aldehydes and ketones - welcome to chemconnections

Aldehydes Aldehydes and Ketonesand Ketones

Nucleophilic AdditionNucleophilic Additionto theto the

Carbonyl GroupCarbonyl Group

NomenclatureNomenclature

IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes

HH

OO

OO

HH

OO

HCCHCHHCCHCH

OOBase the name on theBase the name on thechain that containschain that containsthe carbonyl groupthe carbonyl groupand replace the and replace the -e-eending of theending of thehydrocarbon with hydrocarbon with -al-al..

4,4-dimethylpent4,4-dimethylpentananalal 5-hex5-hexenenalalor or hex-5-enhex-5-enalal

IUPAC 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))

when named as when named as a a substituentsubstituent

formyl formyl groupgroup carbaldehyde carbaldehyde ororcarboxaldehydecarboxaldehyde

when named when named as a suffixas a suffix

CC HH

OO

IUPAC Nomenclature of Aldehydes IUPAC Nomenclature of Aldehydes

Question

• What is the correct IUPAC name of the aldehyde at the right?

• A) 2,3-dihydroxypropanol• B) 1,2-dihydroxypropanal• C) 2,3-dihydroxypropanal• D) 2,3-propanediol-1-aldehyde

CHCH33CHCH22CCHCCH22CHCH22CHCH33

OO

CHCH33CHCHCHCH22CCHCCH33

OO

CHCH33

HH33CC OO

Base the name on the chainBase the name on the chainthat contains the carbonyl groupthat contains the carbonyl groupand replace and replace -e-e with with -one-one..Number the chain in theNumber the chain in thedirection that gives the lowestdirection that gives the lowestnumber to the carbonyl carbon.number to the carbonyl carbon.

Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones

Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones

CHCH33CHCH22CCHCCH22CHCH22CHCH33

OO

CHCH33CHCHCHCH22CCHCCH33

OO

CHCH33

HH33CC OO

3-3-hexanhexanoneoneor or HexanHexan-3-one-3-one

4-methyl4-methyl-2--2-pentanpentanoneoneor or 4-methylpentan-4-methylpentan-2-one2-one

4-methylcyclohexan4-methylcyclohexanoneone

Functional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of Ketones

CHCH33CHCH22CCCHCH22CHCH22CHCH33

OO OO

CHCH22CCCHCH22CHCH33

CHCH CHCH22

OO

HH22CC CHCCHC

List the groupsList the groupsattached to theattached to thecarbonyl separately incarbonyl separately inalphabetical order, andalphabetical order, andadd the word add the word ketoneketone..

CHCH33CHCH22CCCHCH22CHCH22CHCH33

OO

ethylethyl propylpropyl ketone ketone benzylbenzyl ethylethyl ketoneketone

divinyl ketonedivinyl ketone

OO

CHCH22CCCHCH22CHCH33

CHCH CHCH22

OO

HH22CC CHCCHC

Functional Class IUPAC Nomenclature of KetonesFunctional Class IUPAC Nomenclature of Ketones Question• What is the IUPAC name for the ketone shown below?

• A) 5-ethyl-2-methyl-3-hexanone• B) 2,5-dimethyl-3-heptanone• C) 3,6-dimethyl-5-heptanone• D) 2-ethyl-5-methyl-5-hexanone

Question

• A compound (C7H14O) has a strong peak in its IR spectrumat 1710 cm-1. Its 1H-NMR spectrum consists of 3 singlets inthe ratio 9:3:2 at δ1.0, δ2.1, and δ2.3, respectively.

Identify this compound.

• A) 3-heptanone• B) 2,2-dimethyl-3-pentanone• C) 4,4-dimethyl-2-pentanone• D) 2,4-dimethyl-3-pentanone

The Carbonyl GroupThe Carbonyl GroupStructure, BondingStructure, Bonding

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

OO

OO

HH

Heats of combustion ofHeats of combustion ofCC44HH88 isomeric alkenes isomeric alkenes

CHCH33CHCH22CH=CHCH=CH222717 kJ/mol2717 kJ/mol

ciscis-CH-CH33CH=CHCHCH=CHCH332710 kJ/mol2710 kJ/mol

transtrans-CH-CH33CH=CHCHCH=CHCH332707 kJ/mol2707 kJ/mol

(CH(CH33))22C=CHC=CH222700 kJ/mol2700 kJ/mol



OO

OO

HH

Spread is Greater forSpread is Greater forAldehydes andAldehydes and

Ketones than for AlkenesKetones than for Alkenes

Nucleophiles attack carbon; Nucleophiles attack carbon; electrophiles attack oxygen.electrophiles attack oxygen.

Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group

CC

OO •••• ••••

CC

OO

++

––•••••••• ••••SynthesisSynthesis

Aldehydes Aldehydes && KetonesKetones

from alkenesfrom alkenes

ozonolysisozonolysis

from alkynesfrom alkynes

hydration (via enol)hydration (via enol)

from arenesfrom arenes

Friedel-Crafts acylationFriedel-Crafts acylation

from alcoholsfrom alcohols

oxidationoxidation

Synthesis of Aldehydes and KetonesSynthesis of Aldehydes and Ketones

A number of A number of reactions alreadyreactions alreadystudied providestudied provide

efficient syntheticefficient syntheticroutes to routes to

aldehydes aldehydes and and ketonesketones..

Question

• What combination of reagents will transform 1-butyne into 2-butanone?

• A) 1. O3 2. H2O, Zn• B) K2Cr2O7, H2SO4

• C) H2SO4, HgSO4

• D) OsO4 (cat), (CH3)3COOH, (CH3)3OH, HO-

CC

OO

RR OHOH

aldehydes from carboxylic acidsaldehydes from carboxylic acids

RCHRCH22OHOH1. LiAlH1. LiAlH442. H2. H22OO

PCC orPCC orPDC, CHPDC, CH22ClCl22

HHCC

OO

RR

Reduction & OxidationReduction & Oxidation

Benzaldehyde from benzoic acidBenzaldehyde from benzoic acid

COHCOH

OO

CHCH

OO

1. LiAlH1. LiAlH442. H2. H22OO

PCC orPCC orPDCPDCCHCH22ClCl22CHCH22OHOH

(81%)(81%) (83%)(83%)

ExampleExample

CC

OO

RR OROR’’

aldehydes from carboxylic acid estersaldehydes from carboxylic acid esters

1.1. DIBAL-HDIBAL-H((Diisobutyl Diisobutyl aluminum hydride)aluminum hydride)

2. H2. H22OOHH

CC

OO

RR

ReductionReduction

or from or from nitriles nitriles R-CN with DIBAL-HR-CN with DIBAL-H

CC

OO

RR HH

Ketones from aldehydesKetones from aldehydes

R'R'CC

OO

RR

PCC orPCC orPDC, CHPDC, CH22ClCl22

1. 1. R'MgXR'MgX2. H2. H33OO++

RCHRCHR'R'

OHOH

Grignard Grignard & Oxidation& Oxidation

Question

• Which combination of reagents will produce 2-hexanone asthe major organic product?

• A) 2-hexanol + PCC in CH2Cl2• B) 1-hexene + H2O, H2SO4, HgSO4

• C) pentanal + methylmagnesium bromide followed byH3O+

• D) All of the above (a-c) will produce 2-hexanone asthe major product.

CC

OO

CHCH33CHCH22 HH

3-heptanone from propanal3-heptanone from propanal

HH22CrOCrO441. 1. CHCH33(CH(CH22))33MgXMgX2. H2. H33OO++

CHCH33CHCH22CHCH(CH(CH22))3 3 CHCH33

OHOH

OO

CHCH33CHCH22CC(CH(CH22))3 3 CHCH33

(57%)(57%)

ExampleExample

Question

• An alcohol with a molecular formula C7H16O was treated withchromic acid. The product produced 4 signals in its 13C-NMRspectrum: one at 210 ppm and 3 others below 50 ppm.Identify the ketone.

• A) 4-heptanone• B) 2,4-dimethyl-3-pentanone• C) 4,4-dimethyl-2-pentanone• D) 5-methyl-3-hexanone

Reactions of Aldehydes and Reactions of Aldehydes and KetonesKetones

Reduction of C=O to CHReduction of C=O to CH22

Clemmensen Clemmensen reductionreduction

Wolff-Kishner reductionWolff-Kishner reduction

Reduction of C=O to CHOHReduction of C=O to CHOH

Addition of Grignard and organolithium reagentsAddition of Grignard and organolithium reagents

Reactions of Aldehydes and KetonesReactions of Aldehydes and KetonesQuestion

• Which compound will be isolated from the syntheticsequence shown below?

