Optical isomerism

Pharmaceutical organic chemistry 3 B.Pharm IV SEM

1. UNIT 1

2. ISOMERISM
❖Organiccompoundswhichhaveidenticalmolecular
formulabutdifferentinmolecularstructures,physical
andchemicalpropertiesordifferentinspatial
arrangementarecalledisomersandthisphenomenonis
knownasIsomerism.

3. Isomerism
Structural/
constitutional
isomerism
Stereoisomerism
Positional
Chain
Functional
Meta isomerism
Tautomerism
Conformational Configurational

4. ❖Ithassamemolecularformulabutdifferentmolecularstructure.
❖Furtherclassifiedaschain,positional,functional,metamerism,tautomerismand
ringchainisomerism.
1.Chainisomerism:
❑Identicalmolecularformulabutdifferentarrangementofamolecularcarbon
skeleton.
❑eg.ButaneM.F:C4H10
n-butane and isobutane

5. 2.Positionalisomerism:
❑Identicalcarbonskeletonandidenticalfunctionalgroupsbutpositionoffunctionalgroups
aredifferentinthecarbonchain.
❑eg.ButanolM.F:C4H11O
Butan-1-olandButan-2-ol
3.Funcionalisomerism:
❑Identicalmolecularformulabutdifferentfunctionalgroups.
❑eg.AlcoholandetherM.F:C2H6O
Ethanolanddimethylether

6. 4.Metamerism:
❑Identicalmolecularformulabutdifferentalkylgroupsoneithersideoffunctionalgroups.
❑eg.EtherM.F:C4H10O
Methylpropyletheranddiethylether
5.Tautomerism:
❑Identicalmolecularformulabutdifferentpositionofhydrogenatom.
❑eg.KetoneandenolM.F:C3H6O
AcetoneandProp-1-en-2-ol

7. 6.Ringchainisomerism:
❑Identicalmolecularformulabutpossessingopenchainandcyclic
structures.
❑eg.AlkeneandcycloalkaneM.F:C3H6
Prop-1-eneandCyclopropane

8. ➢Stereochemistryisthestudyofthree-dimensionalstructureofmolecules.
➢Stereoisomerism(alsoknownasspatialisomerism)hasidenticalmolecular
formulaandidenticalmolecularstructurebutdifferentinspatialarrangementof
atoms.(threedimensionalstructure).

9. Stereoisomerism
Configurational
Optical
isomerism
Enantiomerism
Diastereoisomerism
Conformational
Geometric
isomerism

10. •Stereoisomersthatareproducedbyrotationaboutsingle
bondandareoftenrapidlyinterconvertedatroom
temperature.
•Eg:

11. •Stereoisomersthatdonotreadilyinterconvertatroom
temperatureandcanbeseparated.
•DifferentspatialformsarisesoutofrotationaboutC=C.

12. ✓Thecompoundswhichhavesimilarchemicaland
physicalpropertiesbutdifferonlyintheiroptical
activityareknownasopticalisomersandphenomenon
asopticalisomerism.
OPTICALACTIVITY:
✓Itisthecapabilityofamoleculetorotatetheplane
polarizedlighteithertowardsleftortowardsright.
✓Compoundswhichcanrotateplanepolarizedlightis
knownasopticallyactive.
✓Compoundswhichcannotrotateplanepolarizedlight
isknownasopticallyinactive.
+ and –Lactic acid

13. •Opticalactivityismeasuredusing
aninstrumentcalledPolarimeter.
•Apolarimeterallowspolarized
lighttotravelthroughasampletube
containinganorganiccompoundand
permitsmeasurementofthedegree
towhichthelightisrotated.

14. •Plane-polarizedlightarisesfrompassingordinarylightthrougha
polarizer.

