Organic Chemistry, 5th ed.
Marc Loudon
Chapter
19
The
Chemistry
of
Aldehydes
and
Ketones.
Carbonyl‐Addi7on
Reac7ons
Eric J. Kantorowski
California Polytechnic State University
San Luis Obispo, CA
Chapter
19
Overview
19.1
Nomenclature
of
Aldehydes
and
Ketones
19.2
Physical
Proper;es
of
Aldehydes
and
Ketones
19.3
Spectroscopy
of
Aldehydes
and
Ketones
19.4
Synthesis
of
Aldehydes
and
Ketones
19.5
Introduc;on
to
Aldehyde
and
Ketone
Reac;ons
19.6
Basicity
of
Aldehydes
and
Ketones
19.7
Reversible
Addi;on
Reac;ons
of
Aldehydes
and
Ketones
19.8
Reduc;on
of
Aldehydes
and
Ketones
to
Alcohols
19.9
Reac;ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
•  19.10
Acetals
and
Their
Use
of
Protec;ng
Groups
•
•
•
•
•
•
•
•
•
2
Chapter
19
Overview
•
•
•
•
•
19.11
Reac;ons
of
Aldehydes
and
Ketones
with
Amines
19.12
Reduc;on
of
Carbonyl
Groups
to
Methylene
Groups
19.13
The
WiQg
Alkene
Synthesis
19.14
Oxida;on
of
Aldehydes
to
Carboxylic
Acids
19.15
Manufacture
and
Use
of
Aldehydes
and
Ketones
3
Carbonyl
Compounds
•  Aldehydes
and
ketones
have
the
following
general
structure
19.1
Nomenclature
of
Aldehydes
and
Ketones
4
Carbonyl
Compounds
19.1
Nomenclature
of
Aldehydes
and
Ketones
5
Common
Nomenclature
19.1
Nomenclature
of
Aldehydes
and
Ketones
6
Prefixes
Used
in
Common
Nomenclature
19.1
Nomenclature
of
Aldehydes
and
Ketones
7
Common
Nomenclature
19.1
Nomenclature
of
Aldehydes
and
Ketones
8
Subs?tu?ve
Nomenclature
19.1
Nomenclature
of
Aldehydes
and
Ketones
9
Subs?tu?ve
Nomenclature
19.1
Nomenclature
of
Aldehydes
and
Ketones
10
Physical
Proper?es
•  Most
simple
aldehydes
and
ketones
are
liquids
19.2
Physical
Proper7es
of
Aldehydes
and
Ketones
11
IR
Spectroscopy
•  Strong
C=O
stretch:
1700
cm‐1
19.3
Spectroscopy
of
Aldehydes
and
Ketones
12
IR
Spectroscopy
•  Conjuga;on
with
a
π
bond
lowers
the
absorp;on
frequency
19.3
Spectroscopy
of
Aldehydes
and
Ketones
13
IR
Spectroscopy
•  The
C=O
stretching
frequency
in
small‐ring
ketones
is
affected
by
ring
size
19.3
Spectroscopy
of
Aldehydes
and
Ketones
14
1H
NMR
Spectroscopy
•  The
reason
for
the
large
δ
value
for
aldehydic
protons
is
similar
to
that
for
vinylic
protons
•  However,
the
electronega;ve
O
increases
this
shi^
farther
downfield
19.3
Spectroscopy
of
Aldehydes
and
Ketones
15
13C
NMR
Spectroscopy
•  Aldehyde
and
ketone
C=O:
δ
190‐220
•  α‐Carbons:
δ
30‐50
19.3
Spectroscopy
of
Aldehydes
and
Ketones
16
UV/Vis
Spectroscopy
•  π
→
π*:
150
nm
(out
of
the
opera;ng
range)
•  n
→
π*:
260‐290
nm
(much
weaker)
19.3
Spectroscopy
of
Aldehydes
and
Ketones
17
UV/Vis
Spectroscopy
19.3
Spectroscopy
of
Aldehydes
and
Ketones
18
Mass
Spectrometry
19.3
Spectroscopy
of
Aldehydes
and
Ketones
19
Mass
Spectrometry
•  What
accounts
for
the
m/z
=
58
peak?
