Dolbier W.R., jr. Guide to fluorine NMR for organic chemists. - Hoboken: Wiley, 2009. - xiv, 256 p.: ill. - Incl. bibl. ref. and index. - ISBN 978-0-470-19341-9  Место хранения:   032 | Институт органической химии им. Н.Н.Ворожцова СО РАН | Новосибирск | Библиотека

Оглавление / Contents

PREFACE ...................................................... xiii 1 GENERAL INTRODUCTION ......................................... 1 1.1 Why Fluorinated Compounds are Interesting ............... 1 1.1.1 Steric Size ...................................... 1 1.1.2 Polar Effects .................................... 1 1.1.3 Effect of Fluorine Substituents on the Acidity and Basicity of Compounds ....................... 2 1.1.4 Effect of Fluorinated Substituents on the Lipophilicity of Molecules ....................... 3 1.1.5 Other Effects .................................... 4 1.1.6 Analytical Applications in Biomedicinal Chemistry ........................................ 4 1.2 Introduction to Fluorine NMR ............................ 4 1.2.1 Chemical Shifts .................................. 5 1.2.2 Coupling Constants ............................... 6 References ................................................... 6 2 AN OVERVIEW OF FLUORINE NMR .................................. 9 2.1 Introduction ............................................ 9 2.2 Fluorine Chemical Shifts ............................... 10 2.2.1 Steric Deshielding of Fluorine .................. 12 2.2.2 Solvent Effects on Fluorine Chemical Shifts ..... 13 2.2.3 Overall Summary of Fluorine Chemical Shift Ranges .......................................... 14 2.3 Spin-Spin Coupling Constants to Fluorine ............... 15 2.3.1 Through-Space Coupling .......................... 18 2.3.2 Fluorine-Fluorine Coupling ...................... 20 2.3.3 Coupling between Fluorine and Hydrogen .......... 20 2.3.4 Coupling between Fluorine and Carbon ............ 21 2.3.5 Second-Order Spectra ............................ 22 2.4 1H Spectra of Fluoroorganic Compounds .................. 27 2.5 13C NMR Spectra of Fluoroorganic Compounds ............. 28 2.6 Isotope Effects on Chemical Shifts ..................... 29 2.7 Advanced Topics ........................................ 31 2.7.1 Multidimensional 19F NMR ........................ 32 References .................................................. 34 3 THE SINGLE FLUORINE SUBSTITUENT 3.1 Introduction ........................................... 35 3.1.1 Chemical Shifts—General Considerations .......... 36 3.1.2 Spin-Spin Coupling Constants—General Considerations .................................. 36 3.2 Saturated Hydrocarbons ................................. 37 3.2.1 Primary Alkyl Fluorides ......................... 37 3.2.2 Secondary Alkyl Fluorides ....................... 40 3.2.3 Tertiary Alkyl Fluorides ........................ 43 3.2.4 Cyclic Alkyl Fluorides .......................... 45 3.3 Influence of Substituents / Functional Groups .......... 47 3.3.1 Halogen Substitution ............................ 47 3.3.2 Alcohol, Ether, Ester, Sulfide, and Sulfone Groups .......................................... 52 3.3.3 Amino and Ammonium Groups ....................... 55 3.3.4 Phosphorous Compounds ........................... 56 3.3.5 Silanes ......................................... 57 3.4 Carbonyl Functional Groups ............................. 58 3.4.1 1H and 13C NMR Data for Aldehydes, Ketones, and Esters ...................................... 59 3.5 Nitriles ............................................... 60 3.5.1 1H and 13C NMR Data for Nitriles ................. 61 3.6 Alkenes with a Single Fluorine Substituent ............. 61 3.6.1 Hydrocarbon Alkenes ............................. 62 3.6.2 Conjugated Alkenyl Systems ...................... 64 3.6.3 Allylic Alcohols, Ethers, and Halides ........... 67 3.6.4 Halofluoroalkenes and Fluorovinyl Ethers ........ 67 3.6.5 Multifluoroalkenes .............................. 69 3.6.6 α,β-Unsaturated Carbonyl Compounds .............. 70 3.7 Acetylenic Fluorine .................................... 75 3.8 Allylic, Propargylic, and Benzylic Fluorides ........... 75 3.8.1 1H and 13C NMR Data .............................. 75 3.9 Fluoroaromatics ........................................ 75 3.9.1 Monofluoroaromatics ............................. 75 3.9.2 Fluoropolycyclic Aromatics: Fluoronaphthalenes .............................. 81 3.9.3 Polyfluoroaromatics ............................. 82 3.10 Fluoroheterocycles ..................................... 83 3.10.1 Fluoropyridines and Quinolines ................. 88 3.10.2 Fluoropyrroles ................................. 