Lecture Notes: Reactions of Aldehydes and Ketones with Alcohols

Formation of Hemiacetals and Acetals

• Reactions of Aldehydes with Alcohols:
  • Reacting an aldehyde with an alcohol in the presence of an acid catalyst produces a hemiacetal.
  • In a hemiacetal, there is an OR group and an OH group.
• Formation of Acetals:
  • The hemiacetal can react further with another alcohol molecule under acidic conditions to form an acetal, which contains two OR groups.
  • This reaction is reversible; reacting an acetal with H3O+ can regenerate the aldehyde.

Mechanism for Acetal Formation

1. Protonation:
   • The reaction starts with the protonation of the carbonyl oxygen, making the carbonyl carbon more electrophilic.
2. Nucleophilic Attack:
   • Methanol attacks the electrophilic carbonyl carbon, breaking the carbon-oxygen double bond and forming a structure with an OH group and a positively charged oxygen.
3. Deprotonation and Rearrangement:
   • A methanol molecule acts as a weak base to remove a hydrogen from the positively charged oxygen, resulting in a hemiacetal.
   • The OH group is turned into a good leaving group by protonation, leading to the formation of water which can leave the structure.
4. Formation of Acetal:
   • Another methanol molecule attacks the electrophilic carbon, resulting in the formation of a second OR group.
   • Final deprotonation gives the acetal.

Reaction with Cyclic Ketones

• Example:
  • When reacting a cyclic ketone with methanol under acidic conditions, the reaction can proceed to form an acetal with two OR groups.
  • The reverse reaction with H3O+ regenerates the original ketone.

Use of Protecting Groups in Reactions

• Ethylene Glycol as a Protecting Group:
  • Ethylene glycol has two alcohol groups and can react with ketones to form cyclic acetals, serving as a protecting group.
• Application in Selective Reduction:
  • Protecting groups allow selective reactions, such as reducing an ester to an alcohol without affecting a ketone.
  • Example: Use ethylene glycol to protect a ketone, then react with lithium aluminum hydride to reduce the ester, and finally remove the protecting group with H3O+ to restore the ketone.
• Reactivity Considerations:
  • Ketones are more reactive than esters, allowing selective protection and reduction strategies.
  • Sodium borohydride cannot reduce esters but lithium aluminum hydride can.

These notes summarize the key concepts and mechanisms discussed in the lecture, focusing on the chemistry of hemiacetals, acetals, and the use of cyclic diols as protecting groups in organic synthesis.