REACTIONS OF α-HYDROGENS :

ALKYLATION AND HALOGENATION

REACTIONS
REACTIONS OF CARBONYL CONTAINING COMPOUNDS

Until now we have looked at reactions

of the C=O group - nucleophilic additions
and substitutions

Chaps 16, 17, 18, 19

..
O: Good nucleophiles
react at C=O

C C
Chap 21
Strong bases
remove the
H
Now we will look at reactions that
α-hydrogens result from the acidity of the alpha
hydrogen
ACIDITY OF α-HYDROGENS

ENOLATE IONS
α-Hydrogens and Enolate Ions
Major resonance
.. - contributor:
:O : charge is best
on oxygen =
C C
.. “enolate
O: base ion”
C C
..
H O:
:B
C C
α-hydrogen ..
- However, the
acidic : pKa ~ 25 ion is more
nucleophilic
at carbon.

Strong bases will remove a hydrogen on the carbon next to a

carbonyl group (α-hydrogen) to make a resonance stabilized
conjugate base.
NaOH, KOH, NaOR, NaH, LDA, etc.
 ACETONE ENOLATE ION
The nucleophilic electron pair is in the HOMO

HOMO density-
HOMO

REACTIVE
.. SITE

Charge is
on oxygen
but carbon is note the NEGATIVE
nucleophilic bonding CHARGE

.. .. -
:O :O :

H3C C H3C C
CH CH2 density-
- .. 2 major electrostatic
potential
 Enolate Ions as Nucleophiles
MORE NUCLEOPHILIC AT CARBON, BUT BEST REPRESENTED AS THE ENOLATE

.. -
Mechanisms are often drawn
from the enolate resonance
:O :
form like this: C C

enolate
I CH3

..
O:
Rather than from the
C C
ketolate form like this:
..
- ketolate

I CH3
 ALKYLATION OF KETONES

NON-CATALYTIC BASES = NaH, LDA REACT ONCE .

one shot

CATALYTIC BASES = NaOH, KOH, NaOR REACT REPEATEDLY

It just keeps
on going and
going …..
Alkylation of a Ketone .
NON-CATALYTIC BASES REACT ONCE one shot

O one mole O one mole

NaH _
..
C CH3 C CH2 + H
2
THF
α-hydrogens
LDA CH3-I
THF one mole
O _ O
.. CH3-I
C CH2 C CH2 CH3
monoalkylation

_ Sodium Hydride
+
: N : Li NaH
CH CH3
“LDA”
H3C CH
Lithium Diisopropyl Amide
CH3 CH3
a strong base
 ALKYLATION OF CYCLOHEXANONE
CATALYTIC BASES REACT REPEATEDLY

.. ..
O :O CH3CH2 I :O
CH2CH3
NaOH :-

enolate difficult to stop

ion at monoalkylation
.. - with NaOH or KOH
:O: (catalyst, not used up)

O
It just keeps
on going and CH3CH2 CH2CH3
going ….. CH3CH2 CH2CH3
Sequence of Alkylation - Cyclohexanone and Base
It is difficult to stop at monoalkylation
O even if one mole of CH3I is used.
Alkylation follows the sequence
KOH shown below.
CH3I Large or bulky groups may follow a
different sequence than this one.

O O O O
CH3 CH3 H3C CH3 H3C CH3
CH3 CH3 H3C CH3

This enolate has O- O-

SAME lower energy -
SIDE the double bond is CH3 CH3
FIRST more substituted.
CH3-I This enolate has
Steric hindrance higher energy.
is not a problem.
ALKYLATION OF KETONES
NON-CATALYTIC BASES = NaH, LDA
 Monoalkylation is Obtained by Using
“Non-Catalytic Bases”
A “non-catalytic base” is used up, and not regenerated.

.. .. .. -
:O :H - :O
Na+
:O :
H
NaH - H
+ H2

:
H H
gone

one CH3I
mole
stoichiometric base
..
:O
. CH3
+ NaI
one shot
H
 Lithium Diisopropyl Amide .
one shot

_ +
: N : Li “LDA”
H3C CH CH CH3
Lithium Diisopropyl Amide
CH3 CH3
a strong base

LDA is also a non-catalytic base.

It is too strong a base to be regenerated after it is
used to remove a proton from an aldehyde or ketone.

