Chapter 21€¦ · · 2010-09-20Chapter 21 The Chemistry of Carboxylic Acid Derivaves Organic...
Transcript of Chapter 21€¦ · · 2010-09-20Chapter 21 The Chemistry of Carboxylic Acid Derivaves Organic...
Chapter21TheChemistryofCarboxylicAcidDeriva7ves
Organic Chemistry, 5th ed. Marc Loudon
Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA
Chapter21Overview
• 21.1NomenclatureandClassifica5onofCarboxylicAcidDeriva5ves
• 21.2StructuresofCarboxylicAcidDeriva5ves• 21.3PhysicalProper5esofCarboxylicAcidDeriva5ves• 21.4SpectroscopyofCarboxylicAcidDeriva5ves• 21.5BasicityofCarboxylicAcidDeriva5ves• 21.6Introduc5ontoReac5onsofCarboxylicAcidDeriva5ves• 21.7HydrolysisofCarboxylicAcidDeriva5ves• 21.8Reac5onsofCarboxylicAcidDeriva5veswith
Nucleophiles• 21.9Reduc5onofCarboxylicAcidDeriva5ves
2
Chapter21Overview
• 21.10Reac5onsofCarboxylicAcidDeriva5veswithOrganometallicReagents
• 21.11SynthesisofCarboxylicAcidDeriva5ves• 21.12UseandOccurrenceofCarboxylicAcidsandTheir
Deriva5ves
3
CarboxylicAcidDeriva8ves
• Acarboxylicacidderiva8veisacompoundthatcanbehydrolyzedunderacidicofbasiccondi5onstogivetherelatedcarboxylicacid
421.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
StructuresofCarboxylicAcidDeriva8ves
521.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
EstersandLactones
621.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
EstersandLactones
• Cyclicestersarecalledlactones• Thenameisderivedfromtheacidwiththesamenumberofcarbonsintheprinciplechain
• TheringsizeisdenotedbyaGreekleUerindica5ngthepointofaUachment
721.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
AcidHalides
• Replacetheicendingwithylfollowedbythenameofthehalide
821.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Anhydrides
• Thenameistheparentacidisfollowedbyanhydride
921.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Nitriles
• Droptheicoroicendingandaddonitrile• Thenitrilecarboncountsaspartofthechainlength
1021.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Amides,Lactams,andImides
• Replacetheicoroicandaddamide
1121.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Amides,Lactams,andImides
• Amidesareclassifiedaccordingtothenumberofhydrogensontheamidenitrogen
• UseNforsubs5tuentsonthenitrogen
1221.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Amides,Lactams,andImides
• Cyclicamidesarecalledlactams• Thenomenclaturefollowsthatoflactones
1321.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
Amides,Lactams,andImides
• Imidesarethenitrogenanalogsofanhydrides• Cyclicimidesareofgreaterimportancethanopen‐chainimides
1421.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
NomenclatureofSubs8tuentGroups
• Thepriori5esforci5ngprinciplegroupsinacarboxylicacidderiva5veare:
1521.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
NomenclatureofSubs8tuentGroups
1621.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
CarbonicAcidDeriva8ves
• Estersofcarbonicacidarenamedlikeanyotherester
• Otherimportantderiva5vesinclude:
1721.1NomenclatureandClassifica7onofCarboxylicAcidDeriva7ves
StructuresofCarboxylicAcidDeriva8ves
• Thederiva5vesareverysimilartoothercarbonylcompounds(bondlengths,angles)
1821.2StructuresofCarboxylicAcidDeriva7ves
StructuresofCarboxylicAcidDeriva8ves
• Becauseofthetrigonalplanargeometryatnitrogen,EandZconformersarepossible
• Theinterconversionisrela5velyrapidatroomtemperature(~10s‐1,Ebarrier≈71kJmol‐1)
1921.2StructuresofCarboxylicAcidDeriva7ves
Esters
• Polar;H‐bondacceptorsonly• Typicallyvola5le,fragrantliquids• Mostareinsolubleinwater
2021.3PhysicalProper7esofCarboxylicAcidDeriva7ves
AnhydridesandAcidChlorides
• Loweranhydridesandacidchloridesaredense,water‐insolubleliquids
• Typicallyhaveacrid,piercingodors
