Guide to fluorine NMR for organic chemists / William R. Dolbier, Jr.

Format:

Book

Author/Creator:

Dolbier, William R.

Language:

English

Subjects (All):

Fluorine compounds--Spectra.

Fluorine compounds.

Nuclear magnetic resonance spectroscopy.

Physical Description:

xvi, 256 pages : illustrations ; 25 cm

Place of Publication:

Hoboken, N.J. : Wiley, [2009]

Summary:

Guide to Fluorine NMR for Organic Chemists provides a unique single source on both fluorine NMR and the impact of fluorine substituents on proton and carbon NMR spectra. Helping working chemists overcome the challenges associated with the synthetic methodologies of fluorinated compounds, this guide enables the effective use of these increasingly popular spectroscopic techniques to accurately characterize compounds that contain fluorine.

Following a thorough introduction of fluorinated compounds, chapters in the text cover:

An overview of fluorine NMR

The Single fluorine substituent

The CF2 group

The trifluoromethyl group

More heavily fluorinated compounds

Compounds and substituents with fluorine directly bound to heteroatoms

With unparalleled depth and completeness, the coverage ranges from those compounds containing only a few fluorinated substituents, typically employed in pharmaceutical and agricultural applications, to more heavily fluorinated compounds.

Featuring NMR data for more than 1,000 specific compunds and including more than 100 exemplary spectra, Guide to Fluorine NMR for Organic Chemists gives the working chemist and advanced student an essential tool for understanding cutting-edge NMR techniques and interpreting the resulting spectroscopic data.

Contents:

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 35

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 αβ-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 97

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 αβ-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 CF2 Group 139

5.2.1 Alkanes Bearing a CF3 Group 139

5.2.2 Cycloalkanes Bearing a CF3 Group 140

5.2.3 1H 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 αβ-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.

Notes:

Includes bibliographical references and indexes.

ISBN:

9780470193419

0470193417

OCLC:

288932908