Friedel-Crafts alkylations formation

Friedel-Crafts alkylation Formation of an alkyl-substituted benzene derivative by substitution of an alkyl carbocation or carbocation-like species on an aromatic ring. (p. 771)... 

Friedel—Crafts alkylation Formation of an alkyl aromatic compound using an alkyl derivative and a Lewis acid as with an alkyl halide and an aluminum trihahde. 

The formation of the (X-delocalized norbornyl cation via ionization of 2-norbornyl precusors in low-nucleophilicity, superacidic media, as mentioned, can be considered an analog of an intramolecnlar Friedel-Crafts alkylation in a saturated system. Indeed, deprotonation gives nortricyclane,... 

Blasius and coworkers have offered a somewhat different approach to systems of this general type. In the first of these, shown in Eq. (6.20), he utilizes a hydroxymethyl-substituted 15-crown-5 residue as the nucleophile. This essentially similar to the Mon-tanari method. The second approach is a variant also, but more different in the sense that covalent bond formation is effected by a Friedel-Crafts alkylation. In the reaction... 

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. 

Other methods for the regioselective SN2-opening of vinyloxiranes include intramolecular enolate addition for formation of cyclohexane systems [135, 136] and Friedel-Crafts alkylations [49, 137, 138]. 

Intermodular Alkylation by Carbocations. The formation of carbon-carbon bonds by electrophilic attack on the ir system is a very important reaction in aromatic chemistry, with both Friedel-Crafts alkylation and acylation following this pattern. These reactions are discussed in Chapter 11. There also are useful reactions in which carbon-carbon bond formation results from electrophilic attack by a carbocation on an alkene. The reaction of a carbocation with an alkene to form a new carbon-carbon bond is both kinetically accessible and thermodynamically favorable. 

Near-critical water has been used as a medium for various C-C bond formation reactions including Friedel-Crafts alkylation and acylation (Eq. 7.12).30 In these reactions, near-critical water solubilizes the organics and acts as a source of both hydronium and hydroxide ions, thereby replacing the normally required hazardous solvents and catalysts that require subsequent neutralization and disposal. 

In all that has gone before a tacit assumption has been made that the proportions of alternative products formed in a reaction, e.g. o-, m- and p-isomers, are determined by their relative rates of formation, i.e. that the control is kinetic (p. 42). This is not, however, always what is observed in practice thus in the Friedel-Crafts alkylation of methyl-benzene (Me o-/p-directing) with benzyl bromide and GaBr3 (as Lewis acid catalyst) at 25°, the isomer distribution is found to be ... 

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

It is well known (March, 1977) that an important synthetic application of Friedel Crafts alkylation and acylation is to effect ring closure. These reactions are most successful when 6-membered rings are formed, but 5- and 7-membered rings can be sythesised as well, although less readily. Quantitative data are not available, but the indication is strong that formation of... 

Table 3.5 Formation of linear alkylbenzene by Friedel Crafts alkylation.

The formation of linear alkylbenzene (LAB) by Friedel-Crafts alkylation is strongly influenced by homogeneous or heterogeneous reaction conditions (Table 3.5).7 The steric bulk of silica reduces over-alkylation and shelf life. Silica also catalyses the formation of ethers. 

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. 

The reaction looks like a simple Friedel-Crafts alkylation, but there is a twist — the leaving group is not on the C which becomes attached to the ring. After formation of the C7 carbocation, a 1,2-hydride shift occurs to give a C6 carbocation. The 1,2-hydride shift is energetically uphill, but the 2° carbocation is then trapped rapidly by the arene to give a 6-6 ring system. 

A similar problem of complex formation may be encountered if either amino or phenol groups are present in the substrate, and the reaction may fail. Under such circumstances, these groups need to be blocked (protected) by making a suitable derivative. Nevertheless, Friedel-Crafts acylations tend to work very well and with good yields, uncomplicated by multiple acylations, since the acyl group introduced deactivates the ring towards further electrophilic substitution. This contrasts with Friedel-Crafts alkylations, where the alkyl substituents introduced activate the ring towards further substitution (see Section 8.4.3). 

Friedel-Crafts Alkylations and Mukaiyama-Michael Reactions The metal-catalyzed addition of aromatic substrates to electron-deficient a- and 7i-systems, commonly known as Friedel-Crafts alkylation, has long been established as a powerful strategy for C-C bond formation. Surprisingly, however, relatively... 

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

Frequently substantially more than catalytic amounts of a Lewis acid metal halide are required to effect Friedel-Crafts alkylation. This is due partly to complex formation between the metal halide and the reagents or products, especially if they contain oxygen or other donor atoms. Another reason is the formation of red oils. Red oils consist of protonated (alkylated) aromatics (i.e., arenium ions) containing metal halides in the counterions or complexed with olefin oligomers. This considerable drawback, however, can be eliminated when using solid acids such as clays,97 98 zeolites (H-ZSM-5),99,100 acidic cation-exchange resins, and perfluoro-alkanesulfonic acid resins (Nafion-H).101-104... 

The mechanism of Friedel-Crafts alkylation with alkyl halides involves initial formation of the active alkylating agent, which then reacts with the aromatic ring. Depending on the catalyst, the solvent, the reaction conditions, and the alkyl halide, the formation of a polarized donor-acceptor complex or real carbocations (as either an ion pair or a free entity) may take place ... 

The stereochemical outcome of Friedel-Crafts alkylation may be either inversion (nucleophilic displacement) or racemization (involvement of a trivalent flat carbocation). Most transformations were shown to occur with complete racemization. In a few instances, inversion or retention was observed. For example, the formation of (—)-l,2-diphenylpropane [(—)-28] from (—)-26 was interpreted to take place through the 27 nonsymmetrically Jt-bridged carbocation, ensuring 50-100% retention of configuration 136... 

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