Chapter7

Stereochemistry7.1

MolecularChirality:

Enantiomers Amoleculeischiralifitstwomirrorimage

formsarenotsuperposableupononeanother.

Amoleculeisachiralifitstwomirrorimage

formsaresuperposable.ChiralityBrClHFBromochlorofluoromethaneischiral Itcannotbesuperposedpointforpointonitsmirrorimage.BrClHFBromochlorofluoromethaneischiralHClBrF Toshownonsuperposability,rotatethismodel180°aroundaverticalaxis.BrClHFBromochlorofluoromethaneischiralHClBrFAnotherlookareenantiomerswithrespecttoeachotherandnonsuperposablemirrorimagesare

calledenantiomersEnantiomersIsomersstereoisomersconstitutionalisomersIsomersstereoisomersconstitutionalisomersdiastereomersenantiomersChlorodifluoromethane

isachiralChlorodifluoromethane

isachiral Thetwostructuresaremirrorimages,butarenotenantiomers,becausetheycanbesuperposedoneachother.7.2

TheStereogenicCenteracarbonatomwithfour

differentgroupsattachedtoit

alsocalled:chiralcenter

asymmetriccenter

stereocenterTheStereogenicCenterwxyzCAmoleculewithasinglestereogenic

centerischiral.Bromochlorofluoromethaneisanexample.ChiralityandstereogeniccentersClFBrHCAmoleculewithasinglestereogenic

centerischiral.2-Butanolisanotherexample.ChiralityandstereogeniccentersCH3OHHCCH2CH3Examplesofmoleculeswith1stereogeniccenterCH3CCH2CH3CH2CH2CH2CH3CH3CH2CH2achiralalkaneExamplesofmoleculeswith1stereogeniccenterLinalool,anaturallyoccurringchiralalcoholOHExamplesofmoleculeswith1stereogeniccenter1,2-Epoxypropane:astereogeniccentercanbepartofaringOH2CCHCH3attachedtothestereogeniccenterare:

—H —CH3

—OCH2

—CH2OExamplesofmoleculeswith1stereogeniccenterLimonene:astereogeniccentercanbepartofaringCH3HCCH3CH2 attachedtothe

stereogeniccenterare:

—H —CH2CH2

—CH2CH=

—C=Examplesofmoleculeswith1stereogeniccenterChiralasaresultofisotopicsubstitutionCH3CDTHAmoleculewithasinglestereogeniccenter

mustbechiral.But,amoleculewithtwoormore

stereogeniccentersmaybechiral

oritmaynot(Sections7.10-7.13).7.3

SymmetryinAchiral

StructuresSymmetrytestsforachiralstructuresAnymoleculewithaplaneofsymmetry

oracenterofsymmetrymustbeachiral.Aplaneofsymmetrybisectsamoleculeintotwo

mirrorimagehalves.Chlorodifluoromethane

hasaplaneofsymmetry.PlaneofsymmetryAplaneofsymmetrybisectsamoleculeintotwo

mirrorimagehalves.Chlorodifluoromethane

hasaplaneofsymmetry.PlaneofsymmetryAplaneofsymmetrybisectsamoleculeintotwo

mirrorimagehalves.

1-Bromo-1-chloro-2-fluoroethenehasaplane

ofsymmetry.PlaneofsymmetryAplaneofsymmetrybisectsamoleculeintotwo

mirrorimagehalves.

1-Bromo-1-chloro-2-fluoroethenehasaplane

ofsymmetry.PlaneofsymmetryApointinthecenterofthe

moleculeisacenterof

symmetryifalinedrawn

fromittosomeelement,

whenextendedanequal

distanceintheopposite

direction,encountersan

identicalelement.

CenterofsymmetryApointinthecenterofthe

moleculeisacenterof

symmetryifalinedrawn

fromittoanyelement,

whenextendedanequal

distanceintheopposite

direction,encountersan

identicalelement.

Centerofsymmetry7.4

PropertiesofChiralMolecules:

OpticalActivity

Asubstanceisopticallyactiveifitrotates

theplaneofpolarizedlight.