.. - .. .. -
(iPr)2N :
+ α-H
(iPr)2NH X
difficult
(iPr)2N :

(need to add Lio)

ALKYLATION OF KETONES
ENAMINES
ALKYLATION OF CYCLOHEXANONE
ENAMINES ALSO GIVE MONOALKYLATION

I
-
.. +
O N CH3CH2 I N
CH2CH2

Alkylates once
and stops !
. O
one shot
CH2CH3
To perform a second alkylation
you must make the enamine all
over again!
Sequence of Alkylation: Enamine
( pyrrolidine + CH3I )
O O
Alkylations go one-at-a-time.
first CH3 You must make a new enamine
time each time.

Notice the different order of

O methylation from that with base.
O
CH3 H3C CH3
Difficult to go beyond dialkylation
second because of steric hindrance.
time

Steric hindrance
N N This enamine
This enamine CH3 CH3 is not favored.
is favored.
yellow area
is planar
α-BROMINATION
OF KETONES
 Bromination
It just keeps
on going and
going …..
.. .. -
O :O .. .. :O:
: Br Br :
.. ..
KOH :
-
Br2

O O O O
Br Br Br Br Br Br
Br Br Br Br

Difficult to stop at monobromination

IODOFORM REACTION
 Iodoform Reaction
O NaOH O

R C CH I2 R C O Na + CHI3 yellow
3
precipitate

NaOH NaOH H2O

O I
O I I -: C I
R C OH
..
R C CH I
2
good
I2 leaving
It just keeps O group
on going and I
going …..
O 2x more R C C I
R C CH I ..-
2 H O: I
..
REACTIONS OF α-HYDROGENS :
ALDOL AND CLAISEN
CONDENSATION REACTIONS
 TYPES OF REACTIVITY FOR
ALDEHYDES AND KETONES

O nucleophilic OH
addition
C CH C CH

Nu:
H Nu H

:B
removal
of α-H O • Good nucleophiles add.
• Strong bases remove α-hydrogens.
C CH
.. Often, both processes compete.
-
ALDOL CONDENSATION
The Aldol Condensation
ald
O +
ol
R CH2 C H
OH O
+ base
R CH2 C CH C H
O H R an aldol
R CH2 C H (β-hydroxyaldehyde)

H3O+ - H2O
O
aldols easily lose R CH2 CH C C H
water to form a
double bond R
α,β-unsaturated aldehyde
Aldol Condensation -- Mechanism
:O : .. _
_ .. fast _ : O: : O:
CH3 C H ..
+ :O.. H CH2 C H H2C C H

: O: .. _ enolate ion
: O:
CH3 C H slow
CH3 C H
:O: : O:
_ forms new
.. CH2 C H
CH2 C H C-C bond

.. _ ..
: O: : O: :O H :O:
fast
CH3 C CH2 C H CH3 C CH2 C H
H H _ ..
+ H2O + :OH
..
 The Bond Forming Step
H carbonyl
(acceptor)
H
+ _ _
H3C C O H3C C O
_
.. CH2
CH2
C O
C O

nucleophile H
H (donor)

enolate
Ketones Also Give Aldol Condensations

O OH
C CH C CH3 C CH3
3
CH2 CH
..
- CH2 NaOH C O C O
C O -H2O

“aldol”
“CROSSED” ALDOL
CONDENSATIONS
 Crossed Aldol Condensations
KETONE + ALDEHYDE

O OH
C H C H

.. - CH2
aldehyde CH2 NaOH C O
C O

ketone

- H2O
Works best to if an aldehyde is
the “acceptor”, since they are O
more reactive; and works really CH CH C
well if the aldehyde has no α-H.
The ketone should have the α-H. a “chalcone”
 IMPORTANT GUIDELINES
1. Aldehyde carbonyl groups are more reactive toward
nucleophilic addition than ketone carbonyl groups.

O
δ- O
δ- Alkyl groups
C δ+ C δ+
+I +I deactivate the
R H R R +I carbonyl ( +I )
to addition.
Nu:

MORE
REACTIVE
RELATIVE REACTIVITY OF C=O GROUPS
THE EFFECT OF ALKYL SUBSTITUTION
Density - LUMO plots ( color scale 0.000 to 0.030 )

O O O
H-C-H CH3-C-H CH3-C-CH3

MORE LESS
REACTIVE REACTIVE
2. Ketones form enolate ions more easily than aldehydes.
.. - .. -
:O : :O :
R R More
C C H C C R substituents
R on the
R
double bond
aldehyde enolate ketone enolate
more stable

Which enolate will .. .. -

:O :O :
form fastest?
CH3CH2 C CH2 CH3CH2 C CH2
..
O -
monosubstituted
CH3CH2 C CH3
.. .. -
:O :O :
CH3CH C CH3 H3C CH C CH3
..
- disubstituted
 ALDEHYDE + KETONE ?

