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15.34: Alkylation of β-Diester Enolates: Malonic Ester Synthesis

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Organic Chemistry

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Alkylation of β-Diester Enolates: Malonic Ester Synthesis

15.34: Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.


The reaction proceeds via abstraction of the acidic α hydrogen from a ꞵ-diester to produce a doubly stabilized enolate ion. The nucleophilic enolate attacks the alkyl halide in an SN2 manner to form an alkylated malonic ester intermediate with a new C–C bond. Further treating the intermediate with aqueous acid or base results in the hydrolysis of the two ester groups to give a 1,3-dicarboxylic acid. The resulting ꞵ-diacid is unstable at high temperatures and readily eliminates CO2 through a cyclic six-membered transition state, forming an enol. The enol tautomerizes to its more stable keto form producing a monosubstituted carboxylic acid. However, a disubstituted carboxylic acid is achieved if the deprotonation and alkylation steps are repeated before hydrolysis and decarboxylation.


Alkylation β-Diester Enolates Malonic Ester Synthesis Carboxylic Acids Diesters Diethyl Malonate Alkyl Halides Enolate Ion Nucleophilic Enolate SN2 Manner Alkylated Malonic Ester Intermediate C-C Bond Formation Hydrolysis Ester Groups 1,3-dicarboxylic Acid Unstable CO2 Elimination Cyclic Six-membered Transition State Enol Tautomerization Keto Form Monosubstituted Carboxylic Acid Disubstituted Carboxylic Acid

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