Reactions of Aldehydes & Ketones

The Grignard Reaction: The reaction of an alkyl, aryl or vinyl halide with magnesium metal in ether solvent, produces an organometallic complex of uncertain structure, but which behaves as if it has the structure R-Mg-X and is commonly referred to as a Grignard Reagent.

The "R" group in this complex (alkyl, aryl or vinyl), acts as if it was a stabilized carbanion and Grignard reagents react with water and other compounds containing acidic hydrogens to give hydrocarbons (just as would be expected for a well-behaved, highly basic carbanion). In the absence of acidic hydrogens, the Grignard reagent can function as a powerful nucleophile, and is most often used in addition reactions involving carbonyl compounds, as shown above. The product of these addition reactions is typically a secondary or tertiary alcohol (primary alcohols can be formed by reaction with formaldehyde), as shown in the examples below; in these the carbonyl and halide portions of the molecules have been colored blue and red, respectively, to assist in understanding the component parts of the final products.

Hydration of Aldehydes & Ketones: The hydration of carbonyl compounds is an equilibrium process and the extent of that equilibrium generally parallels the reactivity of the parent aldehyde or ketone towards nucleophilic substitution; aldehydes are more reactive than ketones and are more highly hydrated at equilibrium.

Formation of Cyanohydrins: The reaction of carbonyl compounds with HCN is an equilibrium process and, again, the extent of that equilibrium generally parallels the reactivity of the parent aldehyde or ketone towards nucleophilic substitution.

Reaction with Amines: The reaction of carbonyl compounds with amines involves the formation of an intermediate carbinolamine which undergoes dehydration to form an immonium cation which can loose a proton to form the neutral imine.

Some examples of common imine-forming reactions are given below:

Imines formed from secondary amines can loose a proton from the a-carbon to form an enamine. Because of resonance, enamines maintain a partial carbanion character on the a-carbon and can be utilized as nucleophiles, as will be discussed in the section on "alpha alkylations".

Ketal and Acetal Formation: Ketones and aldehydes react with excess alcohol in the presence of acid to give ketals and acetals, respectively. The mechanism of acetal formation involves equilibrium protonation, attack by alcohol, and then loss of a proton to give the neutral hemiacetal (or hemiketal). The hemiacetal undergoes protonation and loss of water to give an oxocarbonium ion, which undergoes attack by another mole of alcohol and loss of a proton to give the final product; note that acetal (or ketal) formation is an equilibrium process.

Some examples of acetal and ketal formation are given below:

The Wittig Reaction: Ketones and aldehydes react with phosphorus ylides to form alkenes. Phosphorus ylides are prepared by an SN2 reaction between an alkyl halide and triphenylphosphine, followed by deprotonation by a strong base such as n-butyllithium. The mechanism of the Wittig reaction involves nucleophilic addition to give an intermediate betaine, which decomposes to give the alkene and triphenylphosphine oxide. The Wittig reaction works well to prepare mono-, di-, and tri-substituted alkenes; tetra-substituted alkenes cannot be prepared by this method.

Oxidation & Reduction of Aldehydes and Ketones

Preparation of Alcohols by Reduction of Aldehydes and Ketones: Reduction of simple aldehydes and ketones with BH4- yields the corresponding alcohol directly. The reaction works well for simple compounds, but reaction of BH4- with a-b-unsaturated aldehydes and ketones can result in significant reduction of the double bond.

A much more powerful reductant is LiAlH4, which will reduce aldehydes, ketones, esters, carboxylic acids and nitriles. Some sample reactions are shown below:

As seen in the first example, the reduction of carboxylate esters results in the addition of two moles of hydride to the carbonyl carbon, with loss of the alcohol portion of the ester, forming the corresponding primary alcohol.

Although the reduction of esters with LiAlH4 proceeds to produce the alcohol, reduction of carboxylate esters by diisobutylaluminum hydride (DIBAH) stops at the aldehyde.

Wolff-Kishner Reduction: The imine formed from an aldehyde or ketone on reaction with hydrazine (NH2NH2) is unstable in base, and undergoes loss of N2 to give the corresponding hydrocarbon.

Clemmensen Reduction: Carbonyl compounds can also be reduced by the Clemmensen reduction using zinc-mercury amalgam in the presence of acid; the mechanism most likely involves free radicals.

The Formation of Thioketal and Thioacetals: Ketones and aldehydes react with excess thiol in the presence of acid to give thioketals and thioacetals, respectively. These compounds are smoothly reduced by Raney-Nickel to give the corresponding hydrocarbons.

Oxidation of Aldehydes by Silver Oxide: Reaction of simple aldehydes with aqueous Ag2O in the presence of NH3 yields the corresponding carboxylic acid and metallic silver. The silver is generally deposited in a thin metallic layer which forms a reflective "mirror" on the inside surface of the reaction vessel. The formation of this mirror forms the basis of a qualitative test for aldehydes, called the Tollens Test.

Oxidation of Aldehydes to form Carboxylic Acids: Reaction of simple aldehydes with acidic MnO4-, or CrO3/H2SO4 yields the corresponding carboxylic acid. Aldehydes oxidize very easily and it is often difficult to prevent oxidation, even by atmospheric oxygen.

Oxidation of Ketones: Ketones are more resistant to oxidation, but can be cleaved with acidic MnO4- to yield carboxylic acids.