F

Horst Friebolin

>eplained
ns
1emistry
Basic One- and
Two-Dimensional
NMR Spectroscopy

Sthcompletely revised
and enlarged edition

~
WILEY~
VCH
WILEY-VCH Verlag GmbH & Co. KGaA
p
Contents

1 The Physical Basis of NMR Spectroscopy

1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2 Nuclear Angular Momentum and Magnetic
Moment ...... . .. . . ............ . . . . . . . 2
1.3 Nuclei in a Static Magnetic Field . . . . . . . .. . . . 4
1.3. 1 Directional Quantization . . . . . . . ......... . 4
1.3.2 Energy of the Nuclei in the Magnetic Field ... . 4
1.3.3 Populations of the Energy Levels .......... . 6
1.3.4 Macroscopic Magnetization .... .......... . 6
1.4 Basic Principles of the NMR Experiment .... . 7
1.4.1 The Resonance Condition . ... . . ......... . 7
1.4.2 Basic Principle of the NMR Measurement .. . . 8
1.5 The Pulsed NMR Method ........ . . ... .. . 9
1.5.1 The Pulse . . . .. ....... . . . . . .......... . . 9
1.5.2 The Pulse Angle .. ... ... ..... ..... . .... . 10
1.5.3 Relaxation ............. .... .. . ....... . 13
1.5.4 The Time and Frequency D omains;
the Fourier Transformation ... ........... . 14
1.5.5 Spectrum Accumulation . ... ............. . 16
1.5.6 The Pulsed NMR Spectrometer ........... . 18
1.6 Spectral Parameters: a Brief Survey . ....... . 22
1.6.1 The Chemical Shift ... ....... ..... . .... . . 22
1.6.1.1 Nuclear Shielding .... .. ..... .. .... . . .. . . 22
1.6. 1.2 Reference Compounds and the a-Scale .. . ... . 24
1.6.2 Spin-Spin Coupling . . . ... ...... . . ....... . 26
1.6.2. 1 The Indirect Spin-Spin Coupling . .. .. ...... . 26
1.6.2.2 Coupling to One Neighboring Nucleus
(AX Spin System) ... . ..... .. .......... . 27
1.6.2.3 Coupling to Two Equivalent Neighboring Nuclei
(AX2 Spin System) ....... . . ... ......... . 29
1.6.2.4 Coupling to Three or More Equivalent
Neighboring Nuclei (AXn Spin System) . .... . 30
1.6.2.5 Multiplicity Rules . . . . ... . ........ . . ... . . 30
1.6.2.6 Couplings between Three Non-equivalent
Nuclei (AMX Spin System) ...... . . . ..... . 31
1.6.2.7 Couplings between Equivalent Nuclei
(An Spin Systems) .... ... .... .. ........ . 32
1.6.2.8 The Order of a Spectrum . .. . . .. .. . . . .... . 33

