MARCH’SADVANCED ORGANICCHEMISTRY REACTIONS,MECHANISMS,
ANDSTRUCTURE
EIGHTHEDITION
MichaelB.Smith ProfessorEmeritus
UniversityofConnecticut DepartmentofChemistry
69EldredgeRoad
Willington,CT USA
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LibraryofCongressCataloging-in-PublicationData
Names: Smith,Michael,1946October17-author.|March,Jerry,1929–1997.
Title:March’sadvancedorganicchemistry:reactions,mechanisms,andstructure. Othertitles:Advancedorganicchemistry
Description:Eighthedition/MichaelBSmith(UniversityofConnecticut,DepartmentofChemistry).|Hoboken,NJ:John Wiley&Sons,Inc.,2020.|Includesindex.
Identifiers:LCCN2019023265(print)|LCCN2019023266(ebook)|ISBN9781119371809(cloth)|ISBN 9781119371786(adobepdf)|ISBN9781119371793(epub)
Subjects:LCSH:Chemistry,Organic.
Classification:LCCQD251.2.M372020(print)|LCCQD251.2(ebook)|DDC547—dc23 LCrecordavailableathttps://lccn.loc.gov/2019023265
LCebookrecordavailableathttps://lccn.loc.gov/2019023266
Coverimage:Background©atakan/iStock.com,AllotherimagescourtesyofMichaelB.Smith CoverdesignbyWiley
Setin10/12ptTimesLTStdbyAptaraInc.,NewDelhi,India
10987654321
CONTENTS
NEWREACTIONSECTIONSCORRELATION:7THEDITION → 8TH EDITIONxv
PREFACExxi COMMONABBREVIATIONSxxv
BIOGRAPHICALSTATEMENTxxxi
NEWFEATURESOFTHE8TH EDITIONxxxiii
PARTIINTRODUCTION1
1.LocalizedChemicalBonding3
1.A.CovalentBonding3
1.B.MultipleValence7
1.C.Hybridization7
1.D.MultipleBonds9
1.E.PhotoelectronSpectroscopy12
1.F.ElectronicStructuresofMolecules15
1.G.Electronegativity17
1.H.DipoleMoment19
1.I.InductiveandFieldEffects20
1.J.BondDistances23
1.K.BondAngles27
1.L.BondEnergies29
2.DelocalizedChemicalBonding33
2.A.MolecularOrbitals34
2.B.BondEnergiesandDistancesinCompoundsContaining DelocalizedBonds37
2.C.MoleculesthathaveDelocalizedBonds39
2.D.CrossConjugation44
2.E.TheRulesofResonance46
2.F.TheResonanceEffect48
2.G.StericInhibitionofResonanceandtheInfluencesofStrain48
2.H. pπ–dπ Bonding:Ylids52
2.I.Aromaticity54
2.I.i.Six-MemberedRings58
2.I.ii.Five-,Seven-,andEight-MemberedRings62
2.I.iii.OtherSystemsContainingAromaticSextets67
2.J.AlternantandNonalternantHydrocarbons68
2.K.AromaticSystemswithElectronNumbersOtherThanSix70
2.K.i.SystemsofTwoElectrons72
2.K.ii.SystemsofFourElectrons:Antiaromaticity73
2.K.iii.SystemsofEightElectrons76
2.K.iv.SystemsofTenElectrons77
2.K.v.SystemsofMorethanTenElectrons:4n +2Electrons80
2.K.vi.SystemsofMoreThanTenElectrons:4n Electrons85
2.L.OtherAromaticCompounds89
2.M.Hyperconjugation92
2.N.Tautomerism96
2.N.i.Keto–EnolTautomerism97
2.N.ii.OtherProton-ShiftTautomerism100
3.BondingWeakerThanCovalent105
3.A.HydrogenBonding105
3.B. π–π Interactions113
3.C.AdditionCompounds114
3.C.i.ElectronDonor–Acceptor(EDA)Complexes114
3.C.ii.CrownEtherComplexesandCryptates117
3.C.iii.InclusionCompounds122
3.C.iv.Cyclodextrins125
3.D.CatenanesandRotaxanes127
3.E.Cucurbit[n]Uril-BasedGyroscane131
4.StereochemistryandConformation133
4.A.OpticalActivityandChirality133
4.B.DependenceofRotationonConditionsofMeasurement135
4.C.WhatKindsofMoleculesDisplayOpticalActivity?136
4.D.TheFischerProjection147
4.E.AbsoluteConfiguration148
4.E.i.TheCahn-Ingold-PrelogSystem150
4.E.ii.MethodsOfDeterminingConfiguration152
4.F.TheCauseofOpticalActivity156
4.G.MoleculeswithMoreThanOneStereogenicCenter157
4.H.AsymmetricSynthesis161
4.I.MethodsofResolution166
4.J.OpticalPurity173
4.K. Cis–Trans Isomerism175
4.K.i. Cis–Trans IsomerismResultingfromDoubleBonds175
4.K.ii. Cis–Trans IsomerismofMonocyclicCompounds179
4.K.iii. Cis–Trans IsomerismofFusedandBridgedRingSystems180
4.L. Out–In Isomerism181
4.M.EnantiotopicandDiastereotopicAtoms,Groups,andFaces183
4.N.StereospecificandStereoselectiveSyntheses186
4.O.ConformationalAnalysis187
