Swern oxidation
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The Swern oxidation is a chemical reaction whereby a primary or secondary alcohol is oxidized to a aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine.Template:RefTemplate:RefTemplate:Ref The reaction is known for its mild character and wide tolerance of functional groups.Template:RefTemplate:RefTemplate:Ref
Image:Swern Oxidation Scheme.png
The advantages of this method compared to chromium(VI) reagents such as Jones reagent or PCC are the use of less toxic substances and that further oxidation to the carboxylic acid is not possible with these reagents. The by-product, dimethyl sulfide, is a volatile liquid (B.P. 37 °C) with an unpleasant odour - so the work-up needs to be performed in a fume hood. A convenient way to reduce the stench of dimethyl sulfide is to treat the crude product with oxone, whereupon the sulfide is converted to dimethyl sulfoxide, which has no odor.
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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.
Image:Dimethylchlorosulfonium Formation Mechanism.png
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 or N,N-diisopropylethylamine) 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.
Image:Swern Oxidation Mechanism.png
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.
References
- Template:Note Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.
- Template:Note Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43, 2480–2482.
- Template:Note Mancuso, A. J.; Brownfain, D. S.; Swern, D. J. Org. Chem. 1979, 44, 4148.
- Template:Note Mancuso, A. J.; Swern, D. Synthesis 1981, 165-185. (Review)
- Template:Note Tidwell, T. T. Org. React. 1990, 39, 297-572. (Review)
- Template:Note Tidwell, T. T. Synthesis 1990, 857-870. (Review) (Template:DOI)
- Dondoni, A.; Perrone, D. Org. Syn., Coll. Vol. 10, p.320 (2004); Vol. 77, p.64 (2000). (Article)
- Bishop, R. Org. Syn., Coll. Vol. 9, p.692 (1998); Vol. 70, p.120 (1992). (Article)
- Leopold, E. J. Org. Syn., Coll. Vol. 7, p.258 (1990); Vol. 64, p.164 (1986). (Article)