| Swern oxidation | |
|---|---|
| Named after | Daniel Swern |
| Reaction type | Organic redox reaction |
| Identifiers | |
| Organic Chemistry Portal | swern-oxidation |
| RSC ontology ID | RXNO:0000154 |
 N(what is this?) (verify) | |
Inorganic chemistry, theSwern oxidation also known asMoffatt-Swern, named afterDaniel Swern, is achemical reaction whereby a primary or secondaryalcohol (−OH) isoxidized to analdehyde (−CH=O) orketone (>C=O) usingoxalyl chloride,dimethyl sulfoxide (DMSO) and an organicbase, such astriethylamine.[1][2][3] It is one of the many oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known for its mild character and wide tolerance offunctional groups.[4][5][6][7]
The by-products aredimethyl sulfide ((CH3)2S),carbon monoxide (CO),carbon dioxide (CO2) and—when triethylamine is used as base—triethylammonium chloride (Et3NHCl). Of the volatile by-products, dimethyl sulfide has a strong, pervasive odour and carbon monoxide is acutely toxic, so the reaction and the work-up needs to be performed in a fume hood. Dimethyl sulfide is a volatile liquid (B.P. 99 °F (37 °C)) with an unpleasant odour at even low concentrations.[8][9][10]
The first step of the Swern oxidation is the low-temperature reaction of DMSO,1a, formally asresonance contributor1b, with oxalyl chloride,2. The first intermediate,3, quickly decomposes giving off carbon dioxide and carbon monoxide and producing chloro(dimethyl)sulfonium chloride,4.
After addition of the alcohol5, the chloro(dimethyl)sulfonium chloride4 reacts with the alcohol to give the key alkoxysulfonium ion intermediate,6. The addition of at least 2 equivalents of base — typically triethylamine — willdeprotonate the alkoxysulfonium ion to give the sulfurylide7. In a five-membered ringtransition state, the sulfur ylide7 decomposes to give dimethyl sulfide and the desiredcarbonyl compound8.
When using oxalyl chloride as thedehydration agent, the reaction must be kept colder than −76 °F (−60 °C) to avoid side reactions. Withcyanuric chloride[11] ortrifluoroacetic anhydride[12] instead of oxalyl chloride, the reaction can be warmed to −22 °F (−30 °C) without side reactions. Other methods for the activation of DMSO to initiate the formation of the key intermediate6 are the use ofcarbodiimides (Pfitzner–Moffatt oxidation), asulfur trioxide pyridine complex (Parikh–Doering oxidation) oracetic anhydride (Albright-Goldman oxidation). The intermediate4 can also be prepared from dimethyl sulfide andN-chlorosuccinimide (theCorey–Kim oxidation).
In some cases, the use of triethylamine as the base can lead toepimerisation at thecarbon alpha to the newly formed carbonyl. Using abulkier base, such asdiisopropylethylamine, can mitigate this side reaction.
Dimethyl sulfide, a byproduct of the Swern oxidation, is one of the most notoriously unpleasant odors known in organic chemistry. Humans can detect this compound in concentrations as low as 0.02 to 0.1 parts per million.[13] A simple remedy for this problem is to rinse used glassware withbleach oroxone solution, which will oxidize the dimethyl sulfide back to dimethyl sulfoxide or todimethyl sulfone, both of which are odourless and nontoxic.[14]
The reaction conditions allow oxidation of acid-sensitive compounds, which might decompose under the acidic oxidation conditions such asJones oxidation. For example, in Thompson & Heathcock's synthesis of thesesquiterpene isovelleral,[15] the final step uses the Swern protocol, avoidingrearrangement of the acid-sensitive cyclopropanemethanol moiety.
