Chemistry52

Chapter26

REVIEWOFISOMERS
Isomerismisthephenomenonoftwoormorecompoundshavingthesame numberandkindofatoms. In structuralisomers,thedifferencebetweenisomersisduetodifferentstructural arrangementsoftheatomsthatformthemolecules. Example: CH3CH2CH2CH3 Butane CH3 CH3CHCH3 Isobutane

In stereoisomerism,theisomershavethesamestructuralformula,butdifferin spatialarrangementofatoms. Thesetypesofisomersarecalledstereoisomers. Therearetwo typesofstereoisomers: 1. cistransisomers(geometricisomers) 2. Opticalisomers Opticalisomershavetheabilitytorotateplanepolarizedlight. Planepolarizedlightislightthatisvibratingonlyinoneplane. Ordinary(unpolarized)lightconsistsofelectromagneticwavesvibratinginall directions(planes)perpendiculartothedirectioninwhichitistraveling.

Unpolarizedlightis polarizedbypassing throughafilter

Polarizedlightis rotated bypassing through anoptically activesolution

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Chapter26

OPTICALACITVITY
Manynaturallyoccurringsubstancesareabletorotatetheplaneofpolarizedlight. Thesesubstancesarecalledopticallyactive. Whenplanepolarizedlightpassesthroughanopticallyactivesubstance,theplane ofpolarizedlightisrotated. Theextentofrotationoflightismeasuredasspecificrotation[a]andisan importantpropertyofsubstances.

SpecificRotationofSomeOrganicMolecules Compound PenicillinV Sucrose Camphor [a] D +233 +66.47 +44.26 Compound Cholesterol Morphine Aceticacid [a] D -31.5 -132 0

Inadditiontodeterminingtheextentofrotation,thedirectionofrotationcanalso bemeasured. Fromthevantagepointoftheobserver,therotationcanoccur: Clockwise(Right) Counterclockwise(Left) dextrarotatory(D) levorotatory(L) (+) ()

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Chapter26

CHIRALMOLECULES
Thetetrahedralarrangementofsinglebondsaroundacarbonatom makes asymmetry(lackofsymmetry)possibleinorganicmolecules. An asymmetric objectthatisnotsuperimposableonitsmirrorimageandiscalled chiral. Therightandlefthandsaremirrorimagesofoneanotherthatarenotsuper imposableandarethereforechiral.

A symmetric objectthathasasuperimposablemirrorimageiscalledachiral.Many commonobjectssuchasshoesandscissorsarechiral,whileaglassandsoccerball areexamplesofachiralobjects.

Chiralobjects

Achiralobjects

Acarbonatomthatpossessesfourdifferentfunctionalgroupsiscalledachiral carbonandformsnonsuperimposablemirrorimages.

Chiral

Achiral

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Chapter26

CHIRALMOLECULES
Examples: 1. Identifyeachofthefollowingstructuresaschiralorachiral.Ifchiral,indicatethe chiralcarbon.

a)

b)

2. Identifyallthechiralcarbonsineachofthefollowingmolecules:

a)

b)

H C 3 H O H C 3

Cl CH 3

OH H O

c)
H O

NH 2

d)

3. Labelthe4chiralcarbonsinamoxicillin,anantibioticinthefamilyofpenicillins.

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Chapter26

FISHERPROJECTIONS
ChemistsuseFisherprojectionstoshowthebondstoachiralatom. Inthesediagrams,thebondstothechiralatomaredrawnasintersectinglines,with thechiral carbonbeingatthecenteroftheintersectinglines. Thehorizontallinesrepresentthebondsthatcomeforwardinthethreedimensional structure (boldwedges),andtheverticallinesrepresentthebondsthatthatpointaway (dashlines).

Fisherprojections

Fisherprojectionscanalsobewrittenforlargercompoundsthathavetwoormore chiralcarbons.Forexample,thetwomirrorimagesshownbelowaredifferent. Eachchiralcarbonisbondedtofourdifferentgroups.

CH3 H Br CH3 Br H

CH3 BrH H CH3 Br

NotethatwhendrawingFisherprojectionsformirrorimages,thepositionofthe substituentsonthehorizontallinearereversedwhilethegroupsonthevertical linesareleftunchanged.

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Chapter26

FISHERPROJECTIONS
Similarlythetwoisomersofthecarbohydrateerythrosecanbedrawnasshown below.Notethateachmoleculehastwochiralcarbons.

Lerythrose

Derythrose

Byconvention,Fisherprojectionsarewrittenwiththemosthighlyoxidizedcarbon (carbonyl)writtenontop.TheLisomerisassignedtothelefthandedstereoisomer (with OHontheleftsideofthechiralcarbon),andDisomerisassignedtothe righthandedstereoisomer(with OHontherightsideofthechiralcarbon). Examples: DetermineifeachFisherprojectionshownbelowisachiralcompound.Ifso,identifyitas theDorLisomer,anddrawthemirrorimage.

1)

2)

3)

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Chapter26

ENANTIOMERS
Chiralmoleculesthatarenonsuperimposablemirrorimagesofeachotherare stereoisomersandarecalledenantiomers. Enantiomersarerelatedtooneanother asarighthandisrelatedtoalefthand.

