Transcript Introduction to Organic Chemistry 2 ed William H. Brown

11
Introduction to
Organic
Chemistry
2 ed
William H. Brown
11-1
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11
Aldehydes
&
Ketones
Chapter 11
11-2
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 The Carbonyl Group
• In this and three following chapters we study the
physical and chemical properties of classes of
compounds containing the carbonyl group, C=O
•
•
•
•
aldehydes and ketones (Chapter 11)
carboxylic acids (Chapter 12)
carboxyl derivatives (Chapter 13)
enolate anions (Chapter 14)
11-3
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 The Carbonyl Group
• Consists of
• one sigma bond formed by overlap of sp2 hybrid
orbitals
• one pi bond formed by overlap of parallel 2p orbitals

C  O
electron pairs in
sp2 hybrid orbitals
11-4
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Structure of Aldehydes
• The functional group of an aldehyde is a carbonyl
group bonded to a H atom
• in methanal, it is bonded to two H atoms
• in all other aldehydes, it is bonded to one H and one
carbon atom
H
H
C
O
C
O
H
H3 C
Methanal
Ethanal
(formaldehyde) (acetaldehyde)
11-5
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Structure of Ketones
• The functional group of a ketone is a carbonyl
groups bonded to two carbon atoms
O
O
CH3 -C- CH3
Propanone
(Acetone)
Cyclohexanone
11-6
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Nomenclature - Aldehydes
• IUPAC names: select as the parent alkane the
longest chain of carbon atoms that contains the
carbonyl group
• because the carbonyl group of the aldehyde must be
on carbon 1, there is no need to give it a number
• For unsaturated aldehydes, show the presence of
the C=C by changing the infix -an- to -en• the location of the suffix determines the numbering
pattern
11-7
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Nomenclature - Aldehydes
O
5
4
3
2
CH3
1
4
3
2
O
1
CH3 CHCH 2 CH
3-Methylbutanal
CH3 CH2 CH2 CH2 CH
Pentanal
O
3
O
2 1
CH2 = CHCH
2-Propenal
(Acrolein)
5
7
3
1
H
(2E)-3,7-Dimethyl-2,6-octadienal
(Geranial)
8
6
4
2
11-8
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Nomenclature - Aldehydes
• For cyclic molecules in which the -CHO group is
attached to the ring, the name is derived by
adding the suffix -carbaldehyde to the name of
the ring
1
CHO
CH 3
2 CH
3
2,2-Dimethylcyclohexanecarbaldehyde
CHO
1
2
3
2-Cyclopentenecarbaldehyde
11-9
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Nomenclature - Ketones
• IUPAC names:
• select as the parent alkane the longest chain that
contains the carbonyl group,
• changing the suffix -e to -one
• number to give C=O the smaller number
O
O
CH3
CH3
O
1
2
3 4
5
6
CH3 CCH3
CH3 CH2 CCH2 CHCH3
Propanone
(Acetone)
5-Methyl-3-hexanone
2-Methylcyclohexanone
11-10
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Nomenclature - Ketones
• The IUPAC system retains these names
O
O
CH 3 CCH 3
CCH 3
C-
Acetone
Acetophenone
O
Benzophenone
11-11
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Order of Precedence
• For compounds that contain more than one
functional group indicated by a suffix
Precedene
Functional
Group
-CO 2 H
-CHO
C=O
-OH
-NH 2
-SH
Suffix if Higher Prefix if Lower
in Precedence
in Precedence
-oic acid
-al
-one
-ol
-amine
-thiol
oxooxohydroxyaminomercapto-
11-12
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Physical Properties
• Oxygen is more electronegative than carbon (3.5
vs 2.5) and, therefore, a C=O group is polar
+ C O
• aldehydes and ketones have higher boiling points and
are more soluble in water than nonpolar compounds of
comparable molecular weight
11-13
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Reaction Theme
• One of the most common reaction themes of the
carbonyl group is addition of a nucleophile to
form a tetrahedral carbonyl addition compound
OH
R
H- Nu
C O
+
R
Nu
C
R
R
Tetrahedral carbonyl
addition compound
11-14
