Friedel-Crafts reaction, carbocation reactivity

Antimony pentachloride is a reactive Lewis acid that can be used for Friedel-Crafts reactions and some other Lewis-acid-catalyzed reactions. The HF-SbF5 system is known as magic acid, and carbocations are stabilized in this medium.353 By using the HF-SbF5 system, alkylation of acetophenone (a relatively unreactive aromatic compound) has been achieved (Scheme 87). 

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... 

Besides avoiding carbocation rearrangements, another advantage of preparing alkyl-substituted benzenes by acylation-reduction rather than by direct alkylahon is that a large excess of benzene does not have to be used (Sechon 15.14). Unlike alkyl-substituted benzenes, which are morereachve than benzene (Section 16.3), acyl-substituted benzenes are less reactive than benzene, so they will not undergo addihonal Friedel-Crafts reactions. 

Compound 17 is the result of a Friedel-Crafts reaction of the carbocation intermediate. Changing the solvent from ethylene glycol dimethylether to alcohol modifies the reactive intermediate from 18a to 18b or 18c. The hydrogenolysis of 18b (or 18c) is more difficult than 18a which leads to a lower stationary concentration in carbocation, therefore minimizing the formation of 17. 

It is probable that a very early preparation of an ionic liquid (if not its characterisation) occurred on the isolation of the so-called red oiT in Friedel-Crafts reactions [736]. While the isolation and structural characterisation of carbocations and other reactive cations from strongly acidic media are an extensive and important area of study, only those materials that are stable at ambient temperatures and which have a reported mpt. < 100°C are listed in Table 11.24. These include [CgMey]-" [375, 414, 415], [C6Me6CH2Cl]+ [393, 394] and [CgMegPh]-"... 

Friedel-Crafts reactions are one of the most important methods for introducing carbon substituents onto aromatic rings. The reactive electrophiles can be either discrete carbocations or acylium ions or polarized complexes that still contain the... 

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

With Friedel-Crafts halides (usually A1C13 and BF3) it is necessary to use equimolar or excess catalyst when alcohols are the alkylating agents. With primary alcohols usually 2 mol of catalyst per mole of alcohol must be used. Complexing the alcohol, as well as binding the water formed in the reaction explains the experimental findings. With secondary and tertiary alcohols, lesser amounts of catalyst are needed. The reactivity of different alcohols follows the order methyl < primary < secondary < tertiary, allyl, benzyl. The ease of carbocation formation according to Eq. (5.51) is most probably responsible for this reactivity order ... 

Bakelite, the first synthetic polymer, is an example of a thermoset polymer. It is prepared by the polymerization of phenol and formaldehyde in the presence of ail acid. Carbocations produced by protonation of formaldehyde bond to the ortho and para positions of the highly reactive phenol molecules in a Friedel-Crafts alkylation reaction. The benzylic alcohols that are produced in this step react to produce carbocations that then alkylate additional phenol molecules. A mechanism for the first few steps of this polymerization process is shown in Figure 24.4. 

The reaction of benzene with a carbocation leads to an arene in what is known as Friedel-Crafts alkylation. The reaction of an alkyl halide with a strong Lewis acid gives a carbocation, which is subject to rearrangement. Friedel-Crafts alkylation reactions are subject to poly alkylation because the arene is more reactive than benzene. 

Friedel-Crafts alkylation involves formation of an alkyl carbocation in the presence of benzene or a benzene derivative. In previous chapters, these reactive intermediates are formed by reaction of an alkene with an acid (Chapter 10, Section 10.2), by reaction of an alcohol with an acid (Chapter 11, Section 11.7.1), or by the ionization of an alkyl halide in aqueous solution (Chapter 11, Section 11.4). For reactions with benzene and its derivatives, an alternative method that can generate primary carbocations that are particularly difficult to form by the other methods named is used to form carbocations. 

If the preparation of 45 is typical, Friedel-Crafts alkylation appears to be just another example of electrophilic aromatic substitution where the reactive species is a carbocation. However, problems with a carbocation intermediate do not arise with other cations such as Br, CP, or NO2+. If a stable carbocation such as the benzyhc cation or a tertiary cation is the intermediate, the reaction is relatively straightforward. If a primary or secondary carbocation is formed, however, rearrangement to a more stable cation may occur before the reaction with benzene. 

Before explaining the previous data, it is important to understand why 54 is formed in the Friedel-Crafts alkylation reaction. This means that the reactivity of benzene derivatives must be addressed. If 54 is formed by a reaction of 53, then 53 must react with the intermediate carbocation more quickly than benzene. Why does 53 react more quickly than benzene In addition, this discussion must address the question of why polyalkylation is a problem but polyacylation is not. The answers to these questions will also explain the regioselectivity of the reaction. 

The electrophiles in S Ar reactions may be divided into two basic categories those with fully formed cationic charge centers and those having reactive, polarized bonds. For example, Friedel-Crafts alkylation often occurs through the involvement of discrete carbocation intermediates (see Chapter 2). 

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