2121.3PhysicalProper7esofCarboxylicAcidDeriva7ves
Nitriles
• Highlypolar(3.4DforH3C‐C≡N)
• Nitrileslargerthanpropionitrilearewater‐insoluble
• Acetonitrileisausefulpolar,apro5csolvent
2221.3PhysicalProper7esofCarboxylicAcidDeriva7ves
Amides
• Polarwithhighboilingpoints• Loweramidesarewater‐soluble
• TendtoaggregateduetoH‐bonding
2321.3PhysicalProper7esofCarboxylicAcidDeriva7ves
IRSpectroscopy
2421.4SpectroscopyofCarboxylicAcidDeriva7ves
IRSpectroscopy:Esters
• C=Ostretch:1735‐1745cm‐1
• Readilydis5nguishesthemfromcarboxylicacids,aldehydes,andketones
2521.4SpectroscopyofCarboxylicAcidDeriva7ves
IRSpectroscopy:Anhydrides
• TwoC=Ostretches(alsocommonforacidchlorides)
• Duetosymmetricandasymmetricstretching
2621.4SpectroscopyofCarboxylicAcidDeriva7ves
IRSpectroscopy:Amides
• C=Ostretch:1650‐1675cm‐1
• MuchlowerthanotherC=Ostretches
2721.4SpectroscopyofCarboxylicAcidDeriva7ves
IRSpectroscopy:Amides
• Primary,secondary,andter5aryamidesmayalsobedifferen5ated
2821.4SpectroscopyofCarboxylicAcidDeriva7ves
IRSpectroscopy:Nitriles
• C≡Nstretch:2200‐2250cm‐1
• NormallymuchstrongerthanC≡Cstretchduetothelargebonddipole
2921.4SpectroscopyofCarboxylicAcidDeriva7ves
1HNMRSpectroscopy
• α‐Hydrogensnexttocarbonyl:δ1.9‐3• HydrogensoncarbonnexttoalkoxyO:~+0.6ppmmorethanforthatofalcoholsandethers
3021.4SpectroscopyofCarboxylicAcidDeriva7ves
1HNMRSpectroscopy
• Amidesdisplaynon‐equivalencyforthetwogroupsaUachedtothenitrogen
• Theyarediastereotopic• Althoughtheserotateat~10s‐1,ontheNMR5mescalethesegroupsappearfrozeninposi5on
3121.4SpectroscopyofCarboxylicAcidDeriva7ves
13CNMRSpectroscopy
• C=O:δ165‐180
• C≡N:δ115‐120
3221.4SpectroscopyofCarboxylicAcidDeriva7ves
BasicityofCarboxylicAcidDeriva8ves
• Likecarboxylicacids,theirderiva5vesarealsoweaklybasic
• Protona5onoccursonthecarbonyloxygen
3321.5BasicityofCarboxylicAcidDeriva7ves
BasicityofCarboxylicAcidDeriva8ves
• Amidesareconsiderablymorebasic
• Nitrilesareextremelyweakbases
3421.5BasicityofCarboxylicAcidDeriva7ves
Reac8onsofCarboxylicAcidDeriva8ves
• Therearethreegeneralcategories:1.Reac5onsatthecarbonyl(orcyano)group
a.attheC=OoxygenorC≡Nnitrogen
b.attheC=OcarbonorC≡Ncarbon
2.Reac5onsinvolvingtheα‐carbon
3.Reac5onsatthenitrogenofamides
3521.6Introduc7ontotheReac7onsofCarboxylicAcidDeriva7ves
Reac8onsofCarboxylicAcidDeriva8ves
• Acylsubs8tu8on:Subs5tu5onatthecarbonyl
• Addi7onisatypicalreac5onofnitriles
3621.6Introduc7ontotheReac7onsofCarboxylicAcidDeriva7ves
HydrolysisofEsters
• Saponifica8on
• Saponifica5oniseffec5velyirreversible• Classifiedasanucleophilicacylsubs8tu8on
3721.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofEsters
3821.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofEsters
• Acid‐catalyzedhydrolysis• Thereac5onisslowandrequiresanexcessofwater
3921.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofEsters
• Classifiedasanucleophilicacylsubs8tu8on
4021.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisandForma8onofLactones
4121.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofAmides
4221.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofNitriles
• Moreextremecondi5onsarerequiredcomparedtothoseofestersandamides
4321.7HydrolysisofCarboxylicAcidDeriva7ves
• Imidicacidscanbeviewedasthenitrogen‐analogsofenols
HydrolysisofNitriles
4421.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofNitriles
• Base‐promotedhydrolysisisalsopossible
4521.7HydrolysisofCarboxylicAcidDeriva7ves
HydrolysisofAcidChloridesandAnhydrides
• Bothreactrapidlywithwater
4621.7HydrolysisofCarboxylicAcidDeriva7ves
NucleophilicAcylSubs8tu8onReac8ons
• Thecondi7onsforhydrolysisforthesederiva5vescandifferconsiderably
4721.7HydrolysisofCarboxylicAcidDeriva7ves
NucleophilicAcylSubs8tu8onReac8ons
4821.7HydrolysisofCarboxylicAcidDeriva7ves
