Fischer esterification: ethanoic acid and ethanol

Carboxylic acids react with alcohols, using an acid catalyst, to make esters. The acid activates the carbonyl group so the weakly nucleophilic alcohol can attack. Every step is reversible, so an excess of alcohol or removal of water is used to push the equilibrium towards the ester.

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Fischer esterification (acid-catalysed nucleophilic acyl substitution)

Acetic acid and ethanol combine under acid catalysis to give ethyl acetate and water. The acid activates the carbonyl toward attack by the weakly nucleophilic alcohol, and every step is reversible, so excess alcohol or removal of water drives the equilibrium to the ester.

Overall reaction

1. 1Protonation of the carbonyl oxygenproton transfer · reversible

   acetic acid

   +

   H3O+ (from H2SO4)

   H+

   protonated acid

   +

   water

   Electron movement

   1. A lone pair on the carbonyl oxygen picks up a proton from the acid.
   2. The O–H bond of H3O+ breaks; its electrons stay on the water oxygen.

   Protonating the C=O makes the carbonyl carbon far more electrophilic, so a weak nucleophile like ethanol can attack it.

2. 2Nucleophilic attack by ethanolnucleophilic addition · reversible

   protonated acid

   +

   ethanol

   oxonium tetrahedral intermediate

   Electron movement

   1. A lone pair on the ethanol oxygen attacks the carbonyl carbon.
   2. The C=O pi electrons move onto the oxygen, cancelling its positive charge.

   The alcohol oxygen bonds to the activated carbon, converting the planar sp2 carbon into an sp3 tetrahedral intermediate.

3. 3Proton transfer to an OH groupproton transfer · reversible

   oxonium intermediate

   protonated hydroxyl

   Electron movement

   1. A lone pair on an OH oxygen takes the proton (in practice relayed by solvent molecules).
   2. The O–H bond on the ethyl oxonium breaks, neutralising that oxygen.

   This turns a poor leaving group (OH−) into an excellent one (H2O).

4. 4Loss of waterelimination of leaving group · reversible

   protonated hydroxyl

   −H2O

   protonated ester

   +

   water

   Electron movement

   1. A lone pair on the remaining OH oxygen moves in to form a C=O pi bond.
   2. The C–O bond to the protonated hydroxyl breaks and water leaves.

   Reforming the carbonyl expels water, giving a resonance-stabilised protonated ester.

5. 5Deprotonation to give the esterproton transfer · reversible

   protonated ester

   +

   water

   −H+

   ethyl acetate

   +

   H3O+

   Electron movement

   1. A lone pair on water removes the proton from the carbonyl oxygen.
   2. The O–H electrons return to the carbonyl oxygen, giving the neutral ester.

   Loss of the proton regenerates the acid catalyst and gives the neutral ester.