Baeyer-Villiger rearrangement is an example of the migration of a group from carbon to electron-deficient oxygen.
The reaction involves the oxidation of ketones to esters by the treatment with peracids such as peracetic acid, perbenzoic acid, pertrifluoroacetic acid, permonosulphuric acid. etc.
Cyclic ketones are converted to lactones with ring expansion.
The overall reaction is an insertion of oxygen atom between the carbonyl group and the adjacent carbon in ketone. Organic solvents which are inert under the conditions of reaction may be used. The choice of solvent depends upon the solubility of the reactants. Commonly used solvents are glacial acetic acid and chloroform.
Nucleophilic attack of the peracid on the protonated ketone gives an intermediate peroxide (i). The peroxide then undergoes loss of carboxylate anion and migration of a group from carbon to electron deficient oxygen to yield the protonated ester (ii). Finally the loss of proton gives the ester.
The reaction is catalysed by acids. Electron-releasing groups in the ketone and electron-withdrawing groups in peracids promote the reaction rate. Pertrifluoroacetic acid is very effective because trifluoroacetate ion is a good leaving group.
The mechanism is supported by the fact that the labelled oxygen atom of the ketone is entirely present in the carbonyl oxygen of the ester.
The loss of carboxylate anion and the migration of the group may be concerted. Syrkin has suggested that the peroxide (i) transforms into products by a cyclic mechanism, which shows that the last three steps may be concerted.
The migrating group retains its configuration as in other concerted reactions. For acylic compounds the migrating group, R' must be 2°, 3° or vinylic. However, migration of 1° alkyl group may be brought about by using CF3CO3H or BF3- H2O2 as reagent.
Baeyer-Villiger oxidation can be brought about with H2O2 and base also in some cases.
In unsymmetrical ketones, that group migrates which is more electron-releasing. Thus, the migratory aptitude of alkyl groups is in the order 3° > 2° > 1° > CH3. Electron-releasing substituents in the aryl group facilitate migration. The migratory order of aryl groups is p-anisyl > p-tolyl > phenyl > p-chlorophenyl > p-nitrophenyl, etc. In case of alkyl aryl ketones, it is the aryl group which migrates (except in case of t-butyl group).
The reaction has valuable synthetic applications.
1. Esters Esters which are difficult to synthesize can be prepared by this method.
2. Anhydrides When 1, 2-diketones or o-quinones are subjected to Baeyer-Villiger rearrangement, anhydrides are produced.
The products can be converted to various types of compounds.
3. Lactones Cyclic ketones are converted to lactones with ring expansion.
Long-chain hydroxyesters can be prepared from large ring-size ketones.
With some condensed cyclic ketones, two lactones in varying proportions are formed. For example, camphor gives two lactones (I) and (II).
Lactone (I) is the normal product formed by the migration of the tertiary bridgehead carbon while lactone (II) has been formed by the migration of the methylene group. The reason for the formation of two lactones in different proportions is steric factor.
4. Elucidation of structure The ester obtained as a result of the rearrangement may be hydrolysed to acid and alcohol from which the structure of the substrate can be determined.
The reaction is not successful with aldehydes Aliphatic aldehydes are oxidized to acids by the migration of the hydrogen.
A few aromatic aldehydes have been converted to formates by the migration of the aryl group.