Alkene Reactions
Alkene Reactions: Ozonolysis
Last updated: November 28th, 2022 |
Ozonolysis of Alkenes
Today’s post represents not so much a pattern in alkene reactions, so much as it does a very common reaction that bears mentioning along with the rest. What makes this reaction special is that it does not simply break the carbon-carbon π bond, as we have been accustomed to seeing, but additionally breaks the C-C σ bond as well.
This type of reaction is known as oxidative cleavage [i.e. cleavage of bonds, occuring with oxidation] and the most prominent example of an oxidative cleavage reaction is ozonolysis.
Table Of Contents
- Ozone (O3) Is A Powerful Oxidant For Cleaving Alkenes To Carbonyl Compounds
- Ozonolysis With “Reductive Workup” : All C–H Bonds Are Preserved
- Ozonolysis Of A Ring Results In A Chain With Two Carbonyls
- Ozonolysis Of A Compound With Multiple Bonds Results In Several Fragments
- Ozonolysis With Oxidative Workup Converts Aldehydes To Carboxylic Acids
- Summary: Ozonolysis of Alkenes
- Quiz Yourself!
- (Advanced) References and Further Reading
1. Ozone (O3) Is A Powerful Oxidant For Cleaving Alkenes To Carbonyl Compounds
As mentioned previously, ozone does more than absorb UV radiation in the upper atmosphere and cause breathing problems in traffic-clogged cities. It’s a powerful oxidant, and since its discovery in the mid 1800’s by (Schönbein) has found use in the cleavage of carbon-carbon multiple bonds.
Here’s the pattern for the reaction of alkenes with ozone:
Note that the carbon-carbon double bond is broken and we are forming a carbon-oxygen double bond on each of the two carbons that originally composed the alkene.
The second step in ozonolysis is called the “workup”. There are two different types of “workup”, and the most common is referred to as “reductive workup“. In this step, we add a reducing agent (commonly zinc metal or dimethyl sulfide) that decomposes the intermediate formed at the end of the ozonolysis reaction (called an “ozonide” by the way).
(If you’re wondering where the third oxygen of ozone went – it’s now attached to what used to be our reducing agent (making either zinc oxide (ZnO) or dimethyl sulfoxide (DMSO). [For more details / mechanism everything is written out in this post.]
2. Ozonolysis With “Reductive Workup” – All C–H Bonds Are Preserved
Using “reductive workup” preserves all other aspects of the molecule except for the double bond. So if we start with, say, a trisubstituted alkene, as in the example below, we will end up with a ketone and an aldehyde.
[What happens if the alkene carbon is attached to two hydrogens? It becomes formaldehyde H2C=O, which is then further converted to carbon dioxide CO2]
Note that although I’ve written (CH3)2S as the reductant here, it’s essentially interchangeable with Zn for our purposes.
3. Ozonolysis Of A Ring Results In A Chain With Two Carbonyls
An interesting consequence of ozonolysis is that if the alkene is within a ring, you end up with a chain containing two carbonyls:
Each of the carbons in the alkene have formed C=O bonds.
Note that the numbering here is not IUPAC – it’s just for keeping track of the atoms.
4. Ozonolysis Of A Compound With Multiple Bonds Results In Several Fragments
If your molecule has multiple alkenes, then you will end up with more than two fragments. For many years ozonolysis was used as a method for the structure determination of unknown molecules.
By analyzing the fragments it is then possible to deduce what the original structure was, through “stitching” together the fragments [Note 1]. Here’s one example:
5. Ozonolysis With Oxidative Workup Converts Aldehydes To Carboxylic Acids
This isn’t the end of the story with ozonolysis. There’s a second type of workup that can be used, referred to as oxidative workup. Instead of using Zn or S(CH3)2, if we use the oxidant hydrogen peroxide [H2O2], any aldehydes that form will be oxidized to give carboxylic acids.
Here is an example. Note that the green C-H bond is oxidized to C-OH , but all the other bonds remain intact.
6. Summary: Ozonolysis Of Alkenes
An alternative to using ozone for oxidative workup is to use the reagent KMnO4 , especially in the presence of hot acid; this will lead to the same result.
This is the last category of important alkene reactions we’ll cover for now in this series; in the next post we’ll wrap up the reactions of alkenes with a summary post.
NEXT POST: Summary of Alkene Addition Reactions
Notes
Note 1. This was particularly important in the case of unsaturated molecules known as terpenes
Quiz Yourself!
