High-Resolutio n NMR Techniques i n Organic Chemistry TIMOTHY D W CLARIDGE

High-Resolutio n NMR Techniques i n Organic Chemistry TIMOTHY D W CLARIDGE

Foreword Preface Acknowledgements V VI I X Chapter 1. Introduction 1.1. The development of high-resolution NMR 1 1.2. Modern high-resolution NMR and this book 4 1.2.1. What this book contains 5 1.2.2. Pulse sequence nomenclature 7 1.3. Applying modern NMR techniques 8 References 1 2 Chapter 2. Introducing high-resolution NM R 2.1. Nuclear spin and resonance 1 3 2.2. The vector model of NMR 1 6 2.2.1. The rotating frame of reference 1 6 2.2.2. Pulses 1 8 2.2.3. Chemical shifts and couplings 20 2.2.4. Spin-echoes 2 1 2.3. Time and frequency domains 24 2.4. Spin relaxation 25 2.4.1. Longitudinal relaxation : establishing equilibrium 2 6 2.4.2. Measuring T l with the inversion-recovery sequence 27 2.4.3. Transverse relaxation : loss of magnetisation in the x-y plane 3 0 2.4.4. Measuring T 2 with a spin-echo sequence 3 1 2.5. Mechanisms for relaxation 3 5 2.5.1. The path to relaxation 3 5 2.5.2. Dipole-dipole relaxation 3 7 2.5.3. Chemical shift anisotropy relaxation 3 8 2.5.4. Spin-rotation relaxation 3 9 2.5.5. Quadrupolar relaxation 4 0 References 4 3 Chapter 3. Practical aspects of high-resolution NM R 3.1. An overview of the NMR spectrometer 45 3.2. Data acquisition and processing 48 3.2.1. Pulse excitation 48 3.2.2. Signal detection 5 1 3.2.3. Sampling the FID 5 2 3.2.4. Quadrature detection 5 9 3.2.5. Phase cycling 63 3.2.6. Dynamic range and signal averaging 65 3.2.7. Window functions 70 3.2.8. Phase correction 73 3.3. Preparing the sample 75 3.3.1. Selecting the solvent 75 3.3.2. Reference compounds 77

3.3.3. Tubes and sample volumes 7 8 3.3.4. Filtering and degassing 8 0 3.4. Preparing the spectrometer 8 1 3.4.1. The probe 8 2 3.4.2. Tuning the probe 8 3 3.4.3. The field-frequency lock 8 5 3.4.4. Optimising the field homogeneity : shimming 87 3.5. Spectrometer calibrations 94 3.5.1. Radiofrequency pulses 94 3.5.2. Pulsed field gradients 99 3.5.3. Sample temperature 104 3.6. Spectrometer performance tests 105 3.6.1. Lineshape and resolution 106 3.6.2. Sensitivity 107 3.6.3. Solvent presaturation 109 References 11 0 Chapter 4. One-dimensional technique s 4.1. The single-pulse experiment 11 1 4.1.1. Optimising sensitivity 11 2 4.1.2. Quantitative measurements and integration 114 4.2. Spin decoupling methods 11 6 4.2.1. The basis of spin decoupling 11 7 4.2.2. Homonuclear decoupling 11 7 4.2.3. Heteronuclear decoupling 120 4.3. Spectrum editing with spin-echoes 125 4.3.1. The J-modulated spin-echo 125 4.3.2. APT 12 8 4.4. Sensitivity enhancement and spectrum editing 129 4.4.1. Polarisation transfer 13 0 4.4.2. INEPT 13 2 4.4.3. DEPT 13 9 4.4.4. PENDANT 142 4.5. Observing quadrupolar nuclei 143 References 145 Chapter 5. Correlations through the chemical bond I : Homonuclear shift correlation 5.1. Introducing two-dimensional methods 14 8 5.1.1. Generating a second dimension 14 9 5.2. Correlation spectroscopy (COSY) 15 3 5.2.1. Correlating coupled spins 15 5 5.2.2. Interpreting COSY 15 6 5.2.3. Peak fine structure 15 9 5.3. Practical aspects of 2D NMR 160 5.3.1. 2D lineshapes and quadrature detection 16 1 5.3.2. Axial peaks 167 5.3.3. Instrumental artefacts 16 8 5.3.4. 2D data acquisition 170 5.3.5. 2D data processing 172 5.4. Coherence and coherence transfer 174 5.4.1. Coherence-transfer pathways 17 7 5.5. Gradient-selected spectroscopy 17 8 5.5.1. Signal selection with pulsed field gradients 17 9 5.5.2. Phase-sensitive experiments 18 3 5.5.3. PFGs in high-resolution NMR 18 4 5.5.4. Practical implementation of PFGs 18 6 5.6. Alternative COSY sequences 18 7 5.6.1. Which COSY approach? 18 8 5.6.2. Double-quantum filtered COSY (DQF-COSY) 18 9 5.6.3. COSY-ß 197

