Acylation of anisole

Scheme 1 Acylation of anisole with acetyl chloride...

Tab. 7.6. G raphite-supported acylation of anisole (51) by use of a variety of acylating reagents (RCOX) under the action of MW irradiation3 [27, 66].

Comparative attempts at graphite-supported acylation of anisole, toluene, and naphthalene using classical heating afforded interesting results [66]. With nonvolatile reactants the yields were almost identical with those obtained under the action of MW. In contrast, if at least one reactant was volatile (MeCOCl, PrCOCl) or sublim-... 

Thus, the best compromises for Boc and Fmoc chemistries seem to be cyclohexyl and 2,4-dimethylpent-3-yl (Dmpn), which is of intermediate stability, and the removal of which by trifluoromethanesulfonic acid with the aid of thioanisole (see Section 6.22) leads to minimal imide formation (see Section 6.13). Points to note are that acidolysis of esters by hydrogen fluoride can lead to fission at the oxy-car-bonyl bond instead of the alkyl-oxy bond, thus generating acylium ions that can react with nucleophiles (see Sections 6.16 and 6.22), and that benzyl esters may undergo transesterification if left in methanol. The side reactions of cyclization (see Section 6.16) and acylation of anisole (see Section 6.22) caused by acylium ion formation do not occur at the side chain of aspartic acid.47-51... 

RS Feinberg, RB Merrifield. Modification of peptides containing glutamic acid by hydrogen fluoride-anisole mixtures. y-Acylation of anisole or the glutamyl nitrogen. 

The ionic liquids made of ferric chloride and tin chloride displayed good properties as alternative catalysts in the acylation reactions (127). For the acylation of mesitylene with acetylchloride and for the acylation of anisole with acetylanhydride, the best results were obtained with a ferric chloride-containing ionic liquid. The conversions were much higher, and the selectivity obtained was in the same range relative to those observed with the Al- and Sn-chloride-containing ionic liquids. 

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. 

The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 31). 

Table 5.28. Activity of Nafion Catalysts in the Acylation of Anisole with Octanoic Acid376...

Scheme 6.10 Montmoril Ionite I<10—Fe (111) as reusable catalyst for the quantitative acylation of anisole by p-nitrobenzoyl chloride.

The set of catalysts selected for the dehydration of 2-butanol was also tested for the Friedel-Crafts acylation of anisole [69, 70]. The catalytic test was performed in the liquid phase due to the high boiling points of the reactants and products of this reaction. Anisole was reacted with acetic anhydride at 120 °C in the absence of solvent. In principle, acylation can occur on both the ortho and para positions of anisole. The main product (>99%) over all catalysts in this study was para-methoxyacetophenone, indicating that the reaction predominantly takes place inside the zeolite micropores. The same trend in catalytic activity as in the 2-buta-nol dehydration reaction is observed the conversion of anisole into para-nicihoxy-acetophenone increases upon increasing Ge content of the catalyst (Fig. 9.17) [67]. The main cause of deactivation for this reaction is accumulation of the reaction products inside the micropores of the zeolite. The different behavior of Ge-ZSM-5, compared with ZSM-5, may therefore be due to improved diffusional properties of the former, as the presence of additional meso- and macropores allows for... 

An interesting ring closure has been described in an attempt to effect an acylation of anisole with j3-phenylpropionic acid in the presence of chloroacetic anhydride.78 Only intramolecular acylation occurred, giving hydrindone-1 the yield after heating for forty-eight hours at 170° was 74%. 3,3-Diphenylhydrindone-l was similarly prepared in 67% yield. This further stresses the preference for intra- over inter-molecular acylation. 

A recent article reported the use of strongly acidic mesoporous aluminosilicates prepared from zeolite seeds in the acylation of anisole with octanoyl chloride.[30] The mesoporosity improving the transport of the reactants and the presence of strong acid sites lead to high conversion (>90 %) and high selectivity (100 %). 

Beers, A. E. W., van Bokhoven, J. A., de Lathouder, K. M., Kapteijn, F. and Moulijn, J. A. Optimization of zeolite Beta by steaming and acid leaching for the acylation of anisole with octanoic acid a structure-activity relation, J. Catal., 2003, 218, 239-248. 

Shih, P.-C., Wang, J.-H., Mou, C.-Y. Strongly acidic mesoporous aluminosilicates prepared from zeolite seeds acylation of anisole with octanyl chloride, Catal. Today, 2004, 93-95, 365-370. 

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. 

In place of AICI3, Yb triflate in nitromethane promotes the acylation of anisole, thioanisole and iV.iV-dimethylaniline to the corresponding acetophenones as shown below [165]. 

Subsequently, Corma and coworkers [49] reported the acylation of anisole with phenacetyl chloride over H-Beta and H-Y. The FC acylation of electron-rich heteroaromatics, such as thiophene and fur an, with acetic anhydride over modified ZSM-5 catalysts (Fig. 2.17) in the gas phase [50] or liquid phase [51] was also reported. 

Several metal triflate salts have been tested in the Friedel-Crafts acylation of anisole with benzoyl chloride in [C4Ciim][BF4]. At a reaction temperature of 80°C and catalyst loadings of 10 mol%, all salts led to 100% conversion with reaction rates decreasing in the order Cu(OTf)2 > Zn(OTf)2 > Sn(OTf)2 Sc(OTf)3, see Scheme 9.22.[92]... 

With arenes bearing a single resonance donor substituent (NR2, OMe, F), the addition is strongly preferred at the meta position, with small amounts of ortho substitution (0-10%). " The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 115). ... 

Selvin, R., Sivasankar, B., Rengaraj, K. Kinetic studies on Friedel-Crafts acylation of anisole by clayzic. React. Kinet. Catal. Lett. 1999, 67, 319-324. 

Table 2.9 Comparison of the Friedel-Crafts acylation of anisole using AICI3 (liquid phase) and H-Beta (heterogeneous).

We focus first on the batch acylation of anisole in the liquid phase. By fixing primary reaction parameters we can focus only on the impact of the nature of the catalyst (Table 14.1). 

Rhodia [2] has operated the first industrial application of zeolite for the acylation of anisole to para-methoxyacetophenone, which is a precursor of avobenzone (trade names PARSOL 1789, EUSOLEX 9020, ESCALOL 517, etc.) used in sun creams (Equation 14.1) ... 

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