Aromatic compounds Friedel-Crafts reactions, limitations

Aromatic hydrocarbons substituted by alkyl groups other than methyl are notorious for their tendency to disproportionate in Friedel-Crafts reactions. This tendency has previously limited the application of the isomerization of para- or ortho-) m ky -benzenes to the corresponding meta compounds. At the lower temperature of the present modification, disproportionation can be minimized. 

Cyclopropene and its deuterium-labelled derivatives can be obtained by the photo-decarbonylation of the corresponding furan at 254 nm but the method is of strictly limited value because of the photolability of many cyclopropenes (Section IV.B.2). West and his coworkers have shown that aryltrihalo- and diaryldihalocyclopropenes are available from classical Friedel-Crafts aromatic substitution reactions employing the cyclopropenyl cation as electrophile. Thus tetrachlorocyclopropene is converted to its derived cation which is then allowed to react with an aromatic compound. The exothermic reaction provides monoarylcyclopropene at low ( 0°C) temperature and the diaryl derivative at higher ( > 50° C) temperature (equation 26). In this way 2-phenyl-1,3,3-trichlorocyclopropene can be obtained in 58 % yield and the p-fluorophenyl analogue in... 

Friedel—Crafts reactions with halomethyl aromatic compounds have been used to prepare several types of polymers. The reaction is usually unsatisfactory because of the formation of either low-molecular-weight or crosslinked polymers. Rate studies are complicated by the multifunctional nature of the reactants, and often by limited solubility of the products. The kinetics of the first two steps of the reaction between benzene and p-bis-chloromethylbenzene with SnC catalysts were investigated by Grassie and Meldrum [212]. The activation energy was found to be about 10 kcal mole . ... 

The carbonium ion may also be formed from an alkene or alcohol. The carbonium ion formed from any of these starting materials is particularly prone to rearrangement reactions. These are called Wagner-Meerwein rearrangements, and severely limit the synthetic utility of this reaction to form simple alkyl substituted aromatic compounds. The tendency to rearrange may be reduced if the acyl derivative is used instead. This modification is called the Friedel-Crafts acylation reaction, and it has the further advantage that normally only monoacylation occurs, instead of the polyalkylation that happens using the simple Friedel-Crafts reaction. 

Friedel-Crafts acylation involves the direct introduction of an acyl group on the aromatic rings. This reaction, when carried out using corrosive and liquid catalysts, poses tedious workup and separation problems. An effort to minimize such limitations was made by Alizadeh et al. (2007), who reported a Friedel-Crafts reaction involving the treatment of acetic anhydride with aromatic compounds in the presence of SSA as a reusable, nontoxic, and heterogeneous catalyst (Scheme 5.44). 

The formation of aromatic a-diketo compounds through either inter- [939] or intramolecular [940, 941] Friedel-Crafts reaction with oxalyl chloride is limited to just a few examples. 

Aldehydes cannot be synthesized by the Friedel-Crafts reaction using methanoyl chloride (formyl chloride) because it is an unstable compound. However, a gaseous mixture of carbon monoxide and hydrogen chloride reacts like formyl chloride. The formylation of an aromatic compound using this gaseous mixture and aluminum trichloride is called the Gatterman—Koch synthesis. Like the Friedel-Crafts reaction, this method is limited to activated aromatic compounds. 

Other typical electrophilic aromatic substitution reactions—nitration (second entr-y), sul-fonation (fourth entry), and Friedel-Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo electrophilic substitution reactions that are limited to only the most active aromatic compounds these include nitrosation (third entry) and coupling with diazonium salts (seventh entry). 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

An impressive number of papers and books has been published and numerous patents have been registered on the aq lation of aromatic compounds over solid catalysts. Recently Sartori and Maggi [1] have written an excellent review with 267 references on the use of solid catalysts in Friedel-Crafts acylation. In one section of this review, namely acylation of aromatic ethers or thioethers, the authors report work on acylation by solid catalysts such as zeolites, clays, metal oxides, acid-treated metal oxides, heteropolyacids or Nafion. When examining in details these results, it appeared very difficult for us to build upon these experimental results as the reaction conditions differ drastically from one paper to the next. This prompted us to reinvestigate the scope and limitations of the Friedel-Crafts acylation using heterogeneous solids as catalysts, trying as much as we could to rationalize the observed effects. 

Successively, Friedel and Crafts studied the generality and the limitations of the new synthetic method. They found that the reaction could be successfully applied to a large number of aromatic compounds, as well as alkyl and acyl chlorides or anhydrides in the presence of chlorides of certain metals such as aluminum, zinc, and iron. A mechanistic hypothesis was postulated on the basis of the possible existence of an intermediate compound 3 formed between benzene and aluminum chloride (Scheme 1.2). This intermediate would react with the electrophilic reagent, giving the substitution product and restoring the catalyst. 

The electrophile is usually produced by the reaction between a catalyst and a compound containing a potential electrophile (Eq. 15.3). The second-order nature of the reaction arises from the step shown in Equation 15.4 in which one molecule each of arene and electrophile react to give a cationic intermediate. The formation of this cation is the rate-determining step (rds) in the overall reaction the subsequent deprotonation of the cation (Eq. 15.5) is fast. The bimolecular nature of the transition state for the rate-limiting step and the fact that an electrophile is involved in attacking the aromatic substrate classifies the reaction as S 2 (Substitution Electrophilic Bimolecular). Experiments involving four different such reactions are given in this chapter Friedel-Crafts alkylation and acylation, nitration, and bromination. 

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