15.3
Types of Enols and Enolates
Aldehydes and ketones form enols, although only about 1% of the enol is present at the equilibrium for simple monocarbonyl compounds. The enol form is…
Enols and enolates vary in their stability. Enols from monocarbonyls are the least stable at equilibrium. However, enols formed in the absence of acid or base are kinetically stable, as they revert to their keto forms very slowly.
Enolate ions of β-dicarbonyl compounds, like β-diketones, β-ketoesters, and β-diesters, are thermodynamically stable because they are doubly resonance-stabilized by the adjacent carbonyls. The enols of such compounds are stabilized by intramolecular hydrogen bonding.
Phenols, which predominantly exist in the aromatic enol form, are the most stable enols.
Two types of regioisomeric enols are possible for unsymmetrical ketones. Carbonyls without an α hydrogen cannot be enolized.
Since α-hydrogen acidity is proportional to enolate stability, esters, acyl cyanides, and tertiary amides form less stable enols.
Primary or secondary amides and carboxylic acids do not form typical enolates, as deprotonation first happens at the acidic proton on nitrogen or oxygen.
View the full transcript and gain access to JoVE Core videos
Q1: Why are enols from simple monocarbonyl compounds so unstable?
Enols from monocarbonyls are thermodynamically unstable because the C=C double bond has lower bond energy than the C=O carbonyl group. For example, acetone contains only 1.5 × 10−4% enol at equilibrium, and cyclohexanone contains only 1.2%. However, these enols are kinetically stable and revert to their keto forms very slowly in the absence of acid or base.
Q2: What makes β-dicarbonyl compounds have significantly more enol at equilibrium?
β-Dicarbonyl compounds like pentane-2,4-dione exist as 76–80% enol due to two stabilizing factors: extended delocalization of the conjugated double bond with the adjacent carbonyl group, and intramolecular hydrogen bonding between the enolic hydroxyl and carbonyl oxygen forming a stable 6-membered ring. The enolate ions of β-dicarbonyls are doubly resonance-stabilized by both adjacent carbonyls.
Q3: How do primary and secondary amides differ from other carbonyl compounds in enolization?
Primary and secondary amides do not form typical enolates because the N–H proton is preferentially deprotonated over the α-carbon proton. Instead, amides form enamines, the nitrogen analogs of enols. When enamines are treated with strong base, aza-enolates form. Amides are the least enolizable among acid derivatives due to this competing deprotonation pathway.
Q4: What are regioisomeric enols and why do they form from unsymmetrical ketones?
Unsymmetrical ketones can form two types of regioisomeric enols because deprotonation can occur at either α-hydrogen position. Their combined enol composition totals approximately 1% at equilibrium. Additionally, in acyclic ketones, the enol or enolate can exist as either (E) or (Z) geometrical isomers, and protonation on the same face of each isomer produces enantiomers in solution.
Q5: Why are phenols the most stable enols?
Phenols are the most stable enols because they predominantly exist in the aromatic enol form. The aromatic ring provides exceptional stabilization through resonance delocalization, making the enol form the thermodynamically favored tautomer. This contrasts sharply with simple monocarbonyl enols, which are highly unstable and present in negligible amounts at equilibrium.
Q6: How does α-hydrogen acidity relate to enolate stability?
α-Hydrogen acidity is proportional to enolate stability. Esters, acyl cyanides, and tertiary amides form less stable enols because their α-hydrogens are less acidic. For example, acetone (pKa 19.2) and acetaldehyde (pKa 17) have more acidic α-hydrogens than acetonitrile (pKa 25) and ethyl acetate (pKa 25), resulting in more stable enolates for the former compounds.
Q7: Which carbonyl compounds cannot be enolized and why?
Carbonyls without an α-hydrogen cannot be enolized because enolization requires removal of an α-proton. Additionally, carboxylic acids do not form typical enolates; instead, the acidic carboxylic proton is preferentially deprotonated. Nonenolizable aldehydes require alternative reaction pathways, such as the Cannizzaro reaction, for their transformations.