MCAT Organic Chemistry: Aldehydes and Ketones - Nucleophilic Addition Reactions

May 28, 2024

MCAT Organic Chemistry: Aldehydes and Ketones

Presenter: Iman

Chapter Overview

  • Topic: Aldehydes and Ketones
  • Focus: Nucleophilic addition reactions
  • Key Objective: Understanding generalized reaction mechanism of nucleophilic addition to a carbonyl

Key Concepts

Nucleophilic Addition Reaction Mechanism

  • Carbonyl Bond Polarization: Partial positive charge on the carbon, partial negative charge on the oxygen
  • Nucleophilic Attack: Nucleophile forms a covalent bond with the carbon, breaking the ฯ€ bond in the carbonyl
  • Tetrahedral Intermediate: Formed after nucleophilic attack; question if carbonyl can reform based on leaving group

Outcomes Based on Leaving Group Presence

  • No Good Leaving Group (Aldehydes & Ketones): Carbonyl will not reform, oxygen accepts a proton forming an alcohol
  • Good Leaving Group (Carboxylic Acids and Derivatives): Carbonyl double bond can reform, pushing off the leaving group

Hydration of Aldehydes and Ketones

  • Geminal Diols Formation: Reaction with water forms 1,1-diols (geminal diols)
  • Catalysis: Reaction rate can be increased with small amount of acid or base

Acetals and Hemi-Acetals; Ketals and Hemi-Ketals

  • 1 Equivalent Alcohol + Aldehyde: Forms a hemiacetal
  • 1 Equivalent Alcohol + Ketone: Forms a hemiketal
  • 2 Equivalents of Alcohol: Forms acetal (from aldehyde) or ketal (from ketone)
  • Identification: Hemiacetals/hemiketals retain hydroxy group; Acetals/ketals replace it

Reaction Mechanisms

  • Formation Steps: Electrons from ฯ€ bonds are pushed to oxygen, oxygen accepts protons -> product formation

Nitrogen-Based Functional Groups

Imines and Enamines

  • Primary Amine + Aldehyde/Ketone: Forms imine (double bond between carbon and nitrogen)
  • Secondary Amine + Aldehyde/Ketone: Forms enamine (double bond adjacent to nitrogen)
  • Mechanism: Addition followed by elimination (condensation reaction)
  • Examples: Provided of primary vs. secondary amine reactions

Cyanohydrins Formation

Mechanism

  • Hydrogen Cyanide: Classic nucleophile, dissociates to form cyanide anion
  • Attack on Carbonyl Carbon: Forms covalent bond, oxygen accepts electrons and gets protonated -> cyanohydrin formation

Oxidation-Reduction Reactions

Oxidation of Aldehydes

  • Result: Further oxidation forms carboxylic acids
  • Agents: Potassium permanganate, chromium trioxide, hydrogen peroxide, but not PCC

Reduction by Hydride Reagents

  • Result: Aldehydes/Ketones reduced to alcohols
  • Agents: Lithium aluminum hydride (LiAlH4), sodium borohydride (NaBH4)

Summary

  • Objectives Covered: General mechanisms, specific reactions with aldehydes and ketones
  • Next Steps: Practice problems in following video

Note: Additional in-depth content available in Organic Chemistry playlist (Chap 19 for advanced topics)