Aldehydes and Ketones - Part 1 | Organic Chemistry 2

Aldehydes and ketones are studied in this chapter: nomenclature and properties of carbonyls, synthesis of aldehydes and ketones, nucleophilic addition reactions, addition of water, addition of alcohols, formation of hemiacetals and acetals, acetals as protecting groups, cyclic hemiacetals

Nomenclature of Carbonyls

Name: the -ane ending of the corresponding alkane is replace by -al (aldehyde) or by -one (ketone)

The rules for naming alcohols  also apply to carbonyls, except that it is not necessary to specify the position of the aldehyde ⇒ always carbon 1
Carbaldehyde: aldehyde functional group is attached to a ring and the carbon of -CHO is carbon 1
Cycloalkanones: ketone functional group is part of the ring and carbon of the CO is carbon 1


Aldehydes and ketones take precedence over alcohols, alkenes and alkynes. Aldehydes takes precedence over ketones. If aldehydes or ketones do not have priority, the prefixes formyl- (aldehyde) and acyl- (ketone) or oxo- (ketone in the presence of an aldehyde) must be used


Properties of Carbonyls

Physical properties:

  • Polarity: the carbonyl bond (C=O) is short, strong and highly polar due to the electronegativity difference between carbon and oxygen ⇒ significant dipole moment.
  • Solubility: aldehydes and ketones are soluble in organic solvents. Molecules with fewer than 6 carbons are soluble in water favored by the formation of hydrogen bonds.
  • Boiling and melting points: higher than nonpolar alkanes due to the presence of dipole-dipole interactions.


Geometry and orbitals: 

The carbon of the C=O bond of carbonyls is sp2 hybridized ⇒ trigonal planar geometry.

Absorption spectroscopy: 

  • 1H NMR: δ ~ 9-10 ppm
    Highly deshielded sp2 hybridized C-H proton of aldehydes (downfield absorption).
  • 13C NMR: δ ~ 190-220 ppm
    Highly deshielded carbonyl carbon.
  • IR absorptions: 1700-1750 cm-1 (intense band, C=O stretching), 2700-2850 cm-1 (aldehydic C-H).


Reactivity of carbonyls:

  • Nucleophilic addition: the carbonyl carbon is electrophilic and susceptible to nucleophilic addition reactions.
  • Deprotonation: the protons on the α carbon of a carbonyl group are acidic and can be abstracted to form an enolate ion.

Synthesis of Aldehydes and Ketones

Preparation of aldehydes:

  • Oxidation of primary alcohols with PCC:

  • Ozonolysis of alkenes

  • Hydroboration-oxidation of terminal alkynes

  • Reduction of esters and acid chlorides


Preparation of ketones:

  • Oxidation of secondary alcohols:

  • Ozonolysis of alkenes:

  • Acid-catalyzed hydration of terminal alkynes:

  • Friedel-Crafts acylation:

  • Reaction of acid chlorides with organocuprates

Nucleophilic Addition Reactions

Nucleophilic addition reactions:

Aldehydes are more reactive toward nucleophilic attack than ketones due to:

  • Steric effects: a ketone has 2 alkyl groups that contribute to steric hindrance in the transition state of a nucleophilic attack.
  • Electronic effects: a ketone has 2 electron-donating alkyl groups that stabilize the δ+ on the carbon atom of the carbonyl group.


  • Under basic conditions: 
  1. Nucleophilic attack on the carbonyl group to form a tetrahedral intermediate.
  2. Protonation of the tetrahedral intermediate.


  • Under acidic conditions: 
  1. Protonation of the carbonyl group, making it even more electrophilic.
  2. Nucleophilic attack on the carbonyl group.


Addition of Water

Hydrate formation:


Reversible reaction. The equilibrium generally favors the carbonyl group, except in the case of very simple aldehydes, or ketones with strong electron-withdrawing substituents.

  • Base-catalyzed hydration:
  1. Nucleophilic attack by hydroxide to form a tetrahedral intermediate.
  2. Protonation of the tetrahedral intermediate by water to form the hydrate.


  • Acid-catalyzed hydration:
  1. Protonation of the carbonyl group, making it even more electrophilic.
  2. Nucleophilic attack by water to form a tetrahedral intermediate.
  3. Deprotonation of the tetrahedral intermediate by water to form the hydrate.

