Aldehydes and Aldehydes and KetonesKetones

NomenclatureNomenclature PropertiesProperties Preparation reactions of Aldehydes and Preparation reactions of Aldehydes and

KetonesKetones Characteristic reactions of Aldehydes and Characteristic reactions of Aldehydes and

KetonesKetones Carbanion related reactionsCarbanion related reactions Spectroscopy Spectroscopy

Aldehydes and Aldehydes and KetonesKetones

NomenclatureNomenclature IUPACIUPAC CommonCommon

PropertiesProperties

Preparation of Preparation of Aldehydes and Aldehydes and

KetonesKetones Oxidation reactionsOxidation reactions Hydrolysis of Geminal DihalidesHydrolysis of Geminal Dihalides Hydration of AlkynesHydration of Alkynes Reactions with Acid Derivatives and Reactions with Acid Derivatives and

NitrilesNitriles Reaction with Carboxylic AcidsReaction with Carboxylic Acids Reaction with ThioacetalsReaction with Thioacetals

Aldehydes/Ketones via Aldehydes/Ketones via Oxidation ReactionsOxidation Reactions

From Alcohols via PCCFrom Alcohols via PCC From Alkenes via OzonolysisFrom Alkenes via Ozonolysis From Glycols via Periodic Acid CleavageFrom Glycols via Periodic Acid Cleavage

RCH2OHPCC

R C

O

H

R2CHOH PCC R C

O

R

ozonolysis R C

O

HR'CH CR2' +R C

O

R

R C

OH

CH2OH

R'

HIO4R C

O

R' +H C

O

H

Hydrolysis of Geminal Dihalides

Formation of Aldehydes or KetonesFormation of Aldehydes or Ketones

Cl2H2O

∆+ HCl2CHR C

O

HR

R2CCl2H2O

∆+ HCl2C

O

R R

Hydration of Hydration of AlkynesAlkynes

Markovnikov Addition Anti-Markovnikov Addition

R C CHH2O/H 2SO4

HgSO4R C

OH

CH2 R C

O

CH3

R C CH RCH CH

OH

R CH2 C

O

H1.

2.H2O2/OH -9-BBN

Reactions with Acid HalidesReactions with Acid Halides

Aldehydes via Selective ReductionAldehydes via Selective Reduction Lithium tri-tert-butoxyaluminum hydrideLithium tri-tert-butoxyaluminum hydride Rosenmund reduction Rosenmund reduction

Ketones via Friedel-Crafts AcylationKetones via Friedel-Crafts Acylation Ketones via reaction with OrganometallicsKetones via reaction with Organometallics

Gilman reagent (organocuprates)Gilman reagent (organocuprates)

Aldehydes from Acid Aldehydes from Acid ChloridesChlorides

Lithium tri-t-butoxyaluminum hydride reduction

Rosenmund reduction

R C

O

Clether

R C

O

H

R C

O

Cl R C

O

HH2 / Pd / S

BaSO4Rosenmund catalyst

LiAlH(O-t-bu)3

Aldehydes from Esters and Aldehydes from Esters and AmidesAmides

Diisobutylaluminum hydrideDiisobutylaluminum hydride

(DIBAH or DIBAL-H)(DIBAH or DIBAL-H)

R C

O

OR'or

R C

O

NH2

R C

O

NHR'

R C

O

NR2'

or

or1.Diisobutylaluminum

hydride

2. H3O+

R C

O

H

Ketones via Friedel-Crafts Acylation

R C

O

ClAlCl3

benzene C

O

R +HCl

R C

O

O C

O

RAlCl3

benzene C

O

R +RCOOH

Ketones via Reaction Ketones via Reaction with Organometallicswith Organometallics

Use of Lithium dialkylcuprates

R C

O

Cl(R')2CuLi

R C

O

R' + +LiCl

where R' can be alkyl, aryl, or vinyl

R'-Cu

Reactions with Nitriles

Grignard Addition to give KetonesGrignard Addition to give Ketones DIBAH Addition to give AldehydesDIBAH Addition to give Aldehydes

R CNR'MgX

R C

R'

N MgXH+

H2OR C

O

R'