19.3
Spectroscopy
of
Aldehydes
and
Ketones
20
Mass
Spectrometry
•  The
McLafferty
rearrangement
involves
a
hydrogen
transfer
via
a
transient
six‐
membered
ring
•  There
must
be
an
available
γ‐H
19.3
Spectroscopy
of
Aldehydes
and
Ketones
21
Summary
of
Aldehyde
and
Ketone
Prepara?on
1.
Oxida;on
of
alcohols
2.
Friedel‐Cra^s
acyla;on
3.
Hydra;on
of
alkynes
4.
Hydrobora;on‐oxida;on
of
alkynes
5.
Ozonolysis
of
alkenes
6.
Periodate
cleavage
of
glycols
19.4
Synthesis
of
Aldehydes
and
Ketones
22
Carbonyl‐Group
Reac?ons
•  Reac;ons
with
acids
•  Addi;on
reac;ons
•  Oxida;on
of
aldehydes
19.5
Introduc7on
to
Aldehyde
and
Ketone
Reac7ons
23
Basicity
of
Aldehydes
and
Ketones
•  The
carbonyl
oxygen
is
weakly
basic
•  One
resonance
contributor
reveals
that
carboca;on
character
exists
•  The
conjugate
acids
of
aldehydes
and
ketones
may
be
viewed
as
α‐hydroxy
carboca;ons
19.6
Basicity
of
Aldehydes
and
Ketones
24
Basicity
of
Aldehydes
and
Ketones
•  α‐hydroxy
and
α‐alkoxy
carboca;ons
are
significantly
more
stable
than
ordinary
carboca;ons
(by
~100
kJ
mol‐1)
19.6
Basicity
of
Aldehydes
and
Ketones
25
Addi?on
Reac?ons
•  One
of
the
most
typical
reac;ons
of
aldehydes
and
ketones
is
addi;on
across
the
C=O
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
26
Mechanism
of
Carbonyl‐Addi?on
Reac?ons
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
27
Addi?on
Reac?ons
•  The
addi;on
of
a
nucleophile
to
the
carbonyl
carbon
is
driven
by
the
ability
of
oxygen
to
accept
the
unshared
electron
pair
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
28
Addi?on
Reac?ons
•  The
nucleophile
aiacks
the
unoccupied
π*
MO
(LUMO)
of
the
C=O
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
29
Addi?on
Reac?ons
•  The
second
mechanism
for
carbonyl
addi;on
takes
place
under
acidic
condi7ons
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
30
Equilibria
in
Carbonyl‐Addi?on
Reac?ons
•  The
equilibrium
for
a
reversible
addi;on
depends
strongly
on
the
structure
of
the
carbonyl
compound
1.
Addi;on
is
more
favorable
for
aldehydes
2.
Addi;on
is
more
favorable
if
EN
groups
are
near
the
C=O
3.