15. ➢Asimplepolarimeterconsistsofa
i.Lightsource-produceslightvibratinginalldirections
ii.Polarizinglens-filteronlyallowsthroughlightvibratinginonedirection
iii.Sampletube-Planepolarisedlightpassesthroughsample
iv.Ifsubstanceisopticallyactiveitrotatestheplanepolarisedlight
v.Analysinglens-filteristurnedsothatlightreachesamaximum
vi.Directionofrotationismeasuredcomingtowardstheobserver.

16. •Withachiralcompounds,thelightthatexitsthesampletuberemains
unchanged.Acompoundthatdoesnotchangetheplaneofpolarized
lightissaidtobeopticallyinactive.
•Withchiralcompounds,theplaneofthepolarizedlightisrotated
throughanangleα.Theangleαismeasuredindegrees(°)andis
calledtheobservedrotation.Acompoundthatrotatespolarizedlight
issaidtobeopticallyactive.

17. Opticalrotation:
•Therotationofplanepolarizedlightismeasuredasangulardegreeandexpressedasobserved
rotation(α).
Specificrotation:
•The angle of rotation when plane polarized light is passed through 1 decimeter cell of the
solution having concentration of 1 gram per milliliter.
where α = observed rotation
l = path length of cell (dm) t = temperature
c= concentration of solution (g/ml) λ = wavelength of light
•Specific Rotation depends on the nature of substance, wavelength of light used,
concentration of the solution, thickness of the layer, nature of the solvent and temperature
at which experiment is conducted.

18. Dextrorotatory (+):
•Anopticallyactivecompoundthatrotatesplanepolarizedlight
inaclockwisedirectionortowardsright.
•Indicatedby(+)or(d)
Levorotatory(-):
•Anopticallyactivecompoundthatrotatesplanepolarizedlight
inaanticlockwisedirectionortowardsleft.
•Indicatedby(-)or(l)
•Theangleofrotationofplanepolarizedlightbyanoptically
activesubstanceisproportionaltothenumberofatomsinthe
pathofthelight.

19. •Enantiomersare any pair of stereoisomers that are non-superimposable mirror images
of each other.
•Enantiomers are related to each other like a right hand is related to a left hand.
•Enantiomers are said to be Chiral.

20. Eg: Alanine Lactic acid

21. Tartaric acid Glucose

22. ❖Enantiomershaveidenticalphysicalproperties(bp,mp,density,solubilityand
refractiveindex)butthereisadifferenceindirectionofrotationofplanepolarized
light.
❖Theyhaveidenticalchemicalpropertiesexceptinchemicalreactionswithother
opticallyactivecompounds.

23. ❖Theyhavedifferentbiologicalproperties.
Eg.Thalidomide
❖Whenequalquantitiesofenantiomersaremixedanopticallyinactivecompound
racemicmixtureisformed.

24. •Stereoisomerswhicharenotmirrorimagesofoneanotherand
arenonsuperimposablearetermedasDiastereomers.
•Theyhavedifferentphysicalpropertieslikem.p,b.p,solubility,
densityandrefractiveindex,etc.
•Soitcanbeseparatedeasilythroughconventionalmethodssuchas
distillation,recrystallisationandchromatographyetc.,
•Diastereomershavedifferentspecificrotationbuttheymayhave
sameoroppositesignofrotation.

25. Eg:d-tartaricacidandmesotartaricacid
l-tartaricacidandmesotartaricacid

26. Eg:Pentane-2,3-diol

27. ENANTIOMERS DIASTEREOMERS
Mirror images of each other Not mirror images
Non superimposable images of each
pair
Non superimposable image of different
stereoisomers
Identical physical and chemical
properties
Different physical properties and
similar chemical properties
Noteasy to separate Easy to separate by physical methods
Oneor more stereo centres Twoor more than two stereo centres

28. ➢Amesocompoundisamoleculewithmultiple
stereocenterswhichissuperimposableonitsmirror
image.
➢Mesocompoundsareachiralcompoundsthathas
multiplechiralcenters.
➢Ithasaninternalsymmetryplanethatdividesthe
compoundinhalf.
➢Internalplane(planeofsymmetry)thatsplitsthe
compoundintotwosymmetricalsides,the
stereochemistryofbothleft(-)andrightside(+)
shouldbeoppositetoeachotherwhichbalancedtotal
internalrotation.
➢Therefore,mesocompoundsbecomesoptically
inactive.

