REACTIONS OF ALDEHYDES AND KETONES
Introduction
This page focuses on reactions dealing with aldehydes and ketones. Note the reversibility of many of the below reactions, often with water.
Reactions
Preparation of ketones (review)
Oxidation of secondary alcohols
Ozonolysis of alkenes
Acid-catalyzed hydration of terminal alkynes
Friedel-Crafts acylation
Base-catalyzed hydration of ketones and aldehydes
Acid-catalyzed hydration of ketones and aldehydes
Acetal formation
Note that each step in the mechanism is reversible, so an acetal can be cleaved upon treatment with H3O+.
A cyclic acetal can be used if ethylene glycol is used as the attacking nucleophile. This can be used as a protecting group for aldehydes or ketones, leaving other functional groups such as esters available for reaction. Treatment with H3O+ deprotects the aldehyde or ketone.
Below is shown the mechanism of deprotection, the hydrolysis of acetals.
Thioacetal formation
This mechanism is similar to the mechanism of cyclic acetal formation.
Desulfurization
Treating a cyclic thioacetal with Raney nickel results in two hydrogen atoms replacing the sulfur ring. This provides an excellent step to reduce an aldehyde or ketone (get rid of the carbonyl). Form the thioacetal first, then desulfurize.
Imine formation
Formation of an imine using a primary amine. If the R group is —NH2 (the nucleophile is H2NNH2, hydrazine), a hydrazone is formed. If the R group is —OH (the nucleophile is H2NOH, hydroxylamine), an oxime is formed.
A hydrazone, left, and an oxime, right.
Enamine formation
When using a secondary amine as the nucleophile, an enamine is formed.
Wolff-Kishner reduction
This reaction provides an excellent way to get rid of an aldehyde or ketone. Firstly, form the imine from the carbonyl, then treat with potassium hydroxide, water, and heat.
Reduction with hydride sources
In the first step, a reducing agent (NaBH4 or LAH) gives a hydride. In the second step the oxide is protonated to yield a neutral product.
Reduction with Grignard reagent.
In the first step, the Grignard attacks the carbonyl. In the second step, the oxide is protonated by H3O+ or H2O. To form the Grignard reagent, treat an alkyl chloride or bromide with magnesium.
Cyanohydrin formation
For this reaction, potassium cyanide may be used with either hydrogen cyanide or hydrochloric acid (safer option).
Wittig reaction
The formation of the Wittig reagent is an SN2 process, so the alkyl halide should be primary or secondary. According to the course text, convincing evidence exists that the reaction proceeds with cycloaddition to form an oxaphosphetane (the cyclic compound), while sometimes the carbon of the Wittig is shown attacking the carbonyl first to form a betaine, which then forms an oxaphosphetane.
Baeyer-Villiger Oxidation
Treatment of an aldehyde or ketone with a peroxy acid such as MCPBA yields an ester. A cyclic ester is called a lactone. The reaction is regioselective, preferring H>3˚>2˚>Ph>1˚>methyl.