Friedel-Crafts acylation reactions Lewis acids

Other reactions, such as Friedel-Crafts acylations, require Lewis acids and these too react at nitrogen. Pyridine is a good ligand for metals such as Al(lll) or Sn(lV) and, once again, the complex with its cationic nitrogen is completely unreactive towards electrophiles. 

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). 

An alternative route to anthraquinone, which involves Friedel-Crafts acylation, is illustrated in Scheme 4.3. This route uses benzene and phthalic anhydride as starting materials. In the presence of aluminium(m) chloride, a Lewis acid catalyst, these compounds react to form 2-benzoyl-benzene-1-carboxylic acid, 74. The intermediate 74 is then heated with concentrated sulfuric acid under which conditions cyclisation to anthraquinone 52 takes place. Both stages of this reaction sequence involve Friedel-Crafts acylation reactions. In the first stage the reaction is inter-molecular, while the second step in which cyclisation takes place, involves an intramolecular reaction. In contrast to the oxidation route, the Friedel-Crafts route offers considerable versatility. A range of substituted... 

Sc(OTf)3 catalyzes Friedel-Crafts acylation reactions effectively (Scheme 12).52 While more than stoichiometric amounts of a Lewis acid such as A1C13 or BF3-OEt2 are needed because of consumption of the Lewis acid by coordination to products, a catalyic amount of Sc(OTf)3 is enough to complete the reactions. 

The presence of Lewis acidic species in chloroaluminate ionic liquids has also been used to bring about various acid catalysed transformations that do not require additional catalysts. For example, acidic ionic liquids are ideally suited to Friedel-Crafts acylation reactions. In a traditional Friedel-Crafts acylation an acylium ion is generated by reaction between acyl chloride and A1C13 or FeCL as shown in Scheme 10.7. 

In electrophilic catalysis, the metal ion acts as a Lewis acid. An example from organic chemistry is the formation of an acylium ion from aluminum chloride and an acid chloride in Friedel-Crafts acylation reactions (Figure 2). In this case substrate activation results in cleavage of the C—Cl bond. In most cases, however, substrate activation by Lewis acids involves electron redistribution without bond breaking (Figure 3). 

In recent years the analogy between the Friedel-Crafts acylation reaction and various nitrating systems, particularly those in which Lewis acids act as catalysts, has been stressed,3 but this classification adds nothing new in principle. 

The catalytic activity of ZrCk in acylation [11] and alkylation reactions [12] has been studied for more than half a century and compared with that of AICI3. More recently it has been found that Zr(OTf)4 and Hf(OTf)4 is sometimes an efficient catalyst in Friedel-Crafts acylation reactions [13], although the characteristics of the zirconium Lewis acid in this classical reaction, and the scope of the reaction, have not yet been extensively studied. 

Friedel-Crafts acylation reactions are fundamental and important processes in organic synthesis and in the chemical industry [16]. In these reactions more than a stoichiometric amount of a Lewis acid such as AICI3 or BF3 OEt2 is needed, because... 

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. 

The Friedel-Crafts acylation reaction is one of the oldest reactions for the preparation of ketones by carbon-carbon bond formation, and is one of the major methods used for the preparation of aromatic ketones. However, acylation by an acid chloride in the presence of a Lewis acid is also applicable to nonaromatic substrates. Whilst it has been known for almost as long as its better-known relative, the... 

The similarities between organic tin and silicon compounds, particularly their abilities to stabilize positive charge on a -carbon atom, suggest that vinylic and allylic tin compounds should be useful substrates for Friedel-Crafts acylation reactions. However, very few examples of the acylation of stannanes under the action of Lewis acids have been reported, and this remains a field of Friedel-Crafts reactions not yet fully exploited. The acylation of 1,2-bis(tri-n-butylstannyl)ethylene in the presence of aluminum chloride offers a moderately yielding route to tributylstannyl-substituted enones, useful as precursors to 4,5-dialky lcyclopent-2-enones. 

Nitrobenzene and nitroalkanes are good solvents for Friedel-Crafts acylation reactions. As well as being good solvents they also form addition complexes with Lewis acids such as aluminum chloride. The formation of the complex appears to reduce disproportionation and rearrangement reactions and thus allow acylation to be achieved under mild conditions. The acetylation of toluene in nitrobenzene affords more 4-methylacetophenone than when the reaction is conducted in cafbon disulfide. These results evidently reflect a lower steric demand in the reaction carried out in carbon disulfide. The reaction shown in equation (17) when carried out in nitrobenzene leads to the formation of the products (1) and (2) in good yield. However, when the solvent was changed to nitroethane, an improved yield (82%) was obtained and the ratio of (1) (2) changed from 44 1 to 61 1. ... 

The classical Friedel-Crafts acylation reactions are usually carried out in the presence of a stoichiometric amount of Lewis acid catalyst and are very familiar today to all chemical research workers. 

