Swern Oxidation
The Swern oxidation, developed by Kanji Omura and Daniel Swern in 1978, is a method used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones using activated dimethyl sulfoxide (DMSO), oxalyl chloride, triethylamine (TEA) and dichloromethane (DCM).1
Oxidation Variations
Here you can find the various types of Oxidation conditions and reagent combinations that utilize Swern Oxidation.
General Scheme of the Swern Oxidation
This general scheme only occurs when DMSO is activated using Oxalyl Chloride.
According to Omura and Swern, Oxalyl Chloride was the most effective activator of DMSO which had high yields (>95%) at low temperatures (-60°C to -20°C). There was a minor dependence on reaction temperature reported in the paper. For this reason, Oxalyl chloride is the most preferred oxidizing agent used alongside DMSO in Swern Oxidations for alcohols. 1
General Scheme of Swern Oxidation using TFAA
TFAA was reported as an effective and early Swern Oxidation method from the original paper by Omura & Swern (1978).
As reported by Omura & Swern (1978), Trifluoroacetic anhydride (TFAA) can be used as effective activator of DMSO at -50°C, however, this is quite costly and is usually overshadowed in efficacy by oxalyl chloride. Other activators can be used, however, thier usage is situational and/or are outperformed by other activators.
List of other DMSO Activators
This list of chemicals were compiled from the Omura & Swern (1978).
| Activator | Effectiveness | Specific Cases and Notes |
|---|---|---|
| Oxalyl Chloride | Highest yields, effective for most alcohols | - Generally over 95% yield at -60°C to -20°C regardless of steric factors. Less sensitive to reaction temperature up to -20°C. |
| Thionyl Chloride | Good yields, slightly less effective than oxalyl chloride | - Effective but yields not as high as oxalyl chloride |
| Trifluoroacetic Anhydride (TFAA) | Effective but costly and toxic | - Effective for a wide range of alcohols. Less effective for primary alcohols compared to oxalyl chloride |
| Acetic Anhydride | Lower yields, significant by-products | - Yields of carbonyls typically around 30%. Major by-products include alkyl methylthiomethyl ethers and acetates |
| Cyanuric Chloride | Useful in specific cases, steric effects observed | - Effective with secondary alcohols, especially hindered ones. Yields of carbonyls: DIPEA (95%), DECA (93%), TEA (80%), DEMA (47%) |
| Methanesulfonyl Chloride | Useful in specific cases, steric effects observed | - Effective with secondary alcohols, particularly hindered ones. Yields of carbonyls: DIPEA (94%), DECA (92%), TEA (68%), DEMA (45%) |
Full Articles on Variations
Check out the full articles.
The Preferred Oxidizing Agent
Oxalyl chloride is most preferred. But why?
Among various DMSO activation methods, oxalyl chloride stands out as the most effective, consistently yielding over 95% across a wide range of alcohols, mainly primary and secondary alcohols. Its high efficiency and minimal side reactions make it the **preferred choice** for alcohol oxidation.1
Thionyl chloride also produces good yields but is slightly less effective than oxalyl chloride. TFAA is effective but its *high cost and toxicity*, lower it's desirability despite good results. 1
Acetic anhydride results in lower yields and significant by-products, making it less favorable. Cyanuric chloride and methanesulfonyl chloride are useful in specific cases, particularly with hindered alcohols, yielding up to 95% when used with certain bases like DIPEA. 1
Overall, oxalyl chloride is the most optimal DMSO activator and oxidizing agent due to its high yield and broad applicability in alcohol oxidation. 1
By-Product Concerns
Concerns regarding toxicity and chemical exposure.
Main reagents for Swern Oxidation using DMSO, Oxalyl chloride, TEA and DCM
This is the most optimal combination of reagents to give the highest yield for the oxidation of alcohols.
Dimethyl Sulfide (DMS)
This section details the toxicity and exposure of DMS in detail.
