NoE/Zisomers,both

groupsarethesame.
NOTa
stereocentre!
Onlyhas3
different
groups,not4
limonene

Howmanyisomersdoesthisstructuralisomerof
limonenehave?

Only1!Moleculehasno
stereocentres.
145

Inorganic Stereoisomers
Geometrical Isomers
Same chemical composition, different
ligand arrangement
Have different chemical properties
Found for square planar and octahedral
complexes

Square planar

cisplatin

http://pubs.acs.org/cen/coverstory/83/8325
/8325cisplatin.html

LearningObjectives
(Stereochemistry)
Understandconceptofisomerism.
Recallconceptsofstructureandbondingfromlast
semester.
Distinguishbetweenthedifferenttypesofisomers:
structuralisomers(differentconnectivity)
stereoisomers (sameconnectivity)
configurationalisomers(bondsneedtobebrokento
interconvert)
enantiomers (nonsuperimposablemirrorimages)
diastereoisomers (asappliedtoE/Zisomers)
conformational isomers(rotationofsinglebondsonly)

Systematicallydescribestereochemistry(E/Z,R/S).
148
Appreciatetherelevanceofallthisinbiologyandmedicine.

Youshouldbeableto
Identifyanddefinestructuralisomersandstereoisomers
Defineandgiveexamplesofthefollowingconcepts:
Stereocentre
Enantiomer
Diastereomer
Chiral
Achiral
Conformationalisomers
Determinewhetheranobjectoramoleculeischiral.
Identifystereocentres inamoleculegiventhemolecularstructure.
Definetherelationshipbetweenstereoisomersaseitherenantiomericordiastereomeric.
Applysequencerulestodeterminetheabsoluteconfigurationofastereocentre (R/S)
Applysequencerulestodeterminetheconfigurationofanalkene(E/Z).
Identifyconformationalisomers.
Appreciatetherelevanceofallthisinbiologyandmedicine

ThisisNOTarotelearningexercise!Youneedtobeabletothinkcriticallyabout
molecules,identifyiftherecouldbeisomers,seehowtheyrelatetoeachotherand
whattheimplicationswouldbe!

149

CHEM1021
Chemistry B:
Elements, Compounds and Life

Dr Jon Beves

Part 3 : Structural Determination

(Blackman, 2nd Edition, Chapters 3.4, 7.5, 20)

TextBookReferences
Thissection:
BlackmanChemistry 2nd Ed.
Chapter3.4 Empericalformulae
Chapter7.5 Xraydiffraction
Chapter20.1 Toolsfordeterminingstructure
Chapter20.2 Massspectrometry
Chapter20.3 Infraredspectroscopy
Chapter20.4 Interpretinginfraredspectra
Chapter20.5 Nuclearmagneticresonancespectroscopy
Chapter20.6 InterpretingNMRspectroscopy
Chapter20.7 Othertoolsfordeterminingstructure

LearningObjectives
(structuredetermination)

Knowthecommontoolsusedtodeterminethestructureof
compounds.
Massspectrometry(MS)
UVVisspectroscopy
Infraredspectroscopy(IR)
Nuclearmagneticresonancespectroscopy(NMR)

UnderstandhowMS,UVVis,IR andNMR canbeusedto

identifydifferentfunctionalgroupsorstructuralmotifs.
Interprettheinformationprovidedbyspectrawithfocuson
combininginformationfromdifferenttechniques(e.g.IR and
NMR).
Becomeawareofadditionaltoolsalsoavailableforstructural
3
determination.

Structuraldetermination
Howcanwefigureoutwhatasubstanceis?
Thiscouldbeasuspiciouswhitepowder,anoilysmear

4
Image:kootation.com/csilasvegasallsphoto.html

Structuraldetermination
Howcanwefigureoutwhatasubstanceis?
Thiscouldbeasuspiciouswhitepowder,anoilysmear
oranewmaterialforelectronicsorapharmaceutical.
AlthoughCSIiscrazyfiction,withmoderntechniques
(andapuresample!)itisoftenpossibletoidentifyan
unknowncompoundinamatterofminutesorhours
usingscienceinsteadofscifi

Structuraldetermination
Thereareessentiallytwoprincipalmethodsfor
determiningmolecularstructure:
Directmethods(e.g.Xraycrystallography)
Indirectmethods(e.g.spectroscopicmethods)
Inallcasesweuseorreleasesomeenergyto
interrogate thechemicalstructure.

