Chloride, aluminum reaction with acyl halides

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. 

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. 

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. 

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. 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

The key reactive intermediates in Friedel-Crafts acylations are acylium cations. These spedes can be formed by the reaction of acyl halides with aluminum chloride. The Lewis add initially coordinates to the carbonyl oxygen because of resonance (see Exadse 2-11). This complex is in equilibrium with an isomer in which the aluminum chloride is bound to the halogen. Dissociation then prodnces the acylium ion, which is stabilized by resonance and, unlike alkyl cations, is not prone to rearrangements. As shown in the electrostatic potential map of the acetyl cation in the margin, most of the positive charge (blue) resides on the carbonyl carbon. 

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

While metallocenes are usually acetylated with acid halides, acid anhydrides, or carboxylic acids, a number of other acylating agents have been reported. The reaction of ferrocene with various isocyanates and aluminum chlorides leads to N-substituted ferrocenecarboxamides (IX) (89). Use of ruthenocene in place of ferrocene leads to analogous results (88). The preparation of V-phenyl-ferrocenecarboxamide from phenyl isocyanate in this manner has been used as a proof of structure for the product obtained from the Beckmann rearrangement of benzoylferrocene oxime (124). 

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). 

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). 

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. 

Great interest has been shown in the synthesis of 1,3,5-oxadiazinium salts (209) by the reaction of an aryl carbonitrile (2 equivs.) with an acyl halide (1 equiv.) in the presence of a Lewis acid, generally antimony pentachloride (Scheme 32). Stannic chloride, aluminum chloride and ferric chloride have also been employed but are less effective catalysts <1892CB2266, 56CB209, 65CB334, 67CB3736, 86MI 618-01>. 

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