Substitution reactions aromatic electrophilic: examples illustrating

A point of interest in lithiation mediated aromatic substitution reaction is, how to effect substitution at a less active position (in lithiation reactions) in presence of the more active. In one approach, after effecting lithiation at the more active position, the metallation mixture is treated with ClSiMe, which introduces — SiMcj at that point. Further lithiation now occurs at the second position. After reacting with a suitable electrophile, the SiMcj group is replaced by H by acid cleavage of the C—Si bond. The following example illustrates the approach... 

A simple example illustrates the reaction. When benzene reacts with benzyl chloride in the presence of 0.4 equivalents of AICI3, diphenylmethane (45) is isolated in 59% yield. If this reaction proceeds by electrophilic aromatic substitution, then the sp carbon of benzyl chloride is a precursor to a carbocation. To form a carbocation from benzyl chloride, the chlorine atom must react as a Lewis base with AICI3 to form PhCH2 AlCL. Benzene reacts with this carbocation via electrophilic aromatic substitution in the same manner as the reaction with Br in the previous section to form an arenium ion intermediate (see 40) to give 45. 

In the example (Expt 6.79) the reaction of the diazonium salt from o-chloroaniline with benzene to yield 2-chlorobiphenyl is illustrative. It should be noted, however, that when the liquid aromatic compound in which substitution is to occur is of the type ArZ, the directive influences which are used to explain electrophilic substitution processes are not operative. Thus irrespective of the nature of the substituent Z, ortho-para substitution predominates this result supports the assumption that the substitution process is radical in type. Although the classical reaction occurs in a two-phase system, the use of the more stable diazonium fluoroborates together with the phase-transfer catalyst 18-crown-6 can sometimes be more convenient. The literature method for the preparation of 4-chlorobiphenyl in this way is given as a cognate preparation in Expt 6.19 ... 

Participation by aromatic rings is also possible and there are now several examples of electrophilic aromatic substitution involving Pummerer intermediates. Equation (20), the alkylation of benzene with dimethyl sulfoxide in trifluoroacetic anhydride, illustrates the process in its simplest form. As with al-kenes, reaction with aromatics has been more widely exploited in intramolecular versions for the construction of carbocycles and heterocycles. In many cases the sulfoxide precursor is of the P-keto variety, thus ensuring regiospecificity in the point of cyclization. Equation (21) (formation of a six-member carbocycle), equation (22) (foimation of a six-membered sulfur heterocycle), equation (23) (formation of a six-membered nitrogen heterocycle) and equation (24) (foimation of a seven-membered nitrogen, sulfur heterocycle) provide illustrations of the versatility of this form of intramolecular aromatic alkylation. 

The experiments in Sections 15.2 and 15.3 illustrate the Friedel-Crafts alkylation and acylation of aromatic hydrocarbons, respectively. A complication of Friedel-Crafts reactions is apparent in the alkylation experiment, wherein rearrangements of the carbo-cations generated from the alkyl halide provide mixtures of substitution products. The acylation reaction of Section 15.3 provides an example of how a combination of electronic and steric effects can affect the orientation of electrophilic attack on an aromatic ring. 

Intramolecular Pd-catalyzed aryl-aryl coupling reactions under dehydrohalogenation are assumed to proceed via palladacycles as illustrated by the example in Scheme 47.[33]-P7] Several mechanistic pathways may explain the cyclopalladation step including the C,H-activation however, a reaction of an electrophilic arylpalladium bromide with the electron-rich phenolate in the sense of an electrophilic aromatic substitution is certainly a plausible explanation. C—C bond formation finally takes place by reductive elimination. 

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