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Chapter 20- Carboxylic Acids and Nitriles

The Importance of Carboxylic Acids

• Startingmaterialsforacylderivatives(esters,amides,andacidchlorides)

• Abundant innaturefromoxidationofaldehydesandalcoholsinmetabolism• Acetic acid, CH3CO2H, - vinegar• Butanoic acid, CH3CH2CH2CO2H (rancid

butter) • Long-chain aliphatic acids from the

breakdown of fats

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Why do I care, Dr. P?

• Carboxylicacidspresentinmanyindustrialprocessesandmostbiologicalprocesses

• Theyarethestartingmaterialsfromwhichotheracylderivativesaremade

• Anunderstandingoftheirpropertiesandreactionsisfundamentaltounderstandingorganicchemistry

Nomenclature

• CarboxylicAcids,RCO2H• Ifderivedfromopen-chainalkanes,replacetheterminal-eofthealkanenamewith-oicacid

• ThecarboxylcarbonatomisC1

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Alternative Names

• Compoundswith⎯CO2Hbondedtoaringarenamedusingthesuffix-carboxylicacid

• TheCO2Hcarbonisnot itselfnumberedinthissystem

• Usecommonnamesforformicacid(HCOOH)andaceticacid(CH3COOH)

Common names

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Nitriles, RCN

• Closelyrelatedtocarboxylicacidsnamedbyadding-nitrileasasuffixtothealkanename,withthenitrilecarbonnumberedC1

• Complexnitrilesarenamedasderivativesofcarboxylicacids• Replace -ic acid or -oic acid ending with -

onitrile

Structure and Properties of Carboxylic Acids

• Carboxylcarbonsp2 hybridized: carboxylicacidgroupsareplanarwithC–C=OandO=C–Obondanglesofapproximately120°

• Carboxylicacidshavemuchhigherboilingpointsthanthecorrespondingalcohols• Why do you think that is based on its

structure?

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Structure and Properties of Carboxylic Acids

Dissociation of Carboxylic Acids

• Carboxylicacidsareprotondonorstowardweakandstrongbases,producingmetalcarboxylatesalts,RCO2

− +M• Carboxylicacidswithmorethansixcarbonsareonlyslightlysoluble inwater,buttheirconjugatebasesaltsarewater-soluble

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Acidity Constant and pKa

• CarboxylicacidstransferaprotontowatertogiveH3O+ andcarboxylateanions,RCO2

−,butH3O+ isamuchstrongeracid

• Theacidityconstant,Ka,isabout10-5foratypicalcarboxylicacid(pKa ~5)

Substituent Effects on Acidity

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Inductive Effects on Acidity

• Fluoroacetic,chloroacetic,bromoacetic,andiodoacetic acidsarestrongeracidsthanaceticacid

• Whydoyouthinkthat is?

Biological Acids and the Henderson-Hasselbalch Equation

• IfpKa ofgivenacidandthepHofthemediumareknown,%ofdissociatedandundissociatedformscanbecalculatedusingtheHenderson-Hasselbalch eqn

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Substituent Effects on Acidity

Aromatic Substituent Effects

• Anelectron-withdrawinggroup(-NO2)increasesaciditybystabilizingthecarboxylateanion

• Anelectron-donating(activating)group(OCH3)decreasesaciditybydestabilizingthecarboxylateanion

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Aromatic Substituent Effects

• WecanuserelativepKa’s asacalibrationforeffectsonrelativefreeenergiesofreactionswiththesamesubstituents

Preparation of Carboxylic Acids

• Canyouthinkofwayswecanpreparecarboxylicacids?