• A) B)

• C) D)

Aldehydes and ketones react with nucleophiles to formaddition products: nucleophile addition reactions

Question

• When a nucleophile encounters a ketone, the site of attack is• A) the carbon atom of the cabonyl.• B) the oxygen atom of the carbonyl.• C) both the carbon and oxygen atoms, with

equal probability.• D) No attack occurs--ketones do not react with

nucleophiles.

Hydration ofHydration of Aldehydes Aldehydes andand KetonesKetones HH22OO

Hydration of Aldehydes and KetonesHydration of Aldehydes and Ketones

CC••••OO ••••

HOHO CC OO HH••••

••••

••••

••••

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 Equilibria

C=OC=O hydratehydrate KK %% RelativeRelativeraterate

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

Only when the carbonyl group is Only when the carbonyl group is destabilizeddestabilized

•• alkyl groups alkyl groups stabilizestabilize C=O C=O

•• electron-withdrawing groups electron-withdrawing groups destabilizedestabilize C=O C=O

Equilibrium Can Favor a HydrateEquilibrium Can Favor a Hydrate(But not very often)(But not very often)

OHOH

OHOH

RR RR++ HH22OO CCCCRR RR

OO

Substituent Effects on Hydration EquilibriaSubstituent Effects on Hydration Equilibria

RR = CH = CH33: : KK = 0.0014 = 0.0014

RR = CF = CF33: : KK = 22,000 = 22,000

Mechanism of Hydration (base)Mechanism of Hydration (base)

CC••••OO •••••••• OO ••••

HH

••••

––

Step 1:Step 1:

++

••••HOHO CC OO

••••

••••

••••••••––

Mechanism of Hydration (base)Mechanism of Hydration (base)

Step 2:Step 2:

••••OOHH

HH

••••

••••HOHO CC OO

••••

••••

••••••••––

++••••

••••OO

HH

••••––••••

HOHO CC OOHH••••

••••

••••

Mechanism of Hydration (acid)Mechanism of Hydration (acid)

CC••••OO ••••

Step 1:Step 1:

++ ••••

HH

OOHH

HH++

++

CC••••OOHH++

•••• ••••

HH

OO

HH


Step 2:Step 2:

CC••••OOHH++

++••••

HH

OO

HH

••••CC OOHH

••••

••••

HH

OO

HH

•••• ++


Step 3:Step 3:

++••••

HH

OO

HH

••••CC OOHH

••••

HHOO

HH

••••

••••

•••• OO

HH

••••CC OOHH

••••

••••

++

HH

HHOO

HH ••••

++

Question

• Which one of the compounds below has the fastest hydrationrate?

• A) B)

• C) D)

Cyanohydrin Formation

++

Cyanohydrin FormationCyanohydrin Formation

••••••••CC OO HCNHCN HHCC OONN CC•••• ••••

••••


••••••••CC OO

CC––

NN•••• ••••


––OONN CC CC••••

•••• ••••••••

HH

HH

HH++OO ••••

HH

HH

OO ••••••••OONN CC CC••••

•••••••• HH

2,4-Dichlorobenzaldehyde2,4-Dichlorobenzaldehydecyanohydrin (100%)cyanohydrin (100%)

ExampleExample

ClCl

ClCl CHCH

OOClCl

ClCl CHCNCHCN

OHOHNaCN, waterNaCN, water

then Hthen H22SOSO44

ExampleExample

CHCH33CCHCCH33

OONaCN, waterNaCN, water

then Hthen H22SOSO44

CHCH33CCHCCH33

OHOH

CNCN

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

Acetone cyanohydrin is used in the synthesisAcetone cyanohydrin is used in the synthesisof of methacrylonitrilemethacrylonitrile

Acetal Acetal FormationFormation

Some reactions ofSome reactions of aldehydes aldehydes andand ketones ketones progressprogressbeyond thebeyond the nucleophilic nucleophilic addition stageaddition stage

Acetal Acetal formationformation

Imine Imine formationformation

Enamine Enamine formationformation

Compounds related to imines Compounds related to imines

TheThe Wittig Wittig reactionreaction

Recall Hydration ofRecall Hydration of Aldehydes Aldehydes andand KetonesKetones

HOHHOH

CC••••OO ••••

HOHO CC OO HH••••

••••

••••

••••

RR

R'R'

RR

R'R'

Alcohols Under Analogous ReactionAlcohols Under Analogous Reactionwithwith Aldehydes Aldehydes andand KetonesKetones

R"OR"OHH

CC••••OO ••••

RR

R'R'

R"OR"O CC OO HH••••

••••

••••

••••

RR

R'R'

Product is calledProduct is calledaa hemiacetalhemiacetal..

