Aldehydes and Ketones.Aldehydes and Ketones.Nucleophilic AdditionNucleophilic Addition

to theto theCarbonyl GroupCarbonyl Group

C

O

R H C

O

R R

An aldehydeAn aldehyde A ketoneA ketone

C

C

C

C

CHO

OH

OH

OH

OH

CH2OH

H

H

H

H

RiboseRibose

CCH3

O

H

CH3

CH3

O

ProgresteroneProgresterone

IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes HH

OO OO

HH

OO HCCHCHHCCHCH

OO1) Base the name 1) Base the name on the chain that on the chain that contains the contains the carbonyl group and carbonyl group and replace the replace the -e-e ending of the ending of the hydrocarbon by hydrocarbon by -al-al..

4,4-dimethylpent4,4-dimethylpentananalal5-hex5-hexenenalal

2-phenylprop2-phenylpropaneanedialdial(keep the (keep the -e -e endingendingbefore before -dial-dial))

IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes

2. The aldehyde functional group has priority over 2. The aldehyde functional group has priority over -X, -OH, -OR, double and triple bonds.-X, -OH, -OR, double and triple bonds.

Name –OH as hydroxy substituentName –OH as hydroxy substituentName –OR as alkoxy substituentName –OR as alkoxy substituent

CHCH33CHCH22CCHCCH22CHCH22CHCH33

OOCHCH33CHCHCHCH22CCHCCH33

OO

CHCH33 HH33CC OO

1) Base the name on the 1) Base the name on the chain that contains the chain that contains the carbonyl group and replace carbonyl group and replace --ee by by -one-one. Number the chain . Number the chain in the direction that gives the in the direction that gives the lowest number to the lowest number to the carbonyl carbon.carbonyl carbon.

Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones

3-3-hexanhexanoneone

4-methylcyclohexan4-methylcyclohexanoneone

4-methyl4-methyl-2--2-pentanpentanoneone

Trivial name for common aldehydes and ketones Trivial name for common aldehydes and ketones are widely used. Aldehydes are named after the parent are widely used. Aldehydes are named after the parent carboxylic acids with –carboxylic acids with –oic acidoic acid or – or –ic acidic acid ending ending changed to –changed to –aldehydealdehyde. (Table). (Table)

Propanone is usually called acetone, while the Propanone is usually called acetone, while the other simple ketones are sometimes named by a other simple ketones are sometimes named by a functional-group name. The alkyl or aryl groups functional-group name. The alkyl or aryl groups attached to the carbonyl group are named, then the attached to the carbonyl group are named, then the word ketone is added.word ketone is added.

CH3CCH3

O

IUPAC: propanone

trivial: acetone

CH3CCH2CH3

O

butanonemethyl ethyl ketone

(CH3)2CHCCH2(CH3)3

O

2,2,4-trimethyl-3-pentanoneisopropyl tert-butyl ketone

Trivial names for some carboxylic acids and aldehydes

Carboxylic acid Aldehydes

HCOH

O

formic acid HCH

O

formaldehyde

CH3COH

O

acetic acid CH3CH

O

acetaldehyde

CH3CH2COH

O

propionic acid CH3CH2CH

O

propionaldehyde

CH3CH2CH2COH

O

butyric acid CH3CH2CH2CH

O

butyraldehyde

COH

O

benzoic acid CH

O

benzaldehyde

Other positions in a molecule in relation to the carbonyl Other positions in a molecule in relation to the carbonyl group may be referred to be Greek lettersgroup may be referred to be Greek letters

Preparation of aldehydePreparation of aldehyde

1. Oxidation of primary alcohols 1. Oxidation of primary alcohols

CHCH33CHCH22OH + CrOOH + CrO33.2.2 N CHCH33CHOCHO

EtanolEtanol Kromat piridin oksidaKromat piridin oksida EtanalEtanal

2. Reduction of acid derivates2. Reduction of acid derivates

RCOOHSOCl2

RCOCl RCHOH2/Pt

(H3C)2HC CH3 + CH3COClAlCl3

(H3C)2HC CH3

COCH3

Isopropil toluenaIsopropil toluena Asetil kloridaAsetil klorida 5-isopropil-2-metil5-isopropil-2-metilasetofenonasetofenon

