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Chapter 13:
Aldehydes and Ketones
Sections 13.1-13.8
Chemistry 2060, Spring 2060, LSU
13-1
Sections
Chapter 13: Aldehydes and Ketones
1.
2.
3.
4.
5.
6.
7.
8.
Introduction
Structure and bonding
Nomenclature
Physical properties
Reactions
Addition of Grignard Reagents
Addition of alcohols
Addition of ammonia and amines
Chemistry 2060, Spring 2060, LSU
13-2
The Carbonyl Group
In this and several following chapters, we study the
physical and chemical properties of classes of
compounds containing the carbonyl group, C=O
• aldehydes and ketones (Chapter 13)
• carboxylic acids (Chapter 14)
• acid halides, acid anhydrides, esters, amides (Chapter
15)
• enolate anions (Chapter 16)
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Structure
• 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
O
HCH
Methanal
(Formaldehyde)
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O
CH3 CH
Ethanal
(Acetaldehyde)
O
CH3 CCH3
Propanone
(Acetone)
13-4
Nomenclature
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
Chemistry 2060, Spring 2060, LSU
13-5
Nomenclature
O
O
3
4
O
1
1
3
H
2
2
3-Methylbutan al
HO
Cyclopen tanecarb aldehyde
O
5-Methyl-3h exanone
Chemistry 2060, Spring 2060, LSU
H
8
4
6
3
4
1
H
2
(2E)-3,7-D imeth yl-2,6-octad ienal
(Geran ial)
2-Propen al
(A crolein )
CHO
5
7
1
CHO
trans -4-Hyd roxycyclohexan ecarbald ehyde
O
2-Methylcycloh exanone
O
Acetop hen on e
O
Benzoph enone
13-6
Nomenclature
Functional
Grou p
Su ffix
Carb oxyl
-oic acid
Ald ehyde
-al
Prefix
Example of When the Fun ction al
Grou p Has a Low er Priority
O
oxo-
3-Oxopropan oic acid
COOH
H
O
COOH
Ketone
-one
oxo-
3-Oxobutanoic acid
Alcoh ol
-ol
hydroxy-
Amino
-amine
amino-
COOH
4-Hydroxybutan oic acid HO
NH2
COOH
3-Aminobutan oic acid
Su lfh ydryl -thiol
Chemistry 2060, Spring 2060, LSU
mercapto- 2-Mercaptoethanol
HS
OH
13-7
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
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O
OH
Acetic acid
O
O
Diethyl ketone
Dicyclohexyl ketone
13-8
Physical Properties
Oxygen is more electronegative than carbon (3.5 vs
2.5) and, therefore, a C=O group is polar
O
Polarity of a
carbonyl group
:
C
C
O:
+
C
: :
+ -
O: –
More important
contributing
structure
• 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
Chemistry 2060, Spring 2060, LSU
13-9
Reactions
The most common reaction theme of a carbonyl
group is addition of a nucleophile to form a
tetrahedral carbonyl addition compound
:
:O :
R
+
C
R
O:
:
N u: -
Nu
-
C
R
R
Tetrahedral carbonyl
addition compound
Chemistry 2060, Spring 2060, LSU
13-10
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 alkl or aryl group and X is a halogen
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13-11
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
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MgBr
Butylmagn esium bromide
eth er
MgBr
Phenylmagn esium bromide
13-12
Grignard Reagents
Given the difference in electronegativity between carbon
and magnesium (2.5 - 1.3), the C-Mg bond is polar
covalent, with C- and Mg+
• 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
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13-13
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
CH3 CH2 -H + Mg 2+ + OH- + BrpK a 51
Weaker
Weaker
acid
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
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ArOH
Phenols
RCOOH
Carboxylic
acids
RNH2
Amines
RSH
Thiols
13-14
Grignard Reagents
• reaction with formaldehyde gives a 1° alcohol
O
eth er
CH3 CH2 -MgBr + H-C-H
Formaldeh yd e
O [MgBr]+
HCl
CH3 CH2 -CH2
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
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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)
13-15
Grignard Reagents
• reaction with a ketone gives a 3° alcohol
O [ MgBr] +
O
Ph MgBr + CH3 -C-CH3
Acetone
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
Chemistry 2060, Spring 2060, LSU
13-16
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
Chemistry 2060, Spring 2060, LSU
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)
13-17
Addition of Alcohols
Acetal: a molecule containing two -OR groups
bonded to the same carbon
OH
CH3 C-OCH2 CH3 + CH3 CH2 OH
CH3
A hemiacetal
H
OCH2 CH3
+
CH3 C-OCH2 CH3 + H2 O
CH3
A diethyl acetal
O
H
OH
4-Hydroxypentan al
Chemistry 2060, Spring 2060, LSU
O
OH
CH3 OH
+
H
O
OCH3
+ H2 O
A cy clic acetal
13-18
Acetal Formation
1. Proton transfer from HA to the hemiacetal oxygen
+
H O H
R-C-OCH3 + A
HO
R-C-OCH3 + H A
H
An oxonium ion
H
2. Loss of H2O gives a cation
+
H O H
R-C-OCH3
H
Chemistry 2060, Spring 2060, LSU
+
R-C OCH3
+
R-C OCH3 + H2 O
H
H
A resonan ce-stabilized cation
13-19
