Acetoacetic ester synthesis is a chemical reaction where
ethyl acetoacetate
The organic compound ethyl acetoacetate (EAA) is the ethyl ester of acetoacetic acid. It is a colorless liquid. It is widely used as a chemical intermediate in the production of a wide variety of compounds. It is used as a flavoring for food.
Pr ...
is alkylated at the α-carbon to both carbonyl groups and then converted into a ketone, or more specifically an α-substituted
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscible wi ...
. This is very similar to
malonic ester synthesis
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. The major ...
.
:
Mechanism
A strong base deprotonates the dicarbonyl α-carbon. This carbon is preferred over the methyl carbon because the formed
enolate
In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds.
Bonding and structure
Enolate anions are electr ...
is
conjugated and thus
resonance
Resonance describes the phenomenon of increased amplitude that occurs when the frequency of an applied periodic force (or a Fourier component of it) is equal or close to a natural frequency of the system on which it acts. When an oscillat ...
stabilized. The carbon then undergoes nucleophilic substitution. When heated with aqueous acid, the newly alkylated ester is
hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
to a β-keto acid, which is
decarboxylated to form a methyl ketone.
Acetoacetic Ester Synthesis – Alkylation of Enolates , PharmaXChange.info
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Double deprotonation of ethyl acetoacetate
The classical acetoacetatic ester synthesis utilizes the 1:1 conjugate base. Ethyl acetoacetate is however diprotic:[
:CH3C(O)CH2CO2Et + NaH → CH3C(O)CH(Na)CO2Et + H2
:CH3C(O)CH(Na)CO2Et + BuLi → LiCH2C(O)CH(Na)CO2Et + BuH
The dianion (i.e., LiCH2C(O)CH(Na)CO2Et) adds electrophile to the terminal carbon as depicted in the following simplified form:]
See also
* Malonic ester synthesis
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. The major ...
References
{{Reflist
Organic reactions
Carbon-carbon bond forming reactions