Carbocations from Friedel-Crafts alkylations

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... 

The mechanism of the Friedel-Crafts acylation is the same as the Friedel-Crafts alkylation. It involves an acylium ion instead of a carbocation. Like Friedel-Crafts alkylation, a Lewis acid is needed to generate the acylium ion (R-C = 0) but unlike a carbocation the acylium ion does not rearrange since there is resonance stabilisation from the oxygen ... 

From what has been said thus far, it is evident that the electrophile in Friedel-Crafts alkylation is a carbocation, at least in most cases. This is in accord with the knowledge that carbocations rearrange in the direction primary — secondary —> tertiary (see Chapter 18). In each case, the cation is formed from the attacking reagent and the catalyst. For the three most important types of reagent these reactions are... 

The mechanism for the production of 9-((chlorosilyl)alkyl)(luorenes from the Friedel-Crafts alkylation reaction of biphenyl with (l,2-dichloroethyl)silane in the presence of aluminum chloride as catalyst is outlined in Scheme 4. At the beginning stage of the reaction, one of two C—Cl bondsof (1,2-dichloroethyl)silane (CICH2—CICH—SiXi) interacts with aluminum chloride catalyst to give intermediate 1 (a polar +C-CI - ( +C-C1—Al CI3) or a carbocation C AICU ... 

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. 

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... 

The example of Friedel-Crafts alkylation is the reaction of benzene with 2-chloropropane (Fig. C). The Lewis acid (A1C13) promotes the formation of the carbocation needed for the reaction and does so by accepting a lone pair of electrons from chlorine to form an unstable intermediate that fragments to give a carbocation and AlCly (Fig. D). 

Rates for the key step of Friedel-Crafts alkylations, i.e., the attack of carbocations on arenes have only recently been reported [214,215]. Problems arising from the reversibility of the CC-bond-forming step have been overcome by performing experiments in presence of R4N + MC1,7+i salts, where MCl,r+1 acts as a base for the rapid deprotonation of the intermediate benzenium ions (Scheme 52). 

The formation of stable carbenium ions can be observed visually and/ or spectroscopically. For example, styrene and a-methylstyrene polymerizations are generally colorless because the growing carbenium ions absorb at approximately 340 nm (cf., Sections II.B and IV.B.l). However, these systems may turn brown or dark red at longer reaction times due to formation of indanyl carbenium ions (A 440 nm) [14,26,325] and other delocalized carbocations similar to those in Eq. (121). The stable cyclic diaryl carbenium ions are generated by hydride transfer from the initially formed indanyl end groups [Eq. (124)] in styrene polymerizations, and by methide transfer in a-methylstyrene polymerizations. The prerequisite for this termination is therefore intramolecular transfer by Friedel-Crafts alkylation protons liberated in the first stage can then reinitiate polymerization. 

Because the concentration of carbocations in a real polymerization is very low, model NMR studies have been used to obtain a deeper insight into the nature of the growing species. These experiments are restricted to sufficiently stable carbocations, such as those derived from vinyl ethers. Styrene derivatives are not stable enough and participate in Friedel-Crafts alkylation. For example, derivatives of a-methylstyrene easily deproto-nate, dimerize and then form intramolecularly indan derivatives. 

The alkyl carbocations formed from alkyl halides, aikenes and alcohols act as an electrophile in Friedel-Crafts alkylation reactions. ... 

Carbonium ions can be generated at a variety of oxidation levels. The alkyl carbocation can be generated from alkyl halides by reaction with a Lewis acid (RCl + AICI3) or by protonation of alcohols or alkenes. The reaction of an alkyl halide and aluminium trichloride with an aromatic ring is known as the Friedel-Crafts alkylation. The order of stability of a carbocation is tertiary > secondary > primary. Since many alkylation processes are slower than rearrangements, a secondary or tertiary carbocation may be formed before aromatic substitution occurs. Alkylation of benzene with 1-chloropropane in the presence of aluminium trichloride at 35 °C for 5 hours gave a 2 3 mixture of n- and isopropylbenzene (Scheme 4.5). Since the alkylbenzenes such as toluene and the xylenes (dimethylbenzenes) are more electron rich than benzene itself, it is difficult to prevent polysubsiitution and consequently mixtures of polyalkylated benzenes may be obtained. On the other hand, nitro compounds are sufficiently deactivated for the reaction to be unsuccessful. 

