REACTIONS OF -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
Strong bases
remove the
-hydrogens

Chap 21
Now we will look at reactions that
result from the acidity of the alpha
hydrogen

ACIDITY OF -HYDROGENS
ENOLATE IONS

-Hydrogens and Enolate Ions

.. :O :
C C

..

O:

base

C C
H

acidic :

pKa ~ 25

enolate
ion

..
O:

:B

-hydrogen

Major resonance
contributor:
charge is best
on oxygen =

C C

..

However, the
ion is more
nucleophilic
at carbon.

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

carbonyl group (-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

densityHOMO
REACTIVE
SITE

..
Charge is
on oxygen
but carbon is
nucleophilic

note the
bonding

..

..

:O

:O :

H3C C

CH
.. 2

H3C C
major

NEGATIVE
CHARGE

CH2

densityelectrostatic
potential

Enolate Ions as Nucleophiles

MORE NUCLEOPHILIC AT CARBON, BUT BEST REPRESENTED AS THE ENOLATE

.. :O :

Mechanisms are often drawn

from the enolate resonance
form like this:

C C
enolate

CH3

..
O:

Rather than from the

ketolate form like this:

C C

CH3

..

ketolate

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

one shot

NON-CATALYTIC BASES REACT ONCE

one mole
NaH

O
C CH3

THF
-hydrogens

one mole
_
..
C CH2 + H
2

CH3-I
one mole

LDA
THF
O

..
C CH2

CH3-I

C CH2 CH3

monoalkylation
Sodium Hydride

: N : Li
H3C CH
CH3

CH CH3
CH3

NaH

LDA
Lithium Diisopropyl Amide
a strong base

ALKYLATION OF CYCLOHEXANONE
CATALYTIC BASES REACT REPEATEDLY

CH3CH2 I

:O
NaOH

:O

CH2CH3

:-

.. :O:

It just keeps
on going and
going ..

..

..

enolate
ion

difficult to stop
at monoalkylation
with NaOH or KOH
(catalyst, not used up)

O
CH3CH2
CH3CH2

CH2CH3
CH2CH3

Sequence of Alkylation - Cyclohexanone and Base

It is difficult to stop at monoalkylation
even if one mole of CH3I is used.

Alkylation follows the sequence

shown below.

KOH
CH3I

Large or bulky groups may follow a

different sequence than this one.

O
CH3

This enolate has

SAME lower energy SIDE the double bond is
FIRST more substituted.
Steric hindrance
is not a problem.

O
CH3 H3C

CH3

H3C

CH3

CH3

CH3

H3C

CH3

O-

OCH3

CH3

CH3-I

This enolate has

higher energy.

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.

..

:H -

:O

..

:O

H
NaH

.. :O :

Na+

H2
gone

CH3I

one
mole
stoichiometric base

.
one shot

..

:O
CH3
H

+ NaI

Lithium Diisopropyl Amide

.
one shot

: N : Li
CH CH3
H3C CH
CH3

CH3

LDA
Lithium Diisopropyl Amide
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 :
+ -H

..

(iPr)2NH

X
difficult

.. (iPr)2N :

(need to add Lio)

ALKYLATION OF KETONES
ENAMINES

ALKYLATION OF CYCLOHEXANONE
ENAMINES ALSO GIVE MONOALKYLATION

..

CH3CH2 I

+
N

CH2CH2

Alkylates once
and stops !

.
one shot

To perform a second alkylation

you must make the enamine all
over again!

O
CH2CH3

Sequence of Alkylation: Enamine

( pyrrolidine + CH3I )
O

O
first
time

Alkylations go one-at-a-time.
You must make a new enamine
each time.

CH3

Notice the different order of

methylation from that with base.

CH3

CH3 H3C

Difficult to go beyond dialkylation

because of steric hindrance.

second
time

Steric hindrance
N

This enamine
is favored.

N
CH3

CH3

This enamine
is not favored.
yellow area
is planar

-BROMINATION
OF KETONES

Bromination
It just keeps
on going and
going ..

..

.. ..
: Br Br :
.. ..

:O

KOH

.. :O:

Br2
O

O
Br

O
Br
Br

Br

Br

Br

Br

Br

Br

Br

Difficult to stop at monobromination

IODOFORM REACTION

Iodoform Reaction
O

NaOH

R C O Na + CHI3

R C CH I2
3

yellow

precipitate

NaOH

NaOH

H2O

..
R C CH
2

-: C

R C OH

I
good
leaving
group

I2
It just keeps
on going and
going ..

O
O
R C CH I
2

2x more

R C C

..-

H O:
..

