Oppenauer oxidation
Oppenauer oxidation | |
---|---|
Named after | Rupert Viktor Oppenauer |
Reaction type | Organic redox reaction |
Identifiers | |
Organic Chemistry Portal | oppenauer-oxidation |
RSC ontology ID | RXNO:0000047 |
Oppenauer oxidation, named after
.The reaction is the opposite Meerwein–Ponndorf–Verley reduction.[2] The alcohol is oxidized with aluminium isopropoxide in excess acetone. This shifts the equilibrium toward the product side.
The
Mechanism
In the first step of this
Advantages
An advantage of the Oppenauer oxidation is its use of relatively inexpensive and non-toxic reagents. Reaction conditions are mild and gentle since the substrates are generally heated in acetone/benzene mixtures. Another advantage of the Oppenauer oxidation which makes it unique to other oxidation methods such as pyridinium chlorochromate (PCC) and Dess–Martin periodinane is that secondary alcohols are oxidized much faster than primary alcohols, thus chemoselectivity can be achieved. Furthermore, there is no over oxidation of aldehydes to carboxylic acids as opposed to another oxidation methods such the Jones oxidation.[4]
Modifications
Wettstein-Oppenauer reaction
In the Wettstein-Oppenauer reaction, discovered by Wettstein in 1945, Δ 5–3β-hydroxy steroids are oxidized to Δ 4,6-3-ketosteroids with benzoquinone as the hydrogen acceptor. This reaction is useful in that it affords a one-step preparation of Δ 4,6-3-ketosteroids.[5]
Woodward modification
In the Woodward modification, Woodward substituted potassium tert-butoxide for the aluminium alkoxide. The Woodward modification of the Oppenauer oxidation, also called the Oppenauer–Woodward oxidation, is used when certain alcohol groups do not oxidize under the standard Oppenauer reaction conditions. For example, Woodward used potassium tert-butoxide and benzophenone for the oxidation of quinine to quininone, as the traditional aluminium catalytic system failed to oxidize quinine due to the complex formed by coordination of the Lewis-basic nitrogen to the aluminium centre.[6]
Other modifications
Several modified aluminium alkoxide
In another modification
Synthetic applications
The Oppenauer oxidation is used to prepare analgesics in the pharmaceutical industry such as morphine and codeine. For instance, codeinone is prepared by the Oppenauer oxidation of codeine.[9]
The Oppenauer oxidation is also used to synthesize
A slight variation of the Oppenauer oxidation is also used to synthesize steroid derivatives. For example, an efficient catalytic version of the Oppenauer oxidation which employs a ruthenium catalyst has been developed for the oxidation of 5-unsaturated 3β-hydroxy steroids to the corresponding 4-en-3-one derivative.[11]
The Oppenauer oxidation is also used in the synthesis of
Side reactions
A common side-reaction of the Oppenauer oxidation is the base-catalyzed aldol condensation of aldehyde product, which have α-hydrogens to form either β-hydroxy aldehydes or α, ß-unsaturated aldehydes.[13]
Another side
See also
- Alcohol oxidation
- Pyridinium chlorochromate
- Jones oxidation
- Pfitzner–Moffatt oxidation
- Parikh–Doering oxidation
- Albright-Goldman oxidation
- Swern oxidation
- Corey–Kim oxidation
- Dess–Martin periodinane oxidation
- Ley oxidation (TPAPoxidation)
- TEMPO oxidation
References
- .
- .
- ^ Otvos, L.; Gruber, L.; Meisel-Agoston, J. (1965). "The Meerwein-Ponndorf-Verley-Oppenauer. Investigation of the reaction mechanism with radiocarbon. Racemization of secondary alcohols". Acta Chim. Acad. Sci. Hung. 43: 149–153.
- ^ ISBN 978-7-03-019190-8.
- .
- .
- PMID 12153205.
- PMID 17002323.
- PMID 16836305.
- ISBN 0471496405.
- PMID 11667525.
- .
- .
- .
- .