4.O.i.ConformationinOpen-ChainSystems188
4.O.ii.ConformationinSix-MemberedRings194
4.O.iii.ConformationinSix-MemberedRingsContaining Heteroatoms199
4.O.iv.ConformationinOtherRings202
4.P.MolecularMechanics204
4.Q.Strain206
4.Q.i.StraininSmallRings207
4.Q.ii.StraininOtherRings213
4.Q.iii.UnsaturatedRings215
4.Q.iv.StrainDuetoUnavoidableCrowding218
5.Carbocations,Carbanions,FreeRadicals,Carbenes,andNitrenes223
5.A.Carbocations224
5.A.i.Nomenclature224
5.A.ii.StabilityandStructureofCarbocations224
5.A.iii.TheGenerationAndFateOfCarbocations234
5.B.Carbanions237
5.B.i.StabilityandStructure237
5.B.ii.TheStructureOfOrganometallicCompounds244
5.B.iii.TheGenerationAndFateOfCarbanions249
5.C.FreeRadicals250
5.C.i.StabilityandStructure250
5.C.ii.TheGenerationandFateofFreeRadicals261
5.C.iii.RadicalIons265
5.D.Carbenes266
5.D.i.StabilityandStructure266
5.D.ii.TheGenerationandFateofCarbenes269
5.D.iii. N-HeterocyclicCarbenes(NHCs)274
5.E.Nitrenes276
6.MechanismsandMethodsofDeterminingThem279
6.A.TypesofMechanism279
6.B.TypesofReaction280
6.C.ThermodynamicRequirementsforReaction283
6.D.KineticRequirementsforReaction284
6.E.TheBaldwinRulesforRingClosure288
6.F.KineticandThermodynamicControl290
6.G.TheHammondPostulate291
6.H.MicroscopicReversibility291
6.I.MarcusTheory292
6.J.MethodsofDeterminingMechanisms293
6.J.i.IdentificationofProducts293
6.J.ii.DeterminationofthePresenceofanIntermediate294
6.J.iii.TheStudyofCatalysis295
6.J.iv.IsotopicLabeling296
6.J.v.StereochemicalEvidence296
6.J.vi.KineticEvidence297
6.J.vii.IsotopeEffects304
6.K.CatalystDevelopment308
7.IrradiationProcessesandTechniquesthatInfluenceReactionsin OrganicChemistry313
7.A.Photochemistry314
7.A.i.ExcitedStatesandtheGroundState314
7.A.ii.SingletandTripletStates:“Forbidden”Transitions316
7.A.iii.TypesofExcitation317
7.A.iv.NomenclatureandPropertiesofExcitedStates318
7.A.v.PhotolyticCleavage319
7.A.vi.TheFateoftheExcitedMolecule:PhysicalProcesses320
7.A.vii.TheFateoftheExcitedMolecule:ChemicalProcesses325
7.A.viii.TheDeterminationofPhotochemicalMechanisms330
7.B.Sonochemistry331
7.C.MicrowaveChemistry334
7.D.FlowChemistry336
7.E.Mechanochemistry338
8.AcidsandBases339
8.A.BrønstedTheory339
8.A.i.BrønstedAcids340
8.A.ii.BrønstedBases347
8.B.TheMechanismofProtonTransferReactions350
8.C.MeasurementsofSolventAcidity352
8.D.AcidandBaseCatalysis355
8.E.LewisAcidsandBases357
8.E.i.Hard–SoftAcids–Bases359
8.F.TheEffectsofStructureontheStrengthsofAcidsandBases361
8.G.TheEffectsoftheMediumonAcidandBaseStrength370
9.EffectsofStructureandMediumonReactivity375
9.A.ResonanceandFieldEffects375
9.B.StericEffects377
9.C.QuantitativeTreatmentsoftheEffectofStructureonReactivity380
9.D.EffectofMediumonReactivityandRate390
9.E.HighPressure390
9.F.WaterandOtherNonorganicSolvents391
9.G.IonicLiquidSolvents393
9.H.SolventlessReactions395
PARTIIINTRODUCTION397
10.AliphaticSubstitution,NucleophilicandOrganometallic403
10.A.Mechanisms404
10.A.i.TheSN 2Mechanism404
10.A.ii.TheSN 1Mechanism410
10.A.iii.IonPairsintheSN 1Mechanism414
10.A.iv.MixedSN 1andSN 2Mechanisms418
10.B.SETMechanisms420
10.C.TheNeighboring-GroupMechanism422
10.C.i.Neighboring-GroupParticipationby π and σ Bonds: NonclassicalCarbocations425
10.D.TheSN iMechanism440
10.E.NucleophilicSubstitutionatanAllylicCarbon:Allylic Rearrangements441
10.F.NucleophilicSubstitutionatanAliphaticTrigonalCarbon:The TetrahedralMechanism445
10.G.Reactivity449
10.G.i.TheEffectofSubstrateStructure449 10.G.ii.TheEffectoftheAttackingNucleophile457
10.G.iii.TheEffectoftheLeavingGroup464
10.G.iv.TheEffectoftheReactionMedium469
10.G.v.Phase-TransferCatalysis474
10.G.vi.InfluencingReactivitybyExternalMeans477
10.G.vii.Ambident(Bidentant)Nucleophiles:Regioselectivity478 10.G.viii.AmbidentSubstrates481
