Aromatic Fluorination

Clark James H. Aromatic Fluorination [CRC revivals - New directions in organic and biological chemistry] 2018 [pdf 199sc 186c. 10.49mb] MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict MuPDF error: syntax error: invalid key in dict Cover 1 Half Title 2 Copyright Page 5 Contents 10 Chapter 1: Introduction to Aromatic Fluorination 14 1.1 Historical Developments 14 1.2 Properties of Fluorinated Aromatic Molecules 16 1.2.1 Fundamental Properties 17 1.2.2 Effects of Fluorine on Chemical Reactivity 18 1.2.3 Effects of Fluorine on Physical Properties 19 1.3 Applications for Fluorinated Aromatics 22 1.4 Raw Materials 26 1.5 Laboratory and Industrial Methods of Fluorination 26 References 30 Chapter 2: Halex Chemistry 32 2.1 Introduction 32 2.2 Fluoride Reagents 36 2.2.1 Surface Area 39 2.2.2 Phase Transfer Catalysis and Related Methods 39 2.2.3 Soluble Fluorides 40 2.3 Physical Properties of Fluoroaromatics 41 2.4 Chemical Properties of Fluoroaromatics 44 2.4.1 Nucleophilic Substitution 44 2.4.2 Electrophilic Substitution 48 2.4.3 Radical Substitution 50 2.4.4 Other Chemical Reactivity Effects 50 2.5 Routes to Fluoroaromatics 50 2.5.1 Halex Methods 50 2.5.2 Fluorodenitration Methods 53 2.5.3 Other Aromatic Nucleophilic Fluorinations 64 References 67 Chapter 3 The Balz-Schiemann Reaction and Related Chemistry 70 3.1 Introduction 70 3.2 Synthesis of Aryldiazonium Tetrafluoroborate Salts 71 3.3 Decomposition of Aryldiazonium Tetrafluoroborate Salts 72 3.4 Alternative Diazonium Salts 74 3.5 Mechanistic Aspects of the Balz-Schiemann Reaction 75 3.6 Fluoroaromatics via HF-Based Diazotizations 76 3.7 Synthetic Methods 77 References 79 Chapter 4: Other Aromatic Fluorination Methodologies 82 4.1 Introduction 82 4.2 Direct Fluorination 83 4.3 Fluorination Using O-F-Type Compounds 86 4.3.1 Fluoroxytrifluoromethane and Bis(fluoroxy)trifluoromethane 86 4.3.2 Acetyl Hypofluorite 87 4.3.3 Cesium Fluoroxysulfate 88 4.4 Fluorinations Using Xenon Difluoride 90 4.5 Fluorination Using High-Valency Metal Fluorides 90 4.5.1 Silver (11) Fluoride 91 4.5.2 Cobalt Trifluoride 91 4.6 Electrochemical Fluorination 92 4.7 Fluorination Using N-F-Type Reagents 93 4.8 Miscellaneous Fluorination Methods 96 4.9 Synthetic Methods 97 References 100 Chapter 5 Trifluoromethylaromatics 102 5.1 Introduction 102 5.2 Physical Properties 103 5.3 Chemical Properties 106 5.4 Synthesis of Trifluoromethylated Aromatics 109 5.4.1 Routes from Toluenes Using Hydrogen Fluoride and Related Reactions 109 5.4.2 Routes from Haloaromatics Using Organometallic Reagents 113 5.4.3 Routes from Aromatic Hydrocarbons 119 5.4.4 Routes from Aromatic Carboxylic Acids 123 5.4.5 Routes from Other Aromatic Substrates 124 5.5 Synthetic Methods 125 References 130 Chapter 6 Trifluoromethylthioaromatics and Trifluoromethylsulfonylaromatics 132 6.1 Introduction 132 6.2 Physical Properties of Trifluorornethylthioaromatics and Trifluoromethylsulfonylaromatics 132 6.3 Chemical Properties of Trifluorornethylthioaromatics and Trifluoromethylsulfonylaromatics 135 6.4 Synthesis of Trifluoromethylthioaromatics and Trifluoromethylsulfonylaromatics 135 6.4.1 Routes to Trifluoromethylthioaromatics from Arylmethyl Sulfides via the Trichloromethylthioaromatics 137 6.4.2 Routes to Trifluorornethylthioaromatics from Haloaromatics via Nucleophilic Substitution 137 6.4.3 Routes to Trifluoromethylthioaromatics from Aromatic Hydrocarbons via Electrophilic Substitution 140 6.4.4 Routes to Trifluoromethylthioaromatics from Aromatic Thiols via Radical Substitution 