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..
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
..
O:
base
C C
H
acidic : pK ~ 25
a
enolate
ion
..
O:
:B
-hydrogen
Major resonance
contributor:
charge is best
on oxygen =
C C
..
However, the
ion is more
nucleophilic
at carbon.
HOMO
densityHOMO
REACTIVE
SITE
..
Charge is
on oxygen
but carbon is
nucleophilic
..
..
:O
H3C C
note the
bonding
NEGATIVE
CHARGE
:O :
CH
.. 2
H3C C
major
CH2
densityelectrostatic
potential
.. :O :
C C
enolate
CH3
..
O:
CH3
C C
..
ketolate
ALKYLATION OF KETONES
NON-CATALYTIC BASES = NaH, LDA
REACT ONCE
one shot
REACT REPEATEDLY
It just keeps
on going and
going ..
Alkylation of a Ketone
NON-CATALYTIC BASES REACT ONCE
one mole
NaH
O
C CH3
THF
-hydrogens
..
C CH2
CH3-I
one shot
one mole
_
..
C CH2 + H
CH3-I
one mole
LDA
THF
O
O
C CH2 CH3
monoalkylation
_
: N : Li
H3C CH
CH3
CH CH3
CH3
Sodium Hydride
NaH
LDA
Lithium Diisopropyl Amide
a strong base
ALKYLATION OF CYCLOHEXANONE
CATALYTIC BASES REACT REPEATEDLY
..
CH3CH2 I
:O
:O
CH2CH3
:-
NaOH
.. :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
KOH
CH3I
O
CH3
O
CH3 H3C
CH3
H3C
CH3
CH3
CH3
H3C
CH3
O-
OCH3
CH3
CH3-I
ALKYLATION OF KETONES
NON-CATALYTIC BASES = NaH, LDA
:O
:H H
NaH
..
Na+
:O
..
.. :O :
H2
gone
one
mole
one shot
stoichiometric base
CH3I
..
:O
CH3
H
+ NaI
one shot
: N : Li
CH CH3
H3C CH
CH3
CH3
LDA
Lithium Diisopropyl Amide
a strong base
..
(iPr)2NH
X
difficult
.. (iPr)2N :
ALKYLATION OF KETONES
ENAMINES
ALKYLATION OF CYCLOHEXANONE
ENAMINES ALSO GIVE MONOALKYLATION
..
CH3CH2 I
+
N
CH2CH2
Alkylates once
and stops !
one shot
O
CH2CH3
O
first
time
Alkylations go one-at-a-time.
You must make a new enamine
each time.
CH3
CH3
CH3 H3C
second
time
This enamine
is favored.
N
CH3
Steric hindrance
This enamine
is not favored.
CH3
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
IODOFORM REACTION
Iodoform Reaction
O
NaOH
R C O Na + CHI3
R C CH I2
3
yellow
precipitate
NaOH
NaOH
..
R C CH
2
H2O
-: 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:
..