Chapter Twelve
Aldehydes and Ketones
Key words
 Nomenclature
 Carbonyl carbon
 Nucleophillic reactions
 Grignard reactions
 Reduction of aldehydes anf Ketones
 Selective reduction reagents
Introduction - Aldehydes and Ketones
The functional group of an aldehyde is a carbonyl group bonded to a H atom.
The functional group of a ketone is a carbonyl group bonded to two carbon atoms.
The simplest aldehyde is formaldehyde, while the smallest ketone is acetone molecule
O
H
O
H
C H
3
C H 3
M e th a n a l
P ro p a n o n e
f o r m a ld e h y d e
a c e to n e
O
H
H
O
O
M
e
V
a
n
i
l
l
a
IUPAC names:
The parent chain is the longest chain that contains the carbonyl group.
For an aldehyde, change the suffix from -e to -al.
For an unsaturated aldehyde, show the carbon-carbon double bond by
changing the infix from -an- to -en-; the location of the suffix determines
the numbering pattern.
For a cyclic molecule in which -CHO is bonded to the ring, add the suffix
-carbaldehyde.
O
O
3 - m e th y lb u ta n a l
O
c
y
c
l
o
p
e
n
t
a
n
e
c
a
r
b
a
l
d
e
h
y
d
e
2 -p ro p e n a l
O
(
2
E
)
3
,
7
d
i
m
e
t
h
y
l
2
,
6
o
c
t
a
d
i
e
n
a
l
g
e
r
a
n
i
a
l
Naming - Aldehydes and Ketones
O
O
3
4
1
3
H
2
2
3-Methylbutan al
HO
Cyclopen tanecarb aldehyde
5-Methyl-3h exanone
H
4
5
7
8
6
3
4
1
H
2
(2E)-3,7-D imeth yl-2,6-octad ienal
(Geran ial)
2-Propen al
(A crolein )
CHO
O
O
1
1
CHO
trans -4-Hyd roxycyclohexan ecarbald ehyde
O
2-Methylcycloh exanone
O
Acetop hen on e
O
Benzoph enone
Nomenclature
• Increasing Order of Precedence of Six Functional Groups.
Nomenclature
• Common names
For an aldehyde, the common name is derived from the common name of the
corresponding carboxylic acid.
For a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and
add the word ketone.
O
H
H
Formaldehyde
O
O
H
OH
Formic acid
H
Acetaldehyde
O
Ethyl is opropyl ketone
O
OH
Acetic acid
O
O
Diethyl ketone
Dicyclohexyl ketone
Number Prefixes for Common Names
Prefix
form
acet
propio
butyr
valer
#C
1
2
3
4
5
Prefix
capro
capryl
capr
laur
#C
6
8
10
12
So.... Butyraldehyde is an aldehyde of 4 carbons.
….. The same prefixes are used for acids.
Physical Properties of aldehydes and Ketones
•Formaldehyde, acetaldehyde, and acetone are infinitely soluble in water.
•Aldehydes and ketones become less soluble in water as the hydrocarbon portion of the
molecule increases in size.
Physical Properties of aldehydes and Ketones
• In liquid aldehydes and ketones, there are weak intermolecular attractions are
between the partial positive charge on the carbonyl carbon of one molecule and the
partial negative charge on the carbonyl oxygen of another molecule.
H + C O
H
O
C+
HH
H + C O
H
H
O C
- +H
• No hydrogen bonding is possible between aldehyde or ketone molecules.
• Aldehydes and ketones have lower boiling points than alcohols and carboxylic acids,
compounds in which there is hydrogen bonding between molecules.
Aldehydes and Ketones
Oxygen is more electronegative than carbon (3.5 versus 2.5) and, therefore, a C=O
group is polar.
 Aldehydes and ketones are polar compounds and interact in the pure state by
dipole-dipole interactions.
 They have higher boiling points and are more soluble in water than nonpolar
compounds of comparable molecular weight.
