Master Organic Chemistry Reaction Guide

Baeyer-Villiger Reaction

Description: Treatment of an aldehyde or ketone with a peroxyacid (RCO3H) results in the formation of an ester.

1-baeyer villiger oxidation of ketones aldehydes to esters.gif

Notes: A common peroxyacid for this purpose is m-chloroperoxybenzoic acid (m-CPBA), although other peroxyacids such as peroxyacetic acid can be used.

Examples:

Notes: The reagent in the second example is mCPBA, drawn out. Note that in the second example, the phenyl group “migrates” preferentially over the methyl group. The reason is often not explored deeply in introductory courses, but has to do with the superior ability of the phenyl group to stabilize positive charge in the transition state (relative to methyl). For more information on “migratory aptitudes” see this link.

Mechanism: This is shown with a generic R for the peroxyacid, since a variety of different reagents can be used. Addition (“1,2-addition”) of the peroxyacid oxygen to the ketone (Step 1, arrows A and B) to give a tetrahedral intermediate is followed by a proton transfer (Step 2, arrows C and D). Then, as the C-O π bond reforms, a 1,2-shift of carbon to oxygen occurs, breaking the C–C bond as well as the weak O–O bond, giving an ester (Step 3, arrows E, F and G). Then, deprotonation yields the neutral ketone (Step 4, arrows H and I)

baeyer villiger reaction arrow pushing mechanism protonation of ketone attack of peroxyacid at carbonyl carbon rearrangement step with breakage of oxygen oxygen bond

Notes: The neutral carboxylic acid is a byproduct here. The group “B” for deprotonation could be any atom with a lone pair, such as another equivalent of the carboxylic acid. Finally, it is plausible to show protonation of the carbonyl oxygen first (this would result in a more reactive carbonyl carbon).


(Advanced) References And Further Reading

  1. Einwirkung des Caro’schen Reagens auf Ketone
    Adolf von Baeyer, Victor Villiger
    Ber. 1899, 32 (3), 3625
    DOI: 10.1002/cber.189903203151
    This paper by Nobel Laureate Adolf von Baeyer first describes what is now known as the Baeyer-Villiger rearrangement, using a mixture of sodium persulfate and concentrated sulfuric acid (Caro’s acid).
  2. Cycloadditions. 23. Synthetic approaches to .alpha.-methylene-.gamma.-lactones via cycloadditions of ketenes
    Alfred Hassner, Harold W. Pinnick, and Jay M. Ansell
    The Journal of Organic Chemistry 1978 43 (9), 1774-1776
    DOI: 10.1021/jo00403a032
    This paper has a representative procedure for a Baeyer-Villiger oxidation in the experimental section.
  3. 100 Years of Baeyer–Villiger Oxidations
    Michael Renz and Bernard Meunier
    Eur J. Org. Chem. 1999, 4, 737
    DOI: 1002/(SICI)1099-0690(199904)1999:4<737::AID-EJOC737>3.0.CO;2-B
    This review on the Baeyer-Villiger oxidation includes a detailed historical perspective on the development and history of the reaction.
  4. The Baeyer–Villiger Oxidation of Ketones and Aldehydes
    Krow, G. R. React. 1993, 251
    DOI: 10.1002/0471264180.or043.03
    This long, detailed review includes an in-depth discussion of the mechanism, substrate scope, limitations, and experimental procedures for the Baeyer-Villiger oxidation.
  5. The Baeyer−Villiger Reaction:  New Developments toward Greener Procedures
    E-J. ten Brink,I. W. C. E. Arends, and, and R. A. Sheldon
    Chemical Reviews 2004 104 (9), 4105-4124
    DOI:
    10.1021/cr030011l
    This review gives a modern perspective on the Baeyer-Villiger oxidation and describes procedures using more environmentally friendly oxidants (e.g. O2).

 

Comments

Comment section

2 thoughts on “Baeyer-Villiger Reaction

  1. So when it reacts with an aldehyde it will result in a carboxylic acid, with another carboxylic acid as a by product?

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