Chapter 17
Aldehydes and Ketones II.
Oxidation and Reduction:
Synthesis
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Assignment for
Chapter 17
•
•
•
•
Sections 17.0 through 17.2
Section 17.3 -- SKIP
Sections 17.4 through 17.12
Section 17.13 through 17.15 -SKIP
• Sections 17.16 through 17.20
• Problems
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Problem Assignment
• In-Text Problems
– 17-1 through 17-11
– 17-15 through 17-18
• End-of-Chapter Problems
– 1 through 4 (all parts)
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Reduction of a Carbonyl Group
to an Alcohol
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What If We Had the World’s
Simplest Nucleophile?
_
..
:O:
:O :
R
C
_
R
R
C
H
OH
R
H2O
R
C
R
H
H:
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•If we could make this work, we would
have means of reducing the carbonyl
group.
•Go back and re-read the Special Topics
box at the beginning of Chapter 14.
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Lithium Aluminum Hydride
H
H
Al
H
Li
H
Lithium aluminum hydride, LiAlH4, is a very
powerful hydride donor, and thus it is an
excellent reducing agent.
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Outline
O
O
C
R
R
R
Al
C
R
H
H
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Lithium Aluminum Hydride
Reduction of Aldehydes
and Ketones
R
O
LiAlH4
+
4
H
C
R
R
C
O
Al
Li
+
R
4
R
H
C
O
O
Al
R
4
Li
+
+
4 H2O
4
R
C
H
R
+
Al(OH)3
+
LiOH
H
These reactions typically go in very high yield.
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Learn it this way:
O
O
OH
LiAlH4
C
R
H2O
R
C
R
R
C
R
R
H
H
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Aluminum is required to coordinate
with the oxygen of the carbonyl group.
For example, in the absence of
aluminum (using sodium hydride, NaH
as the reducing agent), there is no
reduction.
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You Must Be Careful!
LiAlH4 + 4 H 2O
LiOH + Al(OH) + 4 H2
3
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A similar, but less reactive,
reducing agent is sodium
borohydride, NaBH4.
H
H
B
H
Na
H
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Sodium Borohydride Reduction
of Aldehydes and Ketones
+
O
O Na
NaBH4
C
R
O H
H2O
R
C
R
R
C
R
R
H
H
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Example
H
O
NaBH4
H2O
OH
or
LiAlH4
In general, the reduction should proceed equally
easily from either side, yielding two mirror-image
products.
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Sodium Borohydride
Reduction of Camphor
CH3
H3C
CH3
H3C
H3C
1) NaBH4
+
H
2) H2O
H3C
O
Camphor
CH3
H3C
OH
H3C
OH
Borneol
(15%) (endo)
H
Isoborneol
(85%)
(exo)
In this case, approach by borohydride from the upper
side is sterically hindered by the bridge methyl group.
The result is a predominance of exo alcohol.
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Sodium Borohydride Reduction
of Norcamphor
1) NaBH4
+
H
2) H2O
O
Bicyclo[2.2.1}heptan-2-one
(Norcamphor)
OH
endo alcohol
(86%)
OH
H
exo alcohol
(14%)
•Here, it is the underside of the molecule that is more
sterically hindered, so the favored alcohol is the endo
alcohol.
•Similar results are obtained with lithium aluminum
hydride.
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Another example:
O
C
H
LiAlH4
CH2 OH
or
NaBH4
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Contrast these two reactions
OH
O
C
CH3
CH2
CH2
O
C
CH3
CH2
1) LiAlH4
2) H2O
CH
CH3
CH2
CH2
OH
CH2
O
O
OH
C
CH3
CH2
CH2
O
C
O
CH3
CH2
1) NaBH4
2) H2O
CH
CH3
CH2
CH2
O
C
CH3
CH2
O
Note that sodium borohydride is more selective.
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Catalytic Hydrogenation of
Aldehydes and Ketones
O
O
C
R
+
R
H2
Ni
R
C
H
R
50°
(1000 psi)
H
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Reduction of a Carbonyl
Group to a Methylene
Group
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We are trying to
accomplish...
O
C
CH2
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Clemmensen Reduction
H
O
Zn(Hg)
R
C
R
R
C
R
HCl (conc.)
H
Zn(Hg) is a zinc amalgam
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•The mechanism of the Clemmensen reduction
involves the formation of some sort of zincketone complex.
•This reaction is a good method for the
reduction of acid-stable carbonyl compounds
(Note that the reaction takes place in the
presence of concentrated HCl).
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Example of a Clemmensen
Reduction
O
O
C
CH2 CH2 C
O
OH
Zn(Hg)
CH2 CH2 CH2 C
OH
conc. HCl
heat
90% yield
Notice that the reduction does not affect the
carboxyl group
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Wolff-Kishner Reduction
H
O
KOH
R
C
R
+ H2N
R
NH2
HO CH2
CH2
C
R
OH
H
190 - 200 °C
+
N2
+
H2O
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• The mechanism involves the formation of a
hydrazine adduct, which loses water to form
a hydrazone.
• The hydrazone then rearranges to lose a
molecule of nitrogen gas, leaving behind a
carbanion.
• The carbanion picks up a proton from the
solvent to form the product.
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This will never show up on any of my exams!
OH
O
H 2N
NH 2
- H 2O
R
C
R
R
C
C
R
acid
R
R
N
NH
NH 2
NH 2
rearrange
H
H
R
H
C
H 2O
R
C
R
R
C
H
R
+
N
R
N
N
N
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The Wolff-Kishner reduction is useful
for the reduction of carbonyl
compounds that are stable in strong
base.
(Note that the reaction takes place in
the presence of concentrated KOH or
other base)
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Example
N
O
H2N
NH 2
NH 2
O
O
N
N
H
H
Isatin
NaOCH2CH3
CH3CH2OH
O
N
H
75% yield
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Desulfurization
CH2 CH2
O
+
C
R
HS CH2 CH2 SH
R
CH2 CH2
S
S
C
R
+
H2
Raney Ni
BF3
S
S
C
diethyl
ether
R
+
H2O
R
H
H
+
C
R
CH3 CH3
R
R
+
2 NiS
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•Advantages: High yields
Mild and nearly neutral
reaction conditions
•Disadvantages: Stinky!
Raney Nickel is
tricky to prepare
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Example of a Raney Nickel
Desulfurization
CH2
HS
SH
CH2
S
O
BF3
ether
S
H2
Raney Ni
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