Chapter19TheChemistryofAldehydesandKetones.

Carbonyl‐Addi7onReac7ons

Organic Chemistry, 5th ed. Marc Loudon

Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA

Chapter19Overview

•  19.1NomenclatureofAldehydesandKetones

•  19.2PhysicalProper;esofAldehydesandKetones•  19.3SpectroscopyofAldehydesandKetones•  19.4SynthesisofAldehydesandKetones•  19.5Introduc;ontoAldehydeandKetoneReac;ons•  19.6BasicityofAldehydesandKetones•  19.7ReversibleAddi;onReac;onsofAldehydesandKetones•  19.8Reduc;onofAldehydesandKetonestoAlcohols•  19.9Reac;onsofAldehydesandKetoneswithGrignardand

RelatedReagents

•  19.10AcetalsandTheirUseofProtec;ngGroups

2

Chapter19Overview

•  19.11Reac;onsofAldehydesandKetoneswithAmines

•  19.12Reduc;onofCarbonylGroupstoMethyleneGroups•  19.13TheWiQgAlkeneSynthesis

•  19.14Oxida;onofAldehydestoCarboxylicAcids•  19.15ManufactureandUseofAldehydesandKetones

3

CarbonylCompounds

•  Aldehydesandketoneshavethefollowinggeneralstructure

419.1NomenclatureofAldehydesandKetones

CarbonylCompounds

519.1NomenclatureofAldehydesandKetones

CommonNomenclature

619.1NomenclatureofAldehydesandKetones

PrefixesUsedinCommonNomenclature

719.1NomenclatureofAldehydesandKetones

CommonNomenclature

819.1NomenclatureofAldehydesandKetones

Subs?tu?veNomenclature

919.1NomenclatureofAldehydesandKetones

Subs?tu?veNomenclature

1019.1NomenclatureofAldehydesandKetones

PhysicalProper?es

•  Mostsimplealdehydesandketonesareliquids

1119.2PhysicalProper7esofAldehydesandKetones

IRSpectroscopy

•  StrongC=Ostretch:1700cm‐1

1219.3SpectroscopyofAldehydesandKetones

IRSpectroscopy

•  Conjuga;onwithaπbondlowerstheabsorp;onfrequency

1319.3SpectroscopyofAldehydesandKetones

IRSpectroscopy

•  TheC=Ostretchingfrequencyinsmall‐ringketonesisaffectedbyringsize

1419.3SpectroscopyofAldehydesandKetones

1HNMRSpectroscopy

•  Thereasonforthelargeδvalueforaldehydicprotonsissimilartothatforvinylicprotons

•  However,theelectronega;veOincreasesthisshi^fartherdownfield

1519.3SpectroscopyofAldehydesandKetones

13CNMRSpectroscopy

•  AldehydeandketoneC=O:δ190‐220•  α‐Carbons:δ30‐50

1619.3SpectroscopyofAldehydesandKetones

UV/VisSpectroscopy

•  π→π*:150nm(outoftheopera;ngrange)•  n→π*:260‐290nm(muchweaker)

1719.3SpectroscopyofAldehydesandKetones

UV/VisSpectroscopy

1819.3SpectroscopyofAldehydesandKetones

MassSpectrometry

1919.3SpectroscopyofAldehydesandKetones

MassSpectrometry

•  Whataccountsforthem/z=58peak?

