Organic Structure Determination Using 2-D NMR Spectroscopy, Second Edition: A Problem-Based Approach

573 Pages·2012·32.545 MB·English

by  Jeffrey H. Simpson

Organic Structure Determination
Using 2-D NMR Spectroscopy
A Problem-Based Approach
Second Edition
Jeffrey H. Simpson
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts, USA
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Simpson,JeffreyH.
Organicstructuredeterminationusing2-DNMRspectroscopy:a
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p.cm.
ISBN978-0-12-384970-0(pbk.)
1.Molecularstructure.2.OrganiccompoundseAnalysis.3.Nuclear
magneticresonancespectroscopy.I.Title.
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2011038670
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Dedicated to
Edward Worcester
teacher, coach, philosopher
1935e2011
Preface
Thesecondeditionofthisbookcomeswithanumberofnewfigures,passages,andproblems.
Increasing the number of figures from 290 to 448 has necessarily impacted the balance
between length, margins, and expense. It is my hope that the book has not lost any of its
readabilityandaccessibility.Ifirmlybelievethatmostoftheconceptsneededtolearnorganic
structure determination using nuclear magnetic resonance spectroscopy do not require an
extensive mathematical background. It is my hope that the manner in which the material
contained in this book is presented both reflects and validates this belief.
Thesecondeditionowesmuchofitsimprovementtotheeffortsofothers.Mostnotably,Letitia
YaooftheUniversityofMinnesotalaboredmightilytoimprovethe2ndeditionmanuscript.A
number of researchers at the Massachusetts Institute of Technology assisted in generating
samples and collecting some of the data that appear in this edition. In this regard, I wish to
thank Jason Cox, Rick Danheiser, John Essigmann, Shaun Fontaine, Tim Jamison, Deyu Li,
Ryan Moslin, Julia Robinson, and Tim Swager. As before, a number of Elsevier personnel
have also assisted in bringing this edition to fruition. Those at Elsevier who helped with
this edition include Gavin Becker, Joy Fisher Williams, Anita Koch, Emily McCloskey,
MohanapriyanRajendran,LindaVersteeg-Buschman,andRickWilliamson.Ithankthosewho
reviewed the 1st edition and shared their comments. I thank my family for supporting me
during manuscript preparation, editing, and proofing.
Since the publication of the first edition, I have received many emails from readers. These
emailshavebeenoverwhelminglypositive,gratifyinglysuggestingthatthebookfillsanichein
the near continuum of NMR books available today. I am interested in finding out how I may
haveerredinpresentinganymaterialcontainedhereinsothatImaycorrecterrorsandthereby
improve the book. As always, I encourage readers to send me email with comments and
suggestions. My email address is [e-mail].
Lastly, I cannot resist suggesting how best to digest the material contained in this book (this
philosophy can also be applied to other learning endeavors). If we have the luxury of not
havingtoreadandworkcontinuously(i.e.,ifwearenotworkingtosatisfyadeadline),wewill
be well served by taking breaks in between reading and working problems. We balance our
workwithotherinterestsandtrynottoletourfriendshipslanguish.Despitetherigorsofwork,
xiii
xiv Preface
I still find time to bewith my family, to garden, to camp in winter in the White Mountainsof
NewHampshire(sometimesbelow(cid:1)20(cid:3)F/(cid:1)29(cid:3)C),todrawastilllifewithoilpastels,toplay
the electric guitar, to drink beer and throw a Frisbee(cid:1), to troll for landlocked salmon and
togue on Sebec Lake, and to occasionally pull an all-nighter while anchored near the Isles of
Shoals six miles off the coast of Maine and New Hampshire. Life is hurtling by; we must
make the most of it.
Jeff Simpson
Epping, NH, USA
July, 2011
Preface to the First Edition
IwrotethisbookbecausethisbookdidnotexistwhenIbegantolearnabouttheapplicationof
nuclear magnetic resonance spectroscopy to the elucidation of organic molecular structure.
This book started as 40 two-dimensional (2-D) nuclear magnetic resonance (NMR)
spectroscopy problem sets, but, with a little cajoling from my original editor (Jeremy
Hayhurst), I agreed to include problem-solving methodology in chapters 9 and 10, and after
that concession was made, the commitment to generate the first 8 chapters was a relatively
small one.
