NMR Spectroscopy: Basic Principles, Concepts and Applications in Chemistry

This third edition of the popular classic retains the clear style and excellent didactical, highly practical approach. It explains this complex topic without mathematical equations, making it ideal for those students who do not have a strong mathematical background, but want to understand the fundamentals of NMR and work with the method in an efficient and accurate way. The contents have been completely revised and updated with approximately 25% new material, including new chapters on biological NMR and on other nuclei, outdated methods are replaced by current ones, and new developments have been added. Many examples are taken from organic chemistry, making this an equally invaluable guide to undergraduate and graduate students from such related fields as biochemistry, medicinal chemistry, pharmaceutical chemistry and materials science. Contains problems complete with solutions.

Table of Contents:
Preface XV 1 Introduction 1 1.1 Literature 8 1.2 Units and Constants 9 References 10 Part I Basic Principles and Applications 11 2 The Physical Basis of the Nuclear Magnetic Resonance Experiment. Part I 13 2.1 The Quantum Mechanical Model for the Isolated Proton 13 2.2 Classical Description of the NMR Experiment 16 2.3 Experimental Verification of Quantized Angular Momentum and of the Resonance Equation 17 2.4 The NMR Experiment on Compact Matter and the Principle of the NMR Spectrometer 19 2.4.1 How to Measure an NMR Spectrum 19 2.5 Magnetic Properties of Nuclei beyond the Proton 25 References 27 3 The Proton Magnetic Resonance Spectra of Organic Molecules - Chemical Shift and Spin-Spin Coupling 29 3.1 The Chemical Shift 29 3.1.1 Chemical Shift Measurements 32 3.1.2 Integration of the Spectrum 35 3.1.3 Structural Dependence of the Resonance Frequency - A General Survey 37 3.2 Spin-Spin Coupling 41 3.2.1 Simple Rules for the Interpretation of Multiplet Structures 46 3.2.2 Spin-Spin Coupling with Other Nuclei 49 3.2.2.1 Nuclei of Spin I = 12 49 3.2.2.2 Nuclei of Spin I > 12 51 3.2.3 Limits of the Simple Splitting Rules 52 3.2.3.1 The Notion of Magnetic Equivalence 52 3.2.3.2 Significance of the Ratio J/nu0delta 56 3.2.4 Spin-Spin Decoupling 58 3.2.5 Two-Dimensional NMR - the COSY Experiment 60 3.2.6 Structural Dependence of Spin-Spin Coupling - A General Survey 62 References 66 4 General Experimental Aspects of Nuclear Magnetic Resonance Spectroscopy 67 4.1 Sample Preparation and Sample Tubes 67 4.2 Internal and External Standards; Solvent Effects 70 4.3 Tuning the Spectrometer 74 4.4 Increasing the Sensitivity 78 4.5 Measurement of Spectra at Different Temperatures 81 References 83 Textbooks 83 Review Articles 83 5 Proton Chemical Shifts and Spin-Spin Coupling Constants as Functions of Structure 85 5.1 Origin of Proton Chemical Shifts 86 5.1.1 Influence of the Electron Density at the Proton 87 5.1.2 Influence of the Electron Density at Neighboring Carbon Atoms 87 5.1.3 The Influence of Induced Magnetic Moments of Neighboring Atoms and Bonds 94 5.1.4 Ring Current Effect in Cyclic Conjugated pi-Systems 101 5.1.5 Alternative Methods to Measure Diatropicity 110 5.1.6 Diamagnetic Anisotropy of the Cyclopropane Ring 113 5.1.7 Electric Field Effect of Polar Groups and the van-derWaals Effect 114 5.1.8 Chemical Shifts through Hydrogen Bonding 117 5.1.9 Chemical Shifts of Protons in Organometallic Compounds 119 5.1.10 Solvent Effects 120 5.1.11 Empirical Substituent Constants 121 5.1.11.1 Tables of Proton Resonances in Organic Molecules 122 