2019.3SpectroscopyofAldehydesandKetones

MassSpectrometry

•  TheMcLaffertyrearrangementinvolvesahydrogentransferviaatransientsix‐memberedring

•  Theremustbeanavailableγ‐H

2119.3SpectroscopyofAldehydesandKetones

SummaryofAldehydeandKetonePrepara?on

1.Oxida;onofalcohols2.Friedel‐Cra^sacyla;on

3.Hydra;onofalkynes

4.Hydrobora;on‐oxida;onofalkynes

5.Ozonolysisofalkenes

6.Periodatecleavageofglycols

2219.4SynthesisofAldehydesandKetones

Carbonyl‐GroupReac?ons

•  Reac;onswithacids

•  Addi;onreac;ons

•  Oxida;onofaldehydes

2319.5Introduc7ontoAldehydeandKetoneReac7ons

BasicityofAldehydesandKetones

•  Thecarbonyloxygenisweaklybasic

•  Oneresonancecontributorrevealsthatcarboca;oncharacterexists

•  Theconjugateacidsofaldehydesandketonesmaybeviewedasα‐hydroxycarboca;ons

2419.6BasicityofAldehydesandKetones

BasicityofAldehydesandKetones

•  α‐hydroxyandα‐alkoxycarboca;onsaresignificantlymorestablethanordinarycarboca;ons(by~100kJmol‐1)

2519.6BasicityofAldehydesandKetones

Addi?onReac?ons

•  Oneofthemosttypicalreac;onsofaldehydesandketonesisaddi;onacrosstheC=O

2619.7ReversibleAddi7onReac7onsofAldehydesandKetones

MechanismofCarbonyl‐Addi?onReac?ons

2719.7ReversibleAddi7onReac7onsofAldehydesandKetones

Addi?onReac?ons

•  Theaddi;onofanucleophiletothecarbonylcarbonisdrivenbytheabilityofoxygentoaccepttheunsharedelectronpair

2819.7ReversibleAddi7onReac7onsofAldehydesandKetones

Addi?onReac?ons

•  Thenucleophileaiackstheunoccupiedπ*MO(LUMO)oftheC=O

2919.7ReversibleAddi7onReac7onsofAldehydesandKetones

Addi?onReac?ons

•  Thesecondmechanismforcarbonyladdi;ontakesplaceunderacidiccondi7ons

3019.7ReversibleAddi7onReac7onsofAldehydesandKetones

EquilibriainCarbonyl‐Addi?onReac?ons

•  Theequilibriumforareversibleaddi;ondependsstronglyonthestructureofthecarbonylcompound

1.Addi;onismorefavorableforaldehydes

2.Addi;onismorefavorableifENgroupsareneartheC=O

3.Addi;onislessfavorablewhengroupsthatdonateelectronsbyresonancetotheC=Oarepresent

3119.7ReversibleAddi7onReac7onsofAldehydesandKetones

EquilibriumConstantsforHydra?on

3219.7ReversibleAddi7onReac7onsofAldehydesandKetones

Rela?veCarbonylStability

3319.7ReversibleAddi7onReac7onsofAldehydesandKetones

CarbonylStability

•  Anyfeaturethatstabilizescarboca;onswillimpartgreaterstabilitytothecarbonylgroup

•  Forexample,alkylgroupsstabilizecarboca;onsmorethanhydrogens

•  Hence,alkylgroupswilldiscourageaddi;onreac;onstothecarbonylgroup

3419.7ReversibleAddi7onReac7onsofAldehydesandKetones

CarbonylStability

•  Resonancecanalsoaddstabilitytothecarbonylgroup

•  However,ENgroupsmaketheaddi;onreac;onmorefavorable

3519.7ReversibleAddi7onReac7onsofAldehydesandKetones

RatesofCarbonyl‐Addi?onReac?ons

•  Rela;veratescanbepredictedfromequilibriumconstants

•  Compoundswiththemostfavorableaddi;onequilibriatendstoreactmostrapidly

•  Generalreac;vity:formaldehyde>aldehydes>ketones

3619.7ReversibleAddi7onReac7onsofAldehydesandKetones

Reduc?onwithLiAlH4andNaBH4

3719.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onwithLiAlH4

•  LiAlH4servesasasourceofhydrideion(H:‐)

