Carboxylic Acid Derivatives and Acylation Reaction

Carboxylic Acid derivatives are similar to carboxylic acids in that they have a carbonyl group, but the hydroxyl group is replaced by a different functional group, e.g. a chlorine atom or carboxylate group

Derivatives of Ethanoic Acid

Both Ethanoyl Chloride and Ethanoic Anhydride are important in synthetic reactions as they easily undergo Nucleophilic Addition Elimination. They can be used to make carboxylic acids, esters, amides and N-substituted amides. The mechanisms are very similar in each case, following the basic mechanism as follows.

General Mechanism for the Nucleophilic Addition-Elimination to Carboxylic Acid derivatives

Reaction with Water

This is a very useful way of making a carboxylic acid. It is also a hydrolysis reaction as water is breaking up the acyl chloride.

Mechanism for the Nucleophilic Addition-Elimination of Water to Ethanoyl Chloride

Reaction with Alcohol

This is a very useful way of making esters. The mechanism is shown below, but there is more inforamtion about the synthesis of esters in the 'Esters' section.

Mechanism for the Nucleophilic Addition-Elimination of Alcohol to Ethanoyl Chloride

Reaction with Ammonia

This mechanism differs slightly from those of the reactions with water and alcohol. In this reaction, a base is needed to deprotonate the nitrogen. This is usually just ammonia again, as it is usually used in excess in the reaction

Mechanism for the Nucleophilic Addition-Elimination of Ammonia to Ethanoyl Chloride

Reaction with an Amine

This mechanism forms an N-substituted amide. it is similar to te reaction with ammonia in that a base is needed to deprotonate the nitrogen. Again the amine is used, as it is in excess.

Mechanism for the Nucleophilic Addition-Elimination of an amine to Ethanoyl Chloride

All of the mechanisms above have been shown using Ethanoyl Chloride. The reactions can also be done using Ethanoic Anhydride. the mechanisms very similar, apart from the leaving group is no longer the chloride ion, but the ethaoate ion. When the reactions are done industrially, the anhydride is used instead of the chloride. this is due to several things:

1. The anhydride is cheaper than the chloride.
2. The chloride is hydrolysed more easily than the anhydride
3. The anhydride is also less corrosive and a lot safer to use than the chloride.

Uses Of Acylation reactions

Acylation reactions are used in the synthesis of the pain killers aspirin and paracetamol.
In the synthesis of aspirin, ethanoic anhydride is reacted with a hydroxyl group in 2-hydroxybenzoic acid.

Synthesis of Aspirin

Paracetamol is N-phenolethanamide, so is made by acylating 4-aminophenol.

The structure of Paracetamol

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