Two distinct features set this book apart from other books available on the practice of NMR
spectroscopyasappliedtoorganicstructuredetermination.Thefirstfeatureisthatthematerial
is presented with a level of detail great enough to allow the development of useful ‘NMR
intuition’skills, and yet is given at a level that can be understood by a junior-level chemistry
major, or a more advanced organic chemist with a limited background in mathematics and
physical chemistry. The second distinguishing feature of this book is that it reflects my
contention that the best vehicle for learning is to give the reader an abundance of real 2-D
NMR spectroscopy problem sets. These two features should allow the reader to develop
problem-solving skills essential in the practice of modern NMR spectroscopy.
Beyondtheloftygoal of makingthereadermoreskilled atNMR spectruminterpretation,the
bookhasotherpassagesthatmayprovideutility.Theinclusionofanumberofpracticaltipsfor
successfully conducting NMR experiments should also allow this book to serve as a useful
resource.
I would like to thank D.C. Lea, my first teacher of chemistry, Dana Mayo, who inspired me
tostudyNMRspectroscopy,RonaldChristensen,whotookmeunderhiswingforawholeyear,
Bernard Shapiro, who taught the best organic structure determination course I ever took,
DavidRice,whotaughtmehowtowriteapaper,PaulInglefieldandAlanJones,whohadmore
faith in me than I had in myself, Dan Reger who was the best boss a new NMR lab manager
could have and who let me go without recriminations, and, of course, Tim Swager, who
inspired me to amass the data sets that are the heart of this book. I thank Jeremy Hayhurst,
JasonMalley,DerekColeman,andPhilBugeauofElsevier,andJodiSimpson,whograciously
agreed to come out of retirement to copyedit the manuscript. I also wish to thank those who
xv
xvi Preface to the First Edition
reviewed the book and provided helpful suggestions. Finally, I have to thank my wife,
ElizabethWorcester,andmychildren,Grant,Maxwell,andEva,forputtingupwithmeduring
manuscript preparation.
Any errors in this book are solely the fault of the author. If you find an error or have any
constructive suggestions, please tell me about it so that I can improve any possible future
editions. As of this writing, e-mail can be sent to me at [e-mail].
Jeff Simpson
Epping, NH, USA
January, 2008
CHAPTER 1
Introduction
Chapter Outline
1.1 What Is Nuclear Magnetic Resonance? 1
1.2 Consequences of Nuclear Spin 2
1.3 Application of a Magnetic Field to a Nuclear Spin 4
1.4 Application of a Magnetic Field to an Ensemble of Nuclear Spins 7
1.5 Tipping the Net Magnetization Vector from Equilibrium 12
1.6 Signal Detection 13
1.7 The Chemical Shift 14
1.8 The 1-D NMR Spectrum 14
1.9 The 2-D NMR Spectrum 16
1.10 Information Content Available Using NMR Spectroscopy 18
Problems for Chapter One 19
1.1 What Is Nuclear Magnetic Resonance?
Nuclear magnetic resonance (NMR) spectroscopy is arguably the most important analytical
technique available to chemists. From its humble beginnings in 1945, the area of NMR
spectroscopy has evolved into many overlapping subdisciplines. Luminaries have been
awardedseveralrecentNobelprizes,includingRichardErnstin1991,JohnPoplein1998,and
Kurt Wu¨thrich in 2002.
Nuclear magnetic resonance spectroscopy is a techniquewherein a sample is placed in
ahomogeneous1(constant)magneticfield,irradiated,andamagneticsignalisdetected.Photon
bombardment of the sample causes nuclei in the sample to undergo transitions2 (resonance)
between their allowed spin states. In an applied magnetic field, spin states that differ
energetically are unequally populated. Perturbing the equilibrium distribution of the spin-state
population is called excitation.3 The excited nuclei emit a magnetic signal called a free
induction decay4 (FID) which we detect with analog electronics and capture digitally. The
1 Homogeneous. Constant throughout.
2 Transition. Thechange inthespinstate ofone ormore NMR-activenuclei.
3 Excitation. Theperturbation ofspins fromtheir equilibrium distributionof spin-statepopulations.
4 Freeinductiondecay,FID.TheanalogsignalinducedinthereceivercoilofanNMRinstrumentcausedbythe
xycomponentofthenetmagnetization.SometimestheFIDisalsoassumedtobethedigitalarrayofnumbers
corresponding totheFID’s amplitude asa functionof time.
OrganicStructureDeterminationUsing2-DNMRSpectroscopy.DOI:10.1016/B978-0-12-384970-0.00001-6
Copyright(cid:1)2012ElsevierInc.Allrightsreserved. 1
2 Chapter 1
digitizedFID(s)is(are)processedcomputationallyto(wehope)revealmeaningfulthingsabout
our sample.
