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Book Details
Abstract
This book is aimed at informing organic chemists and natural products chemists on the use of NMR for structure elucidation to enable them to ensure they yield the most reliable possible data in the minimum possible time. It covers the latest pulse sequences, acquisition and processing methods, practical areas not covered in most texts e.g. detailed consideration of the relative advantages and disadvantages of different pulse sequences, choosing acquisition and processing parameters to get the best possible data in the least possible time, pitfalls to avoid and how to minimize the risks of getting wrong structures. Useful in industrial, pharma or research environments, this reference book is for anyone involved with organic chemistry research and, in particular, natural products research requiring advice for getting the best results from the NMR facilities.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Author Biographies | v | ||
| Acknowledgements | vii | ||
| Dedication | ix | ||
| Contents | xi | ||
| Chapter 1 Introduction | 1 | ||
| References | 3 | ||
| Chapter 2 Basics of the NMR Experiment | 4 | ||
| 2.1 Spin and Magnetic Properties of Nuclei | 4 | ||
| 2.2 Behavior of Magnetic Nuclei in a Static External Magnetic Field | 6 | ||
| 2.3 Alternative Simplified Descriptions of the Basic NMR Experiment | 6 | ||
| 2.4 Key NMR Parameters | 9 | ||
| 2.4.1 Chemical Shifts | 9 | ||
| 2.4.2 Coupling Constants | 12 | ||
| 2.4.3 Relaxation Times | 13 | ||
| 2.4.4 Nuclear Overhauser Enhancements | 16 | ||
| References | 17 | ||
| Chapter 3 Pulsed Fourier Transform NMR | 18 | ||
| 3.1 Historical Background | 18 | ||
| 3.2 Basic Theory of Pulsed FT NMR | 19 | ||
| 3.3 Sampling Rate, Dwell Time, Acquisition Time and Digital Resolution | 24 | ||
| 3.4 Analog to Digital Conversion and Digital Oversampling | 25 | ||
| 3.5 Quadrature Detection | 26 | ||
| 3.6 Fold-in Peaks and Analog or Digital Filters | 28 | ||
| 3.7 Avoiding Partial Saturation in Multi-scan Spectra | 31 | ||
| 3.8 Zero Filling | 33 | ||
| References | 33 | ||
| Chapter 4 The NMR Spectrometer | 34 | ||
| 4.1 The Magnet | 34 | ||
| 4.1.1 Superconducting Solenoids | 34 | ||
| 4.1.2 Potential Future Developments | 35 | ||
| 4.2 NMR Probes | 36 | ||
| 4.2.1 Room Temperature Probes | 36 | ||
| 4.2.2 Cryogenically Cooled Probes | 37 | ||
| 4.2.3 Flow NMR Probes | 38 | ||
| 4.3 Console | 39 | ||
| 4.4 Other Useful Accessories | 40 | ||
| 4.5 Buying an NMR Spectrometer | 40 | ||
| 4.6 Maintaining an NMR Spectrometer | 43 | ||
| References | 44 | ||
| Chapter 5 Acquiring 1H and 13C Spectra | 45 | ||
| 5.1 1H and 13C Spin–Lattice Relaxation Times for Typical Organic Molecules in the 150–450 Dalton Molecular Weight Range | 45 | ||
| 5.2 Sample and Spectrometer Preparation | 48 | ||
| 5.2.1 Solvent Choice | 48 | ||
| 5.2.2 Sample Preparation | 49 | ||
| 5.2.3 Spectrometer Preparation | 50 | ||
| 5.3 Acquiring and Processing Routine 1H Spectra | 54 | ||
| 5.4 Acquiring and Processing Routine 13C Spectra | 56 | ||
| 5.5 Reporting Data for Routine 1H and 3C Spectra | 58 | ||
| 5.6 Acquiring Quantitative 1H Spectra | 60 | ||
| 5.6.1 Reasons for Acquiring Quantitative 1H NMR Spectra | 60 | ||
| 5.6.2 Conditions for Acquiring Quantitative Spectra and Accurately Measuring Peak Areas | 60 | ||
