ONE AND TWO DIMENSIONAL NMR SPECTROSCOPY Atta-ur-Rahman H.E.J. Research Institute of Chemistry, University ofkarachi, Karachi 32, Pakistan ELSEVIER Amsterdam Oxford New York Tokyo 1989
IX CONTENTS Chapter-l 1 BASIC PRINCIPLES OF MODERN NMR SPECTROSCOPY 1 1.1 Introduction 1 1.2 Some Fundamental Considerations in NMR Spectroscopy 2 1.2.1 Instrumentation 2 1.2.1.1 The Magnet 2 1.2.1.2 The Probe 2 1.2.1.3 Probe Tuning 5 1.2.1.4 Shimming 6 1.2.1.5 Deuterium Lock 9 1.2.2 Creating a Signal 10 1.2.3 Pulse NMR 12 1.2.4 Data Acquisition and Storage 13 1.2.4.1 The Dynamic Range Problem 15 1.2.5 Digital Resolution 16 1.2.6 Quadrature Detection 18 1.2.6.1 PeakFolding 20 1.2.7 Fourier Transformation 23 1.2.8 Signal-to-Noise Ratio 24 1.2.9 "Manipulating" the Spectrum - Window Functions 25 1.2.9.1 Sensitivity Enhancement 25 1.2.9.2 Resolution Enhancement 27 1.2.10 Rotating Frame of Reference 27 1.2.10.1 Pulse Angle 29 1.2.10.2 Rotation of Vectors 31 1.2.11 Phase Cycling 34 1.2.11.1 Phase Cycling and Coherence Pathways 37 1.2.12 Pulse Widths 39 1.2.12.1 Composite Pulses 41 1.2.13 Time Proportional Phase Increment (TPPI) 42 1.2.14 Tailored Suppression and Excitation - Solvent Suppression Techniques 42 1.2.14.1 Presaturation 42
X 1.2.14.2 Tailored Excitation Method 44 1.2.14.3 Jump and Retum Method 44 1.2.14.4 The Inversion Recovery Method 45 1.2.14.5 Solvent Suppression by Paramagnetic Reagents 46 1.2.14.6 Selective Excitation by DANTE (Delays Alternating with Nutation for Tailored Excitation) 46 1.2.14.7 Improvements in Instrumentation Design 48 (a) Probehead Design 48 (b) Offset Equivalence of Transmitter and Decoupler Channels 48 (c) Fast Switching of Decoupler Power 48 1.2.15 Nuclear Overhauser Enhancement (NOE) 49 1.2.16 Theoretical Approaches to Pulsed NMR 49 1.2.16.1 Bloch's Semi-classicalApproach 49 1.2.16.2 Density Matrix Approach 50 1.2.16.3 Product OperatorApproach 50 1.2.17 Effect of a Pulse on the Nucleus 54 1.2.18 Coherence Transfer 57 1.2.18.1 Homonuciear Coherence Transfer 57 1.2.18.2 Heteronuclear Coherence Transfer 62 1.2.19 Multiple Quantum Filters 66 1.2.20 Other Selective Detection Techniques 68 1.2.20.1 p-spin Filtering 68 1.2.20.2 z-filters 71 Chapter-2 2 SPIN-ECHO AND POLARISATION TRANSFER 77 2.1 Spin-Echo Formation in Homonuciear and Heteronuclear Systems 77 2.1.1 Spin-Echo Production in Heteronuclear Systems 77 2.1.1.1 180 Pulse Applied Simultaneously to NucleiA andx 11 2.1.1.2 18(f Pulse Applied Selectively to Partner Nucleus X 80 2.1.2 Spin-Echo Production in Homonuciear Systems (or Heteronuclear Systems with
