Enolates are intermediates formed during base catalysed reactions of active methylene compounds with electrophilc reagents/sustrates

1. ICT Teaching –Learning
Department of Chemistry
B.Sc. Part – III
Paper –VII
Topic :Organic Syntheses Via Enolates
Dr. M. T. Bachute (Associate Professor)
K. B. P. Mahavidyalaya, Pandharpur

2. B.Sc. Part –III
Paper -VII
Topic
Organic Syntheses Via Enolates
Points to be studied :
1. Active methylene group and active methylene compounds
2. Enols and enolate ions
3. Enolisation
4. Acid catalysed and base catalysed enolisation
5. Keto-enol tautomerism
6. Synthetic reagents
7. Ethyl aceto acetate
8.Synthesis of ethyl aceto acetate : Claisen condensation
9.Synthetic applications of EAA

3. Organic syntheses via enolates
• Points to be studied :
9. i. Alkylation and further conversions
10. Diethyl malonate
11. Synthesis of Diethyl malonate
12. Synthetic applications of diethyl malonate
12. i. Alkylation and further conversions

4. What do you mean by active methylene group?
Give its General Formula.
A methylene (-CH2-) group which is located between
two electron withdrawing groups.
General Formula:
Z CH2 Z’
Z and Z’ are electron withdrawing
same or different groups

5. What do you mean by active methylene compounds?
Give their examples.
Compounds containing active methylene group are active methylene
compounds.
Examples :
1. Ethyl acetoacetate H3C.CO CH2 COOC2H5
2. Diethyl malonate H5C2OOC CH2 COOC2H5
3.Ethyl cyanoacetate NC CH2 COOC2H5
4.Oxalic acid HOOC CH2 COOH
5. 1,3-Cyclohexadione
OO

6. Enols :
Compounds containing hydroxy group directly
attached to a c=c bond.
C C OH
e.g. H3C-CH=CH-OH
Enolate ions:
Anions of enols are called as enolate ions
C C O
e.g. H3C-CH=CH-O
What are enols and enolate ions?

7. Explain the term Tautomerism
Tautomerism:
Two isomers differing in position of movable atom(generally
H) when exist in dynamic equilibrium are known as
tautomers and the phenomenon is known as tautomerism.
e.g.
CH3
O
CH3 CH3
OH
CH2
CH2 N OH
CH3 N O
CH2 NH
CH3
CH3 N
CH3

8. Mechanism of enolisation
1. Base catalysed
CH3
:O:
CH3 CH3
O
CH2
CH3 CH2
O
+
B
..
BH
+_
CH3
O
CH2
_
_
carbanion
enolate anion
CH3 CH2
O_
BH
+
CH3 CH2
OH
Ketone
Enol
enolate anion
carbanion

9. Mechanism of enolisation
2.Acid catalysed
CH3
:O:
CH3 CH3
OH
CH3
CH3 CH2
OH
+
HA
CH3
OH
CH3
enol
Ketone
A
_
+
+
+ HA

10. Synthetic Reagents
Chemical substances from which various other chemical
substances can be obtained.
Examples :
1. Ethyl acetoacetate CH3-CO-CH2-COOC2H5
3. Meldrums acid
2. Diethyl malonate H5C2OCO-CH2-COOC2H5
O
O
O
O

11. Ethyl acetoacetate
Structure: active methylene
CH3-CO CH2 COOC2H5
CH3 O
O O
CH3

12. Why is methylene group in EAA reactive?
Because :
1. Inductive effect: CH2 group is located between two
electron withdrawing groups(-I effect).hence two C-H
bonds are weak. H
CH3-CO C COOC2H5
H
2.Resonance effect : Base abstracts proton from methylene
group to form a carbanion which is stabilised by
resonance.
CH3
O
C
H
H
O
O C2H5
NaOC 2H5
CH3
O
C
H
O
O C2H5
-
CH3
O
C
H
O
O C2H5
-

13. Synthesis of Ethyl acetoactate
Claisen condensation
Ethyl acetate undergoes self condensation in the presence of
strong base like sodium ethoxide to give ethyl aceto acetate.
2 CH3-COOC2H5 NaOC2H5 CH3-COCH2COOC2H5 + C2H5OH
Ethyl acetate Ethyl acetoacetate
 

14. Synthetic applications of EAA
Syntheses of various carboxylic acids and methyl ketones.
Common steps involved :
1. Na-salt formation: Reaction with Na-alkoxide, one or both
alpha hydrogen atoms get replaced by Na.
2. Alkylation : reaction of Na-salt of EAA with RX to form mono
or dialkylated EAA.
3.Hydrolysis : Depending on nature of product desired one of the
following procedures is used
i) Ketonic hydrolysis :Alkylated EAA is heated with dil. alkali or
acid. Hydrolysis yields ketone as the product.
ii) Acid hydrlysis : Alkylated EAA is heated with con. NaOH
followed by acidification. Hydrolysis yields carboxylic acid as
the product.

