Electrophilic aromatic acyl chlorides

A good and comprehensive review of catalytic electrophilic acylation was published by Pearson and Buehler.i Only the catalysts most widely used were considered, with special attention to iron trichloride, zinc chloride, iodine, and elemental iron. The substrates that can be acylated using small amounts of catalysts include alkylarenes, aryl ethers, biphenyls, naphthalenes, acenaphthenes, fluorene, furans, and thiophenes. Aromatic acyl chlorides lead to better yields than aliphatic ones, reaching a maximum of 96% and a minimum of 34%. In general, fhe reactions are performed af relatively high temperatures (from 50°C to 200°C) af which hydrogen chloride evolution is fairly rapid. 

Ionic liquids can provide an ideal medium for reactions that involve reactive ionic intermediates due to their ability to stabilize charged intermediates such as acyl cations in Friedel-Crafts acylation. As shown in the previous chapter, examples of electrophilic aromatic acylation are reported utilizing ionic liquid-catalysts based on classic Lewis acids, namely, [emim] Cl-aluminum chloride and [emim]Cl-iron trichloride, which can give acylation of both activated and deactivated aromatic compounds. ... 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

A more practical solution to this problem was reported by Larson, in which the amide substrate 20 was treated with oxalyl chloride to afford a 2-chlorooxazolidine-4,5-dione 23. Reaction of this substrate with FeCL affords a reactive A-acyl iminium ion intermediate 24, which undergoes an intramolecular electrophilic aromatic substitution reaction to provide 25. Deprotection of 25 with acidic methanol affords the desired dihydroisoquinoline products 22. This strategy avoids the problematic nitrilium ion intermediate, and provides generally good yields of 3-aryl dihydroisoquinolines. 

The reaction is initiated by formation of a donor-acceptor complex 4 from acyl chloride 2, which is thereby activated, and the Lewis acid, e.g. aluminum trichloride. Complex 4 can dissociate into the acylium ion 5 and the aluminum tetrachloride anion 4 as well as 5 can act as an electrophile in a reaction with the aromatic substrate ... 

Subsequently rates of benzoylation of a range of aromatics were determined under the same conditions (Table 105)407. The high negative entropy of activation is consistent with the high degree of ordering required for the polarised acyl chloride-aluminium chloride complex to be the electrophile. 

Acylation, rather than alkylation, occurs. Acyl chlorides are more reactive than alkyl chlorides toward electrophilic aromatic substitution reactions as a result of the more stable intermediate... 

This electrophilic aromatic substitution allows the synthesis of monoacylated products from the reaction between arenes and acyl chlorides or anhydrides. The products are deactivated, and do not undergo a second substitution. Normally, a stoichiometric amount of the Lewis acid catalyst is required, because both the substrate and the product form complexes. 

A review of solvent properties of, and organic reactivity in, ionic liquids demonstrates the relatively small number of quantitative studies of electrophilic aromatic substitution in these media.3 Studies mentioned in the review indicate conventional polar mechanisms. 1-Methylpyrrole reacts with acyl chlorides in the ionic liquid 1-butylpyridinium tetrafluoroborate to form the corresponding 2-acylpyrrole in the presence of a catalytic amount of ytterbium(III) trifluoromethanesulfonate.4 The ionic liquid-catalyst system is recyclable. Chloroindate(III) ionic liquids5 are catalytic media for the acylation, using acid chlorides and anhydrides, of naphthalene, benzene, and various substituted benzenes at 80-120 °C. Again the ionic liquid is recyclable. 

Draw a mechanism for the acylation of anisole by propionyl chloride. Recall that Friedel-Crafts acylation involves an acylium ion as the electrophile in electrophilic aromatic substitution. 

In a variation of the Gatterman reaction an alkyl cyanide RCN is used in place of HCN as a useful way of preparing ketones from reactive aromatic species that do not react well under Friedel-Crafts conditions. The electrophile involved is effectively R—C NH+, although, perhaps, the imino chloride, R(C NH)C1, the analogue of an acyl chloride, RCOCl, is also involved. As in the Gatterman reaction, the imine is an intermediate. 