Nucleophilic Addition Mechanisms
Always a three-part mechanism involving:
• Nucleophilic addition to the carbonyl carbon
• Protonation of the carbonyl oxygen
• Deprotonation of the Nu-H bond
There are three variants of the addition mechanism, which
differ only in the order in which these three steps take place.
1. Neutral (uncatalyzed)
Addition—Deprotonation—Protonation
Nucleophilic Addition Mechanisms
Always a three-part mechanism involving:
• Nucleophilic addition to the carbonyl carbon
• Protonation of the carbonyl oxygen
• Deprotonation of the Nu-H bond
There are three variants of the addition mechanism, which
differ only in the order in which these three steps take place.
2. Anionic (base catalyzed)
Addition—Deprotonation—Protonation
Nucleophilic Addition Mechanisms
Always a three-part mechanism involving:
• Nucleophilic addition to the carbonyl carbon
• Protonation of the carbonyl oxygen
• Deprotonation of the Nu-H bond
There are three variants of the addition mechanism, which
differ only in the order in which these three steps take place.
3. Cationic (Acid catalyzed)
Addition—Deprotonation—Protonation
Reactions
• The most common reaction theme of a carbonyl group is addition of a nucleophile to
form a tetrahedral carbonyl addition compound.
Grignard Reagents
• Addition of carbon nucleophiles is one of the most important types of
nucleophilic additions to a C=O group.
• A new carbon-carbon bond is formed in the process.
• We study addition of carbon nucleophiles called Grignard reagents.
• Victor Grignard was awarded the Nobel Prize for chemistry in 1912 for
their discovery and application to organic synthesis.
• Grignard reagents have the general formula RMgX, where R is an
alkyl or aryl group and X is a halogen.
Grignard Reagents
• Grignard reagents are prepared by adding an alkyl or
aryl halide to a suspension of Mg metal in diethyl ether.
Br
+ Mg
eth er
1-Bromobutane
Br + Mg
Bromoben zene
MgBr
Butylmagn esium bromide
eth er
MgBr
Phenylmagn esium bromide
Grignard Reagents
• Given the difference in electronegativity between carbon and
magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Cδ- and
Mg δ +.
• in its reactions, a Grignard reagent behaves as a carbanion.
• Carbanion: An anion in which carbon has an unshared pair of electrons
and bears a negative charge.
• A carbanion is a good nucleophile and adds to the carbonyl group of
aldehydes and ketones
C
H
C
H
M
g
B
r
3
I
S
R
E
A
L
L
Y
.
.
.
.
.
3
Grignard Reagents
• Reaction with protic acids
• Grignard reagents are very strong bases and react with proton acids
to form alkanes.
- +
CH3 CH2 - MgBr + H-OH
p Ka 15.7
Stronger
Stron ger
bas e
acid
2+
CH3 CH2 -H + Mg + OH + Br
pK a 51
Weaker
acid
Weaker
base
• Any compound containing an O-H, N-H, or S-H group reacts with a
Grignard reagent by proton transfer.
HOH
Water
ROH
Alcoh ols
ArOH
Phenols
RCOOH
Carboxylic
acids
RNH2
Amines
RSH
Thiols
Grignard Reagents
• Reaction with formaldehyde gives a 1° alcohol.
O [MgBr]+
O
CH3 CH 2 -MgBr + H-C-H
eth er
Formaldeh yd e
CH3 CH 2 -CH2
HCl
H2 O
A magnes ium
alkoxide
OH
CH3 CH2 -CH2 + Mg 2+
1-Propanol
(a 1° alcoh ol)
• Reaction with any aldehyde other than formaldehyde gives a 2°
alcohol.
O
Ph MgBr + CH3 -C-H
eth er
Acetaldeh yd e
O [MgBr]+
Ph CHCH3
A magnes ium
alk oxid e
HCl
H2 O
OH
Ph CHCH3 + Mg 2+
1-Ph enyleth anol
(a 2° alcohol)
Grignard Reagents
• Reaction with a ketone gives a 3° alcohol.
