2.

Molecularshape
Manyofthereactionsand
propertiesofmoleculesarerelated
totheirshape.
Shapeisdependentonbondangles
Video of drug binding to
andbondlengths.
Weusetheconceptof
hybridization ofatomsina
moleculetoexplainshape.

proteins
(e.g. from 1:20 min)
https://www.youtube.com/wat
ch?v=u49k72rUdyc

15

5.6

Revisionofbonding sp3 hybridization

Ones andthreep orbitalscanhybridizetoformfour
equivalentsp3 orbitals:

sp3hybridorbitalshavethelargelobeofeachorbital
pointingtowardthevertexofatetrahedron.

16

5.6

Revisionofbonding sp3 hybridization

ThecarbonatominCH4 hassp3hybridization.Four
equivalentbondsareformedbytheoverlapoffoursp3
orbitalswiththe1s orbitalsofeachofthefourhydrogen
atoms.

17

5.6

Shape sp3 meanstetrahedral

e.g.CH4

e.g.NH3

e.g.H2O
18

Moleculesarethreedimensional:
Drawingin3D
sp3 hybridisedcarbons(thosewith4single
bonds)aretetrahedral andhavethree
dimensionalshape
Thereareseveralwaystorepresent3D
structures;thefirstuseswedgedanddashed
bonds

19

TheShapeofMolecules

2.2

20

TheShapeofMolecules

2.2

21

16.2

Conformers
Moleculesarenotstatic theyaremoving!
Theseresultwhenstructuresappear tobedifferent,but
canbeinterconvertedbyrotatingaboutsinglebonds.
Thebarriertorotationaboutsinglebondsislow andat
roomtemperaturetheycannot(generally)beseparated.
Aninfinitenumberofconformationsexistaboutanysingle
bond.

ethane
22

16.2

Wayswedrawconformers
Thecommonwaysincludeusinghashedandboldbonds
butthereareothers theseincludeSawhorse
representations.

23

WorkedExample16.1

Wayswedrawconformers
Thecommonwaysincludeusinghashedandboldbonds
butthereareothers theseincludeSawhorse
representationsandNewmanprojections.

24

16.2

Convertingbetweentherepresentations

25

16.2

Sawhorseexamples
Considerthebutaneconformationalisomersbelow.

26

16.2

Conformations
Whiletherearemanyconformations,theydohave
differentenergies.Itistheinteractionofthegroupsonthe
carbonthatneedtobeminimised thetwoextremesare
thestaggered andeclipsed conformations.

eclipsed

Energy

12.5kJ/mole
staggered

60

120

180

240

300

360

27

16.2

Conformations
Whiletherearemanyconformations,theydohave
differentenergies.Itistheinteractionofthegroupsonthe
carbonthatneedtobeminimised thetwoextremesare
thestaggered andeclipsed conformations.

eclipsed
conformations

arehigherenergy
(lessstable)
than

staggered
conformations

28

16.2

Thisbecomesmorecomplicated
whentherearesubstituents.Thisisbestseenfor
disubstitutedalkanes.

29

16.2

Thisbecomesmorecomplicated
whentherearesubstituents.Thisisbestseenfor
disubstitutedalkanes.
Eg,nbutaneagain
Spacious!

Crowded!
30

RealWorldApplication
Conformationisparticularlyimportantinbiology.
Considerthereceptorbelow itonlybindsthe
moleculeinoneconformation.

31

WhatisaFunctionalGroup?

2.3

Organiccompoundsareclassifiedaccordingtothe
FUNCTIONALGROUPStheycontain
AFUNCTIONALGROUPisanatom,orgroupof
atoms,thatisresponsibleforthechemicaland
physicalpropertiesofthemolecule
Allmoleculeswiththesamefunctionalgroupcanbe
expectedtoreactsimilarly
Notquitetrue,butagoodfirstapproximation!
32

FunctionalGroups

2.3

33

34

Thespecialcaseof
benzene/aromaticgroups

Theyarethesame!

