Malonic ester synthesis template

Ethoxide deprotonates diethyl malonate, the enolate does SN2 on 1-bromobutane, acid hydrolysis gives butylmalonic acid, and heating loses CO₂ through a cyclic six-membered transition state to give hexanoic acid.

Mechanism step by step

Deprotonate, alkylate, hydrolyse and decarboxylate: R–X becomes R–CH₂–COOH

1. Enolate – Ethoxide removes the doubly activated α-H (pKa ≈ 13); the charge spreads onto both C=O
2. Alkylation (SN2) – The anion attacks the CH₂Br carbon; bromide leaves
3. Hydrolysis – Summarised: both esters are hydrolysed (see Acid-catalysed ester hydrolysis)
4. Decarboxylation – Concerted, through a cyclic six-membered transition state: C=O takes the H of the other CO₂H
5. Tautomerisation – Summarised: the enol of the acid gives the carboxylic acid

Key points

• The CH₂ between two esters is acidic (pKa ≈ 13), so NaOEt deprotonates it fully; the ethoxide matches the ethyl esters, so ester exchange does no harm.
• The alkylation is SN2: methyl, primary, allylic and benzylic halides work. A second deprotonation and alkylation before hydrolysis gives R¹R²CH–COOH.
• Only a 1,3-dicarbonyl acid loses CO₂ on heating: the second C=O accepts the proton in a cyclic six-membered transition state, giving an enol.
• Diethyl malonate is the synthetic equivalent of the ⁻CH₂COOH synthon: R–X → R–CH₂–COOH (two carbons added).

Drawn with 153 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