In “mixed” reactions the ketone enolate

usually adds to the aldehyde.

The ketone forms the lower energy enolate (forms faster)

and it adds to the aldehyde (more reactive C=O).
 WHAT ABOUT
TWO DIFFERENT KETONES ?
HOW MANY PRODUCTS WITH THIS ONE ?
A B
O O
a b c d
H3C C CH2 + CH3CH2 C CH3

x2 four mixed products x2

aB, bB, cA, dA

two different self dimers two different self dimers

aA, bA cB, dB

8 POSSIBLE PRODUCTS !
….. which enolate do you think will form preferentially?
FORMATION OF RINGS
 Formation of Rings
α1 α2
O O
H3C C CH2CH2CH2 C CH3

NaOH

CH3 CH3 CH3

OH
O

- :CH2 O O
O

Why don’t α2 hydrogens react ?

TETRAPHENYLCYCLOPENTADIENONE

O
C O
Ph CH2 CH2 Ph
Ph Ph
KOH
O O EtOH
Ph Ph
Ph Ph
An Interesting Sequence

O
1) O3

2) H3O+
O H OH-
H
KOH
Aldol
OH
H2SO4
- H2O

O O
CLAISEN CONDENSATIONS
 The Claisen Ester Condensation
O
R CH2 C O CH2 CH3

O O
+ NaOCH2CH3
R CH2 C CH C O CH2 CH3
CH3CH2OH
O R
a β-ketoester
R CH2 C O CH2 CH3 +

CH3 CH2 O H

Notice that
the base, the solvent and the leaving group

CH3CH2O- Na+, CH3CH2OH, CH3CH2O-

all match (this is required in most cases).
Claisen Ester Condensation Mechanism
1)
O
CH3 C OC2H5 .. _
_ O : O:
+
_ .. : CH2 C OC2H5 H2C C OC2H5
: O C2H5
..

2)
O .. _
:O :
CH3 C OC2H5
CH3 C OC2H5
_ O
O
: CH2 C OC2H5 CH2 C OC2H5
3) .. _
: O: : O:
CH3 C OC2H5 CH3 C _ ..
O O + : O C2H5
..
CH2 C OC2H5 CH2 C OC2H5
Dieckmann Condensation
A CYCLIC CLAISEN CONDENSATION

MeOOC CH2CH2CH2CH2 COOMe

NaOMe
MeOH
O
O
C O CH O
3

.. C O CH3
CH C O CH3
O
 Type of
PATTERNS Condensation
Reaction

HO O
β-hydroxy to C=O
R CH2 C CH C R 3-hydroxyaldehyde or ALDOL
(H)
R R 3-hydroxyketone
(H)
-H2O

O α,β-unsaturated C=O
R CH2 C C C R 2-propen-1-al or ALDOL
R R 2-propen-1-one (with loss of H2O)

O O β-keto ester
R CH2 C CH C OR CLAISEN
R
SYNTHESIS
Synthesis of a Perfumery Compound
O
α2 α1 cis O cis
C C
H2C CH2 CH2 CH CH CH2 CH3 H2C CH CH2 CH CH CH2 CH3
H2C O H2C
C C OH
α3 KOH
CH3 Aldol Condensation CH3
α4
Dehydration
- H2O
O
CH2 CH2 CH3
C C
H H Why don’t the
CH3 other sets of α-H
react?
cis-Jasmone
Scent of Jasmine in perfumes.
Biological Synthesis of Fructose
O O O
α
CH2 CH C H + CH2 C CH2 O P OH

O OH OH O

Dihydroxyacetone phosphate
O P O
enzyme ALDOL
OH CONDENSATION
Glyceraldehyde-3-phosphate
OH O O

CH2 CH C CH C CH2 O P OH

O OH H OH O

O P O Fructose-1,6-diphosphate

OH
Synthesis of an Insect Repellent
O
OH
CH3 CH2 CH2 C H
NaOH CH3 CH2 CH2 C H
O
CH3 CH2 CH C H
CH3 CH2 CH2 C H ALDOL
α CONDENSATION O
2-Ethyl-3-hydroxyhexanal

OH OH

CH3 CH2 CH2 C H H2 CH3 CH2 CH2 C H

H
Ni
CH3 CH2 CH C H CH3 CH2 CH C H

O HYDROGENATION O H
2-Ethyl-1,3-hexanediol
--used in "6-12" insect repellent
CONJUGATE ADDITION

