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.
By:
S. A. Richards (GlaxoSmithKline R&D Ltd),
J. C. Hollerton (GlaxoSmithKline R&D Ltd)
Imprint: John Wiley & Sons Inc
Country of Publication: United States
Edition: 2nd edition
Dimensions:
Height: 254mm,
Width: 178mm,
Spine: 19mm
Weight: 765g
ISBN: 9781119844808
ISBN 10: 1119844800
Pages: 288
Publication Date: 09 February 2023
Audience:
Professional and scholarly
,
Undergraduate
Format: Hardback
Publisher's Status: Active
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
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.
