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13-1© 2005 John Wile & Sons, IncAll rights reserved
Chapter 13Chapter 13Aldehydes and KetonesAldehydes and Ketones
13-2© 2005 John Wile & Sons, IncAll rights reserved
The Carbonyl GroupThe 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)
13-3© 2005 John Wile & Sons, IncAll rights reserved
StructureStructure• 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
Propanone(Acetone)
Ethanal(Acetaldehyde)
Methanal(Formaldehyde)
O O O
CH3CHHCH CH3CCH3
13-4© 2005 John Wile & Sons, IncAll rights reserved
Aldehydes and KetonesAldehydes and Ketones
In an aldehyde, an H atom is attached to a carbonyl group O carbonyl group
CH3-C-H
In a ketone, two carbon groups are attached to a carbonyl group
O carbonyl group CH3-C-CH3
13-5© 2005 John Wile & Sons, IncAll rights reserved
Naming AldehydesNaming Aldehydes
IUPAC Replace the -e in the alkane name -al Common Add aldehyde to the prefixes form (1C), acet
(2C), propion(3), and butry(4C)
O O O
H-C-H CH3-C-H CH3CH2C-H methanal ethanal propanal (formaldehyde) (acetaldehyde) (propionaldehyde)
13-6© 2005 John Wile & Sons, IncAll rights reserved
Aldehydes as FlavoringsAldehydes as Flavorings
Benzaldehyde Vanillin Cinnamaldehyde(almonds) (vanilla beans) (cinnamon)
CH=CH CH
OCH
O
HO
OCH3
CH
O
13-7© 2005 John Wile & Sons, IncAll rights reserved
Aldehydes: Common ExamplesAldehydes: Common Examples
glucose
C
OH
C
CHO H
CH OH
C
CH2OH
OH
OHH
H
H H
O
O
H
H
O
H
O
H
O
methanal (formaldehyde)
ethanal (acetaldehyde)
propanal (propionaldehyde)
butanal (butyraldehyde)
2-methylpropanal (isobutyraldehyde)
13-8© 2005 John Wile & Sons, IncAll rights reserved
Naming KetonesNaming Ketones
In the IUPAC name, the -e in the alkane name is replaced with -one
In the common name, add the word ketone after naming the alkyl groups attached to the carbonyl group O O
CH3 -C-CH3 CH3-C-CH2-CH3
Propanone 2-Butanone (Dimethyl ketone) (Ethyl methyl ketone)
Cyclohexanone
O
13-9© 2005 John Wile & Sons, IncAll rights reserved
Ketones: common examplesKetones: common examples
O O
Butter flavor CH3-C-C-CH3
O Clove flavor CH3-C-CH2CH2CH2CH2CH3
2-heptanone
Butanedione
D-Fructose
H2OHC
C
CHO H
C
O
H OH
C
CH2OH
OHH
13-10© 2005 John Wile & Sons, IncAll rights reserved
Ketones as HormonesKetones as Hormones
Cortisone
O
CH2OH
OCH3
CH3
O OH
13-11© 2005 John Wile & Sons, IncAll rights reserved
NomenclatureNomenclature• 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--an- to -en--en-; the location of the suffix determines the numbering pattern
• for a cyclic molecule with –CHO bonded to the ring,
use suffix -carbaldehyde
13-12© 2005 John Wile & Sons, IncAll rights reserved
NomenclatureNomenclature
CHO HO CHO
Cyclopentane-carbaldehyde
trans-4-Hydroxycyclo-hexanecarbaldehyde
14
3-Methylbutanal 2-Propenal(Acrolein)
H
O
(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)
1
2
3
4
5
6
7
8
11
223
3
4H
O
H
O
2-Methyl-cyclohexanone
5-Methyl-3-hexanone
Benzophenone Acetophenone
OO
O O
13-13© 2005 John Wile & Sons, IncAll rights reserved
NomenclatureNomenclature
HCOOH
O
COOHO
COOHHO
OHHS
COOHNH2
-al oxo-
Ketone -one oxo-
Alcohol -ol hydroxy-
Amino -amine amino-
3-Oxopropanoic acid
3-Oxobutanoic acid
4-Hydroxybutanoic acid
3-Aminobutanoic acid
Example of When the FunctionalGroup Has a Lower Priority
Sulfhydryl -thiol mercapto- 2-Mercaptoethanol
Functional Group Suffix Prefix
Carboxyl -oic acid
Aldehyde
13-14© 2005 John Wile & Sons, IncAll rights reserved
NomenclatureNomenclature• 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
FormaldehydeFormic acid Acetaldehyde Acetic acid
Ethyl isopropyl ketoneDiethyl ketoneDicyclohexyl ketone
