel-Crafts.) (A. Ch., [6], 1, 518.)—This is an even more important application of the Friedel-Crafts synthesis than the methods of synthesising hydrocarbons (pp. 58, 60). The reactions involved are more readily controlled since the products, in presence of aluminium chloride, do not undergo further condensations. Usually these products have also the advantage of being more easily separated, for, as shown below in (iii.), the formation of isomers can be avoided. 

Acylation of aromatic compounds is a widely used reaction for the production of fine chemicals. The classic methodology for acylation is Friedel-Crafts, this uses stoichiometric amounts of Lewis acids, such as metal halides, but some Bronsted acids, such as polyphosphoric and sulphuric acid, can also be used as catalysts. Moreover, the reaction is carried out homogeneously and the catalyst must be destroyed to obtain the final products, generating a great amount of corrosive and toxic waste. 

Influence of the Catalyst. Several different types of aromatic reactions are catalyzed by Lewis acids, including alkylation, polymerization, isomerization, acylation, and halogenation. The dependence of these reactions on various Lewis acids is shown in Table 12.11. This table shows a few common Lewis acids and the type of reaction(s) for which each is best suited. The relative strength of Lewis acids was discussed in Section 2.3. Olah gives a comprehensive list of Lewis acid catalysts, and includes several typical synthetic applications. Metal alkyl catalysts are also effective catalysts, but the aromatic substrate is usually converted to a mono-, di-, or trialkyl derivative. Both metal halides and their alkyl derivatives are effective Friedel-Crafts catalysts, as shown in Table 12.11,m as are common inorganic and organic acids. Triflate derivatives are trifluorosulfonate ester (—S02CF3 OTf) can be prepared with various metal counterions. Triflates are very effective catalyst in Friedel Crafts reactions. Some of the more common catalysts are B(OTf)3, Al(OTf)3, and Ga(OTf)3.ll3... 

In Friedel-Crafts reactions, benzene is reacted with acyl or alkyl chlorides, in the presence of metal halides as catalysts. The metal halides act as Lewis acids in these reactions. The two types of Friedel-Crafts reactions are alkylation and acylation. 

But there is another important type of acid the Lewis acid. These acids don t donate protons—indeed they usually have no protons to donate. Instead they accept electrons. It is indeed a more general definition of acids to say that they accept electrons and of bases that they donate electrons. Lewis acids are usually halides of the higher oxidation states of metals, such as BF3, AICI3, ZnCl2, SbFj, and TiCl4. By removing electrons from organic compounds, Lewis acids act as important catalysts in important reactions such as the Friedel-Crafts alkylation and acylation of benzene (Chapter 21), the S l substitution reaction (Chapter 15), and the Diels-Alder reaction (Chapter 34). 

---