Most Friedel-Crafts reactions involve carbocation electrophiles. Because the carbocations derived from vinyl halides and aryl halides are highly unstable and do not readily form, these organic halides do not undergo Friedel-Crafts alkylation. 

Product B must arise from a Friedel-Crafts alkylation with the f-butyl cation as intermediate This comes from the loss of carbon monoxide from the acylium ion. Such a reaction happens oniv when the simple carbocation is stable. 

Similarly, carbocation rearrangements can occur by alkyl shifts. For example, Friedel-Crafts alkylation of benzene with l-chIoro-2,2-dimethyl propane yields (l,l-dimethylpropyl)benzene as the sole product. The initially formed primary carbocation rearranges to a tertiary carbocation by shift of a methyl group and its electron pair from C2 to Cl (Figure 26.10). 

Friedel Crafts alkylation (Section 12.6) Car-bocations, usually generated from an alkyl halide and aluminum chloride, attack the aromatic ring to yield alkylbenzenes. The arene must be at least as reactive as a halo-benzene. Carbocation rearrangements can occur, especially with primary alkyl halides. 

The two mechanisms for Friedel-Crafts alkylation are not dissimilar to the two mechanisms for nucleophilic aliphatic substitution. In an S,j1 mechanism, a carbocation is generated from an alkyl halide before the nucleophile attacks, but in an S 2 reaction the halide departs simultaneously with the nucleophile attacking the R group. In the Friedel-Crafts reaction, benzene behaves as the nucleophile. 

Once it was discovered that Friedel-Crafts alkylations and acylations involve cationic intermediates, chemists realized that other combinations of reagents and catalysts could give the same intermediates. We study two of these reactions in this section the generation of carbocations from alkenes and from alcohols. 

Friedel-Crafts alkylation has the problem of cation rearrangement, but there is another problem with this reaction. When benzene reacts with 2-bromopro-pane and AICI3, it gives a mixture of 53 (1-methylethylbenzene or isopropylbenzene, also known as cumene), which is the expected product however, it also gives the disubstituted product 54. The latter may be the major product if an excess of 2-bromopropane is used. Therefore, the reaction with alkyl halides may lead to polyalkylation of the benzene ring, which is the second of the two problems noted for Friedel-Crafts alkylation. The only way to explain formation of 54 is via a Friedel-Crafts alkylation of the initially formed product 53 with 2-bromopropane. This result suggests that 53 must react more quickly with the carbocation derived from 2-bromopropane than does benzene. This point will be discussed in more detail later. 

Reaction of an aromatic compound with a carbocation (called the Friedel-Crafts alkylation) affixes an alkyl group onto the aromatic ring. In this electrophilic aromatic substitution reaction, there are several methods for generating the carbocation, including from alkyl halides (RX plus FeXs, or AICI3), alcohols (ROH, BF3) and alkenes (alkene, acid). 

Friedel-Crafts Alkylation (Section 22.1 C) The electrophile is a carbocation formed as an ion pair by interaction of an alkyl halide with a Lewis acid. Rearrangements from a less stable carbocation to a more stable carbocation are common. The mechanism involves an initial reaction between the alkyl halide and Lewis acid AICI3 to )deld an intermediate that can be thought of as a carbocation, AlCl " ion pair. The carbocation portion of the ion pair reacts as a very strong electrophile with the weakly nucleophilic aromatic 77 cloud to form a resonance-stabilized cation intermediate that loses a proton to give the final product. Because carbocations are involved in the mechanism, rearrangements can be a problem, especially with... 

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