Essential Practical NMR for Organic Chemistry
2. Auflage Februar 2023
288 Seiten, Hardcover
Praktikerbuch
ISBN:
978-1-119-84480-8
John Wiley & Sons
Essential Practical NMR for Organic Chemistry
A hands-on resource advocating an ordered approach to gathering and interpreting NMR data
The second edition of Essential Practical NMR for Organic Chemistry delivers a pragmatic and accessible text demonstrating an ordered approach to gathering and interpreting NMR data. In this informal guide, you'll learn to make sense of the high density of NMR information through the authors' problem-solving strategies and interpretations.
The book also discusses critical aspects of NMR theory, as well as data acquisition and processing strategy. It explains the use of NMR spectroscopy for dealing with problems of small organic molecule structural elucidation and includes a brand-new chapter on Nitrogen-15 NMR. Readers will also find:
* Strategies for preparing a sample, spectrum acquisition, processing, and interpreting your spectrum
* Fulsome discussions of Carbon-13 NMR spectroscopy
* Practical treatments of quantification, safety procedures, and relevant software
An ideal handbook for anyone involved in using NMR to solve structural problems, this latest edition of Essential Practical NMR for Organic Chemistry will be particularly useful for chemists running and looking at their own NMR spectra, as well as those who work in small molecule NMR. It will also earn a place in the libraries of undergraduate and post-graduate organic chemistry students.
Preface xiii
1 Getting Started 1
1.1 The Technique 1
1.2 Instrumentation 2
1.2.1 CW Systems 2
1.2.2 FT Systems 3
1.2.3 Probes 5
1.2.4 Shims 6
1.3 Origin of the Chemical Shift 7
1.4 Origin of 'Splitting' 8
1.5 Integration 11
2 Preparing the Sample 13
2.1 How Much Sample Do I Need? 14
2.2 Solvent Selection 15
2.2.1 Deutero Chloroform (CDCl3) 16
2.2.2 Deutero Dimethyl Sulfoxide (DMSO) 16
2.2.3 Deutero Methanol (CD3 Od) 17
2.2.4 Deutero Water (D2O) 18
2.2.5 Deutero Benzene (C6d 6) 18
2.2.6 Carbon Tetrachloride (CCl 4) 18
2.2.7 Trifluoroacetic Acid (CF3Cooh) 18
2.2.8 Using Mixed Solvents 19
2.3 Spectrum Referencing (Proton NMR) 19
2.4 Sample Preparation 20
2.4.1 Filtration 21
3 Spectrum Acquisition 25
3.1 Number of Transients 25
3.2 Number of Points 26
3.3 Spectral Width 27
3.4 Acquisition Time 27
3.5 Pulse Width/Pulse Angle 27
3.6 Relaxation Delay 29
3.7 Number of Increments 29
3.8 Non-Uniform Sampling (NUS) 30
3.9 Shimming 30
3.10 Tuning and Matching 32
3.11 Frequency Lock 32
3.11.1 Run Unlocked 32
3.11.2 Internal Lock 32
3.11.3 External Lock 32
3.12 To Spin or Not to Spin? 33
4 Processing 35
4.1 Introduction 35
4.2 Zero-Filling and Linear Prediction 35
4.3 Apodization 36
4.4 Fourier Transformation 37
4.5 Phase Correction 37
4.6 Baseline Correction 40
4.7 Integration 40
4.8 Referencing 40
4.9 Peak Picking 41
5 Interpreting Your Spectrum 43
5.1 Common Solvents and Impurities 46
5.2 Group 1 - Exchangeables and Aldehydes 48
5.3 Group 2 - Aromatic and Heterocyclic Protons 50
5.3.1 Monosubstituted Benzene Rings 52
5.3.2 Multi-substituted Benzene Rings 55
5.3.3 Heterocyclic Ring Systems (Unsaturated) and Polycyclic Aromatic Systems 57
5.4 Group 3 - Double and Triple Bonds 61
5.5 Group 4 - Alkyl Protons 64
6 Delving Deeper 67
6.1 Chiral Centres 67
6.2 Enantiotopic and Diastereotopic Protons 72
6.3 Molecular Anisotropy 73
6.4 Accidental Equivalence 75
6.5 Restricted Rotation 77
6.6 Heteronuclear Coupling 81
6.6.1 coupling between Protons and ¯13 C 81