Enantiomersoflacticacid

Enantiomerspossesssimilarchemicalandphysicalproperties(exceptforrotationof light). Theyrotateplanepolarizedlighttothesamedegreebutindifferentdirection. Enantiomerspossessdifferentbiochemicalproperties. Forexample: (+)Glucose(bloodsugar)isusedformetabolicenergywhereas ()glucoseisnot. (+)Lacticacidisproducedbyreactionsoccurringinmuscletissue,and ()lacticacidisproducedbythelacticacidbacteriainthesouringofmilk. Incompoundswithonlyonechiralcarbon,therelationshipbetweenenantiomersissuch thatifwechangethepositionofanytwogroupsattachedtoachiralcarbon,weobtain the structureofitsenantiomer(IsomersIandII). Ifwemakeasecondchange,thestructure of theoriginalisomerisobtained(IsomersIandIII). CH3 COOH COOH

changepositionof changepositionof HOH HOH HOH CH andCOOH HandOH

3

COOH IsomerI

CH3 IsomerII

CH3 IsomerIII

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Chapter26

ENANTIOMERS
WhenevaluatingdifferentFisherprojections, 1. Comparethetwostructures. 2. Makesuccessivechangesuntiltheformulasareidentical. 3. Ifanoddnumberofchangesaremade,thetwooriginalformulasareenantiomers. Ifanevennumberofchangesaremade,thetwooriginalformulasareidentical. Forexample:

(X)

(Y)

Arethesestructuresenantiomersorthesame?

interchange CH 3andCl

interchange CH 3andH

(Y)

(X)

SincetwochangesweremadetoconvertYintoX,thetwostructuresarethesame. Examples: 1. Determineifthestructuresshownbelowareenantiomersoridentical.

(A)

(B)

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Chapter26

RACEMICMIXTURES
Amixturecontainingequalamountsofapairofenantiomersisknownasa racemicmixture. Suchamixtureisopticallyinactiveandshowsnorotationofpolarizedlight. Eachenantiomerrotatestheplaneofpolarizedlightbythesameamount,butin oppositedirections.Thus,therotationbyeachisomeriscanceled. Manypharmaceuticalcompoundsarepreparedasracemicmixtures,sinceorganic synthesisreactionareoftennotstereospecific.Unfortunately,oftenonlyone enantiomerofthesemixtureshasbiologicalactivitybecausemanybiological moleculesarestereospecific. Furthermore,theinactiveenantiomermaycauseadverseaffects.Themost famousexampleofsucheffectistheracemicmixtureofthedrugthalidomide. Whileoneisomeriseffectiveatsuppressingimmuneresponses,theotherisomer causesbirthdefects.

Thalidomide

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Chapter26

DIASTEREOMERS&MESOCOMPOUNDS
Thenumberofstereoisomersincreasesasthenumberof chiralatomsinamolecule increases. Themaximumnumberofstereoisomersforagivencompoundisgivenby n theformula2 ,wherenisthenumberofchiralcarbonsinamolecule.
n 2 = Maximumnumberofstereoisomersforagivenchiralcompound. n=Numberofchiralcarbonatomsinamolecule.

Asanexample,2bromo3chlorobutanehas2chiralcarbonsandthereforefour possiblestereoisomers(structuresIIVshownbelow). CH3 H BrBr CH3 H H CH3 H Cl CH3 CH3 Br H CH3 BrH HCl CH3

HClCl CH3 (I) enantiomers

(II)(III)(IV) enantiomers

NotethatisomesIandIIareenantiomersandisomersIIIandIVarealso enantiomers. Allfourcompoundsareopticallyactive,howeverpropertiesofI andIIdifferfrompropertiesofIIIandIV,becausetheyarenotmirrorimagesof each another. Stereoisomersthatarenotenantiomers(mirrorimagesofeachother)arecalled diastereomers.

Examples: 1. Howmanystereoisomerscanexistforthecompoundshownbelow? Drawtheir structuresandlabelanypairsofenantiomersanddiastereomers. CH3 H H Br Br CH2CH3

10

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Chapter26

DIASTEREOMERS&MESOCOMPOUNDS
Tartaricacidhastwochiralcarbonsandcanthereforehavefourstereoisomersshown below. COOH HO H H H COOH OH H COOH (B) H H COOH OH OH COOH (C) HO HO COOH H H COOH (D)

OH HO COOH (A)

IsomersAandBarenonsuperimposablemirrorimages,andaretherefore enantiomers. CloseexaminationofisomersCandDindicatesthattheyare superimposable,andthereforearethesamecompound. Stereoisomersthatcontainchiralcarbonsandaresuperimposable ontheirmirror imagesarecalledmesocomounds. Duetotheplaneofsymmetryofthesemolecules, therotation oflightinonedirectionbyhalfof themoleculeiscancelledbyrotationin theoppositedirectionbytheotherhalfofthemolecule. Therefore,allmeso compoundsareopticallyinactive. COOH H H OH OH COOH Examples: 1. Howmanystereoisomerscanexistforthecompoundshownbelow? Drawtheir structuresandlabelanypairsofenantiomersandmesocompounds. CH2Br Cl H H Cl CH2Br Planeofsymmetry

11

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Chapter26

SUMMARYOFISOMERISM

different structures

Structural Isomers notinterconvertible bybondrotation GeometricIsomers (cis/trans)

Isomers containchiralcarbon nonsuperimposable mirror image Enantiomers

same structures

Stereoisomers

containchiralcarbon superimposable mirrorimage

Diastereomers

12