5.6.4. Delayed-COSY: detecting small couplings 199 5.6.5. Relayed-COSY 200 5.7. Total correlation spectroscopy (TOCSY) 20 1 5.7.1. The TOCSY sequence 202 5.7.2. Using TOCSY 205 5.7.3. Implementing TOCSY 208 5.8. Correlating dilute spins : INADEQUATE 21 1 5.8.1. 2D INADEQUATE 21 2 5.8.2. 1D INADEQUATE 21 3 5.8.3. Implementing INADEQUATE 21 5 5.8.4. Variations on INADEQUATE 21 6 References 21 8 Chapter 6. Correlations through the chemical bond II : Heteronuclear shift correlatio n 6.1. Introduction 22 1 6.2. Sensitivity 222 6.3. Heteronuclear single-bond correlation spectroscopy 224 6.3.1. Heteronuclear multiple-quantum correlation (HMQC) 224 6.3.2. Heteronuclear single-quantum correlation (HSQC) 229 6.3.3. Practical implementations 23 0 6.3.4. Hybrid experiments 23 8 6.4. Heteronuclear multiple-bond correlation spectroscopy 244 6.4.1. The HMBC sequence 24 5 6.4.2. Applying HMBC 248 6.5. Traditional X-detected correlation spectroscopy 25 1 6.5.1. Single-bond correlations 25 2 6.5.2. Multiple-bond correlations and small couplings 25 4 References 25 6 Chapter 7. Separating shifts and couplings : J-resolved spectroscopy 7.1. Introduction 25 9 7.2. Heteronuclear J-resolved spectroscopy 26 0 7.2.1. Measuring long-range proton-carbon coupling constants 26 3 7.2.2. Practical considerations 26 6 7.3. Homonuclear J-resolved spectroscopy 26 7 7.3.1. Tilting, projections and symmetrisation 26 8 7.3.2. Applications 27 0 7.3.3. Practical considerations 27 3 7.4. `Indirect' homonuclear J-resolved spectroscopy 27 3 References 27 4 Chapter 8. Correlations through space : The nuclear Overhauser effect 8.1. Introduction 27 7 8.2. Definition of the NOE 27 9 8.3. Steady-state NOEs 27 9 8.3.1. NOEs in a two-spin system 27 9 8.3.2. NOEs in a multispin system 28 8 8.3.3. Summary 29 4 8.3.4. Applications 29 6 8.4. Transient NOEs 30 1 8.4.1. NOE kinetics 30 2 8.4.2. Measuring internuclear separations 30 3 8.5. Rotating-frame NOEs 30 4 8.6. Measuring steady-state NOEs : NOE difference 30 6 8.6.1. Optimising difference experiments 30 7 8.7. Measuring transient NOEs : NOESY 31 3 8.7.1. The 2D NOESY sequence 31 4 8.7.2. 1D NOESY sequences 32 0 8.7.3. Applications 323

8.7.4. Measuring chemical exchange: EXSY 32 6 8.8. Measuring rotating-frame NOEs : ROESY 328 8.8.1. The 2D ROESY sequence 329 8.8.2. 1D ROESY sequences 33 2 8.8.3. Applications 33 2 8.9. Measuring heteronuclear NOEs 33 5 8.10. Experimental considerations 33 6 References 33 7 Chapter 9. Experimental method s 9.1. Composite pulses 34 1 9.1.1. A myriad of pulses 344 9.1.2. Inversion vs. refocusing 344 9.2. Broadband decoupling and spin-locks 346 9.2.1. Spin-locks 347 9.2.2. Adiabatic pulses 34 8 9.3. Selective excitation and shaped pulses 34 8 9.3.1. Shaped soft pulses 35 0 9.3.2. DANTE sequences 354 9.3.3. Excitation sculpting 35 5 9.3.4. Practical considerations 35 7 9.4. Solvent suppression 35 9 9.4.1. Presaturation 36 1 9.4.2. Zero excitation 362 9.4.3. Pulsed field gradients 363 9.5. Recent methods 366 9.5.1. Heterogeneous samples and MAS 366 9.5.2. Diffusion-ordered spectroscopy 368 References 37 1 Appendix. Glossary of acronyms 373 Index 375