Ketone - Synthesis

Synthesis

Many methods exist for the preparation of ketones in industrial scale, biology, and in academic laboratories. In industry, the most important method probably involves oxidation of hydrocarbons, often with air. For example, a billion kilograms of cyclohexanone are produced annually by aerobic oxidation of cyclohexane. Acetone is prepared by air-oxidation of cumene.

For specialized or small scale organic synthetic applications, ketones are often prepared by oxidation of secondary alcohols:

R₂CH(OH) + O → R₂C=O + H₂O

Typical strong oxidants (source of "O" in the above reaction) include potassium permanganate or a Cr(VI) compound. Milder conditions make use of the Dess-Martin periodinane or the Moffatt-Swern methods.

Many other methods have been developed including:

• By geminal halide hydrolysis.
• By hydration of alkynes. Such processes occur via enols and require the presence of an acid and HgSO₄. Subsequent enol-keto tautomerization gives a ketone. This reaction always produces a ketone, even with a terminal alkyne.
• From Weinreb Amides using stoichiometric organometallic reagents.
• Aromatic ketones can be prepared in the Friedel-Crafts acylation, the related Houben-Hoesch reaction and the Fries rearrangement.
• Ozonolysis, and related dihydroxylation/oxidative sequences, cleave alkenes to give aldehydes and/or ketones, depending on alkene substitution pattern.
• In the Kornblum–DeLaMare rearrangement ketones are prepared from peroxides and base.
• In the Ruzicka cyclization, cyclic ketones are prepared from dicarboxylic acids.
• In the Nef reaction, ketones form by hydrolysis of salts of secondary nitro compounds.
• In the Fukuyama coupling, ketones form from a thioester and an organozinc compound.
• By the reaction of an acid chloride with organocadmium compounds or organocopper compounds.
• The Dakin-West reaction provides an efficient method for preparation of certain methyl ketones from carboxylic acids.
• Ketones can also be prepared by the reaction of Grignard reagents with nitriles, followed by hydrolysis.
• By decarboxylation of carboxylic anhydride.
• Ketones can be prepared from haloketones in reductive dehalogenation of halo ketones.
• In ketonic decarboxylation symmetrical ketones are prepared from carboxylic acids.