Carbanions - University of Alberta
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Transcript Carbanions - University of Alberta
Aldol reactions
© E.V. Blackburn, 2011
Acidity of the hydrogens
The hydrogens are weakly acidic in comparison with the
hydrogen of the carboxylic acid group. However they are
the most acidic hydrogens of aldehydes and ketones:
H
C H
H
H
C
H
C H
O
R C C
H
Ka = 10-50
Ka = 10-44
Ka = 10-25
Ka= 10-19 - 10-20
Why?
© E.V. Blackburn, 2011
Acidity of the hydrogens
Ionization of an hydrogen gives a resonance stabilized
carbanion:
C C
H O
+ :B
O
C C
-
+ HB +
C C
O
O
C C
-
© E.V. Blackburn, 2011
Keto - enol tautomerism
- H+
H
+ H+
H
OH
O -
stronger
acid
H
-
H
OH
enol structure
H
C C
H O
weaker
acid
O
H
C C
H O
keto structure
Structural isomers that are formally related only by the
shift of a hydrogen and one or more bonds are called
tautomers.
© E.V. Blackburn, 2011
Halogenation of ketones
C C
H O
+ X2
OH- or H+
C C + HX
X O
-haloketone
X2 = Cl2, Br2, or I2
© E.V. Blackburn, 2011
Base catalyzed halogenation
of ketones
CH3COCH 3 + Br2 + :B
CH 3COCH 2Br + Br - + HB +
rate = k[acetone][B:]
H :B
H3C C
C H
H
O
H3C
H3C
H3C
CH2
O- Br-Br
CH2
+ HB
slow
OC
O
CH2Br
+ Br-
fast
© E.V. Blackburn, 2011
Acid catalyzed halogenation of
ketones
CH 3COCH 3 + Br2
acid
CH 3COCH 2Br + HBr
rate= k[HB][acetone]
© E.V. Blackburn, 2011
Acid catalyzed halogenation of
ketones
H3C
C
O
CH3
H+
H3C
H
H3C
H3C
+
C H
H
O
+H
-H
H3C
CH2
C
:OH
H3C
H3C
Br-Br
CH2Br
C
O
+H
+
-H
CH3
C
OH
+
CH2
C
OH
CH2Br
C
O
+H
H3C
C
O
+ Br-
CH2Br
© E.V. Blackburn, 2011
Halogenation of ketones
H+
O + HBr
O + Br2
Br
(CH3)3C C CH3 + Cl2 + OHO
the haloform reaction
(CH3)3C C CCl 3
O
OHCHCl 3 + (CH3)3CCO2-
© E.V. Blackburn, 2011
Carbanions
C C
H O
C C
O
+ :B
+ HB +
The carbanions formed, conjugate bases of very weak
acids, are very strong bases. They are nucleophiles!
O
+
H+
C C O
or base
H
H
C C C O
O
an aldol
© E.V. Blackburn, 2011
Base-promoted aldol addition
-
H OH
H3C C
C H
H
O
H3C
O
CH3
H3C
O
O
H 3C
O
CH3
OCH3
+ H2O
O
CH2 H3C
H3C
CH2
H 2O H 3 C
O
CH3
OCH3
CH3
OH
CH3
© E.V. Blackburn, 2011
Base-promoted aldol
condensation
O
H 3C
CH3
H CH3
+ H C C O
H
OH
-
CH3 H CH3
H3C C
C C O
O
H
H
NaHSO 4
(CH 3)2C=CHCCH 3
O
© E.V. Blackburn, 2011
Base-promoted aldol
condensation
O
H 3C
H H
H C C O
+
H
H
OH
-
H H H
H3C C C C O
O H
H
NaHSO 4
CH3CH=CHCHO
crotonaldehyde
© E.V. Blackburn, 2011
Acid-catalyzed aldol addition
H3C
C
O
H3C
CH3
H+
CH3
H2O
C
H+
OH
+
H3C CH2 H3C +
C
C OH
:OH
H3C
OH
OH
+
H3C
CH3
C
OH
+
H3C CH2
C
OH
OH
OH
+
H2O
OH
O
© E.V. Blackburn, 2011
Dehydration of aldol products
© E.V. Blackburn, 2011
Dehydration of aldol products
H
dilute HCl H
H
C O
+ H 2O
H3C C CH2CHO
C C
H 3C
H
OH
The ease and orientation of the elimination reaction
depends on the particular stability of the alkene
formed. This stability is due to the fact that the
carbon - carbon double bond is conjugated with the
carbon - oxygen double bond - remember 1,3butadiene?
© E.V. Blackburn, 2011
Dehydration of aldol products
O
C
CH3
CH3 H
C
C C
OH H O
+
H 3C
O
C
-H2O
NaOC 2H5
H 3C
O
C
H
© E.V. Blackburn, 2011
Crossed aldol reactions?
H
C
O
+ CH3CHO
OH-
OH
H
C
CH2CHO
This can work! How?
CH=CHCHO
cinnamaldehyde
© E.V. Blackburn, 2011
Crossed aldol condensations
Good yields can be obtained under certain conditions:
• Mix the carbonyl compound having no hydrogen
with the base.
• Slowly add the carbonyl compound having an
hydrogen to this mixture. Why?
© E.V. Blackburn, 2011
Crossed aldol condensations
H
Ph C O
OH-
CH3CHO
H HH
20o
Ph-C=C-C=O
H H
CH3COCH 3
PhC=C-C-C H3
100o
PhCOCH 3
O
H H
Ph-C=C-C- Ph
O
© E.V. Blackburn, 2011