Polymers such as polyetherketones and polyethersulfones can be prepared by electrophilic aromatic substitution using aromatic acid chlorides and aromatic sulfonyl chlorides, respectively [Eq. (25)]. However, due to ortho-substitution in addition to the desired para-substitution, it is difficult for these Friedel-Crafts acylations to compete with nucleophilic aromatic substitution of activated aromatic halides which are usually used for their synthesis. 

In Friedel-Crafts acylation, the Lewis acid AICI3 ionizes the carbon-halogen bond of the acid chloride, thus forming a positively charged carbon electrophile called an acylium ion, which is resonance stabilized (Mechanism 18.7). The po.sitively charged carbon atom of the acylium ion then goes on to react with benzene in the two-step mechanism of electrophilic aromatic substitution. 

Friedel-Crafts acylation (Section 18.5A) An electrophilic aromatic substitution reaction in which benzene reacts with an acid chloride in the presence of a Lewis acid to give a ketone. 

Carbonyl groups form complexes or intermediates with Lewis acids like AICI3, BF3, and SnCl4. For example, in the Friedel-Crafts acylation reaction in nonpolar solvents, an aluminum chloride complex of an acid chloride is often the acylating agent. Because of the basicity of ketones, the products of the acylation reaction are also complexes. For more detail on electrophilic aromatic substitution, see Section 7. 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

We have already considered the use of mixed anhydrides and so in this section we shall be concerned with homocarboxylic anhydrides. The use of anhydrides constitutes the most frequently reported method after the use of an acyl chloride and aluminum chloride. Anhydrides from monocarboxylic acids yield ketones, and cyclic anhydrides derived from dicarboxylic acids afford keto acids. Very nucleophilic aromatic compounds react with trifluoroacetic anhydride in the absence of a catalyst. The confirmation of aromatic character invariably involves establishing reactivity towards a range of electrophiles. Trifluoroacetic anhydride reacts with homoazulene in the presence of an excess of triethylamine to afford 1-tri-fluoroacetylhomoazulene in 91-95% yield. The preparations of 3-aroylpropanoic acids from succinic anhydride and 4-aroylbutanoic acids from glutaric anhydride have been known for many years. Maleic anhydride can be used in a similar way to prepare 3-aroylacrylic acids. We will now concentrate our attention on more recent examples. 

Successively, Friedel and Crafts studied the generality and the limitations of the new synthetic method. They found that the reaction could be successfully applied to a large number of aromatic compounds, as well as alkyl and acyl chlorides or anhydrides in the presence of chlorides of certain metals such as aluminum, zinc, and iron. A mechanistic hypothesis was postulated on the basis of the possible existence of an intermediate compound 3 formed between benzene and aluminum chloride (Scheme 1.2). This intermediate would react with the electrophilic reagent, giving the substitution product and restoring the catalyst. 

The mixed carboxylic-triflic anhydride produced between the acyl chloride and triflic acid has been earlier described to give electrophilic acylation without any catalyst.This acylation method is advantageous in terms of the mild conditions employed and the easy availability of acyl chlorides. The aromatic substrates are mainly limited to electron-rich arenes. However, the methodology can be applied to unactivated aromatics such as benzene and chlorobenzene under special conditions. 

Gallium(lll) oxide supported on MCM-41 mesoporous silica shows high catalytic activity with little or no moisture sensitivity in the acylation of aromatics wifh acyl chlorides. The cafalysf is utilized in 1,2-dichloro-ethane af 80°C for 3 h wifh differenf aromatic compounds, and aromatic as well as aliphatic acyl chlorides, giving ketones in 54%-82% yield. The activity order of fhe aromatic subsfrafes is benzene (43% yield) < toluene (50% yield) < mesifylene (71% yield) < anisole (79% yield), in agreement with the electrophilic substitution trend previously observed. This acylation reaction follows a probable redox mechanism similar to thaf described in Scheme 4.26. ... 

---