Acetoacetic Ester Synthesis
Acetoacetic ester synthesis
Acetoacetic ester synthesis is a chemical reaction where ethyl acetoacetate is alkylated at the α-carbon to both carbonyl groups and then converted into a ketone, or more specifically an α-substituted acetone. This is very similar to malonic ester synthesis.
Mechanism
A strong base deprotonates the dicarbonyl α-carbon. This carbon is preferred over the methyl carbon because the formed enolate is conjugated and thus resonance stabilized. The carbon then undergoes nucleophilic substitution. When heated with aqueous acid, the newly alkylated ester is hydrolyzed to a β-keto acid, which is decarboxylated to form a methyl ketone.
Deprotonates :Deprotonation is the removal of a proton (H+) from a molecule, forming the conjugate base. The proton removal decreases positive charge in the molecule and an increases negative charge. Deprotonation usually occurs from the donation of electrons or acceptance of the proton using a base, which forms its conjugate acid.
Mechanism of Acetoacetic Ester Synthesis
Step 1
In the presence of mild base such as NaOH or NaOEt, the alpha – hydrogen of the beta-keto ester can be abstracted to produce the carbanion which can resonate to form an enolate. Since the enolate can resonate on either side of the ester and the ketone it is more stabilized and hence use of even mild bases can be made for this reaction.
Step 2 and Step 3
The enolate carbanion thus formed is capable of attacking the alkyl halide R-X as the halide is a good leaving group. This yields the mono-alkylated beta-keto ester (i). However, reaction does not stop there. Since the base and alkyl halide are present in the same solution, step 1 and 2 can repeat in step 3 to produce the disubstituted beta-keto ester (ii).
Note – For step 2 the carbanion shown below can exist as enolates in resonance structures (as shown above) – hence it can be shown using the illustration below or using enolates but with proper arrows indicating movement of electrons.
Step 4
Upon acidification of the solution the esters can undergo hydrolysis to yield the acid. Note – this reaction can happen with both mono (as shown) as well as di-substituted beta keto ester (not shown).
Step 5
Under acidic conditions and slight heating the beta-keto carboxylate can undergo a loss of carbon dioxide to yield either mono (as shown) or disubstituted (not shown) ketone
References
- Smith, Janice Gorzynski. Organic Chemistry: Second Ed. 2008. pp 905–906
- Acetoacetic Ester Synthesis – Alkylation of Enolates | PharmaXChange.info
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Related Reactions
Malonic Ester Synthesis
Synthesis of ketones
Example