Non-Selective Application of Pulses) 80 2.1.2.1 18(f x Pulse Applied Simultaneously to NucleiA and X 80 2.1.3 Attached Proton Test (APT), Gated Spin-Echo (GASPE) or Spin-Echo Fourier Transform (SEFT) Measurements 82 2.1.3.1 Escort Editing ofapt Spectra 93 Cross-polarisation 94 2.2.1 Selective Population Transfer 95 2.2.2 Non-Selective Polarisation Transfer 100 2.2.2.1 Insensitive Nuclei Enhanced by Polarisation Transfer (INEPT) 100 2.2.2.1.1 Refocussed INEPT 105 2.2.2.1.2 INEPT + 107 2.2.2.1.3 Reverse INEPT 107 2.2.3 Semi-Selective Excitation for Polarisation Transfer (SESET) 107 2.2.3.1 SESET-RELAY 109 2.2.4 Distortionless Enhancement by Polarisation Transfer (DEPT) and Related Experiments 111 2.2.4.1 DEPT 111 2.2.4.1.1 Anomalies in Polarisation Transfer Experiments 116 (a) Intensity Anomalies 116 (b) Multiplet Anomalies 116 (c) Phase A nomalies 116 (d) Incomplete Separation of Subspectra 116 2.2.4.2 DEPT + 116 2.2.4.3 DEPT ++ 116 2.2.4.4 DEPT GL 117 2.2.4.5 MODEPT 118 2.2.4.6 Universal Polarisation Transfer (UPT) 118 2.2.4.7 Phase Oscillation to Maximise Editing (POMMIE) 118 2.2.4.8 Reverse DEPT 118 2.2.4.9 Subspectral Editing Using a Multiple Quantum Trap (SEMUT) 122 2.2.4.9.1 SEMUT GL 123
XII 23 Problems 125 2.4 Solutions to Problems 133 Chapter-3 3 CARBON-CARBON CONNECTIVITY - ID INADEQUATE 141 SPECTRA 3.1 Introduction 141 3.2 One-dimensional INADEQUATE 13 C-NMR Spectra 143 3.2.1 Factors Affecting the Intensity of the 13 C Satellite Signals 152 3.2.2 Some Practical Suggestions 153 3.2.3 SEMUTEditingof INADEQUATE Spectra (SEMINA) 154 3.2.4 INEPT-INADEQUATE 157 3.2.5 DEPT-INADEQUATE 157 3.2.6 INADEQUATE Sensitivity Improvement by Proton Indirect Detection (INSIPID) 159 3.2.7 Saturation INADEQUATE 159 3.2.8 Double-Quantum Transitions for Chapter-4 Finding Unresolved Lines (DOUBTFUL) 161 4 THE NUCLEAR OVERHAUSER EFFECT 167 4.1 Introduction 167 4.2 Relaxation Pathways 168 4.2.1 Spin-Lattice Relaxation 168 4.2.2 Other Relaxation Mechanisms 168 4.3 How noe Occurs 169 4.4 Other Factors Governing Relaxation and noe 174 4.5 Internuclear Distance and noe 178 4.5.1 Internuclear Distances in Two-Spin Systems 179
XIII 4.5.2 Three-Spin Systems 181 4.5.2.1 Linear Arrangement 181 4.5.2.1.1 Three-Spin Effect 182 4.5.2.2 Non-Linear Arrangement 184 4.6 Heteronuclear noe 184 4.7 NOE Difference Spectra 185 4.7.1 Some Practical Examples of noe Difference Spectroscopy 189 4.8 Problems 194 4.9 Solutions to Problems 197 Chapter-5 5 TWO-DIMENSIONAL NMR SPECTROSCOPY - 203 BASIC PRINCIPLES Chapter-6 6 HETERONUCLEAR 2D J-RESOLVED SPECTROSCOPY 217 6.1 The Gated Decoupler Method 222 6.2 The Refocussed Fold-over Corrected (RE-FOCSY) Gated Decoupler Method 225 6.3 The Spin-Flip Method 226 6.4 The Selective Spin-Flip Method 226 6.5 The Semi-Selective Spin-Flip Method 230 6.6 Indirect J-Spectroscopy with Selective Spin-Flip 234 6.7 Heteronuclear 2D J-resolved Spectra with Polarisation Transfer 235 6.8 Heteronuclear 2D J-resolved Spectra with Driven Pulses 236 6.9 Problems 237 6.10 Solutions to Problems 239
