Friedel-Crafts alkylation reaction examples

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

It should be noted that Scheme 5.1-44 shows idealized Friedel-Crafts allcylation reactions. In practice, there are a number of problems associated with the reaction. These include polyalkylation reactions, since the products of a Friedel-Crafts alkylation reaction are often more reactive than the starting material. Also, isomerization and rearrangement reactions can occur, and can result in a large number of products [74, 75]. The mechanism of Friedel-Crafts reactions is not straightforward, and it is possible to propose two or more different mechanisms for a given reaction. Examples of the typical processes occurring in a Friedel-Crafts alkylation reaction are given in Scheme 5.1-45 for the reaction between 1-chloropropane and benzene. 

An important use of the Friedel-Crafts alkylation reaction is to effect ring closure. The most common method is to heat with aluminum chloride an aromatic compound having a halogen, hydroxy, or alkene group in the proper position, as, for example, in the preparation of tetralin ... 

An alkyl group can be added to a benzene molecule by an electrophile aromatic substitution reaction called the Friedel-Crafts alkylation reaction. One example is the addition of a methyl group to a benzene ring. 

Carbocations can rearrange during the Friedel-Crafts alkylation reaction, leading to the formation of unpredicted products. One example is the formation of isopropyl benzene by the reaction of propyl chloride with benzene. 

The Friedel-Crafts acylation reaction, another example of an electrophilic aromatic substitution reaction, is similar to the Friedel-Crafts alkylation reaction except that the substance that reacts with benzene is an acyl halide,... 

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. 

Sulfated zirconia is a good example of a structural Lewis acid which has been chemically treated to enhance acidity. It has been extensively studied as a solid acid catalyst for vapour phase reactions and we1112 and others14 have found that a mesoporous version of this material is a particularly effective catalyst for liquid phase Friedel-Crafts alkylation reactions and to a lesser extent Friedel-Crafts benzoylations. The commercial (MEL Chemicals Ltd) material SZ999/1 shows a nitrogen isotherm characteristic of a mesoporous solid (surface area 162 m2g, pore volume 0.22 cm3g )- Whereas microporous and mesoporous materials are capable of rapidly catalysing the alkylation of benzene with various alkenes (Table 1), on reuse only the mesoporous... 

Any time an alkyl halide or alcohol is a precursor to a Friedel-Crafts alkylation reaction, rearrangement of the initially formed cation can occur prior to attachment to the aromatic nucleus. Rearrangement can be accompanied by isomerization of the initially formed product, due to the action of the Lewis acid (such as AICI3), required for the reaction. OO Isomerization of groups can occur via 1,2-shifts or via dissociation to a cation and readdition.idl 1,1-Dimethylpropylbenzene (167) dissociates in the presence of aluminum chloride to give 168, for example. The reaction can be reversible under these conditions. When the cation adds to the aromatic ring two products are possible, 169 or 171. Addition to give intermediate cation 169 leads to product... 

Following are the limitations to the Friedel-Crafts alkylation. For example, the reaction of 1-chlorobutane with benzene gives two products with only 34 per cent of the desired product (Fig. F). This is because of the fact that the primary carbocation that is generated can rearrange to a more stable secondary carbocation where a hydrogen (and the two sigma electrons... 

When electron-donating substituents are added, multiple substitution is always a threat. The principal reaction where multiple substitution is a genuine problem is the Friedel-Crafts alkylation reaction. Here s an example preparation of diphenylmethane from benzene and benzyl chloride is a useful reaction but the product has two benzene rings, each more reactive than benzene itself. A 50% yield is the best we can do and that requires a large excess of benzene to ensure that it competes successfully for the reagent with the reactive, electron-rich product. 

ILs may themselves also act as catalyst. For heterogeneous catalysis, the IL has to be immobilized, for example, by covalent bonds on a porous support, as shown by Hoelderich et al. [40] for Friedel-Crafts alkylation reactions. Further examples of reactions tested with grafted ILs are acetylization [41], cycloaddition of CO2 [42, 43], and epoxidation of olefines [44]. 

Azeotropic distillation is a useful technique for removing water from organic solutions. For example, toluene and water form an azeotrope having a composition of 86.5 wt % of toluene and 13.5 wt % water, and so distillation of a mixture of these two effectively removes water from a mixture. This technique is used in the Experimental Procedure of Section 18.4 for driving an equilibrium in which water is being formed to completion. Azeotropic distillation may also be used to dry an organic liquid that is to be used with reagents that are sensitive to the presence of water. This application is found in the Experimental Procedure of Section 15.2, in which anhydrous p-xylene is required for a Friedel-Crafts alkylation reaction. 

Friedel-Crafts Alkylation. One of the first uses for this highly Lewis acidic reagent in organic synthesis was found by Mikami in the Friedel-Crafts alkylation reaction of anisole (eq 2). Here the first example of TMSNTf2 outperforming TMSOTf was found. 

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. 

Acylium ions produced in the Friedel—Crafts reaction do not rearrange. The acyl group in the product can be reduced using a zinc—mercury amalgam and HCl to produce an alkylbenzene. This reaction is called a Clemmensen reduction. This circumvents the rearrangement of primary alkyl groups that occurs in the Friedel—Crafts alkylation reaction. For example, acylation of benzene with propanoyl chloride followed by a Clemmensen reduction yields propylbenzene. 

Charles Friedel, a French chemist, and James M. Crafts, an American chemist, who discovered this method of making alkylbenzenes in 1877.) An example of a Friedel-Crafts alkylation reaction is shown below ... 

Acidic chloroaluminate ionic liquids have already been described as both solvents and catalysts for reactions conventionally catalyzed by AICI3, such as catalytic Friedel-Crafts alkylation [35] or stoichiometric Friedel-Crafts acylation [36], in Section 5.1. In a very similar manner, Lewis-acidic transition metal complexes can form complex anions by reaction with organic halide salts. Seddon and co-workers, for example, patented a Friedel-Crafts acylation process based on an acidic chloro-ferrate ionic liquid catalyst [37]. 

For example /-butyl phenyl ether with aluminium chloride forms para-t-butyl phenol155. Often the de-alkylated phenol is also formed in considerable quantity. The reaction formally resembles the Fries and Claisen rearrangements. Like the Fries rearrangement the question of inter- or intramolecularity has not been settled, although may experiments based on cross-over studies156, the use of optically active ethers157 and comparison with product distribution from Friedel-Crafts alkylation of phenols158 have been carried out with this purpose in view. 

Zinc chloride exchanged clay catalysts have been reported to be highly active for the Friedel-Crafts alkylation and acylation reactions these are commercially sold by Contract Catalysts under the name Envirocats. These are montmorillonite catalysts modified by ZnCU and FeCli. Some of the reported examples of Friedel-Crafts reactions are given below there are claims that some of the processes are commercially practised. 

A number of reactions have been explained on the basis of generation of carbocations. The examples include the Friedel-Crafts alkylation and arylation reactions. Besides pinacol-pinacolne rearrangement, Beckmann rearrangement and Wagner-Merwein rearrangement are other examples. 

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

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