3. From terminus of alkyne (hydroboration)3. From terminus of alkyne (hydroboration)

C CHR + Sia2BH CHR CH BSia2H2O2

OH-/H2ORCH2CHO

disiamilborandisiamilboran Vinyl boranVinyl boran

Preparation of KetonePreparation of Ketone

1. Friedel-Craft Acylation1. Friedel-Craft Acylation

ArH + RCOClAlCl3

ArCOR

2. Oxidation of secondary alcohol2. Oxidation of secondary alcohol

CH3CH(OH)CH3H2CrO4, H+

C

O

CH3H3C

3. From Alkyne3. From Alkyne

C CR RH3O+, Hg2+

H2ORCOCHR RCOCH2R

HidrationHidration

C CR R(1) (BH3)2

(2) H2O2, OH-RC(OH)=CHR RCOCH2R

HidroborationHidroboration

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.

More polar than alkenes, More polar than alkenes, but cannot form but cannot form intermolecular hydrogen intermolecular hydrogen bonds to other carbonyl bonds to other carbonyl groupsgroups

OO

OHOH

nucleophiles attack carbon; nucleophiles attack carbon; electrophiles attack oxygenelectrophiles attack oxygen

Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group

CC

OO •••• ••••

CC

OO

++

––•••••••• ••••

Acid Catalyst Makes Carbon More Electrophilic

CC••••OO ••••

Step 1:Step 1:Step 1:Step 1:++ ••••

HH

OOHH

HH++

++

CC

••••OOHH++

•••• ••••

HH

OO

HH

CC••••OOHH••••++

Nucleophilic Nucleophilic

Addition to Carbonyl GroupsAddition to Carbonyl Groups Basic Reaction

CC••••OO ••••Nu:Nu:

••••

NuNu CC OO••••

••••

••••••••––

Ketones are Less Reactive Than Aldehydes

1. Steric Reasons

2. R Groups are more electron donating than H

Grignard reagents act as nucleophilesGrignard reagents act as nucleophilestoward the carbonyl grouptoward the carbonyl group

RR

MgXMgX

CC

OO••••

••••

–– ++

––

MgXMgX++

RR CC

OO••••

•••• ••••

diethyldiethyletherether

••••

RR CC

OHOH••••

HH33OO++

two-step sequence two-step sequence gives an alcohol as gives an alcohol as the isolated productthe isolated product

ExamplesExamples MgClMgCl CC OO

HH

HH

CCHH22OHOH

HH33OO2)2)++

CHCH33(CH(CH22))44CHCH22MgBrMgBr CC OO

HH33CC

HHCHCH33(CH(CH22))44CHCH22CCHHCHCH33

OHOH

++

2) H2) H33OO++

ExampleExample CC

OHOH

CHCH33

CHCH22CHCH33

CC CHCH22CHCH33

OO

CHCH33MgXMgX

There are two other There are two other possibilities. possibilities.

Can you see them?Can you see them?

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

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

Step 1: Acid CatalystStep 1: Acid CatalystStep 1: Acid CatalystStep 1: Acid Catalyst

CC••••OO•••• ++ ••••

HH

OOHH

HH++ ++

CC

••••OOHH++ •••• ••••

HHOO

HH

Step 2: Nucleophilic attackStep 2: Nucleophilic attackStep 2: Nucleophilic attackStep 2: Nucleophilic attack

CC••••OOHH++

++••••

HH

OO

HH

••••CC OOHH

••••

••••

HH

OO

HH

•••• ++

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

Step 3: Regeneration of catalystStep 3: Regeneration of catalystStep 3: Regeneration of catalystStep 3: Regeneration of catalyst

++••••

HH

OO

HH

••••CC OOHH

••••

HHOO

HH

••••

•••• •••• OO

HH

••••CC OOHH

••••

••••

++

HH

HHOO

HH ••••

++

One Alcohol Will React with a Ketone to FormOne Alcohol Will React with a Ketone to Forma Hemiketal; Two Will Form a Ketala Hemiketal; Two Will Form a Ketal

R"OR"O CC OO HH••••

••••

••••

••••

RR

R'R'a a hemiketalhemiketal..

