7.5.4 Nucleophilic Addition–Elimination

• An important class of reactions that ammonia and amines undergo is nucleophilic substitution with acyl chlorides (or acid chlorides) and acid anhydrides
• These reactions are also called nucleophilic addition-elimination reactions
• Here is a reminder of the functional groups acyl chloride and acid anhydride:

The acyl chloride and acid anhydride group showing the polarity of the functional group

• The delta positive carbon atom is the site of a the nucleophilic attack by the lone pair on the nitrogen in ammonia or the amine
• Chlorine is more electronegative than oxygen, so creates a stronger dipole along the C-Cl bond making the carbon more susceptible to attack from nucleophiles which is which why acyl chlorides are more reactive than acid anhydrides
• The reaction produces HCl as an elimination product (hence the name addition-elimination), but since both ammonia and amines are basic the HCl reacts to form ammonium chloride or the amine salt respectively
• Hence, two moles of ammonia/amine are needed in the overall equation:

RCOCl    + 2NH₃   →    RCONH₂    +   NH₄Cl

and

RCOCl    + 2R’NH₂   →    RCONHR’    +   R’NH₃Cl

Formation of amides: reaction mechanism

• 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 NH₄Cl 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. The HCl then goes on to react with a molecule of NH₃ to form NH₄Cl

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