Organofluorine Compounds Springer-Verlag Berlin Heidelberg GmbH Tamejiro Hiyama

Organofluorine Compounds

Chemistry and Applications

With contributions by Tamejiro Hiyama, Kiyoshi Kanie, Tetsuo Kusumoto, Yoshitomi Morizawa, Masaki Shimizu

With 96 Figures and 37 Tables

'Springer Leading Author Professor Tamejiro Hiyama Department of Material Graduate School of Engineering Kyoto University Yoshida,Sakyo-ku Kyoto 606-8501, Japan

Editor Professor Hisashi Yamamoto Nagoya University Graduate School of Engineering Chikusa Nagoya 464-8603, Japan

ISBN 978-3-642-08596-3

Library of Congress Cataloging-in-Publication Data Hiyama, Tamejiro, 1946- 0rganofluorine compouds : chemistry and applications I Tamejiro Hiyama ; with con• tributions from Kiyoshi Kanie ... [et al.]. p.cm. Includes index. ISBN 978-3-642-08596-3 ISBN 978-3-662-04164-2 ( eBook) DOI 10.1007/978-3-662-04164-2 1. Organofluorine compounds. I. Title.

QD412.F1 H59 2000 547'.02-dc21 99.087168

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© Springer-Verlag Berlin Heidelberg 2000 Originally published by Springer-Verlag Berlin Heidelberg New York in 2000 Softcover reprint of the hardcover 1st edition 2000 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Fotosatz-Service Kohler GmbH, Wiirzburg Coverdesign: design & production, Heidelberg Printed on acid-free paper SPIN 10668915 2/3020 mh- 54 3 2 1 0 List of Contributors

Professor Tamejiro Hiyama Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan

Kiyoshi Kanie Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0023,Japan

Dr. Tetsuo Kusumoto Dainippon Ink and Chemicals, Inc., 4472-1 Komuro, Ina-machi, Kita-adachi-gun, Saitama 362-8577, Japan

Dr. Yoshitomi Morizawa Research Center, Asahi Glass Ltd., 1150 Hazawa, Kanagawa-ku, Yokohama 221-0863, Japan

Dr. Masaki Shimizu Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan Preface

Recently, has become a key element in the remarkable progress of materials and biologically active agents. Since fluorine has quite unique reactivities and properties, fluorine chemistry is recognized as being totally dif• ferent from the chemistry of the other . Accordingly, many books and reviews have been published. Most of them, however, were written by experts in specialized fields. Although many excellent monographs on exist, this new textbook was undertaken with the aim of overviewing organofluorine chemistry on the basis of . Accordingly, the present work will focus on the organic chemistry of organo• , starting with general discussions on the unique properties of the fluorine atom and carbon-fluorine bonds, natural resources, and the salient features of organofluorine compounds in addition to their toxicity. This will be followed by chapters on and methods for the introduction of fluorine into organic compounds, organofluorine building blocks, reactions of C-F bonds, biologically active organofluorine compounds, fluorine-containing materials, fluorous media, and some synthetic reagents containing fluorine. The book focuses as much as possible on information that will be useful for synthe• tic chemists who have experienced or inexperienced organofluorine chemistry. Kiyoshi Kanie contributed to Chapters 1, 2 and 7, Tetsuo Kusumoto to Chapters 2, 5, and 6, Yoshitomi Morizawa to Chapters 5 and 6, and Masaki Shimizu to Chapters 3, 4, and 8; all the coauthors worked very closely both with each other and with the main author Tamejiro Hiyama, who wishes to empha• size that this collaboration was enjoyed by them all. We also thank Dr. Joe Richmond both for his help and his warm encouragement. Finally, the authors thank Professor Hisashi Yamamoto, Nagoya University, Japan, for suggesting that we produce this book. We wish to dedicate this book to Professor Hitoshi Nozaki, Professor Emeritus, Kyoto University, Japan, on the occasion of his 77th birthday. He introduced all of us either directly or indirectly to the fascination of organic chemistry.

Kyoto, January 2000 Tamejiro Hiyama Table of Contents

Chapter 1 General Introduction ...... 1 1.1 Nature of Organofluorine Compounds 1 1.1.1 Brief History ...... 1 1.1.2 Properties of the Fluorine Atom . . . . . 2 1.1.3 Fluorine Effects in Organic Compounds 3 1.1.4 Properties of Fluoroorganic Compounds 10 1.1.5 Properties of Perfluoroorganic Compounds 13 1.1.6 Spectroscopic Properties . 14 1.2 Source of Fluorine . 18 1.2.1 . . . . . 18 1.2.2 Fluorine Gas ...... 18 1.3 Toxicity of Fluorinating Reagents 19 1.3.1 and Fluorine Gas 19 1.3.2 First-Aid Treatment 20 1.3.3 Fluoroacetic Acid 21

Chapter 2 Reagents for Fluorination 25 2.1 Electrophilic Flurorinating Reagents 25 2.1.1 Fluorine Gas ...... 25 2.1.2 Xenon Difluoride ...... 28 2.1.3 Electrophilic Reagents Containing an 0-F Bond 29 2.1.4 Electrophilic Reagents Containing an N-F Bond 34 2.2 Nucelophilic Fluorinating Reagents . 39 2.2.1 Hydrogen Fluoride and Derivatives . 39 2.2.2 Transformation . . 43 2.2.3 Fluoride Reagents ...... 48 2.3 Combination of an and a Fluoride . 56 2.3.1 Halofluorination of Olefins and Acetylenes ...... 56 2.3.2 Thiofluorination and Selenofluorination of Olefins 58 2.3.3 Nitrofluorination ...... 59 2.3.4 Oxidative Fluorination ...... 58 2.3.5 Oxidative Desulfurization-Fluorination . 61 2.3.6 Oxidative Fluorination of Amines 65 2.4 Electrochemical Fluorination ...... 66 X Table of Contents