29. •Eg: 1,2-dichloroethane-1,2-diol

30. •Symmetryisdefinedasabalancedsimilaritythatisfoundintwohalves
ofanobject.
•Itmeansone-halfisthemirrorimageoftheotherhalfandifitisnot
similarthenknownasAsymmetry.
•Elementsofsymmetryplayaimportantroleinidentificationofoptically
activecompounds.
•Foramoleculetobeopticallyactive,itshouldbedevoidofthefollowing
threeelementsofsymmetry:
1.Planeofsymmetry-mirrorplane
2.Centreofsymmetry-inversioncentre
3.AlternatingAxisofsymmetry-improperrotationofaxis

31. ❖Aplaneofsymmetryisanimaginaryplanethatpassesthrougha
moleculesuchthatatomsorgroupsofatomsononesideofplaneforma
mirrorimageofthoseonotherside.
❖Itisparticularlyusefulifthemoleculecontainstwoormorechiralcentres.

32. ❖Eg:

33. ❖Acentreofsymmetryisdefinedasanimaginarypointinamoleculefromwhich
linesdrawnonoppositesidesatequaldistance,meetexactlysimilargroupsoratoms
inthemolecules.
❖Centreofsymmetryispossiblypresentineven-memberedringsystems.

34. ❖Eg: 1,4-dichloro-2,5-dibromobenzene

35. ❖Amoleculeissaidtopossessann-foldalternatingaxissymmetry,ifon
rotatingthroughanangleof360°aboutthisaxisandfollowedbyareflectionof
theresultingmoleculeinaplaneperpendiculartotheaxis,thenthemirror
imageisexactlyidenticaltooriginalmolecule.

36. ❖Eg:Animaginarymolecule1,2,3,4-tetramethylcyclobutane.
❖AandCaresimilarcompoundsandthusitcontainsalternatingaxisofsymmetry.

37. Chiral and achiral molecules
Chiralcentre:
➢Achiralcentreisdefinedasanatominamolecule
whichisbondedtofourdifferentatomsorgroups.
➢i.echiralcentreisatetrahedralatom.
Otherterms:
➢Stereogeniccentre
➢Assymetriccentre
➢Stereocentre

38. Chiral and achiral molecules
•Althougheverythinghasamirrorimage,mirrorimagesmayormay
notbesuperimposable.
•Amoleculewhichissuperimposableonitsmirrorimageissaidtobe
achiral(lackingchirality).
•Amoleculeorobjectthatisnotsuperimposableonitsmirrorimage
issaidtobechiral.
•Generally,achiralcarbonatomissp3withfourdifferent
attachments.

39. CHIRAL MOLECULES (chirality)
•Somemoleculesarelikehands.Leftandrighthandsaremirror
images,buttheyarenotidenticalornotsuperimposable.

40. CHIRAL MOLECULES
•Eg:2-butanol
•AanditsmirrorimagelabeledBarenotsuperimposable.
•Thus,2-butanolisachiralmoleculeandAandBareisomers.
•Non-superimposablemirrorimagestereoisomerslikeAandBarecalled
enantiomers.

41. ACHIRAL MOLECULES
•In general, a molecule with no chiral centre (stereogeniccenter) are
achiral.
•Achiral molecules usually contain a plane of symmetry.
•A plane of symmetry is a mirror plane that cuts a molecule in half, so
that one half of the molecule is a reflection (mirror image) of the
other half.

42. •Two identical attachments on an sp3 carbon atom eliminates the
possibility of a chiral center.