How do you oxidize ketones to carboxylic acid?

To oxidize ketones to carboxylic acids, chemists employ two primary methods, depending on whether the goal is to cleave the carbon chain or to insert an oxygen atom while retaining the original carbon count.

Oxidizing Ketones to Carboxylic Acids

Ketones can be oxidized to carboxylic acids using strong oxidizing agents, particularly at high temperatures. This process often involves the cleavage of carbon-carbon bonds within the ketone structure, leading to a mixture of carboxylic acids. However, for a more controlled oxidation that retains the original number of carbon atoms, a powerful oxidizing agent known as a peroxycarboxylic acid is utilized.

1. Oxidation with Carbon-Carbon Chain Cleavage

When strong oxidizing agents are used, ketones undergo oxidative cleavage, meaning a carbon-carbon bond adjacent to the carbonyl group is broken. This typically requires vigorous conditions.

Reagents: Common strong oxidizing agents include:
- Potassium permanganate (KMnO₄)
- Potassium dichromate (K₂Cr₂O₇) in acidic conditions (e.g., H₂SO₄)
- Concentrated nitric acid (HNO₃)
Conditions: These reactions generally require high temperatures to proceed.
Outcome: The carbon chain breaks, yielding a mixture of carboxylic acids. The specific products depend on the structure of the original ketone and which C-C bond is cleaved.
Popov's Rule: For unsymmetrical ketones, oxidation often preferentially cleaves the C-C bond such that the smaller alkyl group remains with the carbonyl carbon. However, this is not always strictly followed, and mixtures are common.

Example:
Consider the oxidation of a simple ketone like 2-butanone:

CH₃-CO-CH₂-CH₃  +  [O] (strong oxidizer, heat)  →  CH₃COOH (acetic acid)  +  CH₃COOH (acetic acid)
                                                    (if C2-C3 bond breaks)

OR

                                                    CH₃COOH (acetic acid)  +  HCOOH (formic acid)
                                                    (if C1-C2 bond breaks, less common)

In practice, this method is less selective and often not preferred if a single, specific carboxylic acid product is desired from an unsymmetrical ketone.

2. Baeyer-Villiger Oxidation (Oxygen Insertion)

To produce a carboxylic acid with the same number of carbon atoms as the starting ketone, the Baeyer-Villiger oxidation is the method of choice. This reaction involves the insertion of an oxygen atom adjacent to the carbonyl group.

Reagents: This reaction specifically employs peroxycarboxylic acids (also known as peracids). Key examples include:
- m-Chloroperoxybenzoic acid (m-CPBA)
- Peracetic acid (CH₃CO₃H)
- Performic acid (HCO₃H)
- Magnesium monoperoxyphthalate (MMPP)
Mechanism (Simplified): The peroxycarboxylic acid acts as an oxygen donor. The oxygen atom is inserted between the carbonyl carbon and one of the adjacent carbon atoms, forming an ester. The resulting ester can then be hydrolyzed (with acid or base) to yield a carboxylic acid and an alcohol.
```
Ketone + RCO₃H (peroxyacid) → Ester + RCOOH (carboxylic acid)
Ester + H₂O (acid/base catalyst) → Carboxylic Acid + Alcohol
```
Regioselectivity (Migratory Aptitude): In unsymmetrical ketones, there's a preference for which group migrates to the oxygen. The order of migratory aptitude is generally:
- Tertiary alkyl > Secondary alkyl > Phenyl ≈ Primary alkyl > Methyl
  This means the oxygen atom will preferentially insert next to the more substituted carbon atom.
Advantages:
- Preserves the carbon skeleton of the original ketone.
- Provides a highly selective route to form esters, which can then be hydrolyzed to carboxylic acids.

Example:
Oxidation of cyclohexanone using m-CPBA:

Cyclohexanone  +  m-CPBA  →  Caprolactone (an ester)
Caprolactone  +  H₂O (acidic hydrolysis)  →  6-hydroxyhexanoic acid

Alternatively, if an acyclic ketone is used, an ester is formed which, upon hydrolysis, yields a carboxylic acid and an alcohol.

Comparison of Oxidation Methods

Feature	Oxidation with C-C Cleavage	Baeyer-Villiger Oxidation
Oxidizing Agent	Strong oxidizers (KMnO₄, K₂Cr₂O₇, HNO₃)	Peroxycarboxylic acids (m-CPBA, peracetic acid)
Conditions	High temperatures, vigorous	Generally milder
Carbon Chain Integrity	Cleaves C-C bonds; leads to shorter chain products	Retains C-C bonds; inserts oxygen, same carbon count
Products	Mixture of carboxylic acids	Ester (hydrolyzed to carboxylic acid + alcohol)
Selectivity	Lower; often forms mixtures	Higher; specific oxygen insertion
Primary Use	Degradation, or when specific C-C bond cleavage is desired	Synthesizing carboxylic acids with retained carbon skeleton

Conclusion

The choice between these methods depends entirely on the desired outcome. If the goal is to simply break down a ketone into smaller carboxylic acids, strong oxidizing agents at high temperatures are effective. However, if the aim is to synthesize a carboxylic acid while maintaining the original carbon backbone of the ketone, the Baeyer-Villiger oxidation using a peroxycarboxylic acid is the precise and preferred method.

For more detailed information on Baeyer-Villiger oxidation, you can refer to resources like Wikipedia's Baeyer-Villiger Oxidation page.