Electrophilic substitution-acylation of benzene rings

The Friedel-Crafts acylation reaction is very similar to Friedel-Crafts alkylation reactions which are used to produce alkylated aromatic rings or arenes. Friedel-Crafts acylation reactions as the name suggests adds an acyl group (R-C=O) to an aromatic ring to produce aryl ketones.

The acyl group (R-C=O) to be added to the aromatic molecule is usually obtained from an acid chloride or an acid anhydride. Friedel-Crafts acylation reactions have one massive advantage over Friedel-Crafts alkylation reactions in that the acyl group (R-C=O) is an electron withdrawing group and so will deactivate an aromatic ring and so reduce the likelihood of any further substitution onto the aromatic ring, this solves the main polyalkylation problem which occurs with Friedel-Crafts alkylation reactions.

The mechanism of Friedel-Crafts acylation reactions

The mechanism of a Friedel-Crafts acylation reaction is simply what you would expect from an aromatic ring, that is electrophilic substitution. The reactive electrophile is the resonance stabilised acylium ion (RCO⁺). This ion is generated by the reaction of an acyl chloride (acid chloride) or acid anhydride with a Lewis acid catalyst such as aluminium chloride (AlCl₃). This is outlined in the diagram below using the acid chloride ethanoyl chloride as an example:

The acylium ion (RCO⁺) is a resonance stabilised ion, this is outlined below. Note the presence of the double-headed resonance arrow in this equation:

Reaction mechanism

The acylium ion is an excellent electrophile since it carries a full positive charge; this means that the delocalised electrons in an aromatic ring are able to readily attack the acylium ion and the reaction proceeds by the expected electrophilic substitution route:

Overall we can write an equation for this the Friedel-Crafts acylation of benzene using the acid chloride ethanoyl chloride; this is outlined below. The product of this reaction is an aryl ketone acetophenone or 1-phenylethanone. It's a colourless, viscous liquid with a sweet, pungent odour.

Using acid anhydrides as acylating agents

As well as using acid chlorides as the acylating agent it is also possible to use acid anhydrides. Acid anhydrides are very common acylating agents in Friedel-Crafts acylation reactions, especially in industrial settings because they are generally less corrosive and easier to handle than acyl chlorides (acid chlorides), though they are generally less reactive. The reaction mechanism is the same and the electrophile is still the acylium ion, for example the aryl ketone acetophenone can also be prepared by reacting benzene using the acid anhydride ethanoic anhydride, this is outlined below.

Acid anhydride or acid chloride as acylating agents?

The use of acid anhydrides or acid chlorides as acylating agents in an industrial setting will often come down to a balance between a number of factors which include:

• Cost
  • Acid anhydrides are often cheaper to use than acid chlorides, especially in large industrial-scale reactions.
  • Acid chlorides are typically made using expensive and highly corrosive reagents such as phosphorus chlorides (PCl₃, PCl₅) or thionyl chloride (SOCl₂), which produces hazardous by-products like phosphorus oxychloride (POCl₃), hydrogen chloride gas (HCl), and sulfur dioxide gas (SO₂). Equations for the preparation of the acid chloride ethanoyl chloride from ethanoic acid are shown below:
  
  • In contrast, acid anhydrides such as ethanoic anhydride; which is more commonly called acetic anhydride (CH₃COOCOCH₃) can often be produced more economically by simply dehydrating carboxylic acids; as outlined below:


It is fairly easy to imagine from the above equation two molecules of ethanoic acid losing a molecule of water and forming ethanoic anhydride; this is outlined in the image below:


• Handling and Safety
  • Acid chlorides react violently with water, releasing corrosive and fuming hydrogen chloride gas (HCl), making them difficult to handle, store, and transport. This requires specialised equipment and very strict safety protocols.
  
  • Acid anhydrides on the other hand are more stable to moisture and air, and are therefore easier and safer to store and handle on both laboratory and industrial scales.