O OO
H H
O
H OH
O
H
O
OH
O
13-15© 2005 John Wile & Sons, IncAll rights reserved
Physical PropertiesPhysical Properties• Oxygen is more electronegative than carbon (3.5
vs 2.5) and, therefore, a C=O group is polar
• aldehydes /ketones are polar compounds (interact by dipole-dipole interactions)
• they have higher boiling points • more soluble in water than nonpolar compounds of
comparable molecular weight
C O C O –
Polarity of acarbonyl group
-+C O
+
More importantcontributing
structure
::: : :
13-16© 2005 John Wile & Sons, IncAll rights reserved
ReactionsReactions
• The most common reaction theme of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound
Tetrahedral carbonyl addition compound
+ CR
R
O CNu
O -
RR
Nu -: :
:::
:
13-17© 2005 John Wile & Sons, IncAll rights reserved
ReactionsReactions
Tetrahedral carbonyl addition compound
+ CR
R
O CNu
O -
RR
Nu -: :
::
:
:
1. Grignard Reaction
2. Hemiacetal Formation
3. Imine Formation
4. Reductive Amination
5. Keto-enol Tautomerism
6. Alpha-halogenation
7. Oxidation/ Reduction
8. Oximes & Hydrazones
8. Formation of Oximes/ Hydrazones8. Formation of Oximes/ Hydrazones
13-18© 2005 John Wile & Sons, IncAll rights reserved
1. Grignard1. Grignard ReagentsReagents
•Grignard reagents RMgX where R is an alkl or aryl group and X is a halogen
Br Mg MgBr+1-Bromobutane Butylmagnesium bromide
ether
Br Mg MgBr+ ether
Bromobenzene Phenylmagnesium bromide
Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent,
with C- and Mg+
13-19© 2005 John Wile & Sons, IncAll rights reserved
• Hemiacetal: a molecule containing an -OH goup and an -OR group bonded to the same carbon
• hemiacetals are minor components of an equilibrium mixture except where a 5- or 6-membered ring can form
CH3CCH3
O H
OCH2CH3H+
CH3C-OCH2CH3
CH3
OH
A hemiacetal
+
4-Hydroxypentanal A cyclic hemiacetal(major form present at equilibrium)
OHH
O
OH
O
Hredraw to showthe OH close tothe CHO group O OH1
23
45
1
23
451
23
45
2. Hemiacetal Formation2. Hemiacetal Formation
13-20© 2005 John Wile & Sons, IncAll rights reserved
• Acetal: a molecule containing two -OR groups bonded to the same carbon
CH3C-OCH2CH3
CH3
OH
CH3CH2OHH
+CH3C-OCH2CH3
CH3
OCH2CH3
H2O
A diethyl acetal
++
A hemiacetal
OHH
O
O OHCH3OH
H+ O OCH3H2O
4-Hydroxypentanal
+
A cy clic acetal
2. Hemiacetal Formation2. Hemiacetal Formation
13-21© 2005 John Wile & Sons, IncAll rights reserved
1. Proton transfer from HA to the hemiacetal oxygen
2. Loss of H2O gives a cation
HO
H
R-C-OCH3 H A
H
H
O
R-C-OCH3
H
A -+
+
An oxonium ion
+
H O
R-C-OCH3
H
H
R-C
H
OCH3
H
R-C OCH3 H2O+
+
A resonance-stabilized cation
+
+
2. Acetal Formation2. Acetal Formation
13-22© 2005 John Wile & Sons, IncAll rights reserved
3. reaction of the cation (an electrophile) with an alcohol (a nucleophile)
4. proton transfer to A- gives the acetal and regenerates the acid catalyst
CH3-O
H
R-C OCH3
H
H
H
O
R-C-OCH3
CH3+
+
A protonated acetal
+
A
H O
R-C-OCH3
CH3
H
HAH
O
R-C-OCH3
CH3
A protonated acetal An acetal
++
+
2. Acetal Formation2. Acetal Formation
13-23© 2005 John Wile & Sons, IncAll rights reserved
• Draw a structural formula for the acetal formed in each reaction
O HOOH H2SO4+
Ethyleneglycol
(a)
OH
OH
O H2SO4(b) +
2. Acetal Formation2. Acetal Formation
13-24© 2005 John Wile & Sons, IncAll rights reserved
Acetals as Protecting GroupsAcetals as Protecting Groups
• one way to synthesize the ketoalcohol on the right is by a Grignard reaction
• but first the aldehyde of the bromoaldehyde must be protected; one possibility is as a cyclic acetal
Ph H
O
H
OBr
Ph H
OH O
5-Hydroxy-5-phenylpentanal4-BromobutanalBenzaldehyde+
??
