Nomenclature of optical isomerism

Pharmaceutical organic chemistry 3 B.pharm IV SEM

1. NOMENCLATURE OF
OPTICAL ISOMERS

2. Representation of structure of molecules
1.WedgeandDashProjection:
❑Thesearethe3Drepresentationofmolecules.
❑Theseareusedforbothchiralandachiralmolecules.
❑Thisprojectionisusedfortetrahedralstructure,inwhichtwoatoms/groups
areinplaneandothertwogroupsareinaboveorbelowplane.
Eg:Glyceraldehyde

3. Representation of structure of molecules
2.FischerProjection:
❑ItisdevelopedbyEmilFischerin1891.
❑Itisthe2Drepresentationofmolecules.
❑Inthis,allbondsaredrawnassolidlines.
❑Inthismethod,carbonchainisalwayswrittenverticallyandhorizontal
linesrepresentothergroups.
❑Belowtheplane-rightside;Aboveplane-leftside.
Eg:Glyceraldehyde

5. OPTICAL ISOMERISM
CONFIGURATION
❖Configurationmeansthearrangementofatomsorgroupsaround
theasymmetriccentre
❖Twosystemhavebeendeveloped
I.Relativeconfiguration
DandL–systemofnomenclature
II.Absoluteconfiguration
RandS–systemofnomenclature

6. D and L –SYSTEM OF NOMENCLATURE
➢Thisisoneoftheoldestandthemostcommonlyusedsystemforassigningconfigurationtoagiven
enantiomer.
➢ThiswasdevelopedbyFischerandRosanoffaround1900.
➢Fischerfirstdevelopedamethodfordrawingcarbohydratesintwo-dimensionsandaconventionwith
respecttoorientationsoastoindicatetheirthreedimensionalstructures,so-calledFischer
projections.
➢FischerandRosanoffthendevisedanotationfordesignatingtheconfigurationsofstereogenic
centres,depictedinFischerprojections,aseitherDorL.
➢ThisnomenclatureisbaseduponthecomparisonoftheFischerprojectionformulaofoneenantiomerto
whichthenameistobeassigned,withthatofastandardsubstancearbitrarilychosenforcomparison.
➢Thefollowingtwoconventionsareusedforthispurpose.
(i)HydroxyAcidorAminoAcidConvention
(ii)SugarConvention

7. (i) Hydroxy Acid or Amino Acid Convention
•AccordingtothisconventiontheprefixDandLreferstotheconfigurationof
α-hydroxyorα-aminoacids(i.e.thelowestnumberedchiralitycentre)inthe
Fischerprojectionformula.
•Iftheα-OHorα-NH2groupisontherighthandside(oftheviewer),the
prefixDisused.
•Whereasifα-OHorα-NH2groupareonthelefthandsidetheprefixLis
used.

8. Add a Slide Title -2

9. (ii) Sugar Convention
•FischerarbitrarilyassignedDandLconfigurationsto(+)and(–)-
glyceraldehyde,respectively.
•HeassignedDconfiguration(OHontheright)to(+)-glyceraldehydeandL
configuration(OHontheleft)to(–)-glyceraldehyde.

10. •TheenantiomerthatcanbepreparedfromorconvertedtoD(+)
glyceraldehydewillbelongstoD-series.
•SimilarlyanycompoundthatcanbepreparedfromorconvertedtoL(-)
glyceraldehydewillbelongstoL-series.
•NOTE:D&LareconfigurationalsymbolssotherecanbeD(+/d)&D(-/l)
compounds,similarlyL(+/d)&L(-/l)compounds.
•Eg:

11. SEQUENCE RULES
➢Sequenceruleisimportantforassignmentofconfigurationtochiralcentres.
➢ItisusedforassignmentofR&SconfigurationandE&ZPrefixes.
➢Sequencerule1:ifthefouratomsattachedtothechiralcentreareall
different,prioritydependsonatomicnumber,withtheatomofhigher
atomicnumbergettinghighestpriority.
➢Eg:
Higher atomic number –
highest priority
I> Cl> S> H

12. •If two atoms are isotopesof the same element, the atom of
higher mass number has the highest priority.
Br> C> D> H

13. Sequence rule 2:
❖Iftherelativepriorityoftwogroupscannotbedecidedby
rule1,itcanbedeterminedbyasimilarcomparisonofthe
nextatomsinthegroups.
❖Thatis,iftwoatomsattachedtothechiralcentrearethe
same,comparethesecondatoms(firstpointofdifference).
❖Eg:Insec-butylchloride,twooftheatomsattachedtothe
chiralcentrearethemselvescarbon.
❖InCH3,secondatomsareH,H,H
❖InC2H5,secondatomsareC,H,H.
❖Sincecarbonhashigheratomicnumberthanhydrogen,
C2H5hasthehighestpriority.
Cl> C2H5> CH3> H

14. Sequence rule 3:
➢Wherethereisadoubleortriplebond,bothatomsareconsideredtobe
duplicatedortriplicated.
➢Itshouldbetreatedasifitweresinglybondedtotwoorthreeofthoseatoms
respectively.
➢Eg:InGlyceraldehyde,OHgrouphashighestpriorityofallandO,O,Hof–CHOtakes
priorityovertheO,H,Hof–CH2OH.
-OH> -CHO> -CH2OH> -H
Glyceraldehyde