O
Ph MgBr + CH3 -C-CH 3
Acetone
O [ MgBr]
eth er
+
Ph CCH3
CH3
A magnes ium
alkoxide
HCl
H2 O
OH
Ph CCH3
CH3
+ Mg 2+
2-Phen yl-2-propanol
(a 3° alcoh ol)
• Problem: Show how to synthesize this 3° alcohol by three different
routes.
OH
C-CH2 CH3
CH3
Grignard Reagents
Br
Mg
dry ether
Br
Mg
dry ether
B r
M g
d ry e th e r
Grignard Reagents
O
MgBr
dry ether
H
Grignard Reagents
o
MgBr
H
dry ether
H
Grignard Reagents
B r
M g
d ry e th e r
O
H
d ry e th e r
Addition of Alcohols
• Hemiacetal: A molecule containing an -OH group and an -OR group
bonded to the same carbon.
H
O
CH3 CCH3 + OCH2 CH3
OH
CH3 C-OCH2 CH3
CH3
A h emiacetal
H+
• Hemiacetals are minor components of an equilibrium mixture
except where a 5- or 6-membered ring can form.
5
3
4
O
2
1
H
OH
4-Hydroxyp entanal
redraw to show
th e OH close to
th e CHO grou p
3
5 4
2
O
H
1
3
H
O
5
2
4
O
1
OH
A cyclic h emiacetal
(major form presen t
at eq uilibrium)
Addition of Alcohols
• Acetal: A molecule containing two -OR groups bonded to the same
carbon.
OH
CH3 C-OCH 2 CH3 + CH 3 CH2 OH
CH3
A hemiacetal
H
OCH 2 CH 3
+
CH3 C-OCH2 CH3 + H2 O
CH3
A d iethyl acetal
O
H
OH
4-Hydroxypentan al
O
OH
CH 3 OH
+
H
O
OCH3
A cy clic acetal
+ H2 O
Acetal Formation
1. Proton transfer from HA to the hemiacetal oxygen.
+
H
H
O
HO
R-C-OCH3 + H A
R-C-OCH3 + A
-
H
An oxonium ion
H
2. Loss of H2O gives a cation.
+
H
H
O
R-C-OCH3
H
+
R-C OCH3
+
R-C OCH3 + H2 O
H
H
A resonan ce-stabilized cation
Acetal Formation
3. Reaction of the cation (an electrophile) with an alcohol (a nucleophile).
H
+
CH3 -O + R-C OCH3
H
+
H O CH3
R-C-OCH3
H
A p rotonated acetal
4. Proton transfer to A- gives the acetal and regenerates the acid catalyst.
+
H
O CH3
A
+
R-C-OCH3
H
A p rotonated acetal
O
CH3
HA + R-C-OCH3
H
An acetal
Acetal Formation
• Draw a structural formula for the acetal formed in each reaction.
(a)
OH
O + HO
Eth ylen e
glycol
OH
(b)
O
+
OH
H2 SO4
H2 SO4
Acetals as Carbonyl-Protecting Groups
• One way to synthesize the ketoalcohol on the right is by a Grignard
reaction.
O
Ph
O
H
+
Benzaldehyde
Br
H
4-Bromobutanal
OH
??
O
Ph
H
5-Hydroxy-5-phenylpen tanal
• But first the aldehyde of the bromoaldehyde must be protected; one
possibility is as a cyclic acetal.
O
Br
H +
OH
HO
Eth ylene glycol
H
O
+
Br
+ H2 O
O
A cyclic acetal
Acetals as Carbonyl-Protecting Groups
• Now the Grignard reagent can be prepared and the new carbon-carbon
bond formed.
O
O
Br
O
A cyclic acetal
O
ether
O
A Grignard reagent
-
H + BrMg
Ph
BrMg
+ Mg
O MgBr
O
+
O
O
Ph
A magnesiu m alk oxid e
O
• Hydrolysis gives the hydroxyaldehyde.
