Baeyer-Villiger Oxidation
The Baeyer-Villiger Oxidation is an organic reaction used to convert ketones into Esters (or cyclic ketones into Lactones) using peracids as the oxidizing agent. It involves the insertion of an oxygen atom adjacent to the carbonyl group.
1. General Reaction
A ketone reacts with a peroxy acid ($RCO_3H$) to form an ester and a carboxylic acid.
Common Reagents (Peracids):
- m-CPBA: meta-Chloroperbenzoic acid (Most common).
- Peracetic Acid: $CH_3COOOH$.
- Trifluoroperacetic Acid: $CF_3COOOH$ (Highly reactive).
2. Detailed Mechanism
The reaction proceeds via a rearrangement step known as the Criegee intermediate.
Step 1: Nucleophilic Attack
The peracid is protonated (or acts directly) and attacks the carbonyl carbon of the ketone to form the tetrahedral Criegee Intermediate.
Step 2: 1,2-Migration (Rate Determining Step)
One of the alkyl groups ($R$ or $R'$) migrates from the carbon to the electron-deficient oxygen atom, with the simultaneous departure of the carboxylate leaving group ($R''COO^-$). This step determines the regioselectivity.
Step 3: Deprotonation
Loss of a proton yields the final ester.
3. Migratory Aptitude (Crucial Rule)
When dealing with unsymmetrical ketones ($R-CO-R'$), the group that migrates is the one best able to stabilize a positive charge in the transition state.
Order of Migration
$$ H > \text{Tertiary Alkyl} > \text{Cyclohexyl} > \text{Secondary Alkyl} \approx \text{Phenyl} > \text{Primary Alkyl} > \text{Methyl} $$
Note on Aryl Groups: Electron-donating groups (EDG) on the benzene ring increase migratory aptitude, while electron-withdrawing groups (EWG) decrease it.
$p-MeO-Ph > p-Me-Ph > Ph > p-Cl-Ph > p-NO_2-Ph$
4. Stereochemistry
The migration is strictly Intramolecular and proceeds with Retention of Configuration. If a chiral group migrates, its stereochemistry is preserved.
5. Examples
A. Acetophenone ($Ph-CO-Me$)
Migratory aptitude: $Ph > Me$. Therefore, Phenyl migrates to Oxygen.
$$ Ph-CO-CH_3 \xrightarrow{m-CPBA} \underbrace{Ph-O-CO-CH_3}_{\text{Phenyl Acetate}} $$(Not Methyl Benzoate)
B. Cyclohexanone
Cyclic ketones undergo ring expansion (insertion of Oxygen) to form Lactones (Cyclic Esters).
$$ \text{Cyclohexanone} \xrightarrow{m-CPBA} \epsilon\text{-Caprolactone} $$C. Benzaldehyde ($Ph-CHO$)
Migratory aptitude: $H > Ph$. Hydrogen migrates.
$$ Ph-CHO \xrightarrow{m-CPBA} Ph-COOH \text{ (Benzoic Acid)} $$Baeyer-Villiger Quiz
Test your knowledge on Oxidation and Migration. 10 MCQs with explanations.
No comments:
Post a Comment