Malonic Ester Synthesis

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

eg:



reaction 1:



reaction 2:



reaction 3:



reaction 4:



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

eg:



reaction 1:



reaction 2:



reaction 1 (repeat):



reaction 2 (repeat):



reaction 3:



reaction 4:



see also acetoacetic ester synthesis

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