89 3.10.3 Fluorofurans and Benzofurans ................... 89 3.10.4 Fluorothiophene and Benzothiophene ............. 90 3.10.5 Fluoroimidazoles and Pyrazoles ................. 92 3.11 Other Common Groups with a Single Fluorine Substituent ............................................ 92 3.11.1 Acyl Fluorides ................................. 92 3.11.2 Fluoroformates ................................. 94 3.11.3 Sulfinyl and Sulfonyl Fluorides ................ 94 References .................................................. 94 4 THE CF2 GROUP 4.1 Introduction ........................................... 97 4.1.1 Chemical Shifts—General Considerations .......... 98 4.1.2 Spin-Spin Coupling Constants—General Considerations .................................. 99 4.2 Saturated Hydrocarbons Containing a CF2 Group .......... 99 4.2.1 Alkanes Bearing a Primary CF2H Group ........... 100 4.2.2 Secondary CF2 Groups ........................... 101 4.2.3 Comments on Coupling Constants ................. 103 4.2.4 Pertinent 1H Chemical Shift Data ............... 105 4.2.5 Pertinent 13C NMR Data ......................... 107 4.3 Influence of Substituents Functional Groups ........... 108 4.3.1 Halogen Substitution ........................... 109 4.3.2 Alcohol, Ether, Thioether, and Related Substituents ................................... 111 4.3.3 Compounds with Two Different Heteroatom Groups Attached to CF2 Including Chlorodifluoromethyl Ethers .................... 115 4.3.4 Amines, Phosphines, and Phosphonates ........... 116 4.3.5 Silanes ........................................ 118 4.3.6 Organometallics ................................ 118 4.4 Carbonyl Functional Groups ............................ 119 4.4.1 Aldehydes and Ketones .......................... 119 4.4.2 Carboxylic Acids and Derivatives ............... 120 4.5 Nitriles .............................................. 122 4.5.1 1H and 13C NMR Spectra of Nitriles .............. 122 4.6 Bifunctional CF2 Compounds ............................ 123 4.7 Alkenes and Alkynes ................................... 124 4.7.1 Simple Alkenes with Terminal Vinylic CF2 Groups ......................................... 124 4.7.2 Conjugated Alkenes with Terminal Vinylic CF2 Group .......................................... 126 4.7.3 Effect of Vicinal Halogen or Ether Function ....................................... 127 4.7.4 Polyfluoroethylenes ............................ 127 4.7.5 The Trifluorovinyl Group ....................... 127 4.7.6 α,β-Unsaturated Carbonyl Systems with a Terminal Vinylic CF2 Group ................... 128 4.7.7 Allylic and Propargylic CF2 Groups ............. 129 4.8 Benzenoid Aromatics Bearing a CF2 Group ............... 130 4.8.1 1H and 13C NMR Data ............................ 131 4.9 Heteroaromatic CF2 Groups ............................. 132 4.9.1 Pyridines ...................................... 132 4.9.2 Furans, Thiophenes, and Pyrroles ............... 132 4.9.3 Imidazoles and Other Heterocyclic CF2H Compounds ...................................... 133 4.9.4 1H and 13C NMR Data for Heterocyclic-Bound CF2 Groups ..................................... 133 References ................................................. 135 5 THE TRIFLUOROMETHYL GROUP .................................. 137 5.1 Introduction .......................................... 137 5.1.1 NMR Spectra of Compounds Containing the CF3 Group—General Considerations ................... 137 5.2 Saturated Hydrocarbons Bearing a CF3 Group ........... 139 5.2.1 Alkanes Bearing a CF3 Group .................... 139 5.2.2 Cycloalkanes Bearing a CF3 Group ............... 140 5.2.3 1Н and 13C NMR Data, General Information ....... 140 5.3 Influence of Substituents and Functional Groups ....... 142 5.3.1 Impact of Halogens ............................. 143 5.3.2 Ethers, Alcohols, Esters, Sulfides, and Selenides ...................................... 144 5.3.3 Amines and Phosphines .......................... 148 5.3.4 Organometallics ................................ 151 5.4 Carbonyl Compounds .................................... 152 5.4.1 1H and 13C NMR Data ............................ 155 5.5 Nitriles .............................................. 157 5.5.1 13C NMR Data for Nitriles ...................... 157 5.6 Bifunctional Compounds ................................ 158 5.7 Sulfonic Acid Derivatives ............................. 158 5.8 Allylic and Propargylic Trifluoromethyl Groups ........ 159 5.8.1 Allylic Trifluoromethyl Groups ................. 159 5.8.2 α,β-Unsaturated Carbonyl Compounds ............. 163 5.8.3 More Heavily Fluorinated Allylics .............. 165 5.8.4 Propargylic Trifluoromethyl Groups ............. 