- Swern oxidation
The Swern oxidation, named after
Daniel Swern , is achemical reaction whereby a primary or secondaryalcohol is oxidized to analdehyde orketone usingoxalyl chloride , dimethyl sulfoxide (DMSO) and an organic base, such astriethylamine . [cite journal | title = Oxidation of alcohols by “activated” dimethyl sulfoxide. a preparative, steric and mechanistic study | author = Kanji Omura and Daniel Swern | journal = Tetrahedron | year = 1978 | volume = 34 | pages = 1651 | doi = 10.1016/0040-4020(78)80197-5)] [cite journal | author = A. J. Mancuso, D. S. Brownfain and D. Swern | title = Structure of the dimethyl sulfoxide-oxalyl chloride reaction product. Oxidation of heteroaromatic and diverse alcohols to carbonyl compounds | year = 1979 | journal =J. Org. Chem. | volume = 44 | issue = 23 | pages = 4148–4150 | doi = 10.1021/jo01337a028] [cite journal | author = A. J. Mancuso, S.-L. Huang and D. Swern | title = Oxidation of long-chain and related alcohols to carbonyls by dimethyl sulfoxide "activated" by oxalyl chloride | year = 1978 | journal =J. Org. Chem. | volume = 43 | issue = 12 | pages = 2480–2482 | doi = 10.1021/jo00406a041] The reaction is known for its mild character and wide tolerance offunctional group s. [OrgSynth | author = Dondoni, A.; Perrone, D. | title = Synthesis of 1,1-Dimethyl Ethyl-(S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate by Oxidation of the Alcohol | collvol = 10 | collvolpages = 320 | year = 2004 | prep = v77p0064] [OrgSynth | author = Bishop, R. | title =9-Thiabicyclo [3.3.1] nonane-2,6-dione | collvol = 9 | collvolpages = 692 | year = 1998 | prep = cv9p0692] [OrgSynth | author = Leopold, E. J. | title = Selective Hydroboration of a 1,3,7-Triene: Homogeraniol | collvol = 7 | collvolpages = 258 | | year = 1990 | prep = cv7p0258] [cite book | author = Gabriel Tojo and Marcos Fernández | title = Oxidation of Alcohols to Aldehydes and Ketones: A Guide to Current Common Practice | publisher = Springer | year = 2006 | isbn = 0387236074]The by-products are
dimethyl sulfide (Me2S),carbon monoxide (CO),carbon dioxide (CO2) and — whentriethylamine is used as base —triethylammonium chloride (Et3NHCl). Two of the by-products,dimethyl sulfide andcarbon 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. A convenient way to reduce the stench of dimethyl sulfide is to treat the crude product mixture withoxone , whereupon the sulfide is converted todimethyl sulfoxide , which has no odor.Several reviews have been published. [cite journal | author = Mancuso, A. J.; Swern, D. | title = Activated Dimethyl Sulfoxide: Useful Reagents for Synthesis | journal = Synthesis | year = 1981 | volume = 1981 | pages = 165–185 | doi = 10.1055/s-1981-29377 | format = Review] [cite journal | author = Tidwell, T. T. | title = Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides: The Moffatt, Swern, and Related Oxidations | journal =
Org. React. | year = 1990 | volume = 39 | pages = 297–572 | doi = 10.1002/0471264180.or039.03 | format = Review] [cite journal | author = Tidwell, T. T. | title = Oxidation of Alcohols by Activated Dimethyl Sulfoxide and Related Reactions: An Update | journal = Synthesis | year = 1990 | volume = 1990 | pages = 857–870 | format = Review | doi = 10.1055/s-1990-27036]Mechanism
The first step of the Swern oxidation is the low-temperature reaction of
dimethyl sulfoxide (DMSO), 1a & 1b, withoxalyl 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 — will deprotonate the alkoxysulfonium ion to give the sulfurylide 7. In a five-membered ringtransition state , the sulfur ylide 7 decomposes to givedimethyl 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. Withtrifluoroacetic 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 ofcarbodiimides (Pfitzner-Moffatt oxidation ) and pyridine-sulfur trioxide complex (Parikh-Doering 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 basediisopropylethylamine (i-Pr2NEt, Hünig'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 bothersome problem is to rinse used glassware withbleach (usually containingsodium hypochlorite ), which will oxidize the dimethyl sulfide, eliminating the smell.ee also
*
Corey-Kim oxidation
*Pfitzner-Moffatt oxidation References
External links
* [http://www.organic-chemistry.org/namedreactions/swern-oxidation.shtm Organic Chemistry Portal]
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