Post on 02-Jan-2016
transcript
Dr. Wolf's CHM 201 & 202 17- 1
Chapter 17Chapter 17Aldehydes and Ketones.Aldehydes and Ketones.
Nucleophilic AdditionNucleophilic Additionto theto the
Carbonyl GroupCarbonyl Group
Chapter 17Chapter 17Aldehydes and Ketones.Aldehydes and Ketones.
Nucleophilic AdditionNucleophilic Additionto theto the
Carbonyl GroupCarbonyl Group
Dr. Wolf's CHM 201 & 202 17- 3
IUPAC Nomenclature of AldehydesIUPAC Nomenclature of AldehydesIUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes HH
OO OO
HH
OO HCCHCHHCCHCH
OOBase the name on the Base the name on the chain that contains chain that contains the carbonyl group the carbonyl group and replace the and replace the -e-e ending of the ending of the hydrocarbon by hydrocarbon by -al-al..
Dr. Wolf's CHM 201 & 202 17- 4
4,4-dimethylpent4,4-dimethylpentananalal 5-hex5-hexenenalal
IUPAC Nomenclature of AldehydesIUPAC Nomenclature of AldehydesIUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes HH
OO OO
HH
OO HCCHCHHCCHCH
OO
2-phenylprop2-phenylpropaneanedialdial(keep the (keep the -e -e endingendingbefore before -dial-dial))
Dr. Wolf's CHM 201 & 202 17- 5
when named as when named as a substituenta substituent
formyl groupformyl group carbaldehyde orcarbaldehyde orcarboxaldehydecarboxaldehyde
when named when named as a suffixas a suffix
CC HH
OO
IUPAC Nomenclature of Aldehydes IUPAC Nomenclature of Aldehydes IUPAC Nomenclature of Aldehydes IUPAC Nomenclature of Aldehydes
Dr. Wolf's CHM 201 & 202 17- 6
CHCH33CHCH22CCHCCH22CHCH22CHCH33
OO
CHCH33CHCHCHCH22CCHCCH33
OO
CHCH33 HH33CC OO
Base the name on the chain Base the name on the chain that contains the carbonyl that contains the carbonyl group and replace group and replace -e-e by by -one-one. . Number the chain in the Number the chain in the direction that gives the lowest direction that gives the lowest number to the carbonyl number to the carbonyl carbon.carbon.
Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones
Dr. Wolf's CHM 201 & 202 17- 7
Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones
CHCH33CHCH22CCHCCH22CHCH22CHCH33
OO
CHCH33CHCHCHCH22CCHCCH33
OO
CHCH33 HH33CC OO
3-3-hexanhexanoneone
4-methyl4-methyl-2--2-pentanpentanoneone
4-methylcyclohexan4-methylcyclohexanoneone
Dr. Wolf's CHM 201 & 202 17- 8
Functional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of Ketones
CHCH33CHCH22CCCHCH22CHCH22CHCH33
OO OO
CHCH22CCCHCH22CHCH33
CHCH CHCH22
OO
HH22CC CHCCHC
List the groups List the groups attached to the attached to the carbonyl separately in carbonyl separately in alphabetical order, and alphabetical order, and add the word add the word ketoneketone..
Dr. Wolf's CHM 201 & 202 17- 9
CHCH33CHCH22CCCHCH22CHCH22CHCH33
OO
ethylethyl propylpropyl ketone ketone benzylbenzyl ethylethyl ketone ketone
divinyl ketonedivinyl ketone
OO
CHCH22CCCHCH22CHCH33
CHCH CHCH22
OO
HH22CC CHCCHC
Functional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of Ketones
Dr. Wolf's CHM 201 & 202 17- 10
Structure and Bonding:Structure and Bonding:The Carbonyl GroupThe Carbonyl Group
Structure and Bonding:Structure and Bonding:The Carbonyl GroupThe Carbonyl Group
Dr. Wolf's CHM 201 & 202 17- 11
planarplanar
bond angles: close to 120°bond angles: close to 120°
C=O bond distance: 122 pmC=O bond distance: 122 pm
Structure of FormaldehydeStructure of FormaldehydeStructure of FormaldehydeStructure of Formaldehyde
Dr. Wolf's CHM 201 & 202 17- 12
1-butene1-butene propanalpropanal
The Carbonyl GroupThe Carbonyl GroupThe Carbonyl GroupThe Carbonyl Group OO
dipole moment = 0.3Ddipole moment = 0.3D dipole moment = 2.5Ddipole moment = 2.5D
very polar double bondvery polar double bond
Dr. Wolf's CHM 201 & 202 17- 13
2475 kJ/mol2475 kJ/mol
2442 kJ/mol2442 kJ/mol
Alkyl groups stabilize carbonyl groups the sameAlkyl groups stabilize carbonyl groups the sameway they stabilize carbon-carbon double bonds,way they stabilize carbon-carbon double bonds,carbocations, and free radicals.carbocations, and free radicals.
