Reactivity

Esters are fairly reactive due to the electrophilicity of the C=O carbon and to its capacity to stabilize α enolate anions.

Thumbnail of the video on ester hydrolysis

Thumbnail of the video on the Claisen condensation

Acid hydrolysis

This reaction is the reverse of Fischer esterification and its mechanism is the same but inverting the sequence (Principle of Microscopic Reversibility).

The mechanism is the typical addition-elimination activated by the early protonation of the C=O group. If one uses isotopically labelled water with ¹⁸O the alcohol ends up free of the isotopic label clearly indicating that the O–CH₃ bond never breaks and reinforcing the addition-elimination mechanism.

Acid hydrolysis of methyl benzoate with ¹⁸O-labelled water: the labelled oxygen ends up in benzoic acid and the methanol does not contain it

Basic hydrolysis (saponification)

"Saponification" means "making soap". The saponification of fats and oils is the method of choice to obtain long-chain carboxylates.

Click here to remember it.

In the following example the chirality of the alcoholic moiety remains intact strongly pointing to the addition-elimination mechanism and that the O-CH bond never breaks. If hydroxide had attacked the butyloxy group, the leaving alcohol would have either inverted via a S_N2 process or racemized via a S_N1 mechanism.

Mechanism of the saponification of (R)-2-butyl benzoate: the acyl–oxygen bond breaks and (R)-2-butanol keeps its configuration

Transesterification

An ester can be turned into another one by dissolving it in an alcohol in acidic medium. Look at some examples:

Ammonia and amines

Ammonia and amines (with N), either primary or secondary, are excellent nucleophiles that may react with esters yielding amides (with D).

Aminolysis of esters: ethyl chloroacetate with ammonia at 0 °C gives chloroacetamide and ethyl lactate with methylamine at 25 °C gives N-methyllactamide

Would you propose an addition-elimination mechanism for this process?

Reduction with hydrides or metals

Esters are reduced only with strong hydrides like LiAlH₄ (LAH). NaBH₄ does not react. Alkali metals can also be used. Important: Beware of other groups' competition!

Reduction of esters to alcohols: methyl benzoate with LiAlH₄ gives benzyl alcohol and ethyl decanoate with Na in ethanol gives 1-decanol

Click here to recall this reaction within the context of alcohol synthesis.

Organolithium or Grignard reagents

Organometallics react with esters through the addition-elimination mechanism but there's a glitch: the intermediate ketone reacts even faster than the starting ester and the reaction cannot be stopped and leads to a tertiary alcohol. Look at an example below. Important: Beware of other groups' competition!

Methyl benzoate with two equivalents of phenylmagnesium bromide gives benzophenone as an intermediate and, after hydrolysis, triphenylmethanol

Enolate formation

Click here to revisit the acidity of α-hydrogens to a carbonyl group

The enolate ions of esters can undergo various reactions:
1) SN (alkylation) with compounds bearing a good leaving group.
2) addition to other carbonyl groups.
3) addition-elimination to esters (Claisen condensation)

Alkylation of the enolate of ethyl propanoate, formed with LDA in THF at −80 °C, with an allylic bromide

Addition of the enolate of ethyl propanoate, formed with LDA, to benzophenone to give a β-hydroxy ester

Claisen condensation is to esters what aldol condensation is to aldehydes and ketones. It is a very important reaction because it leads to β-dicarbonyl compounds, very versatile in organic synthesis.

Crossed Claisen condensation: the enolate of ethyl propanoate, formed with LDA, attacks methyl benzoate to give a β-keto ester

Dieckmann condensation is the intramolecular version of Claisen condensation. It is a very important reaction because it leads to cyclic β-dicarbonyl compounds, very versatile in organic synthesis.

Diester with the α-hydrogen marked, substrate of the Dieckmann condensation