• 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