Swern oxidation
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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.<ref>Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651. (DOI:10.1016/0040-4020(78)80197-5)</ref><ref>Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43, 2480–2482. (DOI:10.1021/jo00406a041)</ref><ref>Mancuso, A. J.; Brownfain, D. S.; Swern, D. J. Org. Chem. 1979, 44, 4148. (DOI:10.1021/jo01337a028)</ref> The reaction is known for its mild character and wide tolerance of functional groups.<ref>Dondoni, A.; Perrone, D. Org. Syn., Coll. Vol. 10, p.320 (2004); Vol. 77, p.64 (2000). (Article)</ref><ref>Bishop, R. Org. Syn., Coll. Vol. 9, p.692 (1998); Vol. 70, p.120 (1992). (Article)</ref><ref>Leopold, E. J. Org. Syn., Coll. Vol. 7, p.258 (1990); Vol. 64, p.164 (1986). (Article)</ref>
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.
Several reviews have been published.<ref>Mancuso, A. J.; Swern, D. Synthesis 1981, 165-185. (Review)</ref><ref>Tidwell, T. T. Org. React. 1990, 39, 297-572. (Review)</ref><ref>Tidwell, T. T. Synthesis 1990, 857-870. (Review) (DOI:10.1055/s-1990-27036)</ref>
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[edit] 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 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.
[edit] 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 neighbouring the newly formed carbonyl, using diisopropylethylamine (Hünig's base) can stop this side reaction.
[edit] References
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