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Add’n of C Nucleophiles
• 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
11-15
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11 Grignard Reagents
• Magnesium metal reacts with alkyl and aryl
halides to give organomagnesium halides
CH 3 CH 2 CH 2 CH 2 Cl + Mg
1-Chlorobutane
ether
CH 3 CH 2 CH 2 CH 2 MgCl
Butylmagnesium chloride
11-16
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 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+
• a Grignard reagent behaves as a carbanion and as a
nucleophile
• Carbanion: an anion in which carbon has an
unshared pair of electrons and bears a negative
charge
11-17
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• Grignard reagents are very strong bases and
react with a variety of acids to give alkanes
+
CH3 CH2 - MgBr + H-OH
pKa 15.7
Stronger
acid
CH3 CH2 -H + Mg(OH)Br
pKa 51
Weaker
acid
11-18
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• they also react with these acids ( proton donors) to
give alkanes
R2 NH
pK a 38-40
ROH
pK a 16-18
Amines
Alcohols
ArOH
pK a 9-10
RSH
pK a 8-9
RCO2 H
pK a 4-5
Phenols
Thiols
Carboxylic
acids
11-19
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• Grignard reagents provide a way to form new
carbon-carbon bonds
• a carbanion is a good nucleophile and adds to the
carbonyl group of an aldehyde or ketone to form a
tetrahedral carbonyl addition compound
• the driving force for this reaction is the attraction of the
partial negative charge on the carbon of the Grignard
reagent for the partial positive carbon of the carbonyl
group
11-20
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• addition of a Grignard reagent to formaldehyde
followed by H3O+ gives a 1° alcohol
O
+
ether
CH3 CH2 -MgBr + H- C-H
+
Formaldehyde
-
O [ Mg Br ]
+
CH3 CH2 -CH2
A magnesium alkoxide
OH
HCl CH CH -CH + Mg2+
3
2
2
H2 O
1-Propanol
(a primary alcohol)
11-21
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• addition to any other RCHO gives a 2° alcohol
+
O
[
Mg
Br
]
O
- +
ether
+
Mg Br
CHCH3
CH3 - C-H
+
A magnesium
Acetaldehyde
alkoxide
(an aldehyde)
OH
HCl
H2 O
2+
+
Mg
CHCH3
1-Cyclohexylethanol
(a secondary alcohol)
11-22
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• addition to a ketone gives a 3° alcohol
O
- +
ether
+
C6 H5 Mg Br CH3 - C-CH3
+
Acetone
-
O [ MgBr]
C6 H5 CCH3
CH3
A magnesium
alkoxide
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
+
OH
HCl
H2 O
C6 H5 CCH3 + Mg2+
CH3
2-Phenyl-2-propanol
(a tertiary alcohol)
11-23
11 Grignard Reagents
• addition to CO2 gives a carboxylic acid
O
O
- +
ether
Mg Br + C
CO - [ MgBr] +
O
Carbon
dioxide
O
HCl
H2 O
COH
+
Mg 2 +
Cyclopentanecarboxylic acid
11-24
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• addition to ethylene oxide gives a 1° alcohol
C6 H5 - MgBr + CH2 CH2
O
Ethylene oxide
-
C6 H5 CH2 CH2 O [ MgBr ]
+
S N2
ether
HCl
C6 H5 CH2 CH2 OH
H2 O
2-Phenylethanol
11-25
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Grignard Reagents
• Problem: 2-phenyl-2-butanol can be synthesized
by three different combinations of a Grignard
reagent and a ketone. Show each combination
OH
C-CH2 CH3
CH3
11-26
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Addition of Alcohols
• Addition of one molecule of alcohol to the C=O
group of an aldehyde or ketone gives a
hemiacetal
• Hemiacetal: a molecule containing an -OH and an
-OR or -OAr bonded to the same carbon
O
H
CH3 CCH3 + OCH2 CH3
OH
CH3 COCH2 CH3
CH3
A hemiacetal
11-27
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Addition of Alcohols
• Hemiacetals are only minor components of an
equilibrium mixture, except where a five- or sixmembered ring can form
• (the trans isomer is shown here)
O
CH3 CHCH 2 CH2 CH
OH
4-Hydroxypentanal
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
H3 C
O
OH
A cyclic hemiacetal
(major form present
at equilibrium)
11-28
11 Addition of Alcohols