Addition of Alcohols

Formation of a hemiacetal:


Same mechanism as acid-catalyzed hydration, H2O is replaced by ROH.

  1. Protonation of the carbonyl group, making it even more nucleophilic.
  2. Nucleophilic attack by the alcohol to form a tetrahedral intermediate.
  3. Deprotonation of the tetrahedral intermediate by a weak base (e.g., the alcohol) to form a hemiacetal.

It is very difficult to isolate a hemiacetal unless it is a cyclic hemiacetal.


Formation of an acetal:


  1. Formation of the hemiacetal intermediate under acidic conditions.
  2. Protonation of the hydroxyl group, converting it into an excellent leaving group.
  3. Loss of water, to re-form the carbonyl bond.
  4. Nucleophilic attack by a second molecule of alcohol to form a tetrahedral intermediate.
  5. Deprotonation of the tetrahedral intermediate by a weak base (e.g., the alcohol) to form an acetal.



Equilibrium of acetal formation:

Acetal formation is governed by an equilibrium ⇒ reversible reaction.

  • Aldehydes: the equilibrium favors formation of the acetal.
  • Ketones: the equilibrium favors the reactants rather than acetal formation. Removal of H2O drives the equilibrium to favor the products (according to Le Chatelier's principle). A Dean-Stark trap is used for this.

Acetals as Protecting Groups

Aldehyde and ketone protecting groups:

Acetals are widely used as protecting groups for carbonyl-containing functional groups because they are:

  • Easy to add ⇒ acetal is formed under mild reaction conditions using an acid catalyst.
  • Easy to remove ⇒ acetal formation is reversible under mild aqueous acidic conditions.
  • Stable to a wide variety of reaction conditions ⇒ no reaction with base, oxidizing agents (e.g., LiAlH4) or nucleophiles (e.g., RMgX).

1,2-ethanediol is typically used to form a cyclic acetal:


Overall process:

  1. Protect the interfering aldehyde or ketone carbonyl.
  2. Perform the desired reaction (e.g., reduction).
  3. Remove the acetal protecting group with aqueous acid.

Cyclic Hemiacetals

Cyclic hemiacetal:

A cyclic compound formed by the intramolecular reaction between a carbonyl and a hydroxyl group within the same molecule. This reaction results in the closure of a ring in which the carbonyl carbon is bonded to the hydroxyl oxygen, forming a hemiacetal functional group.
Cyclic hemiacetals containing five- and six-membered rings are stable compounds.


Cyclic hemiacetal formation:



Acid-catalyzed intramolecular cyclization of hydroxy aldehydes.

  1. Protonation of the carbonyl group, making it even more nucleophilic.
  2. Intramolecular nucleophilic attack by the hydroxyl group of the molecule.
  3. Deprotonation of the tetrahedral intermediate to form neutral cyclic hemiacetal.

This reaction is important in the formation of carbohydrates (e.g., glucose exists primarily as a cyclic hemiacetal).

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Aldehydes have a carbonyl group (C=O) that is bonded to at least one hydrogen atom and one other carbon-containing group, while ketones have their carbonyl group bonded to two carbon-containing groups. This structural difference affects their physical properties and reactivity; for example, aldehydes are typically more reactive in nucleophilic addition reactions than ketones due to less steric hindrance and a greater partial positive charge on the carbonyl carbon.

Carbonyl compounds, which include aldehydes and ketones, are generally polar due to the presence of a polar carbon-oxygen double bond. The electronegativity difference between the carbon and oxygen atoms causes a dipole moment, with the oxygen atom carrying a partial negative charge and the carbon atom bearing a partial positive charge. This polarity allows carbonyl compounds to engage in dipole-dipole interactions and hydrogen bonding with other molecules, influencing their physical properties such as boiling point and solubility.

The electrophilicity of the carbonyl group is a central feature of its chemical reactivity, especially in nucleophilic addition reactions. The partial positive charge on the carbon atom, due to its double bond with the more electronegative oxygen atom, makes it an attractive target for nucleophiles. This electrophilic character allows carbonyl compounds to undergo a wide variety of nucleophilic addition reactions, including the formation of hydrates, hemiacetals, and acetals.

