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