•  LiAlH4isverybasicandreactsviolentlywithwater;anhydroussolventsarerequired

3819.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onwithLiAlH4

•  Likeotherstrongbases,LiAlH4isalsoagoodnucleophile

•  Addi;onally,theLi+ionisabuilt‐inLewis‐acid

3919.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onwithLiAlH4

•  Eachoftheremaininghydridesbecomeac;vatedduringthereac;on

4019.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onwithNaBH4

•  Na+isaweakerLewisacidthanLi+requiringtheuseofpro;csolvents

•  Hydrogenbondingthenservestoac;vatethecarbonylgroup

4119.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onwithLiAlH4andNaBH4

•  Reac;onsbytheseandrelatedreagentsarereferredtoashydridereduc?ons

•  Thesereac;onsarefurtherexamplesofnucleophilicaddi7on

4219.8Reduc7onofAldehydesandKetonestoAlcohols

Selec?vitywithLiAlH4andNaBH4

•  NaBH4islessreac;veandhencemoreselec7vethanLiAlH4

•  LiAlH4reactswithalkylhalides,alkyltosylates,andnitrogroups,butNaBH4doesnot

4319.8Reduc7onofAldehydesandKetonestoAlcohols

Reduc?onbyCataly?cHydrogena?on

•  Hydridereagentsaremorecommonlyused

•  However,cataly;chydrogena;onisusefulforselec;vereduc;onofalkenes

4419.8Reduc7onofAldehydesandKetonestoAlcohols

GrignardAddi?on

•  Grignardreagentswithcarbonylgroupsisthemostimportantapplica;onoftheGrignardreagentinorganicchemistry

4519.9Reac7onsofAldehydesandKetoneswithGrignardandRelatedReagents

GrignardAddi?on

•  R‐MgXreactsasanucleophile;thisgroupisalsostronglybasicbehavinglikeacarbanion

•  Theaddi;onisirreversibleduetothisbasicity

4619.9Reac7onsofAldehydesandKetoneswithGrignardandRelatedReagents

OrganolithiumandAcetylideReagents

•  ThesereagentsreactwithaldehydesandketonesanalogoustoGrignardreagents

4719.9Reac7onsofAldehydesandKetoneswithGrignardandRelatedReagents

ImportanceoftheGrignardAddi?on

•  Thisreac;onresultsinC‐Cbondforma;on

•  Thesynthe;cpossibili;esarealmostendless

4819.9Reac7onsofAldehydesandKetoneswithGrignardandRelatedReagents

ImportanceoftheGrignardAddi?on

4919.9Reac7onsofAldehydesandKetoneswithGrignardandRelatedReagents

Prepara?onandHydrolysisofAcetals

•  Acetal:Acompoundinwhichtwoetheroxygensareboundtothesamecarbon

5019.10AcetalsandTheirUseofProtec7ngGroups

Prepara?onandHydrolysisofAcetals

•  Useofa1,2‐or1,3‐diolleadstocyclicacetals•  Onlyoneequivalentofthediolisrequired

5119.10AcetalsandTheirUseofProtec7ngGroups

Prepara?onandHydrolysisofAcetals

5219.10AcetalsandTheirUseofProtec7ngGroups

Prepara?onandHydrolysisofAcetals

•  Acetalforma;onisreversible•  Thepresenceofacidandexcesswaterallowsacetalstoreverttotheircarbonylform

•  Acetalsarestableinbasicandneutralsolu7on

5319.10AcetalsandTheirUseofProtec7ngGroups

Hemiacetals

•  Hemiacetalsnormallycannotbeisolated•  Excep;onsincludesimplealdehydesandcompoundsthancanform5‐and6‐memberedrings

5419.10AcetalsandTheirUseofProtec7ngGroups

Hemiacetals

5519.10AcetalsandTheirUseofProtec7ngGroups

Protec?ngGroups

•  Aprotec?nggroupisatemporarychemicaldisguiseforafunc;onalgrouppreven;ngitfromreac;ngwithcertainreagents

