Organic Structure Determination Using 2-D NMR Spectroscopy (eBook)

Front Cover 1
Organic Structure Determination Using 2-D NMR Spectroscopy 4
Copyright Page 5
Contents 8
Preface 14
CHAPTER 1 Introduction 16
1.1 What Is Nuclear Magnetic Resonance? 16
1.2 Consequences of Nuclear Spin 16
1.3 Application of a Magnetic Field to a Nuclear Spin 18
1.4 Application of a Magnetic Field to an Ensemble of Nuclear Spins 20
1.5 Tipping the Net Magnetization Vector from Equilibrium 26
1.6 Signal Detection 27
1.7 The Chemical Shift 28
1.8 The 1-D NMR Spectrum 28
1.9 The 2-D NMR Spectrum 30
1.10 Information Content Available Using NMR 31
CHAPTER 2 Instrumental Considerations 34
2.1 Sample Preparation 34
2.1.1 NMR Tube Selection 35
2.1.2 Sample Purity 35
2.1.3 Solvent Selection 36
2.1.4 Cleaning NMR Tubes Prior to Use or Reuse 36
2.1.5 Drying NMR Tubes 36
2.1.6 Sample Mixing 37
2.1.7 Sample Volume 37
2.1.8 Solute Concentration 39
2.1.9 Optimal Solute Concentration 41
2.1.10 Minimizing Sample Degradation 42
2.2 Locking 42
2.3 Shimming 43
2.4 Temperature Regulation 44
2.5 Modern NMR Instrument Architecture 44
2.5.1 Generation of RF and Its Delivery to the NMR Probe 46
2.5.2 Probe Tuning 46
2.5.3 When to Tune the NMR Probe and Calibrate RF Pulses 47
2.5.4 RF Filtering 48
2.6 Pulse Calibration 49
2.7 Sample Excitation and the Rotating Frame of Reference 51
2.8 Pulse Roll-off 52
2.9 Probe Variations 54
2.9.1 Small Volume NMR Probes 56
2.9.2 Flow-Through NMR Probes 56
2.9.3 Cryogenically Cooled Probes 57
2.9.4 Probe Sizes (Diameter of Recommended NMR Tube) 58
2.9.5 Normal Versus Inverse Coil Configurations in NMR Probes 59
2.10 Analog Signal Detection 60
2.11 Signal Digitization 60
CHAPTER 3 Data Collection, Processing, and Plotting 66
3.1 Setting the Spectral Window 66
3.2 Determining the Optimal Wait Between Scans 68
3.3 Setting the Acquisition Time 71
3.4 How Many Points to Acquire in a 1-D Spectrum 72
3.5 Zero Filling and Digital Resolution 73
3.6 Setting the Number of Points to Acquire in a 2-D Spectrum 74
3.7 Truncation Error and Apodization 76
3.8 The Relationship Between T[sub(2)]* and Observed Line Width 77
3.9 Resolution Enhancement 79
3.10 Forward Linear Prediction 80
3.11 Pulse Ringdown and Backward Linear Prediction 81
3.12 Phase Correction 82
3.13 Baseline Correction 85
3.14 Integration 86
3.15 Measurement of Chemical Shifts and J-Couplings 88
3.16 Data Representation 91
CHAPTER 4 [sup(1)]H and [sup(13)]C Chemical Shifts 98
4.1 The Nature of the Chemical Shift 98
4.2 Aliphatic Hydrocarbons 101
4.3 Saturated, Cyclic Hydrocarbons 103
4.4 Olefinic Hydrocarbons 103
4.5 Acetylenic Hydrocarbons 105
4.6 Aromatic Hydrocarbons 105
