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4. Enolates & the Aldol Reaction

The hydrogens next to a carbonyl — the α hydrogens — are acidic (pKa ~19–20). Removing one gives an enolate, a carbon nucleophile that builds C–C bonds: the aldol and Claisen reactions are the two great enolate reactions.

Enolate Formation

LDA (lithium diisopropylamide) is the standard base: strong, bulky, and non-nucleophilic, it deprotonates cleanly at −78 °C to give the kinetic enolate.

The Aldol Reaction

Example: Two molecules of acetaldehyde (NaOH, cold) undergo aldol addition to 3-hydroxybutanal; on heating, it dehydrates to but-2-enal (crotonaldehyde) — the aldol condensation product. $$\text{CH}_3\text{CHO} + \text{CH}_3\text{CHO} \rightarrow \text{CH}_3\text{–CH(OH)–CH}_2\text{–CHO} \xrightarrow{\Delta} \text{CH}_3\text{–CH=CH–CHO}$$

The Claisen Condensation

Two esters condense (alkoxide base) into a β-keto ester: ethyl acetate → ethyl acetoacetate. The malonic ester synthesis uses the same idea to build substituted carboxylic acids — alkylate, hydrolyze, decarboxylate.

Practice Problems

  1. What is the self-aldol product of acetone (addition only)?
  2. What β-keto ester forms from self-Claisen of ethyl propanoate?
  3. Why is LDA the base of choice for enolate formation?
  4. Diethyl malonate + CH3I, then hydrolysis and decarboxylation, gives what acid?

Answers: 1. 4-hydroxy-4-methyl-2-pentanone (diacetone alcohol)   2. Ethyl 2-methyl-3-oxopentanoate   3. Strong and bulky — it deprotonates without attacking the carbonyl   4. Propanoic acid

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