Aromatic anisole acylation

Friedel-Crafts acylation is widely used for the production of aromatic ketones applied as intermediates in both fine chemicals and pharmaceutical industries. The reaction is carried out by using conventional homogenous catalysts, which represents significant technical and environmental problems. The present work reports the results obtained in the Friedel-Crafts acylation of aromatic substrates (anisole and 2-methoxynaphthalene) catalyzed by Beta zeolite obtained by crystallization of silanized seeds. This material exhibits hierarchical porosity and enhanced textural properties. For the anisole acylation, the catalytic activity over the conventional Beta zeolite is slightly higher than with the modified Beta material, probably due to the relatively small size of this substrate and the weaker acidity of the last sample. However, the opposite occurred in the acylation of a bulky substrate (2-methoxynaphthalene), with the modified Beta showing a higher conversion. This result is interpreted due to the presence of a hierarchical porosity in this material, which favors the accessibility to the active sites. 

Nafion-silica nanocomposite catalysts have also been tested in the Friedel-Crafts acylation of aromatics with acyl chlorides.191,194,371 Anisole, toluene, and... 

The rate of anisole acylation depended on the acetate (Table 2). Initially it was about 1.5 times greater with p-tolyl acetate and with 2-methoxyphenyl acetate than with phenyl acetate, slightly lower with 2-methoxyhydroquinone diacetate, 2.5 times lower with the hydroquinone diacetate and very low with 2,4,6-trimethylphenyl acetate. The low reactivity of this latter acetate can be related to limitations in the rate of diffusion of this bulky compound in the BEA zeolite pores. Furthermore, a greater reactivity of this acetate was found with HFAU zeolites whose pore size is greater. Curiously, with hydroquinone diacetate (but not with the 2-methoxyhydroquinone acetate), there was a quasi immediate deactivation. We are carrying out additional experiments so as to understand how the reactivity of aromatic acetates changes with their nature and the zeolite acidity and porosity. 

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. ... 

Gallium(lll) oxide supported on MCM-41 mesoporous silica shows high catalytic activity with little or no moisture sensitivity in the acylation of aromatics wifh acyl chlorides. The cafalysf is utilized in 1,2-dichloro-ethane af 80°C for 3 h wifh differenf aromatic compounds, and aromatic as well as aliphatic acyl chlorides, giving ketones in 54%-82% yield. The activity order of fhe aromatic subsfrafes is benzene (43% yield) < toluene (50% yield) < mesifylene (71% yield) < anisole (79% yield), in agreement with the electrophilic substitution trend previously observed. This acylation reaction follows a probable redox mechanism similar to thaf described in Scheme 4.26. ... 

Arenediazonium ions are relatively weak electrophiles, and therefore react only with electron-rich aromatic substrates like aryl amines and phenols. Aromatic compounds like anisole, mesitylene, acylated anilines or phenolic esters are ordinarily not reactive enough to be suitable substrates however they may be coupled... 

In exceptional circumstances the acylium ion (or the polarised complex) can decompose to give an alkyl cation so that alkylation accompanies acylation. This occurs in the aluminium chloride-catalysed reaction of pivaloyl chloride which gives acylation with reactive aromatics such as anisole, but with less reactive aromatics such as benzene, the acylium ion has time to decompose, viz. 

Electron-rich aromatic compounds such as durene, p-dimethoxybenzene, mesitylene, anisole, thiophene, and fluorene can be benzoylated or acetylated by the corresponding Af-acylimidazole in trifluoroacetic acid to give the corresponding benzophenone or acetophenone derivative in good yield (Method A). As the actual acylating agent, a mixed anhydride of trifluoroacetic acid and benzoic acid has been proposed 1973... 

Acylation of aromatic ethers in the presence of a variety of metal chlorides and oxides [52]. The rate enhancement was probably caused by large temperature gradients but was not evaluated quantitatively. Reaction conditions a single-mode stirred tank reactor, fourfold excess of anisole, no solvent. 

The high selectivity of homolytic acylation of protonated heteroaromatic bases and the fact that under the same experimental conditions homocyclic substrates (benzene, anisole, nitrobenzene, protonated aniline, and A,A-dimethylaniline) are not attacked, indicate that polar effects play a dominant role. Only aromatic substrates with very strong electron-deficient character give rise to significant homolytic acylation. 

The activity of 42%STA/silica catalysts for the acylation of related aromatic reactants with iso-butyric anhydride was investigated. In the presence of anisole and veratrole, 100% anhydride conversion was observed, leading to the expected para-acylation products. No reaction was observed in the presence of chlorobenzene and other deactivated aromatic systems. 

