Malonic ester synthesis is a synthetic procedure used to convert a compound that has the general structural formula 1 into a carboxylic acid that has the general structural formula 2.
- R1 = alkyl group
- L = leaving group
The group —CH2CO2H in 2 is contributed by a malonic ester, hence the term malonic ester synthesis.
- R2 = alkyl, aryl
Malonic ester synthesis consists of four consecutive reactions that can be carried out in the same pot.
- reaction 1: acid-base reaction
- reaction 2: nucleophilic substitution
- reaction 3: ester hydrolysis (using saponification)
- reaction 4: decarboxylation
A more direct method to convert 3 into 4 is the reaction of 3 with the enolate ion (5) of ethyl acetate followed by hydrolysis of the resultant ester.
However, the generation of 5 from ethyl acetate quantitatively in high yield is not an easy task because the reaction requires a very strong base, such as LDA, and must be carried out at very low temperature under strictly anhydrous conditions.
Malonic ester synthesis provides a more convenient alternative to convert 3 to 4. Malonic ester synthesis can be adapted to synthesize compounds that have the general structural formula 6.
- R3, R4 = identical or different alkyl groups
reaction 1 (repeat):
reaction 2 (repeat):
see also acetoacetic ester synthesis