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13-1Chemistry 2060, Spring 2060, LSU
Chapter 13:Chapter 13:Aldehydes and KetonesAldehydes and Ketones
Sections 13.1-13.8
13-2Chemistry 2060, Spring 2060, LSU
SectionsSectionsChapter 13: Aldehydes and KetonesChapter 13: Aldehydes and Ketones
1. Introduction
2. Structure and bonding
3. Nomenclature
4. Physical properties
5. Reactions
6. Addition of Grignard Reagents
7. Addition of alcohols
8. Addition of ammonia and amines
13-3Chemistry 2060, Spring 2060, LSU
The Carbonyl GroupThe Carbonyl GroupIn this and several following chapters, we study the In this and several following chapters, we study the
physical and chemical properties of classes of physical and chemical properties of classes of compounds containing the carbonyl group, C=Ocompounds 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)
13-4Chemistry 2060, Spring 2060, LSU
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
13-5Chemistry 2060, Spring 2060, LSU
NomenclatureNomenclatureIUPAC names:IUPAC names:
• the parent chain is the longest chain that contains the carbonyl group
• for an aldehyde, change the suffix from -e-e to -al-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 in which -CHO is bonded to the ring, add the suffix -carbaldehydecarbaldehyde
13-6Chemistry 2060, Spring 2060, LSU
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
13-7Chemistry 2060, Spring 2060, LSU
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
13-8Chemistry 2060, Spring 2060, LSU
NomenclatureNomenclatureCommon namesCommon 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
13-9Chemistry 2060, Spring 2060, LSU
Physical PropertiesPhysical PropertiesOxygen is more electronegative than carbon (3.5 vs Oxygen is more electronegative than carbon (3.5 vs
2.5) and, therefore, a C=O group is polar2.5) 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
C O C O –
Polarity of acarbonyl group
-+C O
+
More importantcontributing
structure
::: : :
13-10Chemistry 2060, Spring 2060, LSU
ReactionsReactionsThe most common reaction theme of a carbonyl The most common reaction theme of a carbonyl
group is addition of a nucleophile to form a group is addition of a nucleophile to form a tetrahedral carbonyl addition compoundtetrahedral carbonyl addition compound
Tetrahedral carbonyl addition compound
+ CR
R
O CNu
O -
RR
Nu -: :
::
:
:
13-11Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard ReagentsAddition of carbon nucleophiles is one of the most Addition of carbon nucleophiles is one of the most
important types of nucleophilic additions to a important types of nucleophilic additions to a C=O groupC=O group• a new carbon-carbon bond is formed in the process
We study addition of carbon nucleophiles called We study addition of carbon nucleophiles called Grignard reagentsGrignard 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
13-12Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard ReagentsGrignard reagents are prepared by adding an alkyl Grignard reagents are prepared by adding an alkyl
or aryl halide to a suspension of Mg metal in or aryl halide to a suspension of Mg metal in diethyl etherdiethyl ether
Br Mg MgBr+1-Bromobutane Butylmagnesium bromide
ether
Br Mg MgBr+ ether
Bromobenzene Phenylmagnesium bromide
13-13Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard ReagentsGiven the difference in electronegativity between carbon Given the difference in electronegativity between carbon
and magnesium (2.5 - 1.3), the C-Mg bond is polar and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Ccovalent, with C-- and Mg and Mg++• in its reactions, a Grignard reagent behaves as a
carbanion
CarbanionCarbanion:: an anion in which carbon has an unshared pair an anion in which carbon has an unshared pair of electrons and bears a negative chargeof electrons and bears a negative charge• a carbanion is a good nucleophile and adds to the