heat of combustionheat of combustion
Carbonyl group of a ketone is moreCarbonyl group of a ketone is morestable than that of an aldehydestable than that of an aldehyde
Carbonyl group of a ketone is moreCarbonyl group of a ketone is morestable than that of an aldehydestable than that of an aldehyde
OO
OO
HH
Dr. Wolf's CHM 201 & 202 17- 14
Heats of combustion Heats of combustion ofof
CC44HH88 isomeric isomeric alkenesalkenes
CHCH33CHCH22CH=CHCH=CH22
2717 kJ/mol2717 kJ/molciscis-CH-CH33CH=CHCHCH=CHCH33
2710 kJ/mol2710 kJ/mol
transtrans--CHCH33CH=CHCHCH=CHCH33
2707 kJ/mol2707 kJ/mol(CH(CH33))22C=CHC=CH22
2700 kJ/mol2700 kJ/mol
2475 kJ/mol2475 kJ/mol
2442 kJ/mol2442 kJ/mol
OO
OO
HH
Spread is greater forSpread is greater foraldehydes andaldehydes and
ketones than for alkenesketones than for alkenes
Spread is greater forSpread is greater foraldehydes andaldehydes and
ketones than for alkenesketones than for alkenes
Dr. Wolf's CHM 201 & 202 17- 15
nucleophiles attack carbon; nucleophiles attack carbon; electrophiles attack oxygenelectrophiles attack oxygen
Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group
Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group
CC
OO •••• ••••
CC
OO
++
––•••••••• ••••
Dr. Wolf's CHM 201 & 202 17- 16
Carbon and oxygen are Carbon and oxygen are spsp22 hybridized hybridized
Bonding in FormaldehydeBonding in FormaldehydeBonding in FormaldehydeBonding in Formaldehyde
Dr. Wolf's CHM 201 & 202 17- 17
The half-filledThe half-filledpp orbitals on orbitals oncarbon andcarbon andoxygen oxygen overlapoverlapto form a to form a bondbond
Bonding in FormaldehydeBonding in FormaldehydeBonding in FormaldehydeBonding in Formaldehyde
Dr. Wolf's CHM 201 & 202 17- 18
Physical PropertiesPhysical PropertiesPhysical PropertiesPhysical Properties
Dr. Wolf's CHM 201 & 202 17- 19
boiling pointboiling point
––6°C6°C
49°C49°C
97°C97°C
Aldehydes and ketones have higher boilingAldehydes and ketones have higher boilingthan alkenes, but lower boiling points than alcohols.than alkenes, but lower boiling points than alcohols.
Aldehydes and ketones have higher boilingAldehydes and ketones have higher boilingthan alkenes, but lower boiling points than alcohols.than alkenes, but lower boiling points than alcohols.
More polar than More polar than alkenes, but cannot alkenes, but cannot form intermolecular form intermolecular hydrogen bonds to hydrogen bonds to other carbonyl groupsother carbonyl groups
OO
OHOH
Dr. Wolf's CHM 201 & 202 17- 20
Sources of Aldehydes and KetonesSources of Aldehydes and KetonesSources of Aldehydes and KetonesSources of Aldehydes and Ketones
Dr. Wolf's CHM 201 & 202 17- 21
2-heptanone2-heptanone(component of alarm pheromone of bees)(component of alarm pheromone of bees)
OO
Many aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturally
Dr. Wolf's CHM 201 & 202 17- 22
transtrans-2-hexenal -2-hexenal (alarm pheromone of myrmicine ant)(alarm pheromone of myrmicine ant)
Many aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturally
OO
HH
Dr. Wolf's CHM 201 & 202 17- 23
citral (from lemon grass oil)citral (from lemon grass oil)
Many aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturallyMany aldehydes and ketones occur naturally OO
HH
Dr. Wolf's CHM 201 & 202 17- 24
from alkenesfrom alkenes
ozonolysisozonolysis
from alkynesfrom alkynes
hydration (via enol)hydration (via enol)
from arenesfrom arenes
Friedel-Crafts Friedel-Crafts acylationacylation
from alcoholsfrom alcohols
oxidationoxidation
Synthesis of Aldehydes and KetonesSynthesis of Aldehydes and KetonesSynthesis of Aldehydes and KetonesSynthesis of Aldehydes and Ketones
A number of A number of reactions alreadyreactions alreadystudied providestudied provideefficient syntheticefficient syntheticroutes to routes to aldehydes and aldehydes and ketones.ketones.
Dr. Wolf's CHM 201 & 202 17- 25
CC
OO
RR OHOH
aldehydes from carboxylic acidsaldehydes from carboxylic acids
RCHRCH22OHOH
1. LiAlH1. LiAlH44
2. H2. H22OOPDC, CHPDC, CH22ClCl22
HHCC
OO
RR
What about..?What about..?What about..?What about..?
Dr. Wolf's CHM 201 & 202 17- 26
benzaldehyde from benzoic benzaldehyde from benzoic acidacid
COHCOH
OO CHCH
OO
1. LiAlH1. LiAlH44
2. H2. H22OOPDCPDCCHCH22ClCl22
CHCH22OHOH
(81%)(81%) (83%)(83%)
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 27
CC
OO
RR HH
ketones from aldehydesketones from aldehydes
R'R'CC
OO
RR
PDC, CHPDC, CH22ClCl221. 1. R'MgXR'MgX
2. H2. H33OO++
RCHRCHR'R'
OHOH
What about..?What about..?What about..?What about..?