XIV Chapter-7 7 HOMONUCLEAR 2D J-RESOLVED SPECTROSCOPY 245 7.1 Double Resonance in 2D J-Resolved Spectra 255 7.2 Constant Time 2D J-Resolved Spectra 255 7.3 Absorption mode 2D J-Resolved Spectra 257 7.4 Differentiation of Homonuclear Multiplets by Indirect 2D J-Resolved Spectroscopy 258 7.5 Problems 260 7.6 Solutions to Problems 264 Chapter 8 8. HOMONUCLEAR 2D SHIFT CORRELATED 269 SPECTROSCOPY 8.1 COSY Spectra 269 8.1.1 Introduction 269 8.1.2 The Nuts and Bolts of COSY 272 8.1.2.1 Magnetization Transfer 272 8.1.2.2 Phase Cycling 274 8.1.3 The Birthofa COSY Spectrum 277 8.1.4 Intensity of Cross-Peaks 281 8.1.5 Digital Resolution in COSY 281 8.1.6 Other Practical Considerations in COSY 282 8.1.7 Some Examples of COSY Spectra 284 8.1.8 Improvements in COSY Spectra 287 8.1.8.1 Elimination of Artifact Axial Peaks Parallel to vi from COSY Spectra 287 8.1.8.2 Noise in COSYSpectra 289 8.1.8.3 Quad Detection and Suppressing Quad Images in COSY Spectra 291 8.1.9 Phase-Sensitive COSY Spectra 293 8.1.9.1 Pure-Phase 2D Spectra by Cosine Transformation with respect to ti 299 8.1.9.2 Coupling Constants from Phase-Sensitive COSY Spectra 299
8.1.10 COSY by Echo or Anti-echo Selection 305 8.1.11 Basic Peakshapes in 2D Spectra 306 8.1.11.1 Pure 2D Absorption Peakshape 306 8.1.11.2 Pure 2D Dispersion Peakshape 306 8.1.11.3 Mixed Absorption-Dispersion Peakshape (Phase-twisted Peakshape) 308 8.1.11.4 Absolute Value Peakshape 308 8.1.12 Shaping Functions in 2D Spectra 309 8.1.13 Foldingof Signals in COSY Spectra 313 8.1.14 Symmetrization 313 8.1.15 Coherence Transfer Pathways in COSY 315 8.2 Modifications in COSY Spectra 317 8.2.1 COSY-45 Spectra 317 8.2.1.1 Pattern Recognition 321 8.2.1.2 Signs of Coupling Constants 321 8.2.1.3 COSY-45 Spectra with Decoupling in vi Dimension 323 8.2.2 COSY Optimized for Long Range Couplings (DELAYED COSY) 327 8.2.3 Super COSY 328 8.2.4 Exclusive Correlation Spectroscopy (E. COSY) 329 8.2.5 Homonuclear Relayed Coherence Transfer (Relayed COSY or R COSY) 331 8.2.6 Homonuclear Chemical Shift Correlation by Heteronuclear Relayed Coherence Transfer (HERPECS) 335 8.2.7 Total Correlation Spectroscopy (TOCSY) 337 8.2.8 SECSY 341 8.2.9 z-filtered SECSY Spectra 344 8.2.10 FOCSY Spectra 345 8.2.11 Super SECSY 346 8.2.12 Difference SECSY 347 8.2.13 vi -Decoupled SECSY Spectra 348 8.3 Problems 349
XVI 8.4 Solutions to Problems 352 Chapter-9 9 CHEMICAL SHIFT CORRELATION THROUGH 359 CROSS - RELAXATION AND EXCHANGE 9.1 Introduction 359 9.2 Nuclear Overhauser Enhancement Spectroscopy (NOESY) 360 9.2.1 Homonuclear Relayed NOESY 365 9.2.2 Heteronuclear Relayed NOESY 367 9.3 2D Chemical Exchange Spectra 369 9.3.1 Rate Constant by "Accordion" Spectroscopy - Three-Dimensional NMR 371 9.4 CAMELSPIN OR ROESY (Rotating Frame Overhauser Enhancement Spectroscopy) 373 9.5 Two-Dimensional Heteronuclear NOE Spectroscopy (HOESY) 376 9.6 Combined COSY-NOESY Experiment (COCONOSY) 379 9.7 DQ NOESY 380 9.8 Problems 381 9.9 Solutions to Problems 384 Chapter-10 10 HETERONUCLEAR 2D-SHIFT CORRELATION 391 SPECTROSCOPY 10.1 Principles of Heteronuclear 2D Shift Correlation Spectroscopy 391 10.2 Modifications of Heteronuclear 2D-Shift Correlation Experiment 398 10.2.1 With Homonuclear vi Decoupling 398 10.2.2 Long Range Heteronuclear Chemical Shift Correlation using (TANGO) 399 10.2.3 Improved Decoupling Modulation Procedures