REACTIONS OF -HYDROGENS :
ALDOL AND CLAISEN
CONDENSATION REACTIONS

TYPES OF REACTIVITY FOR

ALDEHYDES AND KETONES
O
C CH

nucleophilic
addition

C CH
Nu H

Nu:

OH

:B
removal
of -H

Good nucleophiles add.

C CH

..

Strong bases remove -hydrogens.

Often, both processes compete.

ALDOL CONDENSATION

The Aldol Condensation

ald
+
ol

O
R CH2 C H

OH
+

base

R CH2 C CH C H

H R

an aldol
(-hydroxyaldehyde)

R CH2 C H
H3O+

- H2O

O
aldols easily lose
water to form a
double bond

R CH2 CH C C H
R

,-unsaturated aldehyde

Aldol Condensation -- Mechanism

:O :

_ ..
+ :O
.. H

CH3 C H

CH3 C H
..
CH2

slow

CH3 C H

:O:

.. _
: O:

: O:
_
..
CH2 C H

: O:

H
+ H2O

: O:

fast

..
:O H

:O:

CH3 C CH2 C
H

C H

forms new
C-C bond

CH2 C H

C H

CH3 C CH2 C H

H2C

enolate ion

.. _
: O:

: O:

fast

.. _
: O:

_ ..
+ :OH
..

The Bond Forming Step

carbonyl
(acceptor)

H
H3C

_
O

+
C

H
H3C

_
O

..
CH2
C
H
enolate

CH2
O

nucleophile
(donor)

C
H

Ketones Also Give Aldol Condensations

OH

C CH
3

..

CH2

CH

C O

C O

- CH2

NaOH

CH3

-H2O

C O

aldol

CH3

CROSSED ALDOL
CONDENSATIONS

Crossed Aldol Condensations

KETONE + ALDEHYDE

aldehyde

OH

C H

.. -

CH2

CH2

NaOH

C O

C O

ketone
- H2O
Works best to if an aldehyde is
the acceptor, since they are
more reactive; and works really
well if the aldehyde has no -H.
The ketone should have the -H.

O
CH CH C

a chalcone

IMPORTANT GUIDELINES
1.

Aldehyde carbonyl groups are more reactive toward

nucleophilic addition than ketone carbonyl groups.
C +

+I

Nu:
MORE
REACTIVE

C +

+I

R +I

Alkyl groups
deactivate the
carbonyl ( +I )
to addition.

RELATIVE REACTIVITY OF C=O GROUPS

THE EFFECT OF ALKYL SUBSTITUTION
Density - LUMO plots ( color scale 0.000 to 0.030 )

O
H-C-H
MORE
REACTIVE

O
CH3-C-H

O
CH3-C-CH3
LESS
REACTIVE

2.

Ketones form enolate ions more easily than aldehydes.

.. .. :O :
:O :
R

C C H

R
aldehyde enolate

ketone enolate
more stable
.. :O :

..
:O

Which enolate will

form fastest?
CH3CH2

C CH2
..

O
CH3CH2

C C R
R

More
substituents
on the
double bond

C CH3

..
:O
CH3CH C CH3
..

CH3CH2

C CH2

monosubstituted

.. :O :
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
a

H3C C CH2

x2

CH3CH2

C CH3

x2

four mixed products

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
1

2
O

H3C C CH2CH2CH2 C CH3

NaOH

CH3

CH3

OH

CH3

- :CH2
O

Why dont 2 hydrogens react ?

TETRAPHENYLCYCLOPENTADIENONE
O
Ph CH2

O
CH2 Ph

Ph

Ph

KOH

EtOH

Ph
Ph

Ph

Ph

An Interesting Sequence
O
1) O3
2) H3O+

O
KOH
Aldol

OH
H2SO4
- H2O

OH-

CLAISEN CONDENSATIONS

The Claisen Ester Condensation

O
R CH2 C O CH2 CH3
+
O

NaOCH2CH3
CH3CH2OH

R CH2 C O CH2 CH3

R CH2 C CH C O CH2 CH3

R

a -ketoester

+
CH3 CH2 O H

Notice that
the base, the solvent and the leaving group
CH3CH2O- Na+, CH3CH2OH, CH3CH2Oall match (this is required in most cases).

Claisen Ester Condensation Mechanism

1)

O
CH3 C OC2H5
+
_ ..
: O C2H5
..

2)

_
: CH2

C OC2H5

.. _
:O :

O
CH3 C OC2H5

CH3 C OC2H5
O

O
_
: CH2 C OC2H5
3)

.. _
: O:

.. _
: O:
H2C C OC2H5

CH2 C OC2H5
: O:

CH3 C OC2H5
O
CH2 C OC2H5

CH3 C
O
CH2 C OC2H5

_ ..
: O C2H5
..

