Upload
buingoc
View
222
Download
0
Embed Size (px)
Citation preview
3/9/16
1
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
3/9/16
2
Why do I care, Dr. P?
• Carboxylicacidspresentinmanyindustrialprocessesandmostbiologicalprocesses
• Theyarethestartingmaterialsfromwhichotheracylderivativesaremade
• Anunderstandingoftheirpropertiesandreactionsisfundamentaltounderstandingorganicchemistry
Nomenclature
• CarboxylicAcids,RCO2H• Ifderivedfromopen-chainalkanes,replacetheterminal-eofthealkanenamewith-oicacid
• ThecarboxylcarbonatomisC1
3/9/16
3
Alternative Names
• Compoundswith⎯CO2Hbondedtoaringarenamedusingthesuffix-carboxylicacid
• TheCO2Hcarbonisnot itselfnumberedinthissystem
• Usecommonnamesforformicacid(HCOOH)andaceticacid(CH3COOH)
Common names
3/9/16
4
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?
3/9/16
5
Structure and Properties of Carboxylic Acids
Dissociation of Carboxylic Acids
• Carboxylicacidsareprotondonorstowardweakandstrongbases,producingmetalcarboxylatesalts,RCO2
− +M• Carboxylicacidswithmorethansixcarbonsareonlyslightlysoluble inwater,buttheirconjugatebasesaltsarewater-soluble
3/9/16
6
Acidity Constant and pKa
• CarboxylicacidstransferaprotontowatertogiveH3O+ andcarboxylateanions,RCO2
−,butH3O+ isamuchstrongeracid
• Theacidityconstant,Ka,isabout10-5foratypicalcarboxylicacid(pKa ~5)
Substituent Effects on Acidity
3/9/16
7
Inductive Effects on Acidity
• Fluoroacetic,chloroacetic,bromoacetic,andiodoacetic acidsarestrongeracidsthanaceticacid
• Whydoyouthinkthat is?
Biological Acids and the Henderson-Hasselbalch Equation
• IfpKa ofgivenacidandthepHofthemediumareknown,%ofdissociatedandundissociatedformscanbecalculatedusingtheHenderson-Hasselbalch eqn
3/9/16
8
Substituent Effects on Acidity
Aromatic Substituent Effects
• Anelectron-withdrawinggroup(-NO2)increasesaciditybystabilizingthecarboxylateanion
• Anelectron-donating(activating)group(OCH3)decreasesaciditybydestabilizingthecarboxylateanion
3/9/16
9
Aromatic Substituent Effects
• WecanuserelativepKa’s asacalibrationforeffectsonrelativefreeenergiesofreactionswiththesamesubstituents
Preparation of Carboxylic Acids
• Canyouthinkofwayswecanpreparecarboxylicacids?
3/9/16
10
Preparation of Carboxylic Acids
• Oxidationofasubstituted alkylbenzene withKMnO4 orNa2Cr2O7 givesasubstitutedbenzoicacid
• 1° and2° alkylgroupscanbeoxidized,buttertiarygroupsarenot
From Alkenes
• OxidativecleavageofanalkenewithKMnO4givesacarboxylicacidifthealkenehasatleastonevinylic hydrogen(Section7.9)
3/9/16
11
From Alcohols
• OxidationofaprimaryalcoholoranaldehydewithCrO3 inaqueousacid
Hydrolysis of Nitriles
• Hotacidorbaseyieldscarboxylicacids• Conversionofanalkylhalidetoanitrile(withcyanideion)followedbyhydrolysisproducesacarboxylicacidwithonemorecarbon(RBr→RC≡N→ RCO2H)
• Bestwithprimaryhalidesbecauseeliminationreactionsoccurwith secondaryortertiaryalkylhalides
3/9/16
12
Hydrolysis of Nitriles
Carboxylation of Grignard Reagents
• GrignardreagentsreactwithdryCO2 toyieldametalcarboxylate
• LimitedtoalkylhalidesthatcanformGrignardreagents
• Theorganomagnesium halideaddstoC=Oofcarbondioxide
• ProtonationbyadditionofaqueousHCl inaseparatestepgivesthefreecarboxylicacid
3/9/16
13
Carboxylation of Grignard Reagents
Learning check
• Howwouldyoupreparethefollowingcarboxylicacids?
3/9/16
14
Reactions of Carboxylic Acids: An Overview
• Carboxylicacidstransferaprotontoabasetogiveanions,whicharegoodnucleophiles inSN2 reactions
• Likeketones,carboxylicacidsundergoadditionofnucleophilestothecarbonylgroup
• Inaddition,carboxylicacidsundergootherreactionscharacteristicofneitheralcoholsnorketones
Reactions of Carboxylic Acids: An Overview
3/9/16
15
Chemistry of Nitriles
• Nitrilesandcarboxylicacidsbothhaveacarbonatomwiththreebondstoanelectronegativeatom,andcontainaπ bond
• Bothbothareelectrophiles
Preparation of Nitriles by Dehydration
• ReactionofprimaryamidesRCONH2 withSOCl2 orPOCl3 (orotherdehydratingagents)
• Not limitedbysterichindranceorsidereactions(asisthereactionofalkylhalideswithNaCN)
3/9/16
16
Mechanism of Dehydration of Amides
• Nucleophilic amideoxygenatomattacksSOCl2followedbydeprotonation andelimination
Reactions of Nitriles
• RCNisstronglypolarizedandwithanelectrophiliccarbonatom
• Attackedbynucleophilestoyieldsp2-hybridizedimineanions
3/9/16
17
Hydrolysis: Conversion of Nitriles into Carboxylic Acids
• Hydrolyzedinwithacidorbasecatalysistoacarboxylicacidandammoniaoranamine
Mechanism of Hydrolysis of Nitriles
3/9/16
18
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
3/9/16
19
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
3/9/16
20
IR of Carboxylic Acids
IR of Nitriles
• NitrilesshowanintenseC≡Nbondabsorptionnear2250cm−1forsaturatedcompounds and2230cm−1foraromaticandconjugatedmolecules
• Thisishighlydiagnosticfornitriles
3/9/16
21
Nuclear Magnetic Resonance Spectroscopy
• Carboxyl13COOHsignalsareatδ165toδ185• Aromaticandα,b-unsaturatedacidsarenearδ165andsaturatedaliphaticacidsarenearδ185
• 13C≡ Nsignalδ115toδ130
Proton NMR
• Theacidic⎯CO2Hprotonisasingletnearδ 12• WhenD2Oisaddedtothesamplethe⎯CO2HprotonisreplacedbyDcausingtheabsorptiontodisappearfromtheNMRspectrum