Essential Practical NMR for Organic Chemistry

216 Pages·2011·7.51 MB·English

by  S. A. RICHARDS AND J. C. HOLLERTON

P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October7,2010 7:16 Printer:Yettocome
Essential Practical NMR for
Organic Chemistry
Essential Practical NMR for Organic Chemistry S. A. Richards and J. C. Hollerton
© 2011 John Wiley & Sons, Ltd. ISBN: 978-0-470-71092-0
i
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October7,2010 7:16 Printer:Yettocome
Essential Practical NMR for
Organic Chemistry
S.A.RICHARDS
AND
J.C.HOLLERTON
A John Wiley and Sons, Ltd., Publication
iii
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October7,2010 7:16 Printer:Yettocome
Thiseditionfirstpublished2011
(cid:1)C 2011JohnWiley&Sons,Ltd
Registeredoffice
JohnWiley&Sons,Ltd,TheAtrium,SouthernGate,Chichester,WestSussex,PO198SQ,UnitedKingdom
Fordetailsofourglobaleditorialoffices,forcustomerservicesandforinformationabouthowtoapplyforpermissiontoreusethecopyrightmaterialin
thisbookpleaseseeourwebsiteatwww.wiley.com.
TherightoftheauthortobeidentifiedastheauthorofthisworkhasbeenassertedinaccordancewiththeCopyright,DesignsandPatentsAct1988.
Allrightsreserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,ortransmitted,inanyformorbyanymeans,electronic,
mechanical,photocopying,recordingorotherwise,exceptaspermittedbytheUKCopyright,DesignsandPatentsAct1988,withoutthepriorpermission
ofthepublisher.
Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsinprintmaynotbeavailableinelectronicbooks.
Designationsusedbycompaniestodistinguishtheirproductsareoftenclaimedastrademarks.Allbrandnamesandproductnamesusedinthisbookare
tradenames,servicemarks,trademarksorregisteredtrademarksoftheirrespectiveowners.Thepublisherisnotassociatedwithanyproductorvendor
mentionedinthisbook.Thispublicationisdesignedtoprovideaccurateandauthoritativeinformationinregardtothesubjectmattercovered.Itissoldon
theunderstandingthatthepublisherisnotengagedinrenderingprofessionalservices.Ifprofessionaladviceorotherexpertassistanceisrequired,the
servicesofacompetentprofessionalshouldbesought.
Thepublisherandtheauthormakenorepresentationsorwarrantieswithrespecttotheaccuracyorcompletenessofthecontentsofthisworkand
specificallydisclaimallwarranties,includingwithoutlimitationanyimpliedwarrantiesoffitnessforaparticularpurpose.Theadviceandstrategies
containedhereinmaynotbesuitableforeverysituation.Inviewofongoingresearch,equipmentmodifications,changesingovernmentalregulations,and
theconstantflowofinformationrelatingtotheuseofexperimentalreagents,equipment,anddevices,thereaderisurgedtoreviewandevaluatethe
informationprovidedinthepackageinsertorinstructionsforeachchemical,pieceofequipment,reagent,ordevicefor,amongstotherthings,any
changesintheinstructionsorindicationofusageandforaddedwarningsandprecautions.ThefactthatanorganisationorWebsiteisreferredtointhis
workasacitationand/orapotentialsourceoffurtherinformationdoesnotmeanthattheauthororthepublisherendorsestheinformationtheorganisation
orWebsitemayprovideorrecommendationsitmaymake.Further,readersshouldbeawarethatInternetWebsiteslistedinthisworkmayhavechanged
ordisappearedbetweenwhenthisworkwaswrittenandwhenitisread.Nowarrantymaybecreatedorextendedbyanypromotionalstatementsforthis
work.Neitherthepublishernortheauthorshallbeliableforanydamagesarisingherefrom.
LibraryofCongressCataloguing-in-PublicationData
Richards,S.A.
EssentialpracticalNMRfororganicchemistry/S.A.Richards,J.C.Hollerton.
p.cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-71092-0(cloth)
1.Protonmagneticresonancespectroscopy. 2.Nuclearmagneticresonancespectroscopy. I.Hollerton,J.C.(JohnC.),1959- II.Title.
