Friedel-Crafts acylation acids

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

The only acid-resistant protective group for carbonyl functions is the dicyanomethy-lene group formed by Knoevenagel condensation with malononitrile. Friedel-Crafts acylation conditions, treatment with hot mineral acids, and chlorination with sulfuryl chloride do not affect this group. They have, however, to be cleaved by rather drastic treatment with concentrated alkaline solutions (J.B. Basttis, 1963 H. Fischer, 1932 R.B. Woodward, 1960, 1961). 

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... 

Friedel-Craft reaction Friedel-Crafts Friedel-Crafts acids Friedel-Crafts acylation... 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Preparation of Arylcarboxylic Acids and Derivatives. The general Friedel-Crafts acylation principle can be successfully appHed to the preparation of aromatic carboxyUc acids. Carbonyl haUdes (phosgene, carbonyl chloride fluoride, or carbonyl fluoride) [353-50-4] are diacyl haUdes of carbonic acid. Phosgene [75-44-5] or oxalyl chloride [79-37-8] react with aromatic hydrocarbons to give aroyl chlorides that yield acids on hydrolysis (133) ... 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

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). 

Friedel-Crafts acylation of unsaturated fatty acids can be carried out with succinic anhydride ia the presence of alkyl aluminium haUde (104). 

Friedel-Crafts Acylation. The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and thein derivatives. Acetyl chloride (acetic anhydride) reacts with benzene ia the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxyHc acid anhydrides to yield benzoyl derivatives of carboxyHc acids. These benzoyl derivatives are often used for constmcting polycycHc molecules (Haworth reaction). For example, benzene reacts with succinic anhydride ia the presence of aluminum chloride to produce P-benzoylpropionic acid [2051-95-8] which is converted iato a-tetralone [529-34-0] (30). 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

Friedel-Crafts acylation usually involves the reaction of an acyl halide, a Lewis acid catalyst, and the aromatic substrate. Several species may function as the active electrophile, depending on the reactivity of the aromatic compound. For activated aromatics, the electrophile can be a discrete positively charged acylium ion or the complex formed... 

Although the Lewis acids used as co-reagents in Friedel-Crafts acylations are often referred to as catalysts, they are, in fact, consumed in the reaction, with the generation of strong acids. There has been considerable interest in finding materials which could function as true catalysts. Considerable success has been achieved using lanthanide triflates. ... 

What combination of acyl chloride or acid anhydride and arene would you choose to prepare each of the following compounds by Friedel-Crafts acylation ... 

Friedel-Crafts acylation In the presence of aluminum chloride, acyl chlorides and carboxylic acid anhydrides acylate the aromatic ring of phenols. 

The most important method for the synthesis of aromatic ketones 3 is the Friedel-Crafts acylation. An aromatic substrate 1 is treated with an acyl chloride 2 in the presence of a Lewis-acid catalyst, to yield an acylated aromatic compound. Closely related reactions are methods for the formylation, as well as an alkylation procedure for aromatic compounds, which is also named after Friedel and Crafts. 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

The mechanism for that step is closely related to that of the Friedel-Crafts acylation. Upon subsequent hydrolysis the o-substituted Lewis acid-coordinated phenolate 7 is converted to the free o-acylphenol 2. By an analogous route, involving an electrophilic aromatic substitution para to the phenolate oxygen, the corresponding para-acylphenol is formed. 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

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