View source for Chemistry:Swern oxidation

{{short description|Organic redox reaction}}
{{Reactionbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 298094479
| Name = Swern oxidation
| Type = Organic redox reaction
| NamedAfter = Daniel Swern
| Section3 = {{Reactionbox Identifiers
   | OrganicChemistryNamed = swern-oxidation
   | RSC_ontology_id = 0000154
 }}
}}

In [[Chemistry:Organic chemistry|organic chemistry]], the '''Swern oxidation''', named after Daniel Swern, is a [[Chemistry:Chemical reaction|chemical reaction]] whereby a primary or secondary [[Chemistry:Alcohol|alcohol]] ({{chem2|\sOH}}) is [[Chemistry:Redox|oxidized]] to an [[Chemistry:Aldehyde|aldehyde]] ({{chem2|\sCH\dO}}) or [[Chemistry:Ketone|ketone]] ({{chem2|>C\dO}}) using [[Chemistry:Oxalyl chloride|oxalyl chloride]], [[Chemistry:Dimethyl sulfoxide|dimethyl sulfoxide]] (DMSO) and an organic [[Chemistry:Base|base]], such as [[Chemistry:Triethylamine|triethylamine]].<ref>{{cite journal | title = Oxidation of alcohols by "activated" dimethyl sulfoxide. A preparative, steric and mechanistic study | author = Omura, K.; Swern, D. | journal = Tetrahedron | year = 1978 | volume = 34 | issue = 11 | pages = 1651–1660 | doi = 10.1016/0040-4020(78)80197-5}}</ref><ref>{{cite journal | author = Mancuso, A. J.; Brownfain, D. S.; Swern, D. | 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}}</ref><ref>{{cite journal | author = Mancuso, A. J.; Huang, S.-L.; Swern, D. | 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}}</ref> It is one of the many oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known for its mild character and wide tolerance of [[Chemistry:Functional group|functional group]]s.<ref>{{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}}</ref><ref>{{OrgSynth | author = Bishop, R. | title = <nowiki>9-Thiabicyclo[3.3.1]nonane-2,6-dione</nowiki> | collvol = 9 | collvolpages = 692 | year = 1998 | prep = cv9p0692}}</ref><ref>{{OrgSynth | author = Leopold, E. J. | title = Selective hydroboration of a 1,3,7-triene: Homogeraniol | collvol = 7 | collvolpages = 258 | year = 1990 | prep = cv7p0258}}</ref><ref>{{cite book |author1=Tojo, G. |author2=Fernández, M. | title = Oxidation of alcohols to aldehydes and ketones: A guide to current common practice | publisher = Springer | year = 2006 | isbn = 0-387-23607-4}}</ref>

[[File:Swern Oxidation Scheme.png|center|400px|The Swern oxidation.]]

The by-products are [[Chemistry:Dimethyl sulfide|dimethyl sulfide]] ((CH<sub>3</sub>)<sub>2</sub>S), [[Chemistry:Carbon monoxide|carbon monoxide]] (CO), [[Chemistry:Carbon dioxide|carbon dioxide]] (CO<sub>2</sub>) and—when triethylamine is used as base—triethylammonium chloride (Et<sub>3</sub>NHCl). Of the volatile by-products, dimethyl sulfide has a strong, pervasive odour and carbon monoxide is acutely toxic, so the reaction and the work-up needs to be performed in a fume hood. Dimethyl sulfide is a volatile liquid (B.P. 37&nbsp;°C) with an unpleasant odour at even low concentrations.<ref>{{cite journal | author = Mancuso, A. J.; Swern, D. | title = Activated dimethyl sulfoxide: Useful reagents for synthesis | journal = Synthesis | year = 1981 | volume = 1981 | issue = 3 | pages = 165–185 | doi = 10.1055/s-1981-29377 | type = Review}}</ref><ref>{{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 | isbn = 0471264180 | type = Review}}</ref><ref>{{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 | issue = 10 | pages = 857–870 | type = Review | doi = 10.1055/s-1990-27036}}</ref>

==Mechanism==
The first step of the Swern oxidation is the low-temperature reaction of DMSO, '''1a''', formally as [[Chemistry:Resonance|resonance]] contributor '''1b''', with oxalyl chloride, '''2'''. The first intermediate, '''3''', quickly decomposes giving off carbon dioxide and carbon monoxide and producing chloro(dimethyl)sulfonium chloride, '''4'''.

[[File:Dimethylchlorosulfonium Formation Mechanism.png|600px|center|Dimethylchlorosulfonium chloride formation.]]

After addition of the alcohol '''5''', the chloro(dimethyl)sulfonium 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 [[Chemistry:Deprotonation|deprotonate]] the alkoxysulfonium ion to give the sulfur [[Chemistry:Ylide|ylide]] '''7'''. In a five-membered ring [[Chemistry:Transition state|transition state]], the sulfur ylide '''7''' decomposes to give dimethyl sulfide and the desired carbonyl compound '''8'''.

[[File:Swern Oxidation Mechanism.png|600px|center|The mechanism of the Swern oxidation.]]