Basic One- and Two-Dimensional Spectroscopy. 5th Edition. Horst Friebolin XVII
Copyright© 2011 WILEY-VCR Verlag GmbH & Co. KGaA, Weinheim
ISBN 978-3-527-32782-9
1.6.2.9 Couplings between Protons and other Nuclei ;
13 C Satellite Spectra .................... · 3 Indirect Sp
33
3.1 Introduction
1.6.3 The Intensities of the Resonance Signals .... . . 34
1H Signal Intensities .................... . 3.2 H,H Couplir
1.6.3.1 34
13 C Signal Intensities .. . .... ... . .. ...... . Structure ..
1.6.3.2 35
3.2.1 Geminal Cm
1.6.4 Summary ....................... . .... . 37
1.7 "Other" Nuclides . . ... ................. . 38 3.2.1.1 D ependence
1.7.1 Nuclides with Spin I = 1/2 ............... . 39 3.2.1.2 Substituent I
3.2.1 .3 Effects of Nc
1.7.2 Nuclides with Spin I > 112 ... . . .......... . 40 Vicinal Coup
3.2.2
Exercises ....... . ................... . . 41
3.2.2.1 Dependence
1.8 Bibliography for Chapter 1 . ........ .... .. . 41
3.2.2.2 Substituent I
3.2.3 H ,H Couplir
2 The Chemical Shift. .... ....... .. .... . . 43 Long-range (
3.2.4
2.1 Introduction .......................... . 43 3.3 C,H Couplin
2.1.1 Influence of the Charge Density on the Shielding 44 Chemical Str
2.1.2 Effects of Neighboring Groups .. .......... . 47 3.3.1 C,H Couplin
2.1.2.1 Magnetic Anisotropy of Neighboring Groups .. 47 3.3.1.1 Dependence
2.1.2.2 Ring Current Effects ................... . 49 3.3.1.2 Substituent E
2.1.2.3 Electric Field Effects ............ . ...... . 51 3.3.2 C,H Couplin
2.1.2.4 Intermolecular Interactions - 3.3.2.1 Geminal Cm
Hydrogen Bonding and Solvent Effects ..... . 51 (i.e. 2J(C ,H:
2.1.2.5 Isotope Effects ... . .................... . 51 3.3.2.2 Vicinal Coup
2.1.3 Summary ............................ . 52 (i.e. 3J(C,Hl
1H 53
2.2 Chemical Shifts of Organic Compounds . . . 3.3.2.3 Long-range <
2.2.1 Alkanes and Cycloalkanes . .. ... ...... ... . 54 3.3.3 C,H Couplin
2.2.2 Alkenes ........ .. ................... . 56 3.4 C,C Couplin;
2.2.3 Arenes .................... . ......... . 56 Chemical Str
2.2.4 Alkynes ............................. . 57 3.5 Correlations
2.2.5 Aldehydes . . .... .. ....... .. .......... . 58 Constants ..
2.2.6 OH,SH,NH .... . .................... . 59 3.6 Coupling Me
2.3 13 C 60 The Electron
Chemical Shifts of Organic Compounds .. . 3.6.1
2.3.1 Alkanes and Cycloalkanes ... ... ......... . 61 3.6.2 H,D Couplin
2.3.2 Alkenes ............................. . 63 3.6.3 Relationship
2.3.3 Arenes ..... . ... . ... .. ......... . ..... . 64 Lifetime of a
2.3.4 Alkynes ............................. . 66 3.6.4 Couplings tlu
2.3.5 Allenes ............................. . 66 3.7 Couplings o~
2.3.6 Carbonyl and Carboxy Compounds ........ . 66 (Heteronucle
2.3.6.1 Aldehydes and Ketones ...... . ... . ...... . 67 Exercises ..
2.3.6.2 Carboxylic Acids and Derivatives .......... . 68 3.8 Bibliography
2.4 Relationships between the Spectrum and the
Molecular Structure . . . . . . . . . . . . . . . . . . . . . 70 4 Spectrum A
2.4.1 Equivalence, Symmetry and Chirality ....... . 70 4.1 Introduction
2.4.2 Homotopic, Enantiotopic and Diastereotopic 4.2 Nomenclatur
Groups ....................... . ...... . 74 4.2.1 Systematic N
2.4.3 Summary .. .. ... . ... . ................ . 77 4.2.2 Chemical anc
2.5 Chemical Shifts of "Other" Nuclides ....... . 78 4.3 Tho-Spin Sy!
Exercises .. . .... . .................... . 83 4.3 .1 The AX Spin
2.6 Bibliography for Chapter 2 . .. .. .. . ....... . 83 4.3.2 The AB Spin

