Modern Fluoroorganic Chemistry E-Book

Peer Kirsch

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 498

Veröffentlichungsjahr: 2013

Beschreibung

The second edition of this classic reference work has been completely revised and updated, as well as being enlarged by 20% to reflect the latest developments in synthetic organic fluorine chemistry, taking into account new applications in materials science and medicinal chemistry.

The new developments in transition-metal-catalyzed methods for the introduction of fluorine and fluorinated groups are discussed. In addition, new chapters have been added on such important applications as organic electronics (OLEDs) and fluorinated dyes. Appendices containing synthetic procedures and conversions round off this comprehensive work.

This work is a valuable reference for fluorine chemists that also provides nonspecialists with an introduction to the field.

From reviews of the first edition:
''... a well-produced book with attractive graphics, photos and schemes. Throughout the book, coloured electrostatic maps of small
organofluorine compounds are used toillustrate charge distributions. These are effective as well as attractive. I would point any organic chemist to this book who wants to learn about and do some fluorine chemistry. It provides uncluttered descriptions and a clear orientation to the literature in this important area of the organic chemistry.''

CHEMBIOCHEM - A European Journal of Chemical Biology

Leseprobe

Table of Contents

Related Titles

Title Page

Copyright

To Annette and Alexander

Preface to the Second Edition

Preface to the First Edition

Abbreviations

1: Introduction

1.1 Why Organofluorine Chemistry?

1.2 History

1.3 The Basic Materials

1.4 The Unique Properties of Organofluorine Compounds

References

Part I Synthesis of Complex Organofluorine Compounds

2: Introduction of Fluorine

2.1 Perfluorination and Selective Direct Fluorination

2.2 Electrochemical Fluorination (ECF)

2.3 Nucleophilic Fluorination

2.4 Synthesis and Reactivity of Fluoroaromatic Compounds

2.5 Transformations of Functional Groups

2.6 “Electrophilic” Fluorination

References

3: Perfluoroalkylation

3.1 Radical Perfluoroalkylation

3.2 Nucleophilic Perfluoroalkylation

3.3 “Electrophilic” Perfluoroalkylation

3.4 Difluorocarbene and Fluorinated Cyclopropanes

References

4: Selected Fluorinated Structures and Reaction Types

4.1 Difluoromethylation and Halodifluoromethylation

4.2 The Perfluoroalkoxy Group

4.3 The Perfluoroalkylthio Group and Sulfur-Based Super-Electron-Withdrawing Groups

4.4 The Pentafluorosulfanyl Group and Related Structures

References

5: The Chemistry of Highly Fluorinated Olefins

5.1 Fluorinated Polymethines

5.2 Fluorinated Enol Ethers as Synthetic Building Blocks

References

Part II Fluorous Chemistry

6: Fluorous Chemistry

6.1 Fluorous Biphase Catalysis

References

7: Fluorous Synthesis and Combinatorial Chemistry

7.1 Fluorous Synthesis

7.2 Separation on Fluorous Stationary Phases

7.3 Fluorous Concepts in Combinatorial Chemistry

References

Part III Applications of Organofluorine Compounds

8: Halofluorocarbons, Hydrofluorocarbons, and Related Compounds

8.1 Polymers and Lubricants

8.2 Applications in the Electronics Industry

8.3 Fluorinated Dyes

8.4 Liquid Crystals for Active Matrix Liquid Crystal Displays

8.5 Fluorine in Organic Electronics

References

9: Pharmaceuticals and Other Biomedical Applications

9.1 Why Fluorinated Pharmaceuticals?

9.2 Lipophilicity and Substituent Effects

9.3 Hydrogen Bonding and Electrostatic Interactions

9.4 Stereoelectronic Effects and Conformation

9.5 Metabolic Stabilization and Modulation of Reaction Centers

9.6 Bioisosteric Mimicking

9.7 Mechanism-Based “Suicide” Inhibition

9.8 Fluorinated Radiopharmaceuticals

9.9 Inhalation Anesthetics

9.10 Blood Substitutes and Respiratory Fluids

9.11 Contrast Media and Medical Diagnostics

9.12 Agricultural Chemistry

References

Appendix A: Typical Synthetic Procedures

A.1 Selective Direct Fluorination

A.2 Hydrofluorination and Halofluorination

A.3 Electrophilic Fluorination with F-TEDA–BF4 (Selectfluor)