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(Advanced) References and Further Reading
- Ueber die Einwirkung des Ozons auf organische Verbindungen
Harries
Just. Lieb. Ann. Chem. 1905, 343 (2-3), 311-344
DOI: 10.1002/jlac.19053430209
The first paper describing the oxidative cleavage of unsaturated compounds with ozone in solution. - OZONE
I. Smith, F. L. Greenwood, and O. Hudrlik
Org. Synth. 1946 26, 63
DOI: 10.15227/orgsyn.026.0063
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
DOI: 1021/ja01245a003
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. - Notes- A Convenient Method for Reduction of Hydroperoxide Ozonation Products
Knowles and Q. Thompson
The Journal of Organic Chemistry 1960 25 (6), 1031-1033
DOI: 10.1021/jo01076a044
Although the current practice is to use dimethyl sulfide in a reductive ozonolysis workup, trimethyl phosphite can also be used, as this paper from Nobel Laureate W. S. Knowles demonstrates. - OZONOLYTIC CLEAVAGE OF CYCLOHEXENE TO TERMINALLY DIFFERENTIATED PRODUCTS: METHYL 6-OXOHEXANOATE, 6,6-DIMETHOXYHEXANAL, METHYL 6,6-DIMETHOXYHEXANOATE
Ronald E. Claus and Stuart L. Schreiber
Synth. 1986, 64, 150
DOI: 10.15227/orgsyn.064.0150
This procedure in Organic Syntheses demonstrates how ozonolysis can be used to quickly generate differentiated bifunctional compounds. - Mechanism of Ozonolysis
Dr. Rudolf Criegee
Angew. Chem. Int. Ed. 1975, 14 (11), 745-752
DOI: 10.1002/anie.197507451
This is an account by Prof. Rudolf Criegee on work done towards determining the mechanism of ozonolysis. Criegee himself carried out extensive work in this area – the ‘Criegee intermediate’ in ozonolysis is named after him.The following papers are further mechanistic studies on ozonolysis: - New evidence in the mechanism of ozonolysis of olefins
Klopman and C. M. Joiner
Journal of the American Chemical Society 1975 97 (18), 5287-5288
DOI: 10.1021/ja00851a049 - Mechanism of ozonolysis. (a) Microwave spectra, structures, and dipole moments of propylene and trans-2-butene ozonides. (b) Orbital symmetry analysis
Robert P. Lattimer, Robert L. Kuczkowski, and Charles W. Gillies
Journal of the American Chemical Society 1974 96 (2), 348-358
DOI:1021/ja00809a006 - Microwave and mass spectral studies of the ozonolyses of ethylene, propylene, and cis- and trans-2-butene with added oxygen-18 formaldehyde and acetaldehyde
Charles W. Gillies, Robert P. Lattimer, and Robert L. Kuczkowski
Journal of the American Chemical Society 1974 96 (5), 1536-1542
DOI:1021/ja00812a043
Thank you for your suggestion, that is certainly something that might work. I should have clarified that my problem involved a cyclic tetrasubstituted alkene and an internal disubstituted alkene. I want the less substituted alkene to be cleaved and the tetrasubstituted one to be left alone. Will my aforementioned dihydroxylation followed by cleavage of the vicinal diol work?
Yes, I would give it a shot. If you have access to the Sharpless AD-Mix that would be a good thing to try since the bulky ligands should keep your osmium away from the bulkier alkene.
See here:
https://hwpi.harvard.edu/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf
It is my understanding that ozonolysis favours more substituted alkenes. Are there any reactions that favours the cleavage of less substituted alkenes? I think dihydroxylation favours less substituted alkenes, the resulting vicinal diols can then be cleaves with sodium periodate. However, I am not certain if my thinking is correct, if I’m wrong are there any other
methods?
Good question. You are indeed correct that greater alkene substitution favors a higher rate of ozonolysis,
Is your problem concerning selectivity on a molecule with multiple alkenes? Is this something that could be avoided through, say, a later-stage reduction of an alkyne to a cis or trans alkene (alkynes are generally slow to cleave with ozonolysis).
Ozonolysis of 3 methylbut-1-ene in the presence of H202
One of the products is methanal my note here in textbook concert it into CO2
Pls why
And not methanoic acid
Methanal (formaldehyde) is quickly oxidized by H2O2 to give carbonic acid which itself loses water to give CO2 (carbon dioxide)
What happens if you run this reaction in
1. O3
—–>
2. Me2S, H2O
… ?
Does the H2O change anything, as compared to the reaction without H2O?
No, it should not. The only thing water might do is form the hydrate of the aldehyde/ketone, which is reversible anyway.
What if we have one mole of an alkene with two double bond and only one mole of ozone?
Hi i was just wondering what the mechanism would be for example if i started with cyclohexene and used 03 and Me2S
The mechanism would be identical to the generic reductive workup example. The product would be a six carbon chain with an aldehyde at each end; hexanedial
What do u mean sir
What about Ozonolysis on O-xylene? I assume the reaction would take place at all of the alkenes? If this is the case, would it require 3 equivalents?