QD96.P7R5292011
543(cid:2).66–dc22
2010033319
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
PrintISBN:9780470710920
ePDFISBN:9780470976395
oBookISBN:9780470976401
ePubISBN:9780470977224
Setin10.5/12.5ptTimesbyAptaraInc.,NewDelhi,India.
PrintedinSingaporebyFabulousPrintersPteLtd.
iv
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October7,2010 7:16 Printer:Yettocome
WewouldliketodedicatethisbooktoourfamiliesandourNMRcolleaguespastandpresent.
v
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October13,2010 21:39 Printer:Yettocome
Contents
Introduction xi
1 GettingStarted 1
1.1 TheTechnique 1
1.2 Instrumentation 2
1.3 CWSystems 2
1.4 FTSystems 3
1.4.1 OriginoftheChemicalShift 6
1.4.2 Originof‘Splitting’ 7
1.4.3 Integration 9
2 PreparingtheSample 11
2.1 HowMuchSampleDoINeed? 12
2.2 SolventSelection 13
2.2.1 DeuteroChloroform(CDCl ) 14
3
2.2.2 DeuteroDimethylSulfoxide(D -DMSO) 14
6
2.2.3 DeuteroMethanol(CD OD) 15
3
2.2.4 DeuteroWater(D O) 16
2
2.2.5 DeuteroBenzene(C D ) 16
6 6
2.2.6 CarbonTetrachloride(CCl ) 16
4
2.2.7 TrifluoroaceticAcid(CF COOH) 16
3
2.2.8 UsingMixedSolvents 17
2.3 SpectrumReferencing(ProtonNMR) 17
2.4 SamplePreparation 18
2.4.1 Filtration 19
3 SpectrumAcquisition 23
3.1 NumberofTransients 23
3.2 NumberofPoints 24
3.3 SpectralWidth 25
3.4 AcquisitionTime 25
3.5 PulseWidth/PulseAngle 25
3.6 RelaxationDelay 27
3.7 NumberofIncrements 27
3.8 Shimming 28
3.9 TuningandMatching 30
3.10 FrequencyLock 30
vii
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October13,2010 21:39 Printer:Yettocome
viii Contents
3.10.1 RunUnlocked 30
3.10.2 InternalLock 30
3.10.3 ExternalLock 31
3.11 ToSpinorNottoSpin? 31
4 Processing 33
4.1 Introduction 33
4.2 ZeroFillingandLinearPrediction 33
4.3 Apodization 34
4.4 FourierTransformation 36
4.5 PhaseCorrection 36
4.6 BaselineCorrection 38
4.7 Integration 39
4.8 Referencing 39
4.9 PeakPicking 39
5 InterpretingYourSpectrum 41
5.1 CommonSolventsandImpurities 44
5.2 Group1–ExchangeablesandAldehydes 46
5.3 Group2–AromaticandHeterocyclicProtons 48
5.3.1 MonosubstitutedBenzeneRings 50
5.3.2 MultisubstitutedBenzeneRings 54
5.3.3 HeterocyclicRingSystems(Unsaturated)andPolycyclic
AromaticSystems 57
5.4 Group3–DoubleandTripleBonds 61
5.5 Group4–AlkylProtons 63
6 DelvingDeeper 67
6.1 ChiralCentres 67
6.2 EnantiotopicandDiastereotopicProtons 72
6.3 MolecularAnisotropy 74
6.4 AccidentalEquivalence 76
6.5 RestrictedRotation 78
6.6 HeteronuclearCoupling 82
6.6.1 CouplingbetweenProtonsand13C 82
6.6.2 CouplingbetweenProtonsand19F 84
6.6.3 CouplingbetweenProtonsand31P 87
6.6.4 Couplingbetween1HandotherHeteroatoms 89
6.6.5 CyclicCompoundsandtheKarplusCurve 91
6.6.6 Salts,FreeBasesandZwitterions 96
7 FurtherElucidationTechniques–Part1 101
7.1 ChemicalTechniques 101
7.2 Deuteration 101
7.3 BasificationandAcidification 103
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October13,2010 21:39 Printer:Yettocome
Contents ix
7.4 ChangingSolvents 104
7.5 Trifluoroacetylation 104
7.6 LanthanideShiftReagents 106
7.7 ChiralResolvingAgents 106
8 FurtherElucidationTechniques–Part2 111
8.1 InstrumentalTechniques 111
8.2 SpinDecoupling(Homonuclear,1-D) 111
