Chem 360 Jasperse Ch. 18 Notes. Aldehydes and Ketones
Synthesis of Ketones and Aldehydes
1
OH
Ph
PCC
OH
2
3
4
Ph
1. BH3•THF
Ph
OH
H2O, H+
Ph
PCC
OH
Ph
2. NaOH, H2O2
Ph
Ph
8.15
O
2. Me2S
Ph
OH
1. RMgBr
H
Ph
2. H+
H
+
O
Ph
R
OH
1. LiAlH4
Ph
OR 2. H+
H
NaOH
Br
Br
9
R
Ph
H
NaOH
10
Ph C C H
H2SO4
Markovnikov
Addition
11
Ph C C H
OH
Ph
"enol"
1. (Sia)2BH
Ph
2. NaOH, H2O2
Anti-Markovnikov
Addition
O
6.8
O
H2CrO4
Hg2+, H2O
6.8
H
R
OH
H
aldehyde
PCC
OH
10.11
O
PCC
acid or ester
R
R
Ketone
O
8
10.9
O
H2CrO4
Aldehyde
Ph
8.7
8.4
1. O3
O
7
O
O
H2CrO4
Ph
5
6
11.2
O
H2CrO4
Ph
11.2
O
Ph
H+, H2O
MECH
OH
"enol"
9.9F
O
Ph
Ketone
OH, H2O
MECH
9.9F
O
Ph
Aldehyde
1
Chem 360 Jasperse Ch. 18 Notes. Aldehydes and Ketones
O
12
Ph
OH
Ph
OLi
2. H+, H2O
acid
carboxylate
anion
O
13
O
1. 2 RLi
R
14
Ph
R
Cl
Ar-H, AlCl3
R
1. RMgBr Ph
R
CN
Nitrile 2. H+, H2O
N
H
18
S
R
H
S
H
Ph
R
ketone
18.9
18.11
Aromatic ketone
(from the acyl group's perspective)
1. BuLi
2. R-Br (1º)
3. Hg2+, H+, H2O
1. BuLi
2. R-Br (1º)
3.
R
H+, H2O
NH
"imine"
MECH
H+ Ph
1. KCN
Br
S
MECH
Aromatic ketone
(from the aryl group's perspective)
Ph
S
R
O
18.11
R
Ph
CN
Nitrile
Intermediate
(after step 1)
Primary Bromide 2. RMgBr
3. H+, H2O
17
Ph
H+, H2O
O
R
Cl
acid chloride
16
OH
O
O
Ph
HO
tetrahedral
"hydrate"
tetrahedral
dianion
AlCl3
15
acid
Ph
R
ketone
O
H
OLi
O
R2CuLi
Ph
Cl
acid chloride
LiO
2
Hg2+,
H+,
H2O
S
S
H
Li
Ph
R
HO NH2
tetrahedral
"aminol"
Steps 2 + 3
Step 2, SN2
H+, H2O
MECH
S
R
Li
18.10
18.10
O
Step 3,
S
S
H
R
S
S
R
R
Step 2, SN2
deprotonated,
carbanion
R
O
ketone
R
Ph
Hydrolysis
deprotonated,
carbanion
S
Ph
Step 3,
Hydrolysis
O
H
R
Aldehyde
18.8
O
R
R
Ketone
18.8
Chem 360 Jasperse Ch. 18 Notes. Aldehydes and Ketones
3
Reactions of Ketones and Aldehydes
19
O
1. RMgBr
R'
R
aldehyde
or ketone
H+
2.
O
R'
OH
Protonate
R
R'
R
anion intermediate
R
R
18.12,
10.9
Anionic
Mech: Addition-Protonation. Strong nucleophile, Strongly anionic. Irreversible.
20
O
R'
R
aldehyde
or ketone
O
NaBH4
or
LiAlH4
OH
Protonate
R'
R
H
anion intermediate
R'
H
R
18.12,
10.11
Anionic
Mech: Addition-Protonation. Strong nucleophile, Strongly anionic. Irreversible.
21
O
O
KCN, HCN
R'
R
aldehyde
or ketone
R'
CN
R
anion intermediate
Anionic
Mech: Addition-Protonation.
buffered. Reversible.
O
22
R'
R
18.15
CN
Medium nucleophile, Weakly anionic; literally
OH
H2O, OH-
R'
R
aldehyde
or ketone
OH
Protonate
R'
OH
R
tetrahedral
"hydrate"
"Hydrates" are present only
as transient equilibrium species.