3.4

Elementalanalysis
Thisliterallyiswhatitsoundslike itis
determinationoftheelementspresentandtheir
ratio.Thisisusuallydonebycombustionanalysis.

3.4

Elementalanalysis
Notethatthedataprovidedistheempirical
formula thesimplestintegralratiobetween
theelementspresent.
Thisdoesnotalwaysmatchthemolecular
formula,whichshowsthenumberofeach
typeofatompresent.Forbutane
C4H10

molecularformula

C2 H 5

empiricalformula

3.4

Elementalanalysis
Q. Howdoyougettheempiricalformula?
A. Youstartwiththepercentagecomposition.
%element=

massofelement
x100%
massofwholesample

Thisisproperlyreferredtoasamassfraction.
Soacompoundmightbereportedas
havingamassfractionofCof92.3%andamass
fractionofHof7.7%,or
havingmassfractionsofC,H,NandOof67.3%,
6.98%,4.62%and21.1%.

Example1
Whatistheempiricalformulaofacompoundwhich
hasamassfractionofCof92.3%andamass
fractionofHof7.7%?
Startbyconsideringtheratiobymass:
C:H=92.3:7.7
Thenconvertittoratioofatomsbydividingbythe
averageatomicmassesofeachspecies.
C:H=(92.3/12.01):(7.7/1.008)
=7.69:7.64
=1:1
(note:roundingoftenneeded)
SotheempiricalformulaisC1H1.

3.4

10

Example2

3.4

Whatistheempiricalformulaofacompoundwhichhas
amassfractionsofC,H,NandOof67.3%,6.98%,4.62%
and21.1%,respectively?
Ratiobymass:
C:H:N:O=67.3:6.98:4.62:21.1
Ratiobyamount:
C:H:N:O=5.60:6.92:0.33:1.32
=17:20.97:1:4 Thisiscocaine!
=17:21:1:4
SotheempiricalformulaisC17H21NO4.

11

Howcanweuseenergysourcesto
revealmolecularinformation?
Theinformationgatheredvarieswiththeenergysource.
ScatteringusinghighenergyXray photons
providesinformationoncrystalstructure
Ionisationbybombardmentwithelectrons
providesions(M+)formassanalysis
Excitationofamoleculebyelectromagnetic
radiation providesspectroscopicinformation.
Theemphasisherewillbeonspectroscopic methods.
12

Somedefinitions
Spectroscopy:
theactoftakingaspectrum,
whichinvolvesresolving
electromagneticradiationinto
componentwavelengths.

Spectra:

Plotsofradiant
intensityvs wavelength.
Itistheabsorptionofparticularwavelengthsof
electromagneticradiationwhichwillbecomecrucial. 13

Electromagneticspectrum

E = hv =

hc

E=Energy,=frequency,l=wavelength
h=Plank'sconstant 6.626x1034 Js,c=2.998x108 ms1

14

Energy

Theenergyscale
XrayCrystallography:
Xrays1.5or8500eV or775,000kJmol1
Massspectrometry:
electronsupto70eV or6700kJmol1
(n.b. electronsarenotpartoftheelectromagneticspectrum)

UVVisspectroscopy:
700200nmor16eVor150600kJmol1
Infraredspectroscopy:
10004000cm1 or0.10.5eV or1040kJmol1
Nuclearmagneticresonancespectroscopy:
60700MHzor0.22meV or0.020.3Jmol1

15

Electromagneticspectrum

Xraycrystallography
(12)

16

7.5

Directstructuraldetermination:
XrayCrystallography
Thiscanbeusedtodeterminethearrangementof
atoms,ionsormoleculesinacrystallinestructure.
WhenthecrystalisexposedtoXrays,diffractedbeams
duetoconstructiveinterferenceappearonlyinspecific
directionsleadingtoadiffractionpattern.
NB:ThisisNOTXrayabsorption!