Dr. Wolf's CHM 201 & 202 17- 28
CC
OO
CHCH33CHCH22 HH
3-heptanone from propanal3-heptanone from propanal
HH22CrOCrO44
1. 1. CHCH33(CH(CH22))33MgXMgX
2. H2. H33OO++
CHCH33CHCH22CHCH(CH(CH22))3 3 CHCH33
OHOH
OO
CHCH33CHCH22CC(CH(CH22))3 3 CHCH33
(57%)(57%)
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 29
Reactions of Aldehydes and Reactions of Aldehydes and
Ketones:Ketones:
A Review and a PreviewA Review and a Preview
Reactions of Aldehydes and Reactions of Aldehydes and
Ketones:Ketones:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 17- 30
Already covered in earlier chapters:Already covered in earlier chapters:
reduction of C=O to CHreduction of C=O to CH22
Clemmensen reductionClemmensen reduction
Wolff-Kishner reductionWolff-Kishner reduction
reduction of C=O to CHOHreduction of C=O to CHOH
addition of Grignard and organolithiumaddition of Grignard and organolithium
reagentsreagents
Reactions of Aldehydes and KetonesReactions of Aldehydes and KetonesReactions of Aldehydes and KetonesReactions of Aldehydes and Ketones
Dr. Wolf's CHM 201 & 202 17- 31
Principles of Nucleophilic Principles of Nucleophilic
Addition to Carbonyl Groups:Addition to Carbonyl Groups:
Hydration of Aldehydes and Hydration of Aldehydes and
KetonesKetones
Dr. Wolf's CHM 201 & 202 17- 32
HH22OO
Hydration of Aldehydes and KetonesHydration of Aldehydes and KetonesHydration of Aldehydes and KetonesHydration of Aldehydes and Ketones
CC••••OO ••••
HOHO CC OO HH••••
••••
••••
••••
Dr. Wolf's CHM 201 & 202 17- 33
compared to Hcompared to H
electronic: electronic: alkyl groups stabilize alkyl groups stabilize reactantsreactants
steric: steric: alkyl groups crowdalkyl groups crowdproductproduct
OHOH
OHOH
RR R'R'++ HH22OO CCCCRR R'R'
OO
Substituent Effects on Hydration EquilibriaSubstituent Effects on Hydration EquilibriaSubstituent Effects on Hydration EquilibriaSubstituent Effects on Hydration Equilibria
Dr. Wolf's CHM 201 & 202 17- 34
C=OC=O hydratehydrate KK %%RelativeRelative
raterate
CHCH22=O=O CHCH22(OH)(OH)22 23002300 >99.9>99.9 22002200
CHCH33CH=OCH=O CHCH33CH(OH)CH(OH)22 1.01.0 5050 1.01.0
(CH(CH33))33CCH=OCCH=O (CH(CH33))33CCH(OH)CCH(OH)22 0.20.2 1717 0.090.09
(CH(CH33))22C=OC=O (CH(CH33))22C(OH)C(OH)22 0.00140.0014 0.140.14 0.00180.0018
Equilibrium Constants and Relative RatesEquilibrium Constants and Relative Ratesof Hydrationof Hydration
Equilibrium Constants and Relative RatesEquilibrium Constants and Relative Ratesof Hydrationof Hydration
Dr. Wolf's CHM 201 & 202 17- 35
when carbonyl group is when carbonyl group is destabilizeddestabilized
alkyl groups alkyl groups stabilizestabilize C=O C=O
electron-withdrawing groups electron-withdrawing groups destabilizedestabilize C=O C=O
When does equilibrium favor hydrate?When does equilibrium favor hydrate?When does equilibrium favor hydrate?When does equilibrium favor hydrate?
Dr. Wolf's CHM 201 & 202 17- 36
OHOH
OHOH
RR RR++ HH22OO CCCCRR RR
OO
Substituent Effects on Hydration EquilibriaSubstituent Effects on Hydration EquilibriaSubstituent Effects on Hydration EquilibriaSubstituent Effects on Hydration Equilibria
RR = CH = CH33: : KK = 0.000025 = 0.000025
RR = CF = CF33: : KK = 22,000 = 22,000
Dr. Wolf's CHM 201 & 202 17- 37
Mechanism of Hydration (base)Mechanism of Hydration (base)Mechanism of Hydration (base)Mechanism of Hydration (base)
CC••••OO •••••••• OO ••••
HH
••••
––
Step 1:Step 1:Step 1:Step 1:
++
••••
HOHO CC OO••••
••••
••••••••––
Dr. Wolf's CHM 201 & 202 17- 38
Mechanism of Hydration (base)Mechanism of Hydration (base)Mechanism of Hydration (base)Mechanism of Hydration (base)
Step 2:Step 2:Step 2:Step 2:
••••OOHH
HH
••••
••••HOHO CC OO
••••
••••
••••••••––
++••••
••••OO
HH
••••––••••
HOHO CC OOHH••••
••••
••••
Dr. Wolf's CHM 201 & 202 17- 39
Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)
CC••••OO ••••
Step 1:Step 1:Step 1:Step 1:
++ ••••
HH
OOHH
HH++
++
CC
••••OOHH++
•••• ••••
HH
OO
HH
Dr. Wolf's CHM 201 & 202 17- 40
Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)
Step 2:Step 2:Step 2:Step 2:
CC••••OOHH++
++••••
HH
OO
HH
••••CC OOHH
••••
••••
HH
OO
HH
•••• ++
Dr. Wolf's CHM 201 & 202 17- 41
Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)Mechanism of Hydration (acid)
Step 3:Step 3:Step 3:Step 3:
++••••
HH
OO
HH
••••CC OOHH
••••
HHOO
HH
••••
•••• •••• OO
HH
••••CC OOHH
••••
••••
++
HH
HHOO
HH ••••
++
Dr. Wolf's CHM 201 & 202 17- 42
Cyanohydrin FormationCyanohydrin FormationCyanohydrin FormationCyanohydrin Formation
Dr. Wolf's CHM 201 & 202 17- 43
++
Cyanohydrin FormationCyanohydrin FormationCyanohydrin FormationCyanohydrin Formation
••••••••CC OO HCNHCN HHCC OONN CC••••
••••
••••
Dr. Wolf's CHM 201 & 202 17- 44
Cyanohydrin FormationCyanohydrin FormationCyanohydrin FormationCyanohydrin Formation
••••••••CC OO
CC––
NN•••• ••••
Dr. Wolf's CHM 201 & 202 17- 45
Cyanohydrin FormationCyanohydrin FormationCyanohydrin FormationCyanohydrin Formation
––OONN CC CC••••
•••• ••••••••
HH HH
HH
++OO ••••
HH
HH
OO ••••••••OONN CC CC••••
•••••••• HH
Dr. Wolf's CHM 201 & 202 17- 46
2,4-Dichlorobenzaldehyde2,4-Dichlorobenzaldehydecyanohydrin (100%)cyanohydrin (100%)
ExampleExampleExampleExample
ClCl ClCl CHCH
OOClCl
ClCl CHCNCHCN
OHOHNaCN, waterNaCN, water
then Hthen H22SOSO44
Dr. Wolf's CHM 201 & 202 17- 47
ExampleExampleExampleExample
CHCH33CCHCCH33
OONaCN, waterNaCN, water
then Hthen H22SOSO44
CHCH33CCHCCH33
OHOH
CNCN
(77-78%)(77-78%)
Dr. Wolf's CHM 201 & 202 17- 49
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Enamine formationEnamine formation
Compounds related to Compounds related to imines imines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 50
Recall Hydration of Aldehydes and KetonesRecall Hydration of Aldehydes and KetonesRecall Hydration of Aldehydes and KetonesRecall Hydration of Aldehydes and Ketones
HOHHOH
CC••••OO ••••
HOHO CC OO HH••••
••••
••••
••••
RR
R'R'
RR
R'R'
Dr. Wolf's CHM 201 & 202 17- 51
Alcohols Under Analogous ReactionAlcohols Under Analogous Reactionwith Aldehydes and Ketoneswith Aldehydes and Ketones
Alcohols Under Analogous ReactionAlcohols Under Analogous Reactionwith Aldehydes and Ketoneswith Aldehydes and Ketones
R"OR"OHH
CC••••OO ••••
RR
R'R'
R"OR"O CC OO HH••••
••••
••••
••••
RR
R'R'
Product is called Product is called a a hemiacetalhemiacetal..
