ISBN-13: 9781119844808 / Angielski / Twarda / 2023 / 282 str.
ISBN-13: 9781119844808 / Angielski / Twarda / 2023 / 282 str.
Preface xiii1 Getting Started 11.1 The Technique 11.2 Instrumentation 21.2.1 CW Systems 21.2.2 FT Systems 31.2.3 Probes 51.2.4 Shims 61.3 Origin of the Chemical Shift 71.4 Origin of 'Splitting' 81.5 Integration 112 Preparing the Sample 132.1 How Much Sample Do I Need? 142.2 Solvent Selection 152.2.1 Deutero Chloroform (CDCl3) 162.2.2 Deutero Dimethyl Sulfoxide (DMSO) 162.2.3 Deutero Methanol (CD3 Od) 172.2.4 Deutero Water (D2O) 182.2.5 Deutero Benzene (C6d 6) 182.2.6 Carbon Tetrachloride (CCl 4) 182.2.7 Trifluoroacetic Acid (CF3Cooh) 182.2.8 Using Mixed Solvents 192.3 Spectrum Referencing (Proton NMR) 192.4 Sample Preparation 202.4.1 Filtration 213 Spectrum Acquisition 253.1 Number of Transients 253.2 Number of Points 263.3 Spectral Width 273.4 Acquisition Time 273.5 Pulse Width/Pulse Angle 273.6 Relaxation Delay 293.7 Number of Increments 293.8 Non-Uniform Sampling (NUS) 303.9 Shimming 303.10 Tuning and Matching 323.11 Frequency Lock 323.11.1 Run Unlocked 323.11.2 Internal Lock 323.11.3 External Lock 323.12 To Spin or Not to Spin? 334 Processing 354.1 Introduction 354.2 Zero-Filling and Linear Prediction 354.3 Apodization 364.4 Fourier Transformation 374.5 Phase Correction 374.6 Baseline Correction 404.7 Integration 404.8 Referencing 404.9 Peak Picking 415 Interpreting Your Spectrum 435.1 Common Solvents and Impurities 465.2 Group 1 - Exchangeables and Aldehydes 485.3 Group 2 - Aromatic and Heterocyclic Protons 505.3.1 Monosubstituted Benzene Rings 525.3.2 Multi-substituted Benzene Rings 555.3.3 Heterocyclic Ring Systems (Unsaturated) and Polycyclic Aromatic Systems 575.4 Group 3 - Double and Triple Bonds 615.5 Group 4 - Alkyl Protons 646 Delving Deeper 676.1 Chiral Centres 676.2 Enantiotopic and Diastereotopic Protons 726.3 Molecular Anisotropy 736.4 Accidental Equivalence 756.5 Restricted Rotation 776.6 Heteronuclear Coupling 816.6.1 coupling between Protons and ¯13 C 816.6.2 Coupling between Protons and ¯19 F 836.6.3 Coupling between Protons and ¯31 P 856.6.4 Coupling between ¯1H and Other Heteroatoms 876.7 Cyclic Compounds and the Karplus Curve 896.8 Salts, Free Bases and Zwitterions 936.9 Zwitterionic Compounds Are Worthy of Special Mention 947 Further Elucidation Techniques - Part 1 977.1 Chemical Techniques 977.1.1 Deuteration 977.1.2 Basification and Acidification 997.1.3 Changing Solvents 997.1.4 Trifluoroacetylation 1007.1.5 Lanthanide Shift Reagents 1017.1.6 Chiral Resolving Agents 1028 Further Elucidation Techniques - Part 2 1058.1 Introduction 1058.2 Spin-Decoupling (Homonuclear, 1-D) 1058.3 Correlated Spectroscopy (COSY) 1068.4 Total Correlation Spectroscopy (TOCSY) 1- and 2-D 1108.5 The Nuclear Overhauser Effect (NOE) and Associated Techniques 1119 Carbon-13 NMR Spectroscopy 1219.1 General Principles and 1-D ¯13 C 1219.2 2-D Proton-Carbon (Single