MICHAEL ADDITION
Addition of Nucleophiles to Enones
Conjugate Addition or Michael Addition
.. .. - .. -
:O :O: : O:
C C C
C C C C + C C
+

:Nu :Nu

1,2-addition 1,4-addition

OH O
C H C
C C C C
Nu
conjugate
Nu addition
 CONJUGATE ADDITION
.. .. -
O: : O:
H C H C
C C CH3 CH3
H C C
H H H
:N C
-
:N C H-OH
..
O:
H H C
In conjugate addition
H C C CH3
the nucleophile adds
:N C H
and then picks up a
hydrogen from the
solvent medium.
 CONJUGATE ADDITION
GENERALIZATION

stereochemistry
conjugated ketone O also matters

H C R
β α
C C
H H strong direct to C=O
bases 1,2-addition

weak
nucleophiles/bases

conjugate addition
1,4-addition
 Strong Bases : 1,2-Addition

• Strong bases give direct addition to C=O (1,2-addition) unless

the C=O group is sterically hindered by large groups

Organolithium compounds RLi

Grignard reagents RMgX

Lithium Aluminum Hydride LiAlH4

 Weak Bases : 1,4-Addition
• Good nucleophiles and weak bases give conjugate addition
(1,4-addition), also known as Michael Addition, especially if
the C=O group is hindered.
..
Amines R-NH2
.. ..
Alcohols R-O-H
.. Water H-O-H..

Enolates

Organocopper and cadmium compounds

( RMgX + CuCl or CdCl2 )

Lithium dialkylcuprates
( RLi + CuCl )

Cyanide ion :C N:
 ADDITION TO CARBONYL
CH3MgI
O CuCl
O
HO CH3
CH3Li (CH3)2CuLi
or or
CH3MgI (CH3)2Cd CH3
strong bases add weaker bases add
by 1,2 addition _ by 1,4 addition
O _ O
:CH3
_
:CH3
+
C-Li and C-Mg bonds are R-Cu and R-Cd bonds are
more ionic (stronger bases) more covalent (weaker bases)
 STEREOCHEMISTRY ALSO MATTERS
LARGE GROUPS ON EITHER SIDE OF THE CARBONYL FAVOR CONJUGATE ADDITION

large groups here

STERIC HINDRANCE
promote 1,4 addition

O OH
CH3 CH3
H C CH3MgBr H C
C C CH CH3 CH CH3
H C C
H H H
CH3
large groups here can major product
also promote 1,4 addition
O OH
H C H H C H
CH3MgBr
C C C C
H H CH3
H H
major product
large groups here
small groups here
promote 1,2 addition make 1,2 addition
more probable
FRONTIER MO THEORY

CONJUGATED KETONES
 FRONTIER MO THEORY
NUCLEOPHILE

HOMO
LUMO
FILLED MOs

HOMO
E+ :Nu-
FILLED MOs

ELECTROPHILE
LUMO MAPPED ONTO ELECTRON
DENSITY
BLUE REPRESENTS MAXIMUM DENSITY OF LUMO
A

A B

B
 ROBINSON ANNELATION

FORMING RINGS BY COMBINING

CONJUGATE ADDITION WITH AN ALDOL CONDENSATION

METHYL VINYL KETONE (MVK)

 Conjugate Addition of Cyclopentanone to MVK
MVK
enolate
methyl vinyl ketone
weak base
.. .. .. -
.. : O:
:O O: :O
H C
- H C CH3
: CH3 C
H H H H
H-OCH3
NaOCH3
CH3OH
.. ..
O :O O:
- .. C
: O-CH
.. 3 CH2 CH2 CH3

- ..
+ : O-CH
.. 3

can continue
 ROBINSON ANNELATION
USES MVK TO BUILD A RING
FROM PREVIOUS SLIDE

O O O O
H C NaOCH3 C
CH3 CH2 CH2 CH3
CH3OH
H H
Michael
addition
O O
- CH
-O O : 2
C
CH2 CH2 O
H3O+
(workup) Annelation
(ring formation)
internal aldol condensation
 ANOTHER EXAMPLE
MICHAEL ADDITION + ALDOL CONDENSATION

2 ALDOL

O H3C O
C O NaOEt
1
CH EtOH
O CH2 O

Most acidic set

of hydrogens MICHAEL
reacts first.
DECARBOXYLATION
OF β-KETOACIDS
HYDROLYSIS OF A β-KETOESTER GIVES A β-KETOACID

