Preface ........................................................ xi
1 Introduction to 1H NMR Chemical Shifts ....................... 1
1.1 Historical Background ................................... 1
1.2 Basic Theory of NMR ..................................... 3
1.3 The 1H Chemical Shift ................................... 4
1.3.1 Nuclear Shielding and Reference Compounds ........ 4
1.4 1H Substituent Chemical Shift (SCS) ..................... 5
1.4.1 Two-bond (H.C.X) Effects ......................... 6
1.4.2 Three-bond (H.C.C.X) Effects ..................... 6
1.4.3 1H SCSs in Olefins and Amniotics ................. 7
1.5 Long-range Effects on 1H Chemical Shifts ................ 9
1.5.1 Steric (van der Waals) Effects .................. 10
1.5.2 Electric Field Effects .......................... 10
1.5.3 π-Electron Effects .............................. 12
1.5.4 Hydrogen Bonding Shifts ......................... 17
1.6 Tables of 1H Chemical Shifts of Common Unsaturated
and Saturated Cyclic Systems ........................... 17
References .................................................. 20
2 Interpretation of 1H NMR Coupling Patterns .................. 23
2.1 Fine Structure due to HH Coupling ...................... 23
2.2 The Analysis of NMR Spectra ............................ 26
2.2.7 Nomenclature of the Spin System, Chemical and
Magnetic Equivalence ............................ 26
2.2.2 Two Interacting Nuclei, the AB Spectrum ......... 29
2.2.3 Three Interacting Nuclei, the ABX Spectrum ...... 32
2.2.4 Four Interacting Nuclei ......................... 32
2.2.5 Iterative Computer Analysis ..................... 37
2.2.5 Automatic Iteration of Complex Spectra .......... 43
2.3 The Mechanism of Spin-Spin Coupling .................... 44
2.3.1 Geminal HH Couplings (2JHH) ...................... 45
2.3.2 Vicinal HH Couplings (3JHH) ..................... 49
2.3.3 Ab initio Calculated Couplings .................. 52
2.3.4 Long-range HH Couplings ......................... 55
2.4 HF Couplings ........................................... 57
2.4.1 Geminal HF Couplings (2JHF) ..................... 57
2.4.2 Vicinal HF Couplings ............................ 58
2.4.3 Long-range HF Couplings ......................... 61
References .................................................. 63
3 Chemical Shift Calculations and Molecular Structure ......... 67
3.1 Introduction ........................................... 67
3.2 Quantum Mechanical Calculations of 1H Chemical
Shifts ................................................. 68
3.3 The Database Approach .................................. 69
3.4 Semi-empirical Calculations ............................ 70
3.5 Theory of the CHARGE Program ........................... 72
3.5.1 Through Bond Effects ............................ 72
3.5.2 1H Chemical Shifts of Substituted Methanes and
Ethanes ......................................... 74
3.5.3 Through Space Effects ........................... 77
3.5.4 Hydrogen Bonding Shifts ......................... 78
3.5.5 Aromatic Compounds .............................. 80
References .................................................. 82
4 Modelling 1H Chemical Shifts, Hydrocarbons .................. 85
4.1 Introduction ........................................... 85
4.2 Alkane Chemical Shifts ................................. 86
4.2.1 H.H and C.H Steric Interactions ................. 86
4.2.2 The Methyl Effect ............................... 89
4.2.3 C—C Bond Anisotropy ............................. 90
4.2.4 Observed versus Calculated Shifts ............... 92
4.3 Alkene Chemical Shifts ................................ 100
4.3.1 Introduction ................................... 100
4.3.2 C=C Bond Anisotropy and Shielding .............. 102
4.3.3 Observed versus Calculated Shifts .............. 104
4.4 Alkyne Chemical Shifts ................................ 116
4.4.1 Introduction ................................... 116
4.4.2 C≡C Bond Anisotropy and Shielding .............. 116
4.4.3 Observed versus Calculated Shifts .............. 118
4.4.4 Acetylene SCSs ................................. 121
4.4.5 Contributions to the Acetylene SCSs ............ 126
4.4.6 Naphthyl and Phenanthryl Acetylenes ............ 128
4.5 Summary ............................................... 129
References ................................................. 130
5 Modelling 1H Chemical Shifts, Aromatics .................... 133
5.1 Aromatic Hydrocarbons ................................. 133
5.1.1 Introduction ................................... 133
5.7.1 Ring Currents, π-Electron Densities and
Steric Effects ................................. 135
5.1.1 Observed versus Calculated Shifts .............. 139
5.2 Heteroaromatics ....................................... 148
5.2.1 Introduction ................................... 148
5.2.2 Theory and Application to Heteroaromatics ...... 149
5.2.3 Observed versus Calculated Shifts .............. 155
5.2.4 Ring Currents and π-Electron Shifts ............ 159
5.3 Summary ............................................... 166
References ................................................. 167
6 Modelling 1H Chemical Shifts, Monovalent Substituents ...... 169
6.1 Introduction .......................................... 169
6.2 Fluorine Substituent Chemical Shifts .................. 169
6.2.1 Electric Field Theory .......................... 170
6.2.2 Fluoroalkanes .................................. 172
6.2.3 Fluoroalkenes and Aromatics .................... 179
6.3 Steric, Anisotropic and Electric Field Effects in
Cl, Br and I SCSs ..................................... 179
6.3.1 Introduction ................................... 179
6.3.2 Aromatic Halides ............................... 182
6.3.3 Alkyl Halides .................................. 184