10.H.Reactions483
10.H.i.OxygenNucleophiles483 10.H.ii.SulfurNucleophiles506 10.H.iii.NitrogenNucleophiles512 10.H.iv.HalogenNucleophiles534
10.H.v.CarbonNucleophiles545
11.AromaticSubstitution,Electrophilic607
11.A.Mechanisms607
11.A.i.TheAreniumIonMechanism608
11.A.ii.TheSE 1Mechanism613
11.B.OrientationandReactivity614
11.B.i.OrientationandReactivityinMonosubstitutedBenzene Rings614
11.B.ii.The Ortho/Para Ratio618
11.B.iii.IpsoAttack620
11.B.iv.OrientationinBenzeneRingsWithMoreThanOne Substituent621
11.B.v.OrientationinOtherRingSystems622
11.C.QuantitativeTreatmentsofReactivityintheSubstrate624
11.D.AQuantitativeTreatmentofReactivityoftheElectrophile:The SelectivityRelationship626
11.E.TheEffectoftheLeavingGroup628
11.F.Reactions629
11.F.i.HydrogenastheLeavingGroupinSimpleSubstitution Reactions629
11.F.ii.HydrogenastheLeavingGroupInRearrangement Reactions675
11.F.iii.OtherLeavingGroups680
12.Aliphatic,Alkenyl,andAlkynylSubstitution:Electrophilicand Organometallic687
12.A.Mechanisms687
12.A.i.BimolecularMechanisms.SE 2andSE i688
12.A.ii.TheSE 1Mechanism691
12.A.iii.ElectrophilicSubstitutionAccompaniedbyDouble-Bond Shifts694
12.A.iv.OtherMechanisms695
12.B.Reactivity695 12.C.Reactions697
12.C.i.HydrogenasLeavingGroup697
12.C.ii.MetalsasLeavingGroups733
12.C.iii.HalogenasLeavingGroup746
12.C.iv.CarbonLeavingGroups751
12.C.v.ElectrophilicSubstitutionAtNitrogen760
13.AromaticSubstitution:NucleophilicandOrganometallic767
13.A.Mechanisms768
13.A.i.TheSN ArMechanism768
13.A.ii.TheSN 1Mechanism771
13.A.iii.TheBenzyneMechanism772
13.A.iv.TheSRN 1Mechanism774
13.A.v.OtherMechanisms776
13.B.Reactivity776
13.B.i.TheEffectofSubstrateStructure776
13.B.ii.TheEffectoftheLeavingGroup778
13.B.iii.TheEffectoftheAttackingNucleophile779
13.C.Reactions779
13.C.i.AllLeavingGroupsExceptHydrogenAndN2 + 779
13.C.ii.HydrogenasLeavingGroup823
13.C.iii.NitrogenasLeavingGroup824
13.C.iv.Rearrangements834
14.RadicalReactions839
14.A.Mechanisms839
14.A.i.RadicalMechanismsinGeneral839
14.A.ii.Free-RadicalSubstitutionMechanisms844
14.A.iii.MechanismsatanAromaticSubstrate845
14.A.iv.Neighboring-GroupAssistanceinFree-RadicalReactions847
14.B.Reactivity848
14.B.i.ReactivityforAliphaticSubstrates848
14.B.ii.ReactivityataBridgehead853
14.B.iii.ReactivityinAromaticSubstrates854
14.B.iv.ReactivityintheAttackingRadical855
14.B.v.TheEffectofSolventonReactivity856
14.C.Reactions856
14.C.i.HydrogenasLeavingGroup856
14.C.ii.MetalsasLeavingGroups880
14.C.iii.HalogenasLeavingGroup883
14.C.iv.SulfurasLeavingGroup883
14.C.v.CarbonasLeavingGroup885
15.AdditiontoCarbon–CarbonMultipleBonds891
15.A.Mechanisms892
15.A.i.ElectrophilicAddition892
15.A.ii.NucleophilicAddition895
15.A.iii.Free-RadicalAddition896
15.A.iv.CyclicMechanisms898
15.A.v.AdditiontoConjugatedSystems898
15.B.OrientationandReactivity899
15.B.i.Reactivity899
15.B.ii.Orientation902
15.B.iii.StereochemicalOrientation904
15.B.iv.AdditiontoCyclopropaneRings906
15.C.Reactions908
15.C.i.IsomerizationofDoubleandTripleBonds908
15.C.ii.ReactionsinWhichHydrogenAddstoOneSide910
15.C.iii.ReactionsinWhichHydrogenAddstoNeitherSide992
15.C.iv.CycloadditionReactions1027
16.AdditiontoCarbon–HeteroatomMultipleBonds1087
16.A.MechanismandReactivity1087
16.A.i.NucleophilicSubstitutionatanAliphaticTrigonalCarbon: TheTetrahedralMechanism1089
16.B.Reactions1094
16.B.i.ReactionsinWhichHydrogenoraMetallicIonAdds totheHeteroatom1095
16.B.ii.AcylSubstitutionReactions1218
16.B.iii.ReactionsinWhichCarbonAddstotheHeteroatom1257
16.B.iv.AdditiontoIsocyanides1264
16.B.v.NucleophilicSubstitutionataSulfonylSulfurAtom1266
17.EliminationReactions1273
17.A.MechanismsandOrientation1273
17.A.i.TheE2Mechanism1274
17.A.ii.TheE1Mechanism1280
