Toluene Friedel-Crafts reaction

The p-methylacetophenone is readily prepared by the Friedel-Crafts reaction cf. p. 254), toluene being treated with acetyl chloride in the presence of alumfnium chloride. The toluene is employed in considerable excess so that it... 

Stereoselectivity was also observed in the Friedel-Crafts reaction of optically active plienyloxirane with toluene and anisole. The product diarylethanol had an enantiomeric ratio of 60 40 (37). 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

Friedel-Crafts. 2-Phenylpropanol results from the catalytic (AlCl, FeCl, or TiCl reaction of ben2ene and propylene oxide at low temperature and under anhydrous conditions (see Friedel-CRAFTS reactions). Epoxide reaction with toluene gives a mixture of 0-, m- and -isomers (75,76). 

There are relatively few kinetic data on the Friedel-Crafts reaction. Alkylation of benzene or toluene with methyl bromide or ethyl bromide with gallium bromide as catalyst is first-order in each reactant and in catalyst. With aluminum bromide as catalyst, the rate of reaction changes with time, apparently because of heterogeneity of the reaction mixture. The initial rate data fit the kinetic expression ... 

What is an immediate precursor of toluene " Benzene, which could be methylated in a Friedel-Crafts reaction. Alternatively, "What is an immediate precursor of bromobenzene " Benzene, which could be brominated. 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

Friedel-Crafts reactions involving electrophilic substitution of aromatic compounds have been reported on solid base catalysts such as thallium oxide and MgO. The rates of benzylation of toluene by benzyl chloride over MgO nanocrystals were found to be of the order CP-MgO > CM-MgO > AP-MgO.56 An important observation in the study was that x-ray diffraction of the spent catalyst... 

The reaction of various A-tosylated a-amino acids (94) with benzene in concentrated sulfuric acid yielded diphenyl derivatives (95)." The mechanism proposed for the reaction (Scheme 9) involves initial protonation of the carboxyl group to give (96), which suffers decarbonylation to the A-tosyliminium salt (97). This reactive electrophile (97) interacts with benzene to give a monophenyl compound (98) which, via a Friedel-Crafts reaction, interacts with another molecule of benzene to yield the diphenyl compound (95)." Toluene and p-xylene reacted analogously to yield diarylated products. 

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

Figure 6.45 Hydroxy-flinctionalized thiourea derivatives (20mol% loading) screened in the enantioselective Friedel-Crafts reaction of indole with trons-P-nitrostyrene at 20°C in toluene.

Thiourea catalyst 139 was also screened in the asymmetric Friedel-Crafts reaction between 2-naphthol trans-nitrostyrene (73% yield 0% ee 18 h in toluene at -20 °C and 10 mol%) [277], in the asymmetric aza-Michael reaction of O-benzyl-hydroxylamine to chalcone (72% conv. 19% ee 72 h in toluene at 20 °C and 20mol% catalyst loading) [293], and in the asymmetric Morita-BayUs-HiUman [176, 177] reaction between cyclohexenecarbaldehyde and 2-cyclohexene-l-one (20% yield 31% ee 46 h at rt and 20mol% DABCO and 139) [310]. In aU these transformations, thiourea 139 proved to be not competitive to the organocatalysts probed for these transformations under identical screening conditions and thus was not employed in the optimized protocols. 

This yield of acetophenone is 10% better than that obtained in the ordinary Friedel-Crafts reaction. A similar method can be applied to the preparation of p-tolyl-methyl-ketone, 20 gms. (1 mol.) of dry toluene, 2 gms. of aluminium powder, 35 gms. of mercuric chloride, and 17 gms. (1 msl.) of acetyl chloride being used. The yield is 45% theoretical (13 gms.). The ketone is obtained as a low-melting solid, B.P. 224°. 

Benzylation of toluene with benzyl chloride, which is a typical example of Friedel-Crafts alkylation, is known to be catalyzed by Lewis-type superacids such as A1C13 and BF3. This type of catalyst has been mostly used for the Friedel-Crafts reaction, which is one of the most studied of organic reactions. This reaction was performed over several metal oxides and sulfates, and iron sulfates showed an unexpected effectiveness for the reaction (102-104). The catalytic activities of FeS04 and Fe2(S04)3 for the reaction were examined in detail the activities were remarkably dependent on calcination temperature, the maximum activity being observed with calcination at 700°C (105-107). Catalytic actions analogous to the above case were also observed with other Friedel-Crafts reactions, the benzoyl-ation of toluene with benzoyl chloride (108), the isopropylation of toluene with isopropyl halides (109), and the polycondensation of benzyl chloride UIO). 

Acid chlorides of the respective half esters are converted to the desired keto esters by Friedel-Crafts reactions resembling those developed by Fieser for preparing the w-(p-chlorobenzoyl)nonanoic acid ester (5). The keto esters are converted to the respective keto acids through saponification with 10% alcoholic potassium hydroxide, acidification and recrystallization from toluene. Yields of the keto acids based upon the respective acid chlorides are 75 and 79%. Properties of the keto acids and their derivatives are given in Tables I and II. 

Padwa and Kuethe have also used vinylogous Pummerer reactions of amido sulfoxides in the preparation of nitrogen-containing heterocycles. Vinyl amido sulfoxide (224) underwent an additive Pummerer reaction, on treatment with trifluoroacetic anhydride, to yield product 226 (Scheme 57).123 The a-thiocarbo-cation 225 generated from the Pummerer reaction of N-methyl-N-phenyl-2-[2-(toluene-4-sulfinyl)phenyl]acetamide (224) underwent a Friedel-Crafts reaction at the y-carbon with the tethered aromatic ring. Reductive removal of the... 

Synthesis.—This hydrocarbon is by far the most important of those in which two or more benzene rings are linked together by intervening aliphatic carbon groups. Just as methyl chloride and benzene by the Friedel-Craft reaction yield phenyl methane (methyl benzene or toluene) and methylene chloride, di-chlor methane, with benzene yields di-phenyl methane so by the same reaction tri-chlor methane, chloroform, yields with benzene a hydrocarbon which by this synthesis must be tri-phenyl methane. 

Commercial benzene (bp 80°) and toluene (bp 111°) contain thiophene and methylthiophene as the main impurities. These impurities are more reactive than benzene or toluene in aromatic substitution reactions and therefore should be removed before using the material for reactions such as the Friedel-Crafts reaction. The thiophenes may be removed by shaking or stirring the hydrocarbon with one-tenth its volume of concentrated sulfuric acid for one-half hour. Because of the reactivity of toluene, the temperature should be maintained under 35° by occasional cooling. This treatment is, however, rarely necessary since thiophene-free benzene and toluene are commercially available at a reasonable cost. 

Next ask yourself, What is an immediate precursor ofp-bromotolueneT Perhaps toluene is an immediate precursor because the methyl group would direct bromination to the ortho and para positions, and the isomeric products could be separated. Alternatively, bromobenzene might be an imme ate precursor because we could carry out a Friedel-Crafts methylation li obtain para product. Both answers are satisfactory, although, in view of 1 difficulties often observed with polyalkylation in Friedel-Crafts reactions, bromination of toluene may be the better route. ... 

What is an immediate precursor of toluene Benzene, which could be methylated in a Friedel-Crafts reaction. 

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