• Hemiacetals react with alcohols to form acetals
• Acetal: a molecule containing two -OR or -OAr
groups bonded to the same carbon
OH
H
+
CH3 COCH2 CH3 + CH3 CH2 OH
CH3
OCH2 CH3
A hemiacetal
CH3 COCH2 CH3
+ H2 O
CH3
A diethyl acetal
11-29
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Addition of Alcohols
••
• Steps 1 and 2: proton transfer from the acid catalyst,
HA, to the carbonyl oxygen followed by loss of H2O
A
H ••+ H
H
••
HO
O
(2)
••
••
(1)
R- C-OCH
R- C-OCH
3
3
••
••
H
H
-
••
••
R- C
••
+
OCH3 + H2 O
••
+ A
H
An oxonium ion
11-30
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Addition of Alcohols
• Steps 3 and 4: reaction of the oxonium ion with ROH
followed by proton transfer to A-
••
A
H
••
CH3 -O
••
+ R- C
+
OCH3
••
CH3
••
O+
(4)
••
R- C-OCH3
••
H
••
••
H
(3)
H
O-CH3
••
R- C-OCH3
••
+ H- A
H
An acetal
11-31
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Addition of Alcohols
• with a glycol, such as ethylene glycol, the product is a
five-membered cyclic acetal
O + HOCH2 CH2 OH
H
+
O
CH2
O CH2
A cyclic acetal
+ H2 O
11-32
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Add’n of N Nucleophiles
• Ammonia, 1° aliphatic amines, and 1° aromatic
amines react with the C=O group of aldehydes
and ketones to give imines (Schiff bases)
O
CH3 CH + H2 N
H
+
CH3 CH =N
Aniline
Ethanal
O + H2 NCH3
Cyclopentanone
Methylamine
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
+ H2 O
An imine
(A Schiff base)
H
+
NCH3
An imine
(a Schiff base)
+ H2 O
11-33
11 Add'n of N Nucleophiles
• Formation of an imine occurs in two steps
• Step 1: formation of a TCAI
• Step 2: loss of water
••
+ H2 N- R
C
O
(1)
-
C
H
+
N -R
••
••
••
O
••
••
••
••
O
(1)
H
••
C
H
••
••
O
H
TCAI
H
••
N -R
(2)
H
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
C
••
••
N
+
R
••
C
N -R
H2 O
11-34
11 Add'n of N Nucleophiles
• Rhodopsin (visual purple) is the imine formed
between 11-cis-retinal (vitamin A aldehyde) and
the protein opsin
2
3
1
6
7
8
4
11
9
12
10
13
5
Rhodopsin
(Visual purple)
14
H
C=N-OPSIN
15
11-35
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Rhodopsin
OPSIN
11-36
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Keto-Enol Tautomerism
• A carbon adjacent to a carbonyl group is called
an a-carbon, and a hydrogen atom bonded to it
is called an a-hydrogen.
a- hydrogens
O
CH3 - C- CH 2 - CH 3
a- carbons
11-37
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Keto-Enol Tautomerism
• A carbonyl compound with an a-hydrogen is in
equilibrium with a constitutional isomer called an
enol (an alkene + an alcohol)
O
OH
CH 3 - C- CH 3
Acetone
(keto form)
CH3 - C= CH 2
Acetone
(enol form)
11-38
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Keto-Enol Tautomerism
• keto-enol
equilibria for
Keto form
simple
aldehydes
O
and ketones
CH3 CH
lie far
O
toward the
keto form
CH3 CCH3
O
% Enol at
Enol form Equilibrium
OH
CH2 = CH
6 x 10-5
OH
CH3 C= CH2 6 x 10-7
OH
4 x 10-5
11-39
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Keto-Enol Tautomerism
• Keto-enol tautomerism is acid catalyzed
Step 1: proton transfer from H-A
••
••
O
H- A
CH3 - C-CH3 +
the conjugate acid
of the ketone
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
••
••
Step 2: proton transfer to A+ •• H
O
slow
CH3 - C-CH2 - H + A -
A-
••
CH3 - C-CH3 +
keto form
fast
+ •• H
O
••
OH
CH3 - C= CH2
Enol form
+
H- A
11-40
11 Racemization
• Racemization at an a-carbon is catalyzed by acid
Ph
O
C
C
H3 C
CH3
H
(R)-3-Phenyl-2butanone
OH
Ph
C
H3 C
Ph
O
C
C
CH3
An achiral enol
C
H
CH3
H3 C
(S)-3-Phenyl-2butanone
11-41
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Oxidation of Aldehydes
• Aldehydes are oxidized to carboxylic acids by a
variety of oxidizing agents, including chromic
acid
O
CH3 ( CH2 ) 4 CH
Hexanal
H2 Cr O4
O
CH3 ( CH2 ) 4 COH
Hexanoic acid
11-42
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Oxidation of Aldehydes
• Aldehydes are also oxidized by Ag(I)
• in one method, a solution of the aldehyde in aqueous