carbonyl group of aldehydes and ketones
13-14Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard ReagentsReaction with protic acidsReaction with protic acids
• Grignard reagents are very strong bases and react with proton acids to form alkanes
• any compound containing an O-H, N-H, or S-H group reacts with a Grignard reagent by proton transfer
CH3CH2-MgBr H-OH CH3CH2-H Mg2+ OH- Br-
Weaker base
Stronger base
Weaker acid
Stronger acid
pKa 51pKa 15.7++
+-+ +
ArOH RSHRCOOHROHHOH RNH2
AminesAlcoholsWater Phenols ThiolsCarboxylicacids
13-15Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard Reagents• reaction with formaldehyde gives a 1° alcohol
• reaction with any aldehyde other than formaldehyde gives a 2° alcohol
Ph MgBr CH3-C-H
O
Ph CHCH3
O [MgBr]+HCl
H2OPh CHCH3
OHMg2+ether
A magnesium alkoxide
Acetaldehyde 1-Phenylethanol(a 2° alcohol)
++
CH3CH2-MgBr H-C-H
O
CH3CH2-CH2
O [MgBr]+ HClH2O
CH3CH2-CH2
OH
Mg2+
Formaldehyde
+
A magnesiumalkoxide
+ ether
1-Propanol(a 1° alcohol)
13-16Chemistry 2060, Spring 2060, LSU
Grignard ReagentsGrignard Reagents• reaction with a ketone gives a 3° alcohol
• problem: show how to synthesize this 3° alcohol by three different routes
Ph MgBr CH3-C-CH3
O
Ph CCH3
CH3
O [MgBr]+
HCl
H2OPh CCH3
OH
CH3
Mg2+ether
2-Phenyl-2-propanol(a 3° alcohol)
Acetone
++
A magnesiumalkoxide
CH3
C-CH2CH3
OH
13-17Chemistry 2060, Spring 2060, LSU
Addition of AlcoholsAddition of AlcoholsHemiacetal:Hemiacetal: a molecule containing an -OH group a molecule containing an -OH group
and an -OR group bonded to the same carbonand 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
13-18Chemistry 2060, Spring 2060, LSU
Addition of AlcoholsAddition of AlcoholsAcetal:Acetal: a molecule containing two -OR groups a molecule containing two -OR groups
bonded to the same carbonbonded 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
13-19Chemistry 2060, Spring 2060, LSU
Acetal FormationAcetal Formation1. 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
+
+
13-20Chemistry 2060, Spring 2060, LSU
Acetal FormationAcetal Formation3. 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
++
+
13-21Chemistry 2060, Spring 2060, LSU
AcetalsAcetalsDraw a structural formula for the acetal formed in Draw a structural formula for the acetal formed in
each reactioneach reaction
O HOOH H2SO4+
Ethyleneglycol
(a)
OH
OH
O H2SO4(b) +
13-22Chemistry 2060, Spring 2060, LSU
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
13-23Chemistry 2060, Spring 2060, LSU
An Acetal as a Protecting GroupAn Acetal as a Protecting Group
• now the Grignard reagent can be prepared and the new carbon-carbon bond formed
• hydrolysis gives the hydroxyaldehyde
BrO
OMg BrMg
O
O
A cyclic acetal A Grignard reagentether
+
Ph
O
H BrMg O
O
O
O
Ph
O-MgBr
+
+
A magnesium alkoxide
O
O
Ph
O-MgBr
+
HCl, H2OOH O
Ph H HOOH+
13-24Chemistry 2060, Spring 2060, LSU
IminesIminesImine:Imine: a compound containing a C=N bond; also a compound containing a C=N bond; also
called a Schiff basecalled 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+
13-25Chemistry 2060, Spring 2060, LSU
IminesImines1. 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
+
+
+ ++
13-26Chemistry 2060, Spring 2060, LSU
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)
13-27Chemistry 2060, Spring 2060, LSU
Reductive AminationReductive AminationReductive amination:Reductive amination: the formation of an imine the formation of an imine
followed by its reduction to an aminefollowed 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
13-28Chemistry 2060, Spring 2060, LSU
Keto-Enol TautomerismKeto-Enol TautomerismEnol:Enol: a molecule containing an -OH group on a a molecule containing an -OH group on a
carbon-carbon double bond of an alkenecarbon-carbon double bond 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