CC••••OO ••••

RR

R'R'

+ + R’’-OHR’’-OH

R"OR"O CC OROR••••

••••

••••

••••

RR

R'R'

+ H+ H22OO

A ketalA ketal

R"OR"O CC OO HH••••

••••

••••

••••

RR

R'R'

R-OHR-OH / /HH++

HClHCl

2CH2CH33CHCH22OOHH++

+ H+ H22OO

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

ExampleExample

CHCH

OO CH(CH(OOCHCH22CHCH33))22

MechanismMechanism; ; Step 1: Protonate O of Carbonyl groupStep 1: Protonate O of Carbonyl group

HH

HH

RR++OO••••CC OO

••

••••••

CC OO••

••HH

RROO

••••HH

++ ••••++

Step 2: Nucleophilic atom (O) attacks electrophilic C.Step 2: Nucleophilic atom (O) attacks electrophilic C.

CC OO••••

HH

++

RR

HH

OO••••••••CC OO

••••OO

••••HH

++••••

RR

HH

CC OO••••

OO••••

HH++••••

RR

HH

OORR HH

••••••••

Step 3: H is abstracted to form hemiketal/hemiacetalStep 3: H is abstracted to form hemiketal/hemiacetal

++HH

OORR HH••••

CC OO••••

OO ••••

HH

••••RR

••••

Step 4: Hemiacteal/hemiketal is protonated to formStep 4: Hemiacteal/hemiketal is protonated to formA good leaving group (HA good leaving group (H22O)O)

CC OO••••

OO ••••

HH

••••RR

••••

HH

HH

RR++OO•••• CC OO

••••OO

HH

••••RR

••••

HH++ ++

HH

RR

OO••••••••

OO••••

OO

HH

••••RR

••••++

HH

CC

Step 5: Leaving group (HStep 5: Leaving group (H22O) leaves andO) leaves and

forms carbocationforms carbocation

Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage

CCOO••••

RR

•• ++ OO••••

HH

HH••••++••••

Carbocation is stabilized by delocalizationCarbocation is stabilized by delocalizationof unshared electron pair of oxygenof unshared electron pair of oxygen

CCOO••••

RR

••••++ CCOO

RR

••••

++

CCOO••••

RR

••••++ OO

••••

HH

RR••••

Step 6: Second nucleophile (ROH) attacks carbocationStep 6: Second nucleophile (ROH) attacks carbocation

Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage

CCOO••••

RR

••••++OO

••••

HH

RR

CCOO••••

RR

••••++OO

••••

HH

RR

OO••••

HH

RR••••

Step 7: Alcohol abstracts acidic H to form acetal/ketal.Step 7: Alcohol abstracts acidic H to form acetal/ketal.

++HH OO••••

HH

RRCCOO••••RR

••

••

OO••••

RR

••••

Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage

CCOO••••

RR

••••++OO

••••

HH

RR

OO••••

HH

RR••••

Step 7: Alcohol abstracts acidic H to form acetal/ketal.Step 7: Alcohol abstracts acidic H to form acetal/ketal.

++HH OO••••

HH

RRCCOO••••RR

••

••

OO••••

RR

••••

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 Acetals

Reduction Reactions

• Reducing Agents; LiAlH4 , NaBH4

ExamplesExamples

CH3CH2CCH2CH3

O+ LiAlH4

2) H 3O+

CH3CH2CHCH2CH3

OH

Reduction of Aldehydes and ketonesReduction of Aldehydes and ketones1. Hydrogenation1. Hydrogenation

2. Metal Hydrides2. Metal Hydrides

Wolff-Kishner reductionWolff-Kishner reduction

CCH3

O H+

NH2NH2CCH3

NNH2

KOHCH2CH3

Clemmensen reductionClemmensen reduction

CH2CH3CCH3

O

Zn/Hg

HCl

in aqueous solutionin aqueous solution

RCHRCH RCHRCH RCOHRCOH

OO OHOH

OHOH

HH22OOOO

Oxidation of AldehydesOxidation of Aldehydes

KK22CrCr22OO77

HH22SOSO44

HH22OO

OO

OO

CHCH

OO

OO

COHCOH

(75%)(75%)

viavia

OO

OHOH

CHCH

OHOH

ExampleExample