A.4 Fluorinations with DAST and BAST (Deoxofluor)

A.5 Fluorination of a Carboxylic Acid with Sulfur Tetrafluoride

A.6 Generation of a Trifluoromethoxy Group by Oxidative Fluorodesulfuration of a Xanthogenate

A.7 Oxidative Alkoxydifluorodesulfuration of Dithianylium Salts

A.8 Electrophilic Trifluoromethylation with Umemoto's Reagents

A.9 Nucleophilic Trifluoromethylation with Me3SiCF3

A.10 Transition Metal-Mediated Aromatic Perfluoroalkylation

A.11 Copper-Mediated Introduction of the Trifluoromethylthio Group

A.12 Substitution Reactions on Fluoroolefins and Fluoroarenes

A.13 Reactions with Difluoroenolates

References

Appendix B: Index of Synthetic Conversions

Index

Related Titles

Wirth, T. (ed.)

Organoselenium Chemistry

Synthesis and Reactions

2012

ISBN: 978-3-527-32944-1

Petrov, V. A.

Fluorinated Heterocyclic Compounds

Synthesis, Chemistry, and Applications

2009

ISBN: 978-0-470-45211-0

Ojima, I. (ed.)

Fluorine in Medicinal Chemistry and Chemical Biology

2009

ISBN: 978-1-4051-6720-8

Mohr, F. (ed.)

Gold Chemistry

Applications and Future Directions in the Life Sciences

2009

ISBN: 978-3-527-32086-8

The Author

Prof. Dr. Peer Kirsch

Merck KGaA

Liquid Crystals R&D Chemistry

Frankfurter Str. 250

64293 Darmstadt

Germany

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form — by photoprinting, microfilm, or any other means — nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-33166-6

ePDF ISBN: 978-3-527-65138-2

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mobi ISBN: 978-3-527-65136-8

oBook ISBN: 978-3-527-65135-1

To Annette and Alexander

“The fury of the chemical world is the element fluorine. It exists peacefully in the company with calcium in fluorspar and also in a few other compounds; but when isolated, as it recently has been, it is a rabid gas that nothing can resist.”

Scientific American, April 1888.

“Fluorine leaves nobody indifferent; it inflames emotions be that affections or aversions. As a substituent, it is rarely boring, always good for a surprise, but often completely unpredictable.”

M. Schlosser, Angew. Chem. Int. Ed. 1998, 37, 1496–1513.

Preface to the Second Edition

Within the few years since the first edition, the landscape of fluorine chemistry has changed dramatically: it is no longer the domain of a highly specialized (and often quite courageous) community, but the field has attracted the attention of mainstream organic and bioorganic chemists. The value of fluorine substitution in bioactive compounds and other functional materials has been widely recognized beyond the boundaries of the traditional fluorine chemistry community. Consequently, the variety of available synthetic methodology has exploded. A review with a reasonable degree of completeness has become impossible, and even the selection of the most significant developments is a very difficult task.

The scope of this book is not to offer a complete review of available methods, but to provide an introduction and a representative overview over the rapidly evolving field for the interested newcomer. It should be used as an entry point for a detailed in-depth study, but it is not intended as a stand-alone encyclopedia of fluorine chemistry. Therefore, there are many omissions, and the selection of the most interesting new developments has often been a matter of taste of the author.

