7.3.5 Acylation

Ethanoic acid derivatives

Answer:

• 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

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

Acyl chlorides are hydrolysed to carboxylic acids

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

Acyl chlorides undergo esterification with alcohols to form esters

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

Acyl chlorides undergo reactions with ammonia and primary amines to form amides

• Acyl chlorides undergo nucleophilic addition-elimination reactions such as hydrolysis, esterification reactions to form esters, and condensation reactions to form amides
• The general mechanism of these nucleophilic addition-elimination reactions involve two steps:
  • Step 1 - Addition of a nucleophile across the C=O bond
  • Step 2 - Elimination of a small molecule such as HCl or H₂O

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

Reaction mechanism of the hydrolysis of acyl chlorides

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

Reaction mechanism of the esterification of acyl chlorides with alcohols

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

Reaction mechanism of the formation of amides from acyl chlorides with ammonia

Reaction mechanism of the formation of amides from acyl chlorides with primary amines