Anisole electrophilic substitution

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

Due to the aromatic character of Cp2Ee predicted by Woodward and confirmed by the reactivity toward electrophilic substitutions, which proceed with rates comparable to anisole, the name ferrocene was coined in analogy to simple aromatic systems [6]. 

As mentioned above, ferrocene is amenable to electrophilic substitution reactions and acts like a typical activated electron-rich aromatic system such as anisole, with the limitation that the electrophile must not be a strong oxidizing agent, which would lead to the formation of ferrocenium cations instead. Formation of the CT-complex intermediate 2 usually occurs by exo-attack of the electrophile (from the direction remote to the Fe center. Fig. 3) [14], but in certain cases can also proceed by precoordination of the electrophile to the Fe center (endo attack) [15]. 

Anisole has charge densities as shown in (85) and (86). This indicates that ground state anisole should undergo electrophilic substitution at the ortho... 

The acetylation over protonic zeolites of aromatic substrates with acetic anhydride was widely investigated. Essentially HFAU, HBEA, and HMFI were used as catalysts, most of the reactions being carried out in batch reactors, often in the presence of solvent. Owing to the deactivation effect of the acetyl group, acetylation is limited to monoacetylated products. As could be expected in electrophilic substitution, the reactivity of the aromatic substrates is strongly influenced by the substituents, for example, anisole > m-xylene > toluene > fluorobenzene. Moreover, with the poorly activated substrates (m-xylene, toluene, and fluoroben-zene) there is a quasi-immediate inhibition of the reaction. It is not the case with activated substrates such as anisole and more generally aromatic ethers. It is why we have chosen the acetylation of anisole and 2-methoxynaphtalene as an example. 

This does not occur in the case of catalyst and reactants here described. With Bronsted-type catalysis, the reaction between the benzoyl cation, Ph-C" =0, and the hydroxy group in phenol is quicker than the electrophilic substitution in the ring. This hypothesis has been also confirmed by running the reaction between anisole and benzoic acid in this case the prevailing products were (4-methoxy)phenylmethanone (the product of para-C-benzoylation) and methylbenzoate (obtained by esterification between anisole and benzoic acid, with the co-production of phenol), with minor amounts of phenylbenzoate, phenol, 2-methylphenol and 4-methylphenol. Therefore, when the 0 atom is not available for the esterification due to the presence of the substituent, the direct C-acylation becomes the more favored reaction. 

The fluorination of other activated aromatic compounds, such as anisole and phenol, undergo monofluorination mainly in the ortho and para positions, whereas the fluorination of deactivated aromatics, such as nitrobenzene, trifluoromethylbenzene and benzoic acid, give predominantly the corresponding meta fluoro-derivatives which is consistent with a typical electrophilic substitution process. Also, fluoro-, chloro- and bromo-benzenes are deactivated with respect to benzene itself but are fluorinated preferentially in the ortho and para positions [139]. At higher temperatures, polychlorobenzenes undergo substitution and addition of fluorine to give chlorofluorocyclohexanes [136]. 

Table 5—Summary of Electrophilic Substitution Reactions of Phenol, Diphenyl Ether, and Anisole... 

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]... 

Anisole acetylation, which was one of the main reactions investigated, was first shown to be catalysed by zeolite ten years ago by Bayer (13), which was confirmed by Harvey et al. (14), then by Rhodia (15). Large pore zeolites and especially those with a tridimensional pore structure such as HBEA and HFAU were found to be the most active at 80°C, in a batch reactor with an anisole/acetic anhydride molar ratio of 5 and after 6 hours reaction, the yield in methoxyacetophenone (MAP) was close to 70% with HBEA and HFAU zeolites, to 30% with HMOR and 12% with HMFI. With all the zeolites and also with clays and heteropolyacids, the selectivity to the para-isomer was greater than 98%, which indicates that this high selectivity is not due to shape selective effects but rather to the reaction mechanism (electrophilic substitution). The lower conversion observed with HMOR can be related to the monodimensional pore system of this zeolite which is very sensitive to blockage by heavy secondary products. Furthermore, limitations in the desorption of methoxyacetophenone from the narrow pores of HMFI are probably responsible for the low activity of this intermediate pore size zeolite. 

A nearly complementary pattern of reactivity has been found for photochemical electrophilic substitution. Proton exchange in the photolysis of toluene 8.4 takes place most rapidly at the meta position. In anisole 8.5, the corresponding reaction is predominantly ortho and meta. Nitrobenzene 8.6, however, exchanges protons most rapidly at the para position. 

When two or more significant resonance structures may be written for a molecule, it will be stabilized with respect to the basic structure. As a result, the energy required to reach the transition state will be increased unless there are corresponding interactions in the transition state. The latter will be the case for electrophilic substitution on anisole. 

For this reaction, only zeolite catalysts were found to show some activity which are presented in Table 2. HY not only stand out as the best material, but in this case, the reaction was much faster, in accordance with the classical electrophilic substitution rules of more activated substrate. The Hb which was as active as the HY in the case of anisole is now much less active with veratrole (entry 3 and 4), underlining the effect of secondary parameters related to the catalyst itself. Such parameters includes, the structure of the zeolite, the size and the shape of the pores, the diffusion and chimisorption of both the substrate and the acylating agent. 

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. ... 

The effect of the cyclodextrins on the regioselectivity of bromination of anisole is similar to that seen with acetanilide (Figure 3.2b). With systems more activated to electrophilic substitution, such as 3-methylacetaiulide and 3-methylanisole, the cyclodextrins... 

MO Calculations and Photoelectron Spectroscopy. Some all-valence-electron CNDO/2 SCF-MO calculations on fluorobenzene, hexafluorobenzene, pentafluoro-anisole, and some derived Wheland intermediates have been reported in a paper which is mainly concerned with derivatives of pyridine and the diazines (see p. 467). An MO-LCAO-SCF study of the electronic structure of fluorobenzene has yielded the electrostatic molecular potential and isopotential maps which are consistent with a poru-directing influence of fluorine in electrophilic substitution, ... 

Anisole, implicated in the preceding paragraph, can be the cause of an additional side reaction, another electrophilic substitution catalyzed by strong acids. To wit, the side chain carboxyl group of glutamyl residues participates in the Friedel-Crafts acylation of the scavenger and yields a stable ketone ... 

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