The route offers the possibility of further simplification, since aromatic hydrocarbons are readily acylated under Friedel-Crafts conditions. Thus, the acetylation of toluene in the presence of perchloric acid yields the trisubstituted pyrylium compound (27CB716). Alkoxy-benzenes behave in a similar manner and anisole gives a good yield of 2,4-di-(4-methoxyphenyl)-6-methylpyrylium perchlorate (51JCS726). 

As reported in the literature, the acylation of aromatic hydrocarbons can be carried out by using zeolites as catalysts and carboxylic acids or acyl chlorides as acylating agents. Thus toluene can be acylated by carboxylic acids in the liquid phase in the presence of cation exchanged Y-zeolites (ref. 1). The acylation of phenol or phenol derivatives is also reported. The acylation of anisole by carboxylic acids and acyl chlorides was obtained in the presence of various zeolites in the liquid phase (ref. 2). The acylation of phenol by acetic acid was also carried out with silicalite (ref. 3) or HZSM5 (ref. 4). The para isomer has been generally favoured except in the latter case in which ortho-hydroxyacetophenone was obtained preferentially. One possible explanation for the high ortho-selectivity in the case of the acylation of phenol by acetic acid is that phenylacetate could be an intermediate from which ortho-hydroxyacetophenone would be formed intramolecularly. 

In the RE(OTf)3-catalyzed Friedel-Crafts acylation, the acylation of aromatic compounds with electron-donating substituents, for example anisole and mesity-lene, proceeded smoothly whereas the reactivity of benzene, toluene, and xylenes was low under the same conditions. On the other hand, it was revealed that the catalyst activity of RE(OTf)3 was increased when combined with LiC104, and that the acceleration effect was strongly dependent on the amount of LiC104. 

A mixture of Yb(OTf)3 (620 mg, 1 mmol), anisole (1, 540 pL, 5 mmol), and acetic anhydride (940 pL, 10 mmol) in nitromethane (5mL) was stirred at 50 °C for 4h. After dilution with water (10 mL), the mixture was extracted with dichlorometh-ane. The organic layers were combined and dried over NaS04. After filtration and evaporation of the solvents, the crude mixture was purified by column chromatography on silica gel to afford 4-methoxyacetophenone (2). The aqueous layer was concentrated in vacuo to give a crystalline residue, which was heated at 190 °C for 4h in vacuo to afford 576.6 mg (93 %) Yb(OTf)3 as colorless crystals. The recovered Yb(OTf)3 was reused in the next acylation reaction. All products of the acylation of aromatic compounds shown in this chapter are known compounds and are commercially available. 

On the other hand, a pure Eley-Rideal mechanism, in which the aromatic compound in the liquid phase reacts with the adsorbed acylating agent was first proposed by Venuto et alP1,22] and more recently by others.[23] However, for acylation reactions of polar substrates (anisole, veratrole), chemisorption of the latter must be taken into account in the kinetic law. A modification, the modified Eley-Rideal mechanism, has been proposed 114,24-26 an adsorbed molecule of acylating agent should react with a nonadsorbed aromatic substrate, within the porous volume of the catalyst. However, the substrate is also competitively adsorbed on the active sites of the zeolite, acting somehow as a poison of the acid sites. That is what we checked through different kinetic studies of various aromatic electrophilic substitution reactions.[24-26]... 

The Friedel-Crafts reaction is polar (ionic) alkylation or acylation of electron-rich aromatics by alkyl cation or acyl cation species, derived from the reactions of alkyl halides or acyl halides with A1C13. Therefore, electron-rich aromatics such as anisole are very reactive, but electron-deficient aromatics such as pyridine are inert. 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

Draw a mechanism for the acylation of anisole by propionyl chloride. Recall that Friedel-Crafts acylation involves an acylium ion as the electrophile in electrophilic aromatic substitution. 

Acylation of aromatic ethers yields the corresponding keto ethers. Typical examples are found in the conversion of anisole with aluminum chloride and appropriate acyl halide to p-methoxybutyrophenone (85%) and p-methoxyphenyl benzyl ketone (84%). Mild catalysts like iodine and phosphorus pentoxide are also effective. 

When (253) reacts with phosgene the 1-acyl chloride product (254) can react with amines to give amides (79LA1756X while in a further transfer reaction with ketones the compounds (255) and (256) are produced (Scheme 146) (80H(14)97). Acylation of aromatic hydrocarbons using 1-acylimidazoles in the presence of trifluoracetic acid gives high yields provided that the aryl compounds are electron rich, e.g. p-dimethoxybenzene, thiophene, anisole <80BCJ1638). 

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