Swern Oxidation

What is Swern Oxidation Reaction?

Swern oxidation is the method that involves the conversion of primary alcohols to an aldehyde, and the secondary alcohol into a ketone, with DiMethyl SulfOxide (DMSO), oxalyl chloride (an organic base), and triethylamine. Unlike other reactions, the aldehydes in these reactions do not undergo any further reactions to form a carboxylic acid. Instead, this oxidation method is used to oxidize alcohols that don't involve any participation of chromium or other harmful metals. However, the Swern oxidation leads to dimethyl sulfide formation, which comes with an inherent and unpleasant smell. 

Swern Oxidation Reaction

Named after the American chemist Daniel Swern, the Swern reaction helps in obtaining aldehydes and ketones from primary and secondary alcohols accordingly. The chemical process of a Swern oxidation reaction can be represented as: 


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Among the other byproducts formed in Swern Oxidation, the main byproducts formed in the reaction are as follows: 

  • Dimethyl Sulfide (DMSO) - highly toxic and volatile with pervasive odour even when it forms at low concentrations

  • Carbon Monoxide - Extremely toxic, almost lethal for human beings as it meddles with the haemoglobin with our blood to form carboxyhemoglobin that restricts the flow of blood to vital tissues. 

  • Carbon Dioxide 

  • Triethylammonium chloride 

Known for its mild characteristics involved in the oxidation of alcohols, the Swern oxidation almost instantaneously stops the oxidation process as soon as the carbonyl group is formed. In this way, it performs similar to that of the other mild oxidizing agents like Pyridinium dichromate (PDC) and Pyridinium Chlorochromate (PCC).  


If the functional group is a primary alcohol, then the yielding functional group would be an aldehyde (see the reaction below).


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Similarly, if the functional group is secondary alcohol then it would oxidize to the ketone, in the following reaction:


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However, tertiary alcohols cannot be oxidized (highlighted below):


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Swern Oxidation Mechanism

Overall, the Dimethyl sulfoxide (DMSO), as well as the oxalyl chloride \[(COCI)_{2}\], are implemented as oxidizing agents in the Swern Oxidation reaction:


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Among the reagents used, the hydroxyl oxygen needs to have a leaving group to remove the neighbouring hydrogen, and thus setting off the C=O π bond in between the two. 


The hydrogen undergoing the elimination process that forms the C=O π bond in the process.

 

The overall Swern oxidation reaction mechanism works in three main steps,

  • In the first step, the mechanism begins with the oxalyl chloride that activates the DMSO and generates the Dimethyl Chlorosulphonic ion and releases CO and \[CO_{2}\] gases. 

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  • In the next step, when the reaction gets introduced to alcohol at -78°C, the formation of alkoxy sulfonium cation takes place as the chloride ion gets released in the equation. 

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  • This results in the deprotonation of the alkoxy sulfonium ion at its position to form alkoxy sulfonium ylide. It again undergoes intramolecular deprotonation to yield respective aldehyde or ketone compounds and release the dimethyl sulfide gas.


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Swern Oxidation Examples

Many reaction processes implement the mild conditions that can be used for synthesizing relatively unstable aldehydes. One such popularly used methods would be that of the synthesis of   \[(thiazinotrienomycin)^{+}\]


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Swern oxidation can also be used in the oxidation of alcohol, yielding aldehyde that can further undergo the Wittig-Horner reaction to form the α,β-unsaturated ester. Here's how the reaction can be expressed:


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Another example of the Swern reaction mechanism would include forming the three-membered rings of the respective methyl-dihydro oxepines that get created by oxidizing isopropenyl-substituted cyclopropylcarbinols. These reactions could lead the parameters to be hetero arranged to form vinyl-cyclopropane-carbaldehyde. The chemical reaction can be expressed as: 


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Paclitaxel, a popular chemical compound, can be synthesized from the Swern preparation. The oxidation reaction of a primary alcohol in the TBDMS compound introduced at -60°C, generates aldehyde, after being treated with triethylamine at average room temperature to yield the critical intermediate for paclitaxel synthesis. It can be represented in the following reaction:


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Conditions of Swern Oxidation


The Swern oxidation requires an extremely low temperature (well below -60ºC) to occur at very mild conditions, as it avoids any side reactions that may disrupt the Swern Oxidation. Since Swern oxidation reactions also lead to the formation of harmful and pervasive gases that can be toxic on human contact,  it requires to be carried out under a fume hood to keep safe.


FAQ (Frequently Asked Questions)

1. What are the alternatives to Swern oxidation?

A. There can be many many other mild reagents that may be used to activate the DMSO. Some of these reagents may include dicyclohexylcarbodiimide (DCC) in the Pfitzner-Moffatt oxidation, Trifluoroacetic Anhydride (TFAA), and the Parikh-Doering oxidation with the execution of SO3-pyridine compounds. The alcohols can also be oxidized under the mild conditions by the help of the DMSO-Ph3P-X2 complexes, which doesn't further yield any Pummerer product. The chemical reaction for the above can be expressed as:


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2. What are the applications of Swern oxidation?

A. As you know that the Swern oxidation is widely used in the oxidation of primary and secondary alcohol to form aldehydes and ketones, this oxidation reaction involves easy exothermic steps. The combination of dimethyl sulfoxide, oxalyl chloride, triethylamine in the anhydrous environment is also referred to as the  Moffatt–Swern oxidation because of its constituents. It is also preferred for bulk aldehyde synthesis for its mildness and low boiling points of the generated byproducts. Therefore, it is convenient to remove from the reaction without using any harmful compounds like Chromium. The Swern reaction also has a unique feature where the aldehyde formed from the oxidation of primary alcohol doesn't get further oxidized into a carboxylic acid.