Dieckmann Condensation
A CYCLIC CLAISEN CONDENSATION

MeOOC CH2CH2CH2CH2 COOMe

NaOMe
MeOH
O
C O CH
3

O
O
C O CH3

..

CH C O CH3
O

PATTERNS
HO
R CH2 C

(H)

-hydroxy to C=O

O
CH C R

3-hydroxyaldehyde or
(H)

Type of
Condensation
Reaction

ALDOL

3-hydroxyketone

-H2O

R CH2 C

O
R CH2 C

,-unsaturated C=O

C R

2-propen-1-al or
2-propen-1-one

O
CH C OR
R

-keto ester

ALDOL
(with loss of H2O)

CLAISEN

SYNTHESIS

Synthesis of a Perfumery Compound

2
H2C
H2C

O
C
C

cis

CH2 CH2 CH CH CH2 CH3

O
KOH

CH3

Aldol Condensation

H2C
H2C

cis
CH CH2 CH CH CH2 CH3

C OH
CH3

Dehydration

- H2O

O
CH2
C
H

CH2 CH3
C
H

CH3

cis-Jasmone
Scent of Jasmine in perfumes.

Why dont the

other sets of -H
react?

Biological Synthesis of Fructose

O
CH2 CH

OH

CH2 C

O
CH2 O

OH

OH

O
Dihydroxyacetone phosphate

OH
Glyceraldehyde-3-phosphate

CH2 CH

CH

OH

OH

OH

ALDOL
CONDENSATION

enzyme

OH

O
CH2 O

P
O

Fructose-1,6-diphosphate

OH

Synthesis of an Insect Repellent

O
CH3 CH2 CH2 C

OH
H

NaOH

CH3 CH2 CH2 C

O
CH3 CH2 CH2 C

CH3 CH2 CH
H

ALDOL
CONDENSATION

OH
CH3 CH2 CH2 C
CH3 CH2 CH

H
C

O
2-Ethyl-3-hydroxyhexanal
OH

H2

H
C
O

CH3 CH2 CH2 C H

Ni

CH3 CH2 CH

HYDROGENATION

H
C

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
+

:Nu

:Nu

1,2-addition

1,4-addition

OH
C
C C

Nu

H C
C C
Nu

conjugate
addition

CONJUGATE ADDITION
..

.. : O:

O:
H

C
C C

H
:N C

H
CH3

H C C
:N C

CH3

H
H-OH

..

O:
H C
CH3
H C C
H
:N C

In conjugate addition
the nucleophile adds
and then picks up a
hydrogen from the
solvent medium.

CONJUGATE ADDITION
GENERALIZATION

conjugated ketone

C C
H

stereochemistry
also matters

C R
H

weak
nucleophiles/bases
conjugate addition
1,4-addition

strong
bases

direct to C=O
1,2-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
Alcohols

..
R-NH2
..
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

HO

CH3

strong bases add

by 1,2 addition

CH3Li

(CH3)2CuLi

or
CH3MgI

or
(CH3)2Cd

_
:CH3

CuCl

CH3
weaker bases add
by 1,4 addition

_
:CH3

+
C-Li and C-Mg bonds are
more ionic (stronger bases)

R-Cu and R-Cd bonds are

more covalent (weaker bases)

STEREOCHEMISTRY ALSO MATTERS

LARGE GROUPS ON EITHER SIDE OF THE CARBONYL FAVOR CONJUGATE ADDITION
large groups here
promote 1,4 addition

O
H

C
C C

CH3
CH CH3

CH3MgBr

STERIC HINDRANCE

H
H C C

CH3

large groups here can

also promote 1,4 addition

OH
CH3
C
CH CH3
H
major product

O
H
C C
H

C H

OH

CH3MgBr

H
large groups here
promote 1,2 addition

C H
C C

CH3
major product

small groups here

make 1,2 addition
more probable

FRONTIER MO THEORY
CONJUGATED KETONES

FRONTIER MO THEORY
NUCLEOPHILE

HOMO
LUMO
FILLED MOs

HOMO

E+
FILLED MOs

ELECTROPHILE

:Nu-

LUMO MAPPED ONTO ELECTRON

DENSITY
BLUE REPRESENTS MAXIMUM DENSITY OF LUMO

A
B

ROBINSON ANNELATION
FORMING RINGS BY COMBINING
CONJUGATE ADDITION WITH AN ALDOL CONDENSATION
METHYL VINYL KETONE (MVK)

Conjugate Addition of Cyclopentanone to MVK

enolate
weak base

MVK
methyl vinyl ketone

..