Likewise,
thesearethesame!

ortho-

ortho-

meta-

meta-

para-

Why?Itsallabouttheconceptofaromaticity
SeelecturesinWeeks48fordetails

=Ar
34

Functionalgroups

2.3

Increasingpriority

Commonfunctionalgroups:
Suffixes(endings)
carboxylicacid
RCO2H
oicacid
acidhalide
RCOCl
oylhalide
amide
RCONHR
amide
nitrile
RCN
nitrile
aldehyde
RCHO
al
ketone
R1COR2
one
alcohol
RCH2OH
ol
phenol
ArOH
ol
amine
RNH2
amine
alkene
R1CH=CHR2 ene
alkyne
R1C=CR2
yne
others,eg halides,nitrocompounds
35

Nomenclature:Alkanes

2.3

Moleculesthatcontainonlycarbonandhydrogenthat
arejoinedbysinglebonds
Saturated
hydrocarbons

36

Nomenclature:Alkanes

2.3

Parentchain:thelongestcarbonchain
Substituents:anybranchofftheparentchain,
namedbasedonalkylgroups

37

LearningObjectives
(Stereochemistry)
Understandconceptofisomerism.
Recallconceptsofstructureandbondingfromlast
semester.
Distinguishbetweenthedifferenttypesofisomers:
structuralisomers
stereoisomers
conformationalisomers
configurationalisomers
enantiomers
diastereoisomers(asitappliestogeometricisomers)

Systematicallydescribestereochemistry(E/Z,R/S).
38
Appreciatetherelevanceofallthisinbiologyandmedicine.

2.2

Whatareisomers?
Isomersare
moleculeswiththe
samemolecular
formulabut
differentstructures.
Differenttypesof
isomersformthe
basisofthissection.
39

16

Hydrocarbons
Literally,hydrocarbonsaremadeupofhydrogenand
carbon.Thesimplestarealkanes thesearesaturated
(haveasmanyhydrogenatomsaspossible,nomultiple
bonds).TheyhavethegeneralformulaCnH2n+2.
H H H

C 3H8

H C C C H
H H H

CH 3 CH 2 CH 3

propane

40

16

Hydrocarbons
Alkanescanbelinearorbranched;therearemanypossible
combinationsallwiththesameformula.Differentbond
connectivityresultsindifferentstructural isomers.
C6H14
C4H10
H H H H
H C C C C H
H H H H
CH 3 CH 2 CH 2 CH 3

n-butane

CH3 CH2 CH2 CH2 CH2 CH3

H
H C H
H
H
H C C C H
H

n-hexane

CH3 CH2 CH2

CH3
CH CH3

2-methylpentane
2-methylpropane

CH3 CH2

CH3
2,2-dimethylbutane
CH3

CH2 CH3
CH3 CH2 CH CH3

2structuralisomers

3-methylpentane

CH3
C CH3

CH3 CH

CH

CH3

CH3
2,3-dimethylbutane

5structuralisomers

41

WorkedExample16.5

Hydrocarbons
Themorecarbons,themorestructuralisomers
MolecularFormula

No.ofIsomers

C3H8

C4H10

C5H12

C6H14

C7H15

C10H22

75

C20H42

366,319
42

16

Structuralisomers
Sometimescalledconstitutionalisomers (Blackman).
Atomsconnectedindifferentways,orinadifferent
order(thelatterwillbeshowninamoment).
Differentphysicalandchemicalproperties
Sometimesthedifferencesaremodest.
Forexample
C6H14
TutorialQ#5

2methylpentane

bp 60C

3methylpentane

bp63C

2,3dimethylbutane

bp58C

43

16

Structuralisomers
Inthecaseswhereheteroatoms(notCorH)are
involved,theorderbecomesmoreimportant.
Oftenthisresultsinachangeinfunctionalgroups
(literallythegroupsthathavefunction;placeswherethe
moleculereacts).
Forexample

TutorialQ#5

C 3 H6 O

44

17

Isomers
(samemolecularformula)

bondconnectivity?

