Ketones and Aldehydes

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Ketones and Aldehydes
sp2 sp2
carbonyl group
dipole
The carbonyl group is best represented by two
resonance forms
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Nomenclature see Text
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• Synthesis of Ketones and Aldehydes
• Review
• Oxidation of Alcohols (see Chapter 17)
• Ozonolysis of Alkenes (see Chapter )
• Friedal-Crafts Acylation (see Chapter 16)
• Hydration of Alkynes (see Chapter )
• New Syntheses
• 5. From 1,3-Dithianes to ketones or aldehydes

ketone
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Mechanism
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Then repeat sequence to place R on molecule if
desired.
1. 2. 3. 4. 5.
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6. Synthesis from Carboxylic Acids to Ketones
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Mechanism
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Hydrate of Ketone -unstable
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7. From Nitriles and Grignard Reagent to Ketones
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Example
1. 2.
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8. From Acid Chlorides to Aldehydes
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acts as H
hydride
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Reactions of Ketones and Aldehydes The most
common reaction is nucleophilic addition
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• Addition of Organometallic Reagents
• Grignard Reagent R-Mg-X
• Organolithium R-Li

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Synthesis of Grignard R-X Mg ?
R-Mg-X Keep dry!! Synthesis of
Organolithium R-X 2Li ? R-Li
Li X-
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a. Ketone
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Tertiary Alcohol
b. Aldehyde
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Secondary Alcohol
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c. Reaction with formaldehyde
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Primary alcohol
Side Reactions of Grignards and
Organolithiums Both of these reagents react as
strong bases and abstract protons from water
R-Mg-X H2O ? R-H Mg(OH)X R-Li
H2O ? R-H LiOH
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In fact, the reagents react as bases with any
protic source including H2O ROH
RCO2H RNH2 water alcohol
carboxylic amine
acid
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2. Addition of Hydride (H ) Sources of
Hydride NaBH4 sodium borohyride
- compatible with protic solvents, e.g.
methanol LiAlH4 lithium aluminum
hydride - incompatible with protic
solvents becauses it reacts to form
H2 gas (plus heat!).
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H
carbonyl alkoxide
alcohol
Functional Group
NaBH4
LiAlH4 H2/catalyst Product
Alkenes no no
yes alkane Alkynes no
no yes alkane or alkene Ketones
yes yes yes 20
alcohol Aldehydes yes yes
yes 10 alcohol Acids no
yes no 10 alcohol Esters no
yes no 10 alcohol (2
equiv) Nitriles no
yes yes 10 amine Imines no
yes yes 10 or 20 amine Amides no
yes no 20 amine
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Conclusion NaBH4 is much less reactive and
selective than LiAlH4 as a
hydride reducing agent.
Examples
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2.
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3. Addition of Water Hydration
The equilibrium usually favors the ketone but not
in every case.
K0.002 K0.7 K2000
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The hydrates of aldehydes are stable compared to
those of ketones. Why? Answer Aldehydes are
more electrophilic
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Methyl group donates electrons to stabilize CO
Only one methyl group to stabilize CO
4. Addition of HCN (hydrogen cyanide)
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H-CN
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cyanohydrin
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Again, an equilibrium is established.
Percent Cyanohydrin 100 95 lt5
Why so little cyanohydrin?
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5. Addition of Ammonia and 10 Amines
H
imine
Mechanism
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This reaction works best at pH 4-5, i.e. slightly
acidic.
Examples
oxime
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This nitrogen addition reaction can be
generalized to make a variety of derivatives of
ketones and aldehydes. Mechanistically, all
reactions are similar. The only difference is
the Z group that is carried along in the
Reaction.
Z Reagent
Product (you draw)
-H NH3 ammonia
imine -R R-NH2 10 amine
imine -OH
HO-NH2 hydroxyl amine oxime -NH2
NH2-NH2 hydrazine hydrazone -NHPh
PhNH-NH2 phenylhydrazine phenylhydrazone -NHC
NH2 NH2CNH-NH2 semi-carbazide
semicarbozone
O
O
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6. Addition of Alcohols Acetals
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Mechanism Blackboard
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Examples
Cyclic Acetals useful protecting groups.
Protecting Group - group that is added onto
the molecule by chemical reaction to prevent
the original functional group from reacting in
a given synthetic step. The original
functional group is regenerated in a later
step.
diol
cyclic acetal
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Acetal as a Protecting Group
What is wrong with the above reaction??
Answer The Grignard reagent contains a carbonyl
group, which means the reagent, once made, would
reacts with the starting bromoaldehyde.
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The aldehyde needs to be protected prior to
formation of the Grignard to avoid the
self-reaction.
protect
deprotect
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7. Deoxygenation of carbonyl groups
Clemmensen Reduction Wolff-Kishner Reduction
8. Addition of Phosphorus Ylides Wittig reaction
This reaction will make an alkene from a carbonyl
compound and a phosphorus ylid.
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alkene
phosphorus ylid
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Mechanism Blackboard
Examples
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How would you synthesize this molecule?
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Georg Wittig Nobel Prize 1979
His most important achievement is the discovery
of the rearrangement reaction which bears his
name. In the Wittig reaction (Fig 3) an organic
phosphorus compound with a formal double bond
between phosphorus and carbon is reacted with a
carbonyl compound. The oxygen of the carbonyl
compound is exchanged for carbon, the product
being an olefin. This method of making olefins
has opened up new possibilities, not the least of
which are for the synthesis of biologically
active substances containing carbon-to-carbon
double bonds. For example, vitamin A is
synthesized industrially using the Wittig
reaction.