Claisen β-Ketoester
Condensation
O NaOCH3 O O
CH3CH2CH2 C OMe CH3CH2CH2 C CH C OMe
CH3OH
CH2CH3
H3O+
hydrolysis

O O O
- CO2
CH3CH2CH2 C CH H CH3CH2CH2 C CH C OH
CH2CH3
CH2CH3
Ketone
… then, the β-ketoacid β-Ketoacid
decarboxylates in acid
 Decarboxylation of a β-Ketoacid
6-ring concerted step
H H O
O O heat + acid O
C C O C C O
C C
enol

tautomerization

Carbon dioxide is easily lost O

since a nice 6-membered C O C O
ring transition state can be CH
formed for a concerted
process. ketone
 SYNTHESIS OF KETONES
FROM β-KETOESTERS

ALKYLATION / DECARBOXYLATION OF β-KETOESTERS

 STEP ONE - MAKING THE β-KETOESTER
….. discussed earlier

O
a β-ketoester
CH3 C O CH2 CH3

O O
O + NaOCH2CH3
CH3 C CH2 C O CH2 CH3
CH3 C O CH2 CH3

+ CH3 CH2 O H
Claisen
condensation

a different R group
could be used here
STEP TWO - ALKYLATE THE β-KETOESTER

O O
CH3 C CH2 C O CH2 CH3

NaOCH2CH3
CH3I
a primary halide
O O
is best
CH3 C C C O CH2 CH3
H3C CH3
 STEP THREE - HYDROYSIS AND DECARBOXYLATION

O O
CH3 C C C O CH2 CH3
H3C CH3
β-ketoester
H3O

this O O β-ketoacid
part will be CH3 C C C O H
the ketone H3C CH3
β-ketoacids decarboxylate
heat - CO2 easily when heated in acid
(see next slide)
O CH3
CH3 C CH ketone
CH3
 ALKYLATION CAN BE SKIPPED

O NaOCH3 O O
CH3CH2CH2 C OMe CH3CH2CH2 C CH C OMe
CH3OH
CH2CH3
H3O+

O
CH3CH2CH2 C CH2CH2CH3

an unbranched ketone
DITHIANE ANIONS
 Conversion of Aldehydes to Ketones
Dithiane Anions
a 1,3-dithiane
O HSCH2CH2SH S S
R C H H2SO4 R H acidic H

aldehyde
-H2O butyllithium
(strong base)

various
methods R' X
O
S S S S - ..
R C R' H2/Ni .. -
or
R R' R C S
ketone R' X
Hg(OAC)2
SN2 anion is stabilized
H2SO4
by empty 3d
orbitals on sulfur
PATTERNS
 Type of
PATTERNS Condensation
Reaction

HO O
β-hydroxy to C=O
R CH2 C CH C R 3-hydroxyaldehyde or ALDOL
(H)
R R 3-hydroxyketone
(H)
-H2O

O α,β-unsaturated C=O
R CH2 C C C R 2-propen-1-al or ALDOL
R R 2-propen-1-one (with loss of H2O)

O O β-keto ester
R CH2 C CH C OR CLAISEN
R
 PATTERNS CONTINUED

O O β-keto acid
R CH2 C CH C OH
R DECARBOXYLATION
H3O+
heat H3O+
R-X (alkylation)

O O O
R CH2 C CH2 + CO2 R CH2 C CH C OR
R H from Claisen
ketone
SOME OTHER APPLICATIONS
ACYLOIN CONDENSATIONS
 Acyloin Condensation

+ +
Na Na
O O O
Na
2 R C OR' R C C R
xylene

OH O
H2 O
R CH C R
mechanism
not required
an acyloin

This is a good way to make large rings. High dilution.

A Cyclic Acyloin Condensation
O
O
C OC2H5
C
Na
(C32H64) (C32H64)
xylene C OH
C OC2H5
H
O
Zn(Hg)
Conc HCl

CH2
(C32H64)
CH2

cyclotetratriacontane

A VERY BIG RING !

