Malonic ester synthesis

The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha (directly adjacent) to both carbonyl groups, and then converted to a substituted acetic acid.^[1]

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Mechanism

A strong base is required to deprotonate the center proton. The protons alpha to carbonyl groups are easily deprotonated. The malonic ester is especially so by virtue of being adjacent to two carbonyl groups. The carbanion formed can undergo nucleophilic substitution on the alkyl halide, to give the alkylated compound. On heating, the di-ester undergoes thermal decarboxylation, yielding an acetic acid substituted by the appropriate R group.^[2] Thus, the malonic ester can be thought of being equivalent to the ^-CH₂COOH synthon.

The esters chosen are usually the same as the base used, i.e. ethyl esters with sodium ethoxide. This is to prevent scrambling by transesterification.

Variations

Dialkylation

The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid.

Cycloalkylcarboxylic acid synthesis

Intramolecular malonic ester synthesis occurs when reacted with a dihalide.^[3]

See also

• Knoevenagel condensation
• Perkin alicyclic synthesis
• Acetoacetic ester synthesis

References

1. ^ House, Herbert O. (1972). Modern Synthetic Reactions. Menlo Park, CA.: W. A. Benjamin. ISBN 0-8053-4501-9. 
2. ^ Malonic Ester Synthesis. Organic Chemistry Portal. Retrieved on 2007-10-26.
3. ^ Smith, Janice Gorzynski. Organic Chemistry: Second Ed. 2008. pp 905-906