Aldehydes can be synthesized by oxidation of primary alcohols through a reaction which typically involves a mild oxidizing agent such as PCC (pyridinium chlorochromate) in dichloromethane. It is important to control the reaction conditions to prevent further oxidation to a carboxylic acid, which is why milder oxidizing agents are preferred over stronger ones like potassium permanganate or chromium trioxide for this transformation.

Ketones can be synthesized using several methods, including:

  • Oxidation of secondary alcohols, where a secondary alcohol is treated with an oxidizing agent such as chromic acid or pyridinium chlorochromate (PCC).
  • Friedel-Crafts acylation, in which an aromatic compound reacts with an acyl chloride in the presence of a Lewis acid catalyst like aluminum chloride to form an aromatic ketone.
  • Ozonolysis of alkenes, where the carbon-carbon double bond of an alkene is cleaved using ozone, followed by reductive workup.

Nucleophilic addition reactions are characteristic of carbonyl compounds because the carbonyl group consists of a carbon atom double-bonded to an oxygen atom, creating a polar bond. This polarization makes the carbon atom electrophilic (electron-poor), rendering it susceptible to attack by nucleophiles (electron-rich species). Additionally, the planar structure of the carbonyl group allows for the approach of nucleophiles from either side, leading to the possibility of stereoisomerism in products when the carbonyl carbon is chiral.

When a nucleophile attempts to add to a carbonyl group in aldehydes or ketones, large substituents around the carbonyl can hinder the approach of the nucleophile, making the reaction slower or less likely to occur compared to carbonyls with smaller substituents. In particular, ketones are generally less reactive towards nucleophilic additions than aldehydes because of the additional alkyl group on the ketone that provides greater steric hindrance than the hydrogen in aldehydes.

The addition of water to aldehydes and ketones is known as hydration and typically results in the formation of a hydrate, which is a geminal diol. In this reaction, water acts as a nucleophile and adds to the carbonyl carbon. The oxygen of the carbonyl group then picks up a proton from water, leading to a 1,1-diol. This reaction is reversible and often favors the aldehyde or ketone in most cases, except when the reaction is catalyzed under acidic or basic conditions or involves highly electrophilic carbonyl compounds.

The addition of alcohols to aldehydes and ketones to form hemiacetals and acetals involves nucleophilic addition followed by a dehydration step. Initially, the lone pair on the alcohol's oxygen attacks the electrophilic carbonyl carbon, resulting in the formation of a tetrahedral intermediate. Proton transfer within the intermediate gives rise to a hemiacetal. In acid-catalyzed conditions, a second molecule of alcohol can react with the hemiacetal, leading to another nucleophilic addition and subsequent loss of water to form an acetal. The presence of an acid catalyst is crucial to protonate the oxygen atoms, making them good leaving groups and activating the carbonyl for attack.

Acetals are useful as protecting groups in organic synthesis because they are stable under basic and neutral conditions but can be converted back to the carbonyl group under acidic conditions. This selective stability allows chemists to modify other parts of the molecule without affecting the carbonyl group. The acetal protection is particularly useful when a molecule with a carbonyl group must undergo reactions that would otherwise react with the carbonyl, such as Grignard reactions or reductions.

Acetals can be selectively hydrolyzed back to aldehydes or ketones using aqueous acid. The acid acts as a catalyst, protonating the acetal oxygen, which increases the electrophilic character of the carbonyl carbon, making it more susceptible to nucleophilic attack by water. This results in the formation of a hemiacetal intermediate, which can then be further hydrolyzed to yield the free aldehyde or ketone along with two equivalents of alcohol.

Cyclic hemiacetals are more stable than acyclic hemiacetals primarily due to the ring strain being relieved when forming a five or six-membered ring. These ring sizes are energetically favorable because they reduce the torsional strain and allow the atoms to adopt a near-ideal tetrahedral geometry. Furthermore, intramolecular reactions, which lead to the formation of cyclic hemiacetals, are more favorable compared to intermolecular reactions because they benefit from the "chelation effect," where a molecule forms two or more bonds to the same metal ion, stabilizing the structure.