8.3 CorrelatedSpectroscopy(2-D) 112
8.4 TotalCorrelationSpectroscopy(1-and2-D) 116
8.5 TheNuclearOverhauserEffectandAssociatedTechniques 116
9 Carbon-13NMRSpectroscopy 127
9.1 GeneralPrinciplesand1-D13C 127
9.2 2-DProton–Carbon(SingleBond)CorrelatedSpectroscopy 130
9.3 2-DProton–Carbon(MultipleBond)CorrelatedSpectroscopy 133
9.4 PiecingItAllTogether 136
9.5 ChoosingtheRightTool 137
10 SomeoftheOtherTools 143
10.1 LinkingHPLCwithNMR 143
10.2 FlowNMR 144
10.3 SolventSuppression 145
10.4 MagicAngleSpinningNMR 146
10.5 Other2-DTechniques 147
10.5.1 INADEQUATE 147
10.5.2 J-Resolved 147
10.5.3 DiffusionOrderedSpectroscopy 148
10.6 3-DTechniques 149
11 SomeoftheOtherNuclei 151
11.1 Fluorine 151
11.2 Phosphorus 152
11.3 Nitrogen 152
12 Quantification 157
12.1 Introduction 157
12.2 RelativeQuantification 157
12.3 AbsoluteQuantification 158
12.3.1 InternalStandards 158
12.3.2 ExternalStandards 158
12.3.3 ElectronicReference 159
12.3.4 QUANTASTechnique 159
12.4 ThingstoWatchOutFor 160
12.5 Conclusion 161
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October13,2010 21:39 Printer:Yettocome
x Contents
13 Safety 163
13.1 MagneticFields 163
13.2 Cryogens 165
13.3 Sample-RelatedInjuries 166
14 Software 167
14.1 AcquisitionSoftware 167
14.2 ProcessingSoftware 167
14.3 PredictionandSimulationSoftware 169
14.3.1 13CPrediction 169
14.3.2 1HPrediction 171
14.3.3 Simulation 172
14.3.4 StructuralVerificationSoftware 172
14.3.5 StructuralElucidationSoftware 172
15 Problems 173
15.1 TenNMRProblems 173
15.2 Hints 194
15.3 Answers 195
Glossary 205
Index 211
P1:OTE/OTE/SPH P2:OTE
fm JWST025-Richards October7,2010 7:16 Printer:Yettocome
Introduction
Thisbookisanup-to-datefollow-uptotheoriginal“LaboratoryGuidetoProtonNMRSpectroscopy”
(Blackwell Scientific Publications, 1988). It follows the same informal approach and is hopefully fun
toreadaswellasausefulguide.WhilststillconcentratingonprotonNMR,itincludes2-Dapproaches
and some heteronuclear examples (specifically 13C and 19F plus a little 15N). The greater coverage is
devotedtothetechniquesthatyouwillbelikelytomakemostuseof.
Thebookisheretohelpyouselecttherightexperimenttosolveyourproblemandtotheninterpretthe
resultscorrectly.NMRisafunnybeast–itthrowsupsurprisesnomatterhowlongyouhavebeendoing
it (at this point, it should be noted that the authors have about 60 years of NMR experience between
themandwestillgetsurprisesregularly!).
ThestrengthofNMR,particularlyinthesmallorganicmoleculearea,isthatitisveryinformationrich
butironically,thisveryhighdensityofinformationcanitselfcreateproblemsforthelessexperienced
practitioner. Information overload can be a problem and we hope to redress this by advocating an
ordered approach to handling NMR data. There are huge subtleties in looking at this data; chemical
shifts,splittingpatterns,integrals,linewidthsallhaveanexistenceduetophysicalmolecularprocesses
and they each tell a storey about the atoms in the molecule. There is a reason for everything that you
observeinaspectrumandthebetteryourunderstandingofspectroscopicprinciples,thegreatercanbe
yourconfidenceinyourinterpretationofthedatainfrontofyou.
