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.[1] The 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.[2]
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.[3] 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
Dialkylation
The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid.
^"Malonic Ester Synthesis". Organic Chemistry Portal. Retrieved 26 October 2007.
^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 1883doi:10.1002/cber.18830160259
February 16, 2023
malonic, ester, synthesis, malonic, ester, synthesis, chemical, reaction, where, diethyl, malonate, another, ester, malonic, acid, alkylated, carbon, alpha, directly, adjacent, both, carbonyl, groups, then, converted, substituted, acetic, acid, major, drawback. 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 1 The 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 2 Malonic ester synthesisReaction type Coupling reactionIdentifiersOrganic Chemistry Portal Malonic ester synthesisRSC ontology ID RXNO 0000107 Contents 1 Mechanism 2 Variations 2 1 Dialkylation 2 2 Cycloalkylcarboxylic acid synthesis 3 Application 4 See also 5 ReferencesMechanism EditThe 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 3 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 EditDialkylation Edit The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid 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 Application EditIn the manufacture of medicines malonic ester is used for the synthesis of barbiturates as well as sedatives and anticonvulsants Used in organic synthesis As a flavoring agent in the food industry See also EditKnoevenagel condensation Acetoacetic ester synthesisReferences Edit House Herbert O 1972 Modern Synthetic Reactions Menlo Park CA W A Benjamin ISBN 0 8053 4501 9 Malonic Ester Synthesis Alkylation of Enolates Malonic Ester Synthesis Organic Chemistry Portal Retrieved 26 October 2007 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 Acetessigather Benzoylessigather und Malonsaureather W H Perkin Jun Berichte der deutschen chemischen Gesellschaft Volume 16 Issue 2 Pages 1787 97 1883 doi 10 1002 cber 18830160259 Retrieved from https en wikipedia org w index php title Malonic ester synthesis amp oldid 1118574641, wikipedia, wiki, book, books, library,
