Alkylation of anisole

Direct Friedel-Crafts alkylation of anisole would give p-f-butylanisole, the sterically less hindered product. The bromine is therefore used to block the para position, then is removed when no longer needed. (For an activated substrate like anisole, a FeBr3 catalyst is not required for step 1.)... 

Cativiela, C., Garcia, J. I., Garcia-Matres, M., Mayoral, J. A., Figueras, F., Fraile, J. M., Cseri, T., Chiche, B. Clay-catalyzed Friedel-Crafts alkylation of anisole with dienes. Appl. Cat. A 1995, 123, 273-287. 

Sakurai reaction + Friedel-Crafts alkylation Two Lewis-catalyzed reactions to generate 3,4,4-triaryl-1-butenes can be performed in sequence in one pot using HfCU- For example, addition of an allylsilane to ArCHO is followed by alkylation of anisole or phenol. 

For the sake of completeness, it should be mentioned that the use of microreactors and miniaturized flow reactors for the Friedel-Crafts alkylation of aromatic compounds has also been documented by other authors. For example, the Friedel-Crafts alkylation ofbenzenewithcydohexene using H2SO4 as a catalyst has been described [7]. The reaction was conducted in a static micromixer giving 58% cyclohexylbenzene. PoUakofi and coworkers have carried out the Friedel-Crafts alkylation of anisole with n-propanol in supercritical CO2, testing five different Bronsted solid acid catalysts under systematic variation of process conditions such as temperature and pressure [8]. 

R. Amandi, P. Licence, S. K. Ross, O. Aaltonen, M. Poliakoff, Friedel-Crafis alkylation of anisole in supercritical carbon dioxide a comparative study of catalysts, Org. Process Res. Dev. 2005, 9, 451-456. 

The alkylation of anisole under the vigorous conditions necessary to introduce an isopropyl group (aluminum chloride at 120-140°) leads to extenave demethylation. Alkylation of phenol under many condi-... 

Extending this reaction to anisole as substrate, no aldehyde product was observed, while extensive de-alkylation of anisole to phenol occurred (Run 3). The important role of an added Bronsted acid (hydrogen fluoride) was confirmed as some aldehyde product was obtained from anisole in the presence of aluminium trichloride together with HF (Run 4). 

Preformed Carbocationic Intermediates. Propargyl cations stabilized by hexacarbonyl dicobalt have been used to effect Friedel-Crafts alkylation of electron-rich aromatics, such as anisole, /V, /V- dim ethyl a n il in e and 1,2,4,-trimethoxybenzene (24). Intramolecular reactions have been found to be regio and stereo-selective, and have been used ia the preparatioa of derivatives of 9JT- uoreaes and dibenzofurans (25). 

TFA, anisole, 75% yield. " Thioanisole has been used in this cleavage reaction to scavenge the benzyl cation7 Its absence results in considerable alkylation of the indolocarbazole nucleus7 ... 

Ethers can be prepared by reaction of an alkoxide or phenoxide ion with a primary alkyl halide. Anisole, for instance, results from reaction of sodium phenoxide with iodomethane. What kind of reaction is occurring Show the mechanism. 

Amyl bromide [Pentane, 1-bromo-], 82 Aniline [Benzenamine], 122 Anilines, o-alkylation of, 15 Anisole [Benzene, methoxy-], 48 Amsyl chloride [Benzene, l-(chloromethyl)-... 

The alkylation of benzenes having electron withdrawing groups, such as chlorobenzene and anisole, with 3 gave only monoalkylated, dialkylated. and trialkylated compounds.but no peralkylated products were obtained even upon heating of... 

Thioacetals eliminate to vinylsulfides in the presence of CuOTf (Scheme 46).192 Cu1 and Cu11 triflates are mild Lewis acids for Friedel-Crafts acylation and alkylation reactions. CuOTf effectively catalyzes the reaction of anisole with selenoesters.193,194 Copper(II) sulfate promotes epoxide ring opening reactions in the presence of pyridine,195 with retention of configuration being observed. Cu(OTf)2 is a catalyst for the ring opening of aziridine by aniline.196... 

Of the substituted phenol ethers the amino-derivatives of anisole (anisidine) and phenetole (pkenetidine) may be mentioned. They are prepared from the nitrophenols by alkylation and subsequent reduction of the nitro-group. 

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... 

As can be seen, asymmetrical carbonates give high chemoselective methylation reactions, provided that R has at least three carbon atoms (R > n-Cs, entries 2-4). Yet, in the case of reactive benzyl or allyl termini, the O-alkylation (forming PhOR) competes significantly with the formation of anisoles (entries 5-6). 

Unsubstituted cycloamyloses have been used to catalyze a number of reactions in addition to acyl group transfer. Brass and Bender (8) showed that cycloamyloses promoted phenol release from diphenyl and bis(p-nitro-phenyl) carbonates and from diphenyl and bis(m-nitrophenyl)methyl phos-phonates. Breslow and Campbell (10,11) showed that the reaction of anisole with HOCL in aqueous solution is catalyzed by cyclohexaamylose and cycloheptaamylose. Anisole is bound by the cyclodextrins and is chlorinated exclusively in the para position while bound. Cycloheptaamylose has been used to promote regiospecific alkylation followed by the highly selective oxidation shown in reaction (3) (95). In addition cycloheptaamylose effec-... 

A continuous procedure for the alkylation of mesitylene and anisole with supercritical propene, or propan-2-ol in supercritical carbon dioxide, with a heterogeneous polysiloxane-supported solid acid Deloxan catalyst has been reported giving 100% selectivity for monoalkylation of mesitylene with 50% conversion at 250 °C and 150 bar by propan-2-ol in supercritical carbon dioxide. p-Toluenesulfonic acid monohydrate has been demonstrated as an efficient catalyst for the clean alkylation of aromatics using activated alkyl halides, alkenes or tosylates under mild conditions. Cyclohexene, for example, reacts with toluene to give 100% cyclohexyltoluenes (o m p-29 18 53) under these circumstances. 

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