7.5.7 Addition-Elimination Reactions of Acyl Chlorides

• Acyl chlorides undergo addition-elimination reactions such as hydrolysis, esterification reactions to form esters, and condensation reactions to form amides
• The general mechanism of these 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
  • The lone pair on the oxygen atoms carry out an initial attack on the carbonyl carbon
  • 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 or phenols act as a nucleophile
  • The lone pair on the oxygen atoms carry out an initial attack on the carbonyl carbon
  • This is again followed by the elimination of an HCl molecule

• With phenols, the reaction requires heat to proceed and needs to be carried out in the presence of a base
• The base deprotonates the phenol to form a phenoxide ion which is a better nucleophile than the phenol molecule
  • The phenoxide ion carries out an initial attack on the carbonyl carbon
  • A small molecule of NaCl is eliminated

Reaction mechanism of the esterification of acyl chlorides with alcohols

Reaction mechanism of the esterification of acyl chlorides with phenols

Formation of amides: reaction mechanism

• The nitrogen atom in ammonia and primary/secondary amines act as a nucleophile
  • The lone pair on the nitrogen atoms carry out an initial attack on the carbonyl carbon
  • This is followed by the elimination of an HCl molecule

• Both reactions of acyl chlorides with ammonia and amines are vigorous however there are also differences
  • With ammonia - The product is a non-substituted amide and white fumes of HCl are formed
  • With amines - The product is a substituted amide and the HCl formed reacts with the unreacted amine to form a white organic ammonium salt

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

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