Addi;on
is
less
favorable
when
groups
that
donate
electrons
by
resonance
to
the
C=O
are
present
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
31
Equilibrium
Constants
for
Hydra?on
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
32
Rela?ve
Carbonyl
Stability
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
33
Carbonyl
Stability
•  Any
feature
that
stabilizes
carboca;ons
will
impart
greater
stability
to
the
carbonyl
group
•  For
example,
alkyl
groups
stabilize
carboca;ons
more
than
hydrogens
•  Hence,
alkyl
groups
will
discourage
addi;on
reac;ons
to
the
carbonyl
group
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
34
Carbonyl
Stability
•  Resonance
can
also
add
stability
to
the
carbonyl
group
•  However,
EN
groups
make
the
addi;on
reac;on
more
favorable
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
35
Rates
of
Carbonyl‐Addi?on
Reac?ons
•  Rela;ve
rates
can
be
predicted
from
equilibrium
constants
•  Compounds
with
the
most
favorable
addi;on
equilibria
tends
to
react
most
rapidly
•  General
reac;vity:
formaldehyde
>
aldehydes
>
ketones
19.7
Reversible
Addi7on
Reac7ons
of
Aldehydes
and
Ketones
36
Reduc?on
with
LiAlH4
and
NaBH4
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
37
Reduc?on
with
LiAlH4
•  LiAlH4
serves
as
a
source
of
hydride
ion
(H:‐)
•  LiAlH4
is
very
basic
and
reacts
violently
with
water;
anhydrous
solvents
are
required
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
38
Reduc?on
with
LiAlH4
•  Like
other
strong
bases,
LiAlH4
is
also
a
good
nucleophile
•  Addi;onally,
the
Li+
ion
is
a
built‐in
Lewis‐acid
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
39
Reduc?on
with
LiAlH4
•  Each
of
the
remaining
hydrides
become
ac;vated
during
the
reac;on
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
40
Reduc?on
with
NaBH4
•  Na+
is
a
weaker
Lewis
acid
than
Li+
requiring
the
use
of
pro;c
solvents
•  Hydrogen
bonding
then
serves
to
ac;vate
the
carbonyl
group
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
41
Reduc?on
with
LiAlH4
and
NaBH4
•  Reac;ons
by
these
and
related
reagents
are
referred
to
as
hydride
reduc?ons
•  These
reac;ons
are
further
examples
of
nucleophilic
addi7on
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
42
Selec?vity
with
LiAlH4
and
NaBH4
•  NaBH4
is
less
reac;ve
and
hence
more
selec7ve
than
LiAlH4
•  LiAlH4
reacts
with
alkyl
halides,
alkyl
tosylates,
and
nitro
groups,
but
NaBH4
does
not
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
43
Reduc?on
by
Cataly?c
Hydrogena?on
•  Hydride
reagents
are
more
commonly
used
•  However,
cataly;c
hydrogena;on
is
useful
for
selec;ve
reduc;on
of
alkenes
19.8
Reduc7on
of
Aldehydes
and
Ketones
to
Alcohols
44
Grignard
Addi?on
•  Grignard
reagents
with
carbonyl
groups
is
the
most
important
applica;on
of
the
Grignard
reagent
in
organic
chemistry
19.9
Reac7ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
45
Grignard
Addi?on
•  R‐MgX
reacts
as
a
nucleophile;
this
group
is
also
strongly
basic
behaving
like
a
carbanion
•  The
addi;on
is
irreversible
due
to
this
basicity
19.9
Reac7ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
46
Organolithium
and
Acetylide
Reagents
•  These
reagents
react
with
aldehydes
and
ketones
analogous
to
Grignard
reagents
19.9
Reac7ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
47
Importance
of
the
Grignard
Addi?on
•  This
reac;on
results
in
C‐C
bond
forma;on
•  The
synthe;c
possibili;es
are
almost
endless
19.9
Reac7ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
48
Importance
of
the
Grignard
Addi?on
19.9
Reac7ons
of
Aldehydes
and
Ketones
with
Grignard
and
Related
Reagents
49
Prepara?on
and
Hydrolysis
of
Acetals
•  Acetal:
A
compound
in
which
two
ether
oxygens
are
bound
to
the
same
carbon
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
50
Prepara?on
and
Hydrolysis
of
Acetals
•  Use
of
a
1,2‐
or
1,3‐diol
leads
to
cyclic
acetals
•  Only
one
equivalent
of
the
diol
is
required
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
