m-CPBA (meta-chloroperoxybenzoic acid)
Last updated: December 1st, 2022 |
m-CPBA (meta-Chloroperoxybenzoic acid) As A Reagent For Epoxidation Of Alkenes And For the Baeyer-Villiger Reaction
Notice how the molecule looks like a carboxylic acid, but has an extra O. That’s what’s called a “per-acid” – it should be reminiscent of the difference between hydrogen per-oxide (HOOH) and hydrogen oxide (H2O). Note that the oxygen-oxygen bond is quite weak (about 33 kcal/mol or 138 kJ/mol). As we shall see, this is what leads to the high reactivity of these compounds.
Oxidation Of Alkenes With mCPBA
mCPBA forms epoxides when added to alkenes. One of the key features of this reaction is that the stereochemistry is always retained. That is, a cis alkene will give the cis-epoxide, and a trans alkene will give a trans epoxide. This is a prime example of a stereoselective reaction.
The Concerted Mechanism For Epoxidation Of Alkenes With mCPBA
The reaction itself happens through a “concerted” transition state. That is, the bond between the oxygen and the alkene is being formed at the same time that the O-O bond is breaking and the proton is being transferred from the OH to the carbonyl oxygen. Those little dotted lines represent partial bonds.
The epoxides that are formed are useful in all kinds of ways. Mostly, they are good electrophiles that will react with nucleophiles such as Grignard or organolithium reagents, hydroxide or alkoxide ions, or (in the presence of acid) water.
The Baeyer-Villiger Oxidation Of Ketones To Esters
Another useful reaction of mCPBA – commonly encountered in Org 2 – is the Baeyer-Villiger reaction. This is a rare example of a reaction that results in the oxidation of a ketone – remember that chromic acid leaves ketones alone, for instance. mCPBA can also oxidize aldehydes.
Mechanism For The Baeyer-Villiger Oxidation Of Ketones With m-CPBA
The first step of the Baeyer-Villiger reaction is a 1,2 addition of the per-acid oxygen to the carbonyl of the ketone. Then there’s a proton transfer. [Note: when the pros do this reaction, they often add a mild base like sodium bicarbonate, which will speed up the reaction by making the conjugate base of mCPBA – a better nucleophile]. Now comes the fun part. The lone pair on the oxygen then re-forms the C=O bond, which then leads to a 1,2-shift of a carbon bond to the oxygen, breaking the (weak) oxygen-oxygen bond and forming an ester in the process. (Remember – if you ever have to sketch this mechanism out, draw the ugly version first).
How do you know which bond will migrate? Great question. Migrating group ability corresponds – somewhat – with carbocation stability. Suffice it to say that H is the best migrating group, tertiary alkyls are next, and methyl groups are the worst. Aryl groups (like this benzene group in the example) are at the lower middle range of the scale.
Why is this reaction useful? Well, let’s say you have a ketone on an aromatic ring (a meta director) and you want to make the ortho or para product. If you do a Baeyer-Villiger with mCPBA, you will transform it into an ester with the oxygen on the ring (an ortho para director). Now you can add your electrophile. This trick comes in handy.
For the record, other peracids like peroxybenzoic acid or peroxyacetic acid will do the same chemistry as mCPBA. mCPBA tends to get a lot of use due to the fact that it is more reactive than peroxybenzoic acid, and also a nicely crystalline white solid.
P.S. You can read about the chemistry of MCPBA and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.
(Advanced) References and Further Reading
- Oxydation ungesättigter Verbindungen mittels organischer Superoxyde
Nikolaus Prileschajew. Chemische Berichte, 1909, 42, 4811. DOI: 10.1002/cber.190904204100
This reaction (epoxidations of alkenes with a peracid) is also known as the Prizelhaev reaction after the author.
- The oxidation of olefins with perbenzoic acids. A kinetic study
M. Lynch and K. H. Pausacker. J. Chem. Soc. 1955, 1525-1531. DOI: 10.1039/JR9550001525
One of the earliest papers on epoxidation with m-CPBA, comparing its reactivity with other substituted peracids. As expected, the reactivity of peroxyacids is increased by electron-withdrawing groups.
- m-CHLOROPERBENZOIC ACID
Richard N. McDonald, Richard N. Steppel, and James E. Dorsey. Synth. 1970, 50, 15. DOI: 10.15227/orgsyn.050.0015
A reliable preparation for m-CPBA (which is commercially available) in Organic Syntheses. As this procedure shows, m-CPBA is not prepared as a pure compound (it is a mixture of the peracid and acid, and commercial samples may contain residual water for stability).
- Epoxidations with m-Chloroperbenzoic Acid
Nelson N. Schwartz and John H. Blumbergs. J. Org. Chem. 1964 29, (7), 1976-1979. DOI: 1021/jo01030a078
This paper describes mechanistic studies of m-CPBA oxidation that demonstrate that ionic intermediates are not involved in the reaction, and that the rate is insensitive to solvent polarity.
- Record of chemical progress
Bartlett, P. D. Chem. Prog. 1950, 11, 47
This is the publication in which Prof. P. D. Bartlett describes the ‘butterfly mechanism’ for m-CPBA epoxidation.
- MCPBA Epoxidation of Alkenes: Reinvestigation of Correlation between Rate and Ionization Potential
Cheal Kim, Teddy G. Traylor, and Charles L. Perrin. J. Am. Chem. Soc. 1998, 120, (37), 9513-9516. DOI: 1021/ja981531e
An interesting paper that describes the development of a kinetic method for measuring the rate of epoxidation of various alkenes with m-CPBA.
