Friedel-Crafts alkylation reaction rearrangements

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... 

We have seen that a carbocation will rearrange if rearrangement leads to a more stable carbocation (Section 6.7). When the carbocation employed in a Friedel-Crafts alkylation reaction rearranges, the major product will be the product with the rearranged alkyl group... 

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. 

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. 

It is not possible to obtain a good yield of an alkylbenzene containing a straight-chain alkyl group via a Friedel-Crafts alkylation reaction, because the incipient primary car-bocation will rearrange to a more stable carbocation. 

The answer is D. This reaction is a Friedel-Crafts alkylation reaction. This rules out Choice A. In an alkylation reaction, there is a possibility of rearrangement. The primary alkyl halide ( -propyl chloride) can form secondary carbocations by rearrangement. To avoid this type of rearrangement, chemists often use Friedel-Crafts acylation reactions which do not involve rearrangement. The carbonyl group in the acylation product can be easily reduced to get the desired hydrocarbon. 

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. 

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. 

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. 

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. 

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... 

Apart from the possibility of rearrangement, the main drawback in the preparative use of this Friedel-Crafts reaction is polyalkylation (cf. p. 153). The presence of an electron-withdrawing substituent is generally sufficient to inhibit Friedel-Crafts alkylation thus nitrobenzene is often used as a solvent for the reaction because A1C13 dissolves readily in it, thus avoiding a heterogeneous reaction. 

BF3 is an effective reagent for various kinds of reaction such as Friedel-Crafts alkylation and acylation reactions (Scheme 63),291 cyclization reactions, rearrangement,292 Diels-Alder reactions,293 and aldol reactions. 

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