17

7.5

XrayCrystallography
TheBraggequation(notexaminable)relates, and
thedistancebetweentheplanesofatoms,d:
n =2dsin

18

7.5

XrayCrystallography
Whatdoyouneed?
a) ahighqualitycrystal
b) computationalmethodstosolvethediffraction
pattern.
Corresponding
Threedimensionalstructure

twodimensionalcartoon
representation

19

XrayCrystallography
Threedimensionalstructure

Corresponding
twodimensionalcartoon
representation

cyclodextrin

Whatifitsnotanicecrystal?
Incaseswherethematerialisnotcrystalline,therearea
numberofindirectmethods.
Massspectrometry: Molecularformula.
UVVisspectroscopy:Conjugation(doublebonds).
Infraredspectroscopy:Keyfunctionalgroups.
Nuclearmagneticresonancespectroscopy:
Detailedstructuralinformation.
Thesearetypicallyusedincombination.
21

20.2

Gettingthemolecularformula:
Massspectrometry
Thisreliesongeneratingachargedmolecularion (M+
orMH+)whichisdeflectedbyamagneticfield

22
One typeofMScalledElectronImpactMassSpectrometry usesabeamofelectronstogenerateions

20.2

Massspectrometry
InEIMS:

M+ =86

C6H14 =86
hexane

M+

=84

C6H12 =84
Molecularion
cyclohexane

Whatisthatlittlepeakjustto
rightoftheM+peakatM+1?It
comesfromthe13Cisotopein
thesamplewellcomebackto
23
this

Example3

3.4

Ifyouhavethemolecularmassandtheempiricalformula,itis
quitestraightforward.Again,anexample.
Whatisthemolecularformulaofacompoundwithan
empiricalformulaC1H1 andamolecularmass of
(a)26u;
(b)78u?
FirstastheempiricalformulaisC1H1 thenthemolecular
formulawillbe(C1H1)n.Asaresultthemolecularmasswillbe
(12.01+1.008)n=13.018n
(a) 13.018n=26thereforen=26/13.018=2
(b)(noterounding!)
somolecularformulais(C1H1)2=C2H2
(c) 13.018n=78thereforen=78/13.018=6(noterounding!)
24
somolecularformulais(C1H1)6=C6H6

Example4

3.4

Ifyouhavethemolecularmassandthemassfraction,youcan
skiptheempiricalformulastage.
Whatisthemolecularformulaofacompoundwithmass
fractionsofC,H,NandOof67.3%,6.98%,4.62%and21.1%,
respectively,andamolecularmassof303.5u?
Foreachelement,youcancalculatethemasspermolecule
andhencethenumberofatomsofthatelement.
C 67.3%of303.5=204.2u
H 6.98%of303.5=21.17u
N 4.62%of303.5=14.01u
O 21.1%of303.5=64.01u

No.ofatomsC=(204.2/12.01)=17
No.ofatomsH=(21.17/1.008)=21
No.ofatomsN=(14.01/14.01)=1
No.ofatomsO=(64.01/16.00)=4

SothemolecularformulaisC17H21NO4
(Notethathereitisthesameastheempiricalformula!)

25

20.1

Usingthemolecularformula
Bylookingatthenumberofeachtypeofelements
present,thenumberofmultiplebondsandringscan
bedetermined.
Note: Theoldtermforthisisdegreesof
unsaturation youwillstillseethisaround.Butwell
talkaboutthenewtermforthis

26

20.1

IndexofHydrogenDeficiency(IHD)

Notethatthereferenceisdependentontypeof
molecule forhydrocarbons,thereferenceisCnH2n+2

27

20.1

IndexofHydrogenDeficiency(IHD)

28
forhydrocarbons,thereferenceisCnH2n+2

20.1

Whenotherelementsareabout
ForcompoundscontainingelementsotherthanCandH
adjustHinreferencehydrocarbon:
Group17 (F,Cl,Br,I):subtract1Hfromthe
reference
e.g.acyclicmonochloroalkane CnH2n+1Cl
Group16 (O,S,Se):Nocorrectionisnecessaryfor
theadditionofe.g.CnH2n+2
Group15(NandP):add1H
e.g.acyclicalkylamine CnH2n+3N
29
forhydrocarbons,thereferenceisCnH2n+2

WorkedExample20.1,20.2

20.1

Example5
Calculatetheindexofhydrogendeficiencyforaspirin
(C9H8O4)fromthemolecularformula.Doesthismatch
thestructure.