R CNdiisobutylaluminum hydride

R C

H

N Al(i-bu)2

H+/H 2OR C

O

H

DIBAH or DIBAL-H

Ketones from Carboxylic Ketones from Carboxylic AcidsAcids

Attack by Alkyl Lithium reagentsAttack by Alkyl Lithium reagents

RCOOH RLi RCOO- Li+ + RH

RCOO- Li+ RLi CR

R

O-

O-

Li+

Li+

CR

R

O-

O-

Li+

Li+H2O C

R

R

OH

OH

CR

R

OH

OH

H2O( )C

O

RR

Ketones from Ketones from ThioacetalsThioacetals Thioacetal formation from an aldehyde precursor

Alkylation of the thioacetal intermediate using alkyl lithium reagents

Hydrolysis of the alkylated thioacetal to give ketone product

R C

O

HHSCH2CH2SH

BF3

S SC

R H

(a thioacetal)

S SC

R H

C4H9Li S SC

RLi+

R'CH2XS S

CR CH2R'

+ LiX

S SC

R CH2R'

HgCl2 / CH3OH / H2OR C

O

CH2R'

( C4H10)

( )HSCH2CH2SH

Characteristic Reactions of Aldehydes and Ketones

Characteristic Reactions of Aldehydes and Ketones

Reduction reactionsReduction reactions Alcohol formationAlcohol formation Alkane formationAlkane formation

Oxidation reactionsOxidation reactions Nucleophilic addition reactionsNucleophilic addition reactions

Grignard additions to form alcoholsGrignard additions to form alcohols Addition of water (hydration) to form gem-diolsAddition of water (hydration) to form gem-diols Addition of alcohols to form acetals/ketalsAddition of alcohols to form acetals/ketals Addition of HCN to form cyanohydrinsAddition of HCN to form cyanohydrins Addition of ammonia and ammonia derivativesAddition of ammonia and ammonia derivatives

Reduction Reactions of Reduction Reactions of Aldehydes and KetonesAldehydes and Ketones

Alcohol formationAlcohol formation HydrogenationHydrogenation Hydride reductionHydride reduction

Alkane formationAlkane formation Clemmensen reductionClemmensen reduction Wolff-Kishner reductionWolff-Kishner reduction

R C

O

HH2 / Pt

R CH2OH

R C

O

H R CH2OHLiAlH4

etherH2O

H+

R C

O

H R CH3conc. HClZn(Hg)

R C

O

H R CH3

NH2NH2

OH- / H2O

Oxidation of Oxidation of Aldehydes and Aldehydes and

KetonesKetones Conversion of Aldehydes to Carboxylic acidsConversion of Aldehydes to Carboxylic acids Oxidation of Aromatic Aldehydes/Ketones to Oxidation of Aromatic Aldehydes/Ketones to

Benzoic acid derivativesBenzoic acid derivatives Haloform reaction of methyl carbonylsHaloform reaction of methyl carbonyls Periodic acid cleavage of vicinal dials/diketonesPeriodic acid cleavage of vicinal dials/diketones

Aldehyde / Ketone Aldehyde / Ketone OxidationsOxidations

HIO4C

O

C

O

HR RCOOH + HCOOH +HIO3

R C

O

H RCOOHAg(NH3)2

+

(Tollens reagent)

C

O

H

or

C

O

R

COOHKMnO4 or K2Cr2O7

∆

CH3 C

O

RX2

OH- / H2OHCX3 + RCOO-

Ar C

O

Hor (ArCOOH)

Aldehyde / Ketone Nucleophilic Aldehyde / Ketone Nucleophilic Addition ReactionsAddition Reactions

R C R'

OR"MgX

H+

H2OR C

OH

R'

R"

R C R'

O

R C R'

O

R C R'

O

H2OC

R

R'

OH

OH

dry HClR''OH

CR

R'

OH

OR"C

R

R'

OR"

OR"

hemiketal ketal

H+ or OH-

gem diol

HCN CR

R'

OH

CNcyanohydrin

R C R'

OH2N G ( H2O)-

C N GR

R'

Carbanion Related ReactionsCarbanion Related Reactions Aldol CondensationAldol Condensation

Self vs. CrossedSelf vs. Crossed Claisen CondensationClaisen Condensation

Self vs. CrossedSelf vs. CrossedDieckmann cyclizationDieckmann cyclization

Reformatsky ReactionReformatsky Reaction Wittig ReactionWittig Reaction Carbanion Carbanion