XVIII
 Indirect Spin-Spin Coupling ........... . 85
3 Introduction ............. ... .......... . 85
3.1
JI,H Coupling Constants and Chemical
3.2
Structure . . ... ... .. ....... ......... . . . 87
Geminal Couplings 2J(H,H) ... . .... ..... . . 87
3.2.1
Dependence on Bond Angle ............. . . 87
3.2.1.1
3.2.1.2 Substituent Effects .................... . . 88
3.2.1.3 Effects of Neighboring n-Electrons ..... . .. . . 88
3.2.2 Vicinal Couplings 31 (H,H) .............. . . 89
3.2.2.1 Dependence on the Dihedral Angle ........ . 90
3.2.2.2 Substituent Effects ... .. ........ . .. .... . . 94
3.2.3 H,H Couplings in Aromatic Compounds .... . 95
3.2.4 Long-range Couplings .......... .. ...... . 96
3.3 C,H Coupling Constants and
Chemical Structure. . . . . . . . . . . . . . . . . . . . . . 97
3.3.1 C,H Couplings through One Bond 1J(C,H) . . . 97
3.3.1.1 Dependence on the s-Fraction ..... ...... . . 97
3.3.1.2 Substituent Effects ....... . ............. . 98
3.3.2 C,H Couplings through 1\vo or More Bonds . . . 99
3.3.2.1 Geminal Couplings
(i.e. 2J(C,H) in H-C- 13 C) . . ... .. . ..... . . 99
3.3.2.2 Vicinal Couplings
(i.e. 3J(C,H) in H-C-C- BC) .. .... .... . . 99
3.3.2.3 Long-range Couplings 3 +nJ(C,H) ........ . . 100
3.3.3 C,H Couplings in Benzene Derivatives ...... . 100
3.4 C,C Coupling Constants and
Chemical Structure. . . . . . . . . . . . . . . . . . . . . . 101
3.5 Correlations between C,H and H,H Coupling
Constants ............. ...... ......... . 101
3.6 Coupling Mechanisms .... .... ..... ..... . 103
3.6.1 The Electron-Nuclear Interaction .... .... .. . 103
3.6.2 H ,D Couplings .......... .... .......... . 105
3.6.3 Relationship between the Coupling and the
Lifetime of a Spin State ............ ... .. . 106
3.6.4 Couplings through Space ...... ..... .. ... . 106
3.7 Couplings of "Other" Nuclides
(Heteronuclear Couplings) ........ . ...... . 107
Exercises .............. ...... ........ . 109
3.8 Bibliography for Chapter 3 ............... . 109
4 Spectrum Analysis and Calculations ..... 111
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.2 Nomenclature ......... ..... ...... .... . 113
4.2.1 Systematic Notation for Spin Systems ....... . 113
4.2.2 Chemical and Magnetic Equivalence .... ... . 114
4.3 Two-Spin Systems ... . . . .... ..... .. .... . 116
4.3.1 The AX Spin System .. .... . . ........ .. . . 116
4.3.2 The AB Spin System ....... ...... . ... .. . 118

