Oxygen Containing Compounds - Aldehydes and Ketones

Description

• 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
  • 
    • 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
  • 
  • 
    • Primary amine + aldehyde or ketone = imine.
    • Secondary amine + aldehyde or ketone = enamine.
• reactions at adjacent positions
  • haloform reactions
  • 
    • 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
  • 
    • 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
• 
  • 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
• 
  • 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
• 
  • 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-
• 
  • C=O + NH₂NH₂ -> -CH₂- + N₂
• Grignard reagents
• 
  • 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
• 
  • Alpha proton is acidic because the resulting carbanion is stabilized by resonance.
• alpha, beta-unsaturated carbonyls - resonance structures
• 
  • 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.

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Old AAMC topics

• acetoacetic ester syntheses (this topic has been moved to the keto acids and esters section)
• 
• 
  • 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.