Dr. Wolf's CHM 201 & 202 17- 52
Product is called Product is called a a hemiacetalhemiacetal..
ROROH, HH, H++
Hemiacetal reacts further in acid to yield an acetalHemiacetal reacts further in acid to yield an acetalHemiacetal reacts further in acid to yield an acetalHemiacetal reacts further in acid to yield an acetal
R"OR"O CC OO HH••••
••••
••••
••••
RR
R'R'
R"OR"O CC OROR••••
••••
••••
••••
RR
R'R'
Product is called Product is called an an acetalacetal..
Dr. Wolf's CHM 201 & 202 17- 53
HClHCl
2CH2CH33CHCH22OOHH++
+ H+ H22OO
Benzaldehyde diethyl acetal (66%)Benzaldehyde diethyl acetal (66%)
ExampleExampleExampleExample
CHCH
OO CH(CH(OOCHCH22CHCH33))22
Dr. Wolf's CHM 201 & 202 17- 54
HHOOCHCH22CHCH22OOHH++CHCH33(CH(CH22))55CHCH
OO
pp-toluenesulfonic acid-toluenesulfonic acidbenzenebenzene
++ HH22OO
(81%)(81%) HH (CH(CH22))55CHCH33
HH22CC CHCH22
OO OO
CC
Diols Form Cyclic AcetalsDiols Form Cyclic AcetalsDiols Form Cyclic AcetalsDiols Form Cyclic Acetals
Dr. Wolf's CHM 201 & 202 17- 55
In general:In general:In general:In general:
Position of equilibrium is usually unfavorablePosition of equilibrium is usually unfavorablefor acetal formation from ketones.for acetal formation from ketones.
Important exception: Important exception: Cyclic acetals can be prepared from ketones.Cyclic acetals can be prepared from ketones.
Dr. Wolf's CHM 201 & 202 17- 56
HHOOCHCH22CHCH22OOHH++
OO
pp-toluenesulfonic acid-toluenesulfonic acidbenzenebenzene
++ HH22OO
HH22CC CHCH22
OO OO
CC(78%)(78%)
CC66HH55CHCH22CCHCCH33
CHCH33CC66HH55CHCH22
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 57
First stage is analogous to hydration andFirst stage is analogous to hydration andleads to hemiacetalleads to hemiacetal
acid-catalyzed nucleophilic additionacid-catalyzed nucleophilic addition of alcohol to C=O of alcohol to C=O
Mechanism of Acetal FormationMechanism of Acetal FormationMechanism of Acetal FormationMechanism of Acetal Formation
Dr. Wolf's CHM 201 & 202 17- 58
MechanismMechanismMechanismMechanism
CC OO•••• ••••
HH
HH
RR++OO ••••
Dr. Wolf's CHM 201 & 202 17- 59
MechanismMechanismMechanismMechanism
CC OO••••
HH
RR
OO ••••
HH
++ ••••
Dr. Wolf's CHM 201 & 202 17- 60
MechanismMechanismMechanismMechanism
CC OO••••
HH
++
RR
HH
OO ••••••••
Dr. Wolf's CHM 201 & 202 17- 61
MechanismMechanismMechanismMechanism
CC OO••••
OO ••••
HH++
••••RR
HH
OORR HH
••••
••••
Dr. Wolf's CHM 201 & 202 17- 62
MechanismMechanismMechanismMechanism
++
HH
OORR HH••••
CC OO••••
OO ••••
HH
••••RR
••••
Dr. Wolf's CHM 201 & 202 17- 63
Second stage is hemiacetal-to-acetal conversionSecond stage is hemiacetal-to-acetal conversion
involves carbocation chemistryinvolves carbocation chemistry
Mechanism of Acetal FormationMechanism of Acetal FormationMechanism of Acetal FormationMechanism of Acetal Formation
Dr. Wolf's CHM 201 & 202 17- 64
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
CC OO••••
OO ••••
HH
••••RR
••••
HH
HH
RR
++OO ••••
Dr. Wolf's CHM 201 & 202 17- 65
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
HH
RR
OO ••••••••CC OO••••
OO
HH
••••RR
••••
HH
++
Dr. Wolf's CHM 201 & 202 17- 66
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
OO••••
OO
HH
••••RR
••••++
HH
CC
Dr. Wolf's CHM 201 & 202 17- 67
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
CCOO••••
RR
••••++ OO
••••
HH
HH
••••
Dr. Wolf's CHM 201 & 202 17- 68
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
CCOO••••
RR
••••++
Carbocation is stabilized by delocalizationCarbocation is stabilized by delocalizationof unshared electron pair of oxygenof unshared electron pair of oxygen
CCOO
RR
••••
++
Dr. Wolf's CHM 201 & 202 17- 69
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
CCOO••••
RR
••••++ OO
••••
HH
RR
••••
Dr. Wolf's CHM 201 & 202 17- 70
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
CCOO••••
RR
••••++OO
••••
HH
RR
OO••••
HH
RR
••••
Dr. Wolf's CHM 201 & 202 17- 71
Hemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal StageHemiacetal-to-acetal Stage
++HH OO
••••
HH
RRCCOO••••
RR
••••OO••••
RR
••••
Dr. Wolf's CHM 201 & 202 17- 72
CCRR R'R'
OO
2R"2R"OOHH++
OOR"R"
RR R'R'CC
OOR"R"
+ H+ H22OO
mechanism:mechanism:
reverse of acetal formation;reverse of acetal formation;hemiacetal is intermediatehemiacetal is intermediate
application:application:
aldehydes and ketones can be aldehydes and ketones can be "protected" as acetals."protected" as acetals.