6.6.2 Coupling between Protons and ¯19 F 83
6.6.3 Coupling between Protons and ¯31 P 85
6.6.4 Coupling between ¯1H and Other Heteroatoms 87
6.7 Cyclic Compounds and the Karplus Curve 89
6.8 Salts, Free Bases and Zwitterions 93
6.9 Zwitterionic Compounds Are Worthy of Special Mention 94
7 Further Elucidation Techniques - Part 1 97
7.1 Chemical Techniques 97
7.1.1 Deuteration 97
7.1.2 Basification and Acidification 99
7.1.3 Changing Solvents 99
7.1.4 Trifluoroacetylation 100
7.1.5 Lanthanide Shift Reagents 101
7.1.6 Chiral Resolving Agents 102
8 Further Elucidation Techniques - Part 2 105
8.1 Introduction 105
8.2 Spin-Decoupling (Homonuclear, 1-D) 105
8.3 Correlated Spectroscopy (COSY) 106
8.4 Total Correlation Spectroscopy (TOCSY) 1- and 2-D 110
8.5 The Nuclear Overhauser Effect (NOE) and Associated Techniques 111
9 Carbon-13 NMR Spectroscopy 121
9.1 General Principles and 1-D ¯13 C 121
9.2 2-D Proton-Carbon (Single Bond) Correlated Spectroscopy 124
9.3 2-D Proton-Carbon (Multiple Bond) Correlated Spectroscopy 127
9.4 Piecing It All Together 130
9.5 Choosing the Right Tool 131
10 Nitrogen-15 NMR Spectroscopy 137
10.1 Introduction 137
10.2 Referencing 138
10.3 Using ¯15 N Data 138
10.4 Amines 141
10.4.1 Alkyl 141
10.4.2 Aryl 143
10.5 Conjugated Amines 145
10.6 Amides 145
10.7 Amidines 146
10.8 Azides 147
10.9 Carbamates 147
10.10 Cyanates and Thiocyanates 148
10.11 Diazo Compounds 149
10.12 Formamides 149
10.13 Hydrazines 150
10.14 Hydroxamic Acids 151
10.15 Hydroxylamines 152
10.16 Imides (Alkyl and Aryl) 152
10.17 Imines 152
10.18 Isocyanates and Isothiocyanates 153
10.19 Nitrogen-Bearing Heterocycles 154
10.20 Nitriles 157
10.21 Nitro Compounds 158
10.22 Nitroso and N-Nitroso Compounds 158
10.23 N-Oxides 159
10.24 Oximes 160
10.25 Sulfonamides 161
10.26 Ureas and Thioureas 162
10.27 Other Unusual Compounds 163
10.28 ¯15 N Topics 166
10.28.1 1-, 2-, 3- and 4-bond Correlations 166
10.28.2 'Through-Space' Correlations 168
10.28.3 Tautomerism in ¯15 N NMR 169
10.28.4 Restricted Rotation 170
10.28.5 Protonation and Zwitterions 170
11 Some Other Techniques and Nuclei 173
11.1 HPLC-NMR 173
11.2 Flow NMR 174
11.3 Solvent Suppression 175
11.4 MAS (Magic Angle Spinning) NMR 176
11.5 Pure Shift NMR 177
11.6 Other 2-D Techniques 178
11.6.1 INADEQUATE 178
11.6.2 J-Resolved 178
11.6.3 DOSY 178
11.7 3-D Techniques 179
11.8 Fluorine (¯19 F) NMR 180
11.9 Phosphorus (¯31 P) NMR 182
12 Dynamics 183
12.1 Linewidths 187
12.2 Chemical Shifts 187
12.3 Splittings 188
12.4 Relaxation Pathways 188
12.5 Experimental Techniques 188
12.6 In Practice 189
12.7 In Conclusion 191
13 Quantification 193
13.1 Introduction 193
13.2 Different Approaches to Quantification 193
13.2.1 Relative Quantification 193
13.2.2 Absolute Quantification 194
13.2.3 Internal Standards 194
13.2.4 External Standards 195
13.2.5 Electronic Reference (ERETIC) 195
13.2.6 QUANTAS196
13.2.7 ERETIC 2 196
13.3 Things to Watch Out For 197
13.4 Quantification of Other Nuclei 197
13.5 Conclusion 198
14 Safety 199
14.1 Magnetic Fields 199
14.2 Cryogens 201
14.3 Sample-Related Injuries 202
15 Software 203
15.1 Acquisition Software 203
15.2 Processing Software 204
15.3 Prediction and Simulation Software 205
15.3.1 ¯13 C Prediction 205
15.3.2 ¯1 H Prediction 207
15.3.3 Incremental Approaches 207
15.3.4 HOSE Code Databases 208
15.3.5 Semi-Empirical Approaches 208
15.3.6 Ab Initio Approaches 208
15.3.7 Neural Networks 208
15.5.8 Hybrid Approaches 209
15.5.9 Simulation 209
15.6 Structural Verification Software 209
