acid anhydride

Acid anhydrides

Acid anhydrides like acid halides are a derivative of carboxylic acids which are commonly used as acylating agents. Perhaps the easiest way to think of the structure of an acid anhydride is to imagine two carboxylic acid molecules that have had a molecule of water removed from them e.g.

structure of a typical acid anhydride molecule

It maybe helpful if you have some knowledge of the reactions of acid chlorides before reading this page, this is simply because the reactions of acid chlorides and acid anhydrides are very similar.

Naming acid anhydrides

Naming acid anhydrides is very straight forward. Symmetrical acid anhydrides, that is molecules where the two acyl groups are the same are simply named after the parent carboxylic acid followed by the word anhydride, e.g. The two acid anhydride molecules shown below are symmetrical, they each contain two identical acyl groups. To name them simply identify the parent carboxylic acid and add the suffix anhydride.

How to name acid anhydride molecules

Reactions of acid anhydrides

Acid anhydrides undergo similar reactions with the same nucleophiles as acid chlorides, that is addition- elimination reactions but this time the reactions are slower and not as violent. The reason for this is simply that the carboxylate anion is not as good a leaving group as a chloride ion (or a halide anion). However the use of acid anhydrides as acylating agents instead of acid chlorides (except during hydrolysis) results in the formation of often unwanted products which can lead to separation problems which will incur additional expense in separating out this mixture of products.

reactions of acid anhydrides

Hydrolysis of acid anhydrides

The only acid anhydride that you are likely to use is ethanoic anhydride. Ethanoic anhydride is a corrosive colourless liquid with a very strong smell of ethanoic acid (or strong vinegar). This is because it is hydrolysed by water or by moisture in the air to produce ethanoic acid:

equations for the hydrolysis of acid anhydrides

Acid anhydrides and ester formation

Acid anhydrides will react with alcohols to forms esters and a carboxylic acid.

acid anhydride and ester formation equations

Acid anhydrides will also react with phenol to form esters. The equations below show the reaction of ethanoic anhydride with phenol to form the ester phenyl ethanoate and the carboxylic acid; ethanoic acid.

ethanoic acid and phenol reacting to make phenyl ethanoate

As a practical example of this esterfication reaction using acid anhydrides consider the preparation of aspirin.

To make aspirin ethanoic anhydride is used to acylate, that is add an acyl group (RCO) to a molecule of 2-hydroxybenzoic acid. This molecule is also called salicyclic acid and a derivative of it was isolated from the bark of willow trees and given as an analgesic to sick patients in hospitals. However salicyclic acid has a bitter taste and irritated the mouth and stomach of those who took it as pain relief. However it was discovered that if the salicyclic acid was acylated to form the ester (shown below) that this ester was effective at relieving pain but also it tasted better and was less irritating to the mouth and stomach. This new ester of salicyclic acid was aspirin.
The equation below shows how ethanoic anhydride is used to acylate 2-hydroxybenzoic acid to form aspirin.

equations to show how aspirin is made

Acid anhydrides and amide formation

Acid anhydrides react with ammonia, primary amines and secondary amines to produce amides and N-substituted amides. These reactions are slower than that with acid chlorides but acid anhydrides are cheaper than acid chlorides, they are also less corrosive and not so easily hydrolysed, they are also safer to use and do not produce corrosive gases such as hydrogen chloride gas (HCl). The equations below show the reactions of acid anhydrides with ammonia, primary amines and secondary amines to form amides and N-substituted amides. The reactions are similar to those of acid chlorides with ammonia and amines.

equations to show the reactions of ammonia, primary amines 
and secondary amines with athe acid anhydride ethanoic anhydride

Key Points