Alkylations/Acylations/ConjugatAlkylations/Acylations/Conjugate Addition reactionse Addition reactions

Aldol Aldol CondensationsCondensations

Aldol Aldol CondensationsCondensations

Self CondensationSelf Condensation Crossed CondensationCrossed Condensation

RCH2 C

O

H2OH- or H+

RCH2 C

H

OH

CH

R

C

O

H

RCH2 C

O

H +R' C

O

HOH- or H+

R' C

OH

H

CH

R

C

O

H

Claisen CondensationsClaisen Condensations Self vs. Crossed CondensationSelf vs. Crossed Condensation Dieckmann CondensationDieckmann Condensation

R'O-

R'OH2RCH2 OR'

O

C RCH2

O

C CH C

O

OR'

R

RCH2 OR'

O

C +R" C

O

OR' R'O-

R'OHO

C CH C

O

OR'

R

R"

+R'OH

+R'OH

R'O C

O

(CH2)4 C

O

OR' R'O-

R'OHO

C

O

OR' +R'OH

R'O C

O

(CH2)5 C

O

OR' R'O-

R'OH+R'OH

O

C

O

OR'

Reformatsky Reaction

Reformatsky Reaction

R C

O

R +Br CH2 C

O

OR'Zn benzene/1.

2.

R C

O

H +Br CH2 C

O

OR'Zn benzene/1.

2. OH

C OR'

O

CCH2

H

R

OH

C OR'

O

CCH2R

R

H3O+

H3O+

Wittig ReactionPhosphonium salt formationPhosphonium salt formation

Ylide formationYlide formation

Alkene formationAlkene formation

RCH2X+Ph3P Ph3P CH2R+

phosphonium salt

Ph3P CH2R+ NaH Ph3P CHR

+ -+NaX+H2

ylide

CHR

P

CR'

O

R'

Ph3+

-+

(R')2C CHR

O PPh3

C CHR'

RR' +Ph3P O

oxaphosphatane alkene+

triphenylphosphineoxide

SN2X

X

Carbanion Carbanion Alkylation/Acylation/Conjugate Alkylation/Acylation/Conjugate

Addition ReactionsAddition Reactions

Malonic Ester Synthesis Acetoacetic Ester Synthesis Stork Enamine Synthesis Michael Addition / Conjugate

Addition

Malonic Ester SynthesisMalonic Ester Synthesis

Formation of Formation of alkylatedalkylated acetic acid acetic acid derivativesderivatives

C2H5O CO

CH2 CO

OC2H5NaOC2H5

C2H5OHC2H5O C

OCH C

OOC2H5

Na+

C2H5O CO

CH CO

OC2H5

Na+RCH2X C2H5O C

OCHCH2R

CO

OC2H5

C2H5O CO

CHCH2R

CO

OC2H5

H+/H 2O CO

OHCO

CHCH2R

HO

CO

OHCO

CHCH2R

HOstrong heat + CO2CH2COOHRCH2

Malonic Ester Synthesis Acylation/Hydrolysis/Decarboxylation

C2H5O C

O

CH2 C OC2H5

O

NaOC2H5

C2H5OHC2H5O C

O

CH C OC2H5

O

Na+

C2H5O C

O

CH C OC2H5

O

Na+

R CO

X C2H5O C

O

CH

COR

(-NaX)C OC2H5

O

C2H5O C

O

CH

COR

C OC2H5

O

H+/H 2O C

O

OHC

O

CH

COR

HO

C

O

OHC

O

CH

COR

HO strong heat R C

O

CH3 +2CO2

Acetoacetic Ester SynthesisAcetoacetic Ester SynthesisFormation of Formation of alkylated alkylated acetoneacetone derivativesderivatives

CH3 C

O

CH2 C

O

OC2H5NaOC2H5

C2H5OHCH3 C

O

CH C

O

OC2H5

Na+

CH3 C

O

CH C

O

OC2H5

Na+

RCH2X

(-NaX)CH3 C

O

CH

CH2R

C

O

OC2H5

CH3 C

O

CH

CH2R

C

O

OC2H5

H+/H 2O CH3 C

O

CH

CH2R

C

O

OH

CH3 C

O

CH

CH2R

C

O

OHstrong heat

CH3 C

O

CH2 CH2RCO2(- )

