The Art of writing reasonable organic mechanism 1有机化学机理书写艺术习题参考答案第一章.docx
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TheArtofwritingreasonableorganicmechanism1有机化学机理书写艺术习题参考答案第一章
AnswersToChapter1Problems.
1.（a）BothNandOinamideshavelonepairsthatcanreactwithelectrophiles.WhentheOreactswith
anelectrophileE+,aproductisobtainedforwhichtwogoodresonancestructurescanbedrawn.Whenthe
Nreacts,onlyonegoodresonancestructurecanbedrawnfortheproduct.
EE
OOO
reactiononOreactiononN
RRRRNRNRN
ERRR
（b）EstersarelowerinenergythanketonesbecauseofresonancestabilizationfromtheOatom.Upon
additionofanucleophiletoeitheranesteroraketone,atetrahedralintermediateisobtainedforwhich
resonanceisnotnearlyasimportant,andthereforethetetrahedralproductfromtheesterisnearlythesame
energyasthetetrahedralproductfromtheketone.Asaresultitcostsmoreenergytoaddanucleophileto
anesterthanitdoestoaddonetoaketone.
（c）Exactlythesameargumentasin（b）canbeappliedtotheacidityofacylchloridesversustheacidityof
esters.NotethatClandOhavethesameelectronegativity,sothedifferenceinaciditybetweenacyl
chloridesandesterscannotbeduetoinductiveeffectsandmustbeduetoresonanceeffects.
（d）Aresonancestructurecanbedrawnfor1inwhichchargeisseparated.Normallyacharge-separated
structurewouldbeaminorcontributor,butinthiscasethetworingsaremadearomatic,soitismuchmore
importantthannormal.
（e）Thedifferencebetween3and4isthattheformeriscyclic.LossofanacidicHfromtheγCof3gives
astructureforwhichanaromaticresonancestructurecanbedrawn.Thisisnottrueof4.
1.1
1.2
H3C
H
O
O
–H+
H3CH3CO
O
O
O
（f）Bothimidazoleandpyridinearearomaticcompounds.ThelonepairoftheH-bearingNinimidazoleis
requiredtomaintainaromaticity,sotheotherN,whichhasitslonepairinansp2orbitalthatisperpen-
diculartothearomaticsystem,isthebasicone.ProtonationofthisNgivesacompoundforwhichtwo
equallygoodaromaticresonancestructurescanbedrawn.Bycontrast,protonationofpyridinegivesan
aromaticcompoundforwhichonlyonegoodresonancestructurecanbedrawn.
H
NH+
H
N
H
N
NHNHN
（g）TheC=Cπbondsofsimplehydrocarbonsareusuallynucleophilic,notelectrophilic.However,whena
nucleophileattackstheexocyclicCatomofthenonaromaticcompoundfulvene,theelectronsfromtheC=C
πbondgototheendocyclicCandmaketheringaromatic.
–NuNu
non-aromaticaromatic
（h）Thetautomerof2,4-cyclohexadienone,anonaromaticcompound,isphenol,anaromaticcompound.
+–
（i）CarbonylgroupsC=OhaveanimportantresonancecontributorC–O.Incyclopentadienone,this
resonancecontributorisantiaromatic.
[Commonerroralert:
Manycumepointshavebeenlostovertheyearswhengraduatestudentsused
cyclohexadienoneorcyclopentadienoneasastartingmaterialinasynthesisproblem!
]
（j）PhOHisconsiderablymoreacidicthanEtOH（pKa=10vs.17）becauseofresonancestabilizationof
theconjugatebaseintheformer.SislargerthanO,sotheS（p）–C（p）overlapinPhS–ismuchsmallerthan
1.3
theO（p）–C（p）overlapinPhO–.ThereducedoverlapinPhS–leadstoreducedresonancestabilization,so
thepresenceofaPhringmakeslessofadifferencefortheacidityofRSHthanitdoesfortheacidityof
ROH.