Inorderforasubstancetoexhibitoptical

activity,itmustbechiralandoneenantiomer

mustbepresentinexcessoftheother.OpticalActivityLight haswaveproperties periodicincreaseanddecreaseinamplitudeofwaveLight opticalactivityisusuallymeasuredusinglighthavingawavelengthof589nm thisisthewavelengthoftheyellowlightfromasodiumlampandiscalledtheDlineofsodiumPolarizedlight

ordinary

(nonpolarized)

lightconsistsof

manybeams

vibratingin

differentplanes

plane-polarized

lightconsistsof

onlythosebeams

thatvibrateinthe

sameplanePolarizationoflightNicolprismPolarizationoflightNicolprismPolarizationoflightRotationofplane-polarizedlightRotationofplane-polarizedlightRotationofplane-polarizedlightaRotationofplane-polarizedlightobservedrotation(a)dependsonthenumber

ofmoleculesencounteredandisproportionalto:

pathlength(l),and

concentration(c)Specificrotationobservedrotation(a)dependsonthenumber

ofmoleculesencounteredandisproportionalto:

pathlength(l),and

concentration(c)

therefore,definespecificrotation[a]as:100aclconcentration=g/100mLlengthindecimetersSpecificrotation[a]=amixturecontainingequalquantities

ofenantiomersiscalledaracemicmixture

aracemicmixtureisopticallyinactive

(a=0)

asamplethatisopticallyinactivecanbe

eitheranachiralsubstanceoraracemic

mixtureRacemicmixtureanopticallypuresubstanceconsistsexclusively

ofasingleenantiomer

enantiomericexcess=

%oneenantiomer–%otherenantiomer

%opticalpurity=enantiomericexcessOpticalpurity7.5

Absolute

and

RelativeConfiguration

Relativeconfigurationcomparesthe

arrangementofatomsinspaceofonecompound

withthoseofanother.

Absoluteconfigurationistheprecise

arrangementofatomsinspace.

Configuration

Relativeconfigurationcomparesthe

arrangementofatomsinspaceofonecompound

withthoseofanother.

untilthe1950s,allconfigurationswererelative

Absoluteconfigurationistheprecise

arrangementofatomsinspace.

wecannowdeterminetheabsolute

configurationofalmostanycompoundConfigurationNobondsaremadeorbrokenatthestereogeniccenter

inthisexperiment.Therefore,when(+)-3-buten-2-ol

and(+)-2-butanolhavethesamesignofrotation,the

arrangementofatomsinspaceisanalogous.Thetwo

havethesamerelativeconfiguration.

CH3CHCH2CH3OHPd[a]+33.2°[a]+13.5°RelativeconfigurationCH3CHCHOHCH2

HHOHOHH2,PdHHOH2,PdHOHTwopossibilities Butintheabsenceofadditionalinformation,wecan'ttellwhichstructurecorrespondsto

(+)-3-buten-2-ol,andwhichoneto(–)-3-buten-2-ol.

HHOHOHH2,PdHHOH2,PdHOHTwopossibilities Norcanwetellwhichstructurecorrespondsto

(+)-2-butanol,andwhichoneto(–)-2-butanol.

HHOHOHH2,PdHHOH2,PdHOHAbsoluteconfigurations[a]+33.2°[a]+13.5°[a]–13.5°[a]–33.2°Notallcompoundsthathavethesamerelative

configurationhavethesamesignofrotation.Nobonds

aremadeorbrokenatthestereogeniccenterinthe

reactionshown,sotherelativepositionsoftheatoms

arethesame.Yetthesignofrotationchanges.

CH3CH2CHCH2BrCH3HBr[a]-5.8°[a]+4.0°RelativeconfigurationCH3CH2CHCH2OHCH37.6

TheCahnIngoldPrelog

R-SNotationalSystem1. needrulesforrankingsubstituentsat

stereogeniccenterinorderofdecreasing

precedence2. needconventionfororientingmoleculeso

thatorderofappearanceofsubstituents

canbecomparedwithrank

Thesystemthatisusedwasdevisedby

R.S.Cahn,SirChristopherIngold,and

V.Prelog.

Tworequirementsforasystem

forspecifyingabsoluteconfiguration1.Rankthesubstituentsatthestereogenic

centeraccordingtosamerulesusedin

E-Znotation.2.Orientthemoleculesothatlowest-ranked

substituentpointsawayfromyou.

TheCahn-Ingold-PrelogRules

(Table7.1)4321Example4321Orderofdecreasingrank:

4>3>2>11.Rankthesubstituentsatthestereogenic

centeraccordingtosamerulesusedin

E-Znotation.2.Orientthemoleculesothatlowest-ranked

substituentpointsawayfromyou.3.Iftheorderofdecreasingprecedencetraces

aclockwisepath,theabsoluteconfiguration

isR.Ifthepathisanticlockwise,the

configurationisS.TheCahn-Ingold-PrelogRules

(Table7.1)4321Example4321Orderofdecreasingrank:

4

?

