a) WritethemechanismofFriedel-Craftsalkylationofethylbenzenetogive1,4-diethylbenzene.Showallarrowpushing.
b) Usingresonanceandinductiveeffects,explainwhyanethylgroupwilldirectasecondethylgrouptotheparapositioninFriedel-Craftsalkylation.
BrAlBr3
c) FortheFriedel-Craftsalkylationreactionshownbelow,thereisonemajorproductwhereallethylsaremeta.Explainwhythisproductispreferredandwhyitsregiochemistryissurprising.
BrAlBr3
heat for a long time
excess
Identifyanystrainspresentinthefollowingmoleculesintheexactconformationdrawn.
(5pts)TherelativeSN1solvolysisratesoftwoalkyltosylatesisshownbelow:
a)Draworbitalstoshowwhythestructureoftheadamantylringpreventstheresonancestabilizationoftheallyliccarbeniumionintermediateformedfromthesecondstructure.(3pts)a) Explainwhytherateofthesolvolysisofthesecondstructureissomuchslower.(2pts)
OTs OTs
1105
1.(22points)Let’smakemeth(anol)!a) DrawtheWalshdiagramforpyramidalCH3.Youcandrawthelinearformifithelpsyou,
butitisnotnecessary.Mixthetwohighestenergyorbitalsthathavethesamesymmetryandpopulatetheorbitalsformethylradical.(8points)
b) Drawtheoccupiedorbitalsfromparta)ontheleftsideofthediagrambelow.Considerthemixingoftheorbitalsasindicatedandfillinthediagramwiththeappropriateamountofelectrons.(14points)
c) Thecalculatedwavefunctionsforallofmethanol’soccupiedorbitalsareshownbelow.Matcheachorbitaltoitscorrectenergylevelontheabovediagrambyfillingintheappropriateletterintheboxesabove.
z x
y
Draw the CH3 orbitals here
4.(23points)Fourpartsonstereochemistry:
a) Circleanychiralmoleculesinthesetbelow(6points):
b) Labeltheindicatedgroupsashomotopic,enantiotopic,ordiastereotopic(8points):
i.
ii.
iii.
iv.
O
OHOH
O ClCl
OCl
Cl
OTsO
TsO
faces of alkene
OTsO
TsO
O
OHOH
c) Forthefollowingreactions,fillintheboxwiththeappropriateterm(enantiomers,diastereomers,samemolecule)thatdefinesthestereochemicalrelationshipbetweenthetwoindicatedmolecules(5points).
i.
ii.
iii.
H-Br H
Br
H
Br
Br
H
Br
H+ ++
O
NaO
H HO
O HH
HOH
OH
H
H+
1.
2. H3O+
OTsO
TsO NaO
HO
TsOO
TsO+
1 equiv.
d) Definethesetsofreactionsbelowasstereospecific,stereoselective,orbothstereoselectiveandstereospecific(4points).
i.
ii.
O
NaO
H HO
O HH
HOH
OH
H
H+
1.
2. H3O+
O
NaO
H H OH
OH
H
1.
2. H3O+
100%
60% 40%
H-Br H
Br
H
Br
Br
H
Br
H+ ++
5% 5% 45% 45%
5.(24points)Mannoseisadiastereomer,specificallyaC2epimer,ofglucose.Insolution,thealphaanomerofD-mannosedominatesoverthebetaform.Thisisincontrasttoglucose,wherethebetaanomerispreferred.
O
H
HO
H
HO
OH
OH
HHH
OH
O
H
HO
H
HO
OH
H
HHOH
OH
O
H
HO
H
HO
H
OH
OHHH
OH
O
H
HO
H
HO
H
H
OHHOH
OH
α-D-mannose67%
β-D-mannose33%
α-D-glucose45%
β-D-glucose55%
5.(continued)Let’sexplainwhymannosehasasmallerpreferenceforthebetaanomer(33%β)comparedtoglucose(55%β).
a) FillinthefollowingNewmanprojectionsforα-D-mannoseandβ-D-mannoselookingdownthehighlightedbondsonthepreviouspage.Theanomericcarbonshouldbeontheleft.Countthetotalnumberofgaucheinteractionsineach,keepinginmindeachgaucheinteractionwithanatomintheringcountsfortwogauche.(6points)Hint:OnceyouhavefilledinoneNewmanprojection,youshouldbeabletoquicklyconstructthenextbyonlyswitchingtwogroupsofonestereocentertocreatetheepimer.
