Swern oxidation

The Swern oxidation is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine. The reaction is known for its mild character and wide tolerance of functional groups.



The by-products are dimethyl sulfide (Me2S), carbon monoxide (CO), carbon dioxide (CO2) and — when triethylamine is used as base — triethylammonium chloride (Et3NHCl). Two of the by-products, dimethyl sulfide and carbon monoxide, are very toxic volatile compounds, so the reaction and the work-up needs to be performed in a fume hood. Dimethyl sulfide, is a volatile liquid (B.P. 37 °C) with an unpleasant odour. A convenient way to reduce the stench of dimethyl sulfide is to treat the crude product mixture with oxone, whereupon the sulfide is converted to dimethyl sulfoxide, which has no odor.

Several reviews have been published.

Mechanism
The first step of the Swern oxidation is the low-temperature reaction of dimethyl sulfoxide (DMSO), 1a & 1b, with oxalyl chloride, 2. The first intermediate, 3, quickly decomposes giving off CO2 and CO and producing dimethylchlorosulfonium chloride, 4.



After addition of the alcohol 5, the dimethylchlorosulfonium chloride 4 reacts with the alcohol to give the key alkoxysulfonium ion intermediate, 6. The addition of at least 2 equivalents of base — typically triethylamine — will deprotonate the alkoxysulfonium ion to give the sulfur ylide 7. In a five-membered ring transition state, the sulfur ylide 7 decomposes to give dimethyl sulfide and the desired ketone (or aldehyde) 8.



Variations
When using oxalyl chloride as the dehydration agent, the reaction must be kept colder than -60 °C to avoid side reactions. With trifluoroacetic anhydride instead of oxalyl chloride, the reaction can be warmed to -30 °C without side reactions.

In some cases, the use of triethylamine as the base can lead to epimerisation at the carbon alpha to the newly formed carbonyl. Using the bulkier base diisopropylethylamine (i-Pr2NEt, Hünig's base) can mitigate this side reaction.

Considerations
Dimethyl sulfide, a byproduct of the Swern oxidation is one of the foulest odors known in organic chemistry. Human olfactory glands can detect this compound in concentrations as low as parts per billion. A simple remedy for this bothersome problem is to rinse used glassware with bleach (NaClO), which will oxidize the dimethyl sulfide, eliminating the hideous scent.