Hydrolysis of AcetalsHydrolysis of AcetalsHydrolysis of AcetalsHydrolysis of Acetals
Dr. Wolf's CHM 201 & 202 17- 73
Acetals as Protecting GroupsAcetals as Protecting GroupsAcetals as Protecting GroupsAcetals as Protecting Groups
Dr. Wolf's CHM 201 & 202 17- 74
The conversion shown cannot be carried outThe conversion shown cannot be carried outdirectly...directly...
CHCHCHCH33CCHCCH22CHCH22CC
OO
CCCHCH33CHCH33CCHCCH22CHCH22CC
OO
1. NaNH1. NaNH22
2. 2. CHCH33II
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 75
because the carbonyl group and thebecause the carbonyl group and thecarbanion are incompatible functionalcarbanion are incompatible functionalgroups.groups.
CC::CHCH33CCHCCH22CHCH22CC
OO––
Dr. Wolf's CHM 201 & 202 17- 76
1) protect C=O 1) protect C=O
2) alkylate2) alkylate
3) restore C=O3) restore C=O
1) protect C=O 1) protect C=O
2) alkylate2) alkylate
3) restore C=O3) restore C=O
StrategyStrategyStrategyStrategy
Dr. Wolf's CHM 201 & 202 17- 77
HHOOCHCH22CHCH22OOHH++
pp-toluenesulfonic acid-toluenesulfonic acidbenzenebenzene
HH22CC CHCH22
OO OO
CC
CHCH33
CHCH33CCHCCH22CHCH22CC
OO
CHCH
CHCH22CHCH22CC CHCH
Example: Example: ProtectProtectExample: Example: ProtectProtect
Dr. Wolf's CHM 201 & 202 17- 78
HH22CC CHCH22
OO OO
CC
CHCH33CHCH22CHCH22CC CHCH
1. NaNH1. NaNH22
2. 2. CHCH33II
HH22CC CHCH22
OO OO
CC
CHCH33CHCH22CHCH22CC CCCHCH33
Example: Example: AlkylateAlkylateExample: Example: AlkylateAlkylate
Dr. Wolf's CHM 201 & 202 17- 79
HH22CC CHCH22
OO OO
CC
CHCH33CHCH22CHCH22CC CCCHCH33
HH22OO
HClHCl
HHOOCHCH22CHCH22OOHH
(96%)(96%)
CCCHCH33CHCH33CCHCCH22CHCH22CC
OO
++
Example: Example: DeprotectDeprotectExample: Example: DeprotectDeprotect
Dr. Wolf's CHM 201 & 202 17- 80
Reaction with Primary Amines:Reaction with Primary Amines:
IminesImines
Reaction with Primary Amines:Reaction with Primary Amines:
IminesImines
Dr. Wolf's CHM 201 & 202 17- 81
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 82
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 83
HH22NN
RR
CC OO••••
++•••• •••• HH
a carbinolaminea carbinolamine
CC OOHHNN
RR
••••
••••
••••
NN
RR
CC + + HH22OO(imine)(imine)••••
Imine (Schiff's Base) FormationImine (Schiff's Base) FormationImine (Schiff's Base) FormationImine (Schiff's Base) Formation
Dr. Wolf's CHM 201 & 202 17- 84
CHCH33NNHH22CHCH
OO
++
CH=CH=NNCHCH33 + + HH22OO
N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 85
CHCH33NNHH22CHCH
OO
++
CH=CH=NNCHCH33 + + HH22OO
N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)
ExampleExampleExampleExample CHCH
OOHH
NNHHCHCH33
Dr. Wolf's CHM 201 & 202 17- 86
(CH(CH33))22CHCHCHCH22NNHH22OO ++
+ + HH22OO
N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)
NNCHCH22CH(CHCH(CH33))22
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 87
(CH(CH33))22CHCHCHCH22NNHH22OO ++
+ + HH22OO
N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)
NNCHCH22CH(CHCH(CH33))22
OOHH
NNHHCHCH22CH(CHCH(CH33))22
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 88
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 89
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 90
Reaction with Derivatives of AmmoniaReaction with Derivatives of AmmoniaReaction with Derivatives of AmmoniaReaction with Derivatives of Ammonia
HH22NN GG ++ RR22CC OO RR22CC NNGG ++ HH22OO
HH22NN OHOH RR22CC NNOHOH
hydroxylaminehydroxylamine oximeoxime
Dr. Wolf's CHM 201 & 202 17- 91
CHCH33(CH(CH22))55CHCH + H+ H22NNOHOH
OO
CHCH33(CH(CH22))55CHCH + H+ H22OO
NNOHOH
(81-93%)(81-93%)
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 92
Reaction with Derivatives of AmmoniaReaction with Derivatives of AmmoniaReaction with Derivatives of AmmoniaReaction with Derivatives of Ammonia
HH22NN GG ++ RR22CC OO RR22CC NNGG ++ HH22OO
HH22NN OHOH RR22CC NNOHOH
hydroxylaminehydroxylamine oximeoxime
HH22NN NHNH22 RR22CC NNNHNH22
hydrazinehydrazine hydrazonehydrazone
etc.etc.
