Organic Structure Determination Using 2-D NMR Spectroscopy: A Problem-Based Approach (Advanced Organic Chemistry)

377 Pages·2008·3.19 MB·English

by  Jeffrey H. Simpson

Organic Structure Determination
Using 2-D NMR Spectroscopy
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Organic Structure Determination
Using 2-D NMR Spectroscopy
A Problem-Based Approach
Jeff rey H. Simpson
Department of Chemistry Instrumentation Facility
Massachusetts Institute of Technology
Cambridge, Massachusetts
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Library of Congress Cataloging-in-Publication Data
Simpson, Jeffrey H.
Organic structure determination using 2-D NMR spectroscopy / Jeffrey
H. Simpson,
p. cm.
Includes bibliographical references and index.
ISBN 978-0-12-088522-0 (pbk. : alk. paper) 1. Molecular structure. 2. Organic
compounds—Analysis. 3. Nuclear magnetic resonance spectroscopy. I. Title.
QD461.S468 2008
541 ’.22—dc22
2008010004
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
ISBN: 978-0-12-088522-0
For information on all Academic Press publications
visit our Web site at www.books.elsevier.com
Printed in Canada
08 09 10 11 9 8 7 6 5 4 3 2 1
Dedicated to
Alan Jones
mentor, friend, and tragic hero
v
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Contents
Preface xiii
CHAPTER 1 Introduction 1
1.1 What Is Nuclear Magnetic Resonance? 1
1.2 Consequences of Nuclear Spin 1
1.3 Application of a Magnetic Field to a Nuclear Spin 3
1.4 Application of a Magnetic Field to an Ensemble of Nuclear Spins 5
1.5 Tipping the Net Magnetization Vector from Equilibrium 1 1
1.6 Signal Detection 1 2
1.7 The Chemical Shift 13
1.8 The 1-D NMR Spectrum 13
1.9 The 2-D NMR Spectrum 15
1.10 Information Content Available Using NMR 16
CHAPTER 2 Instrumental Considerations 19
2.1 Sample Preparation 1 9
2.1.1 NMR Tube Selection 20
2.1.2 Sample Purity 20
2.1.3 Solvent Selection 21
2.1.4 Cleaning NMR Tubes Prior to Use or Reuse 21
2.1.5 Drying NMR Tubes 21
2.1.6 Sample Mixing 2 2
2.1.7 Sample Volume 2 2
2.1.8 Solute Concentration 24
2.1.9 Optimal Solute Concentration 26
2.1.10 Minimizing Sample Degradation 27
2.2 Locking 27
2.3 Shimming 28
2.4 Temperature Regulation 29
2.5 Modern NMR Instrument Architecture 29
2.5.1 Generation of RF and Its Delivery to the NMR Probe 31
2.5.2 Probe Tuning 31
2.5.3 When to Tune the NMR Probe and Calibrate RF Pulses 32
2.5.4 RF Filtering 33
2.6 Pulse Calibration 3 4
2.7 Sample Excitation and the Rotating Frame of Reference 36
vii
viii Contents
2.8 Pulse Roll-off 37
2.9 Probe Variations 39
2.9.1 Small Volume NMR Probes 41
2.9.2 Flow-Through NMR Probes 41
2.9.3 Cryogenically Cooled Probes 42
2.9.4 Probe Sizes (Diameter of Recommended NMR Tube) 43
2.9.5 Normal Versus Inverse Coil Confi gurations in NMR Probes 44
2.10 Analog Signal Detection 45
2.11 Signal Digitization 45
CHAPTER 3 Data Collection, Processing, and Plotting 51
3.1 Setting the Spectral Window 51
3.2 Determining the Optimal Wait Between Scans 53
3.3 Setting the Acquisition Time 56
3.4 How Many Points to Acquire in a 1-D Spectrum 57
3.5 Zero Filling and Digital Resolution 58
3.6 Setting the Number of Points to Acquire in a 2-D Spectrum 59
3.7 Truncation Error and Apodization 61
3.8 The Relationship Between T * and Observed Line Width 62
2
3.9 Resolution Enhancement 64
3.10 Forward Linear Prediction 65
3.11 Pulse Ringdown and Backward Linear Prediction 66
3.12 Phase Correction 67
3.13 Baseline Correction 70
3.14 Integration 71
3.15 Measurement of Chemical Shifts and J-Couplings 73
3.16 Data Representation 76
CHAPTER 4 1 H and 1 3 C Chemical Shifts 83
4 .1 The Nature of the Chemical Shift 83
4.2 Aliphatic Hydrocarbons 86
4.3 Saturated, Cyclic Hydrocarbons 88
4.4 Olefi nic Hydrocarbons 88
4.5 Acetylenic Hydrocarbons 90
4.6 Aromatic Hydrocarbons 90
4.7 Heteroatom Effects 91
CHAPTER 5 Symmetry and Topicity 95
5 .1 Homotopicity 95
5.2 Enantiotopicity 97
5.3 Diastereotopicity 98
Contents ix
5.4 Chemical Equivalence 99
5.5 Magnetic Equivalence 99
CHAPTER 6 Through-Bond Eff ects: Spin-Spin (J) Coupling 101
6 .1 Origin of J-Coupling 101
6.2 Skewing of the Intensity of Multiplets 103
6.3 Prediction of First-Order Multiplets 106
6.4 The Karplus Relationship for Spins Separated by Three Bonds 110
6.5 The Karplus Relationship for Spins Separated by Two Bonds 111
6.6 Long Range J-Coupling 113
6.7 Decoupling Methods 113
6.8 One-Dimensional Experiments Utilizing J-Couplings 115
6.9 Two-Dimensional Experiments Utilizing J-Couplings 1 17
6.9.1 Homonuclear Two-Dimensional Experiments Utilizing
J-Couplings 118
6.9.1.1 COSY 118
6.9.1.1.1 Phase Sensitive COSY 119
6.9.1.1.2 Absolute-Value COSY, Including gCOSY 120
6.9.1.2 TOCSY 120
6.9.1.3 INADEQUATE 123
6.9.2 Heteronuclear Two-Dimensional Experiments Utilizing J-Couplings 124
6.9.2.1 HMQC and HSQC 124
6.9.2.2 HMBC 132
CHAPTER 7 Through-Space Eff ects: The Nuclear Overhauser Eff ect (NOE) 137
7 .1 The Dipolar Relaxation Pathway 137
7.2 The Energetics of an Isolated Heteronuclear Two-Spin System 138
7.3 The Spectral Density Function 139
7.4 Decoupling One of the Spins in a Heteronuclear Two-Spin System 141
7.5 Rapid Relaxation via the Double Quantum Pathway 142
7.6 A One-Dimensional Experiment Utilizing the NOE 144
7.7 Two-Dimensional Experiments Utilizing the NOE 1 47
7.7.1 NOESY 147
7.7.2 ROESY 148
CHAPTER 8 Molecular Dynamics 151
8 .1 Relaxation 152
8.2 Rapid Chemical Exchange 153
8.3 Slow Chemical Exchange 153
8.4 Intermediate Chemical Exchange 154
8.5 Two-Dimensional Experiments that Show Exchange 156