As already underlined in the introduction to this book, catalytic homogeneous acylation reactions represent a remarkable improvement in the preparation of aromatic ketones because, in the conventional Lewis-acid-promoted reactions, formation of a stable complex between the ketone product and the catalyst implies that at least a stoichiometric amount of catalyst must be utilized. This drawback prompted a great number of studies aimed at setting up the experimental conditions to make catalytic Friedel-Crafts acylation reactions. Some positive results from fhe homogeneous catalytic Friedel-Crafts acylations are described here, with special attention to crucial economic and environmental advantages such as the recycling of expensive catalysts and the development of solvenf-free and highly selective synthetic processes. 

Hard Lewis acid chloroaluminate ionic liquids show intense catalytic activity in the Friedel-Crafts acylation reaction however, they suffer from the same issues as anhydrous aluminum chloride. i Of particular interest to these reactions, aluminum chloride may be replaced by indium trichloride to form chloroindate(III) ionic liquids. The advantage of using indium trichloride compared with aluminum chloride is represented by its hydrolytic stability and reduced oxophilicity. Chloroindate(III) ionic liquids are synthesized by mixing l-butyl-3-methylimidazolium chloride [C4mim]Cl with anhydrous indium trichloride at 80°C. In the benzoyla-tion of anisole with benzoic anhydride (BAN) at 80°C, the best yield of... 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

The Friedel-Crafts acylation reaction, named after the French and American chemists who discovered it, used to prepare aryl ketones, is catalyzed by the Lewis acid aluminum chloride. Although aluminum chloride is a catalyst, it must be used (in Friedel-Crafts reactions) in stoichiometric amounts, as the portion of aluminum chloride that is catalytically inactive strongly binds to the product. Because aluminum chloride is corrosive and difficult to handle and must be destroyed when the reaction is complete, chemists continue to seek more environmentally friendly catalysts for this reaction. 

An acylium ion is the electrophile required for a Friedel-Crafts acylation reaction. This ion is formed by the reaction of an acyl chloride or an acid anhydride with AICI3, a Lewis acid. 

A compound with a ketone group attached to a benzene ring can be prepared using a Friedel-Crafts acylation reaction (Section 15.13). Therefore, a cyclic ketone will result if a Lewis acid (AICI3) is added to a compound that contains both a benzene ring and an acyl chloride group separated by the appropriate number of carbon atoms. 

The relative reactivities of the five-membered-ring heterocycles are reflected in the Lewis acid required to catalyze a Friedel-Crafts acylation reaction (Section 15.13). Benzene requires AICI3, a relatively strong Lewis acid. Thiophene is more reactive than benzene, so it can undergo a Friedel-Crafts reaction using SnCl4, a weaker Lewis acid. An even weaker Lewis acid, BF3, can be used when the substrate is furan. Pyrrole is so reactive that an anhydride is used instead of a more reactive acyl chloride, and no catalyst is necessary. 

This paper deals with a novel approach of functionalizing poly (IB-PMS) copolymers using the Friedel-Crafts acylation reaction. Poly (IB-PMS) copolymer was reacted with an acylating agent, succinic anhydride, using aluminum chloride as a Lewis acid. The reaction involves the aluminum chloride-catdyzed substitution of an acyl group on the aromatic ring. 

Mikami s group has also demonstrated the advantage of the fluorous super-Lewis acids such as lanthanide tris(perfluorooctanesulfonyl)methide and perfluorooctane-sulfonimide complexes with respect to temperature-dependent solubility [13bj. For example, these complexes can be re-used for the Friedel-Crafts acylation reaction without fluorous solvents [Eq. (11)]. After the reaction mixture of anisole has been heated with acetic anhydride in 1,2-dichloroefhane in the presence of ytterbium perfluorooctanesulfonimide (10 mol%) at 80 °C for 6 h, the mixture is allowed to stand at -20 °C for 30 min to precipitate the ytterbium complex. The liquid phase is decanted and the residual lanthanide complex is re-used without isolation. No loss of activity is observed for the catalyst recovered. The total isolated yield of the product, which is combined from the three runs, is 78%. 

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. 

The Friedel—Crafts acylation reaction is often carried out by treating the aromatic compound with an acyl halide (often an acyl chloride). Unless the aromatic compound is one that is highly reactive, the reaction requires the addition of at least one equivalent of a Lewis acid (such as AICI3) as well. The product of the reaction is an aryl ketone ... 

Another use of visible light that eliminates the use of substances with environmental concerns has been reported by Kraus (40-41) from Iowa State University. The transformations investigated by Kraus involves the widely used Friedel-Crafts Acylation reaction which is catalyzed by Lewis Acids. By using quinolic moieties and aldehydes, Kraus was able to achieve formal synthesis of a number of target molecules of importance in the pharmaceutical industry including diazapam and analogues. 

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