H
OBr
A cyclic acetal
+H
+
H2OHOOH+ Br O
O
Ethylene glycol
2. Acetal Formation2. Acetal Formation
13-25© 2005 John Wile & Sons, IncAll rights reserved
• 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
An imineAmmoniaCyclohexanone
++ NH3 H2OO NHH+
CH3CH
O
H2N CH3CH=N H2O+ +
Ethanal Aniline An imine
H+
3. Imine Formation3. Imine Formation
13-26© 2005 John Wile & Sons, IncAll rights reserved
1. addition of the amine to the carbonyl carbon followed by proton transfer
2. two proton-transfer reactions and loss of H2O
C
O
H2N-R C
O
HN-R
H
C
OH
N-RH
-
+
A tetrahedral carbonyladdition intermediate
+
H
O H
H
C
OH
N-RH
C
OHH
N-R
H
H
OH
C N-R H2O H OH
H
An imine
+
+
+ ++
3. Imine Formation3. Imine Formation
13-27© 2005 John Wile & Sons, IncAll rights reserved
HH22NN
RR
CC OO••••
++•••• •••• HH
a carbinolaminea carbinolamine
CC OOHNHN
RR
••••
••••
••••
NN
RR
CC + H+ H22OO(imine)(imine)••••
Imine (Schiff's Base) Formation
13-28© 2005 John Wile & Sons, IncAll rights reserved
CHCH33NNHH22CHCH
OO
++
CH=CH=NNCHCH33 + + HH22OO
N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)
ExampleExample
13-29© 2005 John Wile & Sons, IncAll rights reserved
CHCH33NNHH22CHCH
OO
++
CH=CH=NNCHCH33 + + HH22OO
N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)
ExampleExample CHCH
OOHH
NNHHCHCH33
13-30© 2005 John Wile & Sons, IncAll rights reserved
(CH(CH33))22CHCHCHCH22NNHH22OO ++
+ + HH22OO
N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)
NNCHCH22CH(CHCH(CH33))22
ExampleExample
13-31© 2005 John Wile & Sons, IncAll rights reserved
(CH(CH33))22CHCHCHCH22NNHH22OO ++
+ + HH22OO
N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)
NNCHCH22CH(CHCH(CH33))22
OOHH
NNHHCHCH22CH(CHCH(CH33))22
ExampleExample
13-32© 2005 John Wile & Sons, IncAll rights reserved
RhodopsinRhodopsin
• reaction of vitamin A aldehyde (retinal) with an amino group on the protein opsin gives rhodopsin
C=OH
H2N-Opsin+
C=H
N-Opsin
1112
11-cis-Retinal
Rhodopsin(Visual purple)
13-33© 2005 John Wile & Sons, IncAll rights reserved
• Reductive amination: the formation of an imine followed by its reduction to an amine
• reductive amination is a valuable method for the conversion of ammonia to a 1° amine, and a 1° amine to a 2° amine
+
Cyclohex-anone
Cyclohexyl-amine
(a 1° amine)
O-H2OH+
H2N
Dicyclohexylamine(a 2° amine)
An imine(not isolated)
NH2/Ni
NH
4. Reductive Amination4. Reductive Amination
13-34© 2005 John Wile & Sons, IncAll rights reserved
• Enol: molecule with -OH on a C=C of an alkene
• the keto form predominates
for most
simple
aldehydes and
ketones
CH3-C-CH3
O OHCH3-C=CH2
Acetone(keto form)
Acetone(enol form)
CH2=CHOH
CH3C=CH2
OH
OH
CH3CHO
O
CH3CCH3
O
Keto form Enol form% Enol atEquilibrium
6 x 10-5
6 x 10-7
4 x 10-5
5. Keto-enol Tautomerism5. Keto-enol Tautomerism
13-35© 2005 John Wile & Sons, IncAll rights reserved