So, who is this book aimed at? Well, it contains useful information for anyone involved in using
NMRasatoolforsolvingstructuralproblems.Itisparticularlyusefulforchemistswhohavetorunand
look at their own NMR spectra and also for people who have been working in small molecule NMR
for a relatively short time (less than 20 years, say!...). It is focused on small organic molecule work
(molecularweightlessthan1000,commonlyabout300).Ultimately,thebookispragmatic–wediscuss
cost-effective experiments to solve chemical structure problems as quickly as possible. It deals with
someoftheunglamorousbits,likemakingupyoursample.Thesearenecessaryifdull.Italsolooksat
themorechallengingaspectsofNMR.
WhilstthebooktouchesonsomeaspectsofNMRtheory,themainfocusofthetextisfirmlyrooted
in data acquisition, problem solving strategy and interpretation. If you find yourself wanting to know
more about aspects of theory, we suggest the excellent, High-Resolution NMR Techniques in Organic
ChemistrybyTimothyDWClaridge(Elsevier,ISBN-13:978-0-08-054818-0)asanapproachablenext
step before delving into the even more theoretical works. Another really good source is Joseph P.
Hornak’s “The Basics of NMR” website (you can find it by putting “hornak nmr” into your favourite
searchengine).Whilstwritingthesechapters,wehaveoftenfoughtwiththeproblemofstatementsthat
arepartiallytrueanddebatedwhethertoinsertaqualifier.Togetacrossthefundamentalideaswehave
tried to minimise the disclaimers and qualifiers. This aids clarity, but be aware, almost everything is
morecomplicatedthanitfirstappears!
ThirtyyearsinNMRhasbeenfun.Theamazingthingisthatitisstillfun...andchallenging...and
stimulatingevennow!
Pleasenotethatallspectraincludedinthisbookwereacquiredat400MHzunlessotherwisestated.
xi
P1:JYS
c01 JWST025-Richards September27,2010 17:16 Printer:Yettocome
1
Getting Started
1.1 TheTechnique
Thisbookisnotreallyintendedtogiveanin-deptheducationinallaspectsoftheNMReffect(thereare
numerousexcellenttextsifyouwantmoreinformation)butwewilltrytodealwithsomeofthemore
pertinentones.
The first thing to understand about NMR is just how insensitive it is compared with many other
analyticaltechniques.ThisisbecauseoftheoriginoftheNMRsignalitself.
The NMR signal arises from a quantum mechanical property of nuclei called ‘spin’. In the text
here, we will use the example of the hydrogen nucleus (proton) as this is the nucleus that we will be
dealing with mostly. Protons have a ‘spin quantum number’ of 1/. In this case, when they are placed
2
inamagneticfield,therearetwopossiblespinstatesthatthenucleuscanadoptandthereisanenergy
differencebetweenthem(Figure1.1).
Theenergydifferencebetweentheselevelsisverysmall,whichmeansthatthepopulationdifference
isalsosmall.TheNMRsignalarisesfromthispopulationdifferenceandhencethesignalisalsovery
small.Thereareseveralfactorswhichinfluencethepopulationdifferenceandtheseincludethenature
of the nucleus (its ‘gyromagnetic ratio’) and the strength of the magnetic field that they are placed in.
Theequationthatrelatesthesefactors(andtheonlyoneinthisbook)isshownhere:
γhB γ =Gyromagneticratio
(cid:1)E = h =Planck’sconstant
2π B =Magneticfieldstrength
Becausethesensitivityofthetechniquegoesupwithmagneticfield,therehasbeenadrivetoincrease
thestrengthofthemagnetstoimprovesensitivity.
Unfortunately,thisimprovementhasbeenlinearsincethefirstNMRmagnets(withafewkinkshere
andthere).Thismeansthatinpercentageterms,thebenefitshavebecomesmallerasdevelopmenthas
continued. But sensitivity has not been the only factor driving the search for more powerful magnets.
Youalsobenefitfromstretchingyourspectrumandreducingoverlapofsignalswhenyougotohigher
fields.Also,whenyouexamineallthefactorsinvolvedinsignaltonoise,thedependenceonfieldisto
Essential Practical NMR for Organic Chemistry S. A. Richards and J. C. Hollerton
© 2011 John Wiley & Sons, Ltd. ISBN: 978-0-470-71092-0