Conversion of Esters to Amides (Aminolysis of Esters)
Conversion of Esters to Amides (Aminolysis of Esters): An ester reacts with ammonia or an amine to form an amide, by nucleophilic acyl substitution.
What happens
An ester reacts with ammonia or an amine to form an amide, by nucleophilic acyl substitution. NH₃ gives a primary amide (–CONH₂), RNH₂ an N-substituted amide (–CONHR) and R₂NH an N,N-disubstituted amide (–CONR₂). The second product is the alcohol derived from the ester's alkoxy group (–OR′ → R′OH). Often an excess of the amine/ammonia and sometimes heat are used.
Reaction summary
Ester + NH₃ (or RNH₂, R₂NH) → amide + alcohol (COOR → CONR₂)
Reagents and conditions
- Starting material: Methyl 2-phenylacetate (ester)
- Reagents: Ammonia (NH₃)
- Conditions: Excess NH₃ (or amine), sometimes heat
- Products: 2-Phenylacetamide (primary amide); Methanol (alcohol from the –OR′ group)
Mechanism
- Nitrogen Attacks: The nitrogen of NH₃ / RNH₂ / R₂NH has a lone pair. It attacks the electrophilic carbonyl carbon, the C=O opens, and a tetrahedral intermediate forms.
- Proton Transfers: Protons are transferred between the nitrogen and oxygen groups. This prepares the intermediate for elimination.
- Carbonyl Reforms: The oxygen reforms the C=O and the ester's –OR′ group is expelled. After the necessary proton transfers, that portion becomes R′OH.
- Amide Forms: The final product is R–CONH₂, or R–CONHR / R–CONR₂, depending on the nitrogen nucleophile. The other product is the alcohol R′OH.
Common mistakes
- Don't attack the R′ carbon of the ester. The amine attacks the carbonyl carbon, because this is nucleophilic acyl substitution.
- Don't remove the carbonyl: the product is R–CONH₂, not R–CH₂NH₂.
Memory trick
Amine attacks → Amide appears. ESTER + AMINE → AMIDE.