Product is calledProduct is calledaa hemiacetalhemiacetal..

ROROH, HH, H++

HemiacetalHemiacetal reacts further in acid to yield an reacts further in acid to yield an acetal acetal

R"OR"O CC OO HH••••

••••

••••

••••

RR

R'R'

R"OR"O CC OROR••••

••••

••••

••••

RR

R'R'

Product is calledProduct is calledanan acetalacetal..

Question

• The structure shown at the right would be best classified asa(n)

• A) acetal.• B) hemiacetal.• C) hydrate.• D) cyanohydrin.

HClHCl

2CH2CH33CHCH22OOHH++

+ H+ H22OO

Benzaldehyde diethyl acetal (66%)Benzaldehyde diethyl acetal (66%)

ExampleExample

CHCH

OO

CH(CH(OOCHCH22CHCH33))22

HHOOCHCH22CHCH22OOHH++CHCH33(CH(CH22))55CHCH

OO

pp-toluenesulfonic acid-toluenesulfonic acidbenzenebenzene

++ HH22OO

(81%)(81%) HH (CH(CH22))55CHCH33

HH22CC CHCH22

OO OOCC

Diols Form Cyclic AcetalsDiols Form Cyclic Acetals In general:In general:

Position of equilibrium is usually unfavorablePosition of equilibrium is usually unfavorableforfor acetal acetal formation fromformation from ketonesketones..

Important exception:Important exception:CyclicCyclic acetals acetals can be prepared fromcan be prepared from ketonesketones..

HHOOCHCH22CHCH22OOHH++

OO

pp--toluenesulfonictoluenesulfonic acid acidbenzenebenzene

++ HH22OO

HH22CC CHCH22

OO OOCC(78%)(78%)

CC66HH55CHCH22CCHCCH33

CHCH33CC66HH55CHCH22

ExampleExampleQuestion

• What is the product of the reaction between benzaldehyde and 1,3-propanediol?

• A) B)

• C) D)

CCRR R'R'

OO

2R"2R"OOHH++

OOR"R"

RR R'R'CC

OOR"R"

+ H+ H22OO

mechanism:mechanism:

reverse ofreverse of acetal acetal formation;formation;hemiacetal hemiacetal is intermediateis intermediate

application:application:

aldehydes aldehydes andand ketones ketones can be can be "protected" as"protected" as acetalsacetals..

Hydrolysis ofHydrolysis of Acetals Acetals

Acetals Acetals as Protecting Groupsas Protecting Groups

The conversion shown cannot be carried outThe conversion shown cannot be carried outdirectly...directly...

CHCHCHCH33CCHCCH22CHCH22CC

OO

CCCHCH33CHCH33CCHCCH22CHCH22CC

OO

1. NaNH1. NaNH222. 2. CHCH33II

ExampleExample because the carbonyl group and thebecause the carbonyl group and thecarbanion carbanion are incompatible functionalare incompatible functionalgroups.groups.

CC::CHCH33CCHCCH22CHCH22CC

OO––

1) protect C=O 1) protect C=O

2)2) alkylatealkylate

3) restore C=O3) restore C=O

StrategyStrategy

HHOOCHCH22CHCH22OOHH++

pp-toluenesulfonic -toluenesulfonic acidacidbenzenebenzene

HH22CC CHCH22

OO OOCC

CHCH33

CHCH33CCHCCH22CHCH22CC

OO

CHCH

CHCH22CHCH22CC CHCH

Example: Example: ProtectProtect

HH22CC CHCH22

OO OOCC

CHCH33CHCH22CHCH22CC CHCH

1. NaNH1. NaNH222. 2. CHCH33II

HH22CC CHCH22

OO OOCC

CHCH33CHCH22CHCH22CC CCCHCH33

Example: Example: AlkylateAlkylate

HH22CC CHCH22

OO OOCC

CHCH33CHCH22CHCH22CC CCCHCH33

HH22OO

HClHCl

HHOOCHCH22CHCH22OOHH

(96%)(96%)

CCCHCH33CHCH33CCHCCH22CHCH22CC

OO

++

Example: Example: DeprotectDeprotect

Question• What reagent and/or reaction conditions would you choose

to bring about the following conversion?

• A) 1. LiAlH4; 2. H2O• B) H2O, H2SO4, heat• C) H2O, NaOH, heat• D) PCC, CH2Cl2

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