XIX
4.4 Three-Spin Systems . ... ...... · · · · · · · · · · · 120
120 6.3.4 y 1 Measurement
4.4.1 The AX2 , AKz, ABz and A3 Spin Systems . .. .
6.3.5 Chemical Change
4.4.2 The AMX and ABX Spin Systems ... . ...... 121
6.3.6 Solvent and Tern
4.5 Four-Spin Systems . ..... . . ....... . . .... . 123
Shift Reagents .
4.5.1 AzX2 and AzBz Spin Systems .......... .... 123
6.4 Computer-aided
4.5.2 The AA'XX' and AA'BB' Spin Systems . .... 124
of nc NMR Spe
4.6 Spectrum Simulation and Iteration ...... .... 125
6.4.1 Searching for Ide
4.7 Analysis of 13C NMR Spectra .......... . . . . 126
6.4 .2 Spectrum Predic
Exercises ....... .. ................. . .. 127 Exercises .....
4.8 Bibliography for Chapter 4 . . .......... .... 127 Bibliography for
6.5
5 Double Resonance Experiments .... ... . 129 Relaxation .. .
5.1 129
Introduction .. . . . . . . ... .. ... .. .... . ... . 7
7.1 Introduction . . .
5.2 Spin Decoupling in 1H NMR Spectroscopy ... .
130 Spin-Lattice Rei
7.2
5.2.1 Simplification of Spectra Relaxation Mecl
7.2. 1
by Selective Spin Decoupling ............ . . 130 Experimental D
7.2.2
5.2.2 Suppression of a Solvent Signal ••••••••• • 4 . 132 the Inversion Rc
5.3 Spin Decoupling in 13C NMR Spectroscopy . . . 133 R elationships b<
1H Broad-band Decoupling ............ ...
7.2.3
5.3.1 133 and Chemical S1
5.3.2 The Gated Decoupling Experiment ...... ... 135 7.2.3.1 Influence of Pre
1
5.3.3 H Off-Resonance Decoupling ....... . .. . .. 136 Groups . ... . . .
5.3.4 Selective Decoupling 7.2.3.2 Influence of Me
in 13 C NMR Spectroscopy . . . . .. . . . . . . .... 137 7.2.3.3 Segmental Mob
Exercises ..... . . . . . . . . . . . . . ...... . . ... 138 7.2.3.4 Anisotropy of tl
5.4 Bibliography for Chapter 5 .. . . . ........ . . . 138 7.2.4 Suppression of
7.3 Spin-Spin Relru
6 Assignment of 1 H and 13C Signals ....... 139 7.3.1 Relaxation Me<
6.1 139
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.2 Experimental I
6.2 lH NMR Spectroscopy . .............. . . .. 140 the Spin-E cho 1
6.2.1 Defining the Problem .. ................. . 140 7.3.3 Line-widths of:
6.2.2 Empirical Correlations for Exercises ....
Predicting Chemical Shifts ............... . 141 7.4 Bibliography f£
6.2.2.1 Alkanes (Shoolery's Rule) ... .... . . . . . ... . 141
6.2.2.2 Alkenes . .. . . .. ... .... . . . .. ... .. . .. ... 142 8 One-Dimensi
6.2.2.3 Benzene Derivatives .. . . . . . . ............ . 143 using Complc
6.2.3 Decoupling Experiments •••••• 0 ••••••••• • 145 8.1 Introduction ..
6.2.4 Altering the Chemical Structure of the Sample 145 8.2 Basic Techniq11
6.2.5 Effects of Solvent and Temperature ........ . 146 Pulsed Field G
6.2.6 Shift Reagents ....... . ................. 147 8.2.1 The Effect of t
6.2.6.1 Lanthanide Shift Reagents (LSRs) ......... . 147 Magnetization
6.2.6.2 Chiral Lanthanide Shift Reagents ...... . ... . 150 8.2.2 The Effect of t
6.3 DC NMR Spectroscopy . . . .............. . 152 on the Transvf
6.3.1 Defining the Problem .... . .... . . . ... . .. . . 152 (Mx·, My· ) .. .
6.3 .2 Empirical Correlations for Predicting 8.2.3 Spin-Locking
Approximate Chemical Shifts .......... . .. . 154 8.2.4 The Effect of l
6.3.2.1 Alkanes ..... . . . ....... . ............. . 154 Transverse M~
6.3.2.2 Alkenes ........... ... . . .............. 157 8.3 The J-Modula
6.3.2.3 Benzene Derivatives .. ...... . ....... . .... 158 8.4 The Pulsed G1
6.3.3 Decoupling Experiments • 0 0 •••••••••••••• 159 8.5 Signal Enhan<

XX
 y 1 Measurements . . . . . . . . . . . . . . . . . . . . . . . 160
6.3.4
Chemical Changes to the Sample . . . . . . . . . . . 160
6.3.5
Solvent and Temperature Effects and
6.3.6
Shift Reagents . . . . . . . . . . . . . . . . . . . . . . . . . 161
Computer-aided Assignment
6.4
of 13C NMR Spectra. . . . . . . . . . . . . . . . . . . . . 161
6.4.1
Searching for Identical or Related Compounds 161
6.4.2 Spectrum Prediction . . . . . . . . . . . . . . . . . . . . . 162
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
6.5 Bibliography for Chapter 6. . . . . . . . . . . . . . . . 165

