Friedel-Crafts condition

PhenyI-4-benzylidene-5(4H)-thiazolinone (206) reacts with benzene under Friedel-Crafts conditions or with phenylmagnesium bromide to... 

Secondary alkyl halides react by a similar mechanism involving attack on benzene by a secondary carbocation Methyl and ethyl halides do not form carbocations when treated with aluminum chloride but do alkylate benzene under Friedel-Crafts conditions The aluminum chloride complexes of methyl and ethyl halides contain highly polarized carbon-halogen bonds and these complexes are the electrophilic species that react with benzene... 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

These will not react with benzene under Friedel-Crafts conditions... 

Thus ring acylation of phenols is observed under Friedel-Crafts conditions because the presence of aluminum chloride causes that reaction to be subject to thermodynamic (equi librium) control... 

Acylation under Friedel-Crafts conditions goes readily. 

Highly unstable vinyl cations, generated in situ from vinyl triflates have also been arylated (the triflate group is replaced by the aromatics) to give vinyl aromatics under Friedel-Crafts conditions (28). 

Chiral diene—iron tricarbonyl complexes were acylated using aluminum chloride to give acylated diene—iron complexes with high enantiomeric purity (>96% ee). For example, /ra/ j -piperjdene—iron tricarbonyl reacted with acyl haUdes under Friedel-Crafts conditions to give l-acyl-l,3-pentadiene—iron tricarbonyl complex without any racemization. These complexes can be converted to a variety of enantiomericaHy pure tertiary alcohols (180). 

Under Friedel-Crafts conditions, /n j -l,2-dibenzoylethylene [959-28-4] is synthesized by the reaction of one mole of fumaryl chloride with two moles of benzene (30) (see Friedel-CRAFTSreactions). 

Alkylation. Benzene and phenol feedstocks are readily alkylated under Friedel-Crafts conditions to prepare extensive families of alkylated aromatics. These materials generally are intermediates in the production of surfactants or detergents such as linear alkylbenzenesulfonate (LABS) and alkylphenolethoxylate (APE). Other uses include the production of antioxidants, plasticizers, and lube additives. 

Various vinyl chloride adducts can be formed under acid-catalyzed Friedel-Crafts conditions. Vinyl chloride can add tertiary alkyl haHdes (54). It can... 

Thiophene is also readily acylated under both Friedel-Crafts and Vilsmeier-Haack conditions and similarly to pyrrole and furan gives 2-acylated products. An almost quantitative conversion of thiophene into its 2-benzoyl derivative is obtained by reaction with 2-benzoyloxypyridine and trifluoroacetic acid. The attempted preparation of 2-benzoylthiophene under standard Friedel-Crafts conditions, however, failed (80S139). 

Acylation of 3-alkyl-6-hydroxy-l,2-benzisoxazole has also been reported (77JIC875) under Friedel-Crafts conditions to give the 7-acyl product. Fries rearrangement of 6-acetoxy-3-methyl-1,2-benzisoxazole in the presence of AICI3 at 140 °C also provides a route to the 7-acetyl-6-hydroxy derivatives (73UC541). Reactions of these kind are rare in this series. 

Alkyl fluorides are more reactive than other alkyl halides under Friedel-Crafts conditions, whereas trifluoromethyl groups are less reactive than other trihalomethyl groups Thus, a bromoindane is prepared from 1-bromo-l-fluoro-2,2,3,3-tetramethylcyclopropane and benzene [5] (equation 8) whereas 3-tnfluo romethylphenyldiphenylchloromethane is obtained from 3-trifluoromethyl-benzotrichloride and benzene [9] (equation 9)... 

Desilylation-electrophilic substitution of trimethylsilylbenzenes provides a route to a number of mefa-substituted fluorobenzene derivatives such as 3-fluoro-acetophenone, which is unobtainable under normal Friedel-Crafts conditions [36] (equation 25). 

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. 

The behavior of such activated halides as alkylating agents under Friedel-Crafts conditions expands the scope of the synthesis. Aluminum chloride enhances the electrophilic character of the a,/S-unsaturated carbonyl system and permits the nucleophilic attachment of the aromatic addendum (Y ) to the carbon bearing the positive charge, with displacement of halogen [Eq. (5)]. Thus,... 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

Starting material for the first of these agents can in principle be obtained by alkylation of phenol with benzyl chloride 89. Cyclization of the product (90) under Friedel-Crafts conditions leads directly to isoxepac (91). ... 

Despite its utility, the Friedel-Crafts alkylation has several limitations. For one thing, only alkyl halides can be used. Aromatic (atyl) halides and vinylic halides do not react because aryl and vinylic carbocations are too high in energy to form under Friedel-Crafts conditions. 

Friedel-Crafts alkylations and acylations of N-arylamides also proceed normally. For example, benzoylation of acetanilide (iV-acetylaniline) under Friedel-Crafts conditions gives 4-aminobenzophenone in 80% yield after hydrolysis. 

Substituted 2-phenoxyphenylacetic acids readily cyclize under Friedel-Crafts conditions or acid catalysis to give dibenz[Z>,/]oxepin-10(l l//)-ones.71 85,104- 108 When this reaction is carried out in methanolic hydrochloric acid the 10-methoxy-substituted dibenz[6,/]oxepin system 9a can be isolated.109 5-(Nitro-2-phenoxyphenyl)-2-oxopropanoic acid undergoes cyclization in the presence of polyphosphoric acid yielding the carboxylated dibenzoxepin 9b.107... 

This rearrangement ensues principally according to the same scheme as shown in equation 15 yielding o- and/or p-sulfonyl-substituted phenols. Yields under Friedel-Crafts conditions are poor72 only under photochemical conditions73 or in exceptional cases74 are the yields over 10-25%. 

An important role must be attributed to intermediate mixed anhydrides of sulfonic acids and mineral acids sulfonic acid anhydrides are reported to need Friedel-Crafts conditions to generate sulfones327,476. Instead of arenesulfonic acids, their methyl esters may undergo insertion of sulfur trioxide477,478 yielding mixed anhydrides, which in turn furnish... 

The acyclic oligoynes 23-26 can be cyclized under Friedel-Crafts conditions, i. e. by treatment with AICI3 in CS2, which presumably proceeds via the intermediate tertiary propargylic 27 and )3-silyl-substituted vinylic carbocations of type 28 (Scheme 5). 

Beside these free radical reactions of sulfur dioxide, its electrophilic reactions generating sulfmates with organometallic compounds - or sulfinic acids with arenes under Friedel-Crafts conditions are well known. To complete these three-component syntheses, the sulfmates prepared first are transformed to sulfones by reactions with appropriate electrophiles, discussed earlier in this chapter, i.e. equation 82. 

Transition metal complexes containing Si-OH groups have been isolated in low yield after hydrolysis of the products formed in the reaction between (Me2N)2SiCl2 and ferrocene under Friedel-Crafts conditions [Eq. (25)] (151). 

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