Dr. Wolf's CHM 201 & 202 17- 93
+ H+ H22NNNHNH22
+ H+ H22OO
(73%)(73%)
ExampleExampleExampleExample OOCC NNNHNH22
CC
Dr. Wolf's CHM 201 & 202 17- 94
CCHCCH33
ExampleExampleExampleExample OO
+ H+ H22NNNHNH
phenylhydrazinephenylhydrazine
+ H+ H22OO
CCHCCH33
NNNHNH
a phenylhydrazone (87-91%)a phenylhydrazone (87-91%)
Dr. Wolf's CHM 201 & 202 17- 95
CHCH33(CH(CH22))99CCHCCH33
OO
HH22NNNHCNHNHCNH22
OO
++
HH22OOCHCH33(CH(CH22))99CCHCCH33
NNNHCNHNHCNH22
OO
++
ExampleExampleExampleExample
semicarbazidesemicarbazide
a semicarbazone (93%)a semicarbazone (93%)
Dr. Wolf's CHM 201 & 202 17- 96
Reaction with Secondary Amines:Reaction with Secondary Amines:EnaminesEnamines
Reaction with Secondary Amines:Reaction with Secondary Amines:EnaminesEnamines
Dr. Wolf's CHM 201 & 202 17- 97
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 98
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 99
RR22NNHH••••
++ HH22OO
(enamine)(enamine)
CC••••RR22NN
CC
Enamine FormationEnamine FormationEnamine FormationEnamine Formation
CC••••OORR22NN HH
HH CC
•••• ••••CC OO
••••
HH CC
••••
Dr. Wolf's CHM 201 & 202 17- 100
++
(heat in benzene)(heat in benzene)
ExampleExampleExampleExample OO NNHH
viaviaOOHH
N
(80-90%)(80-90%)
NN
Dr. Wolf's CHM 201 & 202 17- 101
The Wittig ReactionThe Wittig ReactionThe Wittig ReactionThe Wittig Reaction
Dr. Wolf's CHM 201 & 202 17- 102
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 103
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 104
The Wittig ReactionThe Wittig ReactionThe Wittig ReactionThe Wittig Reaction
Synthetic method for preparing alkenes.Synthetic method for preparing alkenes.
One of the reactants is an aldehyde or ketone.One of the reactants is an aldehyde or ketone.
The other reactant is a phosphorus ylide.The other reactant is a phosphorus ylide.
(C(C66HH55))33PP CC++
AA
BB
••••––
(C(C66HH55))33PP CC
AA
BB
A key property of ylides is that they have a A key property of ylides is that they have a negatively polarized carbon and are nucleophilic. negatively polarized carbon and are nucleophilic.
Dr. Wolf's CHM 201 & 202 17- 105
Figure 17.12 Charge distribution in a ylideFigure 17.12 Charge distribution in a ylideFigure 17.12 Charge distribution in a ylideFigure 17.12 Charge distribution in a ylide
Dr. Wolf's CHM 201 & 202 17- 106
The Wittig ReactionThe Wittig ReactionThe Wittig ReactionThe Wittig Reaction
(C(C66HH55))33PP CC++
AA
BB
••••––
++
++CC CC
RR
R'R'
AA
BB
(C(C66HH55))33PP OO++
••••––••••
••••
CC OO
RR
R'R'
••••
••••
Dr. Wolf's CHM 201 & 202 17- 107
ExampleExampleExampleExample
++
++ (C(C66HH55))33PP OO++
••••––••••
••••
(C(C66HH55))33PP CHCH22
++ ––
••••OO••••
••••
CHCH22
DMSODMSO
(86%)(86%)
dimethyl sulfoxide (DMSO) or tetrahydrofuran dimethyl sulfoxide (DMSO) or tetrahydrofuran (THF) is the customary solvent(THF) is the customary solvent
Dr. Wolf's CHM 201 & 202 17- 108
MechanismMechanismMechanismMechanism
CC OO
RR
R'R'
••••
••••
P(CP(C66HH55))33
++CC
AA
BB––••••
OOCC
CC P(CP(C66HH55))33
RR
R'R'
BB
AA
•••• ••••
Step 1Step 1Step 1Step 1
Dr. Wolf's CHM 201 & 202 17- 109
MechanismMechanismMechanismMechanism
OOCC
CC P(CP(C66HH55))33
RR
R'R'
BB
AA
•••• ••••
Step 2Step 2Step 2Step 2
P(CP(C66HH55))33++
––OO•••• ••••••••
R'R'RR
AA BB
CC
CC++
Dr. Wolf's CHM 201 & 202 17- 110
Planning an Alkene Synthesis viaPlanning an Alkene Synthesis viathe Wittig Reactionthe Wittig Reaction
Planning an Alkene Synthesis viaPlanning an Alkene Synthesis viathe Wittig Reactionthe Wittig Reaction
Dr. Wolf's CHM 201 & 202 17- 111
Retrosynthetic AnalysisRetrosynthetic AnalysisRetrosynthetic AnalysisRetrosynthetic Analysis
There will be two possible Wittig routes toThere will be two possible Wittig routes toan alkene.an alkene.
Analyze the structure retrosynthetically.Analyze the structure retrosynthetically.
Disconnect the doubly bonded carbons. One Disconnect the doubly bonded carbons. One will come from the aldehyde or ketone, thewill come from the aldehyde or ketone, theother from the ylide.other from the ylide.
CC CC
RR
R'R'
AA
BB
Dr. Wolf's CHM 201 & 202 17- 112
Retrosynthetic Analysis of StyreneRetrosynthetic Analysis of StyreneRetrosynthetic Analysis of StyreneRetrosynthetic Analysis of Styrene
CC66HH55CHCH CHCH22
HCHHCH
OO
++(C(C66HH55))33PP CHCCHC66HH55
++ ––
••••
CC66HH55CHCH
OO
++ (C(C66HH55))33PP CHCH22
++ ––
••••
Both routesBoth routesare acceptable.are acceptable.