Bond) Correlated Spectroscopy 1249.3 2-D Proton-Carbon (Multiple Bond) Correlated Spectroscopy 1279.4 Piecing It All Together 1309.5 Choosing the Right Tool 13110 Nitrogen-15 NMR Spectroscopy 13710.1 Introduction 13710.2 Referencing 13810.3 Using ¯15 N Data 13810.4 Amines 14110.4.1 Alkyl 14110.4.2 Aryl 14310.5 Conjugated Amines 14510.6 Amides 14510.7 Amidines 14610.8 Azides 14710.9 Carbamates 14710.10 Cyanates and Thiocyanates 14810.11 Diazo Compounds 14910.12 Formamides 14910.13 Hydrazines 15010.14 Hydroxamic Acids 15110.15 Hydroxylamines 15210.16 Imides (Alkyl and Aryl) 15210.17 Imines 15210.18 Isocyanates and Isothiocyanates 15310.19 Nitrogen-Bearing Heterocycles 15410.20 Nitriles 15710.21 Nitro Compounds 15810.22 Nitroso and N-Nitroso Compounds 15810.23 N-Oxides 15910.24 Oximes 16010.25 Sulfonamides 16110.26 Ureas and Thioureas 16210.27 Other Unusual Compounds 16310.28 ¯15 N Topics 16610.28.1 1-, 2-, 3- and 4-bond Correlations 16610.28.2 'Through-Space' Correlations 16810.28.3 Tautomerism in ¯15 N NMR 16910.28.4 Restricted Rotation 17010.28.5 Protonation and Zwitterions 17011 Some Other Techniques and Nuclei 17311.1 HPLC-NMR 17311.2 Flow NMR 17411.3 Solvent Suppression 17511.4 MAS (Magic Angle Spinning) NMR 17611.5 Pure Shift NMR 17711.6 Other 2-D Techniques 17811.6.1 INADEQUATE 17811.6.2 J-Resolved 17811.6.3 DOSY 17811.7 3-D Techniques 17911.8 Fluorine (¯19 F) NMR 18011.9 Phosphorus (¯31 P) NMR 18212 Dynamics 18312.1 Linewidths 18712.2 Chemical Shifts 18712.3 Splittings 18812.4 Relaxation Pathways 18812.5 Experimental Techniques 18812.6 In Practice 18912.7 In Conclusion 19113 Quantification 19313.1 Introduction 19313.2 Different Approaches to Quantification 19313.2.1 Relative Quantification 19313.2.2 Absolute Quantification 19413.2.3 Internal Standards 19413.2.4 External Standards 19513.2.5 Electronic Reference (ERETIC) 19513.2.6 QUANTAS19613.2.7 ERETIC 2 19613.3 Things to Watch Out For 19713.4 Quantification of Other Nuclei 19713.5 Conclusion 19814 Safety 19914.1 Magnetic Fields 19914.2 Cryogens 20114.3 Sample-Related Injuries 20215 Software 20315.1 Acquisition Software 20315.2 Processing Software 20415.3 Prediction and Simulation Software 20515.3.1 ¯13 C Prediction 20515.3.2 ¯1 H Prediction 20715.3.3 Incremental Approaches 20715.3.4 HOSE Code Databases 20815.3.5 Semi-Empirical Approaches 20815.3.6 Ab Initio Approaches 20815.3.7 Neural Networks 20815.5.8 Hybrid Approaches 20915.5.9 Simulation 20915.6 Structural Verification Software 20915.7 Structural Elucidation Software 21115.8 Summary 21216 Problems 21316.1 Questions 21316.2 Hints 22716.3 Answers 22816.4 A Closing Footnote 24117 Raising Your Game 24317.1 Spotting the Pitfalls 24317.2 The Wrong Solvent 24417.3 Choosing the Right Experiment 245Appendix A 261Glossary 263Index 269
S.A. Richards and J.C. HollertonThe 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.
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