5.2 Proton-Proton Spin-Spin Coupling and Chemical Structure 122 5.2.1 The Geminal Coupling Constant (2J) 123 5.2.1.1 Dependence on the Hybridization of the Methylene Carbon 123 5.2.1.2 Effect of Substituents 124 5.2.1.3 A Molecular Orbital Model for the Interpretation of Substituent Effects on 2J 126 5.2.2 The Vicinal Coupling Constant (3J) 128 5.2.2.1 Dependence on the Dihedral Angle 129 5.2.2.2 Dependence upon the C-C Bond Length, Rmunu 130 5.2.2.3 Dependence on HCC Valence Angles 132 5.2.2.4 Substituent Effects 133 5.2.3 Long-Range Coupling Constants (4J, 5J) 137 5.2.3.1 Saturated Systems 138 5.2.3.2 Unsaturated Systems 139 5.2.4 Through-Space and Dipolar Coupling 143 5.2.5 Tables of Spin-Spin Coupling Constants in Organic Molecules 144 References 147 Monograph 148 Review Articles 148 6 The Analysis of High-Resolution Nuclear Magnetic Resonance Spectra 149 6.1 Notation for Spin Systems 150 6.2 Quantum Mechanical Formalism 151 6.2.1 The Schrodinger Equation 151 6.3 The Hamilton Operator for High-Resolution Nuclear Magnetic Resonance Spectroscopy 153 6.4 Calculation of Individual Spin Systems 155 6.4.1 Stationary States of a Single Nucleus A 156 6.4.2 Two Nuclei without Spin-Spin Interaction (Jij = 0); Selection Rules 156 6.4.3 Two Nuclei with Spin-Spin Interaction (Jij = 0) 158 6.4.3.1 The A2 Case and the Variational Method 158 6.4.3.2 Calculation of the Relative Intensities 162 6.4.3.3 Symmetric and Antisymmetric Wave Functions 163 6.4.4 The AB System 164 6.4.5 The AX System and the First-Order Approximation 167 6.4.6 General Rules for the Treatment of More Complex Spin Systems 170 6.5 Calculation of the Parameters nui and Jij from the Experimental Spectrum 174 6.5.1 Direct Analysis of the AB System 175 6.5.2 Spin Systems with Three Nuclei 177 6.5.2.1 The AB2 (A2B) System 177 6.5.2.2 The Particle Spin 181 6.5.2.3 The ABX System 182 6.5.3 Spin Systems with Four Nuclei - The AAXX System 192 6.5.4 Computer Analysis 206 References 209 Textbooks 210 Review Articles 210 7 The Influence of Molecular Symmetry and Chirality on Proton Magnetic Resonance Spectra 211 7.1 Spectral Types and Structural Isomerism 211 7.2 Influence of Chirality on the NMR Spectrum 216 7.3 Analysis of Degenerate Spin Systems by Means of 13C Satellites and H/D Substitution 226 References 229 Review Articles 230 Part II Advanced Methods and Applications 231 8 The Physical Basis of the Nuclear Magnetic Resonance Experiment. Part II: Pulse and Fourier-Transform NMR 233 8.1 The NMR Signal by Pulse Excitation 234 8.1.1 Resonance for the Isolated Nucleus 234 8.1.2 Pulse Excitation for a Macroscopic Sample 236 8.2 Relaxation Effects 239 8.2.1 Longitudinal or Spin-Lattice Relaxation 239 8.2.2 Transverse or Spin-Spin Relaxation 243 8.2.3 Experiments for Measuring Relaxation Times 247 8.2.3.1 T1 Measurements - the Inversion Recovery Experiment 247 8.2.3.2 The Spin Echo Experiment 248 8.3 Pulse Fourier-Transform (FT) NMR Spectroscopy 249 8.3.1 Pulse Excitation of Entire NMR Spectra 250 8.3.2 The Receiver Signal and its Analysis 252 8.4 Experimental Aspects of Pulse Fourier-Transform Spectroscopy 254 8.4.1 The FT NMR Spectrometer - Basic Principles and Operation 254 8.4.1.1 The Computer and the Analog-Digital Converter (ADC) 254 8.4.1.2 RF Sources of an FT NMR Spectrometer 258 8.4.1.3 Transmitter and Signal Phase 259 8.4.1.4 Selective Excitation and Shaped Pulses in FT NMR Spectroscopy 260 8.4.1.5 Pulse Calibration 263 8.4.1.6 Composite Pulses 264 8.4.1.7 Single and Quadrature Detection 264 8.4.1.8 Phase Cycles 266 8.4.2 Complications in FT NMR