:O

CH3

- ..
: O-CH
.. 3

C
H

NaOCH3
CH3OH

:O

O:
H

.. : O:

..

..

CH3

H-OCH3

..

:O

..

O:
C
CH2 CH2 CH3

- ..
+ : O-CH
.. 3
can continue

ROBINSON ANNELATION
USES MVK TO BUILD A RING
FROM PREVIOUS SLIDE

O
H
H

O
CH3

NaOCH3

O
C
CH2 CH2 CH3

CH3OH

Michael
addition
O

-O
H3O+
(workup)

- CH
: 2
C
CH2 CH2 O

Annelation
(ring formation)
internal aldol condensation

ANOTHER EXAMPLE
MICHAEL ADDITION + ALDOL CONDENSATION
2

ALDOL

H3C
C O

CH
O

NaOEt
EtOH

CH2

Most acidic set

of hydrogens
reacts first.

MICHAEL

DECARBOXYLATION
OF -KETOACIDS

HYDROLYSIS OF A -KETOESTER GIVES A -KETOACID

Claisen
Condensation
O
CH3CH2CH2

-Ketoester
O

NaOCH3

C OMe
CH3OH

CH3CH2CH2

CH3CH2CH2

C CH

CH2CH3

- CO2

C CH C OMe
CH2CH3

H3O+

hydrolysis

O
CH3CH2CH2

C CH C OH
CH2CH3

Ketone
then, the -ketoacid
decarboxylates in acid

-Ketoacid

Decarboxylation of a -Ketoacid
6-ring

concerted step
O
C

heat + acid

C O
C

O
C

H
C

O
C O

enol
tautomerization
Carbon dioxide is easily lost
since a nice 6-membered
ring transition state can be
formed for a concerted
process.

O
C

CH

O C O

ketone

SYNTHESIS OF KETONES
FROM -KETOESTERS
ALKYLATION / DECARBOXYLATION OF -KETOESTERS

STEP ONE - MAKING THE -KETOESTER

.. discussed earlier
O

a -ketoester

CH3 C O CH2 CH3

O

NaOCH2CH3

CH3 C O CH2 CH3

CH3 C CH2 C O CH2 CH3

+ CH3 CH2 O H

Claisen
condensation

a different R group
could be used here

STEP TWO - ALKYLATE THE -KETOESTER

CH3 C CH2 C O CH2 CH3

NaOCH2CH3
CH3I
O

CH3 C C C O CH2 CH3

H3C CH3

a primary halide
is best

STEP THREE - HYDROYSIS AND DECARBOXYLATION

O

CH3 C C C O CH2 CH3

H3C CH3
-ketoester
H3O

this
part will be
the ketone

-ketoacid

CH3 C C C O H
H3C CH3
heat

easily when heated in acid

(see next slide)

- CO2

CH3
CH3 C CH
CH3

-ketoacids decarboxylate

ketone

ALKYLATION CAN BE SKIPPED

O
CH3CH2CH2

NaOCH3

C OMe
CH3OH

CH3CH2CH2

C CH C OMe
CH2CH3

H3O+

O
CH3CH2CH2

C CH2CH2CH3

an unbranched ketone

DITHIANE ANIONS

Conversion of Aldehydes to Ketones

Dithiane Anions
a 1,3-dithiane

O
R C H

HSCH2CH2SH

H2SO4

aldehyde

-H2O

various
methods

R'

R C R' H2/Ni
R
or
ketone
Hg(OAC)2
H2SO4

acidic H

butyllithium
(strong base)

R'

- ..

.. -

C
R'

SN2

X
anion is stabilized
by empty 3d
orbitals on sulfur

PATTERNS

PATTERNS
HO
R CH2 C

(H)

-hydroxy to C=O

O
CH C R

3-hydroxyaldehyde or
(H)

Type of
Condensation
Reaction

ALDOL

3-hydroxyketone

-H2O

R CH2 C

O
R CH2 C

,-unsaturated C=O

C R

2-propen-1-al or
2-propen-1-one

O
CH C OR
R

-keto ester

ALDOL
(with loss of H2O)

CLAISEN

PATTERNS
O
R CH2 C

-keto acid

O
CH C OH
R

H3O+

H3O+

heat

ketone

DECARBOXYLATION
R-X (alkylation)
O

O
R CH2 C

CONTINUED

CH2 +
R

CO2

R CH2 C

O
CH C OR
H

from Claisen

SOME OTHER APPLICATIONS

ACYLOIN CONDENSATIONS

Acyloin Condensation
Na
O
2

R C OR'

Na

O O

Na
xylene

R C C R

OH O

H2 O
mechanism
not required
This is a good way to make large rings.

