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]
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
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. File:Mechanismus Malonestersynthese V4.svg
Variations
Dialkylation
The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid.[citation needed]
Cycloalkylcarboxylic acid synthesis
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]
Application
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
References
- ↑ 1.0 1.1 "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