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
O CH3
HA + R-C-OCH3
+ R-C-OCH3
A
H
H
A p rotonated acetal
An acetal
Chemistry 2060, Spring 2060, LSU
13-20
Acetals
Draw a structural formula for the acetal formed in
each reaction
(a)
OH
O + HO
Eth ylen e
glycol
OH
(b)
O
+
H2 SO4
H2 SO4
OH
Chemistry 2060, Spring 2060, LSU
13-21
Acetals as 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-phenylpentanal
• but first the aldehyde of the bromoaldehyde must be
protected; one possibility is as a cyclic acetal
O
Br
Chemistry 2060, Spring 2060, LSU
H +
OH
HO
Eth ylene glycol
H
O
+
Br
+ H2 O
O
A cyclic acetal
13-22
An Acetal as a Protecting Group
• now the Grignard reagent can be prepared and the new
carbon-carbon bond formed
O
O
Br
O
A cyclic acetal
O
Ph
BrMg
+ Mg
ether
O
A Grignard reagent
-
H + BrMg
O MgBr
O
+
O
O
Ph
A magnesiu m alk oxid e
O
• hydrolysis gives the hydroxyaldehyde
-
+
O MgBr
Ph
Chemistry 2060, Spring 2060, LSU
OH
O
O
HCl, H2 O
Ph
O
H + HO
OH
13-23
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
Chemistry 2060, Spring 2060, LSU
An imine
+
CH3 CH + H2 N
Ethanal
NH + H2 O
Aniline
H
CH3 CH=N
+ H2 O
An imine
13-24
Imines
1. addition of the amine to the carbonyl carbon followed
by proton transfer
O
C
+ H2 N-R
O- H
+
C N-R
H
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 +
O
H
C
H
N-R
H
H
+
H
O
C
H
C N-R + H2 O + H O H
N-R
H
O
H
An imine
H
Chemistry 2060, Spring 2060, LSU
13-25
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)
Chemistry 2060, Spring 2060, LSU
H
C= N-Opsin
13-26
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
Chemistry 2060, Spring 2060, LSU
13-27
Keto-Enol Tautomerism
Enol: a molecule containing an -OH group on a
carbon-carbon double bond of an alkene
O
CH3 -C-CH3
Acetone
(keto form)
the keto form
predominates
for most
simple
aldehydes and
ketones
Chemistry 2060, Spring 2060, LSU
Keto form
O
CH3 CH
O
CH3 CCH3
O
OH
CH3 -C=CH2
Aceton e
(enol form)
% En ol at
Enol form Equilib rium
OH
CH2 =CH
6 x 10
OH
CH3 C=CH2
6 x 10
-5
-7
OH
4 x 10-5
13-28
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
Chemistry 2060, Spring 2060, LSU
13-29
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
+ •• H
O
•
•
••
O
+
H-A
CH3 -C-CH3
+
Th e conjugate acid
of th e keton e
A-
•
•
CH3 -C-CH3
Keto form
fast
2. proton transfer from the a-carbon to A:+•• H
O
•
•
Chemistry 2060, Spring 2060, LSU
+
•
•
CH3 -C-CH2 -H
••
-
A
slow
OH
CH3 -C=CH2 + H-A
En ol form
13-30
Racemization an at a-Carbon
when an enantiomerically pure aldehyde or ketone
with at least one a-hydrogen 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
C
-
or OH
H3 C
CH3
H
(R)-3-Phenyl-2butanone
Chemistry 2060, Spring 2060, LSU
OH
Ph
+
H3 C
C
CH3
An ach iral en ol
H
+
or OH-
Ph
O
C
C
H
CH3
H3 C
(S)-3-Ph enyl-2b utanone
13-31
a-Halogenation
Aldehydes and ketones with an a-hydrogen react
with Br2 and Cl2 to give an a-haloaldehyde or an
a-haloketone
O
O
+ Br2
A cetophenone
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CH3 COOH
Br
+ HBr
a-Bromoacetophen on e
13-32
a-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
Chemistry 2060, Spring 2060, LSU
Br
+ H-Br
13-33
a-Halogenation
A value of a-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 a-bromok eton e
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Diethylamine
+ HBr
An a-dieth ylaminoketone
13-34
Oxidation
Aldehydes are one of the most easily oxidized of all
functional groups
CHO
H2 CrO4
Hexan al
MeO
HO
Van illin
Hexanoic acid
CHO
+ Ag2 O THF, H2 O
NaOH
2
CHO + O2
Benzald ehyde
Chemistry 2060, Spring 2060, LSU
COOH
HCl
H2 O
2
COOH
+ Ag
MeO
HO
V anillic acid
COOH
Benzoic acid
13-35
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
Chemistry 2060, Spring 2060, LSU
13-36
Reduction
• aldehydes can be reduced to 1° alcohols
• ketones can be reduced to 2° alcohols
O
R-CH
A n aldehyde
reduction
R-CH2 OH
A p rimary
alcohol
O
OH
reduction
R-C-R'
R-CH-R'
A second ary
A k eton e
alcohol
Chemistry 2060, Spring 2060, LSU
13-37
Catalytic Reduction
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)
Chemistry 2060, Spring 2060, LSU
2 H2
Ni
OH
1-Butanol
13-38
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
Chemistry 2060, Spring 2060, LSU
H
Li
+
H- A l- H
H
Lithium aluminum
hydride (LAH)
H:
Hydride ion
13-39
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
4 RCH + NaBH4 methanol
-
+
( RCH2 O) 4 B Na
A tetraalkyl borate
Chemistry 2060, Spring 2060, LSU
H2 O
4 RCH2 OH + borate
salts
13-40
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
from
w ater
O-H
R-C-R'
H
Chemistry 2060, Spring 2060, LSU
13-41
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'
Chemistry 2060, Spring 2060, LSU
+
H2
Rh
OH
RCH= CHCH R'
O
RCH2 CH 2 CR'
13-42
Aldehydes and
Ketones
End Chapter 13
Chemistry 2060, Spring 2060, LSU
13-43