17.A.iii.TheE1cBMechanism1281
17.A.iv.TheE1-E2-E1cBSpectrum1286
17.A.v.TheE2CMechanism1287
17.B.RegiochemistryoftheDoubleBond1288
17.C.StereochemistryoftheDoubleBond1290
17.D.Reactivity1291
17.D.i.EffectofSubstrateStructure1291
17.D.ii.EffectoftheAttackingBase1293
17.D.iii.EffectoftheLeavingGroup1294
17.D.iv.EffectoftheMedium1294
17.E.MechanismsandOrientationinPyrolyticEliminations1295
17.E.i.Mechanisms1295
17.E.ii.OrientationinPyrolyticEliminations1298
17.E.iii.1,4ConjugateEliminations1298
17.F.Reactions1299
17.F.i.ReactionsinWhichC CandC≡CBondsAreFormed1299
17.F.ii.Fragmentations1321
17.F.iii.ReactionsinWhichC≡NorC NBondsAreFormed1325
17.F.iv.ReactionsinWhichC OBondsAreFormed1328
17.F.v.ReactionsinWhichN NBondsAreFormed1329
17.F.vi.ExtrusionReactions1329
18.Rearrangements1335
18.A.Mechanisms1336
18.A.i.NucleophilicRearrangements1336
18.A.ii.TheActualNatureoftheMigration1337
18.A.iii.MigratoryAptitudes1340
18.A.iv.MemoryEffects1343
18.B.LongerNucleophilicRearrangements1344
18.C.Free-RadicalRearrangements1345
18.D.CarbeneRearrangements1349
18.E.ElectrophilicRearrangements1349
18.F.Reactions1350
18.F.i.1,2-Rearrangements1350
18.F.ii.Non1,2-Rearrangements1389
19.OxidationsandReductions1439
19.A.Mechanisms1440
19.B.Reactions1442
19.B.i.Oxidations1442
19.B.ii.Reductions1510
APPENDIXA:THELITERATUREOFORGANICCHEMISTRY1607
APPENDIXB:CLASSIFICATIONOFREACTIONSBYTYPEOF COMPOUNDSSYNTHESIZED1645
INDEXES
AUTHORINDEX1669 SUBJECTINDEX1917
NEWREACTIONSECTIONSCORRELATION:7TH
EDITION → 8THEDITION
7TH → 8TH
10-1 → 10-1
10-2 → 10-2
10-3 → 10-3
10-4 → 10-4
10-5 → 10-5
10-6 → 10-6
10-7 → 10-7
10-8 → 10-8
10-9 → 10-9
10-10 → 10-10
10-11 → 10-11
10-12 → 10-12
10-13 → 10-13
10-14 → 10-14
10-15 → 10-15
10-16 → 10-16
10-17 → 10-17
10-18 → 10-18 10-19 → 10-19
10-20 → 10-20
10-21 → 10-21
10-22 → 10-22
10-23 → 10-23
10-24 → 10-24
10-25 → 10-25
10-26 → 10-26
10-27 → 10-27
10-28 → deleted,now with10-27
10-29 → 10-28
10-30 → 10-29 10-31 → 10-30 10-32 → 10-31
10-33 → 10-32
10-34 → 10-33
10-35 → 10-34
10-36 → 10-35 10-37 → 10-36 10-38 → 10-37
10-39 → 10-38
10-40 → 10-39 10-41 → 10-40 10-42 → 10-41
10-43 → 10-42
10-44 → 10-43
10-45 → 10-44
10-46 → 10-45
10-47 → 10-46
10-48 → 10-47
10-49 → 10-48
10-50 → 10-49
10-51 → 10-50
10-52 → 10-51
10-53 → 10-52
10-54 → 10-53
10-55 → 10-54
New10-55
10-56 → 10-56
10-57 → 10-57
10-58 → 10-58
10-59 → 10-59
10-60 → 10-60
10-61 → 10-61
10-62 → 10-62
10-63 → 10-63
10-64 → 10-64
10-65 → 10-65
10-66 → 10-66
10-67 → 10-67
10-68 → 10-68
10-69 → 10-69
10-70 → 10-70
10-71 → 10-71
10-72 → 10-72
10-73 → 10-73
10-74 → 10-74
New10-75
10-75 → 10-76
10-76 → 10-77
10-77 → 10-78
New10-79
11-1 → 11-1
11-2 → 11-2
11-3 → 11-3
11-4 → 11-6
11-5 → 11-5
11-6 → 11-4
11-7 → 11-7
11-8 → 11-8
11-9 → 11-9
11-10 → 11-10
11-11 → 11-11
11-12 → 11-12
11-13 → 11-13
11-14 → 11-14
11-15 → 11-15
11-16 → 11-16
11-17 → 11-17
11-18 → 11-18
11-19 → 11-19
11-20 → deleted,now with11-19
11-21 → 11-20
New11-21
11-22 → 11-22
11-23 → 11-23 11-24 → 11-24
11-25 → 11-25
11-26 → 11-26
11-27 → 11-27
11-28 → 11-28
11-29 → 11-29
11-30 → 11-30
11-31 → 11-31
11-32 → 11-32
11-33 → 11-33
11-34 → 11-34
11-35 → 11-35
11-36 → 11-36
11-37 → deleted,now with19-61
11-38 → deleted,now with19-74
11-39 → deleted,now with19-58
11-40 → 11-37
11-41 → 11-38
12-1 → 12-1
12-2 → 12-2
12-3 → 12-3
12-4 → 12-4
12-5 → 12-5
12-6 → 12-6
12-7 → 12-7
12-8 → 12-8
12-9 → 12-9
12-10 → 12-10
12-11 → 12-11
12-12 → 12-12
12-13 → 12-13
12-14 → 12-14
12-15 → 12-15
12-16 → 12-16
12-17 → 12-17
12-18 → 12-18
12-19 → 12-19
12-20 → 12-20
12-21 → 12-21
12-22 → 12-22
12-23 → 12-23
12-24 → 12-24
12-25 → 12-25
12-26 → 12-26
12-27 → 12-27
12-28 → deletednow with12-27
12-29 → 12-28
12-30 → 12-29
12-31 → 12-30
12-32 → 12-31
12-33 → 12-32
12-34 → 12-33
