What is a Friedel-Crafts Reaction?
A Friedel-Crafts reaction is an organic coupling reaction involving an electrophilic aromatic substitution that is used for the attachment of substituents to aromatic rings. The two primary types of Friedel-Crafts reactions are the alkylation and acylation reactions. These reactions were developed in the year 1877 by the French chemist Charles Friedel and the American chemist James Crafts.
An illustration describing both the Friedel-Crafts reactions undergone by benzene is provided below.
It can be noted that both these reactions involve the replacement of a hydrogen atom (initially attached to the aromatic ring) with an electrophile. Aluminium trichloride (AlCl3) is often used as a catalyst in Friedel-Crafts reactions since it acts as a Lewis acid and coordinates with the halogens, generating an electrophile in the process.
Friedel-Crafts Alkylation refers to the replacement of an aromatic proton with an alkyl group. This is done through an electrophilic attack on the aromatic ring with the help of a carbocation. The Friedel-Crafts alkylation reaction is a method of generating alkylbenzenes by using alkyl halides as reactants.
The Friedel-Crafts alkylation reaction of benzene is illustrated below.
A Lewis acid catalyst such as FeCl3 or AlCl3 is employed in this reaction in order to form a carbocation by facilitating the removal of the halide. The resulting carbocation undergoes a rearrangement before proceeding with the alkylation reaction.
The Friedel-Crafts alkylation reaction proceeds via a three-step mechanism.
The Lewis acid catalyst (AlCl3) undergoes reaction with the alkyl halide, resulting in the formation of an electrophilic carbocation.
The carbocation proceeds to attack the aromatic ring, forming a cyclohexadienyl cation as an intermediate. The aromaticity of the arene is temporarily lost due to the breakage of the carbon-carbon double bond.
The deprotonation of the intermediate leads to the reformation of the carbon-carbon double bond, restoring aromaticity to the compound. This proton goes on to form hydrochloric acid, regenerating the AlCl3 catalyst.
An illustration describing the mechanism of the Friedel-Crafts alkylation reaction is provided above.
What are the Limitations of the Friedel-Crafts Alkylation Reaction?
Some important limitations of Friedel-Crafts alkylation are listed below.
- Since the carbocations formed by aryl and vinyl halides are extremely unstable, they cannot be used in this reaction.
- The presence of a deactivating group on the aromatic ring (such as an NH2 group) can lead to the deactivation of the catalyst due to the formation of complexes.
- An excess of the aromatic compound must be used in these reactions in order to avoid polyalkylation (addition of more than one alkyl group to the aromatic compound).
- Aromatic compounds that are less reactive than mono-halobenzenes do not participate in the Friedel-Crafts alkylation reaction.
It is important to note that this reaction is prone to carbocation rearrangements, as is the case with any reaction involving carbocations.
The Friedel-Crafts acylation reaction involves the addition of an acyl group to an aromatic ring. Typically, this is done by employing an acid chloride (R-(C=O)-Cl) and a Lewis acid catalyst such as AlCl3. In a Friedel-Crafts acylation reaction, the aromatic ring is transformed into a ketone. The reaction between benzene and an acyl chloride under these conditions is illustrated below.
An acid anhydride can be used as an alternative to the acyl halide in Friedel-Crafts acylations. The halogen belonging to the acyl halide forms a complex with the Lewis acid, generating a highly electrophilic acylium ion, which has a general formula of RCO+ and is stabilized by resonance.
Friedel-Crafts acylations proceed through a four-step mechanism.
A reaction occurs between the Lewis acid catalyst (AlCl3) and the acyl halide. A complex is formed and the acyl halide loses a halide ion, forming an acylium ion which is stabilized by resonance.
The acylium ion (RCO+) goes on to execute an electrophilic attack on the aromatic ring. The aromaticity of the ring is temporarily lost as a complex is formed.
The intermediate complex is now deprotonated, restoring the aromaticity to the ring. This proton attaches itself to a chloride ion (from the complexed Lewis acid), forming HCl. The AlCl3 catalyst is now regenerated.
The regenerated catalyst can now attack the carbonyl oxygen. Therefore, the ketone product must be liberated by adding water to the products formed in step 3. This step can be illustrated as follows.
Thus, the required acyl benzene product is obtained via the Friedel-Crafts acylation reaction.
Despite overcoming some of the limitations of the related alkylation reaction (such as carbocation rearrangement and polyalkylation), the Friedel-Crafts acylation reaction has a few shortcomings.
The acylation reaction only yields ketones. This is because formyl chloride (H(C=O)Cl) decomposes into CO and HCl when exposed to these conditions.
The aromatic compound cannot participate in this reaction if it is less reactive than a mono-halobenzene.
Aryl amines cannot be used in this reaction because they form highly unreactive complexes with the Lewis acid catalyst.