Malonic ester synthesis
Malonic ester synthesis | |||||||||||||||
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Reaction type | Coupling reaction | ||||||||||||||
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Temperature | +Δ[1]
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Organic Chemistry Portal | malonic-ester-synthesis | ||||||||||||||
RSC ontology ID | RXNO:0000107 | ||||||||||||||
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.[2]
![Reaction formula](http://up.wiki.x.io/wikipedia/commons/thumb/8/8e/Malonic_ester_synthesis_equation_formula.svg/595px-Malonic_ester_synthesis_equation_formula.svg.png)
A major drawback of malonic ester synthesis is that the alkylation stage can also produce dialkylated structures. This makes separation of products difficult and yields lower.[3]
Mechanism
[edit]The carbons alpha to carbonyl groups can be deprotonated by a strong base. 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.[1] 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
[edit]Dialkylation
[edit]The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid.[citation needed]
![](http://up.wiki.x.io/wikipedia/commons/thumb/4/4f/Dialkylation_malonic_ester_synthesis_mechanism.png/800px-Dialkylation_malonic_ester_synthesis_mechanism.png)
Cycloalkylcarboxylic acid synthesis
[edit]Intramolecular malonic ester synthesis occurs when reacted with a dihalide.[4][5] This reaction is also called the Perkin alicyclic synthesis (see: alicyclic compound) after investigator William Henry Perkin, Jr.[6]
![](http://up.wiki.x.io/wikipedia/commons/thumb/d/d1/Cycloalkylcarboxylic_acid_mechanism.png/800px-Cycloalkylcarboxylic_acid_mechanism.png)
Application
[edit]In the manufacture of medicines, malonic ester is used for the synthesis of barbiturates, as well as sedatives and anticonvulsants.
Used in organic synthesis.
See also
[edit]References
[edit]- ^ a b "Malonic Ester Synthesis". Organic Chemistry Portal. Retrieved 26 October 2007.
- ^ House, Herbert O. (1972). Modern Synthetic Reactions. Menlo Park, CA.: W. A. Benjamin. ISBN 0-8053-4501-9.
- ^ Malonic Ester Synthesis – Alkylation of Enolates
- ^ Smith, Janice Gorzynski. Organic Chemistry: Second Ed. 2008. pp. 905–906
- ^ Using the non-selective nature of malonic ester synthesis to produce cyclic compounds
- ^ Ueber die Einwirkung von Trimethylenbromid auf Acetessigäther, Benzoylessigäther und Malonsäureäther W. H. Perkin Jun. Berichte der deutschen chemischen Gesellschaft Volume 16 Issue 2, Pages 1787–97 1883 doi:10.1002/cber.18830160259