15. Synthesis of mono alkyl and dialkyl derivatives of EAA
CH3 O CH3
O O
NaOC 2H5
C2H5OH CH3 O CH3
O O
Na
RX
CH3 O CH3
O O
REAA
Sodiumsalt Monoalkyl deriv.
CH3 O CH3
O O
R
Monoalkyl deriv.
NaOC 2H5
C2H5OH CH3 O CH3
O O
R Na
-NaX
-NaX CH3 O CH3
O O
R R'
R'X
Sodiumsalt
Dialkyl derivative

16. 1.Synthesis of acetic acid
CH3 O
O O
CH3
i.KOH/heat
ii. HCl/H 2O,heat
2 CH3 OH
O
EAA
Acetic acid

17. 2. Synthesis of monobasic acids
Derivatives of acetic acid
EAA R-CH2 – COOH
CH3 O CH3
O O
NaOC 2H5
C2H5OH CH3 O CH3
O O
Na
CH3 O CH3
O O
H3CEAA
Sodiumsalt
CH3 O CH3
O O
H3C
Monomethyl deriv. of EAA
-NaX
CH3I
i. KOH/heat
ii. HCl/H 2O
OH
O
H3C
+ C2H5OH
Monomethyl deriv. of EAA
Acetic acid
CH3
OH
O
Propanoic acid

18. Synthesis of 2-methylbutanoic acid
EAA CH3 OH
O
CH3
CH3
O
O O
CH3
NaOC 2H5/C2H5OH
CH3
O
O O
CH3
Na
CH3
O
O O
CH3
CH3
NaOC 2H5/C2H5OH
CH3
O
O O
CH3
CH3 Na
C2H5Br
CH3
O
O O
CH3
CH3
CH3
i. KOH, heat
ii. HCl/H 2O, heat
CH3
OH
O
+
CH3
CH3 OH
O
Acetic acid 2
-
methylbutanoic acid
+ C2H5OH

19. Synthesis of dibasic acids
1.Succinic acid
CH3
O
O O
CH3
NaOC 2H5/C2H5OH
CH3
O
O O
CH3
Na
Cl
-
CH2
-
COOC 2H5
CH3 O
O
CH3
O
Oc2H5
O
i. KOH, heat
ii. HCl/H 2O, heat
CH3
OH
O
+
O
O
OH
OH
+ C2H5OH
Succinic acid
EAA
Salt
Acetic acid

20. Synthesis of dibasic acids
2. Glutaric acid
CH3
O
O O
CH3
EAA
2 NaOC 2H5/C2H5OH2
CH3
O
O O
CH3
Na
2
CH3
O
O O
CH3
Na
CH3O
O
CH3
O
Na
+
I
I
CH2
CH3
O
O O
CH3
CH3O
O
CH3
O
CH2
i. KOH,heat
ii. HCl/H 2O, heat
2CH 3COOH + COOH
COOH
+ 2C2H5OH
Glutaric acid
Acetic acid

21. Synthesis of α,β-unsaturated acids
1. Synthesis of cinnamic acid:
O
H
+
O
CH3
O
O
CH3
pyridine
Knovangel condesation
H
O CH3
O
O
CH3
i.KOH,heat
ii. HCl/H 2O, heat
OH
O
+ CH3COOH + C2H5OH
Benzaldehyde EAA Ketoester
Cinnamic acid Acetic acid Ethyl alcohol


(unsaturated acid)

22. Synthesis of α,β-unsaturated acids
3-methyl-p-methyl cinnamic acid:
O
CH3
CH3
+
O
CH3
O
O
CH3
pyridine
Knovangel condesation
CH3
O CH3
O
O
CH3
CH3
i.KOH,heat
ii. HCl/H 2O, heat
OH
OCH3
CH3
+ CH3COOH + C2H5OH
EAA Ketoester
Acetic acid Ethyl alcohol


(unsaturated acid)
3
-
methyl
-
p
-
methyl cinnamic acid
p
-
methyl acetophenone

23. Synthesis of heterocyclic compounds
1.Synthesis of 4-methyl uracil:
CH3
O
O
OC2H5
CH3
O
OH
OC2H5
EAA EAA
(keto form) (enol form)
+
NH2
NH2
O
POCl 3
-H2O
N
H
N
H
O
CH3
O
12
3
4
4
-
methyl uracil
+C2H5OH

24. Synthesis of heterocyclic compounds
Synthesis of antipyrine:
CH3
O
O
OC2H5
EAA
+ + C2H5OH
NH
Ph
NH2
heat
condensation
N
N
CH3
O
Ph
Phenyl hydrazine Antipyrine
+ H2O