Arylation Friedel-Crafts reaction

Another version of the Friedel-Crafts reaction uses acyl halides instead of alkyl halides and yields aryl ketones... 

Vinylic halides and aryl halides do not form carbocations under conditions of the Friedel-Crafts reaction and so cannot be used in place of an alkyl halide or an acyl halide... 

Friedel-Crafts reactions are normally not successful when attempted on an aryl amine but can be carried out readily once the ammo group is protected... 

Aryl (Ar) phosphines are convenientiy prepared by Friedel-Crafts reactions. 

Halogenated pyridazines are generally inert as arylating agents in Friedel-Crafts reactions. The only example is the reaction of 3,6-dichloropyridazine with resorcinol and hydroquinone to give 3-aryl-6-chloropyridazines. 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

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. 

Answer Ester disconnection gives a tertiary alcohol (4S), Of the three possible Grignard disconnections, (a) is most helpful as it requires the Mannich product (49) of an aryl ketone (50) available by the Friedel-Crafts reaction. 

The FeCls-catalyzed Friedel-Crafts reactions of electron-rich arenes with imines or aziridines provide a facile and convenient route for the synthesis of p-aryl... 

Another methodology that is widely used for C-C bond formation is the Heck coupling (Heck, 1985 T.suji, 1995). The Heck reaction involves the palladium-catalysed arylation of olefinic double bonds (Eqn. (12)) and provides an alternative to Friedel-Crafts reactions for attaching carbon fragments to aromatic rings. 

Under Lewis-acid-catalyzed conditions, electron-rich arenes can be added to alkenes to generate Friedel-Crafts reaction products. This subject will be discussed in detail in Chapter 7, on aromatic compounds. However, it is interesting to note that direct arylation of styrene with benzene in aqueous CF3CO2H containing H2PtCl6 yielded 30-5% zram-PhCH CHR via the intermediate PhPt(H20)Cl4.157 Hydropheny-lation of olefins can be catalyzed by an Ir(III) complex.158... 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

Subsequently, the research groups of Terada and AntiUa reported highly enan-tioselective Friedel-Crafts reactions between N-substituted indoles and N-acyl aryl imines (Scheme 5.9) [17]. Interestingly, Antilla states that under his reaction condi-... 

Unsaturated 5(4H)-oxazolones undergo a Friedel-Crafts reaction with aromatic hydrocarbons in the presence of a Lewis acid. In particular, a 2-aryl-4-benzylidene-5(4H)-oxazolone 598 reacts with o- or p-xylene in the presence of aluminum chloride via ring opening and subsequent dearylation to yield 599 as indicated in Scheme 7.191. ... 

In a similar manner, an intramolecular Friedel-Crafts reaction of 2-aryl-4-(2-thienylidine)-5(477)-oxazolones 600 has been reported and, in this case, cycliza-tion and decarboxylation generates thienopyridines 601 (Scheme 7.192). ... 

Saturated non-acetal dimers, such as 153 and 154, can be prepared from 151 via aluminium acetylide condensations or Friedel-Crafts reactions. Although the acetylenic dimer 153 is /3-linked to C-10 of the artemisinin skeleton, the aryl dimer 154 is a-linked <1999JME4275>. 

Arylation (see also Coupling reactions, Friedel-Crafts reaction)... 

FRIEDEL-CRAFTS REACTION. Aluminum chloride anhydrous, introduced by Friedcl and Crafts, is used as reagent, generally in CS solution to avoid rise in temperature, for the preparation of (I) aryl-alkyl hydrocarbons, (2) di- and triphenylmethane and derivatives, and (3) aryl-alkyl and diaryl ketones, Other chlorides, such as those of zinc, irun(lll), and liniiV), are often effective in certain cases. 

The examples of intramolecular acylation by the use of aluminum chloride in the Friedel-Crafts reaction occur in the literature so frequently that no attempt has been made here to enumerate all of them. Table VII includes several different types of arylpropionic and aryl-butyric acids which have been cyclized by this method. 

Bis(r 6-aryl) derivatives of molybdenum have been prepared by the co-condensation of the arene and molybdenum atoms at 77 K.305 Friedel-Crafts reactions catalysed by [(r 6-arene)Mo(CO)3] complexes have been developed further, and such reactions with organic halides shown to proceed via an ionic mechanism.306... 

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