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