Aldehydes and Ketones: Nucleophilic Addition and Properties

Aldehydes and Ketones: Structure and Nomenclature

Carbonyl Group Structure

The carbonyl group (C=O) is a central feature of both aldehydes and ketones. It consists of one σ-bond formed by the overlap of sp2-hybridized orbitals and one π-bond formed by the overlap of parallel 2p-orbitals. The oxygen atom has two lone pairs in sp2-hybridized orbitals, while the carbon atom forms bonds with other atoms.

• σ-bond: Overlap of sp2 orbitals

• π-bond: Overlap of 2p orbitals

• Lone pairs: Oxygen has two lone pairs

Aldehyde Structure and Nomenclature

An aldehyde is characterized by a carbonyl group bonded to at least one hydrogen atom. The simplest aldehyde, methanal (formaldehyde), has the carbonyl group attached to two hydrogens. Other aldehydes have the carbonyl group attached to one hydrogen and one carbon atom.

• Formaldehyde: Methanal, C=O bonded to two H atoms

• Acetaldehyde: Ethanal, C=O bonded to one H and one methyl group

• Naming: IUPAC names use the suffix -al (e.g., propanal, butanal)

• Aromatic aldehydes: Benzaldehyde is the accepted name for benzenecarbaldehyde

Ketone Structure and Nomenclature

A ketone has a carbonyl group bonded to two carbon atoms. The simplest ketone is acetone (propanone), with the carbonyl group attached to two methyl groups. Ketones are named using the suffix -one (e.g., propanone, butanone).

• Acetone: Propanone, C=O bonded to two methyl groups

• Acetophenone: 1-Phenylethanone, C=O bonded to a phenyl and methyl group

• Benzophenone: Diphenylmethanone, C=O bonded to two phenyl groups

Spectroscopic Properties of Aldehydes and Ketones

Infrared (IR) Spectroscopy

Aldehydes and ketones exhibit characteristic IR absorptions:

• Aldehyde C-H stretch: 2700–2830 cm-1 (two peaks)

• Carbonyl (C=O) stretch: ~1700 cm-1 (frequency increases with decreasing ring size)

• Conjugated C=O: 1680 cm-1

NMR Spectroscopy

1H NMR: Aldehyde protons appear at 9–10 ppm, methyl/methylene protons at 2–2.5 ppm. 13C NMR: Carbonyl carbons appear at 190–215 ppm.

Biologically and Industrially Important Aldehydes and Ketones

Geranial (Citral)

Geranial is a component of essential oils, such as lemongrass oil (65–85%). It is a highly conjugated aldehyde used in fragrances and flavorings.

Cortisone

Cortisone is an adrenocorticoid hormone (glucocorticoid) that regulates carbohydrate metabolism and reduces inflammation.

Preparation of Aldehydes and Ketones

Preparation from Carboxylic Acids

Aldehydes can be prepared by partial reduction of carboxylic acids using reagents such as LiAlH4 followed by water, or by oxidation of primary alcohols using PCC in CH2Cl2.

• Reduction: $\mathrm{RCOOH} \xrightarrow{LiAlH_4} \mathrm{RCH_2OH}$

• Oxidation: $\mathrm{RCH_2OH} \xrightarrow{PCC} \mathrm{RCHO}$

Preparation of Ketones

Ketones can be synthesized by oxidation of secondary alcohols or by addition of Grignard reagents to aldehydes followed by dehydration.

• Oxidation: $\mathrm{R_2CHOH} \xrightarrow{Cr(VI)} \mathrm{R_2CO}$

• Grignard addition: $\mathrm{RCHO} + \mathrm{R'MgX} \rightarrow \mathrm{RCR'OH}$

Reactivity of Aldehydes and Ketones: Nucleophilic Addition

General Mechanism

The most common reaction of aldehydes and ketones is nucleophilic addition to the carbonyl carbon. The nucleophile attacks the electrophilic carbon, breaking the π-bond and forming a tetrahedral intermediate.

• Electrophilic carbon: Partial positive charge (δ+)

• Nucleophile: Adds to carbonyl carbon

• Tetrahedral intermediate: sp3-hybridized carbon

Acid-Catalyzed Nucleophilic Addition

Protonation of the carbonyl oxygen increases the electrophilicity of the carbonyl carbon, making it more reactive toward nucleophiles. Weak nucleophiles require protonation before attack.

• Oxonium ion: Formed by protonation

• Carbocation: Stabilized intermediate

Nucleophilic Addition of Cyanide: Cyanohydrin Formation

Hydrogen cyanide (HCN) adds to the carbonyl group of aldehydes and ketones to form cyanohydrins. The reaction is reversible under basic conditions, and cyanohydrins can be hydrolyzed to carboxylic acids.

• Mechanism: Cyanide ion adds to carbonyl carbon, forming a tetrahedral intermediate, which is then protonated.

• Hydrolysis: Cyanohydrins can be converted to carboxylic acids.

The Wittig Reaction

The Wittig reaction converts a carbonyl group (C=O) to an alkene (C=C) by forming two new C–C bonds. The Wittig reagent (ylide) is prepared by SN2 reaction of triphenylphosphine and an alkyl halide, followed by deprotonation with a strong base.

• Ylide: A species with two charged atoms bonded together

• Mechanism: Nucleophilic attack forms oxaphosphetane, elimination of Ph3P=O forms alkene

• Isomer ratio: Both E and Z isomers can form

Addition of Amines: Imine and Enamine Formation

Primary Amines: Imine Formation

Primary amines react with aldehydes and ketones to form imines (Schiff bases) via nucleophilic addition followed by elimination of water. The reaction is fastest under mildly acidic conditions.

• Carbinolamine intermediate: Formed by nucleophilic attack

• Imine: Formed after loss of water

• Application: Chemistry of vision (rhodopsin formation)

Secondary Amines: Enamine Formation

Secondary amines react with aldehydes and ketones to give enamines. Hydrolysis of enamines regenerates the original carbonyl compound.

• Enamine: Formed by nucleophilic addition and elimination

• Hydrolysis: Returns to aldehyde or ketone

Addition of Water and Alcohols: Hydration and Acetal Formation

Hydration

Water adds to the carbonyl group to form hydrates. The equilibrium amount of hydrate decreases as the number of alkyl groups on the carbonyl carbon increases.

• Chloral hydrate: Used as a sedative

Acetal Formation

Alcohols add to aldehydes and ketones to form acetals (from aldehydes) or ketals (from ketones). Two equivalents of alcohol are required, and the reaction is acid-catalyzed.

• Hemiacetal: Intermediate formed after addition of one alcohol

• Acetal: Formed after addition of second alcohol

• Cyclic acetals: Formed from diols

• Acetals as protecting groups: Used to protect carbonyls during synthesis

Hydrolysis of Acetals

Acetals can be hydrolyzed back to aldehydes or ketones by treatment with aqueous acid. The process is reversible and involves conversion of acetal to hemiacetal, then to carbonyl compound.

Cyclic Hemiacetals

Cyclic hemiacetals, also called lactols, are stable five- and six-membered ring compounds formed by intramolecular cyclization of hydroxy aldehydes.

• Formation: Nucleophilic addition of hydroxy group to carbonyl group

• Stability: Five- and six-membered rings are particularly stable