-
+
O MgBr
Ph
OH
O
O
HCl, H2 O
Ph
O
H + HO
OH
Imines
• Imine: A compound containing a C=N bond; also called a Schiff base.
• Formed by the reaction of an aldehyde or ketone with ammonia or a
1° amine.
+
O
+
H
NH3
Cycloh exanone A mmonia
O
An imine
+
CH3 CH + H2 N
Ethanal
NH + H2 O
Aniline
H
CH3 CH=N
An imine
+ H2 O
Formation of Imines
1. Addition of the amine to the carbonyl carbon followed by proton transfer
gives an aminoalcohol.
O- H
+
C N-R
H
O
C
+ H2 N-R
O
H
N-R
H
A tetrah edral carb on yl
ad dition intermediate
C
2. Two proton-transfer reactions and loss of H2O.
H
+
O H +
H
O
C
H
N-R
H
H
+
H
O
C
H
C N-R + H2 O + H O H
N-R
H
O
H
H
An imine
Rhodopsin
• Reaction of vitamin A aldehyde (retinal) with an amino group on the
protein opsin gives rhodopsin.
11
12
+ H2 N-Opsin
11-cis -Retinal
H
C=O
Rhodopsin
(Vis ual purple)
H
C= N-Opsin
Reductive Amination
• Reductive amination: The formation of an imine followed by its reduction to
an amine.
+
O + H2 N
Cyclohexanone
Cyclohexylamine
(a 1° amine)
H
-H2 O
N
H2 / Ni
An imine
(n ot isolated)
H
N
D icyclohexylamin e
(a 2° amine)
• Reductive amination is a valuable method for the conversion of
ammonia to a 1° amine, and a 1° amine to a 2° amine.
Keto-Enol Tautomerism
Enol: A molecule containing an -OH group bonded to a carbon of
a carbon-carbon double bond.
O
CH3 -C-CH3
Acetone
(keto form)
The keto form predominates
for most simple aldehydes and
ketones.
OH
CH3 -C=CH2
Aceton e
(enol form)
Keto-Enol Tautomerism
• Problem: Draw two enol forms for each ketone.
O
O
(b)
(a)
• Problem: Draw the keto form of each enol.
O
OH
CHOH
(a)
(b)
OH
(c)
OH
Keto-Enol Tautomerism
• Interconversion of keto and enol forms is catalyzed by both
acid and base.
• Following is a mechanism for acid catalysis
1. Proton transfer to the carbonyl oxygen.
2. Proton transfer from the a-carbon to A:-
Racemization at α-Carbon
• When an enantiomerically pure aldehyde or ketone with at least one ahydrogen is treated with a trace of acid or base, it gradually becomes a
racemic mixture; it loses all optical activity.
Ph
O
C
C
H
OH
Ph
+
C
-
or OH
H3 C
CH3
H
(R)-3-Phenyl-2butanone
H3 C
C
H
Ph
+
-
CH3 or OH
An ach iral en ol
O
C
C
H
CH3
H3 C
(S)-3-Ph enyl-2b utanone
α-Halogenation
• Aldehydes and ketones with an α-hydrogen react with Br2 and Cl2 to give
an a-haloaldehyde or an α-haloketone.
O
O
+ Br2
A cetophenone
CH3 COOH
Br
+ HBr
-Bromoacetophen on e
α -Halogenation
• The key intermediate in a-halogenation is an enol.
1. Formation of the enol.
OH
O
+
H
Keto form
En ol form
2. Nucleophilic attack of the enol on the halogen.
H
O
O
+ Br Br
Br
+ H-Br
α -Halogenation
• A value of α -halogenation is that the carbon adjacent to the aldehyde or
ketone now bears a good leaving group and is susceptible to nucleophilic
attack.
O
O
Br
N
+ H N
A n -bromok eton e
D iethylamine
+ HBr
An -dieth ylaminoketone
Oxidation
• Aldehydes are one of the most easily oxidized of all functional groups.