ethanol or THF is shaken with a slurry of silver oxide
O
CH3 O
HO
Vanillin
CH
+ A g 2 O T HF, H 2 O
N aOH
HCl
H2 O
CH3 O
O
COH
+ Ag
HO
Vanillic acid
11-43
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Oxidation of Aldehydes
• Tollens’ reagent, another form of Ag(I), is
prepared by dissolving silver nitrate in water,
adding NaOH to precipitate Ag(I) as Ag2O, and
then adding aqueous ammonia to redissolve Ag(I)
as a silver-ammonia complex ion
+
Ag NO3
-
+ 2 NH3
NH3 , H 2 O
Ag(NH 3 ) 2
+
NO3 -
11-44
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Oxidation of Aldehydes
• Tollens’ reagent oxidizes an aldehyde to a carboxylic
anion and silver(1) is reduced to metallic silver
• this reaction is used to silver mirrors
O
RCH + 2 Ag(NH 3 ) 2
+
NH3 , H 2 O
RCO2
-
+ 2 Ag + 4 NH3
Precipitates as
silver mirror
11-45
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Oxidation of Aldehydes
• aldehydes are oxidized by molecular oxygen and by
hydrogen peroxide
O
O
2
CH + O 2
Benzaldehyde
2
COH
Benzoic acid
• liquid aldehydes are so sensitive to air that they must
stored under N2
11-46
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Reduction
• An aldehyde can be reduced to a 1° alcohol and a
ketone to a 2° alcohol
O
reduction
RCH
An aldehyde
RCH2 OH
A 1° alcohol
O
reduction
RCR'
A ketone
OH
RCHR'
A 2° alcohol
11-47
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Catalytic Reduction
• Catalytic reductions are generally carried out
from 25° to 100°C under 1 to 5 atm H2
O
OH
+
H2
Cyclohexanone
Pt
25oC, 2 atm
Cyclohexanol
11-48
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Catalytic Reduction
• A carbon-carbon double bond may also be
reduced under these conditions
O
CH
H
C C
H3 C
H
trans -2-Butenal
(Crotonaldehyde)
2 H2
Ni
CH3 CH2 CH2 CH2 OH
1-Butanol
• by careful choice of experimental conditions, it is often
possible to selectively reduce a carbon-carbon double
in the presence of an aldehyde or ketone
11-49
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Metal Hydride Reduction
• 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
powerful nucleophile
H
H
H
Sodium
borohydride
Li + H- A l- H
H
Lithium aluminum
hydride (LAH)
••
+
N a H- B- H
H
Hydride ion
11-50
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 NaBH Reduction
4
• Reductions with NaBH4 are most commonly
carried out in aqueous methanol, in pure
methanol, or in ethanol
• one mol of NaBH4 reduces four mol of aldehyde or
ketone
O
methanol
4 RCH + N aBH4
+ H2 O
4 RCH2 OH + borate
( RCH 2 O) 4 B Na
salts
A tetraalkyl borate
11-51
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 NaBH Reduction
4
• the key step in metal hydride reduction is transfer of a
hydride ion to the C=O group to form a tetrahedral
carbonyl addition compound
H
O
+
N a H- B- H + R- C-R'
H
O-BH3 N a+
R- C-R'
H
from the hydride
reducing agent
H2 O
OH
from
water
R- C-R'
H
11-52
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 LiAlH Reduction
4
• Unlike NaBH4, LiAlH4 reacts violently with water,
methanol, and other protic solvents
• reductions using this reagent are carried out in diethyl
ether or tetrahydrofuran (THF)
O
ether
+
LiA
lH
4 RCR
4
-
+
( R2 CH O) 4 A l Li
A tetraalkyaluminate
H2 O
OH
4 RCHR + aluminum salts
11-53
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Metal Hydride Reduction
• 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
1 . Na BH 4
RCH= CHCR'
2 . H2 O
O
RCH= CHCR'
+
H2
Rh
OH
RCH= CHCH R'
O
RCH2 CH 2 CR'
11-54
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11 Reductive Amination
• A value of imines is that the carbon-nitrogen
double bond can be reduced to a carbon-nitrogen
single bond
O
+
Cyclohexanone
H2 N
H+
-H 2 O
Cyclohexylamine
H
N
(An imine)
H2 /Ni
N
Dicyclohexylamine
11-55
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
11
Aldehydes
&
Ketones
End Chapter 11
11-56
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.