==Variations==
When using oxalyl chloride as the [[Chemistry:Dehydration reaction|dehydration]] agent, the reaction must be kept colder than &minus;60&nbsp;°C to avoid side reactions. With [[Chemistry:Cyanuric chloride|cyanuric chloride]]<ref>{{cite journal|doi=10.1021/jo015935s | volume=66 | title=A Mild and Efficient Alternative to the Classical Swern Oxidation | journal=The Journal of Organic Chemistry | pages=7907–7909 | author=De Luca Lidia| year=2001 | issue=23 | pmid=11701058 }}</ref> or [[Chemistry:Trifluoroacetic anhydride|trifluoroacetic anhydride]]<ref>{{cite journal|doi=10.1021/jo00868a012|title=Dimethyl Sulfoxide-Trifluoroacetic Anhydride. New Reagent for Oxidation of Alcohols to Carbonyls|last1=Omura|first1=Kanji|last2=Sharma|first2=Ashok K.|last3=Swern|first3=Daniel|journal=J. Org. Chem.|year=1976|volume=41|issue=6|pages=957–962}}</ref> instead of oxalyl chloride, the reaction can be warmed to &minus;30&nbsp;°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 ([[Chemistry:Pfitzner–Moffatt oxidation|Pfitzner–Moffatt oxidation]]), a [[Chemistry:Sulfur trioxide pyridine complex|sulfur trioxide pyridine complex]] ([[Chemistry:Parikh–Doering oxidation|Parikh–Doering oxidation]]) or [[Chemistry:Acetic anhydride|acetic anhydride]] ([[Chemistry:Albright-Goldman oxidation|Albright-Goldman oxidation]]). The intermediate '''4''' can also be prepared from dimethyl sulfide and [[Chemistry:N-Chlorosuccinimide|''N''-chlorosuccinimide]] (the [[Chemistry:Corey–Kim oxidation|Corey–Kim oxidation]]).

In some cases, the use of triethylamine as the base can lead to epimerisation at the [[Chemistry:Alpha and beta carbon|carbon alpha]] to the newly formed carbonyl. Using a [[Chemistry:Steric effects|bulkier]] base, such as diisopropylethylamine, can mitigate this side reaction.

==Considerations==
Dimethyl sulfide, a byproduct of the Swern oxidation, is one of the most notoriously unpleasant odors known in organic chemistry. Humans can detect this compound in concentrations as low as 0.02 to 0.1 parts per million.<ref>{{cite book | author = Morton, T. H. | year = 2000 | chapter = Archiving Odors |editor1=Bhushan, N. |editor2=Rosenfeld, S. | title = Of Molecules and Mind | pages = 205–216 | location = Oxford | publisher = Oxford University Press}}</ref> A simple remedy for this problem is to rinse used glassware with [[Chemistry:Bleach|bleach]] or oxone solution, which will oxidize the dimethyl sulfide back to dimethyl sulfoxide or to dimethyl sulfone, both of which are odourless and nontoxic.<ref>{{cite journal |title= Safe Handling of Boranes at Scale | first1=William J. Jr. | last1=Atkins |first2= Elizabeth R. |last2= Burkhardt |first3= Karl |last3= Matos |journal= Org. Process Res. Dev. |year= 2006 | volume= 10 |issue= 6 |pages= 1292–1295 |doi= 10.1021/op068011l}}</ref>

The reaction conditions allow oxidation of acid-sensitive compounds, which might decompose under the acidic oxidation conditions such as [[Chemistry:Jones oxidation|Jones oxidation]].  For example, in Thompson & Heathcock's synthesis of the [[Chemistry:Sesquiterpene|sesquiterpene]] isovelleral,<ref name="Thompson1992">{{cite journal|last=Thompson|first=S. K.|author2=Heathcock, C. H. |year=1992|title=Total synthesis of some marasmane and lactarane sesquiterpenes|journal=J. Org. Chem.|volume=57|issue=22|pages=5979–5989|doi=10.1021/jo00048a036}}</ref> the final step uses the Swern protocol, avoiding [[Chemistry:Rearrangement reaction|rearrangement]] of the acid-sensitive cyclopropanemethanol moiety.

[[File:IsovelleralPreparationViaSwernOxidation.png|500px|center]]

==See also==
* [[Chemistry:Alcohol oxidation|Alcohol oxidation]]
* [[Chemistry:Sulfonium-based oxidation of alcohols to aldehydes|Sulfonium-based oxidation of alcohols to aldehydes]]
* [[Chemistry:Pyridinium chlorochromate|Pyridinium chlorochromate]]
* [[Chemistry:Jones oxidation|Jones oxidation]]
* [[Chemistry:Oppenauer oxidation|Oppenauer oxidation]]
* [[Chemistry:Pfitzner–Moffatt oxidation|Pfitzner–Moffatt oxidation]]
* [[Chemistry:Parikh–Doering oxidation|Parikh–Doering oxidation]]
* [[Chemistry:Albright-Goldman oxidation|Albright-Goldman oxidation]]
* [[Chemistry:Corey–Kim oxidation|Corey–Kim oxidation]]
* [[Chemistry:Dess–Martin periodinane|Dess–Martin periodinane]] oxidation
* [[Chemistry:Ley oxidation|Ley oxidation]] ([[Chemistry:Tetrapropylammonium perruthenate|TPAP]] oxidation)
* [[Chemistry:TEMPO|TEMPO]] oxidation

==References==
{{reflist}}

==External links==
* [https://www.organic-chemistry.org/namedreactions/swern-oxidation.shtm Organic Chemistry Portal]

{{DEFAULTSORT:Swern Oxidation}}
[[Category:Organic oxidation reactions]]
[[Category:Name reactions]]

{{Sourceattribution|Swern oxidation}}