StereoisomerismandChiralityChapter3第1頁/共43頁第一頁，共44頁。IsomersIsomers:differentcompoundswiththesamemolecularformulaConstitutionalisomers:isomerswithadifferentconnectivityStereoisomers:

isomerswiththesameconnectivitybutadifferentorientationoftheiratomsinspace第2頁/共43頁第二頁，共44頁。ChiralityChiral:fromtheGreek,cheir,handanobjectthatisnotsuperposableonitsmirrorimageAchiral:anobjectthatlackschirality;onethatlackshandednessanachiralobjecthasatleastoneelementofsymmetryplaneofsymmetry:

animaginaryplanepassingthroughanobjectdividingitsothatonehalfisthemirrorimageoftheotherhalfcenterofsymmetry:apointsosituatedthatidenticalcomponentsarelocatedonoppositesidesandequidistantfromthatpointalongtheaxispassingthroughit第3頁/共43頁第三頁，共44頁。ElementsofSymmetrySymmetryinobjects第4頁/共43頁第四頁，共44頁。ElementsofSymmetryPlaneofsymmetry(cont’d)第5頁/共43頁第五頁，共44頁。ChiralCenterThemostcommon(butnottheonly)causeofchiralityinorganicmoleculesisatetrahedralatom,mostcommonlycarbon,bondedtofourdifferentgroupsAcarbonwithfourdifferentgroupsbondedtoitiscalledachiralcenterallchiralcentersarestereocenters,butnotallstereocentersarechiralcenters(seeFigure3.5)Enantiomers:stereoisomersthatarenonsuperposablemirrorimagesreferstotherelationshipbetweenpairsofobjects第6頁/共43頁第六頁，共44頁。Enantiomers2-Butanolhasonechiralcenterherearefourdifferentrepresentationsforoneenantiomerusing(4)asamodel,herearetwodifferentrepresentationsfortheenantiomerof(4)第7頁/共43頁第七頁，共44頁。EnantiomersTheenantiomersoflacticaciddrawnintwodifferentrepresentations第8頁/共43頁第八頁，共44頁。Enantiomers2-Chlorobutane第9頁/共43頁第九頁，共44頁。Enantiomers3-Chlorocyclohexene第10頁/共43頁第十頁，共44頁。EnantiomersAnitrogenchiralcenter第11頁/共43頁第十一頁，共44頁。R,SConventionPriorityrules1.Eachatombondedtothechiralcenterisassignedaprioritybasedonatomicnumber;thehighertheatomicnumber,thehigherthepriority2.Ifprioritycannotbeassignedpertheatomsbondedtothechiralcenter,looktothenextsetofatoms;priorityisassignedatthefirstpointofdifference第12頁/共43頁第十二頁，共44頁。R,SConvention3.Atomsparticipatinginadoubleortriplebondareconsideredtobebondedtoanequivalentnumberofsimilaratomsbysinglebonds第13頁/共43頁第十三頁，共44頁。NamingChiralCenters1.Locatethechiralcenter,identifyitsfoursubstituents,andassignpriorityfrom1(highest)to4(lowest)toeachsubstituent2.Orientthemoleculesothatthegroupoflowestpriority(4)isdirectedawayfromyou3.Readthethreegroupsprojectingtowardyouinorderfromhighest(1)tolowestpriority(3)4.Ifthegroupsarereadclockwise,theconfigurationisR;iftheyarereadcounterclockwise,theconfigurationisS

(S)-2-Chlorobutane第14頁/共43頁第十四頁，共44頁。NamingChiralCenters(R)-3-Chlorocyclohexene(R)-Mevalonicacid第15頁/共43頁第十五頁，共44頁。Enantiomers&DiastereomersForamoleculewith1chiralcenter,21=2stereoisomersarepossibleForamoleculewith2chiralcenters,amaximumof22=4stereoisomersarepossibleForamoleculewithnchiralcenters,amaximumof2n

stereoisomersarepossible第16頁/共43頁第十六頁，共44頁。Enantiomers&Diastereomers2,3,4-Trihydroxybutanaltwochiralcenters22=4stereoisomersexist;twopairsofenantiomersDiastereomers:stereoisomersthatarenotmirrorimagesreferstotherelationshipamongtwoormoreobjects第17頁/共43頁第十七頁，共44頁。Enantiomers&Diastereomers2,3-Dihydroxybutanedioicacid(tartaricacid)twochiralcenters;2n=4,butonlythreestereoisomersexistMesocompound:

