Acetoacetic ester synthesis template

Ethoxide deprotonates ethyl acetoacetate, the enolate does SN2 on benzyl bromide, acid hydrolysis gives the β-keto acid, and heating loses CO₂ (cyclic six-membered transition state) to the enol of 4-phenylbutan-2-one.

Mechanism step by step

Alkylate ethyl acetoacetate, then hydrolyse and decarboxylate to a methyl ketone

1. Enolate – Ethoxide removes the α-H between the two C=O (pKa ≈ 11)
2. Alkylation (SN2) – The enolate carbon attacks benzyl bromide
3. Hydrolysis – Summarised: the ethyl ester is hydrolysed to the β-keto acid
4. Decarboxylation – Cyclic six-membered transition state: the ketone C=O takes the CO₂H proton as CO₂ leaves
5. Tautomerisation – Summarised: the enol gives the methyl ketone

Key points

• Ethyl acetoacetate is the synthetic equivalent of the acetone enolate ⁻CH₂COCH₃: R–X → R–CH₂–CO–CH₃.
• The doubly activated CH₂ (pKa ≈ 11) is deprotonated completely by NaOEt, so the ketone does not self-condense; a second alkylation gives R¹R²CH–COCH₃.
• Hydrolysis and heating lose CO₂ from the β-keto acid via the enol (see Decarboxylation of a β-keto acid).
• Hot concentrated NaOH instead cleaves the C–C bond (retro-Claisen) to two carboxylates, so dilute acid is used.

Drawn with 164 atoms, 13 arrows, 9 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 25 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 10 Textbook