The by-products are dimethyl sulfide ((CH3)2S), carbon monoxide (CO), carbon dioxide (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.[8][9][10]
Mechanism
The first step of the Swern oxidation is the low-temperature reaction of DMSO, 1a, formally as resonance 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 the alkoxysulfonium ion to give the sulfur ylide7. In a five-membered ring transition state, the sulfur ylide 7 decomposes to give dimethyl sulfide and the desired carbonyl compound 8.
In some cases, the use of triethylamine as the base can lead to epimerisation at the carbon alpha to the newly formed carbonyl. Using a bulkier base, such as diisopropylethylamine, 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.[13] A simple remedy for this problem is to rinse used glassware with bleach or oxone solution, which will oxidize the dimethyl sulfide back to dimethyl sulfoxide or to dimethyl sulfone, both of which are odourless and nontoxic.[14]
The reaction conditions allow oxidation of acid-sensitive compounds, which might decompose under the acidic oxidation conditions such as Jones oxidation. For example, in Thompson & Heathcock's synthesis of the sesquiterpene isovelleral,[15] the final step uses the Swern protocol, avoiding rearrangement of the acid-sensitive cyclopropanemethanol moiety.
^Mancuso, A. J.; Brownfain, D. S.; Swern, D. (1979). "Structure of the dimethyl sulfoxide-oxalyl chloride reaction product. Oxidation of heteroaromatic and diverse alcohols to carbonyl compounds". J. Org. Chem.44 (23): 4148–4150. doi:10.1021/jo01337a028.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Mancuso, A. J.; Huang, S.-L.; Swern, D. (1978). "Oxidation of long-chain and related alcohols to carbonyls by dimethyl sulfoxide "activated" by oxalyl chloride". J. Org. Chem.43 (12): 2480–2482. doi:10.1021/jo00406a041.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Tidwell, T. T. (1990). "Oxidation of alcohols to carbonyl compounds via alkoxysulfonium ylides: The Moffatt, Swern, and related oxidations". Org. React. (Review). 39: 297–572. doi:10.1002/0471264180.or039.03. ISBN0471264180.
^Tidwell, T. T. (1990). "Oxidation of alcohols by activated dimethyl sulfoxide and related reactions: An update". Synthesis (Review). 1990 (10): 857–870. doi:10.1055/s-1990-27036.
^De Luca Lidia (2001). "A Mild and Efficient Alternative to the Classical Swern Oxidation". The Journal of Organic Chemistry. 66 (23): 7907–7909. doi:10.1021/jo015935s. PMID11701058.
^Omura, Kanji; Sharma, Ashok K.; Swern, Daniel (1976). "Dimethyl Sulfoxide-Trifluoroacetic Anhydride. New Reagent for Oxidation of Alcohols to Carbonyls". J. Org. Chem.41 (6): 957–962. doi:10.1021/jo00868a012.
^Morton, T. H. (2000). "Archiving Odors". In Bhushan, N.; Rosenfeld, S. (eds.). Of Molecules and Mind. Oxford: Oxford University Press. pp. 205–216.
^Atkins, William J. Jr.; Burkhardt, Elizabeth R.; Matos, Karl (2006). "Safe Handling of Boranes at Scale". Org. Process Res. Dev. 10 (6): 1292–1295. doi:10.1021/op068011l.
^Thompson, S. K.; Heathcock, C. H. (1992). "Total synthesis of some marasmane and lactarane sesquiterpenes". J. Org. Chem.57 (22): 5979–5989. doi:10.1021/jo00048a036.