Introduction ................................................... xi
1 Getting Started .............................................. 1
1.1 The Technique ........................................... 1
1.2 Instrumentation ......................................... 2
1.3 CW Systems .............................................. 2
1.4 FT Systems .............................................. 3
1.4.1 Origin of the Chemical Shift ..................... 6
1.4.2 Origin of 'Splitting' ............................ 7
1.4.3 Integration ...................................... 9
2 Preparing the Sample ........................................ 11
2.1 How Much Sample Do I Need? ............................. 12
2.2 Solvent Selection ...................................... 13
2.2.1 Deutero Chloroform (CDCl3) ...................... 14
2.2.2 Deutero Dimethyl Sulfoxide (D6-DMSO) ............ 14
2.2.3 Deutero Methanol (CD3OD) ........................ 15
2.2.4 Deutero Water (D20) ............................. 16
2.2.5 Deutero Benzene (C6D6) .......................... 16
2.2.6 Carbon Tetrachloride (CCl4) ..................... 16
2.2.7 Trifluoroacetic Acid (CF3COOH) .................. 16
2.2.8 Using Mixed Solvents ............................ 17
2.3 Spectrum Referencing (Proton NMR) ...................... 17
2.4 Sample Preparation ..................................... 18
2.4.1 Filtration ...................................... 19
3 Spectrum Acquisition ........................................ 23
3.1 Number of Transients ................................... 23
3.2 Number of Points ....................................... 24
3.3 Spectral Width ......................................... 25
3.4 Acquisition Time ....................................... 25
3.5 Pulse Width/Pulse Angle ................................ 25
3.6 Relaxation Delay ....................................... 27
3.7 Number of Increments ................................... 27
3.8 Shimming ............................................... 28
3.9 Tuning and Matching .................................... 30
3.10 Frequency Lock ......................................... 30
3.10.1 Run Unlocked .................................... 30
3.10.2 Internal Lock ................................... 30
3.10.3 External Lock ................................... 31
3.11 To Spin or Not to Spin? ................................ 31
4 Processing .................................................. 33
4.1 Introduction ........................................... 33
4.2 Zero Filling and Linear Prediction ..................... 33
4.3 Apodization ............................................ 34
4.4 Fourier Transformation ................................. 36
4.5 Phase Correction ....................................... 36
4.6 Baseline Correction .................................... 38
4.7 Integration ............................................ 39
4.8 Referencing ............................................ 39
4.9 Peak Picking ........................................... 39
5 Interpreting Your Spectrum .................................. 41
5.1 Common Solvents and Impurities ......................... 44
5.2 Group 1 - Exchangeables and Aldehydes .................. 46
5.3 Group 2 - Aromatic and Heterocyclic Protons ............ 48
5.3.1 Monosubstituted Benzene Rings ................... 50
5.3.2 Multisubstituted Benzene Rings .................. 54
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 ................................ 63
6 Delving Deeper .............................................. 67
6.1 Chiral Centres ......................................... 67
6.2 Enantiotopic and Diastereotopic Protons ................ 72
6.3 Molecular Anisotropy ................................... 74
6.4 Accidental Equivalence ................................. 76
6.5 Restricted Rotation .................................... 78
6.6 Heteronuclear Coupling ................................. 82
6.6.1 Coupling between Protons and 13C ................ 82
6.6.2 Coupling between Protons and 19F ................ 84
6.6.3 Coupling between Protons and 31P ................ 87
6.6.4 Coupling between 1H and other Heteroatoms ....... 89
6.6.5 Cyclic Compounds and the Karplus Curve .......... 91
6.6.6 Salts, Free Bases and Zwitterions ............... 96
7 Further Elucidation Techniques - Part 1 .................... 101
7.1 Chemical Techniques ................................... 101
7.2 Deuteration ........................................... 101
7.3 Basification and Acidification ........................ 103
7.4 Changing Solvents ..................................... 104
7.5 Trifluoroacetylation .................................. 104
7.6 Lanthanide Shift Reagents ............................. 106
7.7 Chiral Resolving Agents ............................... 106
8 Further Elucidation Techniques - Part 2 .................... 111
8.1 Instrumental Techniques ............................... 111
8.2 Spin Decoupling (Homonuclear, 1-D) .................... 111
8.3 Correlated Spectroscopy (2-D) ......................... 112
8.4 Total Correlation Spectroscopy (1-and 2-D) ............ 116
8.5 The Nuclear Overhauser Effect and Associated
Techniques ............................................ 116
9 Carbon-13 NMR Spectroscopy ................................. 127
9.1 General Principles and 1-D 13C ........................ 127
9.2 2-D Proton-Carbon (Single Bond) Correlated
Spectroscopy .......................................... 130
9.3 2-D Proton-Carbon (Multiple Bond) Correlated
Spectroscopy .......................................... 133
9.4 Piecing It All Together ............................... 136
9.5 Choosing the Right Tool ............................... 137
10 Some of the Other Tools .................................... 143
10.1 Linking HPLC with NMR ................................. 143
10.2 Flow NMR .............................................. 144
10.3 Solvent Suppression ................................... 145
10.4 Magic Angle Spinning NMR .............................. 146
10.5 Other 2-D Techniques .................................. 147
10.5.1 INADEQUATE ..................................... 147
10.5.2 J-Resolved ..................................... 147
10.5.3 Diffusion Ordered Spectroscopy ................. 148
10.6 3-D Techniques ........................................ 149
11 Some of the Other Nuclei ................................... 151
11.1 Fluorine .............................................. 151
11.2 Phosphorus ............................................ 152
11.3 Nitrogen .............................................. 152
12 Quantification ............................................. 157
12.1 Introduction .......................................... 157
12.2 Relative Quantification ............................... 157
12.3 Absolute Quantification ............................... 158
12.3.1 Internal Standards ............................. 158
12.3.2 External Standards ............................. 158
12.3.3 Electronic Reference ........................... 159
12.3.4 QUANTAS Technique .............................. 159
12.4 Things to Watch Out For ............................... 160
12.5 Conclusion ............................................ 161
13 Safety ..................................................... 163
13.1 Magnetic Fields ....................................... 163
13.2 Cryogens .............................................. 165
13.3 Sample-Related Injuries ............................... 166
14 Software ................................................... 167
14.1 Acquisition Software .................................. 167
14.2 Processing Software ................................... 167
14.3 Prediction and Simulation Software .................... 169
14.3.1 13C Prediction ................................. 169
14.3.2 1H Prediction .................................. 171
14.3.3 Simulation ..................................... 172
14.3.4 Structural Verification Software ............... 172
14.3.5 Structural Elucidation Software ................ 172
15 Problems ................................................... 173
15.1 Ten NMR Problems ...................................... 173
15.2 Hints ................................................. 194
15.3 Answers ............................................... 195
Glossary ...................................................... 205
Index ......................................................... 211
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