4.7 Heteroatom Effects 106
CHAPTER 5 Symmetry and Topicity 110
5.1 Homotopicity 110
5.2 Enantiotopicity 112
5.3 Diastereotopicity 113
5.4 Chemical Equivalence 114
5.5 Magnetic Equivalence 114
CHAPTER 6 Through-Bond Effects: Spin-Spin (J) Coupling 116
6.1 Origin of J-Coupling 116
6.2 Skewing of the Intensity of Multiplets 118
6.3 Prediction of First-Order Multiplets 121
6.4 The Karplus Relationship for Spins Separated by Three Bonds 125
6.5 The Karplus Relationship for Spins Separated by Two Bonds 126
6.6 Long Range J-Coupling 128
6.7 Decoupling Methods 128
6.8 One-Dimensional Experiments Utilizing J-Couplings 130
6.9 Two-Dimensional Experiments Utilizing J-Couplings 132
6.9.1 Homonuclear Two-Dimensional Experiments Utilizing J-Couplings 133
6.9.1.1 COSY 133
6.9.1.1.1 Phase Sensitive COSY 134
6.9.1.1.2 Absolute-Value COSY, Including gCOSY 135
6.9.1.2 TOCSY 135
6.9.1.3 INADEQUATE 138
6.9.2 Heteronuclear Two-Dimensional Experiments Utilizing J-Couplings 139
6.9.2.1 HMQC and HSQC 139
6.9.2.2 HMBC 147
CHAPTER 7 Through-Space Effects: The Nuclear Overhauser Effect (NOE) 152
7.1 The Dipolar Relaxation Pathway 152
7.2 The Energetics of an Isolated Heteronuclear Two-Spin System 153
7.3 The Spectral Density Function 154
7.4 Decoupling One of the Spins in a Heteronuclear Two-Spin System 156
7.5 Rapid Relaxation via the Double Quantum Pathway 157
7.6 A One-Dimensional Experiment Utilizing the NOE 159
7.7 Two-Dimensional Experiments Utilizing the NOE 162
7.7.1 NOESY 162
7.7.2 ROESY 163
CHAPTER 8 Molecular Dynamics 166
8.1 Relaxation 167
8.2 Rapid Chemical Exchange 168
8.3 Slow Chemical Exchange 168
8.4 Intermediate Chemical Exchange 169
8.5 Two-Dimensional Experiments that Show Exchange 171
CHAPTER 9 Strategies for Assigning Resonance to Atoms Within a Molecule 172
9.1 Prediction of Chemical Shifts 173
9.2 Prediction of Integrals and Intensities 174
9.3 Prediction of [sup(1)]H Multiplets 174
9.4 Good Bookkeeping Practices 175
9.5 Assigning [sup(1)]H Resonances on the Basis of Chemical Shifts 177
9.6 Assigning [sup(1)]H Resonances on the Basis of Multiplicities 178
9.7 Assigning [sup(1)]H Resonances on the Basis of the gCOSY Spectrum 181
9.8 The Best Way to Read a gCOSY Spectrum 184
9.9 Assigning [sup(13)]C Resonances on the Basis of Chemical Shifts 186
9.10 Pairing [sup(1)]H and [sup(13)]C Shifts by Using the HSQC/HMQC Spectrum 188
9.11 Assignment of Nonprotonated [sup(13)]C's on the Basis of the HMBC Spectrum 193
CHAPTER 10 Strategies for Elucidating Unknown Molecular Structures 198
10.1 Initial Inspection of the One-Dimensional Spectra 199
10.2 Good Accounting Practices 202
10.3 Identification of Entry Points 206
10.4 Completion of Assignments 206
