Swern oxidation
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.
[Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.][Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43, 2480â€"2482.][Mancuso, A. J.; Brownfain, D. S.; Swern, D. J. Org. Chem. 1979, 44, 4148.] The reaction is known for its mild character and wide tolerance of
functional groups.
[Mancuso, A. J.; Swern, D. Synthesis 1981, 165-185. (Review)][Tidwell, T. T. Org. React. 1990, 39, 297-572. (Review)][Tidwell, T. T. Synthesis 1990, 857-870. (Review) ()]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.
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.
|
Dimethylchlorosulfonium chloride formation |
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.
|
The mechanism of the Swern oxidation |
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.
# 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)
*
Corey-Kim oxidation*
Pfitzner-Moffatt oxidation*
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