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.
FAQs on Swern Oxidation
1. What is the Swern oxidation reaction and what does it produce?
Swern oxidation is a chemical reaction that converts primary alcohols into aldehydes and secondary alcohols into ketones. It is known for its mild reaction conditions and high yield. A key feature is that it stops at the aldehyde stage for primary alcohols, preventing over-oxidation to carboxylic acids.
2. What are the key reagents used in Swern oxidation and what is the function of each?
The primary reagents for Swern oxidation and their functions are:
- Dimethyl sulfoxide (DMSO): Acts as the primary oxidizing agent.
- Oxalyl chloride (COCl)₂ or Trifluoroacetic anhydride (TFAA): Used as an activator for DMSO. It reacts with DMSO to form the electrophilic species that reacts with the alcohol.
- A hindered organic base, usually Triethylamine (Et₃N): This base is added in the final step to abstract a proton and facilitate the elimination reaction that forms the final carbonyl product.
3. Why is Swern oxidation considered a mild method for alcohol oxidation?
Swern oxidation is considered mild because it operates at very low temperatures (typically -78°C to -60°C) and uses non-metallic, selective reagents. These conditions prevent unwanted side reactions and protect sensitive functional groups elsewhere in the molecule. Unlike strong oxidants like potassium permanganate, it does not cleave carbon-carbon bonds and effectively stops the oxidation of primary alcohols at the aldehyde stage.
4. What is the step-by-step mechanism of the Swern oxidation?
The mechanism of Swern oxidation involves three main steps:
- Activation of DMSO: At a low temperature, dimethyl sulfoxide (DMSO) reacts with the activator, oxalyl chloride, to form an electrophilic sulfur species known as the chlorosulfonium salt. This step releases carbon monoxide and carbon dioxide.
- Nucleophilic Attack: The alcohol attacks the electrophilic sulfur atom of the activated complex, forming a new intermediate called an alkoxysulfonium salt.
- Deprotonation and Elimination: Triethylamine, a hindered base, removes a proton from the carbon adjacent to the oxygen. This triggers an intramolecular elimination reaction, which yields the final aldehyde or ketone, along with dimethyl sulfide (DMS) and triethylammonium chloride.
5. Why can't tertiary alcohols be oxidised by the Swern oxidation method?
Tertiary alcohols cannot be oxidised by the Swern method because they lack a crucial alpha-hydrogen. The final step of the Swern mechanism requires a base (triethylamine) to remove a hydrogen atom from the carbon that is bonded to the hydroxyl group. Since a tertiary alcohol has three alkyl groups attached to this carbon and no alpha-hydrogen atoms, this deprotonation and subsequent elimination step cannot occur.
6. What are the byproducts of Swern oxidation and what safety precautions are necessary?
The main byproducts of Swern oxidation include dimethyl sulfide (DMS), carbon monoxide (CO), carbon dioxide (CO₂), and triethylammonium chloride. Special precautions are essential because:
- Dimethyl sulfide (DMS) is a volatile liquid with an extremely strong and unpleasant odour.
- Carbon monoxide (CO) is a highly toxic and odourless gas.
Due to the generation of these hazardous substances, the reaction must always be performed in a well-ventilated fume hood.
7. How does Swern oxidation selectively produce aldehydes from primary alcohols without further oxidation to carboxylic acids?
Swern oxidation prevents the over-oxidation of aldehydes to carboxylic acids because the reaction is conducted in the complete absence of water (anhydrous conditions). For an aldehyde to be oxidised further to a carboxylic acid, it must first be hydrated to form a geminal diol, which can then be oxidised. Since Swern conditions are non-aqueous and run at very low temperatures, this hydration step is prevented, and the reaction effectively stops once the aldehyde is formed.
8. What are some common applications and examples of Swern oxidation in organic synthesis?
Swern oxidation is widely used in complex organic synthesis due to its reliability and mildness, especially when dealing with molecules containing sensitive functional groups. A notable example is its use in the total synthesis of complex natural products like Paclitaxel (Taxol), a potent anti-cancer drug. In this synthesis, it is used to oxidise a protected primary alcohol to a crucial aldehyde intermediate without disturbing other parts of the complex molecule.
9. Are there any alternative methods to Swern oxidation for achieving similar results?
Yes, there are several other mild oxidation methods that can convert primary and secondary alcohols to aldehydes and ketones, respectively. Some common alternatives include:
- Dess-Martin Periodinane (DMP) oxidation: Uses a hypervalent iodine compound and works at room temperature.
- Parikh-Doering oxidation: Uses the sulfur trioxide pyridine complex as the activator for DMSO.
- Pfitzner-Moffatt oxidation: Uses a carbodiimide (like DCC) to activate DMSO.
- Pyridinium Chlorochromate (PCC) oxidation: Another popular reagent for stopping the reaction at the aldehyde stage.
10. According to the CBSE 2025-26 syllabus, which chapter covers the Swern oxidation reaction?
In the CBSE Class 12 Chemistry syllabus for the 2025-26 academic year, the Swern oxidation reaction is typically studied as an important named reaction within the chapter on 'Alcohols, Phenols and Ethers'. It is presented as a key method for the oxidation of alcohols.
