Formation of Hemiacetals from Aldehydes and Ketones

Overview

• Previous video discussed making hydrates from aldehydes and ketones.
• Current focus: forming hemiacetals by adding alcohol instead of water.
• Reaction at equilibrium, product is a hemiacetal.

Mechanism

• Similar to hydrate formation.
• Carbonyl Group:
  • Oxygen is more electronegative—withdraws electron density from the carbonyl carbon.
  • Carbonyl carbon is electrophilic (partially positive).
• Alcohol as Nucleophile:
  • Lone pair of electrons on oxygen attacks the carbonyl carbon.
  • Pi electrons from carbonyl move onto oxygen.

Steps of Reaction

1. Nucleophilic Attack:
   • Alcohol molecule attacks carbonyl carbon.
   • New bond forms between oxygen (alcohol) and carbon (carbonyl).
   • Intermediate forms with oxygen carrying a +1 formal charge.
2. Deprotonation:
   • Another alcohol molecule acts as a base.
   • Takes proton, leaving electrons on oxygen.
   • Removes the +1 formal charge from oxygen.
3. Final Steps:
   • Another alcohol molecule donates a proton.
   • Electrons rearrange to form hemiacetal.
   • For a ketone: R prime group replaces hydrogen.

Equilibrium Considerations

• Generally favors formation of aldehyde/ketone.
• Exception: Intra-molecular hemiacetal formation (5/6-membered rings) shifts equilibrium to the right, forming cyclic hemiacetal.

Intramolecular Hemiacetal Formation

• Cyclic Reaction:
  • Alcohol and aldehyde within the same molecule react.
  • Nucleophilic oxygen attacks carbonyl carbon.
  • Forms cyclic hemiacetal.
  • Important in carbohydrate chemistry.

Example Mechanism

• Number carbons to follow process:
  • Oxygen swings around to attack carbonyl carbon.
• Conformational Change:
  • Rotation of sigma bonds allows nucleophilic attack.
  • Formation of a ring structure.

Two Possible Outcomes

1. Oxygen Equatorial:
   • Oxygen moves up in the plane.
   • Deprotonation and protonation steps follow.
2. Oxygen Axial:
   • Oxygen moves down relative to the plane.
   • Forms a different stereoisomer.

Importance in Carbohydrate Chemistry

• Formation of cyclic hemiacetals crucial in biochemistry.
• Chirality at Carbon 1 (Anomeric Carbon):
  • Anomers differ based on OH group position (up/down).
  • Essential for understanding glucose and carbohydrate chemistry.

Conclusion

• Understanding hemiacetal formation is vital for further exploration of biochemical processes, especially related to carbohydrates.
• Further videos will cover acid/base catalysis and more detailed carbohydrate chemistry.