Limitations of Friedel-Crafts Alkylations

The alkylation of benzenes under Friedel-Crafts conditions is accompanied by two important side reactions One is polyalkylation the other, carbocation rearrangement. Both cause the yield of the desired products to diminish and lead to mixtures that may be difficult to 

Consider first polyalkylation. Benzene reacts with 2-bromopropane in the presence of FeBrs as a catalyst to give products of both single and double substitution. The yields are low because of the formation of many by-products. 

The electrophilic aromatic substitutions that we studied in Sections 15-9 and 15-10 can be stopped at the monosubstitution stage. Why do Friedel-Crafts alkylations have the problem of multiple electrophilic substimtion It is because the substituents differ in electronic structure (a subject discussed in more detail in Chapter 16). Bromination, nitration, and sulfonation introduce an electron-withdrawing group into the benzene ring, which renders the product less susceptible than the starting material to electrophilic attack. In contrast, an alkylated benzene is more electron rich than unsubstituted benzene and thus more susceptible to electrophilic attack. 

Treatment of benzene with chloromethane in the presence of aluminum chloride results in a conplex mixture of tri-, tetra-, and pentamethylbenzenes. One of the components in this mixture crystallizes out selectively m.p. = 80°C molecular formula = C10H14 H NMR d = 2.21 (s, 12 H) and 7.15 (s, 2 H) ppm NMR 5 = 19.2, 131.2, and 133.8 ppm. Draw a structure for this product. 

The second side reaction in aromatic alkylation is skeletal rearrangement (Section 9-3). For example, the attempted propylation of benzene with 1-bromopropane and AICI3 produces (l-methylethyl)benzene. 

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The combination of Friedel-Crafts acylation and Wolff-Kishner or Clemmensen reduction allows synthesis of alkylbenzenes free of the limitations of Friedel-Crafts alkylation. 

The third limitation of Friedel-Crafts alkylation reaction is the structural rearrangement of the alkyl carbocation generated from the alkyl halide. A rearrangement of the alkyl group gives a different product than the one desired. For example, the reaction with 1-chloropropane in the presence of AlCl yields a small amount of propylbenzene, but a larger amount of the isomer, isopropylbenzene. 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

This involvement of carbocations actually limits the utility of Friedel-Crafts alkylations, because, as we have already noted with carbocations, rearrangement reactions complicate the anticipated outcome (see Section 6.4.2). For instance, when a Lewis acid... 

We have encountered three limitations to the use of Friedel-Crafts alkylation (a) the danger of polysubstitution (b) the possibility that the alkyl group will rearrange and (c) the fact that aryl halides cannot take the place of alkyl halides. Besides these, there are several other limitations. 

There are two major limitations on Friedel-Crafts alkylations. The first is that it is practical only with stable carbocations, such as 3° carbocations, resonance-stabilized car-bocations, or 2° carbocations that cannot undergo rearrangement (Section 5.4). Primary carbocations will undergo rearrangement, resulting in multiple products as well as bonding of the benzene ring to unexpected carbons in the former haloalkane. 

The third limitation on Friedel-Crafts alkylation is that it is hard to stop the reaction at monoallylation because the alkylated product is more reactive than benzene itself. We will discuss reactivity in detail in Section 22.2, but in general, allylated benzenes are more reactive than unsubstituted compounds. This limitation can be overcome if if is feasible to use a large excess of benzene, often as both the solvent and the reactant. 

Friedel-Crafts acylation is free of a second major limitation on Friedel-Crafts alkylations acylium ions do not undergo rearrangement. Thus, the carbon skeleton of an acyl halide is transferred unchanged to the aromatic ring. 

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. 

The Friedel-Crafts alkylation reaction does not proceed successfully with aromatic reactants having EWG substituents. Another limitation is that each alkyl group that is introduced increases the reactivity of the ring toward further substitution, so polyalkylation can be a problem. Polyalkylation can be minimized by using the aromatic... 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the case of sulfonation and nitration milder reagents can be employed, i.e. the pyridine-sulfur trioxide complex and acetyl nitrate, respectively. Attempts to carry out the Friedel-Crafts alkylation of furan are often unsuccessful because the catalysts required cause polymerization. 

Here we report the synthesis and catalytic application of a new porous clay heterostructure material derived from synthetic saponite as the layered host. Saponite is a tetrahedrally charged smectite clay wherein the aluminum substitutes for silicon in the tetrahedral sheet of the 2 1 layer lattice structure. In alumina - pillared form saponite is an effective solid acid catalyst [8-10], but its catalytic utility is limited in part by a pore structure in the micropore domain. The PCH form of saponite should be much more accessible for large molecule catalysis. Accordingly, Friedel-Crafts alkylation of bulky 2, 4-di-tert-butylphenol (DBP) (molecular size (A) 9.5x6.1x4.4) with cinnamyl alcohol to produce 6,8-di-tert-butyl-2, 3-dihydro[4H] benzopyran (molecular size (A) 13.5x7.9x 4.9) was used as a probe reaction for SAP-PCH. This large substrate reaction also was selected in part because only mesoporous molecular sieves are known to provide the accessible acid sites for catalysis [11]. Conventional zeolites and pillared clays are poor catalysts for this reaction because the reagents cannot readily access the small micropores. 

Limitations of the Friedel-Crafts Alkylation Although the Friedel-Crafts alkylation looks good in principle, it has three major limitations that severely restrict its use. 

Limitation 3 Because alkyl groups are activating substituents, the product of the Friedel-Crafts alkylation is more reactive than the starting material. Multiple alkylations are hard to avoid. This limitation can be severe. If we need to make ethylbenzene, we might try adding some A1C13 to a mixture of 1 mole of ethyl chloride and 1 mole of benzene. As some ethylbenzene is formed, however, it is activated, reacting even faster than benzene itself. The product is a mixture of some (ortho and para) diethylbenzenes, some triethylbenzenes, a small amount of ethylbenzene, and some leftover benzene. 

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