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Chapter 18 – Ketones and Aldehydes

Nomenclature
o Ketones have priority over alcohols
 Find the longest chain with the carbonyl in it.
 Name the parent and replace the “e” with “one”
 Say where the carbonyl is.
octan-3-one


When the ketone is not the high-priority group, you call the carbonyl
“oxo” to name it.
Common names: Name the two pieces coming off the carbonyl and call it
“ketone”
ethyl butyl ketone
o Aldehydes have priority over ketones
 Find the longest chain with the carbonyl at the end.
 Name the parent and replace the “e” with “al.”
3-oxo-octanal

Synthesis of ketones and aldehydes
o Oxidation of alcohols
Chromic Acid
1° ROH
RCOOH
2° ROH
Ketone
3° ROH
NR
o Ozonolysis of alkenes
KMnO4
RCOOH
Ketone
NR
PCC
RCHO
Ketone
NR
Swern
RCHO
Ketone
NR
1) O3
2) DMS
 See Chapter 8 for review
o Friedel-Crafts Acylation
AlCl3
 See Chapter 17 for review
o Hydration of alkynes
 Acid-catalyzed
H2SO4 (aq)
HgSO4

Hydroboration-oxidation
1) Sia2BH
2) H2O2, -OH
 See Chapter 8 for review
o Synthesis from carboxylic acids and acid chlorides
 Acids are first converted to acid chlorides.
SOCl2
OH

Acid chlorides are reduced to aldehydes with LiAlH(OtBu)3
1) LiAlH(OtBu)3
2) H2O

LiCuR2
o LiCuR2 is like a specialty version of a Grignard that only replaces the Cl of acid
chlorides.
LiCu(CH2CH3)2

Wittig Reactions
o Overall reaction: turn a carbonyl into a carbon-carbon double bond.
 The carbon of the alkyl halide replaces the oxygen of the carbonyl.
BuLi
Ph3P
CH3
o Step one: Triphenylphosphine attacks an alkyl halide
Ph
Ph
CH3
Ph
Ph
Ph
Ph
o Step two: Grignard deprotonates to form the ylide
 What’s an ylide?
 An ylide is when you have two atoms next to each other where
one has a negative charge, the other has a positive charge, and
they both have full octets.
Bu
Ph
Ph
-
Ph
Ph
Ph
Ph
o Step 3: ylide attacks the carbonyl
Ph Ph
Ph
-
o Step 4: O- forms bond with P+
Ph3
Ph3
Ph3
o Ring collapses – fun with arrows
Ph3
o

Considerations: You want alkyl halide to be methyl or primary because they are best for
SN2
Hydration
o Acid-catalyzed
OH
OH
H+
OH
H2O
o Base-catalyzed
OH
H2O
OH
OH
-
OH

o Rates
 This reaction doesn’t happen to a large degree with most ketones
 It happens a little more with aldehydes
 Keq for formaldehyde is 40
Formation of Cyanohydrins
o HCN is a toxic gas, so most often it is made in situ from excess NaCN and HCl.
o Step one: cyanide ion attacks the carbonyl.
CN
-CN
o Step two: protonation
CN
CN
H--CN
OH
o Things you can do with cyanohydrins.
 Catalytic hydration
CN

Hydrolysis
CN

H2/Pt
H3O+
COOH
NH4+
Formation of imines
o Overall: The nitrogen replaces the oxygen of the carbonyl, forming a carbonnitrogen double bond.
 It should be mildly acidic; pH between 4 and 5.
NH3, H+
o Mr. Baker said that you are not responsible for the mechanism, but here it is in
case you want to look at it.
o Step one: protonation of the carbonyl
H+
o Step two: Amine attacks the activated carbonyl
OH
o Step three: Deprotonation
OH
OH
o Step four: Protonation of hydroxyl
OH
H+
OH
o Step five: Loss of water
o Step six: Deprotonation

Formation of acetals
o You could call an acetal a geminal diether
 A hemiacetal is what you have when you’re halfway there.
 It is one hydroxyl and one alkoxy group coming off the same carbon.
o Step one: protonation of the carbonyl
H+
o Step two: the alcohol attacks the activated carbonyl
o Step three: deprotonation to give the hemiacetal
o Step four: Protonation of the hydroxyl
H+
o Step five: water falls off
o Step six: another alcohol adds
o Step seven: deprotonation gives the acetal


Removing acetals
o Use very dilute acid
o The mechanism of hydrolysis of an acetal is just the same thing going backwards.
Acetals and hemiacetals in sugars
o Sugars exist in their cyclic forms as hemiacetals
 The carbon which is the hemiacetal or acetal is called the anomeric
carbon.
 When the OH is up, it’s Beta; when it’s down, it’s alpha.
OH
OH
OH
OH
anomeric carbon
OH
o When they link up to become polysaccharides, they become acetals.
OH
OH
OH
O
OH
OH
OH
OH
OH
o Something you don’t need to know for this class, but the MCAT expects you to
know:
 Sugars that differ by only one chiral center are called epimers.
CHO
CHO
H
OH
H
OH
OH
HO
H
OH
H
OH
H
OH
H
OH
H
H
CH2OH
CH2OH
D-allose



D-glucose
Protecting groups
o Requirements of a good protecting group
 Easy to put on
 Nonreactive under the reaction conditions
 Easily removable
Oxidation of aldehydes
o Aldehydes are oxidized to carboxylic acids by KMnO4 and chromic acid
Reductions of ketones and aldehydes
o The following reductions which have already been seen work on ketones and
aldehydes:
NaBH4
LiAlH4
H2/ Raney
Zn(Hg)/HCl
N2H4/base
Ni
(aq)
Ketone
2° ROH
2° ROH
2° ROH
Alkane
Alkane
Aldehyde
1° ROH
1° ROH
1° ROH
Alkane
Alkane