Friedel-Crafts aromatic substitutions

Friedel-Crafts aromatic substitution reactions have been widely explored in polymer chemistry [29,30] and generally proceed with Lewis acids such as AICI3 with elimination of hydrogen halides. In superacid solutions, however, the Friedel-Crafts reactions take place with dehydration from the oxygen of the carbonyl group and the proton of aromatics. The reactivity of the pro-tonated carbonyl group in the superacid can be further increased by the... 

The Friedel-Crafts alkylation and acylation are of very little, if any, synthetic interest when applied to heterocyclic aromatic bases the substitution of protonated heterocycles by nucleophilic carbon-centered radicals is instead successful. This reaction, because of the dominant polar effect which is mainly related to the charge-transfer character of the transition state (Scheme 1), reproduces most of the aspects of the Friedel-Crafts aromatic substitution, but reactivity and selectivity are the opposite. 

The parallelism with the Friedel-Crafts aromatic substitution arises because the more stable the carbocation, the more nucleophilic the corresponding radical will usually be. Thus, in principle, all the electrophilic species employed in the Friedel-Crafts reaction, when used as the corresponding radicals, should behave as nucleophiles in the selective substitution of heteroaromatic bases. 

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... 

Six-membered N-heteroaromatic bases are known to be deactivated systems toward electrophilic substitution. Thus, reactions following the Friedel-Crafts protocol generally give on them products substituted onto the less electron-poor positions. Otherwise, their reactions with nucleophilic carbon-centered radicals reproduce most of the Friedel-Crafts aromatic substitutions, but with opposite reactivity and selectivity. The general reaction mechanism is shown in Scheme 6. 

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 second takes place if the organic halide contains aromatic rings this is a classical Friedel-Crafts electrophilic substitution, e.g. ... 

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

The resins are made by batch processes employing Friedel-Crafts reactions or nucleophilic aromatic substitution. Udel resin and Radel R resin are produced by the nucleophilic displacement of chloride on 4,4 -dichlorodiphenyl sulfone by the potassium salts of bisphenol A and 4,4 -biphenol, respectively (97) ... 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

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