 PATTERN

HO O α-hydroxyketone
R CH C R ACYLOIN
an acyloin
CATENANES
 Catenanes
O Interlocked
C rings.
(C32H64) OC2H5 Na
(C34H68) OC2H5 xylene
C cyclo-C34
O

O
C
(C32H64)
(C34H68)
CH
OH

a Catenane
(1 - 2% yield)
HELL-VOLHARD-ZELINSKY

α-BROMOACIDS AND α-BROMOESTERS

Hell-Volhard-Zelinsky Reaction
O O
1) P, Br2
R CH C OH R CH C OH
2) H3O+
H Br α-bromoacid
PBr3

O
R CH C Br H3O+
H (workup step)
Acid halides have
.. a larger enol content
:O H than ketones. O
R CH C Br R CH C Br
Br
Br Br
Double bonds react Resonance increases the electron
with bromine! density in the double bond. Enols
are more reactive than alkenes.
Synthesis of Aminoacids and a-Hydroxyacids
neutralization step not shown

O O
CH C OH + NH3 CH C OH
Br NH2
phenylalanine

O O
NaOH
CH3 CH C OH CH3 CH C OH
Br OH lactic acid
REFORMATSKY REACTION
A COUSIN TO THE GRIGNARD REACTION
 Reformatsky Reaction
O O
R CH C OH R CH C O CH2CH3
Fischer
Br Br
Esterification α-bromoester
or via the
acid chloride
Zn, ether

O
R CH C O CH2CH3 O
H3C C OH R CH C O CH2CH3
H 1) O ZnBr
Reformatsky
H3C C H
reagent
2) H O+
3
Reacts like a
Grignard reagent!
ENOL CONTENT
Keto-Enol Tautomerism
H
O O
K
C C C C

H
keto enol

For most ketones, the keto form

predominates in the equilibrium
AS A GENERAL RULE: ENOLS ARE
UNSTABLE
ol
O H ENOLS :
( have -OH attached to a double bond)
Think of this combination as unstable.
C C
ene
OH
NOTE :
Phenols are not “enols” and they are
very stable (benzene resonance).
 TAUTOMERISM
ENOL KETO TAUTOMERS :
O H O
species in
H3C C CH2 H3 C C CH2 equilibrium
that differ in
unstable enol
H
the position
of a proton or
other group.

Most enols are not favored, To interconvert tautomers,

a proton is transferred
E from oxygen to carbon.
enol
N
E Mechanism, next
R slide…..
G
keto Y

they rapidly change to keto.

 Tautomerism is Catalyzed by Traces of
Either Acid or Base
BASE
CATALYSIS .. ..
O: O: enolate
ion
C C C C
H
- ..
keto
.. -
H-O:
..
..
H H-O:
- .. H
.. - : O: : O:
H-O: + C C C C
..
enol
resonance structures
 Tautomerism is Catalyzed by Traces of
Either Acid or Base
..
ACID H-O-H
CATALYSIS + .. H
.. H
O: +O
C C C C
H keto H ..
:O-H
H

H ..
: O: H-O-H
C C + +
H
enol
CONVERSION OF AN ENOL TO A KETONE
( catalyzed by small amounts of acid )
ENOL
H H
O O H +O
H3 C C CH 2 H3 C C CH 2 H3 C C CH 2
+
+ H H
H O H
H
H H
+
O H H O H
H
+O O
H3 C C CH2 H3 C C CH2
H H
KETONE
 Enol Percentages are Low
in Most Ordinary Ketones
O OH
4.1 x 10-4 %

O OH
CH3 C CH3 H2C C CH3 < 2 x 10-4 %

O OH
H2C CH C CH3 H2C CH C CH2

2.5 x 10-3 %
FACTORS THAT STABILIZE
THE ENOL FORM

…… increasing the amount in the equilibrium

 MOSTLY RESONANCE
H H
O O O O

R R R R
H H

1. Resonance helps stabilize the enol.

2. Phenyl substituents R also help to stabilize

the enol by extending the resonance system.

3. Equivalent R groups results in symmetry

which also stabilizes the enol.
(i.e., equivalent resonance contributors )
 Enol Percentages in 1,3-Diketones
are Higher
O O OH O
H3C C CH2 C H H3C C C C H 98 %

O O OH O
H3C C CH2 C CH3 H3C C C C CH3 80 %

O O OH O
H3C C CH2 C OC2H5 H3C C C C OC2H5 8 %
SOME ADDTIONAL PROPERTIES OF ENOLS

ENOLS ARE MORE ACIDIC THAN THEIR KETO FORM

ENOLS ARE NUCLEOPHILIC / REACT RAPIDLY WITH X2

ARE AN IMPORTANT INTERMEDIATE IN

ACID-CALTALYZED ALDOL CONDENSATIONS

MAKE COMPLEXES WITH FeCl3 (like phenols)

Discussed in class (if time).