7 Relaxation. . . . . . . . . . . . . . . . . . . . . . . . . . . 167
7.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . 167
1 .2 Spin-Lattice Relaxation of13C Nuclei (T1) . . . . 168
7.2.1 Relaxation Mechanisms . . . . . . . . . . . . . . . . . . 168
7.2.2 Experimental Determination of T 1;
the Inversion Recovery Experiment . . . . . . . . . 170
7.2 .3 Relationships between T1
and Chemical Structure . . . . . . . . . . . . . . . . . . 17 4
7.2.3.1 Influence of Protons inCH, CH2 and CH3
Groups .................... .... ... ... . 174
7.2.3 .2 Influence of Molecular Size ............. . . 175
7.2.3.3 Segmental Mobilities .. ........... ... ... . 176
7.2.3.4 Anisotropy of the Molecular Mobility .... ... . 176
7.2.4 Suppression of the Water Signal . ........ .. . 177
7.3 Spin-Spin Relaxation (T2 ) . . . . . . . . . . . . . . . . 177
7.3.1 Relaxation Mechanisms .............. ... . 177
7.3.2 Experimental Determination of T2 ;
the Spin-Echo Experiment ...... ...... . . . . 179
7.3 .3 Line-widths of NMR Signals ........... ... . 183
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
7.4 Bibliography for Chapter 7. . . . . . . . . . . . . . . . 185

8 One-Dimensional NMR Experiments

using Complex Pulse Sequences . . . . . . . . 187
8.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . 187
8.2 Basic Techniques Using Pulse Sequences and
Pulsed Field Gradients . . . . . . . . . . . . . . . . . . . 18 8
8.2.1 The Effect of the Pulse on the Longitudinal
Magnetization (Mz) . . . . . . . . . . . . . . . . . . . . . 189
8.2.2 The Effect of the Pulse
on the Transverse Magnetization Components
(Mx·, My·) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
8.2.3 Spin-Locking . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.2.4 The Effect of Pulsed Field Gradients on the
Transverse Magnetization. . . . . . . . . . . . . . . . . 195
8.3 The ]-Modulated Spin-Echo Experiment... . . 199
8.4 The Pulsed Gradient Spin-Echo Experiment . . 208
8.5 Signal Enhancement by Polarization Transfer. . 210

