Acyl halides, reaction with aluminum

Friedel-Crafts acylation An analogous reaction occurs when acyl halides react with benzene in the presence of aluminum chloride. The products are acylben-zenes. 

Glycosyl halides, a very important group of carbohydrate derivatives, are commonly prepared14 from per-O-acylated sugars by reaction with hydrogen halides or halides of aluminum or titanium. The selection of the method depends mainly on the anomeric configuration of the substrate, the kind of its O-acyl groups, and the stability of the product to be prepared. 

The 3-oxo-2//-furans (260) obtained from the reaction of a-halogenoacyl halides with /3-ketonic esters at -20 °C show no tendency to enolize to the hydroxyfurans (261) but rather behave as unsaturated ketones (Scheme 71) (73RTC731). 2,4-Dialkylfurans (262) are obtained by condensation of acyl halides with allyl halides catalyzed by aluminum chloride (73KGS1434). The acid catalyzed condensation of 2-chlorocyclopentanone with dimethyl /3-oxoglutarate leads to the furan ester (263) (77JHC711). 

The acylation of unsaturated ketones constitutes one of the earliest routes to pyrylium salts (19CB1195). The reaction is better achieved with acyl halides than by anhydrides, and aliphatic are preferable to aromatic acid derivatives. The presence of a Lewis or Bronsted acid is usually necessary and iron(III) chloride, aluminum chloride, boron trifluoride and perchloric acid have found frequent application. It is considered that these interact with the acid derivative to generate the actual acylating agent. 

Other diprotonated acyl-pyridines have likewise been studied.61 In studies of 5-, 6-, 7-, and 8-hydroxyquinolines and 5-hydroxyisoquinoline, dicationic intermediates like 185 (Table 4) were found to be involved in superacid catalyzed reactions with benzene and cyclohexane.59 For example, 8-hydroxyquinoline (187) reacts in CF SOsH-SbFs to generate dications (188 and 189) and undergoes ionic hydrogenation in the presence of cyclohexane (eq 64). Compound 187 also reacts with benzene in suspensions of aluminum halides (eq 65). 

Many other types of organometallics which are not acylated directly acid chlorides and which do not undergo addition to ketones may still transmetallate into the acylpalladiumfll) complex. Simple alkyl organomercurials have been acylated in this fashion to give moderate to good yields of ketones. " Larock has studied the palladium-catalyzed acylation of vinylmercury(II) compounds with acyl halides (equation 104). The reaction was only modestly productive and could not compare to the yield provided by aluminum chloride catalysis. 

Crafts process is to generate carbonium ions from the alkyl or acyl halides. It would be expected, then, that a number of other combinations of starting materials and reagents which lead to carbonium ions should be capable of effecting acylation or alkylation. Indeed we find that olefins (p. 35), alcohols (p. 36), ethers (p. 36), and esters (p. 37) can be used as starting materials for aromatic alkylation reactions in the presence of such catalysts as boron trifluoride, sulfuric acid, or anhydrous hydrogen fluoride.69 Acylations can be carried out with acids (p. 37),64 acid halides (p. 230), and acid anhydrides (p. 37). The Fries reaction65 (in which phenolic esters are converted to hydroxy aromatic ketones by means of aluminum chloride) appears to be an example of a typical acylation reaction in which the ester itself acts as the source of an acyl carbonium ion ... 

This reaction involves an acylating reagent (acyl halides, carboxylic acids or anhydrides) in the presence of an activator, usually a Lewis acid. However, as a result of the complexation of this Lewis acid with the formed ketone, more than one mole of catalyst is required per mole of reagent. It cannot be reused because the ketone is isolated after hydrolysis of the complex. Such is the dilemma of Friedel-Crafts acylation (refs. 4-6) in the presence of the traditional catalyst, aluminum chloride (eqn. 2). 

Aluminum chloride is the most fiequently used Lewis acid in aliphatic Friedel-Crafts acylations, and is one of the strongest. Its complexes with acyl halides are strong, producing very active acylating species. Titanium and tin tetrachlorides also find use as catalysts, and are powerful enough to induce reaction at low temperatures. 

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 spite of the impression that may have been gained from the earlier part of this chapter, reactions involving the use of aluminum halides, and especially aluminum chloride, constitute the majority of Friedel-Crafts acylation reactions. The interaction of the three components, i.e. the acyl halide, the aromatic substrate and the aluminum halide, results in the formation of hydrogen halide and a complex of the aromatic ketone with aluminum halide from which the ketone is literated after hydrolysis. There are a number of sequences in which the three components can be mixed. 

The least satisfactory method involves the addition of an acyl halide to a mixture of the aluminum halide and the aromatic compound (the Bouveault procedure). The problem with this sequence relates to the presence of hydrogen halide, which may be present as a result of the reaction of moisture with the aluminum halide or which will be present in increasing amounts as the reaction proceeds. The hydrogen halide can result in isomerization or disproportionation of, for example, alkylbenzenes. 

The use of an acyl chloride in the presence of aluminum chloride constitutes the most frequently used type of Friedel-Crafts ketone synthesis. Many examples from the earlier literature are reported in the reviews mentioned at the beginning of this chapter.The reactivity of acyl halides in reactions of acyl halides with aluminum halides decreases in the order I > Br > Cl > F, but a different order was report for reactions catalyzed by boron halides. In the latter case the order was acyl fluoride > acyl bromide > acyl chloride. We shall concentrate our attention on recently reported examples. 

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