Chapter 19: Aldehydes and Ketones: Nucleophilic Addition Reactions
The carbonyl group, and how aldehydes and ketones are named
The carbonyl group, a carbon–oxygen double bond, is the most important functional group in the second half of an organic chemistry course, and aldehydes and ketones are its simplest carriers. The distinction between the two families rests entirely on what else is bonded to the carbonyl carbon. In an aldehyde that carbon carries at least one hydrogen, which forces the CHO group to the end of a carbon chain; formaldehyde (H₂C=O) is the parent case with two hydrogens. In a ketone the carbonyl carbon is bonded to two other carbons, so the C=O sits within the skeleton. Systematic names follow…
Where aldehydes and ketones come from
Aldehydes and ketones sit at a crossroads of functional-group chemistry, and their preparations are largely reactions met earlier in the course, now read in the synthetic direction. The most common laboratory route is alcohol oxidation. A primary alcohol can be oxidized to either of two levels, and the choice of reagent decides which: anhydrous oxidants — pyridinium chlorochromate (PCC) or the Dess–Martin periodinane — remove one hydrogen equivalent and stop cleanly at the aldehyde, whereas aqueous chromium(VI) conditions allow the aldehyde to hydrate — to add water reversibly, giving a…
Aldehydes oxidize easily; ketones do not
The single structural difference between the two families — the hydrogen on an aldehyde's carbonyl carbon — produces their sharpest chemical contrast. Oxidation of an aldehyde formally replaces that C–H with a C–OH, giving a carboxylic acid, and the reaction proceeds under remarkably mild conditions. In aqueous solution a small fraction of the aldehyde exists as its hydrate — the gem-diol formed by reversible addition of water across the C=O, with both hydroxyls on the former carbonyl carbon (the equilibrium itself is developed in the hydration section) — and the hydrate is oxidized exactly…
The master mechanism: nucleophilic addition to C=O
Nearly every reaction of an aldehyde or ketone follows the same two-step pattern, which makes this the most economical mechanism in the course to learn well. The carbonyl π bond is polarized toward oxygen, leaving the carbon electron-poor: the electron-accepting site of Chapter 2's donor-acceptor pair. A nucleophile — hydride, a carbanion, water, an alcohol, an amine, cyanide — attacks that carbon along the Bürgi–Dunitz trajectory — roughly 107°, tilted back from perpendicular over the carbonyl plane toward the π lobe. As the new σ bond forms, the π electrons shift entirely onto oxygen, the…
Water and HCN as nucleophiles: gem-diols and cyanohydrins
Water is a weak nucleophile, but the carbonyl group is electrophilic enough for a slow, reversible addition: one water oxygen bonds to the carbonyl carbon and a proton transfers to the carbonyl oxygen, giving a geminal diol, or hydrate, with two hydroxyl groups on the same carbon. Both acid and base catalyze the approach to equilibrium without changing its position. Where the equilibrium lies depends on the same steric and electronic factors that govern all nucleophilic additions. Formaldehyde, the most electrophilic simple carbonyl, is more than 99% hydrate in aqueous solution; acetaldehyde…
Hydride and Grignard reagents: reduction and C–C bond formation
Viewed through the nucleophilic-addition mechanism, carbonyl reduction and Grignard addition are the same reaction with different nucleophiles. Sodium borohydride and lithium aluminum hydride both act as sources of hydride delivered to the electrophilic carbonyl carbon; the π electrons shift onto oxygen and the resulting alkoxide is protonated on workup. An aldehyde therefore becomes a primary alcohol and a ketone a secondary alcohol. NaBH₄ is mild, selective for aldehydes and ketones, and tolerant of protic solvents; LiAlH₄ is far stronger, reacts violently with water, and also reduces…
Primary amines give imines; secondary amines give enamines
Ammonia and amines are good nucleophiles, and their addition to aldehydes and ketones opens a family of condensation products in which the carbonyl oxygen is ultimately replaced by nitrogen. The first stage is familiar: the amine nitrogen attacks the carbonyl carbon and, after a proton shuffle, the product is a carbinolamine — a tetrahedral intermediate with OH and NR₂ on the same carbon. What happens next depends on how many hydrogens remain on nitrogen. With a primary amine, protonation of the hydroxyl converts it into water, which leaves to give a resonance-stabilized iminium ion;…
Hemiacetals, acetals, and protecting the carbonyl
Alcohols react with aldehydes and ketones the way water does, but the products can be isolated and used. The first addition, catalyzed by acid, gives a hemiacetal: the former carbonyl carbon now carries one hydroxyl and one alkoxy group. For most open-chain carbonyl compounds the hemiacetal is a minor component of an unfavorable equilibrium and cannot be isolated. The important exceptions are intramolecular: when a hydroxyl group within the same molecule can reach the carbonyl through a five- or six-membered ring, the cyclic hemiacetal is favored — this is precisely the chemistry by which…
The Wittig reaction converts C=O into C=C
Alkenes can be made from carbonyl compounds in one step by the Wittig reaction, which joins the carbonyl carbon to a carbanion carbon and removes the oxygen entirely. The reagent is a phosphorus ylide — a neutral molecule with adjacent positive and negative charges. Its preparation is a two-step sequence worth knowing in its own right: triphenylphosphine, a good nucleophile, displaces halide from a methyl or primary alkyl halide to give an alkyltriphenylphosphonium salt, and a strong base such as butyllithium then removes a proton from the carbon bonded to phosphorus. The resulting carbanion…
1,2 versus 1,4: conjugate addition to enones
When a carbon–carbon double bond is conjugated with a carbonyl group, the two π systems behave as one. Drawing the resonance forms of an enone shows the carbonyl oxygen accepting electron density and positive character appearing at two carbons: the carbonyl carbon and the beta carbon, two atoms away. Both are legitimate electrophilic sites, and the outcome of a nucleophilic attack is classified by which one is attacked. Direct addition at the carbonyl carbon is called 1,2 addition and proceeds exactly as with any aldehyde or ketone. Conjugate addition — 1,4 addition, or the Michael-type…
Recognizing aldehydes and ketones spectroscopically
The strongly polarized C=O bond gives aldehydes and ketones spectroscopic signatures that are both intense and tightly clustered, which makes spectroscopy the practical first step in identifying an unknown carbonyl compound. In the infrared, the carbonyl stretching vibration produces one of the strongest absorptions in any spectrum, landing where Chapter 12's four-region map reserves space for C=O. Saturated aldehydes absorb near 1730 cm⁻¹ and saturated ketones near 1715 cm⁻¹ — close enough that the two families are not reliably distinguished by this band alone. Conjugation is read directly…
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