Chapter 3 Organofluorine Building Blocks ...... 77 3.1 Fluorine-Substituted Nucleophilic Reagents 77 3.1.1 Alkylmetals . . 77 3.1.2 Alkenylmetals 84 3.1.3 Alkynylmetals 91 3.1.4 Metal Enolates 93 3.2 Fluorine-Substituted Electrophilic Reagents 99 3.3 Fluorine-Substituted Radicals ...... 103 3.4 Fluorine-Substituted ...... 107 3.5 Electrophilic Perfluoroalkylating Reagents . 111 3.5.1 (Perfluoroalkyl)aryliodonium Salts .. . 111 3.5.2 (Polyfluoroalkyl)aryliodonium Salts . . . 112 3.5.3 (Trifluoromethyl)chalcogenium Salts 113

Chapter 4 Reactions of C-F Bonds 119 4.1 Fluorine . 119 4.1.1 1-Fluoro Sugars 119 4.1.2 Aromatic Nucleophilic Substitution 121 4.2 C-F Bond Activation by Metal Complexes 125 4.2.1 Activation of an Aliphatic C-F Bond 125 4.2.2 Activation of an Aromatic C-F Bond .. .. . 126 4.3 Interaction of Fluorine with a Proton or Metal 128 4.3.1 Fluorine-Hydrogen Interaction 128 4.3.2 Fluorine-Metal Interaction ...... 129

Chapter 5 Biologically Active Organofluorine Compounds 137 5.1 Fluorine Effect in Biological Activity 137 5.2 Strategies for Design and Synthesis ...... 141 5.2.1 Structure-Activity Relationship ...... 141 5.2.2 Commercially Available Fluorinated Materials . . . 143 5.3 Fluorinated Amino Acids and Carbohydrates 144 5.3.1 Amino Acids ...... 144 5.3.2 Protease Inhibitors 148 5.3.3 Carbohydrates . . . . . 150 5.3.4 Nudeosides ...... 151 5.4 Fluorine-Containing Pharmaceuticals 154 5.4.1 Prostanoids ...... 154 5.4.2 Vitamin D3 • •• • • • • • • • • • • 157 5.4.3 Central Nervous System Agents 160 5.4.4 Antibacterials and Antifungals 161 5.4.5 P-Lactam Antibiotics ...... 164 5.4.6 ...... 164 5.4.7 Artificial Blood Substitutes ...... 165 5.4.8 18F-Labeled Tracers for Positron Emission Tomography ...... 166 5.5 Fluorine-Containing Agrochemicals . . . . . 166 Table of Contents XI

5.5.1 Insecticides 167 5.5.2 Herbicides 173 5.5.3 Fungicides 177

Chapter 6 Fluorine-Containing Materials 183 6.1 Fluorine Effect in Materials . . 183 6.1.1 Boiling Points and Melting Points 184 6.1.2 Solubility . . . . 186 6.1.3 Surface Tension 186 6.1.4 Refractive Index 187 6.1.5 Viscosity . . . . , 187 6.2 , Hydrochlorofluorocarbons, , and Alternatives . . 188 6.2.1 Brief History ...... 188 6.2.2 Production of Chlorofluorocarbons and Hydrochlorofluorocarbons ...... 191 6.2.3 Syntheses of CFC Alternatives ...... 192 6.2.4 Evaluation of Safety and Environmental Effects 195 6.2.5 Alternatives to the Third Generation 196 6.3 Fluorine-Containing Liquid Crystals . 196 6.3.1 Nematic Liquid Crystals . .... 197 6.3.2 Ferroelectric Liquid Crystals . . 202 6.3.3 Antiferroelectric Liquid Crystals 209 6.4 Fluorine-Containing Polymers 212 6.4.1 Brief History . . . . 212 6.4.2 Monomer Synthesis 214 6.4.3 Fluoroplastics 216 6.4.4 Fluoroelastomers 220 6.4.5 Coatings 224 6.4.6 Fluorosurfactants . . . . . 225 6.4.7 Fluorinated Membranes 228

Chapter 7 Fluorous Media ...... 235 7.1 Organic Reactions in Perfluorocarbons 235 7.2 Fluorous Biphase Reactions ...... 237 7.2.1 Hydroformylation ...... 237 7.2.2 Oxidation ...... 239 7.3 Purification and Isolation by Phase Separation 243

Chapter 8 Organic Reactions with Fluorinated Reagents 249 8.1 Fluoride Ion in Organic Synthesis ...... 249 8.1.1 Fluoride Base ...... 249 8.1.2 Desilylative Elimination and Deprotection . . 250 8.1.3 Naked Anions and Fluorosilicates ...... 252 8.2 and 255 8.2.1 Trifluoroacetic Acid ...... 255 XII Table of Contents

8.2.2 Trifluoroperacetic Acid ...... 256 8.3 Trifluoromethanesulfonic Acid and Derivatives 257 8.3.1 Trifluoromethanesulfonic Acid ...... 257 8.3.2 Trimethylsilyl Trifluoromethanesulfonate 258 8.3.3 Metal Trifluoromethanesulfonates 259

Subject Index ...... 265