Dr. Wolf's CHM 201 & 202 17- 1 Chapter 17 Aldehydes and Ketones. Nucleophilic Addition to the Carbonyl Group.

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- 2

NomenclatureNomenclatureNomenclatureNomenclature

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


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


transtrans--CHCH33CH=CHCHCH=CHCH33

2707 kJ/mol2707 kJ/mol(CH(CH33))22C=CHC=CH22




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%)


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)


••••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 ••••


++ ••••

HH

OOHH

HH++

++

CC

••••OOHH++

•••• ••••

HH

OO

HH

Dr. Wolf's CHM 201 & 202 17- 40



CC••••OOHH++

++••••

HH

OO

HH

••••CC OOHH

••••

••••

HH

OO

HH

•••• ++

Dr. Wolf's CHM 201 & 202 17- 41



++••••

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

++


••••••••CC OO HCNHCN HHCC OONN CC••••

••••

••••

Dr. Wolf's CHM 201 & 202 17- 44


••••••••CC OO

CC––

NN•••• ••••

Dr. Wolf's CHM 201 & 202 17- 45


––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%)


ClCl ClCl CHCH

OOClCl

ClCl CHCNCHCN

OHOHNaCN, waterNaCN, water

then Hthen H22SOSO44

Dr. Wolf's CHM 201 & 202 17- 47


CHCH33CCHCCH33

OONaCN, waterNaCN, water

then Hthen H22SOSO44

CHCH33CCHCCH33

OHOH

CNCN

(77-78%)(77-78%)

Dr. Wolf's CHM 201 & 202 17- 48

Acetal FormationAcetal FormationAcetal FormationAcetal Formation

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


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%)


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


++ HH22OO

HH22CC CHCH22

OO OO

CC(78%)(78%)

CC66HH55CHCH22CCHCCH33

CHCH33CC66HH55CHCH22


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


CC OO••••

HH

RR

OO ••••

HH

++ ••••

Dr. Wolf's CHM 201 & 202 17- 60


CC OO••••

HH

++

RR

HH

OO ••••••••

Dr. Wolf's CHM 201 & 202 17- 61


CC OO••••

OO ••••

HH++

••••RR

HH

OORR HH

••••

••••

Dr. Wolf's CHM 201 & 202 17- 62


++

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


HH

RR

OO ••••••••CC OO••••

OO

HH

••••RR

••••

HH

++

Dr. Wolf's CHM 201 & 202 17- 66


OO••••

OO

HH

••••RR

••••++

HH

CC

Dr. Wolf's CHM 201 & 202 17- 67


CCOO••••

RR

••••++ OO

••••

HH

HH

••••

Dr. Wolf's CHM 201 & 202 17- 68


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


CCOO••••

RR

••••++ OO

••••

HH

RR

••••

Dr. Wolf's CHM 201 & 202 17- 70


CCOO••••

RR

••••++OO

••••

HH

RR

OO••••

HH

RR

••••

Dr. Wolf's CHM 201 & 202 17- 71


++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


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++


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





Compounds related to iminesCompounds related to imines

EnaminesEnamines


Dr. Wolf's CHM 201 & 202 17- 82






EnaminesEnamines


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%)


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


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


Dr. Wolf's CHM 201 & 202 17- 88






EnaminesEnamines


Dr. Wolf's CHM 201 & 202 17- 89






EnaminesEnamines


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%)


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

++


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






EnaminesEnamines


Dr. Wolf's CHM 201 & 202 17- 98






EnaminesEnamines


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






EnaminesEnamines


Dr. Wolf's CHM 201 & 202 17- 103






EnaminesEnamines


Dr. Wolf's CHM 201 & 202 17- 104


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


(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


++

++ (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


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


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


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


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


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


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"


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.


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 ••••

++

Dr. Wolf's CHM 201 & 202 17- 142

End of Chapter 17End of Chapter 17End of Chapter 17End of Chapter 17

Dr. Wolf's CHM 201 & 202 17- 1 Chapter 17 Aldehydes and Ketones. Nucleophilic Addition to the Carbonyl Group.

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