XVII in 2D Long-Range Heteronuclear Chemical Shift Correlation Spectra 401 10.2.4 Correlation Spectroscopy via Long-Range Coupling (COLOC) 404 10.2.5 1 H-Detected Heteronuclear Multiple-Quantum Coherence (HMQC) for Correlating Directly Bonded X H- 13 C Nuclei 406 10.2.6 Sensitivity Enhanced Detection of Heteronuclear Multiple Bond Connectivity (HMBC) by 2D Multiple-Quantum NMR 409 10.2.7 2D DEPT Heteronuclear Shift Correlation Spectroscopy 412 10.3 Sensitivity of Heteronuclear Coherence Transfer Experiments 414 10.4 Heteronuclear Relayed Coherence Transfer Spectroscopy (or Heteronuclear Relayed COSY) 416 10.4.1 Low Pass J-Filtered 2D Heteronuclear Shift Correlated Spectra 422 10.4.2 Relayed Coherence Transfer From a Heteronucleus through Proton Spin Systems 423 10.4.3 Heteronuclear Relayed Coherence Transfer via Hartmann-Hahn type Cross-Polarisation 423 10.5 Problems 427 10.6 Solutions to Problems 429 Chapter-11 11 CROSS POLARISATION IN THE ROTATING FRAME 435 11.1 Introduction 11.2 Homonuclear Hartmann-Hahn Spectroscopy (HÖHAHA) 435 436
XVIII Chapter-12 12 2D MULTIPLE-QUANTUM SPECTROSCOPY 447 12.1 Introduction 447 12.2 Multiple-Quantum Spectra oftwo Spin Systems 450 12.2.1 Two Dimensional INADEQUATE 13 C-NMR Spectroscopy 450 12.2.1.1 Proton MonitoredINADEQUATE (INSIPID) 456 12.3 Multiple-Quantum Spectra of Three-Spin Systems 459 12.3.1 Double-Quantum Spectra of Three-Spin Systems 459 12.3.1.1 Linear Systems 459 (i) Signals due to Direct Connectivity 462 (ü) Magnetically Equivalent Nuclei 462 (iii) Remote Nuclei 462 12.3.2 Triple-Quantum Spectra of Three-Spin Systems 463 12.3.2.1 Constant Time Double-Quantum Spectroscopy 466 12.4 Multiple-Quantum Spectra in Four-Spin Systems 467 12.5 Uniform Excitation of Multiple-Quantum Coherence 468 12.6 Multiple-Quantum Filtered COSY Spectra 470 12.7 Homonuclear Zero-Quantum Spectroscopy 475 12.7.1 Improved HZQC Method 478 12.7.2 SUCZESS 481 12.8 Problems 484 12.9 Solutions to Problems 487 Chapter-13 13 TACKLING THE STRUCTURE 493 13.1 Choice of Experiment 493 13.2 ACase Study 495 (a) 1D 'H-NMR Studies 496 (b) Homonuclear 2D J-Resolved Spectrum 499
XIX (c) 2D Homonuclear Shift Correlated Spectrum (COSY-45) 499 (d) DEPTSpectra 499 (e) 2D Heteronuclear Shift Correlated Experiment 503 (f)! H, 13 C-COLOC 505 (g) NOESY and NOE Difference Spectra 507 (h) 2D1NADEQUA TE Spectrum 510 Chapter-14 14 PRODU CT OPERATOR APPROACH TO 2D-NMR 511 SPECTROSCOPY 14.1 Scalar Coupling 514 14.2 Dipolar Coupling 518 14.3 Phase Cycling and Product Operators 521 Appendix-1 SOME TERMS, SYMBOLS AND ACRONYMS USED IN NMR SPECTROSCOPY 527 Appendix-2 SUMMARY OF IMPORTANT 2D NMR TECHNIQUES 537 Index 553