Acylation (Oxford AQA International A Level Chemistry)

Acyl Groups

• Acyl chlorides are derivatives of carboxylic acids by substitution of the -OH group by a chlorine atom

  • Acyl chlorides are named by identifying the parent hydrocarbon chain and adding the suffix -oyl chloride

• Acid anhydrides are also derivatives of carboxylic acids formed by substitution of the -OH group by an alkanoate

  • Acid anhydrides are named by identifying the parent hydrocarbon chain and adding the suffix -oic anhydride

• Amides are organic compounds with an -CONR₂ functional group

  • They can be prepared from the condensation reaction between an acyl chloride and ammonia or amine

Derivatives of ethanoic acid

Nucleophilic Addition–Elimination Mechanism

• Acyl chlorides are reactive organic compounds that undergo many reactions such as nucleophilic addition-elimination reactions

• In nucleophilic addition-elimination reactions, the nucleophilic addition of a small molecule across the C=O bond takes place followed by elimination of a small molecule

• Examples of these nucleophilic addition-elimination reactions include:

  • Hydrolysis

  • Reaction with alcohols to form esters

  • Reaction with ammonia and primary amines to form amides

Hydrolysis

• The hydrolysis of acyl chlorides results in the formation of a carboxylic acid and HCl molecule

• This is a nucleophilic addition-elimination reaction

• A water molecule adds across the C=O bond

• A hydrochloric acid (HCl) molecule is eliminated

• For example the hydrolysis of propanoyl chloride to form propanoic acid and HCl is:

Mechanism of hydrolysis of acyl chlorides

• In the hydrolysis of acyl chlorides, the water molecule acts as a nucleophile

  • Step 1 - Nucleophilic addition; the lone pair on the oxygen atoms carry out an initial attack on the carbonyl carbon

  • Step 2 - Elimination; this is followed by the elimination of a hydrochloric acid (HCl) molecule
    

Formation of esters

• Acyl chlorides can react with alcohols to form esters

• The esterification of acyl chlorides is also a nucleophilic addition-elimination reaction

  • The alcohol adds across the C=O bond

  • A HCl molecule is eliminated

Formation of esters: reaction mechanism

• In the esterification reaction of acyl chlorides, the alcohols act as a nucleophile

• Step 1 - Nucleophilic addition; the lone pair on the oxygen atoms carry out an initial attack on the carbonyl carbon

• Step 2 - Elimination; this is again followed by the elimination of an HCl molecule

Formation of amides

• Acyl chlorides can form amides with primary amines and ammonia

• The nitrogen atom in ammonia and primary amine has a lone pair of electrons which can be used to attack the carbonyl carbon atom in the acyl chlorides

• The product is an amide (when reacted with ammonia) or N-substituted amide (when reacted with primary amines)

• This is also an example of a nucleophilic addition-elimination reaction as

  • The amine or ammonia molecule adds across the C=O bond

  • A HCl molecule is eliminated

Formation of amides: reaction mechanism

• The nitrogen atom in ammonia and primary amines act as a nucleophile

  • Step 1 - Nucleophilic addition; the lone pair on the nitrogen atoms carry out an initial attack on the carbonyl carbon

  • Step 2 - Elimination; this is followed by the elimination of an HCl molecule

  • Step 3 - Acid-Base reaction; the HCl formed would immediately react with excess ammonia to give ammonium chloride in an acid-base reaction

Mechanism with ammonia

Mechanism with a primary amine

Manufacture of Aspirin

• Acylation reactions have many uses, such as in the pharmaceutical and textile industries for making drugs, e.g. aspirin, and textiles, e.g. cellulose acetate

• In the industrial manufacture of aspirin, salicylic acid and ethanoic anhydride are reacted together in an acylation reaction to form aspirin and ethanoic acid

salicylic acid + ethanoic anhydride aspirin + ethanoic acid

• The reaction of acyl chlorides with water or alcohols produces carboxylic acid and esters respectively

  • However it is normally a fast, exothermic process with a rapid production of highly corrosive hydrogen chloride gas

  • In general, acid anhydrides are preferred over acyl chlorides in the production of aspirin because they are also cheaper to produce, less reactive and the reactions can be more easily controlled

  • For acid anhydrides, the by-product is the less corrosive carboxylic acid compared to hydrogen chloride for acyl chlorides