（k）AttackofanelectrophileE+onC2givesacarbocationforwhichthreegoodresonancestructurescan
bedrawn.AttackofanelectrophileE+onC3givesacarbocationforwhichonlytwogoodresonance
structurescanbedrawn.
H
2
HHHH
EEE
HHH
E+
OOOO
HHHH
HHHH
HHH
HH
E+
H
3
O
EE
OO
HHH
HHH
2.（a）
F3C
OO
Cl3C
inductiveelectron-withdrawing
effectofFisgreaterthanCl
OHOH
（b）
Ingeneral,AH+ismore
N
H2
N
H
acidicthanAH
1.4
（c）
OOOO
EtOCH3H3CCH3
Ketonesaremore
acidicthanesters
（d）
Deprotonationof5-membered
ringgivesaromaticanion;deprotonationof7-membered
ringgivesanti-aromaticanion.
（e）
TheN（sp2）lonepairderivedfromdeprotonation
NHNH2
ofpyridineisinlowerenergyorbital,hencemore
stable,thantheN（sp3）lonepairderivedfrom
deprotonationofpiperidine.
（f）
PH2NH2
Acidityincreasesasyoumovedowna
columnintheperiodictabledueto
increasingatomicsizeandhenceworse
overlapintheA–Hbond
（g）
CO2EtCO2Et
Theanionofphenylacetate
isstabilizedbyresonance
intothephenylring.
（h）
EtO2CCO2EtEtO2C
CO2Et
Anionsof1,3-dicarbonyl
compoundsarestabilized
byresonanceintotwo
carbonylgroups
1.5
（i）
OH
O2NO2N
OH
Theanionof4-nitrophenolisstabilized
byresonancedirectlyintothenitro
group.Theanionof3-nitrophenolcan't
dothis.Drawresonancestructuresto
convinceyourselfofthis.
O
–O
NO–
–O
NO
–O
（j）
O
H3COH
OMoreelectronegativeatomsaremore
acidicthanlesselectronegativeatoms
H3CNH2inthesamerowoftheperiodictable
（k）
PhPhH
CH3
C（sp）ismoreacidicthanC（sp3）,
evenwhentheanionofthelattercan
bedelocalizedintoaPhring.
（l）
OO
Theanionofthelattercannotoverlap
withtheC=Oπbond,hencecannot
delocalize,henceisnotmadeacidicby
thecarbonylgroup.
（m）
thisCatom
O
thisCatom
TheC（sp2）–Hbondontheupperatomistheplaneofthepaper,
orthogonaltotheporbitalsoftheC=Obond,sotheC=Obond
providesnoacidifyinginfluence.TheC（sp3）–Hbondsonthe
loweratomareinandoutoftheplaneofthepaper,sothereis
overlapwiththeC=Oorbitals.
3.
（a）Free-radical.（Catalyticperoxidetipsyouoff.）
1.6
（b）Metal-mediated.（Os）
（c）Polar,acidic.（Nitricacid.）
（d）Polar,basic.（Fluorideionisagoodbase.Clearlyit’snotactingasanucleophileinthisreaction.）
（e）Free-radical.（Air.）Yes,anoveralltransformationcansometimesbeachievedbymorethanone
mechanism.
（f）Pericyclic.（Electronsgoaroundincircle.Nonucleophileorelectrophile,nometal.）
（g）Polar,basic.（LDAisstrongbase;allylbromideiselectrophile.）
（h）Free-radical.（AIBNtipsyouoff.）
（i）Pericyclic.（Electronsgoaroundincircle.Nonucleophileorelectrophile,nometal.）
（j）Metal-mediated.
（k）Pericyclic.（Electronsgoaroundincircle.Nonucleophileorelectrophile,nometal.）
（l）Polar,basic.（Ethoxidebase.Goodnucleophile,goodelectrophile.）
（m）Pericyclic.（Electronsgoaroundincircle.Nonucleophileorelectrophile,nometal.）
4.（a）Themechanismisfree-radical（AIBN）.Sn7andBr6aremissingfromtheproduct,sothey’re
probablyboundtooneanotherinaby-product.Made:
C5–C3,Sn7–Br6.Broken:
C4–C3,C5–Br6.