XXI
• 8.5.1 The SPI Experiment. ............... . .... 210
1().2.1 The Two-Spin
8.5.2 The INEPT Experiment ................ .. 213
10.2.2 Enhancement
8.5.3 The Reverse INEPT Experiment
Multi-Spin Sy~
with Proton Detection .................. . 221 10.2.3
10.2.4 From the One
8.6 The DEPT Experiment .................. 226
to the Two-Di
8.7 The Selective TOCSY Experiment . ... ... . .. 230 NOESYand I
8.8 The One-Dimensional INADEQUATE Experimental
)0.3
Experiment .......................... . 233 Applications.
10.4
Exercises .......................... ... 237 Exercises ...
8.9 Bibliography for Chapter 8 ............... . 237 Bibliography
)0.5
9 Two-Dimensional NMR Spectroscopy ... 239 Dynamic Nl
11
9.1 Introduction . . . ... . .... .. .............. 239 Introduction .
11.1
9.2 The Two-Dimensional NMR Experiment ... .. 240 11.2 Quantitative '
9.2.1 Preparation, Evolution and Mixing, 11.2.1 Complete Lin
Data Acquisition . ...................... 240 11.2.2 The Coalesce
9.2.2 Graphical Representation ................. 244 the Corresp01
9.3 Two-Dimensional ]-Resolved 11.2.3 Activation Pa
NMR Spectroscopy ..................... 245 11.2.3.1 The Arrhenil
9.3.1 Heteronuclear Two-Dimensional 11.2.3.2 The Free Ent
I- Resolved NMR Spectroscopy 0 0 •••••••••• 245 11.2.3.3 Estimating th
9.3.2 Homonuclear Two-Dimensional 11.2.4 Rate Constar
]-Resolved NMR Spectroscopy ............ 249 with Interme•
9.4 Two-Dimensional Correlated 11.2.5 Intermolecul;
NMR Spectroscopy .. ................... 254 U.3 Applications
9.4.1 Two-Dimensional Heteronuclear 11.3.1 Rotation abo
(C,H)-Correlated NMR Spectroscopy 11.3.1.1 C(sp3 )-C(sp
(HETCOR or C,H-COSY) 0 •••••••••••••• 255 11.3.1.2 C(sp2) - C(sp
9.4.2 Two-Dimensional Homo nuclear 11.3.1.3 C(sp2)-C(sp
(H,H)-Correlated NMR Spectroscopy 11.3.2 Rotation abc
(H,H-COSY; Long-Range COSY) .......... 263 11.3.3 Inversion at
9.4.3 Reverse Two-Dimensional 11.3.4 Ring Inversi1
Heteronuclear (H,C)-Correlated 11.3.5 Valence Taut
NMR Spectroscopy (HSQC; HMQC) ....... 271 11.3.6 Keto-Enol1l
9.4.4 The Gradient-Selected 11.3.7 Intermolecul
(gs-)HMBC Experiment. ................. 276 11.3.8 Reactions a11
9.4.5 The TOCSY Experiment ........... . ..... 281 Exercises ..
9.4.6 Two-Dimensional Exchange ll.4 Bibliograph~

NMR Spectroscopy: The Experiments NOESY

ROESY and EXSY ..................... 284 12 Synthetic I
9.5 The Two-Dimensional INADEQUATE 12.1 Introductio11
Experiment ........ .. ................. 289 12.2 The Tacticit:
9.6 Summary of Chapters 8 and 9 . ........... .. 294 12.3 Polymerizati
Exercises ............................. 295 12.4 Copolymers
9.7 Bibliography for Chapter 9 . ............... 295 12.5 Solid-State I
Exercises ..
10 The Nuclear Overhauser Effect ......... 297 12.6 Bibliograph
10.1 Introduction . . ...... ........ .. .... .... . 297
10.2 Theoretical Background .. .. . .... ......... 298

XXII
-----------------------------------
The Two-Spin System. . . . . . . . . . . . . . . . . . . . 298
10.2.1
Enhancement Factors... . . . . . . . . . . . . . . . . . 301
10.2.2
Multi-Spin Systems. . . . . . . . . . . . . . . . . . . . . . 302
]0.2.3
From the One-Dimensional
10.2.4
to the Two-Dimensional Experiments,
NOESY and ROESY. . . . . . . . . . . . . . . . . . . . 303
Experimental Aspects . . . . . . . . . . . . . . . . . . . 305
10.3
Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . 306
10.4
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
10.5
Bibliography for Chapter 10 . . . . . . . . . . . . . . . 311

u Dynamic NMR Spectroscopy (DNMR) . . 313

U.1 Introduction . .. ... . . . . .... ...... . ..... . 313
U.2 Quantitative Calculations ................ . 317
11.2.1 Complete Line-shape Analysis ........ : .. . . 317
11.2.2 The Coalescence Temperature Tc and
the Corresponding Rate Constant kc ...... . . 319
11.2.3 Activation Parameters .................. . 320
11.2.3.1 The Arrhenius Activation Energy EA . ...... . 320
11.2.3.2 The Free Enthalpy of Activation llG ...... . . 321
11 .2.3 .3 Estimating the Limits of Error ............ . 322
11.2.4 Rate Constants in Reactions
with Intermediate Stages .... .. .......... . 323
11.2.5 Intermolecular Exchange Processes ....... . . 324
U.3 Applications . ......................... . 325
11.3.1 Rotation about CC Single Bonds .......... . 325
11.3.1.1 C(sp3)-C(sp 3 ) Bonds ................... . 326
11.3.1.2 C(sp 2 )-C(sp3 ) Bonds ................... . 326
11.3.1.3 C(sp 2)-C(sp2 ) Bonds ................. .. . 327
11.3.2 Rotation about a Partial Double Bond ..... . . 327
11.3.3 Inversion at Nitrogen and Phosphorus Atoms .. 329
11.3.4 Ring Inversion ........................ . 330
11.3.5 Valence Tautomerism . . .......... . ...... . 333
11.3.6 Keto-Enol Tautomerism ................. . 334
11.3.7 Intermolecular Proton Exchange .......... . 335
11.3.8 Reactions and Equilibration Processes ...... . 337
Exercises ............................ . 340
11.4 Bibliography for Chapter 11 ............. . . 340

