Overall reaction
(R)-butan-2-ol + PhCOOH → (PPh₃, DEAD, THF) (S)-sec-butyl benzoate
PPh₃ and DEAD activate an alcohol for SN2 by a carboxylate, with inversion.
Name reaction · mechanism
Mitsunobu Reaction
The Mitsunobu reaction converts an alcohol into an ester (or ether, imide, azide) with clean inversion at the alcohol carbon. Triphenylphosphine adds to DEAD, the betaine deprotonates the acidic nucleophile, the alcohol attacks phosphorus to form an alkoxyphosphonium ion, and the carboxylate displaces triphenylphosphine oxide by SN2.
Mechanism step by step
- Betaine. PPh₃ adds to the N=N of DEAD
- Deprotonation. The betaine takes the acid proton
- Alcohol activation. O attacks P; the hydrazide leaves
- Proton transfer. The alkoxyphosphonium ion
- SN2 with inversion. Benzoate attacks from the back; Ph₃P=O leaves
Each step is checked electron by electron: the curly arrows give exactly the structures drawn.
Key points
- Clean inversion at the alcohol carbon: (R)-alcohol → (S)-ester.
- The nucleophile needs pKa < ~13 (carboxylic acids, phenols, imides, HN₃).
- By-products Ph₃P=O and the hydrazine dicarboxylate can be hard to remove.
- Hydrolysis of the ester gives the inverted alcohol.
For JEE and NEET
- Inversion of configuration at the alcohol carbon.
- Ph₃P=O formation drives the reaction.
- Hydrolysing the ester gives the inverted alcohol.
- Tertiary alcohols do not react (SN2).
FAQ
Why does the Mitsunobu reaction invert the stereocentre?
The last step is an SN2 backside attack of the nucleophile on the carbon bonded to the O–P⁺Ph₃ leaving group.
Why must the nucleophile be acidic?
It must protonate the betaine; weakly acidic partners leave the hydrazide anion to compete as the nucleophile.
What are the by-products?
Triphenylphosphine oxide and diethyl hydrazine-1,2-dicarboxylate.
Draw it in MolDraw
The button above opens the complete figure — overall reaction, numbered mechanism and key points — as ordinary editable structures. Change substituents, recolour atoms, or export a PNG, SVG or chemfig code for notes and slides. The same figure is in the Templates panel under Name reactions.