51
Prepara?on
and
Hydrolysis
of
Acetals
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
52
Prepara?on
and
Hydrolysis
of
Acetals
•  Acetal
forma;on
is
reversible
•  The
presence
of
acid
and
excess
water
allows
acetals
to
revert
to
their
carbonyl
form
•  Acetals
are
stable
in
basic
and
neutral
solu7on
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
53
Hemiacetals
•  Hemiacetals
normally
cannot
be
isolated
•  Excep;ons
include
simple
aldehydes
and
compounds
than
can
form
5‐
and
6‐
membered
rings
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
54
Hemiacetals
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
55
Protec?ng
Groups
•  A
protec?ng
group
is
a
temporary
chemical
disguise
for
a
func;onal
group
preven;ng
it
from
reac;ng
with
certain
reagents
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
56
Protec?ng
Groups
19.10
Acetals
and
Their
Use
of
Protec7ng
Groups
57
Reac?ons
with
Primary
Amines
•  Imines
are
some;mes
called
Schiff
bases
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
58
Reac?ons
with
Primary
Amines
•  The
dehydra;on
of
water
is
typically
the
rate‐
limi;ng
step
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
59
Deriva?ves
•  Before
the
advent
of
spectroscopy,
aldehydes
and
ketones
were
characterized
as
deriva?ves
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
60
Some
Imine
Deriva?ves
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
61
Reac?ons
with
Secondary
Amines
•  Like
imine
forma;on,
enamine
forma;on
is
reversible
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
62
Reac?ons
with
Secondary
Amines
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
63
Reac?ons
with
Ter?ary
Amines
•  Ter;ary
amines
do
not
react
with
aldehydes
or
ketones
to
form
stable
deriva7ves
•  They
are
good
nucleophiles,
but
the
lack
of
an
N‐H
prevents
conversion
to
a
stable
compound
19.11
Reac7ons
of
Aldehydes
and
Ketones
with
Amines
64
Reduc?on
of
Aldehydes
and
Ketones
•  Complete
reduc;on
to
a
methylene
(‐CH2‐)
group
is
possible
by
two
different
methods
•  Wolff‐Kishner
reduc?on:
19.12
Reduc7on
of
Carbonyl
Groups
to
Methylene
Groups
65
Reduc?on
of
Aldehydes
and
Ketones
•  The
Wolff‐Kishner
reduc;on
takes
place
under
highly
basic
condi7ons
•  It
is
an
extension
of
imine
forma;on
19.12
Reduc7on
of
Carbonyl
Groups
to
Methylene
Groups
66
Reduc?on
of
Aldehydes
and
Ketones
•  Clemmensen
reduc?on:
•  This
reduc;on
occurs
under
acidic
condi7ons
•  The
mechanism
is
uncertain
19.12
Reduc7on
of
Carbonyl
Groups
to
Methylene
Groups
67
The
WiVg
Alkene
Synthesis
•  This
reac;on
is
completely
regioselec;ve,
assuring
the
loca;on
of
the
alkene
19.13
The
WiUg
Alkene
Synthesis
68
The
WiVg
Alkene
Synthesis
•  Occurs
via
an
addi;on‐elimina;on
sequence
using
a
phosphorous
ylide
•  An
ylid
(or
ylide)
is
any
compound
with
opposite
charges
on
adjacent,
covalently
bound
atoms
19.13
The
WiUg
Alkene
Synthesis
69
The
WiVg
Alkene
Synthesis
19.13
The
WiUg
Alkene
Synthesis
70
Prepara?on
of
the
WiVg
Reagent
•  Any
alkyl
halide
that
readily
par;cipates
in
SN2
reac;ons
can
be
used
19.13
The
WiUg
Alkene
Synthesis
71
The
WiVg
Alkene
Synthesis
•  Retrosynthe;cally
•  Stereochemistry
19.13
The
WiUg
Alkene
Synthesis
72
Carboxylic
Acids
from
Aldehydes
•  The
hydrate
is
the
species
oxidized
19.14
Oxida7on
of
Aldehydes
to
Carboxylic
Acids
73
Carboxylic
Acids
from
Aldehydes
•  This
is
known
as
the
Tollen’s
test
•  A
posi;ve
indicator
for
an
aldehyde
is
the
deposi;on
of
a
metallic
silver
mirror
on
the
walls
of
the
reac;on
flask
19.14
Oxida7on
of
Aldehydes
to
Carboxylic
Acids
74
Produc?on
and
Use
of
Aldehydes
•  The
most
important
commercial
aldehyde
is
formaldehyde
•  Its
most
important
use
is
in
the
synthesis
of
phenol‐formaldehyde
resins
19.15
Manufacture
and
Use
of
Aldehydes
and
Ketones
75
Produc?on
and
Use
of
Ketones
•  The
most
important
commercial
ketone
is
acetone
•  It
is
co‐produced
with
phenol
by
the
autoxida;on‐rearrangement
of
cumene
19.15
Manufacture
and
Use
of
Aldehydes
and
Ketones
76