Dr. Satish S. Kola discusses organic synthesis via enolates, specifically focusing on ethyl acetoacetate. Ethyl acetoacetate is prepared through the heating of ethyl acetate with sodium ethoxide followed by acidification. It undergoes Claisen condensation, forming an alcohol and β-keto ester. Ethyl acetoacetate displays properties of both the keto and enol forms. It is acidic, forming salts when treated with bases through the ionization of the methylene hydrogen. Its acidity is enhanced by inductive effects and resonance stabilization of the carbanion. Ethyl acetoacetate is used synthetically to produce carboxylic acids, ket

1. Dr. Satish S. Kola
(Assistant professor)
Topic : Organic synthesis via Enolate
M.G Arts science and late N.P commerce college
Armori.
Dr. SATISH S. KOLA 1

2. ENOLATES
The class of compounds which contain a methylene group (–CH2–)
directly bonded to the electron withdrawing groups such as –
COCH3, –COOC2H5, –CN, are called active methylene compounds.
This is so because the –CH2 group in them is acidic and reactive.
The two examples are
a) Ethyl acetoacetate (Acetoacetic ester)
b) Diethyl molonote (Molonic ester)
The structure of (a) and (b) are as
This reaction is known as claisen condensation
D R . S A T I S H S . K O L A 2

3. Ethyl acetoacetate
(CH3COOCH2COOC2H5)
• It's IUPAC name is ethyl 3-oxobutanoate
• Preparation: Ethyl acetoacetate is prepared by
heating ethyl acetate with sodium ethoxide in
ethanol, followed by acidification.
Dr. SATISH S. KOLA 3

4. Claisen condensation
• It is a condensation reaction in which, two ester
molecules condensed to form an alcohol and a
-Keto ester. Therefore ethyl acetoacetate is a
-Keto ester.
• Mechanism: The mechanism involves three
steps:
• Step-I :- First sodium ethoxide (C2H5O–Na+)
breaks into ethoxide ion and sodium ion. This
ethoxide ion attacks ethyl acetoacetate to give
ethyl alcohol and ester anion.
Dr. SATISH S. KOLA 4

5. Step -II: Ester anion attacks the carbonyl group of a second
molecules of ethyl acetate.
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6. • Step-III: Ethoxide ion is eliminated
Properties
• It is a colourless pleasant smelling liquid
• b.p. - 180.4oC
• It is sparingly soluble in water but freely so in
organic solvent.
• It is neutral to litmus.
Dr. SATISH S. KOLA 6

7. Chemical properties
• It is a tautomeric mixture of Keto and enol forms.
Therefore it gives the reaction of the various
functional groups present in the two forms.
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8. Acidity of methylene hydrogen
(Formation of salt)
• In ethyl acetoacetate methylene group (–CH2–) flank by
two carbonyl group. There C—H bond in CH2 group is
readily ionisable because the proton removal forms a
very stable carbonion.
• The acidity of the C—H bond of methylene group is due
to two factors that is inductive effect and resonance
stabilitization of carbanion.
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9. • (a) Inductive effect:- The inductive effect caused by the electron
attracting power of the electronegative oxygen of the two carbonyl
group weaker the C—H bonds. Therefore H atom can dissociate to
give a stable anion.
• (b) Resonance stabilization of carbonion:- The acidity of theC—H
bond is greatly enhanced because the negative charge in the
carbanion is delocalized into the two carbonyl group by resonance.
Dr. SATISH S. KOLA 9

10. Salt formation
• Ethyl acetoacetate is acidic and when treated
with a strong base such as sodium ethoxide
(C2H5ONa) forms it sodium salt
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11. • Ethyl acetoacetate anion is nucleophilic
and reacts with alkyl halides to give alkyl
acetoacetic ester.
ALKYLATION
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12. Kenotic hydrolysis
 When ethyl acetoacetate is hydrolysed with did
HCl, acetoacetic acid is formed. Which
undergoes decarboxylation on heating.
Dr. SATISH S. KOLA 12

13. Acid Hydrolysis
• When ethyl acetoacetate is hydrolysed, with
concentration NaOH and then acidified with dil
HCl, acetic acid is formed.
• Synthetic uses of ethyl acetoacetate :- It is
used in the synthesis of carboxylic acids, ketones
and heterocyclic compounds.
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14. Synthesis of alkylacetic acids
• This involves the reaction of sodium ethyl
acetoacetate with on alkyl halide followed by
acid hydrolysis.
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15. Synthesis of succinic acids
• The reaction of sodium ethyl acetoacetate with
ethyl chloroacetate followed by acid hydrolysis
gives succinic acid
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16. Synthesis of higher normal diacids
(Synthesis of Adipic acid)
• The reaction of sodium ethyl acetoacetate with
an alkylene diiodede followed by acids
hydrolysed gives a normal dicarboxylic acid.
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17. Synthesis of -unsaturated
acids
• This involves base catalysed reaction of ethyl
acetoacetate with an aldehyde or a ketone
followed by acid hydrolysis.
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18. Synthesis of methyl ketones
• This involves the reaction of sodium ethyl
acetoacetate with an alkyl halide (Rx) followed
by ketonic hydrolysis.
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19. Synthesis of 4-methyl uracil
• Ethyl acetoacetate reacts with urea in the
presence of phosphoryl chloride to give 4-methyl
uracil.
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20. Synthesis of antipyrine
• Ethyl acetoacetate reacts with phenyl
hydrozene to give antipyrine.
Dr. SATISH S. KOLA 20