| Attribute | Details |
|---|---|
| Formation | DMS is produced as a by-product post oxidation. |
| Toxicity | DMS is flammable and poses health hazards including irritation of the eyes, skin, and respiratory system. Prolonged exposure can lead to more severe health effects such as headaches, dizziness, and nausea. |
| Odor | DMS is known for its strong, unpleasant odor, which can be a significant issue in laboratory settings.To effectively manage the strong, unpleasant odor of DMS (dimethyl sulfide), several methods have been documented.2  Chemical oxidation is one method which is commonly employed, where bleach oxidation through the usage of sodium hypochlorite pentahydrate (NaOCl·5H2O) can oxidize DMS into less odorous compounds such as dimethyl sulfoxide and dimethyl sulfone.3 Another solution is using activated carbon to absorb DMS from vent streams, providing a straightforward scrubbing solution.2 Additionally, Atkins et al. (2006) describe using potassium persulfate (Oxone) for similar oxidation processes, further reducing the presence of DMS 2 |
Database Info
Oxalyl Chloride
| Attribute | Details |
|---|---|
| Reaction | Oxalyl chloride is the most effective activator for DMSO in Swern oxidation, yielding high amounts of carbonyl products. |
| Toxicity | Oxalyl chloride is highly toxic and corrosive, producing harmful gases such as carbon monoxide and phosgene upon decomposition. It can cause severe respiratory damage, skin burns, and eye irritation upon contact. |
Database Info
Triethylamine (TEA)
| Attribute | Details |
|---|---|
| Role | TEA acts as a base in the Swern oxidation, facilitating the formation of the carbonyl product. |
| Toxicity | TEA is corrosive and can cause severe burns to the skin and eyes. Inhalation of TEA vapors can result in respiratory irritation and, at higher concentrations, pulmonary edema. It is also flammable and should be handled with care. |
Database Info
Dichloromethane (DCM)
| Attribute | Details |
|---|---|
| Use | DCM is commonly used as a solvent in Swern oxidation. |
| Toxicity | DCM is toxic and a potential carcinogen. It can cause central nervous system depression, and chronic exposure may result in liver and kidney damage. Inhalation of high concentrations can lead to dizziness, nausea, and loss of consciousness. |
Database Info
Tribute to Dr. Daniel A. Swern
Tribute dedicated to Daniel Swern (1916-1982)
Dr. Daniel A. Swern (1916–1982) was a distinguished chemist known for his works on flexible plastics and advancements in lipid chemistry. During World War II, his work with the USDA led to breakthroughs in transforming polyvinyl chlorides into more versatile plastics.11
Later, as a professor at Temple University, he published over 280 research papers and received numerous awards, including the AOCS Bailey Award and Temple University Faculty Award for Research and Creative Achievements. Dr. Swern sadly passed away aged 66, leaving behind a lasting impact on chemists and materials scientists.12
Rest in Peace,
Dr. Daniel A. Swern
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References
1. Omura, K.; Swern, D. Oxidation of Alcohols by “Activated” Dimethyl Sulfoxide. A Preparative, Steric and Mechanistic Study. Tetrahedron 1978, 34 (11), 1651–1660. DOI: 10.1016/0040-4020(78)80197-5. ↩
2. Atkins, W. J., Jr.; Burkhardt, E. R.; Matos, K. Safe Handling of Boranes at Scale. Org. Process Res. Dev. 2006, 10 (6), 1292–1295. DOI: 10.1021/op068011l. ↩
3. Okada, T.; Matsumuro, H.; Kitagawa, S.; Iwai, T.; Yamazaki, K.; Kinoshita, Y.; Kimura, Y.; Kirihara, M. Selective Synthesis of Sulfoxides through Oxidation of Sulfides with Sodium Hypochlorite Pentahydrate Crystals. Synlett 2015, 26 (18), 2547–2552. DOI: 10.1055/s-0035-1560482. ↩
4. PubChem Compound Summary for CID 1068, Dimethyl Sulfide. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Dimethyl-sulfide. Accessed July 29, 2024. ↩
5. Occupational Safety and Health Administration (OSHA). Dimethyl Sulfide. Available at: https://www.osha.gov/chemicaldata/912. Accessed July 29, 2024. ↩
6. PubChem Compound Summary for CID 7891, Oxalyl Chloride. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Oxalyl-chloride. Accessed July 29, 2024. ↩
7. PubChem Compound Summary for CID 8471, Triethylamine. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Triethylamine. Accessed July 29, 2024. ↩
8. Occupational Safety and Health Administration (OSHA). Triethylamine. Available at: https://www.osha.gov/chemicaldata/165. Accessed July 29, 2024. ↩
9. PubChem Compound Summary for CID 6344, Dichloromethane. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/dichloromethane. Accessed July 29, 2024. ↩
10. Occupational Safety and Health Administration (OSHA). Dichloromethane. Available at: https://www.osha.gov/chemicaldata/572. Accessed July 29, 2024. ↩
11. After Deadline. J. Am. Oil Chem. Soc. 1983, 60 (1), 5. DOI: 10.1007/BF02540885. ↩
12. Daniel Swern, 66, Researcher Who Developed New Plastics. The New York Times, December 8, 1982. Available at: https://www.nytimes.com/1982/12/08/obituaries/daniel-swern-66-researcher-who-developed-new-plastics.html. Accessed July 29, 2024. ↩