12-35 → 12-34
12-36 → 12-35
12-37 → 12-36
12-38 → 12-37
12-39 → 12-38
12-40 → 12-39
12-41 → 12-40
12-42 → 12-41
12-43 → 12-42
12-44 → 12-43
12-45 → 12-44
12-46 → 12-45
12-47 → 12-46
12-48 → 12-47
12-49 → 12-48
12-50 → 12-49
12-51 → 12-50
12-52 → 12-51
12-53 → 12-52
13-1 → 13-1
13-2 → deleted,now with13-1
13-3 → 13-2
13-4 → 13-3
13-5 → 13-4 13-6 → 13-5
13-7 → 13-6 New13-7
13-8 → 13-8 13-9 → 13-9
13-10 → 13-13
13-11 → 13-10
13-12 → 13-11
13-13 → 13-14
13-14 → 13-15
13-15 → 13-16
13-16 → 13-17
13-17 → 13-12 13-18 → 13-18
13-19 → 13-19
13-20 → 13-20
13-21 → 13-21
13-22 → 13-22
13-23 → deleted,now with13-22
New13-23
13-24 → 13-24
13-25 → 13-25
New13-26
13-26 → 13-27
13-27 → 13-28
13-28 → 13-29 13-29 → 13-30
13-30 → 13-31
13-31 → 13-32
13-32 → 13-33 13-34 → 13-34
14-1 → 14-1
14-2 → 14-2
14-3 → 14-3
14-4 → deleted,now with14-1
14-5 → 14-4
14-6 → 14-5
14-7 → 14-6
14-8 → 14-7
14-9 → 14-8
14-10 → 14-9
14-11 → 14-10
14-12 → 14-11
14-13 → 14-12
14-14 → 14-13 14-15 → 14-14 14-16 → 14-15 14-17 → 14-16
14-18 → 14-17
14-19 → 14-18
14-20 → movedto 13-22
14-21 → movedto 13-7
14-22 → movedto 13-21
14-23 → movedto 13-26
14-24 → 14-19
14-25 → 14-20
14-26 → 14-21
14-27 → 14-22
14-28 → deleted,now with14-22
14-29 → 14-23
14-30 → 14-24
14-31 → 14-25
14-32 → 14-26
15-1 → 15-1
15-2 → 15-2
15-3 → 15-3
15-4 → 15-4
15-5 → 15-5
15-6 → 15-6
15-7 → 15-7
15-8 → 15-8
15-9 → 15-9
15-10 → 15-10
15-11 → movedto 19-34
15-12 → movedto 19-35
15-13 → movedto 19-36
15-14 → movedto 19-37
15-15 → movedto 19-38
15-16 → 15-11
15-17 → 15-12
15-18 → 15-13
15-19 → 15-14
15-20 → 15-15
15-21 → 15-16 New15-17
15-22 → 15-18
15-23 → 15-19
15-24 → 15-20
15-25 → 15-21
15-26 → 15-22
15-27 → 15-23
15-28 → 15-24
15-29 → 15-25
15-30 → 15-26
15-31 → 15-27
15-32 → 15-28
15-33 → 15-29
15-34 → 15-30
15-35 → 15-31
15-36 → 15-32
15-37 → 15-33
15-38 → 15-34
15-39 → 15-35
15-40 → 15-36
15-41 → 15-37
15-42 → 15-38
15-43 → 15-39
15-44 → 15-40
15-45 → 15-41
15-46 → 15-42
15-47 → 15-43
15-48 → 15-44
15-49 → 15-45
15-50 → 15-46
15-51 → 15-47
15-52 → 15-48
15-53 → 15-49
15-54 → 15-50
15-55 → 15-51
15-56 → 15-52
15-57 → 15-53
15-58 → 15-54
15-59 → 15-55
15-60 → 15-56
15-61 → 15-57
15-62 → 15-58
15-63 → 15-59
15-64 → 15-60
15-65 → 15-61
15-66 → 15-62
16-1 → 16-1
16-2 → 16-2
16-3 → 16-3
16-4 → 16-4
16-5 → 16-5
16-6 → deleted,now with16-5
16-7 → 16-6
16-8 → 16-7
16-9 → 16-8
16-10 → 16-9
16-11 → 16-10
16-12 → 16-11
16-13 → 16-12
16-14 → 16-13
16-15 → deleted,now with16-13
16-16 → 16-14
16-17 → 16-15
16-18 → 16-16
16-19 → 16-17
16-20 → 16-18
16-21 → 16-19
16-22 → 16-20
16-23 → 16-21
16-24 → 16-22
16-25 → 16-23
New16-24
16-26 → 16-25
16-27 → 16-26
16-28 → 16-27
16-29 → 16-29
16-30 → 16-30
16-31 → 16-31
16-32 → 16-32
16-33 → 16-33
16-34 → 16-34
16-35 → 16-35
16-36 → 16-36
16-37 → 16-37
16-38 → 16-38
16-39 → 16-39
16-40 → 16-40
16-41 → 16-41
16-42 → 16-42
16-43 → 16-43
16-44 → 16-44
16-45 → 16-45
16-46 → 16-46
16-47 → 16-47
16-48 → 16-48
16-49 → deleted,now with16-48
16-50 → 16-49
16-51 → 16-50
16-52 → 16-51
16-53 → 16-52
16-54 → 16-53
16-55 → 16-54
16-56 → 16-55
16-57 → 16-56
16-58 → 16-57
16-59 → 16-58
16-60 → 16-59
16-61 → 16-60
16-62 → 16-61
16-63 → 16-62
16-64 → 16-63
16-65 → 16-64
16-66 → 16-65
16-67 → 16-66
16-68 → 16-67
16-69 → 16-68
16-70 → 16-69
16-71 → 16-70
16-72 → 16-71
16-73 → 16-72
16-74 → 16-73
16-75 → 16-74
16-76 → 16-75
16-77 → 16-76
16-78 → 16-77
16-79 → 16-78
16-80 → deleted,now with16-78
16-81 → 16-28
16-82 → moved,now with18-29
16-83 → 16-79
16-84 → 16-80
16-85 → 16-81
16-86 → 16-82
16-87 → deleted,now with16-82
16-88 → 16-83
16-89 → moved,now with12-10
16-90 → 16-84
16-91 → 16-85
16-92 → 16-86
16-93 → 16-87
16-94 → 16-88
16-95 → 16-89
16-96 → 16-90
16-97 → 16-91
16-98 → 16-92
16-99 → 16-93