Acetoacetic Ester SynthesisFormation of Formation of acylated acylated acetoneacetone derivativesderivatives

CH3 C

O

CH2 C

O

OC2H5NaOC2H5

C2H5OHCH3 C

O

CH C

O

OC2H5

Na+

CH3 C

O

CH C

O

OC2H5

Na+

(-NaX)CH3 C

O

CHC

RO

C

O

OC2H5

H+/H 2O

strong heatCH3 C

O

CH2 C

O

RCO2(- )

R CO

X

CH3 C

O

CHC

RO

C

O

OC2H5 CH3 C

O

CHC

RO

C

O

OH

CH3 C

O

CHC

RO

C

O

OH

Stork Enamine SynthesisStork Enamine SynthesisFormation of Formation of AlkylatedAlkylated Aldehydes/Ketones Aldehydes/Ketones

R' C C

O

H

H

+R2NH R' C C H

OH

NHR2

H

aminolan

(-H2O)

( )

R' C C H

NR2

H

H+( )

R' C C H

NR2

(an enamine)

R' C C H

NR2

(a disguised carbanion)

R' C C H

NR2

R"CH2X

S N2R' C C H

NR2

CH2R"

R' C C H

NR2

CH2R"hydrolysis R' C C H

CH2R"

O

+R2NH

+

+

+

+ +

+

Stork Enamine SynthesisStork Enamine SynthesisFormation of Formation of AcylatedAcylated Aldehydes/KetonesAldehydes/Ketones

R' C C

O

H

H

+R2NH R' C C H

OH

NHR2

H

aminolan

(-H2O)

+

( )

R' C C H

NR2

H

H+( )

R' C C H

NR2

(an enamine)

R' C C H

NR2

(a disguised carbanion)

R' C C H

NR2

R' C C H

NR2

CO

R"

hydrolysis R' C C H

O

CO

R"

+R2NH

R" C

O

X

R' C C H

NR2

CO

R"

+

+

+ +

+

Conjugate Addition to Conjugate Addition to Unsaturated Unsaturated

SystemsSystems

Nu C C C

O

+ CNu C C

O

CNu C C

OH+

CNu C C

O

H

where Nu = CN-1, NH3 , RNH2 , & R2NH

Michael AdditionMichael Addition Michael DonorsMichael Donors Michael AcceptorsMichael Acceptors

Michael Product

C C C

O

C

C

C

CH C

O

H2O

(Michael donor)

CH(COOR)2malonic ester

CH COORC

O

R'

-ketoester

CHC

O

R'

C

O

R'

-diketone

R2CuLi dialkyl cuprate

RCH CH C

O

H

,− unsaturated aldehyde

RCH CH C

O

R'

,− unsaturated ketone

RCH CH C

O

OR'

,− unsaturated ester

RCH CH C N,− unsaturated nitrile

RCH CH NO 2,− unsaturated nitroalkeneN C C

enamine

Michael AdditionMichael AdditionRobinson AnnulationRobinson Annulation

OC

CC

OMichael donor

C

CC

O

H3C

Michael acceptor

CC

CC

O

H3C

CO

CO

Michael product

OR-

ROH

OR- ROH

CC

CC

O

CO

CO

H2C

CC

CC

O

CO

C

H2C

HO

Aldol

CC

CC

O

CO

C

C H2O

Direct vs. Conjugate Addition to Direct vs. Conjugate Addition to Unsaturated Carbonyl SystemsUnsaturated Carbonyl Systems

C C C

O

+ Nu

H+

H+

C C C

OH

Nu

conjugate addition

C C C

OH

Nu

direct addition

Conjugate addition Direct addition

NH3, RNH2, & R2NH

CN-1

R SH

R2CuLi− carbanions

( )Michael addition

LiAlH 4

RLi or ArLi

RMgX)considerations

(subjecttosteric

Spectroscopy of Spectroscopy of Aldehydes and Aldehydes and

KetonesKetones Mass SpectrometryMass Spectrometry Infrared SpectroscopyInfrared Spectroscopy Pmr SpectroscopyPmr Spectroscopy Cmr SpectroscopyCmr Spectroscopy