3

?2clockwiseRanticlockwiseS(S)-2-ButanolCOHH3CHCH3CH2Enantiomersof2-butanolCHOCH3HCH2CH3(R)-2-ButanolVeryimportant!Twodifferentcompoundswith

thesamesignofrotationneednothavethesame

configuration. VerifythisstatementbydoingProblem7.7onpage269.Allfourcompoundshavepositiverotations.WhataretheirconfigurationsaccordingtotheCahn-Ingold-Prelogrules?HH3CHHStereogeniccenterinaringR—CH2C=C>—CH2CH2>

—CH3>—H7.7

FischerProjectionsPurposeofFischerprojectionsistoshowconfigurationatstereogeniccenterwithoutnecessityofdrawingwedgesanddashesorusingmodels.RulesforFischerprojections Arrangethemoleculesothathorizontalbondsatstereogeniccenterpointtowardyouandverticalbondspointawayfromyou.BrClFHRulesforFischerprojections Projectionofmoleculeonpageisacross.Whenrepresentedthiswayitisunderstoodthathorizontalbondsprojectoutward,verticalbondsareback.BrClFHRulesforFischerprojections Projectionofmoleculeonpageisacross.Whenrepresentedthiswayitisunderstoodthathorizontalbondsprojectoutward,verticalbondsareback.BrClFH7.8

PhysicalPropertiesofEnantiomersSame:

meltingpoint,boilingpoint,density,etc

Different:

propertiesthatdependonshapeofmolecule

(biological-physiologicalproperties)canbe

different

PhysicalpropertiesofenantiomersOOCH3CH3H3CH3CCH2CH2Odor(–)-Carvone

spearmintoil(+)-Carvone

carawayseedoilIbuprofenischiral,butnormallysoldas

aracemicmixture.TheSenantiomer

istheoneresponsibleforitsanalgesic

andantiinflammatoryproperties.

ChiraldrugsCH2CH(CH3)2HH3CCOCHO7.13

ChemicalReactionsThat

ProduceDiastereomersInordertoknowunderstandstereochemistryof

product,youneedtoknowtwothings:(1)stereochemistryofalkene(cisortrans;

ZorE)(2)stereochemistryofmechanism(synoranti)

StereochemistryofAdditiontoAlkenesCC+E—YCCEYBr2RSRSmeso antiadditiontotrans-2-butenegivesmesodiastereomerBromineAdditiontotrans-2-Butene

Fig.7.14(p284)Br2RRSS50%50%BromineAdditiontocis-2-Butene

Fig.7.15(p285) antiadditiontocis-2-butenegivesracemicmixtureofchiraldiastereomer+RCO3HRRSS synadditiontotrans-2-butenegivesracemicmixtureofchiraldiastereomerEpoxidationoftrans-2-Butene

Problem7.17(p285)50%50%+RSRSEpoxidationofcis-2-Butene

Problem7.17(p285) synadditiontocis-2-butenegivesmesodiastereomerRCO3Hmesooftwostereoisomersofaparticularstarting

material,eachonegivesdifferent

stereoisomericformsoftheproductrelatedtomechanism:termssuchas

synadditionandantiadditionreferto

stereospecificityStereospecificreaction.trans-2-butene

cis-2-butenetrans-2-butenecis-2-butenebrominationanti2R,3R+2S,3Sbromination

epoxidationepoxidationanti

synsynmeso

meso2R,3R+2S,3SStereospecificreactionasinglestartingmaterialcangivetwoormore

stereoisomericproducts,butgivesoneofthem

ingreateramountsthananyother+CH3HCH3H68%32%StereoselectivereactionCH3CH2HCH3HCH3HH2Pt7.14

ResolutionofEnantiomers separationofaracemicmixtureintoitstwoenantiomericformsenantiomersC(+)C(-)StrategyenantiomersC(+)C(-)2P(+)C(+)P(+)C(-)P(+)diastereomersStrategyenantiomersC(+)C(-)2P(+)C(+)P(+)C(-)P(+)diastereomersC(+)P(+)C(-)P(+)StrategyenantiomersC(+)C(-)2P(+)C(+)P(+)C(-)P(+)diastereomersC(+)P(+)C(-)P(+)P(+)P(+)C(+)C(-)Strategy7.15

StereoregularPolymersatacticisotacticsyndiota