• Problem: draw two enol forms for each ketone
• Problem: draw the keto form of each enol
(a) (b)
OO
OCHOH OH
OH
OH(c)(b)(a)
5. Keto-enol Tautomerism5. Keto-enol Tautomerism
13-36© 2005 John Wile & Sons, IncAll rights reserved
• Mechanism (acid catalysed)
1. proton transfer to the carbonyl oxygen
2. proton transfer from the -carbon to A:-
CH3-C-CH3
O
H-A CH3-C-CH3
OH
A-+
+
fast+
Keto form
• •
• • ••••
The conjugate acidof the ketone
CH3-C-CH2-H
OH
A-CH3-C=CH2
OHH-A
Enol form+
+
slow+
• •
• • ••••
5. Keto-enol Tautomerism5. Keto-enol Tautomerism
13-37© 2005 John Wile & Sons, IncAll rights reserved
• Aldehydes and ketones with an -hydrogen react with Br2 and Cl2 to give an -haloaldehyde or an -haloketone
O
Br2CH3COOH
OBr
HBr+ +
Acetophenone -Bromoacetophenone
6. 6. -Halogenation-Halogenation
13-38© 2005 John Wile & Sons, IncAll rights reserved
• the key intermediate in -halogenation is an enol1. formation of the enol
2. nucleophilic attack of the enol on the halogen
O OH
Keto form Enol form
H+
OH
Br Br
OBr
H-Br+ +
6. 6. -Halogenation-Halogenation
13-39© 2005 John Wile & Sons, IncAll rights reserved
• Aldehydes are one of the most easily oxidized of all functional groups
CHO
HO
MeOAg2O
THF, H2O
NaOHHClH2O
COOHMeO
HOAg
Vanillic acidVanillin
++
CHO H2CrO4 COOH
Hexanal Hexanoic acid
2 CHO O2 2 COOH
Benzoic acidBenzaldehyde
+
7. Oxidation-Reduction7. Oxidation-Reduction
13-40© 2005 John Wile & Sons, IncAll rights reserved
• 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
• adipic acid is one of the starting materials for the synthesis of nylon 66
O OH
HNO3
O
HOOH
O
Hexanedioic acid(Adipic acid)
Cyclohexanone(keto form)
Cyclohexanone(enol form)
7. Oxidation-Reduction7. Oxidation-Reduction
13-41© 2005 John Wile & Sons, IncAll rights reserved
• aldehydes can be reduced to 1° alcohols• ketones can be reduced to 2° alcohols
R-CH
O
R-C-R'O
R-CH-R'OH
R-CH2OHA primaryalcohol
A secondaryalcohol
An aldehyde
reduction
A ketone
reduction
7. Oxidation-Reduction7. Oxidation-Reduction
13-42© 2005 John Wile & Sons, IncAll rights reserved
• Catalytic reductions are generally carried out from 25° to 100°C and 1 to 5 atm H2
• a carbon-carbon double bond may also be reduced under these conditions
+25oC, 2 atm
Pt
Cyclohexanone Cyclohexanol
O OH
H2
1-Butanol trans-2-Butenal(Crotonaldehyde)
2H2
NiH
O
OH
7. Oxidation-Reduction7. Oxidation-Reduction
13-43© 2005 John Wile & Sons, IncAll rights reserved
Metal Hydride ReductionsMetal Hydride Reductions• The most common laboratory reagents for the
reduction of aldehydes and ketones are NaBH4 and LiAlH4
• both reagents are sources of hydride ionhydride ion, H:H:--, a very strong nucleophile
Hydride ionLithium aluminum hydride (LAH)
Sodium borohydride
H
H H
H
H-B-H H-Al-HLi +Na+
H:
7. Oxidation-Reduction7. Oxidation-Reduction
13-44© 2005 John Wile & Sons, IncAll rights reserved
