Oxidation — activated DMSO
Swern oxidation of a primary alcohol
How the Swern oxidation of a primary alcohol 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: DMSO, (COCl)₂, then Et₃N. Conditions: CH₂Cl₂, –78 °C then warm to 25 °C. Bonds formed: C=O; Me₂S, CO, CO₂, Et₃NH⁺Cl⁻; bonds broken: O–H, α C–H, S–O. Stereochemistry: Retains α-stereocentres (no epimerization). Rate and selectivity: Activation at –78 °C; ylide collapse fast on warming.
At a glance
Step 1: DMSO is activated by oxalyl chloride
Oxalyl chloride activates DMSO's oxygen, forming a chlorosulfonium species — now a good electrophile with a far better leaving group than plain DMSO oxygen.
Step 2: Alkoxysulfonium salt, then ylide
The alcohol's oxygen displaces chloride, forming an alkoxysulfonium salt; a mild base then deprotonates sulfur's methyl group intermolecularly, forming a sulfonium ylide that collapses through a concerted, intramolecular five-membered cyclic (Ei-like) proton transfer.
Step 3: Five-membered cyclic proton transfer
This ejects dimethyl sulfide and delivers the aldehyde directly — a mild alternative to chromium-based oxidants, gentle enough to avoid over-oxidizing to the carboxylic acid.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- DMSO
- Dimethyl sulfoxide. Polar aprotic solvent; also the oxidant in Swern/Kornblum-type reactions.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- HCl
- Hydrochloric acid / hydrogen chloride. Strong acid; chloride is the nucleophile in additions/substitutions.
- CO
- Carbon monoxide (carbonyl ligand). σ-donor / strong π-acceptor ligand; also a C1 building block.
How it compares with related reactions
| Swern oxidation of a primary alcohol | Baeyer-Villiger oxidation of a ketone | Corey-Kim oxidation | |
|---|---|---|---|
| Reagents | DMSO, (COCl)₂, then Et₃N | mCPBA or CH₃CO₃H (peracid) | NCS, Me₂S, then alcohol, then Et₃N |
| Conditions | CH₂Cl₂, –78 °C then warm to 25 °C | CH₂Cl₂, 25 °C; cat. acid helps | CH₂Cl₂ or toluene, −25 → 0 °C (higher than Swern) |
| Stereochemistry | Retains α-stereocentres (no epimerization) | Retention at the migrating carbon | No stereocentre at carbonyl; α-epimerisation possible with Et₃N |
| Rate / selectivity | Activation at –78 °C; ylide collapse fast on warming | Migratory aptitude: tert > cyclohexyl ≈ sec > Ph > prim > Me | Alkoxysulfonium formation fast; ylide elimination via 5-membered TS |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Swern oxidation of a primary alcohol?
DMSO, (COCl)₂, then Et₃N. Conditions: CH₂Cl₂, –78 °C then warm to 25 °C.
Which bonds are formed and which are broken?
Formed: C=O; Me₂S, CO, CO₂, Et₃NH⁺Cl⁻. Broken: O–H, α C–H, S–O.
What is the stereochemical outcome?
Retains α-stereocentres (no epimerization)
What controls the rate or the selectivity?
Activation at –78 °C; ylide collapse fast on warming
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go