b) DrawtheNewmanprojectionsofα-D-glucoseandβ-D-glucose.Again,youshouldbeabletoquicklyconstructthembyswitchingtwogroupsatonestereocenter.Countthetotalnumberofgaucheinteractions.(6points)
CH
O
OHCH
O
OH
CH
O
OHCH
O
OH
β-D-mannose#gauche________
α-D-glucose#gauche________ β-D-glucose#gauche________
α-D-mannose#gauche________
c) BasedontheNewmanprojectionsyouhavejustdrawn,circlethepreferredanomerofeachpairbelowandwriteintheirenergydifferences,assumingeachgaucheisworththesamevalue.(4points)α-D-mannoseorβ-D-mannose energydifference:__________kcal/molα-D-glucoseor β-D-glucose energydifference:__________kcal/mol
d) Usetheenergydifferencesfrompartc)toestimatetheratiosofthealphaandbetaanomersofbothsugarsatequilibrium.Whichsugar,mannoseorglucose,hasthehigherpreferenceforthebetaanomer(prefersthealphaanomertoalesserextent)?(5points)
α-D-mannose:β-D-mannose
α-D-glucose:β-D-glucose
e) ExperimentalevidenceshowsthatthealphaanomerofD-mannoseispreferredoverthebeta67:33.Drawtherelevantorbitalstohelpexplainwhyα-D-mannoseispreferred.CommentonhowyourdiagramaffectsanygaucheinteractionsyouidentifiedintheNewmanprojections.(3points)
8.(10points)Theeffectofvaryingthesubstituent,X,ontherate-determiningchloridedepartureintheSN1reactionofthestartingmaterialsbelowwasmeasuredusingHammettplots.
a) Fillinthemissingx-axisfortheHammettplotabove.Whichparameterdidyouchoose,σ,σ+,orσ-,andwhy?(2points)
b) Whyaretheslopesinthisplotallnegative?(2points)
c) Assigntheletterscorrespondingtothestartingmaterialstoeachofthethreelinesintheplot.Justifyyourchoiceforeachstartingmaterial.(6points)
X
O
X
O
O
XCl ClCl
A B C
log (kX')
9.(6points,2each)Describethekineticisotopeeffectsyouwouldexpecttoobserveforthefollowingreactionsusingthetermsprimary,secondary,normal,andinverse.
a)
b)
(D)H
(D)HH(D)H(D)
H(D)Br
(D)H
Br
2 HBr H(D)Br
HH
BrH(D)
13.(12pts,3each)Drawthepredominantproductforeachofthefollowingreactions.StatewhetheryouexpectthereactiontoproceedbyanSN1/E1,SN2,E2,orE1CBmechanism.
a)
b)
c)
d)
OTstBuOH (solvent)
heat
Cl NaSeH
EtOH
O
TsO
NaOEt
H
OTsH
NaOH/H2O
14.(6pts)TherateofSN2reactionswasfoundtoreversedependingonthecounterionofthenucleophileusedforthefollowingSN2reaction:
a) CirclethehalogenthatwillreactthefastestwhenthecounterionisLi+.Explainyour
choice.(3points)
Cl- Br- I-
b) Circlethehalogenthatwillreactthefastestwhenthecounterionistetrabutylammonium.Explainyourchoice.(3points)
Cl- Br- I-
BrOSOO
OH3C CH3X BrOSO
O
OX+ +
15.(10points)Inthefollowing4+2cyclization,theendoproductdominates.Let’sfigureoutwhy!
a) FillinthecorrectphasingfortheHOMOofcyclobutadieneonthefollowingdiagram(2points):
b) Treatthedienophile,methylvinylketone,asthoughitwerebutadiene.DrawthecorrectphasingfortheLUMOonthefollowingtwodiagramsthataresimplydifferentconformersofthesamedienophile(2points):
O
+
O O
endo exo
+
HOMO
LUMO
O
LUMO
O
c) Usethephasingfrompartsa)andb)tofillintheorbitaldiagramsbelowtoshowthe
reactionisindeedallowedforbothendoandexo.(4points)
d) Usetheorbitaldiagramsfrompartc)toexplainwhytheendoproductispreferredforDiels-Aldercyclization.(2points)
O
endo exo
O
16.(5points)YourTAAlexusesavarietyofdyestocreateherrainbowhair.OneofthesedyesisBrilliantBlueFCF,adyeapprovedforfood,drug,andcosmeticuse:
BrilliantBlueFCF
a) Giventhatthedyeappearsblue,usethecolorwheeltodeterminethewavelengthsof
lightitabsorbs.(2points)
b) Fromthechoicesbelow,circletheabsorptionspectrumthatbestcorrespondstothatofBrilliantBlueFCF.(1point)
ThemajorityofAlex’shairisdyedpinkusingEosinB.ThisdyeemitsviafluorescencewhenexposedtoUVradiation.
