Nucleophilic addition-elimination

Nucleophilic addition-elimination is the mechanism by which acyl chlorides, such as ethanoyl chloride (CH₃COCl), react with nucleophiles. A nucleophile first adds to the δ+ carbon of the C=O group; then the C=O bond re-forms and a chloride ion is eliminated, along with an H⁺. With water it makes a carboxylic acid, with an alcohol an ester, with ammonia an amide and with a primary amine an N-substituted amide. HCl is the other product each time.

Acyl chlorides and acylation

An acyl chloride has the functional group −COCl: a carbonyl group with a chlorine on the same carbon. Ethanoyl chloride is CH₃COCl. Reactions that add the acyl group (RCO−) to another molecule are called acylation. AQA A-level Chemistry covers the reactions of acyl chlorides and acid anhydrides with water, alcohols, ammonia and primary amines, and asks you to outline the addition-elimination mechanism for the acyl chloride reactions.

Acyl chlorides are very reactive. The carbon of −COCl has both an oxygen and a chlorine pulling electron density away from it, so it carries a large δ+ charge and attracts nucleophiles strongly. The chloride ion is also a good leaving group. Reactions are fast at room temperature, and the HCl produced is given off as steamy fumes.

The nucleophilic addition-elimination mechanism

Here is the reaction of ethanoyl chloride with water. Every version follows the same steps:

1. Addition: a lone pair on the oxygen of the water molecule attacks the δ+ carbon of the C=O (curly arrow from the lone pair to the carbon).
2. At the same time, the electrons of the C=O π bond move onto the oxygen, giving it a negative charge (curly arrow from the double bond to O). The carbon now has four groups attached.
3. Elimination: a lone pair on that O⁻ moves back to re-form the C=O (curly arrow from O⁻ to the C-O bond), and the C-Cl bond breaks, with Cl⁻ leaving (curly arrow from the C-Cl bond to Cl).
4. The oxygen from the water now has a positive charge. Cl⁻ removes an H⁺ from it (curly arrow from a lone pair on Cl⁻ to the H, and from the O-H bond to O), giving HCl.

Swap water for another nucleophile and the mechanism is the same: only the attacking atom changes. With an alcohol it is the O of the OH group; with ammonia or an amine it is the N, which uses its lone pair.

The four reactions of ethanoyl chloride

With ammonia and amines, two molecules are needed. The first acts as the nucleophile; the second is a base that reacts with the HCl formed, giving ammonium chloride or an alkylammonium chloride.

Making esters this way

Esters can also be made from a carboxylic acid and an alcohol, but that reaction is slow and reversible, needing an acid catalyst and heat. With an acyl chloride, the reaction is fast, goes at room temperature and is not reversible, so the yield is higher.

Acid anhydrides

An acid anhydride, such as ethanoic anhydride, (CH₃CO)₂O, reacts with the same four nucleophiles in the same way. The difference is the leaving group: instead of Cl⁻ and HCl, the second product is a carboxylic acid.

Anhydrides react more slowly than acyl chlorides, usually needing gentle warming.

Why aspirin is made with ethanoic anhydride

AQA asks for the industrial advantages of ethanoic anhydride over ethanoyl chloride in making aspirin. Ethanoic anhydride is cheaper, less corrosive, and reacts less violently, so the reaction is easier to control. It does not give off corrosive HCl fumes, and it reacts less readily with water in the air, so it is safer to store and handle.

Check your understanding.

Common mistakes

• Starting a curly arrow from the H or from a negative sign. The first arrow starts at the nucleophile's lone pair.
• Forgetting to break the C=O π bond in the addition step, or forgetting to re-form it in the elimination step.
• Missing the final step: the positive O or N must lose an H⁺.
• Using one ammonia molecule. The equation needs two: one nucleophile, one base.
• Calling it nucleophilic substitution. The overall change replaces Cl, but AQA expects the addition-elimination mechanism.
• Naming esters backwards. The alcohol part comes first: ethanoyl chloride + methanol gives methyl ethanoate.

For the related mechanism with aldehydes and ketones, where nothing is eliminated, see nucleophilic addition; for halogenoalkanes, nucleophilic substitution.

Practise with a short timed paper

Acylation is in the second year of A-level Chemistry. The daily A-level Chemistry: Year 2 paper is a short timed paper of 8 questions, with a new one every day.

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Chemistry · Organic chemistryNucleophilic addition: mechanism, NaBH₄ and KCNNucleophilic addition for A-level Chemistry: why aldehydes and ketones react this way, the curly arrow mechanism, reduction with NaBH₄ and KCN with acid.