Swern Oxidation reaction mechanism reagents conditions and applications
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 in Organic Chemistry
1. What is Swern oxidation?
Swern oxidation is a mild organic reaction that converts primary and secondary alcohols into aldehydes and ketones using dimethyl sulfoxide (DMSO), oxalyl chloride (COCl)2, and a base such as triethylamine (Et3N).
It is widely used in organic synthesis because:
- Primary alcohols form aldehydes (without overoxidation to acids).
- Secondary alcohols form ketones.
- The reaction is performed at low temperature (typically −78 °C).
Example: CH3CH2OH → CH3CHO (ethanol to ethanal under Swern conditions).
"2. What reagents are used in Swern oxidation?
The reagents used in Swern oxidation are dimethyl sulfoxide (DMSO), oxalyl chloride (COCl)2, and a tertiary amine base such as triethylamine (Et3N).
The role of each reagent is:
- DMSO – forms the activated sulfonium intermediate.
- Oxalyl chloride – activates DMSO and generates the reactive species.
- Triethylamine – acts as a base to promote elimination and form the carbonyl compound.
The reaction is typically carried out in anhydrous solvent at −78 °C to control side reactions.
"3. What is the mechanism of Swern oxidation?
The mechanism of Swern oxidation involves activation of DMSO, formation of an alkoxysulfonium ion, and base-induced elimination to form a carbonyl compound.
The key steps are:
- Activation: DMSO reacts with oxalyl chloride to form a chlorodimethylsulfonium intermediate.
- Nucleophilic attack: The alcohol attacks the activated DMSO, forming an alkoxysulfonium ion.
- Elimination: Triethylamine removes a proton, leading to elimination and formation of the aldehyde or ketone.
The reaction also produces byproducts such as CO, CO2, and dimethyl sulfide (DMS).
"4. What does Swern oxidation convert?
Swern oxidation converts primary alcohols to aldehydes and secondary alcohols to ketones under mild, non-acidic conditions.
Specifically:
- RCH2OH → RCHO (primary alcohol to aldehyde)
- R2CHOH → R2C=O (secondary alcohol to ketone)
Tertiary alcohols do not undergo Swern oxidation because they lack a hydrogen on the carbon bearing the hydroxyl group.
"5. Why is Swern oxidation performed at low temperature?
Swern oxidation is performed at low temperature (typically −78 °C) to prevent side reactions and decomposition of reactive intermediates.
Low temperature helps to:
- Stabilize the activated DMSO intermediate.
- Prevent overoxidation or unwanted rearrangements.
- Control the exothermic activation step.
Maintaining low temperature ensures high selectivity for aldehyde or ketone formation.
"6. What are the byproducts of Swern oxidation?
The main byproducts of Swern oxidation are carbon monoxide (CO), carbon dioxide (CO2), and dimethyl sulfide (CH3–S–CH3).
These form because:
- Oxalyl chloride decomposes to CO and CO2.
- DMSO is reduced to dimethyl sulfide (DMS) during the elimination step.
Dimethyl sulfide has a strong odor, which is a practical drawback of the reaction.
"7. What is the difference between Swern oxidation and PCC oxidation?
The main difference between Swern oxidation and PCC oxidation is that Swern uses DMSO-based reagents without chromium, while PCC uses a chromium(VI) oxidant.
Key differences include:
- Swern oxidation: Uses DMSO, oxalyl chloride, and base; chromium-free; low temperature required.
- PCC (pyridinium chlorochromate): Contains Cr(VI); operates at room temperature; generates toxic chromium waste.
- Both convert primary alcohols to aldehydes and secondary alcohols to ketones without overoxidation.
Swern oxidation is often preferred when avoiding heavy metal reagents.
"8. Does Swern oxidation overoxidize aldehydes to carboxylic acids?
No, Swern oxidation does not overoxidize aldehydes to carboxylic acids under normal anhydrous conditions.
This is because:
- The reaction conditions are mild and water-free.
- No strong oxidizing metal species are present.
Thus, primary alcohols stop at the aldehyde stage, making Swern oxidation highly useful in selective organic synthesis.
"9. Can tertiary alcohols undergo Swern oxidation?
No, tertiary alcohols cannot undergo Swern oxidation because they lack a hydrogen atom on the carbon bearing the –OH group.
The reaction requires:
- Formation of an alkoxysulfonium intermediate.
- Elimination involving removal of a hydrogen from the same carbon.
Since tertiary alcohols have no such hydrogen, oxidation to a carbonyl compound cannot occur.
"10. What are the advantages of Swern oxidation in organic synthesis?
The main advantages of Swern oxidation are its mild conditions, high selectivity, and avoidance of heavy metal oxidants.
Important benefits include:
- Selective formation of aldehydes and ketones.
- No overoxidation of primary alcohols to acids.
- Chromium-free conditions (environmentally safer than Cr(VI) reagents).
- Compatibility with many sensitive functional groups.
These features make Swern oxidation a widely used method in modern organic chemistry and laboratory synthesis.
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