Aluminum chloride acylation reaction

Friedel-Crafts acylation of aromatic compounds (Section 12.7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of aluminum chloride. The reaction is electrophilic aromatic substitution in which acylium ions are generated and attack the ring. 

The importance of acyl cations in acetylation is indicated in several studies (Gore, 1955). Friedel-Crafts catalysts alter the rate of acylation but do not modify the selectivity of the reaction. For example, the antimony pentachloride-catalyzed benzoylation of toluene proceeds 1.3 x 103 more rapidly than the aluminum chloride-catalyzed reaction. 

Balaban, Mateescu, and Nenitzescu,495 diacylatcd l,3-diphenyl-2-propanone (213, R = Ph) to 3,5-diphcnyl-4-pyrones (215), the former with acetic and polyphosphoric acids, the latter with acetyl chloride and aluminum chloride. This reaction follows the usual course of ketone acylation,13 235, z36> 409 and has been studied in detail by several research groups in the last 3 years.102 107 A similar reaction takes... 

Intramolecular acylations of the Bischler-Napieralski type have been used as crucial steps in the synthesis of indole alkaloids of the yohimbine class <94JCS(Pl)299, 94TL1071>. Also, the aluminum chloride-catalysed reaction of the indolosuccinic anhydride (46) gave the bridged cyclic product (47) rather than the cyclopentanone (49), presiunably because the reaction involves initial acylation at C-3 and reaction via the less strained intermediate is favored. Formation of the cyclopentanone (49) can be achieved using the polyphosphate ester cyclodehydration of the modified intermediate (48) (Scheme 13) <90JCS(Pi)2487>. 

Anionic surfactants with the general structure RpCONH-X-COONa (e.g., X = -(0112)5-) have been reported in the patent literature. These surfactants are synthesized from the corresponding isopropyl ester and 6-amino-hexanoic acid sodium or ammonium salt (H2N(CH2) 5COOM). Another class of anionic surfactants derived from PFCA derivatives are perfluoroacylbenzenesulfo-nates (Scheme 18.11). This group of surfactants is synthesized by Friedel-Crafts acylation of benzene with a PFCA halide (e.g., perfluorooctanoyl chloride) in the presence of at least one equivalent of a Lewis acid (e.g., anhydrous aluminum chloride). This reaction proceeds smoothly and in good yields at subambient or ambient temperatures. The perfluoroacylbenzene is sulfonated with oleum or sulfur trioxide and neutralized with a base (e.g., sodium hydroxide). 

Partial rate factors may be used to estimate product distributions in disubstituted benzene derivatives The reactivity of a particular position in o bromotoluene for example is given by the product of the partial rate factors for the corresponding position in toluene and bromobenzene On the basis of the partial rate factor data given here for Fnedel-Crafts acylation predict the major product of the reaction of o bromotoluene with acetyl chlonde and aluminum chloride... 

As shown in the sixth entry of Table 24 4 C acylation of phenols is observed under the customary conditions of the Friedel-Crafts reaction (treatment with an acyl chloride or acid anhydride m the presence of aluminum chloride) In the absence of aluminum chloride however O acylation occurs instead... 

The preference for O acylation of phenols arises because these reactions are kmetically controlled O acylation is faster than C acylation The C acyl isomers are more stable how ever and it is known that aluminum chloride is a very effective catalyst for the conversion of aryl esters to aryl ketones This isomerization is called the Fries rearrangement... 

Thus ring acylation of phenols is observed under Friedel-Crafts conditions because the presence of aluminum chloride causes that reaction to be subject to thermodynamic (equi librium) control... 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

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. 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). 

Anthraquinone dyes are derived from several key compounds called dye intermediates, and the methods for preparing these key intermediates can be divided into two types (/) introduction of substituent(s) onto the anthraquinone nucleus, and (2) synthesis of an anthraquinone nucleus having the desired substituents, starting from benzene or naphthalene derivatives (nucleus synthesis). The principal reactions ate nitration and sulfonation, which are very important ia preparing a-substituted anthraquiaones by electrophilic substitution. Nucleus synthesis is important for the production of P-substituted anthraquiaones such as 2-methylanthraquiQone and 2-chloroanthraquiaone. Friedel-Crafts acylation usiag aluminum chloride is appHed for this purpose. Synthesis of quinizatia (1,4-dihydroxyanthraquiQone) is also important. 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

The strong para-directing influence of fluorine in Fnedel-Crafts acylation is illustrated by the reaction of fluorotoluenes with acetyl chloride Treatment of 2-fluorotoluene, 3-fluorotoluene, and 2-fluoro-3-methyltoluene with acetyl chloride and aluminum chloride gives, respectively, 91, 82, and 80% substitution para to fluorine [27]... 

One of the most useful reactions of acyl chlorides was presented in Section 12.7. Friedel-Crafts acylation of aromatic rings takes place when arenes are treated with acyl chlorides in the presence of aluminum chloride. 

On reaction with acyl chlorides and acid anhydrides, phenols may undergo either acylation of the hydroxyl group (O-acylation) or acylation of the ring (C-acylation). The product of C-acylation is more stable and predominates under conditions of thennodynamic control when aluminum chloride is present (see entry 6 in Table 24.4, Section 24.8). O-acylation is faster than C-acylation, and aryl esters are fomned under conditions of kinetic control. 

Friedel became internationally known for the synthetic method called the Friedel-Crafts Reaction using aluminum chloride as a catalyst in the the introduction of an alkyl or acyl group into benzene. James Mason Crafts was an American professor from MIT working with Friedel in 1877 at the Sorbonne. Crafts later became president of MIT. 

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