Ozonolysis on an aromatic molecule is generally a no-go, except under forcing conditions.
I aspire to reach your level of orgo proficiency. Like for real, reading your answers to these questions is awesome. Orgo 2 final coming up for me
hi i am in 11th grade and i got a question where i was given the final products that were obtained whilst the reactants underwent ozonolysis. how do i find out the reactant(IUPAC name) if the product is given. Pls help
You need to work backwards. Analyze the bonds formed and broken in the forward direction of ozonolysis. Now apply the same pattern, but in reverse.
What happens if a compound containing both double and triple bond is introduced to ozonolysis?which one will get reduced and why?
Alkynes are considerably more resistant towards ozonolysis than alkenes. It’s possible to selectively cleave alkenes in the presence of alkynes.
I found a question
Ozonolysis of cyclohexanone using Zn as a catalyst yields which products ?
Thanks !
Zn is used in the workup step, not with ozonolysis itself. Your product would be hexanedial.
What is the difference between oxidative ozonolysis and reductive ozonolysis
And does their products area same or different
It’s “oxidative workup” and “reductive workup”. The difference is discussed in the article. Oxidative workup will convert aldehydes to carboxylic acids.
What is the difference for ozonolysis by zinc and water
Ozonolysis is not done with zinc and water. Ozonolysis is done with ozone. The workup is done with zinc and water.
Give me mechanism for types of oxidative and reductive ozonolysis
Oxidative workup and reductive workup. There’s a comprehensive treatment in the Reaction Guide.
What is the pros and cons using ozonolysis?
Pros: works well at gram-scale, and ease of workup. Basically add reductant at -78 and let warm, followed by concentration. Cons: poor at explorative scale (e.g. 100 mg and less) where it’s more convenient to use OsO4/NaIO4 (Johnson-Lemieux cleavage).
when comparing the ozonolysis reaction to the KMnO4 (hot) reaction, why is it that ozonolysis doesn’t form carboxylic acids on alkenes but will on alkynes? KMnO4 will form carboxylic acids on both alkynes and alkenes.
Ozonolysis cleaves all C-C bonds and converts to C-O bonds. In an alkyne three bonds are cleaved, and instead of forming C(triple bond)O, which would have a positive formal charge at oxygen, one forms a carboxylic acid instead.
If there are multiple alkenes within the original molecule but there is only one equivalent of O3, how do you determine which alkene to cleave and which to leave as is? Thanks!
Hi – good question!
Generally, the more highly substituted the alkene, the more electron rich it is, and the more reactive it will be towards O3 (sterics are not a significant factor in most cases).
It’s possible to selectively ozonize an alkene assuming there is a significant difference in substitution pattern.
For instance it’s possible to selectively ozonize a tetrasubstituted alkene in the presence of a disubstituted alkene. The trick is to use a dye as an indicator (an example is Sudan Red) that is intermediate in reactivity between the alkene you are trying to ozonize and the less reactive alkene. When the dye starts getting chewed up you will notice a color change and you can stop the reaction.
Benzene ring breaks on ozonolysis in all cases
Absolutely not. Only under extremely forcing conditions.
does ozonolysis take place at any temperature please ?? thanx
Usually -78 degrees, temperature of dry ice-acetone bath.
when there is a cyclopentene attached to benzene ring, and ozonolysis is carried out then will the reaction take place only on pentene…? why does that happen..?
Yes, benzene is relatively inert to ozonolysis unless it is extremely electron rich (e.g. has alkoxy groups)
well from what reactant by ozonlysis can we form cyclohexanone???
You’ll need to learn how to think backwards.
Cyclohexane double bounded to CH2 should give you cyclohexanone
With formaldehyde as by product
Correct?
Yes, methylenecyclohexane is the simplest precursor that will work.
The acid is needed to hydrolise the Carbon Oxygen bond in the Ozonide intermediate
Now ‘aldehyd’ is still written under this carboxylic acid.
This has been fixed. Thank you
I believe there is a typo- in the last mechanism, it is described c=o,-oh to be an “aldehyde” where it should be a carboxylic acid? (In oxidative workup, where the H is replaced with OH).
Ah yes, it should be a carboxylic acid. Will fix. Thanks!
I had a question where it was a reaction map for turning a generic terminal alkyne into a generic aldehyde. I was going for using hydrogenization in the presence of Lindlar’s and ozonolysis.
In the answer provided (one of many ways), the alkyne underwent ozonolysis with ozone followed by zinc in acid (h3O+) what would the purpose of the acid be?
The acid helps to break up the intermediate ozonide – it protonates one of the oxygens and makes it a better leaving group, in a way similar to how acid helps to cleave acetals.