StructuralIsomers

Stereoisomers

(differentbondconnectivity)

(samebondconnectivity
butdifferentarrangementinspace)

45

17

Isomers
Isomers
(samemolecularformula)

Samebondconnectivity?
yes

no

Structural
isomers

Stereoisomers

Me

H
Me

Me

Me

Diastereoisomers Enantiomers

Alkene
E/Z isomers

Diastereoisomers
withstereogeniccentres

46

Stereoisomers
Stereoisomershavethesamemolecularformulaandthe
sameorderofattachmentofatomsintheirmolecules
BUTdifferentthreedimensionalorientationsoftheir
atomsinspace.
H

Me

H
Me

Me

Me
H

47

17.2

Enantiomers
Astereoisomerthatisnonsuperimposablewithits
mirrorimageisknownasanenantiomer. Anobject
whichisnonsuperimposablewithitsmirrorimageis
saidtobechiral.
Chiralityishandedness (commonintheworldin
whichwelive).

48

17.2

Intherealworld
yourleftandrighthandsarenonsuperimposable
mirrorimages.Theyarehenceapairofenantiomers.

49

17.2

Chiralvs Achiral
Objectsthatarenot
chiral(achiral)possessa
planeofsymmetry this
isanimaginaryplane
passingthroughan
objectdividingitsothat
onehalfisthemirror
imageoftheotherhalf.

Planeofsymmetry;
achiral

Cricketball:achiral

Tennisracket:achiral

Cricketwicketkeepersglove:chiral

Noplaneofsymmetry;
chiral

50

17.2

Formolecules
theprincipleisthesame;checkwhethertheobject
possessesaplaneofsymmetry.
H

Br
Br

Planeofsymmetry;
achiral

51

17.2

Structuralrequirements
Q:Whatisthestructuralrequirementformolecular
chirality?
A:Acarbonatomwithfourdifferentgroups attached
willresultinamoleculethatisnonsuperimposable
withitsmirrorimage(i.e.chiral).Thisresultsinapairof
enantiomers
A

TutorialQ#1,2

A
B
C

B
C

mirror

52

TutorialQ#1,2

Example1

Thiscompoundis2bromobutane thesecondcarbon
atomhasfourdifferentgroupsattachedtoit.
Ansp3 carbonwithfourdifferentgroupsiscalleda
stereogeniccentre (orjuststereocentre).
Forthismolecule,twopossiblestructurescanexist,
whicharenotsuperimposableandaremirrorimagesof
53
oneanother hence2bromobutaneischiral.

TutorialQ#1,2

Example1

Thiscompoundis2bromobutane thesecondcarbon
atomhasfourdifferentgroupsattachedtoit.
Ansp3 carbonwithfourdifferentgroupsiscalleda
stereogeniccentre (orjuststereocentre).
Forthismolecule,twopossiblestructurescanexist,
whicharenotsuperimposableandaremirrorimagesof
54
oneanother hence2bromobutaneischiral.

Example2
Identifyandlabelthestereocentres inthefollowing
molecules. Iseachmoleculechiral?
ACHIRAL
CHIRAL
stereocentre

ACHIRAL

TutorialQ#1,2

55

Example3
Identifyandlabelthestereocentres inthefollowing
molecules. Iseachmoleculechiral?
ACHIRAL
CHIRAL
stereocentre
2

CHIRAL

3
iv

TutorialQ#1,2

stereocentres

56

iii
ii

17.2

Propertiesofenantiomers
Enantiomers havethesamephysicalandchemical
properties theseincludebp,mp,density,reactivity
withachiralreagents.
ie,chiralrightandleftgloves
reactequallywithanachiral
cricketball

Theonlywaystotellenantiomersapartare
a)thattheyreactdifferentlywithotherchiralreagents
(eg,handsingloves!enzymes)
b)thattheyinteractdifferentlywithplanepolarised
57
light.

17.2

Propertiesofenantiomers
OH

OH

H
CO2H

H
HO2C

()Mandelicacid

(+)Mandelic acid
[]D

Density (g/cm3)

Stereoisomer

m.p.