15.7 Structural Elucidation Software 211
15.8 Summary 212
16 Problems 213
16.1 Questions 213
16.2 Hints 227
16.3 Answers 228
16.4 A Closing Footnote 241
17 Raising Your Game 243
17.1 Spotting the Pitfalls 243
17.2 The Wrong Solvent 244
17.3 Choosing the Right Experiment 245
Appendix A 261
Glossary 263
Index 269
1 Getting Started 1
1.1 The Technique 1
1.2 Instrumentation 2
1.2.1 CW Systems 2
1.2.2 FT Systems 3
1.2.3 Probes 5
1.2.4 Shims 6
1.3 Origin of the Chemical Shift 7
1.4 Origin of 'Splitting' 8
1.5 Integration 11
2 Preparing the Sample 13
2.1 How Much Sample Do I Need? 14
2.2 Solvent Selection 15
2.2.1 Deutero Chloroform (CDCl3) 16
2.2.2 Deutero Dimethyl Sulfoxide (DMSO) 16
2.2.3 Deutero Methanol (CD3 Od) 17
2.2.4 Deutero Water (D2O) 18
2.2.5 Deutero Benzene (C6d 6) 18
2.2.6 Carbon Tetrachloride (CCl 4) 18
2.2.7 Trifluoroacetic Acid (CF3Cooh) 18
2.2.8 Using Mixed Solvents 19
2.3 Spectrum Referencing (Proton NMR) 19
2.4 Sample Preparation 20
2.4.1 Filtration 21
3 Spectrum Acquisition 25
3.1 Number of Transients 25
3.2 Number of Points 26
3.3 Spectral Width 27
3.4 Acquisition Time 27
3.5 Pulse Width/Pulse Angle 27
3.6 Relaxation Delay 29
3.7 Number of Increments 29
3.8 Non-Uniform Sampling (NUS) 30
3.9 Shimming 30
3.10 Tuning and Matching 32
3.11 Frequency Lock 32
3.11.1 Run Unlocked 32
3.11.2 Internal Lock 32
3.11.3 External Lock 32
3.12 To Spin or Not to Spin? 33
4 Processing 35
4.1 Introduction 35
4.2 Zero-Filling and Linear Prediction 35
4.3 Apodization 36
4.4 Fourier Transformation 37
4.5 Phase Correction 37
4.6 Baseline Correction 40
4.7 Integration 40
4.8 Referencing 40
4.9 Peak Picking 41
5 Interpreting Your Spectrum 43
5.1 Common Solvents and Impurities 46
5.2 Group 1 - Exchangeables and Aldehydes 48
5.3 Group 2 - Aromatic and Heterocyclic Protons 50
5.3.1 Monosubstituted Benzene Rings 52
5.3.2 Multi-substituted Benzene Rings 55
5.3.3 Heterocyclic Ring Systems (Unsaturated) and Polycyclic Aromatic Systems 57
5.4 Group 3 - Double and Triple Bonds 61
5.5 Group 4 - Alkyl Protons 64
6 Delving Deeper 67
6.1 Chiral Centres 67
6.2 Enantiotopic and Diastereotopic Protons 72
6.3 Molecular Anisotropy 73
6.4 Accidental Equivalence 75
6.5 Restricted Rotation 77
6.6 Heteronuclear Coupling 81
6.6.1 coupling between Protons and ¯13 C 81
6.6.2 Coupling between Protons and ¯19 F 83
6.6.3 Coupling between Protons and ¯31 P 85
6.6.4 Coupling between ¯1H and Other Heteroatoms 87
6.7 Cyclic Compounds and the Karplus Curve 89
6.8 Salts, Free Bases and Zwitterions 93
6.9 Zwitterionic Compounds Are Worthy of Special Mention 94
7 Further Elucidation Techniques - Part 1 97
7.1 Chemical Techniques 97
7.1.1 Deuteration 97
7.1.2 Basification and Acidification 99
7.1.3 Changing Solvents 99
7.1.4 Trifluoroacetylation 100
7.1.5 Lanthanide Shift Reagents 101
7.1.6 Chiral Resolving Agents 102
8 Further Elucidation Techniques - Part 2 105
8.1 Introduction 105
8.2 Spin-Decoupling (Homonuclear, 1-D) 105
8.3 Correlated Spectroscopy (COSY) 106
8.4 Total Correlation Spectroscopy (TOCSY) 1- and 2-D 110
8.5 The Nuclear Overhauser Effect (NOE) and Associated Techniques 111
9 Carbon-13 NMR Spectroscopy 121
9.1 General Principles and 1-D ¯13 C 121
9.2 2-D Proton-Carbon (Single Bond) Correlated Spectroscopy 124
9.3 2-D Proton-Carbon (Multiple Bond) Correlated Spectroscopy 127
9.4 Piecing It All Together 130
9.5 Choosing the Right Tool 131
10 Nitrogen-15 NMR Spectroscopy 137
10.1 Introduction 137
10.2 Referencing 138
10.3 Using ¯15 N Data 138
10.4 Amines 141
10.4.1 Alkyl 141
10.4.2 Aryl 143