NaBHNaBH44 Reductions 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
4RCHO
NaBH4
(RCH2O)4B- Na
+ H2O4RCH2OH
A tetraalkyl borateborate salts
+
+ methanol
7. Oxidation-Reduction7. Oxidation-Reduction
13-45© 2005 John Wile & Sons, IncAll rights reserved
NaBHNaBH44 Reductions 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
Na+H-B-H
H
R-C-R'
O
H
R-C-R'
H
O BH3 Na+
H2O
R-C-R'
H
O-H
from water
from the hydride reducing agent
+
7. Oxidation-Reduction7. Oxidation-Reduction
13-46© 2005 John Wile & Sons, IncAll rights reserved
Metal Hydride ReductionsMetal 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 OH
RCH=CHCR' RCH=CHCHR'1. NaBH4
2. H2O
+Rh
O
RCH=CHCR' RCH2 CH2CR'H2
O
7. Oxidation-Reduction7. Oxidation-Reduction
13-47© 2005 John Wile & Sons, IncAll rights reserved
W W U W W U - -- - C h e m i s t r yC h e m i s t r y
A l d e h y d e sA l d e h y d e s c a n b e p r e p a r e d c a n b e p r e p a r e d b yb y r e d u c t i o nr e d u c t i o n ..
• T h i s w o u l d b e d e s i r a b l e t o d o :
• T h e p r o b l e m i s , h o w t o s t o p t h e r e d u c t i o n a t t h e a l d e h y d e s t a t e , w i t h o u t r e d u c i n g a l l t h e w a y t o a p r i m a r y a l c o h o l ?
R C Cl
O
R C H
O
[H]
[ H ] r e p r e s e n t s a n y g e n e r a l r e d u c t i o n
13-48© 2005 John Wile & Sons, IncAll rights reserved
Among the most useful modified aluminum
hydride (LiAlH4) reducing agents is
Diisobutylaluminum Hydride, also known as DIBALH.
CH3 CH CH2 Al CH2 CH CH3
CH3CH3 H
13-49© 2005 John Wile & Sons, IncAll rights reserved
Nitriles can also be reduced to Nitriles can also be reduced to aldehydes, using DIBALHaldehydes, using DIBALH
C N
DIBALH
toluene -78°C
H2O
HCl
C
H
O
Benzaldehyde (90% yield)
13-50© 2005 John Wile & Sons, IncAll rights reserved
+ + H2OC O
R
R
NH2 OH C
R
R
N OH..
an oxime
acid
•Aldehydes and ketones react with hydroxylamine to yield oximes.
•Oximes are important derivatives in qualitative organic analysis.
8. Formation of Oximes/ Hydrazones8. Formation of Oximes/ Hydrazones
13-51© 2005 John Wile & Sons, IncAll rights reserved
+ + H2O..
a hydrazone
C O
R
R
NH2 NH R C
R
R
N NH Racid
•Aldehydes and ketones react with substituted hydrazines to yield substituted hydrazones.
•The equilibrium is generally unfavorable.
•Exception: when R is an aromatic ring.
8. Formation of Oximes/ Hydrazones8. Formation of Oximes/ Hydrazones
13-52© 2005 John Wile & Sons, IncAll rights reserved
2,4-Dinitrophenylhydrazones2,4-Dinitrophenylhydrazones
+
+ H2O
C O
R
R
NH2 NH NO2
NO2
C
R
R
N NH
NO2
NO2
..
a 2,4-dinitrophenylhydrazone
a 2,4-DNP
acid
2,4-DNP’s are the most important of all derivatives for aldehydes and ketones.
8. Formation of Oximes/ Hydrazones8. Formation of Oximes/ Hydrazones
13-53© 2005 John Wile & Sons, IncAll rights reserved
Aldehydes andAldehydes andKetonesKetones
End Chapter 13End Chapter 13