2x9+2 - 8
IHD =
2
= 6 multiple bonds/rings
Fromthestructure 1ring,5doublebonds(3inthe
ring,2outside)whichmatches.
TutorialQ#1
forhydrocarbons,thereferenceisCnH2n+2

30

20.2

Otherinfofrommassspectrometry
Becausemassspectrometry
observesindividualmolecules,
thepresenceofdifferent
isotopesgivesdifferent
signals.
Rememberthe13Cpeaksfrom
previously

31

20.2

Otherinfofrommassspectrometry
Theisotopeabundancehelpsdeterminethepresenceof
particularelements
e.g.Brmassdifferenceis2,equalintensity
e.g.Clmassdifferenceis2,ratiois3:1

32

20.2

Otherinfofrommassspectrometry
Theisotopeabundancehelpsdeterminethepresenceof
particularelements
e.g.Brmassdifferenceis2,equalintensity
e.g.Clmassdifferenceis2,ratiois3:1

35ClC

3H5

37ClC

3H5

33

TutorialQ#2

Example6

20.2

CompoundBhasamolecularformulaC6H5Xandgives
thefollowingmassspectra.WhatisX?

Thereisamolecularion(M+)peakaround112with
peakatM+2thatis1/3oftheintensityoftheM+ peak.
Thisischaracteristicofthe35Cl/37Clisotopepattern.
C6H535Cl=12x6+5x1+35=112 and
XisCl
C6H537Cl=12x6+5x1+37=114
34

Example6

TutorialQ#2

20.2

Someelementshaveverycomplexnaturalisotope
patterns,egruthenium(atomicnumber44,atomicweight
101.07):
35%
30%

% Abundance

25%
20%
15%
10%
5%
0%
95.9

96.9

97.9

98.9

99.9
mass

100.9

101.9

102.9

103.9

35

RealWorldExample1
MarionJones(USA)wongoldmedalsatthe
Sydney2000Olympics.

TestingrevealedtheuseofthesteroidTHG
(admittedin2007)andshewasstrippedofall
medals.Thiswasdeterminedusingmass
spectrometrywhichcouldtellbetweennatural Tetrahydrogestrinone
(THG)
andsyntheticTHG.
STEROID SOURCES
Human Body
Synthesised (from plant material)
13C
1.1%
1.0%
12C
98.9%
99.0%
36
More 13C
Less 13C
graphics8.nytimes.com/images/2007/10/05/sports/medals600.jpg,seattletimes.com/ABPub/2007/12/14/2003929187.jpg

20

Spectroscopictechniques
Rememberthatthisinvolvesabsorptionofspecific
wavelengthsofelectromagneticradiation.The
moleculesmovetoanexcitedstate.

37

20

Spectroscopictechniques
Thenatureoftransitionandexcitedstatedependson
thefrequency(andthereforeenergy)oftheradiation
absorbed.

Electronic
transitions

Molecular
vibrations

Nuclearspin
transitions

38

20.2

UVVisiblespectroscopy
Correspondstotransitionsbetweendifferentelectronic
energylevelsinamolecules.

39

20.7

UVVisiblespectroscopy
Rememberthatspectroscopyinvolvesabsorptionof
specificwavelengthsofelectromagneticradiation.The
moleculesmovetoanexcitedstate.

40

20.7

UVVisiblespectroscopy
Theenergygapbetweenstatesisstronglydependenton
theextentofconjugation thatis,thepresenceof
alternatingdoubleandsinglebonds.
max 258nm

max 254nm

41

20.7

UVVisiblespectroscopy
AbsorptionofUVVisradiationusuallyindicatesa
conjugatedsystem thegreaterthedegreeof
conjugation,thelongerthewavelengthabsorbed.
max 258nm

max 254nm

42
Image:www.fitho.in/wpcontent/uploads/2010/08/CarrotVegetable.jpg

20.7

UVVisiblespectroscopy
Andthesecancontainheteroatoms

max 219nm

max 257nm

43

20.7

RealWorldExample2
Conjugatedcompoundscontainingheteroatomsare
importantbecauseofthewavelengthofradiation
absorbed.

max 310nm

max 299nm

ThesecompoundsabsorbharmfulUVB (290320
nm)radiationfromthesunandareused
extensivelyinsunscreens.
http://www.dumpaday.com/wpcontent/uploads/2013/06/sunburnpicturesdumpaday2.jpg

44

20.7

Sowhatinfodoyouget?
DoesthecompoundhaveanabsorptionintheUV
visibleregionoftheelectromagneticspectrum?
Yes indicatesthatthemoleculecontainsconjugation.
No indicatesthatthemoleculedoesnotcontain
conjugation.

45