Br
6
MeOOMe
3
5
4
2
1
CO2Me
7
Bu3SnH
cat.AIBN
MeOOMe
176
5CO2Me+Bu3SnBr
2
H4
3
（b）Ag+isagoodLewisacid,especiallywherehalidesareconcerned,sopolaracidicmechanismisa
reasonableguess,butmechanismisactuallypericyclic（bondsformingtobothC10andC13ofthefuran
andC3andC7oftheenamine）.Cl8ismissingfromtheproduct;itmustgettogetherwithAgtomake
insoluble,verystableAgCl.AnextraOappearsintheproduct;itmustcomefromH2Oduringworkup.
OneoftheH’sinH2OgoeswiththeBF4–,whiletheotherisattachedtoN1intheby-product.Made:
C3–C10,C7–C13,C2–O（water）,Ag–Cl.Broken:
N1–C2,C7–Cl8.
1.7
8
1
N
Cl
7
6
2
34
5
+
10
11
9
O
1213
AgBF4
6
5
4
9
O
13
7
2
103
O
1112
fromwater
1
NH
HBF4
8
AgCl
（c）Thismechanismisalsopericyclic.Usethecarbonyl,Me3SiO,andCH3groupsasanchorsfor
numberingtheatoms.Made:
C2–C12,C3–C11.Broken:
C2–C8.
4
5
HC
3
6
7
3
9
O
1
2
10
8
OSiMe3
1112
Δ
9
Me3SiO
7
H3C
6
8
10
4
3
11
H
5
O
2
12
1
（d）Ph3PisaLewisbase.Themechanismispolarunderbasicconditions.Made:
C1–C7,O2–C4,
O3–C6.Broken:
O3–C4.
2
O
PhCN
1
5
+
OOMe
3
4
6
7
8
CO2Me
cat.Ph3P
5
O
4
23
O
6
OMe
1
NC7
Ph
CO2Me
8
（e）ThemechanismispolarunderacidicconditionsduetothestrongacidRSO3H.Made:
C13–C6.
Broken:
C13–C8.
13
12
Me
H
Me
14
9
MeOH
8
6
10
11
5
O
7
4
3
1
Me
2
cat.RSO3H
CH2Cl2,RT
Me
14
Me
13
12
MeH
11
Me
4
8
10
3
5
67
O
O
9
2
1
（f）Themechanismispolarunderbasicconditions（NaOEt）.Twoequivalentsofcyanoacetatereactwith
eachequivalentofdibromoethane.OneoftheCO2Etgroupsfromcyanoacetateismissingintheproduct
1.8
andisreplacedbyH.TheHcancomefromEtOHorHOH,sotheCO2EtisboundtoEtOorHO.The
twoproductsdifferonlyinthelocationofaHatomandaπbond;theirnumberingisthesame.Made:
C2–C5,C2'–C6,C2'–C3,C1'–OEt.Broken:
C1'–C2',C5–Br,C6–Br.
134
EtO2CCNNaOEt,EtOH;
2
1/2BrCH2CH2Br
56
1
EtO2C
5
4
NH2
1'
23
2'3'4'EtO2COEt
CN+
6
（g）Polarunderacidicconditions.Theenzymeservestoguidethereactionpathwaytowardoneparticular
result,butthemechanismremainsfundamentallyunchangedfromasolutionphasemechanism.TheMe
groupsprovidecluesastothenumbering.Made:
C1–C6,C2–C15,C9–C14.Broken:
C15–O16.
Me
7
56
4
3
2
Me
1
MeMe
8
15
9
14
10
111213
Me
16
–
OPO3PO3
H+
enzyme
Me
5
4
3
6
H
1
2
78
Me
Me
9
Me
1
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