16-100 → 16-94
16-101 → 16-95
16-102 → 16-96
16-103 → 16-97
16-104 → moved, nowwith19-75
16-105 → 16-98
17-1 → 17-1
17-2 → 17-2
17-3 → 17-3
17-4 → 17-4
17-5 → 17-5
17-6 → deleted,now with17-5
17-7 → 17-6
17-8 → deleted,now with17-2
17-9 → 17-7
17-10 → 17-8
17-11 → 17-9
17-12 → 17-10
17-13 → 17-11
17-14 → 17-12
17-15 → 17-13
17-16 → 17-14
17-17 → 17-15
17-18 → 17-16
17-19 → 17-17
17-20 → 17-18
17-21 → 17-19
17-22 → 17-20
17-23 → 17-21
17-24 → 17-22
17-25 → 17-23
17-26 → 17-24
17-27 → 17-25
17-28 → 17-26
17-29 → 17-27
17-30 → 17-28
17-31 → 17-29
17-32 → 17-30
17-33 → 17-31
17-34 → 17-32
17-35 → 17-33
17-36 → 17-34
17-37 → 17-35
17-38 → 17-36
18-1 → 18-1
18-2 → 18-2
18-3 → 18-3
18-4 → 18-4
18-5 → 18-5
18-6 → 18-6
18-7 → 18-7
18-8 → 18-8
18-9 → 18-9
18-10 → 18-10
18-11 → 18-11
18-12 → 18-12
18-13 → 18-13
18-14 → 18-14
18-15 → 18-15
18-16 → 18-16
18-17 → 18-17
18-18 → 18-18
18-19 → 18-19
18-20 → 18-20
18-21 → 18-21
18-22 → 18-22
18-23 → 18-23
18-24 → 18-24
18-25 → 18-25
18-26 → 18-26
18-27 → 18-27
18-28 → 18-28
18-29 → 18-29
18-30 → 18-30
18-31 → 18-31
18-32 → 18-32
18-33 → 18-33
18-34 → 18-34
18-35 → 18-35
18-36 → 18-36
18-37 → 18-37
18-38 → 18-38
18-39 → 18-39
18-40 → 18-40
18-41 → 18-41
18-42 → 18-42
18-43 → 18-43
18-44 → 18-44
19-1 → 19-1
19-2 → 19-2
19-3 → 19-3
19-4 → 19-4
19-5 → 19-5
19-6 → 19-6
19-7 → 19-7
19-8 → 19-8
19-9 → 19-9
19-10 → 19-10
19-11 → 19-11
19-12 → 19-12
19-13 → 19-13
19-14 → 19-14
19-15 → 19-16
19-16 → 19-17
19-17 → 19-18
19-18 → 19-15
19-19 → 19-19
19-20 → 19-20
19-21 → 19-21
19-22 → 19-22
19-23 → 19-23
19-24 → 19-24
19-25 → 19-25
19-26 → 19-26
19-27 → 19-27
19-28 → deleted,now with19-27
19-29 → 19-28
19-30 → 19-29
19-31 → 19-30
19-32 → 19-31
19-33 → 19-32
19-34 → 19-33
19-35 → 19-39
19-36 → 19-40
19-37 → 19-41
19-38 → 19-42
19-39 → 19-43
19-40 → 19-44
19-41 → 19-45
19-42 → 19-46
19-43 → 19-47
19-44 → 19-48
19-45 → 19-49
19-46 → 19-50
19-47 → 19-51
19-48 → 19-52
19-49 → 19-53
19-50 → 19-54
19-51 → 19-55
19-52 → 19-56
19-53 → 19-57
19-54 → 19-59
19-55 → 19-60
19-56 → 19-61
19-57 → 19-63
19-58 → 19-64
19-59 → 19-62
19-60 → 19-65
19-61 → 19-66
19-62 → 19-67
19-63 → deleted,now with19-67
19-64 → 19-68
19-65 → 19-69
19-66 → 19-70
19-67 → 19-71
19-68 → 19-72
19-69 → 19-73
19-70 → 19-74
19-71 → 19-75
19-72 → 19-76
19-73 → 19-77
19-74 → 19-78
19-75 → 19-79
19-76 → 19-80
19-77 → 19-81
19-78 → 19-82
19-79 → 19-83
19-80 → 19-84
19-81 → 19-85
19-82 → 19-86
19-83 → 19-87
19-84 → 19-88
PREFACE
Thiseightheditionof March’sAdvancedOrganicChemistry hasbeenthoroughlyupdated toincludenewadvancesinareasoforganicchemistrypublishedbetween2011and2017. Everytopicretainedfromtheseventheditionhasbeenbroughtuptodateiftherewas activityinthatareaduringthatsix-yearperiod.Changesalsoincludeasignificantrewrite ofmostofthebook.Morethan5800newreferenceshavebeenaddedforworkpublished since2011.Aswiththeseventhedition,manyolderreferencesweredeletedtomakeroom fornewones.Incaseswhereaseriesofpapersbythesameprincipalauthorwerecited,most butthemostrecentweredeleted.Beawarethattheoldercitationscanusuallybefoundby referringtothemorerecentpublications.Itisnotedthatmorethan250000articlesforthe years2011–2017,from31journals,werescannedforthisedition.Ofthishugenumberof articles,justover8000wereexaminedindetailforinclusioninthiswork,with5853finally chosen.Withsuchnumbers,itisinevitablethatsomeworkwasnotincluded,anditwas impossibletoincluderepresentativeresearchinmanyareas.Forexample,over2000ofthe 8000articlesexaminedwererelevanttothetransitionmetal-catalyzedreactionscovered inreactions 13-3 to 13-13.Itwassimplyimpossibletokeeparepresentativenumberof articlesforthissubjectarea.Therewereotherareasofresearchthatwerealsotooextensive forcompleteinclusionofallreferences.