Althoughexcitationanddetectionmaysoundverycomplicatedandesoteric,wearereallyjust
tweaking the nuclei of atoms in our sample and getting information back. How the nuclei
behaveoncetweakedconveysinformationaboutthechemistryoftheatomsinthemoleculesof
our sample.
TheacronymNMRsimplymeansthatthenuclearportionsofatomsareaffectedbymagnetic
fields and undergo resonance as a result.
1.2 Consequences of Nuclear Spin
Observation of the NMR signal5 requires a sample containing atoms of a specific atomic
numberandisotope,i.e.,aspecificnuclidesuchasprotium,thelightestisotopeoftheelement
hydrogen, also commonly referred to as simply a proton. A magnetically active nuclide will
havetwoormoreallowednuclearspinstates.6Magneticallyactivenuclidesarealsosaidtobe
NMR-active. Table 1.1 lists several NMR-active nuclides in approximate order of their
importance to chemists.
An isotope’s NMR activity is caused by the presence of a magnetic moment7 in its nucleus.
Thenuclearmagneticmomentarisesbecausethepositivechargeprefersnottobewelllocated,
as described by the Heisenberg uncertainty principle (see Figure 1.1). Instead, the nuclear
chargecirculates.Becausethechargeandmassarebothinherenttotheparticle,themovement
ofthechargeimpartsmovementtothemassofthenucleus.Themotionofallrotatingmassesis
Table 1.1: NMR-active nuclides.
Nuclide Element-Isotope Spin NaturalAbundance(%) FrequencyRelativeto1H
1H Hydrogen-1 ½ 99.985 1.00000
13C Carbon-13 ½ 1.108 0.25145
15N Nitrogen-15 ½ 0.37 0.10137
19F Fluorine-19 ½ 100. 0.94094
31P Phosphorus-31 ½ 100. 0.40481
2H(or2D) Deuterium-2 1 0.015 0.15351
5 Signal.An electrical current containinginformation.
6 Spinstate.Syn. spinangular momentum quantumnumber. Theprojection of themagnetic momentofa spin
ontothez-axis.Theorientationofacomponentofthemagneticmomentofaspinrelativetotheappliedfield
axis(fora spin-½ nucleus,this canbe +½ore½).
7 Magneticmoment.Avectorquantityexpressedinunitsofangularmomentumthatrelatesthetorquefeltbythe
particletothemagnitudeand direction ofan externally appliedmagnetic field. The magneticfield associated
withacirculating charge.
Introduction 3
Figure 1.1:
The structure of an atom with the positive charge unequally distributed in the nucleus inside
the electron cloud.
expressed in units of angular momentum. In a nucleus, this motion is called nuclear spin.8
Imaginethemotionofthenucleusasbeinglikethatofawildanimalpacingincirclesinacage.
Nuclear spin (see column three of Table 1.1) is an example of the motion associated with
zero-point energy in quantum mechanics, whose most well-known example is perhaps the
harmonic oscillator.
Thesmallsizeofthenucleusdictatesthatthespinningofthenucleusisquantized;thatis,the
quantummechanicalnatureofsmallparticlesforcesthespinoftheNMR-activenucleustobe
quantized into only a few discrete states. Nuclear spin states are differentiated from one
anotherbasedonhowmuchtheaxisofnuclearspinalignswithareferenceaxis(theaxisofthe
applied magnetic field, see Figure 1.2).
We can determine how many allowed spin states there are for a given nuclide by multiplying
the nuclear spin number (I) by 2 and adding 1. For a spin-½ nuclide, there are therefore
2 (1/2)þ1¼2 allowed spin states.
In the absence of an externally applied magnetic field, the energies of the two spin states of
a spin-½ nuclide are degenerate9 (the same).
The circulation of the nuclear charge, as is expected of any circulating charge, gives rise
to a tiny magnetic field called the nuclear magnetic moment (m) e also commonly
referred to as a spin (recall that the mass puts everything into a world of angular
momentum). Magnetically active nuclei are rotating masses, each with a tiny magnet,
and these nuclear magnets interact with other magnetic fields according to Maxwell’s
equations.
8 Nuclear spin.The circular motionof thepositive chargeof anucleus.
9 Degenerate. Two spinstates are saidtobe degeneratewhen theirenergies are thesame.