Oxidative cleavage of alkenes to give ketones/carboxylic acids using ozone (O3) – (“oxidative workup”)
Description: Ozone will cleave carbon-carbon double bonds to give ketones/carboxylic acids after oxidative workup.
Notes: The initial product of this reaction is an ozonide. Treatment of the ozonide with acid and an oxidant such as hydrogen peroxide (H2O2) will convert any aldehydes to carboxylic acids. Note that any C–H bonds on the alkenes are converted to C–OH bonds, giving carboxylic acids.
Notes: Note how every C–H bond on the alkene is converted into a C–OH bond to give a carboxylic acid. Also note that example 3 shows cleavage of a cyclic alkene to give a linear compound. In example 4, cleavage of a terminal alkene results in CO2.
Mechanism: The first step of the reaction is a cycloaddition of ozone with the alkene (Step 1, arrows A, B, and C). The second step is a reverse cycloaddition, resulting in cleavage of the carbon-carbon single bond (Step 2, arrows D, E, and F). The oxygen of the carbonyl oxide then performs a 1,2-addition on the other carbonyl (Step 3, arrows G and H) giving a negatively charged oxygen that performs a 1,2-addition on the carbonyl carbon of the carbonyl oxide to give the ozonide (Step 4, arrows I and J).
With warming, the ozonide breaks down to the aldehyde and a carbonyl oxide (Step 5, arrows K, L, and M). Addition of peroxide to the aldehyde then occurs (Step 6, arrows N and O). This is followed by proton transfer (Step 7, arrows P and Q) and then removal of a proton with base to give the carbonyl (C=O) (Step 8, arrows R, S, and T).
Notes: There are other reasonable ways to draw this mechanism, particularly other ways of drawing proton transfer in Step 7 and other species that could act as bases in Step 8.
(Advanced) References and Further Reading
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- Ueber die Einwirkung des Ozons auf organische Verbindungen
Just. Lieb. Ann. Chem. 1905, 343 (2-3), 311-344
The first paper describing the oxidative cleavage of unsaturated compounds with ozone in solution.
L. I. Smith, F. L. Greenwood, and O. Hudrlik
Org. Synth. 1946 26, 63
This procedure from Organic Syntheses, a source of reliable, reproducible and independently tested organic chemistry laboratory experimental procedures, provides a detailed explanation of how to build a laboratory ozonizer.
- The Preparation of Aldehydes, Ketones, and Acids by Ozone Oxidation
Albert L. Henne and Philip Hill
Journal of the American Chemical Society 1943 65 (5), 752-754
This paper shows that carboxylic acids are formed in good yields from aldehydes when the ozonolysis reaction mixture is worked up in the presence of excess hydrogen peroxide.
- Synthesis of sesquiterpene antitumor lactones. 7. Studies directed toward the total synthesis of pentalenolactone. Intramolecular ene reaction.
Frank Plavac, Clayton H. Heathcock
Tetrahedron Letters 1979, 20 (23), 2115-2118
This paper shows how ozonolysis with oxidative workup (7 -> 8) can be used in organic synthesis.
- Ozonolysis of Cyclic Olefins
E. Franz, W. S. Knowles, and C. Osuch
The Journal of Organic Chemistry 1965, 30 (12), 4328-4330
The transformation of VII to IX involves oxidative workup of the intermediate VIII using peracetic acid. One of the authors in this paper, W. S. Knowles, later received the Nobel Prize in Chemistry in 2001 for his work on asymmetric reduction reactions.
- Ozonolysis of unsaturated phosphorus compounds
John K. Stille and J. L. Eichelberger
The Journal of Organic Chemistry 1971, 36 (13), 1840-1841
This paper is by the same Prof. J. K. Stille of Stille reaction fame. As he says in the first paragraph, ozone is rarely used in organophosphorous chemistry, but here he demonstrates its utility in accessing phosphines that would be difficult to make by other means.
- Oxidative cleavage of mono-, di-, and trisubstituted olefins to methyl esters through ozonolysis in methanolic sodium hydroxide
James A. Marshall and Albert W. Garofalo
The Journal of Organic Chemistry 1993, 58 (14), 3675-3680
This paper describes workup conditions that directly yield esters. Using alcohols in the workup along with neutral or oxidative conditions will trap the resulting acids as carboxylic esters.