CHAPTER 11 Simple Assignment Problems 214
11.1: 2-Acetylbutyrolactone in CDCl[sub(3)] (Sample 26) 214
11.2: & #945
11.3: (1R)-endo-(+)-Fenchyl Alcohol in CDCl[sub(3)] (Sample 30) 220
11.4: (–)-Bornyl Acetate in CDCl[sub(3)] (Sample 31) 224
11.5: N-Acetylhomocysteine Thiolactone in CDCl[sub(3)] (Sample 35) 229
11.6: Guaiazulene in CDCl[sub(3)] (Sample 52) 232
11.7: 2-Hydroxy-3-Pinanone in CDCl[sub(3)] (Sample 76) 236
11.8: (R)-(+)-Perillyl Alcohol in CDCl[sub(3)] (Sample 81) 239
11.9: 7-Methoxy-4-Methylcoumarin in CDCl[sub(3)] (Sample 90) 242
11.10: Sucrose in D[sub(2)]O (Sample 21) 245
CHAPTER 12 Complex Assignment Problems 248
12.1 Longifolene in CDCl[sub(3)] (Sample 48) 248
12.2 (+)-Limonene in CDCl[sub(3)] (Sample 49) 253
12.3 L-Cinchodine in CDCl[sub(3)] (Sample 53) 256
12.4 (3aR)-(+)-Sclareolide in CDCl[sub(3)] (Sample 54) 261
12.5 (–)-Epicatechin in Acetone-d[sub(6)] (Sample 55) 266
12.6 (–)-Eburnamonine in CDCl[sub(3)] (Sample 71) 270
12.7 trans-Myrtanol in CDCl[sub(3)] (Sample 72/78) 273
12.8 cis-Myrtanol in CDCl[sub(3)] (Sample 73/77) 276
12.9 Naringenin in Acetone-d[sub(6)] (Sample 89) 279
12.10 (–)-Ambroxide in CDCl[sub(3)] (Sample Ambroxide) 283
CHAPTER 13 Simple Unknown Problems 286
13.1 Unknown 13.1 in CDCl[sub(3)] (Sample 20) 286
13.2 Unknown 13.2 in CDCl[sub(3)] (Sample 41) 289
13.3 Unknown 13.3 in CDCl[sub(3)] (Sample 22) 293
13.4 Unknown 13.4 in CDCl[sub(3)] (Sample 24) 295
13.5 Unknown 13.5 in CDCl[sub(3)] (Sample 34) 297
13.6 Unknown 13.6 in CDCl[sub(3)] (Sample 36) 300
13.7 Unknown 13.7 in CDCl[sub(3)] (Sample 50) 302
13.8 Unknown 13.8 in CDCl[sub(3)] (Sample 83) 305
13.9 Unknown 13.9 in CDCl[sub(3)] (Sample 82) 308
13.10 Unknown 13.10 in CDCl[sub(3)] (Sample 84) 310
CHAPTER 14 Complex Unknown Problems 314
14.1 Unknown 14.1 in CDCl[sub(3)] (Sample 32) 314
14.2 Unknown 14.2 in CDCl[sub(3)] (Sample 33) 317
14.3 Unknown 14.3 in CDCl[sub(3)] (Sample 51) 320
14.4 Unknown 14.4 in CDCl[sub(3)] (Sample 74) 324
14.5 Unknown 14.5 in CDCl[sub(3)] (Sample 75) 327
14.6 Unknown 14.6 in CDCl[sub(3)] (Sample 80) 330
14.7 Unknown 14.7 in ACETONE-d[sub(6)] (Sample 86) 334
14.8 Unknown 14.8 in CDCl[sub(3)] (Sample 87) 337
14.9 Unknown 14.9 in CDCl[sub(3)] (Sample 88) 341
14.10 Unknown 14.10 in CDCl[sub(3)] (Sample 72) 344
Glossary of Terms 348
A 348
B 348
C 348
D 349
E 350
F 351
G 353
H 353
I 353
J 353
K 354
L 354
M 354
N 354
O 355
P 355
Q 357
R 357
S 358
T 359
U 360
V 360
W 360
Z 360
Glossary of Acronyms and Abbreviations 361
Glossary of Symbols 361
Index 364
A 364
B 364
C 364
D 366
E 366
F 367
G 367
H 368
I 369
J 369
K 370
L 370
M 370
N 371
O 371
P 372
Q 373
R 373
S 374
T 375
U 376
V 377
W 377
Z 377