anachiralcompoundpossessingtwoormorechiralcentersthatalsohaschiralisomers第18頁/共43頁第十八頁，共44頁。Enantiomers&Diastereomers2-Methylcyclopentanol第19頁/共43頁第十九頁，共44頁。Enantiomers&Diastereomers1,2-CyclopentanediolHHOHHOHHOHHOHHOOHHOHHHHOcis-1,2-Cyclopentanediol(amesocompound)trans-1,2-Cyclopentanediol(apairofenantiomers)diastereomers第20頁/共43頁第二十頁，共44頁。Enantiomers&Diastereomerscis-3-Methylcyclohexanol第21頁/共43頁第二十一頁，共44頁。Enantiomers&Diastereomerstrans-3-Methylcyclohexanol第22頁/共43頁第二十二頁，共44頁。Isomers第23頁/共43頁第二十三頁，共44頁。PropertiesofStereoisomersEnantiomershaveidenticalphysicalandchemicalpropertiesinachiralenvironmentsDiastereomersaredifferentcompoundsandhavedifferentphysicalandchemicalpropertiesmesotartaricacid,forexample,hasdifferentphysicalandchemicalpropertiesfromitsenantiomers(seeTable3.1)第24頁/共43頁第二十四頁，共44頁。Plane-PolarizedLightOrdinarylight:

lightvibratinginallplanesperpendiculartoitsdirectionofpropagationPlane-polarizedlight:

lightvibratingonlyinparallelplanesOpticallyactive:referstoacompoundthatrotatestheplaneofplane-polarizedlight第25頁/共43頁第二十五頁，共44頁。Plane-PolarizedLightplane-polarizedlightisthevectorsumofleftandrightcircularlypolarizedlightcircularlypolarizedlightreactsonewaywithanRchiralcenter,andtheoppositewaywithitsenantiomertheresultofinteractionofplane-polarizedlightwithachiralcompoundisrotationoftheplaneofpolarization第26頁/共43頁第二十六頁，共44頁。Plane-PolarizedLightPolarimeter:

adeviceformeasuringtheextentofrotationofplane-polarizedlight第27頁/共43頁第二十七頁，共44頁。OpticalActivityobservedrotation:

thenumberofdegrees,,throughwhichacompoundrotatestheplaneofpolarizedlightdextrorotatory(+):

referstoacompoundthatrotatestheplaneofpolarizedlighttotherightlevorotatory(-):

referstoacompoundthatrotatesoftheplaneofpolarizedlighttotheleftspecificrotation:

observedrotationwhenapuresampleisplacedinatube1.0dminlengthandconcentrationing/mL(density);forasolution,concentrationisexpresseding/100mL第28頁/共43頁第二十八頁，共44頁。OpticalPurityOpticalpurity:awayofdescribingthecompositionofamixtureofenantiomersEnantiomericexcess:thedifferencebetweenthepercentageoftwoenantiomersinamixtureopticalpurityisnumericallyequaltoenantiomericexcess,butisexperimentallydetermined第29頁/共43頁第二十九頁，共44頁。EnantiomericExcess

Example:

acommercialsynthesisofnaproxen,anonsteroidalanti-inflammatorydrug(NSAID),givestheSenantiomerin97%ee CalculatethepercentagesoftheRandSenantiomersinthismixture第30頁/共43頁第三十頁，共44頁。ResolutionRacemicmixture:

anequimolarmixtureoftwoenantiomersbecausearacemicmixturecontainsequalnumbersofdextrorotatoryandlevorotatorymolecules,itsspecificrotationiszeroResolution:

theseparationofaracemicmixtureintoitsenantiomers第31頁/共43頁第三十一頁，共44頁。ResolutionOnemeansofresolutionistoconvertthepairofenantiomersintotwodiastereomersdiastereomersaredifferentcompoundsandhavedifferentphysicalpropertiesAcommonreactionforchemicalresolutionissaltformationafterseparationofthediastereomers,theenantiomericallypureacidsarerecovered第32頁/共43頁第三十二頁，共44頁。Resolutionracemicacidscanberesolvedusingcommerciallyavailablechiralbasessuchas1-phenylethanamineracemicbasescanberesolvedusingchiralacidssuchas第33頁/共43頁第三十三頁，共44頁。第34頁/共43頁第三十四頁，共44頁。ResolutionEnzymesasresolvingagents第35頁/共43頁第三十五頁，共44頁。AminoAcidsthe20mostcommonaminoacidshaveacentralcarbon,calledana-carbon,bondedtoanNH2groupandaCOOHgroupin19ofthe20,thea-carbonisachiralcenter18ofthe19a-carbonshavetheRconfiguration,onehastheSconfigurationintheD,Lsystem,allhavetheLconfigurationatneutralpH,anaminoacidexistsasaninternalsaltinthisstructuralformula,thesymbolR=asidechain第36頁/共43頁第三十六頁，共44頁。Proteinsproteinsarelongchainsofaminoacidscovalentlybondedbyamidebondsformedbetweenthecarboxylgroupofoneaminoacidandtheaminogroupofanotheraminoacid第37頁/共43頁第三十七頁，共44頁。ChiralityintheBiologicalWorldExceptforinorganicsaltsandafewlow-molecular-weightorganicsubstances,themoleculesoflivingsystemsarechiralAlthoughthesemoleculescanexistasanumberofstereoisomers,generallyonlyoneisproducedandusedinagivenbiologicalsystemIt’sachiralworld!第38頁/共43頁第三十八頁，共44頁。ChiralityintheBiologicalWorldConsiderchymotrypsin,aprotein-digestingenzymeinthedigestivesystemofanimalschymotrypsincontains251chiralcentersthemaximu