Spectroscopy 267 8.4.3 Data Improvement 269 8.5 Double Resonance Experiments 272 8.5.1 Homonuclear Double Resonance - Spin Decoupling 272 8.5.2 Heteronuclear Double Resonance 273 8.5.3 Broadband Decoupling 275 8.5.3.1 Broadband Decoupling by CW Modulation 275 8.5.3.2 Broadband Decoupling by Pulse Methods 276 8.5.4 Off-Resonance Decoupling 277 References 279 Textbooks 280 Review articles 280 9 Two-Dimensional Nuclear Magnetic Resonance Spectroscopy 281 9.1 Principles of Two-Dimensional NMR Spectroscopy 281 9.1.1 Graphical Presentation of Two-Dimensional NMR Spectra 284 9.2 The Spin Echo Experiment in Modern NMR Spectroscopy 285 9.2.1 Time-Dependence of Transverse Magnetization 285 9.2.2 Chemical Shifts and Spin-Spin Coupling Constants and the Spin Echo Experiment 286 9.3 Homonuclear Two-Dimensional Spin Echo Spectroscopy: Separation of the Parameters J and delta for Proton NMR Spectra 289 9.3.1 Applications of Homonuclear 1H J,delta-Spectroscopy 291 9.3.2 Practical Aspects of 1H J,delta-Spectroscopy 294 9.4 The COSY Experiment - Two-Dimensional 1H,1H Shift Correlations 296 9.4.1 Some Experimental Aspects of 2D-COSY Spectroscopy 300 9.4.2 Artifacts in COSY Spectra 302 9.4.3 Modifications of the Jeener Pulse Sequence 304 9.4.3.1 COSY-45 304 9.4.3.2 Long-Range COSY (COSY-LR) 305 9.4.3.3 COSY with Double Quantum Filter (COSY-DQF) 307 9.5 The Product Operator Formalism 309 9.5.1 Phenomenon of Coherence 309 9.5.2 Operator Basis for an AX System 311 9.5.3 Zero- and Multiple-Quantum Coherences 312 9.5.4 Evolution of Operators 313 9.5.5 The Observables 316 9.5.6 The COSY Experiment within the Product Operator Formalism 317 9.5.7 The COSY Experiment with Double-Quantum Filter (COSY-DQF) 320 9.6 Phase Cycles 322 9.6.1 COSY Experiment 324 9.7 Gradient Enhanced Spectroscopy 326 9.8 Universal Building Blocks for Pulse Sequences 329 9.8.1 Constant Time Experiments: omega1-Decoupled COSY 329 9.8.2 BIRD Pulses 329 9.8.3 Low-Pass Filter 330 9.8.4 z-Filter 331 9.9 Homonuclear Shift Correlation by Double Quantum Selection of AX Systems - the 2D-INADEQUATE Experiment 331 9.10 Single-Scan 2D NMR 336 References 337 Textbooks and Monographs 338 Methods Oriented 338 Application Oriented 338 Review articles 338 10 More 1D and 2D NMR Experiments: the Nuclear Overhauser Effect - Polarization Transfer - Spin Lock Experiments - 3D NMR 341 10.1 The Overhauser Effect 341 10.1.1 Original Overhauser Effect 341 10.1.2 Nuclear Overhauser Effect (NOE) 343 10.1.3 One-Dimensional Homonuclear NOE Experiments 345 10.1.3.1 NOE Measurements of Relative Distances between Protons 345 10.1.3.2 NOE Difference Spectroscopy 346 10.1.4 Complications during NOE Measurements 348 10.1.5 Two-Dimensional Homonuclear Overhauser Spectroscopy (NOESY) 350 10.1.6 Two-Dimensional Heteronuclear Overhauser Spectroscopy (HOESY) 355 10.2 Polarization Transfer Experiments 357 10.2.1 SPI Experiment 357 10.2.2 INEPT Pulse Sequence 360 10.3 Rotating Frame Experiments 364 10.3.1 Spin Lock and Hartmann-Hahn Condition 364 10.3.2 Spin Lock Experiments in Solution 366 10.3.2.1 Homonuclear Hartmann-Hahn or TOCSY Experiments 366 10.3.2.2 One-Dimensional Selective TOCSY Spectroscopy 368 10.3.2.3 ROESY Experiment 369 10.4 Multidimensional NMR Experiments 371 References 376 Textbooks 376 Review articles 376 11 Carbon-13 Nuclear Magnetic Resonance Spectroscopy 377 11.1 Historical Development and the Most Important Areas of Application 378 11.2 Experimental Aspects of Carbon-13 Nuclear Magnetic Resonance Spectroscopy 381 11.2.1 Gated Decoupling 382 11.2.2 Assignment Techniques 383 