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Preparation of Carboxylic Acids

• Oxidationofasubstituted alkylbenzene withKMnO4 orNa2Cr2O7 givesasubstitutedbenzoicacid

• 1° and2° alkylgroupscanbeoxidized,buttertiarygroupsarenot

From Alkenes

• OxidativecleavageofanalkenewithKMnO4givesacarboxylicacidifthealkenehasatleastonevinylic hydrogen(Section7.9)

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From Alcohols

• OxidationofaprimaryalcoholoranaldehydewithCrO3 inaqueousacid

Hydrolysis of Nitriles

• Hotacidorbaseyieldscarboxylicacids• Conversionofanalkylhalidetoanitrile(withcyanideion)followedbyhydrolysisproducesacarboxylicacidwithonemorecarbon(RBr→RC≡N→ RCO2H)

• Bestwithprimaryhalidesbecauseeliminationreactionsoccurwith secondaryortertiaryalkylhalides

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Hydrolysis of Nitriles

Carboxylation of Grignard Reagents

• GrignardreagentsreactwithdryCO2 toyieldametalcarboxylate

• LimitedtoalkylhalidesthatcanformGrignardreagents

• Theorganomagnesium halideaddstoC=Oofcarbondioxide

• ProtonationbyadditionofaqueousHCl inaseparatestepgivesthefreecarboxylicacid

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Carboxylation of Grignard Reagents

Learning check

• Howwouldyoupreparethefollowingcarboxylicacids?

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Reactions of Carboxylic Acids: An Overview

• Carboxylicacidstransferaprotontoabasetogiveanions,whicharegoodnucleophiles inSN2 reactions

• Likeketones,carboxylicacidsundergoadditionofnucleophilestothecarbonylgroup

• Inaddition,carboxylicacidsundergootherreactionscharacteristicofneitheralcoholsnorketones

Reactions of Carboxylic Acids: An Overview

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Chemistry of Nitriles

• Nitrilesandcarboxylicacidsbothhaveacarbonatomwiththreebondstoanelectronegativeatom,andcontainaπ bond

• Bothbothareelectrophiles

Preparation of Nitriles by Dehydration

• ReactionofprimaryamidesRCONH2 withSOCl2 orPOCl3 (orotherdehydratingagents)

• Not limitedbysterichindranceorsidereactions(asisthereactionofalkylhalideswithNaCN)

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Mechanism of Dehydration of Amides

• Nucleophilic amideoxygenatomattacksSOCl2followedbydeprotonation andelimination

Reactions of Nitriles

• RCNisstronglypolarizedandwithanelectrophiliccarbonatom

• Attackedbynucleophilestoyieldsp2-hybridizedimineanions

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Hydrolysis: Conversion of Nitriles into Carboxylic Acids

• Hydrolyzedinwithacidorbasecatalysistoacarboxylicacidandammoniaoranamine

Mechanism of Hydrolysis of Nitriles

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Reduction: Conversion of Nitriles into Amines

• ReductionofanitrilewithLiAlH4 givesaprimaryamine

• Nucleophilic additionofhydrideiontothepolarC≡Nbond,yieldsanimineanion

• TheC=Nbond undergoesasecondnucleophilic additionofhydridetogiveadianion,which isprotonatedbywater

Reaction of Nitriles with Organometallic Reagents

• Grignardreagentsaddtogiveanintermediateimineanionthatishydrolyzedbyadditionofwatertoyieldaketone

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Learning check

• Predicttheproductsforthefollowingreactionsbelow.

Spectroscopy of Carboxylic Acids and Nitriles

• InfraredSpectroscopy• O–Hbond ofthecarboxylgroupgivesaverybroadabsorption2500to3300cm−1

• C=Obondabsorbssharplybetween1710and1760cm−1

• Freecarboxylgroupsabsorbat1760cm−1

• Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm−1

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IR of Carboxylic Acids

IR of Nitriles

• NitrilesshowanintenseC≡Nbondabsorptionnear2250cm−1forsaturatedcompounds and2230cm−1foraromaticandconjugatedmolecules

• Thisishighlydiagnosticfornitriles

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Nuclear Magnetic Resonance Spectroscopy

• Carboxyl13COOHsignalsareatδ165toδ185• Aromaticandα,b-unsaturatedacidsarenearδ165andsaturatedaliphaticacidsarenearδ185

• 13C≡ Nsignalδ115toδ130

Proton NMR

• Theacidic⎯CO2Hprotonisasingletnearδ 12• WhenD2Oisaddedtothesamplethe⎯CO2HprotonisreplacedbyDcausingtheabsorptiontodisappearfromtheNMRspectrum