• Reactivity and Waste
  • Acid chlorides are highly reactive electrophiles and readily react with nucleophiles including water, alcohols, and amines. Their reactions release corrosive hydrogen chloride (HCl) gas as a waste product.
  • Acid anhydrides are less reactive than acid chlorides and may require harsher conditions or catalysts to achieve the desired reaction. However, they produce less hazardous carboxylic acids as by-products, which are less hazardous and easier to handle or recycle.


• Corrosivity
  • The HCl gas produced by acid chlorides is highly corrosive to reaction vessels and equipment, increasing maintenance and replacement costs and initial set-up costs.
  • Acid anhydrides largely avoid these issues, making them less damaging to industrial equipment and less expensive to deal with on a daily basis.


• By-products
  • Acid chlorides produce hydrogen chloride gas, which must be scrubbed or neutralised to avoid serious environmental harm.
  • Acid anhydrides produce carboxylic acids, which are often less problematic, they may even be able to be recycled, or even sold depending on the individual process.

Preparation of ethylbenzene

While discussing Friedel-Crafts alkylation reactions we looked at the preparation of ethylbenzene which was then dehydrogenated to form phenylethene or styrene; which is the monomer used to make the polymer polystyrene. This reaction can be shown as:

However due to the limitations of the Friedel-Crafts alkylation reaction, in particular the issue of polyalkylation during the synthesis of ethylbenzene this is not a particularly efficient way to produce the styrene monomer. However the problem of polyalkylation can be overcome by simply using of a Friedel-Crafts acylation reaction to produce acetophenone and then reducing this to form ethylbenzene using hydrogen and a nickel catalyst; as shown below:

Limitations of Friedel-Craft acylation reactions

Like Friedel-Crafts alkylation reactions Friedel-Crafts acylation reactions also have their limitations; these include:

• Like Friedel-Crafts alkylation reactions the acylation reactions also fail on strongly deactivated aromatic rings, for example aromatic rings which contain a deactivating group such as a nitro group (-NO₂) will not undergo Friedel-Crafts acylation reactions; if the aromatic ring has a group which is withdrawing electron density from it then its ability to act as a nucleophile and attack an electrophile such as an acylium ion will be greatly reduced.


• Friedel-Crafts acylation and alkylation reactions will both fail on aromatic rings which contain basic groups such as an amino group (-NH₂) simply because a key step in the mechanism of the acylation reaction is the reaction of the acid chloride or the acid anhydride with the Lewis acid, however if the aromatic molecule contains a basic group then the Lewis acid will simply react with this which will stop the acylation reaction or lead to unwanted side-reactions taking place.

Self-check- summary

Use the flashcards below to test your understanding of some of the main points on Friedel-Crafts acylation covered above:

What functional group is added to the aromatic ring in an acylation reaction?

An acyl group (R-C=O).

What type of reaction mechanism is Friedel-Crafts acylation?

Electrophilic substutition.

What is a Lewis acid?

An electron pair acceptor.

How is electrophile generated.

By the reaction of an acid chloride/anhydride with a Lewis acid catalyst.

Why are acid anhydrides often used instead of acid chlorides in acylation reactions?

Acid anhydrides are generally cheaper, safer to handle and less corrosive and produce less corrosive by-products.

Draw the structure of the acylium ion

The acylium ion has the formula R–C≡O⁺, where R is an alkyl group.

Why does polyacylation not occur in Friedel-Crafts acylation?

The acyl group deactivates the ring and prevents further reactions.

The acylium ion is described as resonance stabilised. What does this mean?

Resonance stabilisation means the positive charge on the acyium ion is delocalised across more than one structure.

Explain why aromatic rings with a nitro group (-NO₂) do not undergo Friedel-Crafts acylation reactions.

The nitro group is strongly electron withdrawing, reducing the electron density of the aromatic ring, so it is less able to act as a nucleophile.

Suggest why acid chlorides must be handled with great care.

They react violently with water, releasing corrosive HCl gas .

Key Points

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