12 Synthetic Polymers . .................. . 343

12.1 Introduction .......................... . 343
U.2 The Tacticity of Polymers . ............... . 343
12.3 Polymerization of Dienes . .. . . ......... . . . 347
12.4 Copolymers ............ .. . . .......... . 348
12.5 Solid-State NMR Spectroscopy of Polymers . . . 349
Exercises ............................ . 352
U.6 Bibliography for Chapter 12 . ............. . 352

XXIII
 The Two-Spin System . ..... · · · · · · · .... . . . 298
10.2.1 Enhancement Factors ......... · . . . . . . .. . . 301
J().2.2 Multi-Spin Systems ... · · · · · · · · · · · · · · · · · .. 302
J(J.2.3 From the One-Dimensional
]0.2.4 to the Two-Dimensional Experiments,
NOESY and ROESY . · · · · · · · · · · · .... · · . . 303
Experimental Aspects ........ · ... .... .. . 305
J0.3 306
Applications ... · · · · · · · · · · · · · · · · · · · · · · · ·
J0.4
Exercises . . . . · · · · · · · · · · · · · · · · · · · · · · . . . 311
Bibliography for Chapter 10 . . . . . . . . . . . . . . . 311
10.5
Dynamic NMR Spectroscopy (DNMR) . . 313
11
11.1 Introduction .. · · · · · · · · · · · · · · · · · · · · · · · .. 313
Quantitative Calculations . . . . . . . . . . . . . . , . . 317
11.2
Complete Line-shape Analysis ............ . 317
J1.2.1
The Coalescence Temperature Tc and
11.2.2
the Corresponding Rate Constant k c ....... . 319
11.2.3 Activation Parameters ........ . ......... . 320
J1.2.3.1 The Arrhenius Activation Energy EA . ..... . . 320
11.2.3 .2 The Free Enthalpy of Activation tlG ....... . 321
11.2.3.3 Estimating the Limits of Error ............ . 322
11.2.4 Rate Constants in Reactions
with Intermediate Stages ...... . ...... ... . 323
11.2.5 Intermolecular Exchange Processes . . . .... . . 324
11.3 Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . 325
11.3.1 Rotation about CC Single Bonds ......... . . 325
11.3.1.1 C(sp3) -C(sp3) Bonds ......... . .... .. ... . 326
11.3.1.2 C(sp 2)-C(sp3) Bonds .. . . . .............. . 326
11.3.1.3 C(sp2)-C(sp2) Bonds . .................. . 327
11.3.2 Rotation about a Partial Double Bond ...... . 327
!1 .3.3 Inve r i n at itrogen and Phosphoru Atom . . 329
11.3.4 Ring fnver ion ... ..... ........ .. . ... .. . 330
11 . .5 Valenc Tautomerism . ... .. ..... ...... . . . 333
11.3.6 Keto-Enol Tautomerism ..... ........ ... . . 334
11.3.7 Intermolecula r Pro to n Exchange . .. . . . .. .. . 335
11 .3.8 Reaction and quilibrati n Processes .. . . .. . 337
Exercises .... ...... ...... . .. .. . . .. ... . 340
11.4 Bibliography for Chapter 11 . ...... ... . ... . 340

