Nucleophilic acyl substitution
Base-catalyzed transesterification
How the Base-catalyzed transesterification works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Ester, R′O⁻ (cat. NaOMe or KOH/ROH), alcohol in excess. Conditions: MeOH, 25–65 °C. Bonds formed: new C–OR′ ester; bonds broken: C–OR (original alkoxy). Stereochemistry: No stereocentre at carbonyl; reversible, driven by excess alcohol. Rate and selectivity: Addition of alkoxide is rate-limiting; equilibrium (Le Chatelier).
At a glance
Step 1: Alkoxide adds to C=O
An alkoxide attacks the electrophilic carbonyl carbon of an ester, forming a tetrahedral alkoxide intermediate — identical in shape to the intermediate in ester hydrolysis, just with a different incoming nucleophile.
Step 2: Original alkoxide leaves
The original alkoxy group is expelled as the C=O reforms, exactly mirroring nucleophilic acyl substitution's addition-elimination pattern.
Step 3: Biodiesel: triglyceride → methyl ester
The net effect swaps one ester's alkoxy group for another — this exact reaction is how triglycerides are converted into biodiesel by reaction with methanol, swapping out glycerol for methoxy groups.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- MeOH
- Methanol. Polar protic solvent (also a nucleophile in solvolysis).
- NaOMe
- Sodium methoxide. Alkoxide base matched to methyl esters.
- KOH
- Potassium hydroxide. Strong aqueous/alcoholic base.
How it compares with related reactions
| Base-catalyzed transesterification | Acid-catalyzed amide hydrolysis | Amide synthesis from an acid chloride and amine | |
|---|---|---|---|
| Reagents | Ester, R′O⁻ (cat. NaOMe or KOH/ROH), alcohol in excess | Amide, H₃O⁺ (HCl or H₂SO₄), H₂O | Benzoyl chloride, methylamine, aqueous NaOH |
| Conditions | MeOH, 25–65 °C | 6 M acid, reflux (hours) | CH₂Cl₂ / H₂O (biphasic), 0–25 °C |
| Stereochemistry | No stereocentre at carbonyl; reversible, driven by excess alcohol | No stereocentre created; α-stereocentres retained | No stereocentre; planar amide |
| Rate / selectivity | Addition of alkoxide is rate-limiting; equilibrium (Le Chatelier) | Water attack / C–N cleavage rate-limiting; far slower than ester hydrolysis | Very fast; base neutralises HCl so the amine is not lost as its salt |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Base-catalyzed transesterification?
Ester, R′O⁻ (cat. NaOMe or KOH/ROH), alcohol in excess. Conditions: MeOH, 25–65 °C.
Which bonds are formed and which are broken?
Formed: new C–OR′ ester. Broken: C–OR (original alkoxy).
What is the stereochemical outcome?
No stereocentre at carbonyl; reversible, driven by excess alcohol
What controls the rate or the selectivity?
Addition of alkoxide is rate-limiting; equilibrium (Le Chatelier)
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go
Related mechanisms
- Acid-catalyzed amide hydrolysis
- Amide synthesis from an acid chloride and amine
- Base hydrolysis (saponification) of an ester
- Ester synthesis from an acid chloride and alcohol
- Fischer esterification
- In-line phosphoryl transfer (SN2 at phosphorus)
- Weinreb amide addition
- Hydride adds to acetaldehyde's carbonyl