Zinc chloride Friedel-Crafts acylation catalyst

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Significant advances resulting from the use of aluminosilicate solids were made during the last few years [3-6] and the first industrial application of zeolites in large scale Friedel-Crafts acylations was reported very recently [7]. However, most of the efforts devoted so far focused on the acylation of aromatic compounds. To the best of our knowledge, recourse to heterogeneous aluminosilicate catalysts for the acylation of alkenes has not yet been reported. Conventional methods for alkene acylation [8] involve the use of Br0nsted or Lewis acids such as sulfuric acid [9], boron trifluoride [10], zinc chloride [11], or... 

The preparation and use of indium trichloride, gallium trichloride, and zinc chloride supported on MCM-41 as Lewis acids in the Friedel-Crafts acylation of aromatics with acyl chlorides was investigated. The support itself shows no catalytic activity in the benzoylation of benzene with BC, whereas the highest activity is showed by the supported indium trichloride. The order for acylation activity of the supported metal chloride (indium trichloride > gallium trichloride zinc chloride) is quite similar to that of the redox potential of the metals [E , +/, (-0.34 V) > E°Ga /Ga ( 0.53 V) > E 2n +/zn ( 0.74 V)] and confirms a possible relationship between the redox potential and the catalytic activity of the supported metal chloride. The reaction can be efficiently applied to a variety of aromatic compounds, including toluene, para-xylene, mesitylene, anisole, and 2-MN (70%-90% yield), confirming the moisture insensitivity of the catalyst. ... 

Zinc oxide, an inexpensive and commercially available inorganic solid, can be utilized as an efficient catalyst in the Friedel-Crafts acylation of activated and unactivated aromatic compounds with acyl chlorides at room temperature for 5 to 120 min (Table 4.14). Acylation is claimed to occur exclusively at the para-position of the monosubstituted aromatic compounds. The catalyst can be recovered and reused, after washing with methylene chloride, for at least two further cycles, showing quite similar high yield (-90%) in the model benzoylation of anisole. Mechanistically, it seems that zinc chloride can be the true catalyst, generated in situ by the reaction of zinc oxide with hydrogen chloride. 

A much more environmentally sound procedure was advocated by Paul et al. [164], who used Zn powder as a catalyst for Friedel-Crafts acylation of aromatic compounds. Zinc is a nontoxic, safe, and inexpensive metal which can be used in solvent-free conditions. It was shown to have a remarkably high activity in the acylation of a series of aromatic compounds with acetyl and benzoyl chlorides when performed under microwave irradiation. Yields were much more better than when using conventional thermal heating (Eq. (80), Table 4.28). The Zn powder could also be re-used up to six times after simple washing with diethyl ether and dilute HCl. 

One of the salient features of the original Friedel-Crafts acylation reaction is the requirement of one or more than one equivalent of Lewis acid catalyst that cannot be recovered and reused [1]. The possibility to carry out the reaction with only catalytic amounts of Lewis acids (such as iron trichloride, zinc chloride, iron, and iodine, or, better, with metal triflates such as lanthanide triflates) represents a significant development [113]. Metal triflates, developed in particular by Kobayashi, are very active (1-5% mol with respect to the acylating agent) and insensitive to the water content of the reaction medium and can be reused [126]. 

In contrast to the aromatic counterpart, very few works have been devoted to the mechanism of the aliphatic Friedel-Crafts acylation. Several mechanisms have been proposed to explain the reaction of 1-methylcyclohexene in acetic acid with zinc chloride catalyst that exclusively gives the 6-acetyl-l-methylcyclohexene. Early discussions by Deno suggest a carbo-cation intermediate. Finally, the observations by Beak of a product isotope effect in the absence of a corresponding kinetic isotope effect in the series of deuterated cyclenes is compelling evidence for a reaction intermediate, such as carbocation species. In the meantime, H.M.R. Hoffmann observed that the acylation of various olefins with acetyl hexachloroantimonate in methylene chloride in the presence of hindered amines affords 8,T-unsaturated ketones. He suggested that the non-conjugated enone is formed via an ene reaction. 

Zinc chloride exchanged clay catalysts have been reported to be highly active for the Friedel-Crafts alkylation and acylation reactions these are commercially sold by Contract Catalysts under the name Envirocats. These are montmorillonite catalysts modified by ZnCU and FeCli. Some of the reported examples of Friedel-Crafts reactions are given below there are claims that some of the processes are commercially practised. 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

Acylations with Nitriles. With particularly reactive aromatic nuclei such as phenols, a Friedel-Crafts type reaction may be effected with nitriles in the presence of an acid catalyst such as hydrogen chloride, aluminum chloride, or zinc chloride. The reaction is usually called the IIouben-Hoesch synthesis.700 When hydrogen cyanide is employed, the process leads to aromatic aldehydes even with a number of aromatic... 

The generation of the appropriate electrophile (carbocation, carbocation complex, or acylium ion) in the presence of an aromatic ring system (nucleophile) can lead to alkylation or acylation of the aromatic ring. This set of reactions, discovered by Charles Friedel and James Crafts in 1877, originally used aluminum chloride as the catalyst. The reaction is now known to be cat-al) ed by a wide range of Lewis acids, including ferric chloride, zinc chloride, boron trifluoride, and strong acids, such as sulfuric, phosphoric, and hydrofluoric acids. 

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. 

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