EosinB
c) Usethecolorwheelandthegivenabsorption/emissionspectraofEosinBtodetermine
whatcolorAlex’shairappearswhenexcitedusingaUVlamp.(2points)
17.(10points)Thisissimplyanarrow-pushingproblem.Startingfromtheimine,pusharrowscorrectlytomakethefollowingindole.Makesuretodrawalllonepairs,protontransfers,andrelevantarrowsandsteps.Thereisonestepthatinvolvesa[3,3]sigmatropicshiftandonestepthatinvolvesa5-exo-trigcyclization.
HN NH2H
O
H2SO4/H2O
HN
+ H2O + NH3
HN N
imine
2.(10points)a)Circlethestrongestacidforthefollowingpairsofcompoundsandbrieflyexplainyourchoice.(6pts)
b)Indicatewhichofthefollowingcompoundswouldbethestrongestacidinthegasphase.Explainyourchoice.(2pts)
c)Insolutiontheorderreverses.Brieflyexplainwhy.(2pts)
3. (6points)a) Circlethestructurethathasahigherhydrideaffinityvalue,andexplainyour
choice.(3pts)
b) CirclethesolventthatwillgivetheslowestrateofthefollowingSN2reaction,
andexplainyourchoice.(3pts)
or
11. (18points,6each)Thefollowingthreereactionsfolloweitherspecificbase,generalbase,ornocatalysis.
a. Predictwhichcorrespondstoeachmechanisticalternative.(1pt)b. Drawthetransitionstateoftherate-determiningstepforeachreactioninthe
bracketsgiven.(3pts)c. Drawthecorrespondingreactioncoordinatediagramforeachmechanistic
alternative,whereyouincludeallintermediates.(2pts)
a) Reaction1:__________________________
b)
c)
Reactioncoordinate
ΔG⁰
a) Reaction2:__________________________
b)
c)
Reactioncoordinate
ΔG⁰
a) Reaction3:__________________________
b)
c)
Reactioncoordinate
ΔG⁰
7. (12points)Thefollowingreactionshowsa1,4-additionofathioltoanenoneinbasicconditions.
a) Whattypeofcatalysisdoesthereactionaboveshow?(1pt)
b) Fortheabovemechanism,writetheratelawfortheformationof“D”using
thesteadystateapproximation.Usethelettersprovidedtowritetheratelaw.(4pts)
c) Doesthisreactionhaveanykineticdependenceon?Brieflyexplainwhy.(2pts)
d) Doesthisreactionhaveanykineticdependenceonthebase(:B)?Brieflyexplainwhy.(2pts)
e) Givenyouranswerinpart(d),andthepKaoftriethylamine,isthisreaction
goingtobefasteratpH7or12?Brieflyexplainyouranswer.(3pts)
10. (15points)Thedecompositionofaryl-substitutedacetophenonemethyl
hemiacetalwasstudiedunderbase-catalyzedconditionswithanaddedbase(A:ϴ)anditsconjugateacid(HA).
Tounderstandthetransitionstate,thefollowingBronstedplotwasgeneratedbyvaryingthepKaofHAandmeasuringtherateofdecompositionofthehemiacetalgroup.
a) Whatkindofcatalysiswillthekineticsoftheabovemechanismindicate?(2pts)Hint:theratedeterminingstepusesageneralacidafterpriorequilibriumdeprotonation.
b) DoestheBronstedplotsupportyouranswertopart(a)?(1pt)
c) Now,weteachyouthatα+β=1ingeneralcatalyzedreactions.Sogiventhis
informationandβ=0.61,what is theα-value for therds in themechanismgivenabove?(1pt)
d) For the rds, fill in the remaining corners and axes on the More O’Ferrall-
Jencksplotwiththecorrespondentspecies.(4pts)e) Approximate theplacementof the transitionstateusing theanswer thatyou
foundonpart(c)anda βLG of -0.3,labelingthispointas“E”.(1pt)
f) Starting from “E”, howwould the transition state change using a strongerbase?Labelthisnewtransitionstateas“F”.(2pts)
g) Withastrongerbase,howwouldtheextentofprotonationby itsconjugateacidchangeintherds?(2pts)
h) Witha strongerbase,howwould theextentofβLG change in the rds?Why
doesthismakesense?(2pts)
12. (9points)Thefollowingmethylationreactionproceedsthrougharadicalmechanism.Thisreactionproducestwodifferentproducts,whereBisthefavoredproduct.
a) UsingtheoneconformerofA1givenabove,drawallthreeconformersand
labelthetwonewonesasA2andA3.(5pts)
b) Circlethelowestenergyconformerinpart(a),andbrieflyexplainthetypeofstrainthatisminimizedinthisconformer.(2pts)
c) Whatisthepostulateorprinciplethatyoushouldconsiderwhenattemptingtoexplaintheproductratiosobservedinthereaction?(2pts)
6. (4points)Thefollowingrearrangementcanoccurviaradicalorcarbocationintermediatesshownbelow.
a) Proposetwoexperimentstodistinguishbetweenthesemechanisms.
