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Swern oxidation
From Wikipedia, the free encyclopedia

The Swern oxidation, named after Daniel Swern, 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.[1][2][3] The reaction is known for its mild character and wide
[4][5][6][7]
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.

Several reviews have been published.[8][9][10]

Contents
1 Mechanism
2 Variations
3 Considerations
4 See also
5 References
6 External links

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

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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 triuoroacetic anhydride
instead of oxalyl chloride, the reaction can be warmed to 30 C without side
reactions. Other methods for the activation of DMSO to initiate the formation of
the key intermediate 6 are the use of carbodiimides (PtznerMoatt oxidation)
and pyridine-sulfur trioxide complex (Parikh-Doering oxidation). The
intermediate 4 can also be prepared from dimethyl sulfide and
N-chlorosuccinimide (the Corey-Kim oxidation).

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 (iPr2NEt, Hnig's base) can mitigate this side reaction.

Considerations
Dimethyl sulfide, a byproduct of the Swern oxidation, is one of the most foul
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

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Swern oxidation - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Swern_oxidation

problem is to rinse used glassware with bleach (usually containing sodium

hypochlorite), which will oxidize the dimethyl sulfide, eliminating the smell.

The reaction conditions allow oxidation of acid-sensitive compounds, which

might decompose under the acidic conditions of a traditional method such as
Jones oxidation. For example, in Thompson & Heathcock's synthesis of the
sesquiterpene isovelleral,[11] the final step uses the Swern protocol, avoiding
rearrangement of the acid-sensitive cyclopropanemethanol moiety.

See also
Parikh-Doering oxidation
DessMartin periodinane
CoreyKim oxidation
PtznerMoatt oxidation

References
1. ^ Omura, K.; Swern, D. (1978). "Oxidation of alcohols by "activated" dimethyl
sulfoxide. A preparative, steric and mechanistic study". Tetrahedron 34: 1651.
doi:10.1016/0040-4020(78)80197-5 (http://dx.doi.org
/10.1016%2F0040-4020%2878%2980197-5) .)
2. ^ Mancuso, A. J.; Brownfain, D. S.; Swern, D. (1979). "Structure of the dimethyl
sulfoxide-oxalyl chloride reaction product. Oxidation of heteroaromatic and
diverse alcohols to carbonyl compounds". J. Org. Chem. 44 (23): 41484150.
doi:10.1021/jo01337a028 (http://dx.doi.org/10.1021%2Fjo01337a028) .
3. ^ Mancuso, A. J.; Huang, S.-L.; Swern, D. (1978). "Oxidation of long-chain and
related alcohols to carbonyls by dimethyl sulfoxide "activated" by oxalyl chloride".
J. Org. Chem. 43 (12): 24802482. doi:10.1021/jo00406a041 (http://dx.doi.org
/10.1021%2Fjo00406a041) .
4. ^ Dondoni, A.; Perrone, D. (2004), "Synthesis of 1,1-Dimethyl Ethyl-(S)-4-formyl-
2,2-dimethyl-3-oxazolidinecarboxylate by Oxidation of the Alcohol"
(http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v77p0064) , Org.
Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v77p0064;
Coll. Vol. 10: 320
5. ^ Bishop, R. (1998), "9-Thiabicyclo[3.3.1]nonane-2,6-dione"
(http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv9p0692) , Org.
Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv9p0692;

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Swern oxidation - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Swern_oxidation

Coll. Vol. 9: 692

6. ^ Leopold, E. J. (1990), "Selective hydroboration of a 1,3,7-triene: Homogeraniol"
(http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0258) , Org.
Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0258;
Coll. Vol. 7: 258
7. ^ Tojo, G.; Fernndez, M. (2006). Oxidation of alcohols to aldehydes and
ketones: A guide to current common practice. Springer. ISBN 0387236074.
8. ^ Mancuso, A. J.; Swern, D. (1981). "Activated dimethyl sulfoxide: Useful
reagents for synthesis" (Review). Synthesis 1981: 165185. doi:10.1055/s-
1981-29377 (http://dx.doi.org/10.1055%2Fs-1981-29377) .
9. ^ Tidwell, T. T. (1990). "Oxidation of alcohols to carbonyl compounds via
alkoxysulfonium ylides: The Moffatt, Swern, and related oxidations" (Review).
Org. React. 39: 297572. doi:10.1002/0471264180.or039.03 (http://dx.doi.org
/10.1002%2F0471264180.or039.03) .
10. ^ Tidwell, T. T. (1990). "Oxidation of alcohols by activated dimethyl sulfoxide and
related reactions: An update" (Review). Synthesis 1990: 857870. doi:10.1055/s-
1990-27036 (http://dx.doi.org/10.1055%2Fs-1990-27036) .
11. ^ Thompson, S. K.; Heathcock, C. H. (1992). "Total synthesis of some marasmane
and lactarane sesquiterpenes". J. Org. Chem. 57 (22): 59795989.
doi:10.1021/jo00048a036 (http://dx.doi.org/10.1021%2Fjo00048a036) .

External links
Organic Chemistry Portal (http://www.organic-chemistry.org
/namedreactions/swern-oxidation.shtm)
Retrieved from "http://en.wikipedia.org/wiki/Swern_oxidation"
Categories: Organic redox reactions | Name reactions

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