Manyofthereactiondrawingsconsideredtoberedundantornotveryusefulweredeleted whencompilingtheeighthedition.Afewnewsectionsoftextwereaddedtobetterreflect someareasofresearch.Severaloftheoldersectionsweremovedtonewchapters,especiallytheonesthatdealwithhydrogenationofalkenesandalkynes;astheseareclearly reductionstheyweremovedtoChapter19.Somesectionswerecombinedwithothersand theoriginalsectiondeleted.Theseactionsrequiredrenumberingthesectionsfortheeighth edition.Acorrelationtableofthesectionsintheseventheditionandtheirplacementinthe eightheditionisprovidedbelow.However,thefundamentalstructureoftheeighthedition isessentiallythesameasthatofallpreviouseditions.
Thegoal,asinpreviouseditions,istogiveequalweighttothreefundamentalaspects ofthestudyoforganicchemistry:reactions,mechanisms,andstructure.Referencesare provided,andeveryefforthasbeengiventoprovideasnapshotofcurrentresearch. Specificbutspecializedareasoforganicchemistry—terpenes,carbohydrates,proteins, manyorganometallicreagents,combinatorialchemistry,polymerizationandelectrochemicalreactions,steroids,etc.—havebeenincorporatedintoagreatmanypertinentsections ratherthansegregatedintotheirownsections.
Thisbookislargelydirectedatgraduatestudentsintheirfirstyearofstudyandtoundergraduatesadvancedintheirstudies,butpreviouseditionshave,formanyyears,beenused asanoff-the-shelfreferencebook.Thispracticeshouldcontinuewiththeeighthedition.It ishopedthatthisbookwillleadastudenttoconsultthemanyexcellentbooksandreview articlescitedforvarioustopicsinordertounderstandthesubjectinmoredetail.Indeed, mostofthesetopicsaresovasttheycannotbeexplainedcompletelyinthisbook.
ThestructureoforganiccompoundsisdiscussedinChapters1–5(foundinPartI);these chaptersprovidethebackgroundthatisnecessaryforunderstandingmechanisms,butare importantintheirownright.Thediscussionbeginswithchemicalbonding(Chapter1)and endswithachapteronstereochemistry(Chapter4).Chapter5discussesthestructureof intermediates.Chapters6and7thenaddressreactionmechanismsingeneral,Chapter6 forordinaryreactionsandChapter7forphotochemicalreactions.Othermethodsrelatedto reactionsareincludedinChapter7,includingmicrowavechemistry,theuseofultrasound, mechanochemistry,andtherelativelynewareaofreactionsdoneunderflowconditions. PartIconcludeswithChapters8and9,whichgivefurtherbackgroundtothestudyof mechanismsandreactionconditions.
TheIntroductiontoPartIIbrieflydescribeshowthesecondpartofthebookisorganized.Theorganizationisbasedonreactiontypes,andarelativelyfewprinciplessuffice toexplainnearlyallthetypes,despitethelargenumberoforganicreactions.Accordingly, thereactionsandmechanismssectionofthisbook(PartII)isdividedintotenchapters, eachbeingconcernedwithadifferenttypeofreaction.Inthefirstpartofeachchapterthe appropriatebasicmechanismsarediscussed,alongwithconsiderationsofreactivityand orientation.Thesecondpartofeachchapterisdevotedtoindividualreactiontypes,where thescopeandthemechanismofeachreactionarediscussed.Numberedsectionsareusedfor thereactionsandthesesaresetinboldfacewhengivenascross-references.Sincethemethodsforthepreparationofindividualclassesofcompounds(e.g.,ketones,nitriles,etc.)are nottreatedallinoneplace,anupdatedandrevisedindexhasbeenprovided(AppendixB) byuseofwhichthesynthesisofagiventypeofcompoundmaybefound.
Itisimportanttonotethatthereactionnumbers(e.g., 10-25)formanyreactionsinthe eightheditionare different fromthoseinthesixthandseventheditions.Atableisincluded thatprecedesthisPrefacethatdirectlycorrelatesthereactionnumbersfoundintheeighth editionwiththereactionnumbersthatwereusedinthesixthandseventheditions.Notealso thatchangesinthesixtheditionmadethereactionnumbersfromeditions1–5differentin manycasestothoseinthesixthedition.Toseethedifferencesbetweenthefifthandsixth editions,thereaderisreferredtothesixthedition.
AlthoughIUPAChaspublishedasystemfordesignatingreactionmechanisms,thedesignationsforreactionsthatwerefeaturedineditions1–7havebeenremoved,inlargepart becausetheyarenotextensivelyusedandinpartbecausemanyreactionsweredeemedby thisauthorasdifficulttocategorizeusingonlyonedesignation.
Intreatingsubjectsasbroadasstructure,reactions,andmechanismsoforganicchemistry,itisimpossibletocovereachtopicingreatdepth,thoughthiswouldnotbedesirable evenifpossible.Thisbookisintendedtopointthereadertotheprimaryliterature(the originaljournalpublications).Secondaryliteraturessources,includingreviews,books,and monographs,havealsobeenincluded.
