Swern oxidation

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Swern oxidation
Named after Daniel Swern
Reaction type Organic redox reaction
Identifiers
Organic Chemistry Portal swern-oxidation
RSC ontology ID RXNO:0000154
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In organic chemistry, the Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol (−OH) is oxidized to an aldehyde (−CH=O) or ketone (>C=O) using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine.[1][2][3] It is one of the many oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known for its mild character and wide tolerance of functional groups.[4][5][6][7]

The Swern oxidation.
The Swern oxidation.

The by-products are

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.

Dimethylchlorosulfonium chloride formation.
Dimethylchlorosulfonium chloride formation.

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

carbonyl
compound 8.

The mechanism of the Swern oxidation.
The mechanism of the Swern oxidation.

Variations

When using oxalyl chloride as the

Albright-Goldman oxidation). The intermediate 4 can also be prepared from dimethyl sulfide and N-chlorosuccinimide (the Corey–Kim oxidation
).

In some cases, the use of triethylamine as the base can lead to

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.

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.

See also

References

  1. doi:10.1016/0040-4020(78)80197-5.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  2. doi:10.1021/jo01337a028.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  3. doi:10.1021/jo00406a041.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  4. ^ Dondoni, A.; Perrone, D. (2004). "Synthesis of 1,1-Dimethyl Ethyl-(S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate by Oxidation of the Alcohol". Organic Syntheses{{cite journal}}: CS1 maint: multiple names: authors list (link); Collected Volumes, vol. 10, p. 320.
  5. ^ Bishop, R. (1998). "9-Thiabicyclo[3.3.1]nonane-2,6-dione". Organic Syntheses; Collected Volumes, vol. 9, p. 692.
  6. ^ Leopold, E. J. (1990). "Selective hydroboration of a 1,3,7-triene: Homogeraniol". Organic Syntheses; Collected Volumes, vol. 7, p. 258.
  7. ISBN 0-387-23607-4
    .
  8. doi:10.1055/s-1981-29377.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  9. ISBN 0471264180
    .
  10. doi:10.1055/s-1990-27036
    .
  11. PMID 11701058
    .
  12. doi:10.1021/jo00868a012
    .
  13. ^ Morton, T. H. (2000). "Archiving Odors". In Bhushan, N.; Rosenfeld, S. (eds.). Of Molecules and Mind. Oxford: Oxford University Press. pp. 205–216.
  14. doi:10.1021/op068011l
    .
  15. doi:10.1021/jo00048a036
    .

External links
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