(+)

131-133

+ 153

1.341

(-)

131-133

- 153

1.341

()

206

1.300

Whatdothe(+)&()mean?

58

17.5

Opticalactivity
Whenplanepolarizedlightispassedthroughasolution
ofamoleculecontainingastereocentre,theplaneof
polarizedlightisrotated(henceopticalrotation).
Eachenantiomerrotatestheplaneanequalamount,in
oppositedirections
Thedeviceusedtomeasurethiseffectiscalleda
polarimeter:

59

17.5

Opticalactivity

19th Century:Tartaricacidwhenisolatedfromnaturalsources
rotatedplanepolarisedlight.Whenitwassynthesisedinthelab,
itdidnot,despiteallotherpropertiesbeingidentical!
Howwasthispossible?

1849 LouisPasteurseparatedcrystalsoftheenantiomersoftartaric
60
acidbyhand provedmoleculescouldhavehandedness
http://plato.stanford.edu/entries/chemistry/

17.5

Opticalactivity

Thetwoenantiomersof2butanolrotateplanepolarised
lighttothesameextentbutinoppositedirections.An
equalmixtureoftwoenantiomersiscalledaracemic
mixture (orracemate) andhasanopticalrotationof
zero.
61

17.3

Namingenantiomers
Opticalrotationisaphysicalmeasurementandhasno
directcorrelationwithstructure(similartomelting
point).
Sodeterminationofopticalrotationdoesnotindicatethe
absoluteconfigurationoftheenantiomer.
Weassignabsoluteconfigurationbyapplicationofa
standardsetofsequencerules CahnIngoldPrelog
SequenceRules.

62

17.3

CahnIngoldPrelogRules
1. Assignprioritiestothefouratomsdirectlyattached
tothestereogeniccentre,sothattheatomwiththe
highestatomicnumberisranked1 andthatwiththe
lowestatomicnumberisranked4.
2. Ifprioritycannotbedecideddirectlyonthebasisof
(1),thenrankthesecondatomineachsubstituent,
continuingonthroughthethird&fourthatomsuntil
thefirstpointofdifferenceisreached.
3.Multiplebondedatomsareequivalenttothesame
numberofsinglebondedatoms(C=Oiscountedas
63
2xCO)

17.3

CahnIngoldPrelogRules
Havingassignedthepriorityofthefoursubstituents,the
atomorgroupwithlowestpriority(i.e.ranked4)is
pointedawayfromtheviewer.
Thedirectionofrotationofthegroupsranked1,2&3
nowdeterminestheconfiguration:
Ifdirectionofrotationofthegroupsranked1,2&3isclockwise,
thentheconfigurationisdesignatedasR
(Latinrectus,right).
Ifdirectionofrotationofthegroupsranked1,2&3is
anticlockwise,thentheconfigurationisdesignatedasS
(Latinsinister,left).
64

17.3

R andS configurations
1

65

CIP;Rule1Example
1
I

Br

Cl

Groupsareassignedprioritybyatomicnumber.
Atomicnumber: 53

35

17

I>Br>Cl>F

Priority: 1

66

CIP;Rule1Example
1
I

Br

F
Cl

Withthelowestprioritygrouppointingawayfrom
theviewer,directionofrotationofgroupsranked
1,2&3isanticlockwise.
TheconfigurationisthereforeS.
67

CIP;Rule2Example
OCH3
Br

Br
H

Groupsareassignedprioritybyatomicnumber.
35

Br>C=C>H
Thisdoesnotdistinguishbetweenthetwoofthe
groups,sogotothenextatom.
68

CIP;Rule2Example
3

OCH3

Br

Br

Groupsareassignedprioritybyatomicnumber.
35

Br>C=C>H
Thisdoesnotdistinguishbetweenthetwoofthe
groups,sogotothenextatom.
35

635

68

Br>CBr>CO>H
Priority:

69

CIP;Rule2Example1
3

OCH3

Br

Br

Directionofrotationofgroupsranked1,2&3is
clockwisehowever thelowestprioritygroupis
pointingtowards theviewer.
TheconfigurationisthereforeS.
70