11.2.2.1 Multiplicity Selection with the Heteronuclear Spin Echo Experiment (SEFT, APT) 383 11.2.2.2 Polarization Transfer Experiments 387 11.2.2.3 Heteronuclear Two-Dimensional 1H,13C Chemical Shift Correlation 389 11.2.2.4 The 13C,13C INADEQUATE Experiment 398 11.2.2.5 Heteronuclear J, delta Spectroscopy 401 11.2.2.6 Assignment Techniques with Selective Excitation 403 11.2.2.7 Alternative Assignment Techniques 405 11.3 Carbon-13 Chemical Shifts 407 11.3.1 Theoretical Models 409 11.3.2 Empirical Correlations 418 11.4 Carbon-13 Spin-Spin Coupling Constants 420 11.4.1 Carbon-13 Coupling Constants and Chemical Structure 422 11.4.1.1 13C,13C Coupling Constants 422 11.4.1.2 13C,1H Coupling Constants 424 11.4.1.3 13C,X Coupling Constants 427 11.5 Carbon-13 Spin-Lattice Relaxation Rates 428 References 430 Textbooks and Monographs 430 Review articles 430 12 Selected Heteronuclei 431 12.1 Semimetals and Non-metals with the Exception of Hydrogen and Carbon 435 12.1.1 Boron-11 435 12.1.1.1 Referencing and Chemical Shifts 437 12.1.1.2 Polyhedral Boranes 438 12.1.2 Nitrogen-15 439 12.1.2.1 Referencing and Chemical Shifts 441 12.1.2.2 Spin-Spin Coupling 445 12.1.3 Oxygen-17 445 12.1.3.1 Referencing and Chemical Shifts 446 12.1.4 Fluorine-19 447 12.1.4.1 Referencing and Chemical Shifts 448 12.1.4.2 Spin-Spin Coupling 452 12.1.5 Silicon-29 454 12.1.5.1 Referencing and Chemical Shifts 454 12.1.5.2 Spin-Spin Coupling 457 12.1.6 Phosphorus-31 458 12.1.6.1 Referencing and Chemical Shifts 458 12.1.6.2 Spin-Spin Coupling 461 12.2 Main Group Metals 462 12.2.1 Lithium-6,7 462 12.2.1.1 Referencing and Chemical Shifts 463 12.2.1.2 Spin-Spin Coupling 463 12.2.2 Aluminum-27 468 12.2.2.1 Referencing and Chemical Shifts 469 12.2.3 Tin-119 471 12.2.3.1 Referencing and Chemical Shifts 472 12.2.3.2 Spin-Spin Coupling 473 12.3 Transition Metals 474 12.3.1 Vanadium-51 476 12.3.2 Platinum-195 480 12.3.2.1 Spin-Spin Coupling 482 12.3.3 Cobalt-59 482 12.3.4 Copper-63 484 12.3.5 Rhodium-103 485 12.3.6 Cadmium-113 488 12.3.7 Iron-57 489 12.3.8 Manganese-55 491 12.3.9 Molybdenum-95 492 12.3.10 Tungsten-183 492 12.3.11 Mercury-199 494 12.3.12 Osmium-187 496 References 496 Textbooks 498 Monographs 498 General Review Articles 498 Selected Review Articles dealing with Individual Nuclei not cited Above 498 13 Influence of Dynamic Effects on Nuclear Magnetic Resonance Spectra 501 13.1 Exchange of Protons between Positions with Different Larmor Frequencies 501 13.1.1 Quantitative Description of Dynamic Nuclear Magnetic Resonance 504 13.1.2 Relationships to Reaction Kinetics 505 13.1.3 Approximate Solutions and Sources of Error 509 13.1.4 More Complex Exchange Phenomena 512 13.1.5 Application of Inversion-Recovery Experiments to the Determination of Rate Constants 513 13.1.6 Two-Dimensional Exchange Spectroscopy (EXSY) 514 13.1.7 Measurements of First-Order Rate Constants by Integration 516 13.2 Internal Dynamics of Organic Molecules 517 13.2.1 Hindrance to Internal Rotation 518 13.2.1.1 Bonds with Partial Double Bond Character 518 13.2.1.2 Substituted Ethanes 521 13.2.2 Inversion of Configuration 523 13.2.3 Ring Inversion 526 13.2.4 Valence Tautomerism and Bond Shifts 532 13.2.5 Dynamic Processes in Organometallic Compounds and Carbocations 542 13.3 Intermolecular Exchange Processes 549 13.4 Line Broadening by Fast Relaxing Neighboring Nuclei 554 References 555 Textbooks 556 Review Articles 556 14 Nuclear Magnetic Resonance of Partially Oriented Molecules and Solid State NMR 557 14.1 Nuclear Magnetic Resonance of Partially Oriented Molecules 557 14.1.1 