| 5.6.3 Internal Versus External Referencing | 64 | ||
| 5.7 Summary of Recommendations for Chapter 5 | 66 | ||
| References | 67 | ||
| Chapter 6 One-dimensional Pulse Sequences | 68 | ||
| 6.1 Relaxation Time Measurements | 68 | ||
| 6.1.1 T1 Measurements | 68 | ||
| 6.1.2 T2 Measurements | 70 | ||
| 6.2 Pulse Sequences for 13C Spectral Editing | 71 | ||
| 6.2.1 INEPT and DEPT | 71 | ||
| 6.2.2 APT and CRAPT | 74 | ||
| 6.3 Pulse Sequences for Solvent Suppression | 77 | ||
| 6.4 Pure Shift Pulse Sequences | 79 | ||
| References | 80 | ||
| Chapter 7 Two-dimensional NMR Basics | 82 | ||
| 7.1 Alternative Methods of Generating Information During the Evolution Period | 83 | ||
| 7.2 Homonuclear or Heteronuclear 2D Spectra | 84 | ||
| 7.3 Direct Detection or Inverse Detection for Heteronuclear 2D Sequences | 87 | ||
| 7.4 Absolute Value or Phase Sensitive 2D Spectra | 87 | ||
| 7.5 Weighting Functions for Processing 2D Data Sets | 88 | ||
| 7.6 Coherence Pathways, Phase Cycling and Gradient Selection | 89 | ||
| 7.6.1 Coherence Pathways | 89 | ||
| 7.6.2 Phase Cycling | 91 | ||
| 7.6.3 Gradient Selection | 92 | ||
| 7.7 Alternative Acquisition and Processing Methods for Saving Time When Acquiring 2D Spectra | 94 | ||
| 7.7.1 Forward Linear Prediction | 94 | ||
| 7.7.2 Non-uniform (Sparse) Sampling | 95 | ||
| 7.7.3 CRAFT-2D | 100 | ||
| 7.7.4 Co-variance Processing | 101 | ||
| 7.7.5 Simultaneous Acquisition or Sequential Acquisition of 2D Spectra | 102 | ||
| 7.8 Specialized Pulses to Replace Hard Pulses | 103 | ||
| 7.8.1 Adiabatic Pulses | 103 | ||
| 7.8.2 Frequency-selective Shaped Pulses | 104 | ||
| 7.8.3 Broad-band Decoupling Sequences | 105 | ||
| References | 106 | ||
| Chapter 8 Two-dimensional Homonuclear Spectroscopy | 108 | ||
| 8.1 1H Correlation Spectra Based on Homonuclear Coupling Constants | 108 | ||
| 8.1.1 COSY Spectra | 108 | ||
| 8.1.2 2D TOCSY and Selective 1D TOCSY Spectra | 117 | ||
| 8.2 1H Correlation Spectra Based on Nuclear Overhauser Enhancements | 120 | ||
| 8.2.1 2D NOESY and ROESY Spectra | 120 | ||
| 8.2.2 1D NOESY Spectra and Accurate Distance Measurements | 125 | ||
| 8.2.3 EXSY Spectra | 128 | ||
| 8.3 Recommended Acquisition and Processing Methods and Parameters for 2D and Selective 1D Homonuclear Correlation Spectra | 131 | ||
| 8.3.1 Absolute Value COSY Spectra | 133 | ||
| 8.3.2 Double Quantum Filtered COSY Spectra | 134 | ||
| 8.3.3 2D TOCSY and 1D TOCSY Spectra | 135 | ||
| 8.3.4 2D NOESY and ROESY Spectra and 1D NOESY Spectra | 136 | ||
| 8.4 Summary of Key Recommendations from Chapter 8 | 136 | ||
| References | 137 | ||
| Chapter 9 Heteronuclear Shift Correlation Sequences | 139 | ||
| 9.1 Direct Detection Sequences | 139 | ||
| 9.1.1 One-bond Correlation Spectra | 139 | ||
| 9.1.2 Long-range Heteronuclear Shift Correlation Spectra | 140 | ||
| 9.2 Sequences for Generating 1-bond 13C–1H Shift Correlation Spectra by 1H Detection | 143 | ||
| 9.2.1 HMQC | 143 | ||
| 9.2.2 HSQC | 144 | ||
| 9.2.3 ASAP-HMQC and ASAP-HSQC | 148 | ||
| 9.3 1H-detected 1H–13C Long-range Shift Correlation Spectra | 151 | ||
| 9.3.1 HMBC Spectra | 151 | ||
| 9.3.2 Modified HMBC Sequences | 153 | ||
| 9.3.3 Sequences That Can Distinguish Between 2-Bond and Longer-range 13C–1H Correlations | 154 | ||
| 9.3.4 Longer-range 13C–1H Shift Correlation Sequences | 159 | ||
