Overview
This lecture covers the chemistry of enols and enolates, focusing on their formation, nucleophilicity, reactions (especially halogenation and alkylation), and the acetoacetic ester alkylation process.
Enols and Enolates
- Enols are compounds with an alcohol group attached to a carbon-carbon double bond.
- Enols and their tautomers (keto forms) differ only by the position of hydrogens and electrons.
- Formation of enols involves protonation of a carbonyl oxygen and deprotonation at the alpha carbon.
- Enolates are the conjugate bases of enols, formed by deprotonating alpha hydrogens with a strong base.
- Enolates are resonance-stabilized anions and very good nucleophiles.
Alpha Hydrogens and Acidity
- Alpha hydrogens (adjacent to carbonyl groups) are acidic and can be removed by bases.
- The lower the pKa, the more acidic the hydrogen and more enolate forms.
- Compounds with two carbonyls (like beta-dicarbonyls) have more acidic alpha hydrogens.
- Esters and amides have less acidic alpha hydrogens due to resonance from oxygen/nitrogen.
Halogenation of Carbonyl Compounds
- Enolates react with halogens (e.g., Br2), leading to halogenation at the alpha carbon.
- Basic conditions make controlling mono-halogenation hard; multiple halogenations occur.
- Over-halogenation can lead to Haloform reactions, creating carboxylic acids and haloforms like chloroform and bromoform.
- Acidic halogenation (using enols not enolates) is better for controlled mono-halogenation.
Alkylation of Enolates
- Enolates react with alkyl halides in SN2 reactions to form new C–C bonds (alkylation).
- Primary or methyl alkyl halides are preferred; secondary/tertiary lead to unwanted side reactions (E2).
- Enolates can react at either the oxygen or the carbon, leading to product mixtures unless conditions are controlled.
Acetoacetic Ester Alkylation
- Acetoacetic ester (ethyl acetoacetate) has very acidic alpha hydrogens due to two carbonyls.
- Complete enolate formation occurs with sodium ethoxide base.
- Alkylation can be done once or twice by adding different alkyl halides in steps.
- Final product is converted to a methyl ketone by hydrolysis and decarboxylation (loss of CO₂).
Key Terms & Definitions
- Alpha Hydrogen — hydrogen attached to the carbon adjacent to a carbonyl group.
- Enol — a compound with a hydroxyl group bonded to a carbon with a double bond.
- Enolate — resonance-stabilized anion formed by deprotonating an alpha hydrogen of a carbonyl compound.
- Tautomer — isomers that differ by the placement of a proton and electrons.
- Halogenation — addition of a halogen atom (Cl, Br, etc.) to a molecule.
- Haloform Reaction — formation of a trihalomethane and carboxylic acid from a carbonyl compound under basic conditions.
- Alkylation — substitution reaction where an alkyl group is introduced.
- Acetoacetic Ester — ethyl acetoacetate, a beta-keto ester used in alkylation reactions.
Action Items / Next Steps
- Review aldol and Claisen reactions in the upcoming episode.
- Revise key mechanisms: enol/enolate formation, halogenation, and acetoacetic ester alkylation.
- Practice problems on controlling mono- vs. poly-halogenation and SN2 alkylation conditions.