Dr. Wolf's CHM 201 & 202 17- 113
Preparation of YlidesPreparation of YlidesPreparation of YlidesPreparation of Ylides
Ylides are prepared from alkyl halides by aYlides are prepared from alkyl halides by atwo-stage process.two-stage process.
The first step is a nucleophilic substitution.The first step is a nucleophilic substitution.Triphenylphosphine is the nucleophile.Triphenylphosphine is the nucleophile.
(C(C66HH55))33PP •••• ++ CHCH
AA
BB
XX
++
(C(C66HH55))33PP CHCH
AA
BB
++ XX––
Dr. Wolf's CHM 201 & 202 17- 114
Preparation of YlidesPreparation of YlidesPreparation of YlidesPreparation of Ylides
In the second step, the phosphonium salt isIn the second step, the phosphonium salt istreated with a strong base in order to removetreated with a strong base in order to removea proton from the carbon bonded to a proton from the carbon bonded to phosphorus.phosphorus.
(C(C66HH55))33PP CC
AA
BB
++HH
basebase ••••––
(C(C66HH55))33PP CC
AA
BB
++••••
––
HHbasebase
Dr. Wolf's CHM 201 & 202 17- 115
Preparation of YlidesPreparation of YlidesPreparation of YlidesPreparation of Ylides
Typical strong bases include organolithium Typical strong bases include organolithium reagents (RLi), and the conjugate base of reagents (RLi), and the conjugate base of dimethyl sulfoxide as its sodium saltdimethyl sulfoxide as its sodium salt[NaCH[NaCH22S(O)CHS(O)CH33].].
(C(C66HH55))33PP CC
AA
BB
++HH
basebase ••••
(C(C66HH55))33PP CC
AA
BB
++••••
––
––HHbasebase
Dr. Wolf's CHM 201 & 202 17- 116
Stereoselective Addition to Stereoselective Addition to
Carbonyl GroupsCarbonyl Groups
Stereoselective Addition to Stereoselective Addition to
Carbonyl GroupsCarbonyl Groups
Nucleophilic addition to carbonyl Nucleophilic addition to carbonyl groups sometimes leads to a mixture groups sometimes leads to a mixture
of stereoisomeric products.of stereoisomeric products.
Dr. Wolf's CHM 201 & 202 17- 11720%20%
ExampleExampleExampleExample CHCH33HH33CC
OO
80%80%
OOHH
HH
CHCH33HH33CC
OOHH
HH
CHCH33HH33CCNaBHNaBH44
Dr. Wolf's CHM 201 & 202 17- 118
this methyl group hindersapproach of nucleophilefrom top
this methyl group hindersapproach of nucleophilefrom top
HH33B—HB—H––
preferred direction ofapproach is to less hindered(bottom) face of carbonyl group
preferred direction ofapproach is to less hindered(bottom) face of carbonyl group
Steric Hindrance to Approach of ReagentSteric Hindrance to Approach of ReagentSteric Hindrance to Approach of ReagentSteric Hindrance to Approach of Reagent
Dr. Wolf's CHM 201 & 202 17- 119
Biological reductions are highly stereoselectiveBiological reductions are highly stereoselectiveBiological reductions are highly stereoselectiveBiological reductions are highly stereoselective
pyruvic acid pyruvic acid SS-(+)-lactic acid-(+)-lactic acid
OO
CHCH33CCOCCO22HHNADNADHH
HH++
enzyme is enzyme is lactate dehydrogenaselactate dehydrogenase
COCO22HH
HHOO HH
CHCH33
Dr. Wolf's CHM 201 & 202 17- 120
Figure 17.14Figure 17.14Figure 17.14Figure 17.14
One face of the One face of the substrate can bind to substrate can bind to the enzyme better the enzyme better than the other.than the other.
Dr. Wolf's CHM 201 & 202 17- 121
Figure 17.14Figure 17.14Figure 17.14Figure 17.14
Change in geometry Change in geometry from trigonal to from trigonal to tetrahedral is tetrahedral is stereoselective. stereoselective. Bond formation Bond formation occurs preferentially occurs preferentially from one side rather from one side rather than the other.than the other.
Dr. Wolf's CHM 201 & 202 17- 122
in aqueous solutionin aqueous solution
RCHRCH RCHRCH RCOHRCOH
OO OHOH
OHOH
HH22OOOO
Oxidation of AldehydesOxidation of AldehydesOxidation of AldehydesOxidation of Aldehydes
Dr. Wolf's CHM 201 & 202 17- 123
KK22CrCr22OO77
HH22SOSO44
HH22OO
OO
OO
CHCH
OO
OO
COHCOH
(75%)(75%)
viavia
OO
OHOH
CHCH
OHOH
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 17- 124
The Baeyer-Villiger OxidationThe Baeyer-Villiger Oxidation
of Ketonesof Ketones
The Baeyer-Villiger OxidationThe Baeyer-Villiger Oxidation
of Ketonesof Ketones
Oxidation of ketones with peroxy acidsOxidation of ketones with peroxy acidsgives esters by a novel rearrangement.gives esters by a novel rearrangement.
Dr. Wolf's CHM 201 & 202 17- 125
R"COR"COOOHH
OO
RRCCR'R'
OO
++ R"COHR"COH
OO
++
KetoneKetone EsterEster
RROOCCR'R'
OO
GeneralGeneralGeneralGeneral
Dr. Wolf's CHM 201 & 202 17- 126
CC66HH55COCOOOHH
OO
(67%)(67%)
Oxygen insertion occurs between carbonyl Oxygen insertion occurs between carbonyl carbon and larger group.carbon and larger group.
Methyl ketones give acetate esters.Methyl ketones give acetate esters.
