Swern Oxidation
Swern Oxidation: DMSO is activated by oxalyl chloride to form a reactive chlorosulfonium intermediate, which the alcohol displaces to form an…
What happens
DMSO is activated by oxalyl chloride to form a reactive chlorosulfonium intermediate, which the alcohol displaces to form an alkoxysulfonium salt; a base then removes a proton to trigger an intramolecular elimination, the actual oxidation step, releasing dimethyl sulfide and the aldehyde.
Reaction summary
BnOH + (COCl)₂/DMSO, then Et₃N → PhCHO (no over-oxidation to the acid)
Reagents and conditions
- Starting material: Benzyl alcohol
- Reagents: Oxalyl chloride ((COCl)₂); Dimethyl sulfoxide (DMSO); Triethylamine (Et₃N)
- Conditions: −78°C; then aqueous workup
- Products: Benzaldehyde
Mechanism
- DMSO activation: Oxalyl chloride reacts with DMSO's oxygen, releasing CO, CO₂, and chloride, and generating an electrophilic chlorosulfonium ion.
- Alkoxysulfonium formation: The alcohol's oxygen displaces chloride on sulfur, forming an alkoxysulfonium salt.
- Base-mediated elimination: Triethylamine removes a proton adjacent to sulfur; a five-membered cyclic transition state collapses, expelling dimethyl sulfide and forming the new C=O bond.
Selectivity
- Chemoselectivity: Oxidizes primary alcohols cleanly to aldehydes (not over-oxidizing to carboxylic acids) and secondary alcohols to ketones.
Common mistakes
- Confusing Swern with PCC/Dess-Martin, all three stop cleanly at the aldehyde for primary alcohols, but Swern is run at −78°C and releases a foul-smelling dimethyl sulfide byproduct.
- Forgetting the order of addition matters, DMSO is activated by oxalyl chloride FIRST, then the alcohol is added, then the base last.
Memory trick
"Swern smells": the telltale dimethyl sulfide byproduct is why Swern oxidations are run in a well-ventilated fume hood.