Friedel-Crafts reaction, reversibility

Review Problem 6 Some chemists who were investigating the possibility of reversible Friedel-Crafts reactions, wanted an activated aromatic ring cormected to a branched alkyl chain and chose to make TM 82. How would you do it ... 

Zirconium monochloride reacts with sodium ethoxide to form additional adducts which hydrolyze in water. The monochloride does not react with benzene in a Friedel-Crafts reaction, and does not enter into intercalation reactions similar to those of zirconium disulfide. Both monohaUdes add hydrogen reversibly up to a limiting composition of ZrXH (131). 

In principle, sulfonyl compounds bearing highly-electron-accepting substituents are able to transfer the sulfonyl group as an electrophile. Thus, the exchange of aryl substituents in methyl aryl sulfones under catalysis of trifluoromethanesulfonic acid takes place258 (equation 46). This reaction represents a further example for the reversibility of Friedel-Crafts reactions. 

Friedel-Crafts reactions in the ionic liquid system l-methyl-3-ethylimidazolium chlo-ride-aluminium(ni) chloride can be performed with excellent yields and selectivities, and in the case of anthracene, have been found to be reversible. This ionic liquid has been shown to demonstrate catalytic activity in reactions such as Friedel-Crafts acylations (Surette et al., 1996 Boon et al., 1986) alkylation reactions (Koch et al., 1976),... 

The action of zinc in this case resembles that of anhydrous aluminium chloride in the Friedel-Crafts reaction. Phthalyl chloride here reacts in the s- form (cf. Reaction XX. (6) (vi.)). Both forms have been prepared (A., 392, 245 M., 40, 81). The s- form melts at 15°—16°, the as-at 88°—89°, while both boil at 275° at 720 mms. The s- form is converted into the as- by the action of aluminium chloride, while the reverse change is effected by the action of heat or of hydrogen chloride. (B., 55, 1305.)... 

The postulated generation of PM-128 + from HM-128 was observed as early as 1965 in sulfuric acid [378], We view this reaction as a reverse Friedel-Crafts reaction, not unlike that complementing the formation of heptamethylben-zenonium ion from HM-128 [379]. Although the formation of PM-128 + requires several consecutive reactions, its observation under radiolysis-ESR conditions cannot be ruled out categorically, since the sample preparation requires several hours... 

The carbocation intermediate in the Friedel-Crafts reaction (Chapter 22) is rather stable, being tertiary and benzylic, and the formation of the cation, normally the rate-determining step, with inevitably a negative p value, goes faster and faster as the electron-donating power of the substituents increases until it is faster than the cyclization which becomes the rate-determining step. The cycliza-tion puts electrons back into the carbocation and has a positive p value. As the two steps have more or less the reverse electron flow to and from the same carbon atom, it is reasonable for the size of p to be about the same but of opposite sign. 

The decarboxylation is a kind of reverse Friedel-Crafts reaction in which the electrophile is a proton (provided by the carboxylic acid itself) and the leaving group is carbon dioxide. The protonation may occur anywhere but it leads to reaction only if it occurs where there is a CO2H group. 

One rather interesting aspect of the Friedel-Crafts reaction is that trialkylation of benzene often leads to a symmetrical 1,3,5-isomer rather than a 1,2,4-derivative as would be expected from the ortho-para orientation of the alkyl group introduced initially. Since alkylation by the Friedel-Crafts method has been shown to be a reversible reaction,68 this anomalous orientation has been explained on the basis that both alkylation and dealkylation occur readily in the ortho and para positions. Simultaneously, however, some alkylation occurs in the meta position but no dealkylation68 If the reaction mixture is allowed to stand in contact with aluminum chloride for some length of time, then principally meta trialkyl derivatives will be formed ... 

Tliis reaction is reversible. In a reversed Friedel-Crafts reaction or Friedel-Crafts dealkylation, alkyl groups can be removed in the presence of protons and a Lewis acid. 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

Can t do it in the reverse order. The Friedel-Crafts reaction fails with the SO3H group there. 

Umpolung.—The proposition to convert available nucleophilic centres into electrophilic centres, and vice versa, would in principle double the number of reactions available to synthetic chemists. For instance, two papers have been noted from Seebach on the reversal of various carbonyl reactions, while the anionic equivalent of the Friedel-Crafts reaction has been provided by Whitlock and co-workers. 

This unwanted rearrangement can be reversed by treatment of the product with sodium bicarbonate in water, but not without some accompanying hydrolysis. Several other shortcomings of the method are known, such as the HF catalyzed Friedel-Crafts reaction between y-carboxyl groups in glutamyl residues and aromatic nuclei in the polymer ... 

Transfer of selectivity from the lower to the upper rim is the most useful method for the selective synthesis of partially functionalized calixarenes at the upper rim. Indeed, one can exploit the different reactivity of aryl ethers compared to phenols to introduce, regioselectively, additional functional groups at the upper rim of partially alkylated calixarenes. Moreover, if l,3-dialkoxy-/ -r rt-butylcalix[4]arenes are submitted to the reverse Friedel-Crafts reaction, the tert-hwiyX groups are detached only from the para position of the phenolic nuclei, obtaining compounds where only two diametral aromatic rings are available for further functionalization. 

Although most of the methylbenzene (toluene, C6FI5CFI3) isolated from light naphtha is either used as an octane enhancer in gasoline or it is converted to benzene (by the acid-catalyzed reverse of the Friedel-Crafts reaction), some small amount is diverted to other ends as demanded by local economy and needs. Among these is its exhaustive nitration (Equation 6.108) to 2,4,6-trinitrotoluene (TNT), which continues to be used as an explosive. 

We have uncovered seven synthetically important reactions in this chapter so far. We can (1) brominate and (2) chlorinate benzene. We can (3) nitrate and reversibly (4 and 5) sulfonate benzene. The two Friedel-Crafts reactions (6 and 7) allow the construction of carbon-carbon bonds to give some alkyl benzenes and give you another synthetic route to compounds containing carbon-oxygen double bonds. Figure 14.48 summarizes the situation. 

Removal of the fert-butyl groups by a reverse Friedel-Crafts reaction is not applicable to p-ferf-butyUiomooxacalixarenes due to the fragility of the dibenzyl ether bonds in strongly acidic conditions. The introduction of different functional groups at the upper rim must therefore be done by varying the p-substituent in the starting phenol. 

Since alkylation by the Friedel-Crafts reaction has been demonstrated to be a reversible reaction,it has been suggested that the various anomalous orientations can be expUuned on this baris. Jacobs sen was the first of many to point out that normal alkyla-... 

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