10.5 Conjugated Amines 145
10.6 Amides 145
10.7 Amidines 146
10.8 Azides 147
10.9 Carbamates 147
10.10 Cyanates and Thiocyanates 148
10.11 Diazo Compounds 149
10.12 Formamides 149
10.13 Hydrazines 150
10.14 Hydroxamic Acids 151
10.15 Hydroxylamines 152
10.16 Imides (Alkyl and Aryl) 152
10.17 Imines 152
10.18 Isocyanates and Isothiocyanates 153
10.19 Nitrogen-Bearing Heterocycles 154
10.20 Nitriles 157
10.21 Nitro Compounds 158
10.22 Nitroso and N-Nitroso Compounds 158
10.23 N-Oxides 159
10.24 Oximes 160
10.25 Sulfonamides 161
10.26 Ureas and Thioureas 162
10.27 Other Unusual Compounds 163
10.28 ¯15 N Topics 166
10.28.1 1-, 2-, 3- and 4-bond Correlations 166
10.28.2 'Through-Space' Correlations 168
10.28.3 Tautomerism in ¯15 N NMR 169
10.28.4 Restricted Rotation 170
10.28.5 Protonation and Zwitterions 170
11 Some Other Techniques and Nuclei 173
11.1 HPLC-NMR 173
11.2 Flow NMR 174
11.3 Solvent Suppression 175
11.4 MAS (Magic Angle Spinning) NMR 176
11.5 Pure Shift NMR 177
11.6 Other 2-D Techniques 178
11.6.1 INADEQUATE 178
11.6.2 J-Resolved 178
11.6.3 DOSY 178
11.7 3-D Techniques 179
11.8 Fluorine (¯19 F) NMR 180
11.9 Phosphorus (¯31 P) NMR 182
12 Dynamics 183
12.1 Linewidths 187
12.2 Chemical Shifts 187
12.3 Splittings 188
12.4 Relaxation Pathways 188
12.5 Experimental Techniques 188
12.6 In Practice 189
12.7 In Conclusion 191
13 Quantification 193
13.1 Introduction 193
13.2 Different Approaches to Quantification 193
13.2.1 Relative Quantification 193
13.2.2 Absolute Quantification 194
13.2.3 Internal Standards 194
13.2.4 External Standards 195
13.2.5 Electronic Reference (ERETIC) 195
13.2.6 QUANTAS196
13.2.7 ERETIC 2 196
13.3 Things to Watch Out For 197
13.4 Quantification of Other Nuclei 197
13.5 Conclusion 198
14 Safety 199
14.1 Magnetic Fields 199
14.2 Cryogens 201
14.3 Sample-Related Injuries 202
15 Software 203
15.1 Acquisition Software 203
15.2 Processing Software 204
15.3 Prediction and Simulation Software 205
15.3.1 ¯13 C Prediction 205
15.3.2 ¯1 H Prediction 207
15.3.3 Incremental Approaches 207
15.3.4 HOSE Code Databases 208
15.3.5 Semi-Empirical Approaches 208
15.3.6 Ab Initio Approaches 208
15.3.7 Neural Networks 208
15.5.8 Hybrid Approaches 209
15.5.9 Simulation 209
15.6 Structural Verification Software 209
15.7 Structural Elucidation Software 211
15.8 Summary 212
16 Problems 213
16.1 Questions 213
16.2 Hints 227
16.3 Answers 228
16.4 A Closing Footnote 241
17 Raising Your Game 243
17.1 Spotting the Pitfalls 243
17.2 The Wrong Solvent 244
17.3 Choosing the Right Experiment 245
Appendix A 261
Glossary 263
Index 269
S.A. Richards and J.C. Hollerton
The authors have worked in NMR for GlaxoSmithKline R&D for over 40 years each, solving organic chemistry structural problems supporting synthetic and medicinal chemists. This work has required the inference of structural information from complex NMR data as well as the design of experiments to test structural hypotheses. Their breadth of experience includes instrumental, chemical, and informatics approaches to answering those important structural questions.
The authors have worked in NMR for GlaxoSmithKline R&D for over 40 years each, solving organic chemistry structural problems supporting synthetic and medicinal chemists. This work has required the inference of structural information from complex NMR data as well as the design of experiments to test structural hypotheses. Their breadth of experience includes instrumental, chemical, and informatics approaches to answering those important structural questions.