15. R and S –System of nomenclature
(CIP SYSTEM)
•RandSsystemwasdevisedbyR.S.Cahn,ChristopherIngoldandVladimirPrelog(CIP).
•TheCahn-Ingold-Prelogconventionisusedtoidentifytheconfigurationofeachasymmetric
carbonatompresentinastereoisomer.
•AssigningtheAbsoluteConfiguration
STEPI:UsetheCahn-Ingold-Prelogpriorityrulestoassignpriority(onethroughfour)tothe
fourgroupsonthechiralatom.
STEPII:Orientthemoleculesothatthelowestpriorityatomisintheback(awayfromyou).
Lookattheremainingthreegroupsofpriority1-3.
Iftheremainingthreegroupsarearrangedsothatthepriorities1>2>3areinaclockwisedirection,
thenassignthechiralcenterasR(“rectus”orright).
Iftheremainingthreegroupsarearranged1>2>3inaanti-clockwisemanner,thenassignthe
chiralcenterasS(“sinister”orleft).

16. R,S –SYSTEM OF NOMENCLATURE
StepI:Accordingtosequencerule(priority)
Rule1:Ifthefouratomsattachedtothechiralcentrearealldifferent,priority
dependsonatomicnumber,withtheatomofhigheratomicnumbergetting
highestpriority.
I> Br> Cl> H

17. Rule 2:If two atoms are isotopesof the same element, the atom of
higher mass number has the highest priority.
Br> C> D> H

18. •Rule3:Iftherelativepositionsoftwogroupscannotbe
determinedasearlier,theyaredecidedbyacomparisonofpriority
atomatthefirstpointofdifference.

19. Rule4:Wherethereisadoubleortriplebond,bothatomsareconsideredto
beduplicatedortriplicated.
➢Itshouldbetreatedasifitweresinglybondedtotwoorthreeofthose
atomsrespectively.
➢Eg:InGlyceraldehyde,OHgrouphashighestpriorityofallandO,O,Hof
–CHOtakespriorityovertheO,H,Hof–CH2OH.
-OH> -CHO> -CH2OH> -H
Glyceraldehyde

20. Step II: According to orientation of molecule
1.Assignprioritiestofourdifferentatomsattachedtochiralcentrebasedontheir
atomicnumber.
2.Traceacirclefrom1to2to3
3.Determinetheorientationof4prioritygroup.
Ifitisorientatedintotheplaneofpaper(awayfromyou),followstep4a.
Ifitisorientatedoutoftheplaneofpaper(towardyou),followstep4b.
4a.4grouppointingawayfromyou:clockwisedirection–Rconfiguration;
anticlockwisedirection-Sconfiguration.
4b.4grouppointingtowardyou:configurationisreversed.
clockwisedirection–Sconfiguration;anticlockwisedirection-Rconfiguration.

21. •Eg-4a •4b

22. Absolute configuration of Fischer Projection
(Golden Rule)
❑Step 1: Assign priorityto four groups bonded to the chiral centre using CIP priority system.
❑Step 2:
a) Vertical position
❑If the lowest priority group is on a vertical bond: clockwise direction –R configuration;
anticlockwise direction-Sconfiguration.

23. Absolute configuration of Fischer Projection
(Golden Rule)
b) Horizontal position
❑If the lowest priority group is on a horizontal bond: clockwise direction –S configuration;
anticlockwise direction-Rconfiguration.

24. Interchanging between groups
I.InFischerprojection,theleastprioritynumberisnot
atthebottomoftheplane.
•Insuchcases,theFisherprojectionformulaofthe
compoundisconvertedintoanotherequivalent
projectionformulainsuchamannerthatatomthe
lowestpriorityisplacedverticallydownward.
•Thismaybedrawnbytwointerchangesbetween
fourprioritynumbers.Thefirstinterchangeinvolves
thetwoprioritynumbers,oneistheleastpriority
numberandtheotheristheprioritynumberwhichis
presentatthebottomoftheplane.
•Secondinterchangebetweenremaininggroups.
•clockwisedirection–Rconfiguration;anticlockwise
direction-Sconfiguration.

25. II.Ifthegroupoflowestpriorityisnotbondedbydashedlinetheninterchangea
pairofgroupssothatthegroupwiththelowestpriorityisbondedbydashedline.
•Nowseethesequence(123),ifitisclockwisethentheconfigurationis
assignedasSandifanticlockwiseasR.
Interchange 3
and 4
Clockwise
direction -S

26. SUMMARY
Orientation of moleculeAway from youTowards you
Clockwise direction R S
Anticlockwise direction S R
Interchanging group ruleFischer formulaFlying wedge formula
Clockwise direction R S
Anticlockwise direction S R
Fischer formula (Golden rule)Vertical bondHorizontal bond
Clockwise direction R S
Anticlockwise direction S R

27. IMPORTANCE OF ENANTIOMERS AS
CHIRAL DRUGS:
•Eg:

28. Pain killer
more active
Less active
Beta blocker Inactive