142 6.4.5 Routes to Trifluorornethylsulfonylaromatics from Aromatic Hydrocarbons via Electrophilic Substitution 143 6.4.6 Routes to Trifluorornethylsulfonylaromatics from Trifluoromethylthioaromatics via Oxidation 145 6.4.7 Routes to Trifluorornethylsulfonylaromatics from other Aromatic Substrates 147 6.5 Synthetic Methods 149 References 151 Chapter 7 Other Aromatic Ring Substituents 152 7.1 Introduction 152 7.2 Physical Properties 153 7.3 Chemical Properties 153 7.4 Synthesis of Trifluoromethoxy-Substituted Aromatics 154 7.4.1 Halogen Exchange Reactions of α, α, α-Trichloromethoxy Aromatics 155 7.4.2 Conversion of Phenols to Trifluoromethoxybenzenes 155 7.5 Synthesis of Fluoroalkoxy-Substituted Aromatics 156 7.6 Synthesis of Perfluoroalkyl-Substituted Aromatics 158 7.6.1 Direct Incorporation of Perfluoroalkyl Groups 158 7.6.2 Fluorination of Existing Side Chains 160 7.6.3 Nucleophilic Substitution Reactions 160 7.7 Synthesis of Fluoroalkyl-Substituted Aromatics 163 7.8 Synthesis of Aryl Difluoromethyl Ethers and Thioethers 164 7.9 Synthetic Methods 166 7.9.1 Trifluoromethoxy-Substituted Aromatics 166 7.9.2 Fluoroalkoxy-Substituted Aromatics 167 7.9.3 Perfluoroalkyl-Substituted Aromatics 167 7.9.4 Fluoroalkyl-Substituted Aromatics 168 7.9.5 Aryl Difluoromethyl Ethers and Thioethers 169 References 169 Chapter 8 Industrial Aspects of Aromatic Fluorine Chemistry 172 8.1 Introduction 172 8.2 The Demand for Aromatic Fluorine Compounds 172 8.3 The Supply of Aromatic Fluorine Compounds 174 8.4 Industrial Methods 175 8.5 Industrial Products 177 8.6 Key Intermediates and Synthetic Routes 184 References 192 Index 194 "Academia and industry join forces in Aromatic Fluorination, as an expert from each domain contributes to this new text on fluorination of carbocyclic and heterocyclic rings. The book begins with a discussion of fluorine's unique combination of properties, including size, electronic effects, and hydrophobicity, as well as the historical development of its product applications. It explains methods for introducing fluorine into an aromatic ring, focusing on nucleophilic fluorine transfer reactions. The role of catalysts, solvents, and other variables are examined, and the scope and limitations of the methods are discussed. Of particular interest to those working in non-specialist laboratories, Aromatic Fluorination includes detailed descriptions of the new electrophilic routes to fluoroaromatics, in addition to traditional routes and alternative methods involving radical chemistry. Because one of the most important fluorine-containing substituent is CF3, the book explains routes to benzotrifluorides (ArCF3), including traditional industrial methods and modern alternatives employing C-1 halofluorocarbons and other fluoroaliphatics. An alternative to CF3 is CF3S, and several methods of synthesizing aromatic CF3S-containing molecules are described. Since the successful development and diverse applications of aromatic fluorine compounds have led to the search for new compounds and novel substituents, the incorporation of other substituents is also explored. Aromatic Fluorination concludes with discussion of the factors responsible for the successful development of pharmaceutical, agrochemical and liquid crystal applications and the potential for applications in high-performance polymers and other areas. This section also describes in detail important industrial aromatic fluorination processes and the relative merits of different process technologies and their costs."--Provided by publisher