Anisole Friedel-Crafts alkylation

Tertiary, benzyl, and aHyhc nitro compounds can also be used as Friedel-Crafts alkylating agents eg, reaction of (CH2)3CN02 (2-nitro-2-methyl propane [594-70-7]) with anisole in the presence of SnCl gives 4-/-butylanisole [5396-38-3] (7). SoHd acids, such as perfluorodecanesulfonic acid [335-77-3], and perfluorooctanesulfonic acid [1763-23-1] have been used as catalysts for regio-selective alkylations (8). 

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). 

Tricarbonylcyclopentadienyl manganese undergoes Friedel-Crafts alkylation and acylation and sulfonation competition experiments 18) gave the reactivity order ferrocene >anisole>C5H5Mn(CO)3>C6H6, but again no comparative calculations of ring-electron densities are available. 

Friedel Crafts alkylation has been studied by Poliakoff in a continuous-flow reactor (Hitzler et al., 1998a). The reaction of mesitylene and anisole with propene or 2-propanol over a solid acid catalyst (based on a Deloxan support) in sc C02 provided exclusive formation of the monoalkylated products at 50% conversion. Use of the continuous-flow reactor prevents catalyst deactivation, and permits use of comparatively small reactors. The... 

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.)... 

Figure 17.50 shows how a benzyl alkoxide can be reduced in this way. Here, the reduction is part of the synthesis of an alkylated aromatic system. The target molecule contains a primary alkyl group. It is not possible to introduce this alkyl group by way of a Friedel-Crafts alkylation into the ortho-position of anisole in a regioselective fashion and without rearrangements (see Section 5.2.5). 

Friedel-Crafts Alkylation Reactions. The activation of glyoxylate esters,trifluoromethyl pyruvate esters, and unsaturated a-ketoesters by catalyst 2 converts these materials into effective electrophiles for asymmetric Friedel-Crafts alkylation reactions with activated arenes (eqs 16 and 17). In fact, bis(triflate) (2) is far superior to tbe bis(hexafluoroantimonate) complex at catalyzing the enantioselective alkylation of benzene derivatives. Aniline and anisole derivatives both give the reaction, as do heterocyclic aromatic compounds such as indole and furan. 

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]. 

The following steps can be used to convert anisole to o-t-butylanisole. Give the reagent for each step. Explain why the overall result cannot be achieved in one step by a Friedel-Crafts alkylation. Hint Sections 4.10 and 4.11 may be helpful for the second part of this question.)... 

Consider the Friedel-Crafts alkylation of toluene and anisole, C H50CH3, with l-chloropropane/AlCl3. Given your understanding of substituent effects on Sg2 reactions, how would you expect the ratio of n-propyl alkylation to isopropyl alkylation to differ for these two arenes Explain your answer. 

Friedel-Crafts alkylations of chlorobenzene, chloropropylbenzenes, and p-xylene by cyclopropane have been examined, employing sulphuric acid and aluminium trichloride as catalysts. The alkylation of benzene, toluene, and anisole by 1-bromo-1-fluorocyclopropane results in indanes, indenes, and alkenylbenzenes. Intramolecular acylation of (183) affords products of attack at C-1 and C-2 of the cyclo-... 

Friedel-Crafts Alkylation. One of the first uses for this highly Lewis acidic reagent in organic synthesis was found by Mikami in the Friedel-Crafts alkylation reaction of anisole (eq 2). Here the first example of TMSNTf2 outperforming TMSOTf was found. 

Hitzler et al. (316) report the Friedel-Crafts alkylation of mesitylene (C6H3Me3) and anisole with propene or 2-propanol using a heterogeneous polysiloxane-supported solid acid catalyst (Degussa s Deloxan) in a small fixed-bed continuous reactor (10-ml volume) using SCF propene or CO2 as the reaction solvent. For the alkylation of mesitylene with propene at 160-180°C and 200 bar, yield of the monoalkylated product (l-isopropyl-2,4,6-trimethylbenzene) was only approximately 25% due to the formation of the dialkylated product as well as dimers and trimers of propene. Selectivity to the monoalkylated product was significantly higher (40% yield) for alkylation with 2-propanol in scCOa. 

The redox system between Ga(I) and Ga(III) could be used in organic synthesis. Saigo showed that the reaction of Ga2Cl4 with benzaldehyde in the presence of anisole gave 0- or p-benzylated arenes by reductive Friedel-Crafts alkylation (Scheme 7.66) [100]. Acetals could also be used for this transformation [101]. 

Benzene has been amido-alkylated by reaction with ArC6H4CHClNR COR and AICI3 (R and R are various alkyl and phenyl) to ArCHPhNR COR in fair to good yields.Anisole and phenetole have been alkylated with l-chloro-2,3-epoxy-5-methylhex-5-ene and AlCls. A dissertation on apparent anomalies in the Friedel-Crafts alkylation of 2,6-dimethylphenol and its alkyl ethers has been cited. 

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... 

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