12 Synthetic Polymers ................... . 343

12.1 Introduction . ...... ......... . .. . ...... . 343
U.2 The Tacticity of Polymers .. .......... . ... . 343
12.3 Polymerization ofDienes .... .. . ......... . 347
12.4 op lyn1er ...... .......... ......... . . 348
12.5 Soljd- tate NMR Spectroscopy of P Jyo1e r . . . 349
~ xercises . . . . . .... ....... .. . . .. .. . .. . . 352
U.6 Bibliography for Chapter 12 ..... . ....... . . 352

XXIII
13 NMR Spectroscopy in
Biochemistry and Medicine . . . . . . ... . .. 355
Introduction ...... . · · · · · · · · · · · · · · · · · · · · 355
1 The Ph~
13.1
13.2
Elucidating Reaction Pathways in Biochemistry 355
Syntheses using Singly 13C-Labeled Precursors 356
ofNMF
L3.2.J
13.2.1.1 Low Levels of J3C Enrichment .. · · · · ... .... 356
13.2.1.2 High Levels of 13C Enrichment. ........... . 357
13.2.2 Syntheses using D oubly 13 C-Labeled Precursors 358
13.3 Biopolymers . . . . . .. . . .... ........... . .. 360
13.3.1 Peptides and Proteins ...... ........ .. ... . 361 1.1 Introducti~
13.3.1.1 Sequence Analysis . ... ..... . ........ .... 362
13.3.1.2 The Three-Dimensional Structure of Proteins .. 363
13.3.2 Polynucleotides .. ... ..... . . ... . . . . ..... 365 In 1946 two research gr
13.3.3 Oligosaccharides and Polysaccharides .. . ... . . 367 and M. E . Packard and th
13.4 Saturation Transfer Difference NMR Spectros- R.V. Pound , independen
copy (STD) .. ............ .... . ...... .. 371 nance signals for the first
Exercises .... . . . .. .. . .. ........... . . .. 372 awarded the Nobel Prize 1
13.5 Bibliography for Chapter 13 . ............. . 372 Since then nuclear magn
has developed into an i1
14 In vivo NMR Spectroscopy in chemists, physicists, anc
Biochemistry and Medicine • •• •• •• • 0 ••• 375 During the first three deca
14.1 Introduction . ....... . . . . . ....... . .. . ... 375 ments relied on one-dim
14.2 High-Resolution in vivo NMR Spectroscopy . . . 376 gives spectra having just
14.2.1 The Problem and its Solution .. .. . . ... . .... 376 being used to display the 1
14.2.2 3lp NMR Experiments ....... ........ .... 377 two-dimensional NMR e>
14.2.3 1H and 13 C NMR Experiments . ....... . . . ..
380 the start of a new era in l
14.3 Magnetic Resonance Tomography ....... . . . 381 by these methods have
14.3.1 Basic Principles and Experimental being displayed in the tt
Considerations .. .... ................. .. 381 even become possible to
14.3.2 Applications ... ........... .......... ... 387 more dimensions, althoug
14.4 Magnetic Resonance Spectroscopy, 1H MRS .. 391 techniques. The importa
Exercises .... ..... ..... . .... . .. . ...... 393 troscopy now occupies
14.5 Bibliography for Chapter 14 . ...... .. ... . .. 393 Nobel Prize for Chemistr
to K. Wi.ithrich , and of t
Solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395 to P. Lauterbur and P. M
on NMR methods in ch
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . 407 The new techniques tha
years show that develop1
Index of Compounds . . . . . . . . . . . . . . . . . . . . 411 far from coming to an em
This book aims to exr
cially, NMR spectroscoJ
important of all spectrosc
The main field of appli
determining the structure
mation for this is obtaint
preting high-resolution r
low viscosity (or in some
niques and instruments tt
years) . In this book we w

XXIV Basic One- and Two-Dimensi'

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ISBN 978-3-527-32782-9