Swern oxidation
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The Swern oxidation, named after
Daniel Swern Daniel Swern (January 21, 1916 – December 5, 1982) was an American chemist who discovered the Swern oxidation The Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an alde ...
, is a
chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
whereby a primary or secondary alcohol is
oxidized Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
to an
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
or ketone using
oxalyl chloride Oxalyl chloride is an organic chemical compound with the formula (COCl)2. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis. Preparation Oxalyl chloride was first prepared in 1892 ...
, dimethyl sulfoxide (DMSO) and an organic base, such as
triethylamine Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine or tetraethylammonium, for which TEA ...
. 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
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...
s. The by-products are dimethyl sulfide ((CH3)2S),
carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
(CO),
carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
(CO2) and—when triethylamine is used as base— triethylammonium chloride (Et3NHCl). 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 °C) with an unpleasant odour at even low concentrations.


Mechanism

The first step of the Swern oxidation is the low-temperature reaction of DMSO, 1a, formally as
resonance Resonance describes the phenomenon of increased amplitude that occurs when the frequency of an applied Periodic function, periodic force (or a Fourier analysis, Fourier component of it) is equal or close to a natural frequency of the system ...
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. 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
deprotonate Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...
the alkoxysulfonium ion to give the sulfur
ylide An ylide or ylid () is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms ...
7. In a five-membered ring
transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...
, the sulfur ylide 7 decomposes to give dimethyl sulfide and the desired
carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...
compound 8.


Variations

When using oxalyl chloride as the
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
agent, the reaction must be kept colder than −60 °C to avoid side reactions. With
cyanuric chloride Cyanuric chloride is an organic compound with the formula (NCCl)3. This white solid is the chlorinated derivative of 1,3,5-triazine. It is the trimer of cyanogen chloride. Cyanuric chloride is the main precursor to the popular but controver ...
or
trifluoroacetic anhydride Trifluoroacetic anhydride (TFAA) is the acid anhydride of trifluoroacetic acid. It is the perfluorinated derivative of acetic anhydride. Preparation Trifluoroacetic anhydride was originally prepared by the dehydration of trifluoroacetic acid with ...
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 In organic chemistry, a carbodiimide (systematic IUPAC name: methanediimine) is a functional group with the formula RN=C=NR. They are exclusively synthetic. A well known carbodiimide is dicyclohexylcarbodiimide, which is used in peptide synthesis. ...
(
Pfitzner–Moffatt oxidation The Pfitzner–Moffatt oxidation, sometimes referred to as simply the Moffatt oxidation, is a chemical reaction for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively. The oxidant is a combination of dimethyl ...
), a sulfur trioxide pyridine complex (
Parikh–Doering oxidation The Parikh– Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively. The procedure uses dimethyl sulfoxide (DMSO) as the oxidant and the solvent, activated by the sulf ...
) or acetic anhydride ( Albright-Goldman oxidation). The intermediate 4 can also be prepared from dimethyl sulfide and ''N''-chlorosuccinimide (the
Corey–Kim oxidation The Corey–Kim oxidation is an oxidation reaction used to synthesise aldehydes and ketones from primary and secondary alcohols. It is named for American chemist and Nobel Laureate Elias James Corey and Korean-American chemist Choung Un Kim. ...
). In some cases, the use of triethylamine as the base can lead to
epimerisation In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite absolute configuration, configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in ...
at the carbon alpha to the newly formed carbonyl. Using a bulkier base, such as
diisopropylethylamine ''N'',''N''-Diisopropylethylamine, or Hünig's base, is an organic compound and an amine. It is named after the German chemist Siegfried Hünig. It is used in organic chemistry as a base. It is commonly abbreviated as DIPEA, DIEA, or ''i''-Pr2N ...
, 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. A simple remedy for this problem is to rinse used glassware with bleach or
oxone Potassium peroxymonosulfate is widely used as an oxidizing agent. It is the potassium salt of peroxymonosulfuric acid. Usually potassium peroxymonosulfate refers to the triple salt known as oxone. The standard electrode potential for potassium ...
solution, which will oxidize the dimethyl sulfide back to dimethyl sulfoxide or to
dimethyl sulfone Methylsulfonylmethane (MSM) is an organosulfur compound with the formula (CH3)2SO2. It is also known by several other names including methyl sulfone and dimethyl sulfone (DMSO2). This colorless solid features the sulfonyl functional group and is ...
, both of which are odourless and nontoxic. The reaction conditions allow oxidation of acid-sensitive compounds, which might decompose under the acidic oxidation conditions such as
Jones oxidation The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation of ...
. For example, in Thompson & Heathcock's synthesis of the
sesquiterpene Sesquiterpenes are a class of terpenes that consist of three isoprene units and often have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be cyclic or contain rings, including many unique combinations. Biochemical modificat ...
isovelleral, the final step uses the Swern protocol, avoiding rearrangement of the acid-sensitive cyclopropanemethanol moiety.


See also

* Alcohol oxidation *
Sulfonium-based oxidation of alcohols to aldehydes Sulfonium-based oxidations of alcohols to aldehydes summarizes a group of organic reactions that transform a primary alcohol to the corresponding aldehyde (and a secondary alcohol to the corresponding ketone). Selective oxidation of alcohols to alde ...
*
Pyridinium chlorochromate Pyridinium chlorochromate (PCC) is a yellow-orange salt with the formula 5H5NHsup>+ rO3Clsup>−. It is a reagent in organic synthesis used primarily for oxidation of alcohols to form carbonyls. A variety of related compounds are known with simil ...
*
Jones oxidation The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation of ...
*
Oppenauer oxidation Oppenauer oxidation, named after , is a gentle method for selectively oxidizing secondary alcohols to ketones. The reaction is the opposite Meerwein–Ponndorf–Verley reduction. The alcohol is oxidized with aluminium isopropoxide in excess ...
*
Pfitzner–Moffatt oxidation The Pfitzner–Moffatt oxidation, sometimes referred to as simply the Moffatt oxidation, is a chemical reaction for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively. The oxidant is a combination of dimethyl ...
*
Parikh–Doering oxidation The Parikh– Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively. The procedure uses dimethyl sulfoxide (DMSO) as the oxidant and the solvent, activated by the sulf ...
* Albright-Goldman oxidation *
Corey–Kim oxidation The Corey–Kim oxidation is an oxidation reaction used to synthesise aldehydes and ketones from primary and secondary alcohols. It is named for American chemist and Nobel Laureate Elias James Corey and Korean-American chemist Choung Un Kim. ...
* Dess–Martin periodinane oxidation *
Ley oxidation Ley may refer to: Toponyms * Ley (landform), name for a crag, rock or cliff in the north German language area * Ley (crater), crater on the Moon * Ley, Moselle, commune in France * Ley Hill, hill in England People * Ley Matampi (born 198 ...
( TPAP oxidation) *
TEMPO In musical terminology, tempo ( Italian, 'time'; plural ''tempos'', or ''tempi'' from the Italian plural) is the speed or pace of a given piece. In classical music, tempo is typically indicated with an instruction at the start of a piece (ofte ...
oxidation


References


External links


Organic Chemistry Portal
{{DEFAULTSORT:Swern Oxidation Organic oxidation reactions Name reactions