| 9.3.5 Sequences Requiring 13C–13C Coupling Constants | 160 | ||
| 9.3.6 1H–15N Correlation Spectra | 163 | ||
| 9.3.7 Hybrid HSQC Sequences | 164 | ||
| 9.4 Recommended Acquisition and Processing Methods and Parameters for 2D Heteronuclear Correlation Spectra | 164 | ||
| 9.4.1 HSQC Spectra | 165 | ||
| 9.4.2 ASAP-HMQC and ASAP-HSQC Spectra | 165 | ||
| 9.4.3 HMBC and CIGAR Spectra | 166 | ||
| 9.4.4 H2BC Spectra | 167 | ||
| 9.4.5 LR-HSQMBC and HSQMBC-TOCSY Spectra | 168 | ||
| 9.4.6 1, 1-ADEQUATE and 1, n-ADEQUATE Spectra | 168 | ||
| 9.4.7 1H–15N Correlation Spectra | 169 | ||
| 9.5 Summary of Recommendations from Chapter 9 | 169 | ||
| References | 171 | ||
| Chapter 10 Sample Dereplication and Data Archiving | 174 | ||
| 10.1 Sample Dereplication | 174 | ||
| 10.2 Databases and Data Archiving | 176 | ||
| References | 179 | ||
| Chapter 11 Using Combinations of 2D NMR Spectral Data for Ab Initio Structure Elucidation of Natural Products and Other Unknown Organic Compounds | 180 | ||
| 11.1 Determining the Skeletal Structures of Unknown Organic Compounds | 180 | ||
| 11.1.1 Tabulating Basic 1H and 13C Data | 181 | ||
| 11.1.2 Determining Molecular Fragments of a Target Molecule, Based on Networks of Coupled Protons | 183 | ||
| 11.1.3 Assembling the Complete Molecular Skeleton | 186 | ||
| 11.1.4 What to do if Further Information is Needed to Determine the Skeletal Structure | 191 | ||
| 11.2 Determining the Stereochemistry of an Unknown Organic Compound | 197 | ||
| 11.2.1 Using Vicinal 1H–1H Coupling Constants and Nuclear Overhauser Enhancements to Deduce Stereochemistry | 197 | ||
| 11.2.2 What to Do If Further Information Is Needed to Determine the Stereochemistry of a Molecule | 200 | ||
| References | 203 | ||
| Chapter 12 Avoiding Getting the Wrong Structure | 206 | ||
| 12.1 Possible Reasons for Making a Structure Assignment Error When Using Modern NMR Methods | 207 | ||
| 12.2 Basic Precautions That Minimize the Risk of Getting the Wrong Structure | 207 | ||
| 12.3 Two Examples Where an Incorrect Structure Was Reported for a Natural Product and Later Corrected | 208 | ||
| 12.3.1 Hexacyclinol | 208 | ||
| 12.3.2 Aquatolide | 210 | ||
| 12.4 Ten Spectroscopic Traps in NMR That Could Lead to Wrong Structures and How to Avoid Them | 211 | ||
| 12.4.1 The Significance of Not Observing Expected Peaks and of Observing Unexpected Peaks in HMBC Spectra | 211 | ||
| 12.4.2 Carbon Chemical Shifts Can Sometimes Have Unexpected Values | 212 | ||
| 12.4.3 Beware of Accidentally Equivalent Proton Chemical Shifts | 213 | ||
| 12.4.4 Be Aware of the Significance of Apparent One-bond HMBC Peaks | 215 | ||
| 12.4.5 COSY Artifacts Can Confuse NOESY (or ROESY) Spectra | 218 | ||
| 12.4.6 Multiplet Splittings Are Not Always the Same as Coupling Constants; Virtual Coupling | 219 | ||
| 12.4.7 It Is Possible to Determine Coupling Constants Between Equivalent or Near-equivalent Protons on Adjacent Carbons | 222 | ||
| 12.4.8 Be Aware of Possible Long-range 1H–1H Coupling Constants | 223 | ||
| 12.4.9 Resolving Proton Overlap; a Ten Cent Solution | 225 | ||
| 12.4.10 Other Techniques for Resolving Overlap Problems | 228 | ||
| References | 228 | ||
| Chapter 13 What Does the Future Hold for Small Molecule Structure Elucidation by NMR? | 231 | ||
| References | 234 | ||
| Subject Index | 235 |