6.3.4 Contributions to the 1H SCSs in
Halocyclohexanes ............................... 191
6.3.5 Steric Coefficients for Halogens ............... 197
6.4 Alcohols and Phenols .................................. 199
6.4.1 Introduction ................................... 199
6.4.2 Alcohols and Diols ............................. 200
6.4.3 Phenols ........................................ 209
6.5 Amines ................................................ 215
6.5.1 Introduction ................................... 215
6.5.2 Theory and Application to Amines ............... 216
6.5.3 Observed versus Calculated Shifts .............. 217
6.5.4 Conformational Analysis ........................ 217
6.6 Cyanides .............................................. 224
6.6.1 Introduction ................................... 224
6.6.2 Theory and Application to the Cyano Group ...... 225
6.6.3 Observed versus Calculated Shifts .............. 226
6.6.4 Cyano SCSs ..................................... 231
6.7 Nitro Compounds ....................................... 233
6.7.1 Introduction ................................... 233
6.7.2 Theory and Application to Nitro Compounds ...... 234
6.7.3 Observed versus Calculated Shifts .............. 236
6.7.4 SCSs of the Nitro Group ........................ 237
6.7.5 Conformational Analysis ........................ 238
6.8 Summary ............................................... 241
References ................................................. 242
7 Modelling 1H Chemical Shifts, Divalent Substituents ........ 247
7.1 Introduction .......................................... 247
7.2 Aliphatic Aldehydes and Ketones ....................... 247
7.2.2 Aromatic Aldehydes and Ketones ................. 256
7.2.3 Conformational Analysis ........................ 261
7.3 Esters ................................................ 263
7.3.1 Introduction ................................... 263
7.3.2 Theory, Application to Esters .................. 264
7.3.3 Observed versus Calculated Shifts .............. 266
7.4 Amides ................................................ 273
7.4.1 Introduction ................................... 273
7.4.2 Theory, Application to Amides .................. 214
7.4.3 Aliphatic and Cyclic Amides .................... 275
7.4.4 Aromatic Amides ................................ 279
7.5 Steric and Electric Field Effects in Acyclic and
Cyclic Ethers ......................................... 282
7.5.1 Introduction ................................... 282
7.5.2 Theory, Application to Ethers .................. 283
7.5.3 Oxygen SCSs in Ethers .......................... 284
7.5.4 Observed versus Calculated Shifts .............. 286
7.6 Sulfoxides and Sulfones ............................... 290
7.6.1 Introduction ................................... 290
7.6.2 Theory, Application to Sulfoxides and
Sulfones ....................................... 290
7.6.3 Molecular Geometries ........................... 290
7.6.4 Observed versus Calculated Shifts .............. 291
7.7 Summary ............................................... 297
References ................................................. 298
8 1H Chemical Shifts and Structural Chemistry ................ 303
8.1 Introduction .......................................... 303
8.2 Electronic Structure Calculations ..................... 304
8.2.1 Basis Sets ...................................... 306
8.3 Molecular Mechanics Calculations ...................... 306
8.3.1 Conformer Generation ........................... 307
8.4 Molecular Geometries and 1H Chemical Shift
Calculations .......................................... 309
8.4.1 Methyl Anthracene-9-carboxylate ................ 310
8.4.2 N-Formyl Aniline (1) ........................... 312
8.4.3 Benzosuberone (2) .............................. 313
8.5 Rate Processes and NMR Spectra ........................ 314
8.5.1 Theory ......................................... 314
8.5.2 Amide Rotation ................................. 317
5.5.1 Proton Exchange Equilibria ..................... 318
8.5.1 Rotation about Single Bonds, Ring Inversion
Processes ...................................... 319
8.6 Solvent Effects ....................................... 322
8.6.1 Introduction ................................... 322
8.6.2 Non-polar Compounds ............................ 324
8.6.3 Polar Aprotic Compounds ........................ 325
8.6.4 Protic Compounds ............................... 331
8.6.5 Diols and Polyhydroxy Compounds ................ 340
8.6.6 Chemical Shift Contributions ................... 340
8.7 Summary ................................................ 345
References ................................................. 346
9 A Practical Approach to 1H NMR Calculation and
Prediction ................................................. 349
9.1 Introduction .......................................... 349
9.2 A Step-by-Step Description of Calculating !H NMR
Spectra ............................................... 350
9.2.1 Molecular Modelling and Conformational
Searching - PCModel ............................ 350
9.2.2 Calculating 1H Chemical Shifts and J-Coupling
Constants - HNMRSPEC ........................... 357
9.2.3 Displaying the Calculated 1H Spectrum -
1HPLOT ......................................... 361
9.2.4 Advanced Use of HNMRSPEC_S ..................... 362
9.2.5 Iteration of 2nd Order 1H Spectra from Pre-
specified δs and Js-LAOCOON .................... 363
9.3 Automated Spectral Prediction Using the NMRPredict
Software .............................................. 365
9.4 Concluding Remarks .................................... 368
Index ......................................................... 369
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