- Experimental Geometry of the Epoxidation Transition State
Daniel A. Singleton, Steven R. Merrigan, Jian Liu, and K. N. Houk. J. Am. Chem. Soc. 1997, 119, (14), 3385-3386. DOI: 1021/ja963656u
Combined experimental and theoretical studies of the epoxidation transition state, showing that both C-O bond forming events are nearly synchronous.
- The mechanism of epoxidation of olefins by peracids
V. G. Dryuk. Tetrahedron. Volume 32, Issue 23, 1976, 2855-2866. DOI:10.1016/0040-4020(76)80137-8
An account of the author’s work on kinetic studies of the epoxidation of olefins with peracids in order to determine the exact mechanism.
37 thoughts on “m-CPBA (meta-chloroperoxybenzoic acid)”
Is this an electrophilic addition reaction
Yes, it is an addition reaction, and the reagent (mCPBA) is an electrophile. So this would qualify.
What if there’s two double bonds? Would the one that has more aklye halides get priority?
The double bond attached to more alkyl groups (or fewer hydrogens, if you prefer) gets priority, as it would be more electron-rich.
This seems a little odd to me because if you look at the stability of products, the one with note hyperconjugation would be more stable, which in the case dec mentioned would mean that the double bond attached to less alkyl groups would be preferred?
Why only meta Cpba is used. Why not the para Cpba is used for the oxidation?
The meta isomer is used because it’s cheap. It’s easier to prepare from chlorination of (cheap) benzoic acid, since the carboxylic acid is a meta-directing group. Adding electron withdrawing groups on to the aromatic ring would make it more reactive.
Hi, I have a question,
For my masters project the mCPBA didn’t work to epoxides my olefin, how can I explain this? (it was an epoxidation of an allyl ether)
And are there any references I could use to explain this mechanism?
Thank you :)
It’s hard to answer a general question like this without more specifics. There are lots of reasons why it might not work, such as the quality of the reagent, the electron density of the alkene, steric effects around the alkene, etc.
Why is the oxygen oxygen bond in per acid is too weak??
The oxygen-oxygen bond is weak due to repulsion between the lone pairs residing on the adjacent oxygens.
can epoxides exhibit geometrical isomerism??/
The two C-O bonds to the epoxide will always be on the same face.
Do migrating aptitude of phenyl greater than H in baeyer villager oxidation .. ?
If yes then ph-CHO with per acid will not give ph-COOH?.. Please reply
No, H has the best migratory aptitude. BV oxidation of an aldehyde will give a carboxylic acid.
Why does the oxygen with the hydrogen function as a nucleophile and not the other oxygen?
Because after the initial nucleophilic attack, the oxygen with the hydrogen can be quickly neutralized by removal of a proton, whereas the “other oxygen” cannot go back to being a neutral species without breaking C-O or O-O. Try and draw out the arrows for a reaction with that oxygen.
does the reaction vary when mCPBA is in acidic or basic solvent or does it strictly depend on the reactant being cis/trans
The epoxidation reaction is stereospecific. Under identical conditions, epoxidation of a cis alkene and a trans alkene will give two stereoisomeric products. This is true whether mCPBA is used in its acidic form, or if a mild base (e.g. NaHCO3) is used with mCPBA to promote the reaction.
What if the ketone is cyclic, like 4-methyl cyclohexanone? Does the ring break?
Great question! You form a lactone – a cyclic ester – in that case a 7-membered ring.
I understand that the reaction of peroxy acid and styrene will give me epoxystyrene. However, there
is a by product in about 25 percent yield which is benzoic acid. What is the mechanism for this reaction.
Are you sure it’s not a byproduct from the peroxyacid?
Styrene + perbenzoic acid gives great yields of styrene oxide. See:
Which o in mcpba the is electron deficient and y electron defficient plzz ans
Answer me this: What’s a better leaving group: R-CO2(-) or HO(-) ? Therein lies your answer.
I have a question about epoxy.
i want to form a epoxy while i have on the left side an alcohol and on the right side a dubble bound. so for an example [(2R,3S)-3-Allyl-2-oxrianyl]methanol. can someone help me? because i know how to form the left side but not the right side.
Sounds like glycidol. You can buy that.
What happend when a compound on reaction with mcpba which has both doble bond and a ketonic moeity
It depends! I once used mCPBA in a reaction which had a diene and two ketones. The diene was electron poor (connected to an ester) and only one of the ketones was really accessible. So it did a Baeyer-Villiger!
Hi!!! Is mCPBA able to react with alkynes? I have a feeling no but I am not 100% sure (I want to make sure that I don’t get this wrong on an exam later).
Funny you should ask, I was very close to putting something up about this! For your purposes, I would say, “No”, as the reaction between alkynes and mCBA is not very useful.
However… the reaction between alkynes and mCPBA that *does* happen is quite a trip. I can say with 99.9% certainty it will not show up on an exam. https://imgur.com/a/Ibvqy8y
Why does m-CPBA acts as a electrophile in epoxidation reaction?
The O-O bond is quite weak (about 35 kcal/mol) and the carboxylate is a good leaving group. So nucleophilic attack at the terminal oxygen is quite easy.
How to quench mcbpa if sm material is acid and product also acid
Just quench with bisulfite to get rid of the oxidant, acidify and extract. You can run columns on carboxylic acids if you acidify your eluent.
Then what if there is ketone with vinyl group like ‘1-phenylbut-3-en-1-one’, is there epoxidation or electrophilic addition?
Epoxidation won’t happen except with electron-rich alkenes. The most likely outcome is a Baeyer-Villiger.