AppendixAprovidesabriefintroductiontousingmoderncomputer-basedsearch enginessuchas Reaxys® and SciFinder® .
Althoughbasicallydesignedasareferencetextforaone-yearcourseatgraduatelevel, thisbookcanalsobeusedinadvancedundergraduatecoursesbutismostusefulaftercompletionofaone-yearcourseinorganicchemistry.Ithasbeenmyexperiencethatstudents whohavecompletedthefirst-yearcoursesoftenhaveahazyrecollectionofthematerialand greatlyprofitfromare-presentationofthematerialifitiseasilyaccessible.Thematerialin thefirstninechapters,particularlychapters1,2,4,6,and8,maybehelpfulforreviewing suchmaterialwhenthisbookisusedinconnectionwithacourse.
Thisbookisprobablymostvaluableasareasonablyup-to-datereferencework.Both studentspreparingforqualifyingexaminationsandpracticingorganicchemistswillfind thatPartIIcontainsasurveyofthemechanismandscopeofalargenumberofreactions, arrangedinanorderlymannerbasedonreactiontypeandonwhichbondsarebrokenand formed.
IUPACmandatesjoulesforunitsofenergy,butmanyjournalsdonotusethisunitexclusively.Indeed,organicchemistswhopublishinUnitedStates’journalscommonlyusecalories.Virtuallyallenergyvaluesarepresentedhereinbothcaloriesandjoules.
AlthoughIUPACdoesnotrecommendangstromunits( ˚ A)forbonddistances,preferring insteadpicometers(pm),avastnumberofbonddistancespublishedintheliteraturearein angstromunits,andthisbookthereforeusesangstromunits.
Iwouldliketoacknowledgethecontributionsofthosechemistscitedandthankedby ProfessorMarchinthefirstfoureditions,andthoseIthankedinthefifth,sixth,andseventh editions.Thisbookwouldnotbepossiblewithouttheircontributions.Ithankthemany peoplewhohavecontributedcommentsorhavepointedouterrorsineditions5–7thatwere invaluabletoputtingtogetherthisedition.IthankWarrenHehreandSeanOhlingerof Wavefunction,Inc.,Irvine,CA(www.wavefun.com)forprovidingSpartan10Macintosh (v.1.0.1),allowingtheincorporationofSpartanmodelsforselectedmoleculesandintermediates.AllstructuresandlinedrawingsinthisbookweredoneusingChemDraw® Professional15.1.0.144(2348350),graciouslyprovidedbyPerkinElmerCorporation,Waltham, MA.
SpecialthanksareduetotheIntersciencedivisionofJohnWiley&SonsandtoStefanie VolkandtoJonathanRose,andalsotoKatrinaMacedaatWileyfortheirfineworkas editorsinturningthemanuscriptintothefinishedbook.IalsothankTimJacksonforan excellentjobofcopyeditingthemanuscript.
Withgratitude,IacknowledgetheworkofthelateJerryMarch,uponwhoseworkallthe editionsIhaveauthoredisbuilt,althoughupdatesandchangeshavebeenmade,beginning withthefifthedition,However,Jerryisresponsiblefortheconceptandfundamentalorganizationofthisbookandhecarrieditthroughfourverysuccessfuleditions.IusedJerry’s bookasastudentanditisanhonortocontinuethistradition.
Iencouragethosewhoreadandusetheeighteditiontocontactmedirectlywithcommentsanderrorsandwithpublicationsthatmightbeappropriateforfutureeditions.Ihope thatthisneweditionwilldojusticetothetraditionthatProfessorMarchbegannearly 60yearsago.
Myemailaddressis: michael.smith@uconn.edu
Finally,IwanttothankmywifeSarahforherpatienceandunderstandingduringthe preparationofthismanuscript.IalsothankmysonSteven.Withoutthem,thisworkwould nothavebeenpossible.
MichaelB.Smith ProfessorEmeritus
October,2018
COMMONABBREVIATIONS
Notethatother,lesscommon,abbreviationsareexplainedinthetextwhenthetermisused.
1° primary
2° secondary
3° tertiary
3Dthree-dimensional
Acacetyl
acacligandacetylacetonate
AIBN azo-bis-isobutyronitrile
Amberlystanion-exchangeresin
aq.aqueous axaxial
BDEbonddissociationenergy
BERborohydrideexchangeresin
BINAP(2R,3S)-2,2′ -bis-(diphenylphosphino)1,1′-binaphthyl
BINOL1,1′-bi(2-binaphthol)
BMSboranemethylsulfide
9-BBN9-borabicyclo[3.3.1]nonane
Bnbenzyl
CH2 Ph
Boc tert-butoxycarbonyl CO2 -t-Bu
9-borabicyclo[3.3.1]nonylboryl
B
Bpy(Bipy)2,2′-bipyridyl
Bromamine-T N-bromo-4-methylbenzenesulfonamide, sodiumsalt
Bsbrosylate O-(4-bromophenyl)sulfonate
BSAbis(trimethylsilyl)acetamide
Bu n-butyl
Bzbenzoyl
°CtemperatureindegreesCelsius
CH2 CH2 CH2 CH3
CANcericammoniumnitrate(NH4 )2 Ce(NO3 )6 catcatalytic
Cbzcarbobenzyloxy CO2 CH2 Ph
CDcirculardichroism
ChapChapter(s)
Chirald(2S,3R)-(+)-4-dimethylamino-1,2diphenyl-3-methylbutan-2-ol
Chloramine-T N-chloro-4-methylbenzenesulfonamide, sodiumsalt