R CH C R

an acyloin
High dilution.

A Cyclic Acyloin Condensation

O
O

C OC2H5
Na

(C32H64)

xylene

C
(C32H64)
C OH
H

C OC2H5
O

Zn(Hg)
Conc HCl

(C32H64)

CH2
CH2

cyclotetratriacontane
A VERY BIG RING !

PATTERN

HO

R CH C R

-hydroxyketone
an acyloin

ACYLOIN

CATENANES

Catenanes
Interlocked
rings.

O
(C34H68)

(C32H64)

C
OC2H5
OC2H5
C
O

Na
xylene
cyclo-C34
O
C
(C34H68)

(C32H64)
CH

a Catenane
(1 - 2% yield)

OH

HELL-VOLHARD-ZELINSKY
-BROMOACIDS AND -BROMOESTERS

Hell-Volhard-Zelinsky Reaction
O
R CH C OH
H

1) P, Br2

R CH C OH

2) H3O+

-bromoacid

Br

PBr3
O

H3O+
(workup step)

R CH C Br
H

..

:O H

Acid halides have

a larger enol content
than ketones.

R CH C Br
Br

O
R CH C Br
Br

Br
Double bonds react
with bromine!

Resonance increases the electron

density in the double bond. Enols
are more reactive than alkenes.

Synthesis of Aminoacids and a-Hydroxyacids

neutralization step not shown

O
CH C OH +

NH3

CH C OH
NH2

Br

phenylalanine

O
CH3 CH C OH
Br

NaOH

CH3 CH C OH
OH

lactic acid

REFORMATSKY REACTION
A COUSIN TO THE GRIGNARD REACTION

Reformatsky Reaction
O

O
R CH C OH
Fischer
Esterification
or via the
acid chloride

Br

R CH C O CH2CH3
Br

-bromoester
Zn, ether

O
R CH C O CH2CH3

H3C C OH
H

R CH C O CH2CH3
1)

O
H3C C H

2) H O+
3

ZnBr

Reformatsky
reagent
Reacts like a
Grignard reagent!

ENOL CONTENT

Keto-Enol Tautomerism
H
O

C C

O
C C

H
keto
For most ketones, the keto form
predominates in the equilibrium

enol

AS A GENERAL RULE: ENOLS ARE

UNSTABLE
ol

ENOLS :
( have -OH attached to a double bond)
Think of this combination as unstable.

ene
OH

NOTE :
Phenols are not enols and they are
very stable (benzene resonance).

TAUTOMERISM
ENOL

H3C

KETO

O H
C

CH2

H3 C

TAUTOMERS :

O
C CH2
H

unstable enol

Most enols are not favored,

enol

keto
they rapidly change to keto.

E
N
E
R
G
Y

species in
equilibrium
that differ in
the position
of a proton or
other group.

To interconvert tautomers,
a proton is transferred
from oxygen to carbon.
Mechanism, next
slide..

Tautomerism is Catalyzed by Traces of

Either Acid or Base
BASE
CATALYSIS

..

O:

O:
C C

C C

enolate
ion

- ..
keto

.. H-O:
..
H

.. H-O: +
..

..

: O:

- ..

: O:

C C

C C
enol

resonance structures

..
H-O:
H

Tautomerism is Catalyzed by Traces of

Either Acid or Base
..

ACID
CATALYSIS

..

O:

H-O-H
+
H

C C
H

keto

.. H

+O
C C

..

:O-H
H

: O:
C C

..
+

enol

H-O-H
+
H

CONVERSION OF AN ENOL TO A KETONE

( catalyzed by small amounts of acid )
ENOL

O
H3 C

O H
CH 2

H3 C
+

H O H

C
+

+O

CH 2

H3 C

H
H

H O H

O H
O

+O
H3 C

CH 2

H
H

CH2
H

H3 C

C CH2
H

KETONE

Enol Percentages are Low

in Most Ordinary Ketones
O

OH

4.1 x 10-4 %

OH

CH3 C CH3

H2C

C CH3

O
H2C

CH C CH3

H2C

< 2 x 10-4 %

OH
CH C CH2

2.5 x 10-3 %

FACTORS THAT STABILIZE

THE ENOL FORM
increasing the amount in the equilibrium

MOSTLY RESONANCE
O

O
R

O
R

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

H3C C CH2 C H

H3C C CH2 C CH3

H3C C CH2 C OC2H5

OH

H3C C C C H

OH

98 %

H3C C C C CH3

OH

80 %

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).