5619.10AcetalsandTheirUseofProtec7ngGroups

Protec?ngGroups

5719.10AcetalsandTheirUseofProtec7ngGroups

Reac?onswithPrimaryAmines

•  Iminesaresome;mescalledSchiffbases

5819.11Reac7onsofAldehydesandKetoneswithAmines

Reac?onswithPrimaryAmines

•  Thedehydra;onofwateristypicallytherate‐limi;ngstep

5919.11Reac7onsofAldehydesandKetoneswithAmines

Deriva?ves

•  Beforetheadventofspectroscopy,aldehydesandketoneswerecharacterizedasderiva?ves

6019.11Reac7onsofAldehydesandKetoneswithAmines

SomeImineDeriva?ves

6119.11Reac7onsofAldehydesandKetoneswithAmines

Reac?onswithSecondaryAmines

•  Likeimineforma;on,enamineforma;onisreversible

6219.11Reac7onsofAldehydesandKetoneswithAmines

Reac?onswithSecondaryAmines

6319.11Reac7onsofAldehydesandKetoneswithAmines

Reac?onswithTer?aryAmines

•  Ter;aryaminesdonotreactwithaldehydesorketonestoformstablederiva7ves

•  Theyaregoodnucleophiles,butthelackofanN‐Hpreventsconversiontoastablecompound

6419.11Reac7onsofAldehydesandKetoneswithAmines

Reduc?onofAldehydesandKetones

•  Completereduc;ontoamethylene(‐CH2‐)groupispossiblebytwodifferentmethods

•  Wolff‐Kishnerreduc?on:

6519.12Reduc7onofCarbonylGroupstoMethyleneGroups

Reduc?onofAldehydesandKetones

•  TheWolff‐Kishnerreduc;ontakesplaceunderhighlybasiccondi7ons

•  Itisanextensionofimineforma;on

6619.12Reduc7onofCarbonylGroupstoMethyleneGroups

Reduc?onofAldehydesandKetones

•  Clemmensenreduc?on:

•  Thisreduc;onoccursunderacidiccondi7ons•  Themechanismisuncertain

6719.12Reduc7onofCarbonylGroupstoMethyleneGroups

TheWiVgAlkeneSynthesis

•  Thisreac;oniscompletelyregioselec;ve,assuringtheloca;onofthealkene

6819.13TheWiUgAlkeneSynthesis

TheWiVgAlkeneSynthesis

•  Occursviaanaddi;on‐elimina;onsequenceusingaphosphorousylide

•  Anylid(orylide)isanycompoundwithoppositechargesonadjacent,covalentlyboundatoms

6919.13TheWiUgAlkeneSynthesis

TheWiVgAlkeneSynthesis

7019.13TheWiUgAlkeneSynthesis

Prepara?onoftheWiVgReagent

•  Anyalkylhalidethatreadilypar;cipatesinSN2reac;onscanbeused

7119.13TheWiUgAlkeneSynthesis

TheWiVgAlkeneSynthesis

•  Retrosynthe;cally

•  Stereochemistry

7219.13TheWiUgAlkeneSynthesis

CarboxylicAcidsfromAldehydes

•  Thehydrateisthespeciesoxidized

7319.14Oxida7onofAldehydestoCarboxylicAcids

CarboxylicAcidsfromAldehydes

•  ThisisknownastheTollen’stest•  Aposi;veindicatorforanaldehydeisthedeposi;onofametallicsilvermirroronthewallsofthereac;onflask

7419.14Oxida7onofAldehydestoCarboxylicAcids

Produc?onandUseofAldehydes

•  Themostimportantcommercialaldehydeisformaldehyde

•  Itsmostimportantuseisinthesynthesisofphenol‐formaldehyderesins

7519.15ManufactureandUseofAldehydesandKetones

Produc?onandUseofKetones

•  Themostimportantcommercialketoneisacetone

•  Itisco‐producedwithphenolbytheautoxida;on‐rearrangementofcumene

7619.15ManufactureandUseofAldehydesandKetones