CHClCHCl33
ExampleExampleExampleExample
CCHCCH33
OO
OOCCHCCH33
OO
Dr. Wolf's CHM 201 & 202 17- 127
CC66HH55COCOOOHH
OO
(66%)(66%)
Reaction is stereospecific.Reaction is stereospecific.
Oxygen insertion occurs with retention ofOxygen insertion occurs with retention ofconfiguration.configuration.
CHClCHCl33
StereochemistryStereochemistryStereochemistryStereochemistry
OO
CCHCCH33HH33CC
HH HH
OOCCHCCH33
OO
HH33CC
HH HH
Dr. Wolf's CHM 201 & 202 17- 128
R"COR"COOOHH
OO
RRCCR'R'
OO
++ RROOCCR'R'
OO
R"COHR"COH
OO
++
First step is nucleophilicFirst step is nucleophilicaddition of peroxy acidaddition of peroxy acidto the carbonyl group of to the carbonyl group of the ketone. the ketone.
OO
OO
CC
OO HH
RR R'R'
OCR"OCR"
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 17- 129
R"COR"COOOHH
OO
RRCCR'R'
OO
++ RROOCCR'R'
OO
R"COHR"COH
OO
++
OO
OO
CC
OO HH
RR R'R'
OCR"OCR"
Second step is migrationSecond step is migrationof group of group RR from carbon from carbonto oxygen. The weakto oxygen. The weakOO—O —O bond breaks in thisbond breaks in thisstep. step.
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 17- 130
Certain bacteria use hydrocarbons as a Certain bacteria use hydrocarbons as a source of carbon. Oxidation proceeds via source of carbon. Oxidation proceeds via ketones, which then undergo oxidation of the ketones, which then undergo oxidation of the Baeyer-Villiger type.Baeyer-Villiger type.
Biological Baeyer-Villliger OxidationBiological Baeyer-Villliger OxidationBiological Baeyer-Villliger OxidationBiological Baeyer-Villliger Oxidation OObacterialbacterial
oxidationoxidation
OO
OO
OO22..
cyclohexanonecyclohexanone
monooxygenase,monooxygenase,
coenzymescoenzymes
Dr. Wolf's CHM 201 & 202 17- 131
Spectroscopic Analysis ofSpectroscopic Analysis ofAldehydes and KetonesAldehydes and Ketones
Spectroscopic Analysis ofSpectroscopic Analysis ofAldehydes and KetonesAldehydes and Ketones
Dr. Wolf's CHM 201 & 202 17- 132
Presence of a C=O group is readily Presence of a C=O group is readily apparentapparentin infrared spectrumin infrared spectrum
C=O stretching gives an intense absorptionC=O stretching gives an intense absorptionat 1710-1750 cm-1at 1710-1750 cm-1
In addition to peak for C=O, aldehydes giveIn addition to peak for C=O, aldehydes givetwo weak peaks near 2720 and 2820 nm two weak peaks near 2720 and 2820 nm for H—C=Ofor H—C=O
Infrared SpectroscopyInfrared SpectroscopyInfrared SpectroscopyInfrared Spectroscopy
Dr. Wolf's CHM 201 & 202 17- 133Francis A. Carey, Organic Chemistry, Fifth Edition. Copyright © 2003 The McGraw-Hill Companies, Inc. All rights reserved.
2000200035003500 30003000 25002500 1000100015001500 500500
Wave number, cmWave number, cm-1-1
Figure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of Butanal
C=OC=O
CHCH33CHCH22CHCH22CH=OCH=O
H—C=OH—C=O
2720 cm2720 cm-1-1
2820 cm2820 cm-1-1
1720 cm1720 cm-1-1
Dr. Wolf's CHM 201 & 202 17- 134
Aldehydes: H—C=O proton is at very low fieldAldehydes: H—C=O proton is at very low field(( 9-10 ppm). 9-10 ppm).
Methyl ketones: CHMethyl ketones: CH33 singlet near singlet near 2 ppm. 2 ppm.
11H NMRH NMR11H NMRH NMR
Dr. Wolf's CHM 201 & 202 17- 135
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
HH CC
OO
CH(CHCH(CH33))22
Dr. Wolf's CHM 201 & 202 17- 136
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
CHCH33CC
OO
CHCH33CHCH22
Dr. Wolf's CHM 201 & 202 17- 137
1313C NMRC NMR1313C NMRC NMR
Carbonyl carbon is at extremely low field-near Carbonyl carbon is at extremely low field-near 200 ppm 200 ppm
Intensity of carbonyl carbon is usually weakIntensity of carbonyl carbon is usually weak
Dr. Wolf's CHM 201 & 202 17- 138Chemical shift (Chemical shift (, ppm), ppm)
020406080100120140160180200
CHCH33CHCH22CCCHCH22CHCH22CHCH22CHCH33
OO
Dr. Wolf's CHM 201 & 202 17- 139
UV-VISUV-VISUV-VISUV-VIS
Aldehydes and ketones have two bands in the Aldehydes and ketones have two bands in the
UV region:UV region:
* * andand nn**
*: excitation of a bonding *: excitation of a bonding electron to electron to
an antibonding an antibonding * orbital * orbital
*: excitation of a nonbonding electron on *: excitation of a nonbonding electron on
oxygen to an antibonding oxygen to an antibonding * orbital * orbital
Dr. Wolf's CHM 201 & 202 17- 140
UV-VISUV-VISUV-VISUV-VIS
HH33CC
HH33CC
CC OO•••• ••
••* * maxmax 187 nm 187 nm
nn* * maxmax 270 nm 270 nm
Dr. Wolf's CHM 201 & 202 17- 141
Molecular ion fragments to give an acyl cationMolecular ion fragments to give an acyl cation
m/z m/z 8686
++
m/z m/z 5757
Mass SpectrometryMass SpectrometryMass SpectrometryMass Spectrometry
CHCH22CHCH33••
CHCH33CHCH22CCCHCH22CHCH33
••++OO ••
••
CHCH33CHCH22CC OO ••••
++