Friedel-Crafts 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 ... 

When the reverse order of steps is attempted it is observed that the Friedel-Crafts acylation of nitrobenzene fails... 

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). 

Friedel-Crafts acylation sometimes shows a modest kinetic isotope effect. This observation suggests that the proton removal is not much faster than the formation of the (j-complex and that the formation of the n-complex may be reversible under some conditions. 

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. 

Aryl halides can be dehalogenated by Friedel-Crafts catalysts. Iodine is the most easily cleaved. Dechlorination is seldom performed and defluorination apparently never. The reaction is most successful when a reducing agent, say, Br or 1 is present to combine with the I" or Br coming off." Except for deiodination, the reaction is seldom used for preparative purposes. Migration of halogen is also found," both intramolecular and intermolecular." The mechanism is probably the reverse of that of 11-11." ... 

Rearrangement can also occur after the initial alkylation. The reaction of 2-chloro-2-methylbutane with benzene is an example of this behavior.35 With relatively mild Friedel-Crafts catalysts such as BF3 or FeCl3, the main product is 1. With A1C13, equilibration of 1 and 2 occurs and the equilibrium favors 2. The rearrangement is the result of product equilibration via reversibly formed carbocations. 

The topics analysed here include reversible termination and the formation of p-tolyl end-groups on polystyrenes made in toluene. For unknown reasons, most authors have very largely ignored this Friedel-Crafts alkylation, which in a polymer context is a transfer reaction. It was unfortunately termed molecular termination by Overberger and was explored by his and Smets groups. 

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),... 

Reversal of Friedel—Crafts Alkylation Hydro-de-alkylation or Dealkylation... 

The dicyclopentadienyl metal compounds undergo Friedel-Crafts alkylation and acylation, sulfonation, metalation, arylation, and formyla-tion in the case of ferrocene, dicyclopentadienyl ruthenium, and dicyclopentadienyl osmium, whereas the others are unstable to such reactions ( ). Competition experiments (128) gave the order of electrophilic reactivity as ferrocene > ruthenocene > osmocene and the reverse for nucleophilic substitution of the first two by n-butyl lithium. A similar rate sequence applies to the acid-catalysed cleavage of the cyclopentadienyl silicon bonds in trimethylsilylferrocene and related compounds (129), a process known to occur by electrophilic substitution for aryl-silicon bonds (130). 

Alkylation of the C(2) or C(3) carbons of the pyrrole ring can be accomplished by electrophilic aromatic substitution. Such substitution reactions may be carried out on the neutral heterocycle or on a metal salt. The magnesium salts are of most synthetic importance for the alkylation of both pyrroles and indoles. As discussed in Section 3.05.1.2.7, there is a reversal of the preferred site of electrophilic substitution between pyrroles and indoles. Thus Friedel-Crafts-type substitution of pyrroles gives 2-aIkylpyrroles while similar reaction... 

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.)... 

It has been demonstrated9 that photo-protonation of 2-diphenylmethyl-l,3-dimethoxy-benzene (4) to the cyclohexadienyl cation (5) not only results in dissociative cleavage of the diphenylmethyl cation (the reverse of the step in a Friedel-Crafts alkylation that produces the cyclohexadienyl cation), but is accompanied by a surprising rearrangement to the isomeric 2,4-dimethoxybenzenium ion (6). This (see Scheme 3) represents the first example of a system where rearrangement involving two isomeric... 

The acetyl group is attached to the ring by Friedel-Crafts acylation. It is a meta director, and its nitration gives the proper orientation of substituents. The order of the first two steps cannot be reversed, because Friedel-Crafts acylation of nitrobenzene is not possible (Section 12.16). Once prepared, m-nitroacetophenone can be reduced to m-nitroaniline by any of a number of reagents. Indeed, all three reducing combinations described in the text have been employed for this transformation. 

Reversing the order of introduction of the nitro and acyl groups is incorrect. It is possible to nitrate ethyl phenyl ketone but not possible to carry out a Friedel-Crafts acylation on nitrobenzene, owing to the strong deactivating influence of the nitro group. 

The mechanism for solvolysis of A3-iodane 22a involves generation of the intimate cyclohexenyl cation-iodobenzene pair 28. Friedel-Crafts vinylation of iodobenzene within the intimate ion-molecular pair 28 will produce a mixture of rearranged products 23 with selective formation of the ortho isomer [Eq. (17)]. The fact that solvolysis of 22a in methanol in the presence of an excess amount (50 equiv) of p-methyliodobenzene affords the exchanged vinyliodane 22b (4 %) in addition to the formation of 23 (o m p = 86 5 9) and the recovered vinyliodane 22a (49 %) suggests the reversible formation of the free cation 29 during solvolysis. 

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... 

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