They never form to 100% and are
never isolable. Always in equilbrium
their aldehyde or ketone.
18.14
Anionic
Mech Forward: Addition-Protonation. Nucleophile, anionic mechanism. Reversible.
Mech Reverse: Deprotonation-Elimination. Anionic mechanism. Reversible.
O
23
R'
R
aldehyde
or ketone
OH
H2O, H+
R'
OH
R
tetrahedral
"hydrate"
"Hydrates" are present only
as transient equilibrium species.
They never form to 100% and are
never isolable. Always in equilbrium
with their aldehyde or ketone.
Cationic
Mech Forward: Protonation-Addition-deprotonation. Weakly nucleophile, cationic
mechanism. Reversible.
Mech Reverse:
Protonation-Elimination-deprotonation.
Cationic E1-type
mechanism. Reversible.
18.14
Chem 360 Jasperse Ch. 18 Notes. Aldehydes and Ketones
24
O
OH
ROH, H+
R'
R
aldehyde
or ketone
H2O, H+
R'
OR
R
tetrahedral
"hemiacetal"
OR
ROH, H+
H2O, H+
4
18.18,
18.19
R'
OR
R
acetal
Cationic
Mech Forward: Protonation-Addition-deprotonation (hemiacetal) Protonationelimination-addition-deprotonation (acetal).
Weak nucleophile, cationic
mechanism. Reversible.
Mech Reverse:
Protonation-Elimination-Addition-deprotonation. (hemiacetal)
protonation-elimination-deprotonation (aldehyde or ketone). Reversible.
Notes:
•
•
•
•
•
•
•
•
25
O
Reactions are reversible
The “hemiacetal” is an intermediate, and can never be isolated
The acetal can be isolated.
Equilibrium considerations (LeChatelier’s principle) apply. When water is
plentiful, things go to the left. When water is scarce or removed, and alcohol
is abundant, things drive to the right.
Use H2O/H+ to hydrolyze an acetal back to an aldehyde or ketone
Use MeOH/H+ to convert an aldehyde to an acetal
Use HOCH2CH2OH/H+ to convert a ketone to an acetal
Aldehydes or ketones can be temporarily “protected” as their acetals, then
later “deprotected” by hydrolysis
OH
ZNH2, H+
R'
R
+
aldehyde H2O, H , -ZNH2
or ketone
R'
NHZ
R
tetrahedral
"aminol"
NZ
H+, -H2O
H2O, H+
R'
18.16,
18.17
R
imine
Cationic
Mech Forward:
Protonation-Addition-deprotonation (aminol)
Protonationelimination- deprotonation (imine). Mild nucleophile, cationic mechanism, buffered
conditions. Reversible. Note: sometimes addition precedes protonation, or is
concerted with protonation.
Mech Reverse: Protonation-Addition-deprotonation (aminol)
elimination- deprotonation (aldehyde or ketone). Reversible.
Protonation-
Notes:
• “Z” can be a carbon, nitrogen, oxygen, or hydrogen atom/group.
• The “aminol” can’t be isolated, it’s only present at equilibrium.
• Equilibrium factors apply. Water drives to the carbonyl side; removal of
water drives to the imine side.
Chem 360 Jasperse Ch. 18 Notes. Aldehydes and Ketones
O
26
R'
O
H2CrO4 or Ag+ etc.
H
5
R'
18.20
OH
No Mech Responsibility
“Tollens test” is a common chemical test for aldehydes. Ag+ undergoes redox
reaction with aldeydes to produce shiny Ag metal, or a “silver mirror”.
O
27
R'
Zn(Hg), HCl
R'
R
R
Acidic!
Works best for aromatic ketones.
18.21
Notes:
• Acidic conditions. Doesn’t work well for molecules with acid-sensitive
functionality.
• Works best for aromatic carbonyls. Saturated carbonyls are slower and less
efficient.
• Acidic nature is complementary to the basic analog below.
1. H2N-NH2
O
28
R'
R
R'
2. KOH, heat
R
Basic!
18.21
No Mech Responsibility
Notes:
• Basic conditions. Doesn’t work well for molecules with base-sensitive
functionality.
Basic nature is complementary to the acidic analog above.
OH
29
R'
CN
OH
H+, H2O
R
(for prep,
see Rxn 21)
R'
OH
R
O
hydroxy-acid
No Mech Responsibility
Notes:
• Unique access to 2-hydroxyacids..
Used in combination with reaction 21, the formation of the hydroxy-nitrile.
18.15