Malonic Ester Synthesis
- Last updated
- Jan 23, 2023
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- 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:
Malonic Ester Synthesis
Due to the fact that Malonic ester’s α hydrogens are adjacent to two carbonyls, they can be deprotonated by sodium ethoxide (NaOEt) to form Sodio Malonic Ester.
Because Sodio Malonic Ester is an enolate, it can then be alkylated with alkyl halides.
After alkylation the product can be converted to a dicarboxylic acid through saponification and subsequently one of the carboxylic acids can be removed through a decarboxylation step.
Mechanism
1) Saponification
2) Decarboxylation
3) Tautomerization
All of the steps together form the Malonic ester synthesis.
RX \rightarrow RCH_2CO_2H
Example
- Gamini Gunawardena from the OChemPal site (Utah Valley University)
