Nucleophilic Addition Reactions to Aldehydes and Ketones

Overview

• Nucleophilic addition to aldehydes and ketones forms hydrates, also known as geminal diols.
• Reaction involves the addition of water to the carbonyl group.
• Reaction is at equilibrium.

Mechanism

• Polarization of Carbonyl:

  • Oxygen (more electronegative) withdraws electron density from carbon.
  • Carbonyl carbon becomes partially positive (electrophilic).

• Nucleophile Attack:

  • Water acts as a nucleophile with lone pairs on the oxygen.
  • Oxygen attacks the carbonyl carbon, transferring pi electrons to carbonyl oxygen.
  • Formation of an intermediate negatively charged oxygen.

• Acid-Base Reaction:

  • Water molecule donates H+ to intermediate to form final hydrate.

Reaction Equilibrium

• Formaldehyde:

  • Equilibrium favors hydrate formation.
  • Highly polarized carbonyl and low steric hindrance.

• Acetone (Ketone):

  • Equilibrium favors ketone.
  • Ketones are less reactive due to steric hindrance.

• Acetaldehyde:

  • Similar mechanism; aldehydes generally more reactive than ketones.

Enhancing Reactivity

• Electron Withdrawal:

  • Adding electronegative atoms (e.g., halogens) to adjacent carbon enhances reactivity.
  • Increases electrophilicity of carbonyl carbon.

• Example:

  • Addition of chlorines increases partial positive charge.
  • Trichloroacetaldehyde forms chloral hydrate ("knockout drops").

Special Note

• Chloral hydrate has historical significance as a sedative ("slip someone a Mickey Finn").

• Understanding the balance of equilibrium and how electron withdrawing groups affect reactivity is crucial for predicting the outcome of these reactions.
• The mechanism highlights how nucleophile-electrophile interactions drive the formation of hydrates from carbonyl compounds.