CHEMISTRY OF ENOLS & ENOLATES
PRESENTED BY- UNDER THE SUPERVISION OF-
Dr. A. Behera
Ipsita Tripathy
Roll No. PG19CH011 RK Satpathy
Exam Roll No. 19PGCH007
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CONTENTS –
1. Introduction
2. Formation of enols by proton transfer: Tautomerism
3. Acid and base catalysed enolization
4. Stable enolate formation
5. Control of E- & Z- enolate stereochemistry
6. Stable equivalent of enolates
7. Reaction of enolates
8. Conclusion
9. Question asked
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What are enols and enolates?
The keto and enol form of carbonyl compound are constitutional isomers.
An enol is exactly what the name implies: an ene-ol. It has a C=C double bond and
an OH group joined directly to it.
Easily interconverted by proton transfer in the presence of acid or base.
Interconversible keto and enol form are called tautomers and their
interconversion is called tautomerism.
In the case of dimedone, the enol must be formed by a transfer of a proton from the central
CH2 group of the keto form to one of the OH groups, a reaction known as enolization.
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Acid catalysed enolizaton-
In the acid-catalysed reaction, the molecule is first protonated on oxygen and
then loses a proton from C in a second step.
In the acidic medium ketone coexist with its enolic form.
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Base catalysed enolization-
In the base-catalysed reaction the C–H proton is removed first by the base,
hydroxide ion, and the proton added to the oxygen atom in a second step.
The intermediate in base catalyzed enolization is an enolate ion.
Enolate ion is the conjugate base of the corresponding enol.
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Stable enolate formation-
Thermodynamic Enolate-
The thermodynamic enolate predominates under the conditions of
thermodynamic control.
Thermodynamic enolates are more highly substituted enolates and are more
stable.
:B
O
O H
H Weak base in a
Protic solvent
H
2-methylcyclohexanone thermodynamic enolate
(more stable)
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Kinetic Enolate-
The kinetic enolate is that which is formed fastest.
It is usually formed by the removal of the least sterically hindered α hydrogen.
Kinetic enolates formed with sterically hindered base in an aprotic solvent, such
as: LDA (lithiumdiisopropylamide) in tetrahydrofuran (THF) or dimethoxyethane
(DME).
O This enolate is
H formed faster
O
Li – N(i-Pr)2 because the hindered
H strong base removes
the less hindered
proton faster.
(Kinetic enolate)
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Control of E- & Z- enolate stereochemistry -
1. LHMDS(Lithium hexamethyldisilazide) generally provides the Z-enolate as the
major product.
2. LTMP (Lithium tetramethylpiperidide), very bulky, affords the E-enolate as the
major product.
3. LDA gives intermediate results.
4. Use of HMPA (Hexamethyl phosphoramide) as a strong base also leads to Z-
enolate.
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Ireland deprotonation model is used to determine the stereochemistry of E- & Z-
enolate, in which proton transfer occurs through a chair-like transition state.
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HMPA solvates the lithium cation, leading to an "open" transition state. Li atom is not readily
available to form a chair like conformation.
To avoid the 1,3-diaxial interaction the N-atom shifts away from the bulky group because it
is not coordinatively rigid.
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Stable enol equivalent-
O Li₊
Lithium enolate
(Z)-enolates are more stereoselective than (E)-enolates.
When the reaction is stereospecific, (Z)-enolates give the syn
products and (E)-enolates afford the anti product.
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Silyl enol ether Si
O
Silicon is less electropositive than lithium, and silyl enol ethers are
more stable, and less reactive, than lithium enolates.
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Reaction of enolates-
Halogenation to α carbon-
O
O Br2 /AcOH ׃OH Br - Br
CH2 Br
Ph CH3
Ph CH2 Ph
In basic medium, enolate ion is formed which leads to multihalogenation depending
upon the number of alpha-H.
O Br-Br
‖ O -
O
Br Br Br
H
H - Br-
-
OH
Br
(Dibromoacetone)
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Alkylation –
O- alkylation
SiMe3
O
O-
TMSCL
OH O- OCH3
CH2N2
+
CH3
Ph Ph
Ph
C- alkylation
O- O
CH3 - Br CH3
Ph Ph
O- alkylation is the affinity towards oxygen atom and C- alkylation is the affinity
towards carbon atom.
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Enolate as a nucleophile-
Aldol condensation
O
O- ‖
O
O CH3 H
OH-
‖
CH3
-
CH2 – C - H CH2 H
H
(Nucleophilic attack)
OH
H3C-C-H
CH2
O=C-H
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Conclusion-
We can find stable enols in nature also.
Leptospermone is a herbicide produced by Callistemon
citrinus, the bottle-brush plant, and it has been used
commercially as ‘Callisto’ to protect maize. It is a
tetraketone, but exists entirely as a mixture of tautomeric
enols.
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1) What will be the major product of bromination of
2-methylcyclohexanone?
2) Give the product in each step:
RCHO
2-methylcyclohexanone TMSCL A B
TiCl4 /OH-
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