Acylation & the Manufacture of Aspirin (AQA A Level Chemistry): Video

Hi, I'm Eleanor with 3 years of experience teaching chemistry, and this video is about acylation and the manufacture of aspirin.

The two are covered together because the industrial manufacture of aspirin is an acylation reaction.

Acyl groups can be introduced into many molecules using acyl chlorides or acid anhydrides, which are known as acylating agents. Acylation reactions are widely used in industry, and the manufacture of aspirin is one of them, so the difference between the two acylating agents is what decides which one industry uses.

We start with the acylating agents themselves, what acyl chlorides and acid anhydrides are and how they are named. Then the reaction they undergo, nucleophilic addition–elimination, and the products it gives. Then the manufacture of aspirin, and why an acid anhydride is used rather than an acyl chloride.

Acyl groups can be introduced into many molecules using acyl chlorides or acid anhydrides. Both are known as acylating agents, and both are derivatives of carboxylic acids.

In an acyl chloride, the O H group of the carboxylic acid has been substituted by a chlorine atom. In an acid anhydride, the O H group is replaced by an alkanoate group. Ethanoic acid gives ethanoyl chloride and ethanoic anhydride.

Both are named from the parent acid. Identify the parent hydrocarbon chain and add the suffix –oyl chloride or –oic anhydride, or take –oic acid off the corresponding carboxylic acid name and replace it with –oyl chloride or –oic anhydride.

These are the two reagents that acylate other molecules, including the salicylic acid that becomes aspirin.

Acyl chlorides and acid anhydrides are very reactive organic compounds, and the reaction they undergo is nucleophilic addition–elimination. A nucleophile adds to the carbon with the carbon-oxygen double bond, and then a small molecule is eliminated.

The hydrolysis of acyl chlorides produces a carboxylic acid and hydrogen chloride, and the hydrolysis of acid anhydrides produces two molecules of the carboxylic acid.

With alcohols, acyl chlorides form esters and hydrogen chloride, and acid anhydrides form an ester and a carboxylic acid.

With ammonia or primary amines, both form amides. A lone pair on the nitrogen atom attacks the carbonyl carbon. With acyl chlorides all of these reactions form hydrogen chloride. But it is not observed as a separate product from reactions with ammonia or amines, it is neutralised by excess ammonia or amine, so the final products are an amide and an ammonium salt.

This is the reaction that transfers the acyl group, and it is the reaction the aspirin process runs.

Acylation reactions are widely used in industry, including in the pharmaceutical industry to manufacture drugs such as aspirin, and in the textile industry to produce materials such as cellulose acetate.

In the industrial manufacture of aspirin, salicylic acid reacts with ethanoic anhydride in an acylation reaction to form aspirin, which is acetylsalicylic acid, and ethanoic acid.

Acyl chlorides can also undergo acylation reactions, but reactions involving acyl chlorides are usually fast and highly exothermic, and they produce toxic hydrogen chloride gas. For this reason acid anhydrides are preferred in the manufacture of aspirin. They are generally less reactive, easier to control, and cheaper to produce, and the by-product formed is a carboxylic acid, which is less hazardous than hydrogen chloride.

The word anhydride means without water. It should not be a surprise that adding water to an acid anhydride turns it back into the corresponding carboxylic acid.

Acyl groups are introduced using acyl chlorides or acid anhydrides, the two acylating agents, and both are derivatives of carboxylic acids.

They react by nucleophilic addition–elimination: a nucleophile adds to the carbonyl carbon and a small molecule is eliminated.

That gives carboxylic acids with water, esters with alcohols, and amides with ammonia or primary amines.

The manufacture of aspirin is that same acylation, run with ethanoic anhydride rather than an acyl chloride because the anhydride is less reactive, easier to control, cheaper, and gives a less hazardous by-product.