13-29Chemistry 2060, Spring 2060, LSU
Keto-Enol TautomerismKeto-Enol Tautomerism• 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)
13-30Chemistry 2060, Spring 2060, LSU
Keto-Enol TautomerismKeto-Enol TautomerismInterconversion of keto and enol forms is catalyzed Interconversion of keto and enol forms is catalyzed
by both acid and baseby both acid and base• following is a mechanism for acid catalysis
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+
• •
• • ••••
13-31Chemistry 2060, Spring 2060, LSU
Racemization an at Racemization an at -Carbon-Carbon
when an enantiomerically pure aldehyde or ketone when an enantiomerically pure aldehyde or ketone with at least one with at least one -hydrogen is treated with a -hydrogen is treated with a trace of acid or base, it gradually becomes a trace of acid or base, it gradually becomes a racemic mixture; it loses all optical activityracemic mixture; it loses all optical activity
C C
O
CH3
Ph
HH3C
OH
CH3
C CPh
H3C
C C
O
CH3
Ph
H3CH
An achiral enol(R)-3-Phenyl-2-butanone
(S)-3-Phenyl-2-butanone
H+
or OH-
H+
or OH-
13-32Chemistry 2060, Spring 2060, LSU
-Halogenation-HalogenationAldehydes and ketones with an Aldehydes and ketones with an -hydrogen react -hydrogen react
with Brwith Br22 and Cl and Cl22 to give an to give an -haloaldehyde or an -haloaldehyde or an
-haloketone-haloketoneO
Br2CH3COOH
OBr
HBr+ +
Acetophenone -Bromoacetophenone
13-33Chemistry 2060, Spring 2060, LSU
-Halogenation-Halogenationthe key intermediate in the key intermediate in -halogenation is an enol-halogenation is an enol
1. 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+ +
13-34Chemistry 2060, Spring 2060, LSU
-Halogenation-HalogenationA value of A value of -halogenation is that the carbon -halogenation is that the carbon
adjacent to the aldehyde or ketone now bears a adjacent to the aldehyde or ketone now bears a good leaving group and is susceptible to good leaving group and is susceptible to nucleophilic attacknucleophilic attack
OBr
NH+
ON
+ HBr
An -bromo-ketone
An -diethylaminoketoneDiethyl-amine
13-35Chemistry 2060, Spring 2060, LSU
OxidationOxidationAldehydes are one of the most easily oxidized of all Aldehydes are one of the most easily oxidized of all
functional groupsfunctional groups
CHO
HO
MeOAg2O
THF, H2O
NaOHHClH2O
COOHMeO
HOAg
Vanillic acidVanillin
++
CHO H2CrO4 COOH
Hexanal Hexanoic acid
2 CHO O2 2 COOH
Benzoic acidBenzaldehyde
+
13-36Chemistry 2060, Spring 2060, LSU
OxidationOxidationKetones are not normally oxidized by HKetones are not normally oxidized by H22CrOCrO44; in ; in
fact this reagent is used to oxidize 2° alcohols to fact this reagent is used to oxidize 2° alcohols to ketonesketones• 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)
13-37Chemistry 2060, Spring 2060, LSU
ReductionReduction• 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
13-38Chemistry 2060, Spring 2060, LSU
Catalytic ReductionCatalytic ReductionCatalytic reductions are generally carried out from Catalytic reductions are generally carried out from
25° to 100°C and 1 to 5 atm H25° to 100°C and 1 to 5 atm H22
• 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
13-39Chemistry 2060, Spring 2060, LSU
Metal Hydride ReductionsMetal Hydride ReductionsThe most common laboratory reagents for the The most common laboratory reagents for the
reduction of aldehydes and ketones are NaBHreduction of aldehydes and ketones are NaBH44
and LiAlHand LiAlH4 4
• 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:
13-40Chemistry 2060, Spring 2060, LSU
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
13-41Chemistry 2060, Spring 2060, LSU
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
+
13-42Chemistry 2060, Spring 2060, LSU
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
13-43Chemistry 2060, Spring 2060, LSU
Aldehydes andAldehydes andKetonesKetones
End Chapter 13End Chapter 13