NucleophilicAcylSubs8tu8onReac8ons
• Energiesinthereac5oncoordinatediagramareaffectedby:
• Stabilityofthecarbonylcompound
• TheleavinggroupabilityofX:‐
4921.7HydrolysisofCarboxylicAcidDeriva7ves
NucleophilicAcylSubs8tu8onReac8ons
5021.7HydrolysisofCarboxylicAcidDeriva7ves
Reac8onsofAcidChlorideswithNucleophiles
5121.8Reac7onsofCarboxylicAcidDeriva7veswithNucleophiles
Reac8onsofAcidChlorideswithNucleophiles
5221.8Reac7onsofCarboxylicAcidDeriva7veswithNucleophiles
Reac8onsofAcidChlorideswithNucleophiles
• Relatedreac5onsofsulfonylchlorides
5321.8Reac7onsofCarboxylicAcidDeriva7veswithNucleophiles
Reac8onsofAnhydrideswithNucleophiles
5421.8Reac7onsofCarboxylicAcidDeriva7veswithNucleophiles
Reac8onsofEsterswithNucleophiles
• Transesterifica8on:
5521.8Reac7onsofCarboxylicAcidDeriva7veswithNucleophiles
Reduc8onofEsterstoPrimaryAlcohols
5621.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAmidestoAmines
• NotethataprotonolysisstepwithaqueousacidfollowstheLiAlH4reduc5on
• Thisisfollowedbybasetofreetheamine
5721.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAmidestoAmines
• Notehowtheamidereduc5ondiffersfromthatofesterreduc5on
5821.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAmidestoAmines
5921.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAmidestoAmines
6021.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofNitrilestoPrimaryAmines
• Twosuccessivenucleophilicaddi5onsoccur
6121.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofNitrilestoPrimaryAmines
6221.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAcidChloridestoAldehydes
• TheRosenmundreduc8on:
6321.9Reduc7onofCarboxylicAcidDeriva7ves
Reduc8onofAcidChloridestoAldehydes
• Useofderiva5vesofLiAlH4:
6421.9Reduc7onofCarboxylicAcidDeriva7ves
Rela8veReac8vi8es
6521.9Reduc7onofCarboxylicAcidDeriva7ves
Reac8onsofEsterswithGrignardReagents
6621.10Reac7onsofCarboxylicAcidDeriva7veswithOrganometallicReagents
Reac8onsofAcidChlorideswithR2CuLi
• Dialkylcupratesarelessreac5vethanGrignardreagents
6721.10Reac7onsofCarboxylicAcidDeriva7veswithOrganometallicReagents
SummaryofC.A.Deriva8vePrepara8on
Synthesisofesters:• Acid‐catalyzedesterifica5onofRCO2H
• Alkyla5onofRCO2HorRCO2‐
• AcidchloridesoranhydrideswithROH• Transesterifica5on
Synthesisofacidchlorides:
• RCO2HwithSOCl2orPCl3
6821.11SynthesisofCarboxylicAcidDeriva7ves
SummaryofC.A.Deriva8vePrepara8on
Synthesisofanhydrides:• RCO2Hwithdehydra5ngagents
• AcidchlorideswithRCO2‐
Synthesisofamides:
• Acidchlorides,anhydrides,oresterswithamines
6921.11SynthesisofCarboxylicAcidDeriva7ves
SummaryofC.A.Deriva8vePrepara8on
Synthesisofnitriles:• Cyanohydrinforma5on
• SN2reac5onofcyanideionwithalkylhalidesorsulfonateesters
7021.11SynthesisofCarboxylicAcidDeriva7ves
NylonandPolyesters
• Nylonisagenericnamegiventopolyamides
7121.12UseandOccurrenceofCarboxylicAcidsandTheirDeriva7ves
NylonandPolyesters
• Polyestersarecondensa8onpolymersderivedfromdiolsanddicarboxylicacids
7221.12UseandOccurrenceofCarboxylicAcidsandTheirDeriva7ves
Waxes,Fats,andPhospholipids
• AwaxisanesterofafaUyacidanda“faUyalcohol”
7321.12UseandOccurrenceofCarboxylicAcidsandTheirDeriva7ves
• AfatisderivedformamoleculeofglycerolandthreemoleculesoffaUyacid
Waxes,Fats,andPhospholipids
• Fatswithnodoublebondsarecalledsaturatedfats
• Fatscontainingdoublebondsarecalledunsaturatedfats
• TreatmentoffatswithKOHorNaOHgivesglycerolandthesaltofthefaUyacid(asoap)
• Thisreac5onistheoriginofthetermsaponifica8on
7421.12UseandOccurrenceofCarboxylicAcidsandTheirDeriva7ves
Waxes,Fats,andPhospholipids
• Phospholipidsarealsoestersofglycerol• Thekeystructuraldifferenceisthepresenceofapolarphosphoricacidderiva5ve
7521.12UseandOccurrenceofCarboxylicAcidsandTheirDeriva7ves