21.11: Decarboxylation Reactions

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Enolates can act as a nucleophile in S_N2 type reactions. Overall an α hydrogen is replaced with an alkyl group. This reaction is one of the more important for enolates because a carbon-carbon bond is formed. These alkylations are affected by the same limitations as S_N2 reactions previously discussed. A good leaving group, X= chloride, bromide, iodide, tosylate, should be used. Also, secondary and tertiary leaving groups should not be used because of poor reactivity and possible competition with elimination reactions. Lastly, it is important to use a strong base, such as LDA or sodium amide, for this reaction. Using a weaker base such as hydroxide or an alkoxide leaves the possibility of multiple alkylation’s occurring.

Malonic Ester Synthesis

Malonic ester is a reagent specifically used in a reaction which converts alkyl halides to carboxylic acids called the 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.

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

The Acetoacetic Ester Synthesis

The acetoacetic ester synthesis allows for the conversion of ethyl acetoacetate into a methyl ketone with one or two alkyl groups on the alpha carbon.

Steps

1) Deprotonation with ethoxide

2) Alkylation via and SN2 Reaction

3) Hydrolysis and decarboxylation

Addition of a second alky group

After the first step and additional alkyl group can be added prior to the decarboxylation step. Overall this allows for the addition of two different alkyl groups.

Exercise

18. Propose a synthesis for each of the following molecules from this malonic ester.

(a)

(b)

(c)

19. Why can't we prepare tri substituted acetic acids from a malonic ester?

20. Propose a synthesis for the following molecule via a malonic ester.

Answer

18.

(a) 1) Malonic Ester, NaOEt, 2) 4-Methylbenzyl Bromide, 3) Base, 4) Acid, Heat

(b) 1) Malonic Ester, NaOEt, 2) 3-bromohexane, 3) Base, 4) Acid, Eat

19. Malonic esters only contain two acid protons.

20.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Prof. Steven Farmer (Sonoma State University)