CHO
H2 CrO4
Hexan al
MeO
HO
Van illin
2
COOH
Hexanoic acid
CHO
+ Ag2 O THF, H2 O
NaOH
CHO + O2
Benzald ehyde
HCl
H2 O
2
COOH
+ Ag
MeO
HO
V anillic acid
COOH
Benzoic acid
Oxidation
• Ketones are not normally oxidized by H2CrO4; in fact this reagent is used
to oxidize 2° alcohols to ketones.
• They are oxidized by HNO3 at higher temperatures.
• Oxidation is via the enol.
O
OH
O
HNO3
HO
OH
O
Cycloh exanone
(k eto form)
Cyclohexan one
(enol form)
Hexan edioic acid
(Ad ipic acid )
• Adipic acid is one of the starting materials for the synthesis of nylon 66.
Oxidation
• Tollens’ reagent: Prepared by dissolving AgNO3 in water, adding NaOH to
precipitate Ag2O and then adding aqueous ammonia to redissolve silver
ion as the silver-ammonia complex ion. Tollens’ reagent is specific for the
oxidation of aldehydes. If done properly, silver deposits on the walls of the
container as a silver mirror.
O
+
R-C-H + 2 Ag( NH3 ) 2 + 3 OH
A ldehyde Tollens'
reagen t
O
R-C-O + 2 Ag + 4 NH3 + 2 H2 O
Carboxylic Silver
an ion
mirror
Reduction
• Aldehydes are reduced to 1° alcohols.
• Ketones are reduced to 2° alcohols.
O
R-CH
A n aldehyde
reduction
R-CH 2 OH
A p rimary
alcohol
O
OH
reduction
R-C-R'
R-CH-R'
A second ary
A k eton e
alcohol
Catalytic Reductions
• Catalytic reductions are generally carried out from 25° to
100°C and 1 to 5 atm H2.
OH
O
+
H2
Pt
25 o C, 2 atm
Cyclohexanone
Cyclohexanol
• A carbon-carbon double bond may also be reduced under
these conditions.
O
H
trans- 2-Butenal
(Crotonaldehyde)
2 H2
Ni
OH
1-Butanol
Metal Hydride Reductions
• The most common laboratory reagents for the reduction of aldehydes and
ketones are NaBH4 and LiAlH4.
• Both reagents are sources of hydride ion, H:-, a very strong nucleophile.
H
Na
+
H- B- H
H
Sodium
borohydride
H
Li
+
H- A l- H
H
Lithium aluminum
hydride (LAH)
H:
Hydride ion
NaBH4 Reductions
• Reductions with NaBH4 are most commonly carried out in aqueous
methanol, in pure methanol, or in ethanol.
• One mole of NaBH4 reduces four moles of aldehyde or ketone.
O
methanol
4 RCH + NaBH 4
-
+
( RCH2 O) 4 B Na
A tetraalkyl borate
H2 O
4 RCH2 OH + borate
salts
NaBH4 Reductions
• The key step in metal hydride reductions is transfer of a hydride ion to the
C=O group to form a tetrahedral carbonyl addition compound.
H
O
+
Na H-B-H + R-C-R'
H
O BH3 Na
+
R-C-R'
H
from the hydride
reducing agent
H2 O
O-H
R-C-R'
H
from
w ater
Metal Hydride Reductions
• Metal hydride reducing agents do not normally reduce carbon-carbon
double bonds, and selective reduction of C=O or C=C is often possible.
O
RCH= CHCR'
1 . Na BH 4
2 . H2 O
O
RCH= CHCR'
+
H2
Rh
OH
RCH= CHCH R'
O
RCH2 CH 2 CR'
3H
2,
Ni
H
O
O
1 .2 e q C H 3 M g B r
d ry e th e r
2. H+
N aBH 4
in
m e t h a n o l ( s o lv e n t )
End of Chapter Twelve
Aldehydes and Ketones
Key words
 Nomenclature
 Carbonyl carbon
 Nucleophillic reactions
 Grignard reactions
 Reduction of aldehydes anf Ketones
 Selective reduction reagents