165 5.9 Aryl-Bound Trifluoromethyl Groups ..................... 166 5.9.1 13C NMR Data ................................... 167 5.10 Heteroaryl-Bound Trifluoromethyl Groups ............... 168 5.10.1 Pyridines and Quinolines ....................... 168 5.10.2 Pyrroles and Indoles ........................... 169 5.10.3 Thiophenes and Benzthiophenes .................. 170 5.10.4 Furans ......................................... 170 5.10.5 Imidazoles and Benzimidazoles .................. 172 5.10.6 Oxazoles, Thiazoles, Benzoxazoles, and Benzthiazoles .................................. 173 5.10.7 Pyrazoles and Pyridazines ...................... 174 References ............................................ 175 6 MORE HIGHLY FLUORINATED GROUPS ............................. 177 6.1 Introduction .......................................... 177 6.2 The 1,1,2- and 1,2,2-Trifluoroethyl Groups ............ 178 6.3 The 1,1,2,2-Tetrafluoroethyl and 2,2,3,3-Tetrafluoropropyl Groups ...................... 180 6.4 The 1,2,2,2-Tetrafluoroethyl Group .................... 183 6.5 The Pentafluoroethyl Group ............................ 185 6.5.1 Pentafluoroethyl Carbinols ..................... 188 6.5.2 Pentafluoroethyl Ethers and Sulfides ........... 188 6.5.3 Pentafluoroethyl Organometallics ............... 189 6.6 The 2,2,3,3,3-Pentafluoropropyl Group ................. 189 6.7 The 1,1,2,3,3,3-Hexafluoropropyl Group ................ 192 6.8 The Hexafluoro-iso-Propyl Group ....................... 192 6.9 The Heptafluoro-n-Propyl Group ........................ 194 6.10 The Heptafluoro-iso-Propyl Group ...................... 195 6.11 The Nonafluoro-n-Butyl Group .......................... 195 6.12 Fluorous Groups ....................................... 195 6.13 1-Hydro-Perfluoroalkanes .............................. 197 6.14 Perfluoroalkanes ...................................... 197 6.15 Perfluoro-n-Alkyl Halides ............................. 201 6.16 Perfluoroalkyl Amines, Ethers, and Carboxylic Acid Derivatives ........................................... 201 6.17 Polyfluoroalkenes ..................................... 201 6.17.1 Trifluorovinyl Groups .......................... 201 6.17.2 Perfluoroalkenes ............................... 205 6.18 Polyfluorinated Aromatics ............................. 206 6.18.1 2,3,5,6-Tetrafluorobenzene Compounds ........... 206 6.18.2 The Pentafluorophenyl Group .................... 206 6.19 Polyfluoroheterocyclics ............................... 207 6.19.1 Polyfluoropyridines ............................ 207 6.19.2 Polyfluorofurans ............................... 207 6.19.3 Polyfluorothiophenes ........................... 207 6.19.4 Polyfluoropyrimidines .......................... 207 References ................................................. 210 7 COMPOUNDS AND SUBSTITUENTS WITH FLUORIDE DIRECTLY BOUND TO A HETEROATOM ............................................ 211 7.1 Introduction .......................................... 211 7.2 Boron Fluorides ....................................... 212 7.3 Fluorosilanes ......................................... 213 7.4 Nitrogen Fluorides .................................... 213 7.4.1 Electrophilic Fluorinating Agents .............. 214 7.5 Phosphorous Fluorides ................................. 214 7.5.1 Phosphorous (III) Fluorides .................... 214 7.5.2 Phosphorous (V) Fluorides ...................... 215 7.5.3 Phosphorous (V) Oxyfluorides ................... 217 7.6 Oxygen Fluorides (Hypofluorites) ...................... 217 7.7 Sulfur Fluorides ...................................... 218 7.7.1 Inorganic Sulfur Fluorides and Oxyfluorides .... 218 7.7.2 Aryl and Alkyl SF3 Compounds ................... 219 7.7.3 Dialkylaminosulfur Trifluorides ................ 219 7.7.4 Hypervalent Sulfur Fluorides ................... 221 7.7.5 Related Hypervalent Selenium and Tellurium Fluorides ...................................... 221 7.7.6 Organic Sulfinyl and Sulfonyl Fluorides ........ 222 7.8 The Pentafluorosulfanyl (SF5) Group ................... 222 7.8.1 Saturated Aliphatic Systems .................... 225 7.8.2 Vinylic SF5 Substituents ....................... 228 7.8.3 Acetylenic SF5 Substituents .................... 229 7.8.4 Aromatic SF5 Substituents ...................... 229 7.9 Bromine Trifluoride and Iodine Pentafluoride .......... 230 7.10 Aryl Halogen Difluorides and Tetrafluorides ........... 231 7.11 Xenon Difluoride ...................................... 231 References ................................................. 232 GENERAL INDEX ................................................. 233 COMPOUND INDEX ................................................ 236