Oxygen Containing Compounds - Aldehydes and Ketones


  • nomenclature
    • Aldehyde suffix: -al, -aldehyde.
    • Ketone prefix: keto-, oxo-.
    • Ketone suffix: -one, ketone.
  • physical properties
    • C=O bond is polar, with the carbon partially positive and oxygen partially negative.
    • Dipole-dipole interactions give these molecules higher boiling points than their corresponding alkanes, but not as high as the corresponding alcohols or carboxylic acids.
  • infrared absorption of C=O bond: 1700 cm-1

Important reactions

  • nucleophilic addition reactions at C=O bond
    • acetal, hemiacetal
    • acetal mechanism
      • Aldehydes and ketones react with 1 equivalent of alcohols to make hemiacetals.
      • Aldehydes and ketones react with 2 equivalent of alcohols to make acetals.
      • Hemiketal and ketal are the same as acetals except the starting compound must be a ketone and not an aldehyde. This is an old naming scheme that is no longer used.
    • imine, enamine
    • imine mechanism
    • enamine mechanism
      • Primary amine + aldehyde or ketone = imine.
      • Secondary amine + aldehyde or ketone = enamine.
  • reactions at adjacent positions
    • haloform reactions
    • haloform mechanism
      • Ketones + halogen = halogenation of the alpha position (carbon adjacent to the C=O group).
      • Methyl ketone + halogen = haloform + carboxylate.
      • Trihalogenated methyl = good leaving group.
    • aldol condensation
    • aldol condensation mechanism
      • Occurs because of the acidic alpha proton.
      • 2 acetaldehyde -> aldo.
      • Works for carbonyl compounds with an acidic alpha proton.
    • oxidation: aldehydes oxidize to carboxylic acids. Ketones do not oxidize further.
  • 1,3-dicarbonyls: internal H-bonding
  • intramolecular (internal) bonding
    • 1,3-dicarbonyls have 2 carbonyl groups flanking a carbon atom with an acidic proton.
    • Also referred to as active methylene compounds.
    • Tautomerism causes one of the carbonyls to switch to its enol form, which contains an -OH group that hydrogen bonds with the other carbonyl C=O group on the same molecule. This is called intramolecular (internal) hydrogen bonding.
  • keto-enol tautomerism
  • tautomerism
    • Enol form is the one with the alcohol.
    • Keto form is the one with the ketone.
    • Keto form is more stable, it is the predominant form.
  • organometallic reagents
  • organolithium
    • Organometallic compounds makes R-, which attacks C=O to make R-C-OH.
    • The purpose of organometallic compounds is to make carbon-carbon bonds.
    • R-X + Li -> R-Li (byproduct: LiX)
    • R-X + BuLi -> R-Li (byproduct: Bu-X)
    • R-Li + C=O -> R-C-OH
  • Wolff-Kishner reaction: reduces C=O to -CH2-
  • wolff-kishner mechanism
    • C=O + NH2NH2 -> -CH2- + N2
  • Grignard reagents
  • grignard mechanism
    • Grignard reagents are just like organometallic reagents, they produce R-.
    • R-X + Mg -> R-Mg-X
    • R-Mg-X + C=O -> R-C-OH

General principles

  • effect of substituents on reactivity of C=O; steric hindrance: bulky groups on either side of C=O blocks access to the electrophilic carbon, so reactivity goes down.
  • acidity of alpha H; carbanions
  • acidic alpha H proton
    • Alpha proton is acidic because the resulting carbanion is stabilized by resonance.
  • alpha, beta-unsaturated carbonyls - resonance structures
  • unsaturated carbonyl
    • α,β-unsaturated carbonyl + nucleophile -> addition of the nucleophile at the β position.
    • Nucleophile attacks the beta carbon, pushing the α,β-unsaturated carbonyl into the enol form, which tautomerizes to the original carbonyl.

Old AAMC topics

  • acetoacetic ester syntheses (this topic has been moved to the keto acids and esters section)
  • acetoacetic ester synthesis
  • acetate vs acetoacetate
    • Acetoacetic ester is synthesized by Claisen condensation of ethyl acetate in a process called acetoacetic ester condensation
      • 2 x ethylacetate → ethyl acetoacetate
      • acetoacetic ester = β-keto ester
      • Claisen condensation = 1. alpha proton of ester leaves, 2. the resulting carbanion attacks the carbonyl group of another ester molecule, 3. Carbonyl group reforms and kicks off the alcohol group.
    • "Acetoacetic ester synthesis" is a reaction where acetoacetic ester is used to synthesize a new ketone.
      1. Acidic alpha proton comes off, resulting carbanion attacks new R group.
      2. Hydrolysis of ester turns it into a β-keto carboxylic acid.
      3. β-keto acids undergo decarboxylation because the β-keto group stabilizes the resulting carbanion via enol formation. Enol converts back to keto form, and the net result of this reaction is that an R group is made to attach to the α carbon of acetone.