Nuclear Magnetic Resonance in Liquid Crystals 558 14.1.2 Other Alignment Methods - Residual Dipolar Couplings 565 14.2 High-Resolution Solid State Nuclear Magnetic Resonance Spectroscopy 568 14.2.1 Experimental Techniques of High-Resolution Solid State NMR Spectroscopy 570 14.2.1.1 Line Narrowing 570 14.2.1.2 Assignment Methods 576 14.2.1.3 Quadrupolar Nuclei 577 14.2.2 Applications of High-Resolution Solid State NMR Spectroscopy 580 14.2.2.1 Spin 12 Nuclei 580 14.2.2.2 Quadrupolar Nuclei 584 14.2.2.3 Dynamic Processes 588 References 589 Textbooks 590 Review Articles 590 15 Selected Topics of Nuclear Magnetic Resonance Spectroscopy 591 15.1 Isotope Effects in Nuclear Magnetic Resonance 591 15.1.1 Isotopic Perturbation of Equilibrium 595 15.2 Nuclear Magnetic Resonance Spectroscopy of Paramagnetic Materials 597 15.2.1 Contact Shifts 597 15.2.2 Pseudo-contact Shifts - Shift Reagents 599 15.3 Chemically Induced Dynamic Nuclear Polarization (CIDNP) 604 15.3.1 Energy Polarization (Net Effect) 605 15.3.2 Entropy Polarization (Multiplet Effect) 608 15.3.3 The Kaptein Rules 611 15.4 Diffusion-Controlled Nuclear Magnetic Resonance Spectroscopy - DOSY 612 15.4.1 Measurement of Diffusion Coefficients 612 15.4.2 Mixture Analysis by Diffusion-Ordered Spectroscopy (DOSY) 615 15.5 Unconventional Methods for Sensitivity Enhancement - Hyperpolarization 617 15.5.1 Hydrogenation Reactions and the Effect of para-Hydrogen 617 15.5.2 Optical Pumping - Xenon-129 NMR 621 15.5.3 Dynamic Nuclear Polarization 623 15.6 Nuclear Magnetic Resonance in Biochemistry and Medicine 625 15.6.1 Biomolecules 625 15.6.2 Peptides and Proteins 627 15.6.3 Nucleic Acids 634 15.6.4 Oligo- and Polysaccharides 636 15.6.5 Solvent Suppression 639 15.6.6 NMR of Body Fluids and In-vivo NMR Spectroscopy 640 15.6.7 NMR Imaging 642 References 647 Review Articles 648 Appendix 649 1 The "Ring Current Effect" of the Benzene Nucleus 649 2 Tables of Proton Resonance Frequencies and Substituent Effects S(delta) 650 2.1 Substituent Effects S(delta) or SCS 652 3 Tables of 1H,1H Coupling Constants 654 4 Chemical Shifts and Substuent Effects S(delta) of 13C Resonances in Organic Compounds 659 5 The Hamiltonian Operator in Polar Coordinates 664 6 Intensity Distribution in A-multiplets Caused by n Neighbouring X-Nuclei with Spin I = 1 or I = 32 664 7 Commutable Operators 665 8 The Fz Operator 665 9 Equations for the Direct Analysis of AABB Spectra 666 10 Bloch Equations 667 11 Bloch Equations Modified for Chemical Exchange 668 12 Phase Behavior of Cross Peaks in 2D Nuclear Overhauser Spectroscopy (NOESY), Rotating-Frame Overhauser Spectroscopy (ROESY), and Total Correlation Spectroscopy (TOCSY) and Chemical Exchange (EXSY) Experiments 671 13 The International System (SI) of Units (MKSA System) 672 References 673 Solutions for Exercises 675 Glossary 691 Index 695

About the Author :
Harald Gunther studied at the University of Heidelberg, Germany, followed by a Postdoctoral Fellowship at Mellon Institute, Pittsburgh, USA. He then became an assistent at the Institute of Organic Chemistry at the Unversity of Cologne, Germany, where he also completed his habilitation. He became Professor of Organic Chemistry at the University of Siegen, Germany in 1978.

Review :
“Few good textbooks on NMR Spectroscopy are available at either the undergraduate or graduate levels.  For those who want to go beyond elementary organic chemistry but without delving into all the mathematics Friebolin’s book is probably the best among this category.”  (Journal of Chemical Education, 5 June 2014)