The focus of the second edition is application fields where fluorine is essential for function, and also the chemistry needed to access such compounds. This applies not only to the material sciences but of course also to the biomedical field. On the synthetic side, the most remarkable new development is a huge variety of transition metal-catalyzed methods for the introduction of fluorine and fluorinated groups.

From the conceptual side, the author's choice of the most important new developments has been covered. From the application side, two new areas have been added: fluorinated dyes as one of the first areas of the industrial application of fluorine chemistry was recognized as a gap in the previous edition. In the last 10 years, the field of organic electronics has developed tremendously, and also here fluorine chemistry has found a very specific range of applications. A short review of the role and function of fluorine chemistry in this rapidly developing field has been added.

The author would like to thank the friends and colleagues who have provided their help and valuable input during the update of the text. In particular, Matthias Bremer, Alois Haas, Ingo Krossing, David O'Hagan, Gerd Röschenthaler, Georg Schulz, Peter and Marina Wanczek, John Welch, and Yurii Yagupolskii supported my project with information and critical discussions. From Wiley-VCH, Anne Brennführer and Lesley Belfit provided me with steady support and encouragement. Most of all, I owe my gratitude to my wife Annette and my son Alexander, who received much less attention than they deserved and who provided an environment where I could make the time for writing a book on top of many other things.

Seeheim-Jugenheim

Peer Kirsch

January 2013

Preface to the First Edition

The field of fluoroorganic chemistry has grown tremendously in recent years, and fluorochemicals have permeated nearly every aspect of our daily lives. This book is aimed at the synthetic chemist who wants to gain a deeper understanding of the fascinating implications of including the highly unusual element fluorine in organic compounds.

The idea behind this book was to introduce the reader to a wide range of synthetic methodology, based on the mechanistic background and the unique chemical and physicochemical properties of fluoroorganic compounds. There are quite some barriers to entering the field of preparative fluoroorganic chemistry, many based on unfounded prejudice. To reduce the threshold to practical engagement in fluoroorganic chemistry, I include some representative synthetic procedures which can be performed with relatively standard laboratory equipment.

To point out what can be achieved by introducing fluorine into organic molecules, a whole section of this book is dedicated to selected applications. Naturally, because of the extremely wide range of sometime highly specialized applications, this part had to be limited to examples which have gained particular importance in recent years. Of course, this selection is influenced strongly by the particular “taste” of the author.

I could not have completed this book without help and support from friends and colleagues. I would like to thank my colleagues at Merck KGaA, in particular Detlef Pauluth for his continuous support of my book project, and Matthias Bremer and Oliver Heppert for proof reading and for many good suggestions and ideas how to improve the book. The remaining errors are entirely my fault. G. K. Surya Prakash, Karl O. Christe, and David O'Hagan not only gave valuable advice but also provided me with literature. Gerd-Volker Röschenthaler, Günter Haufe, and Max Lieb introduced me to the fascinating field of fluorine chemistry. Andrew E. Feiring and Barbara Hall helped me to obtain historical photographs. Elke Maase from Wiley-VCH accompanied my work with continuous support and encouragement.

In the last 18 months I have spent most of my free time working on this book and not with my family. I would, therefore, like to dedicate this book to my wife Annette and my son Alexander.

Darmstadt

Peer Kirsch

May 2004

Abbreviations

acac

Acetylacetonate ligand

aHF

Anhydrous hydrofluoric acid

AIBN

Azobis(isobutyronitrile)

AM

Active matrix

ASV

“Advanced super-V”

ATPH

Aluminum tri[2,6-bis(

tert

-butyl)phenoxide]

BAST

N

,

N

-Bis(methoxyethyl)amino sulfur trifluoride

BINOL

1,1′-Bi-2-naphthol

Boc

tert

-Butoxycarbonyl protecting group

Bop-Cl

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

BSSE

Basis set superposition error

BTF

Benzotrifluoride

CFC

Chlorofluorocarbon

COD

Cyclooctadiene

CSA

Camphorsulfonic acid

Cso

Camphorsulfonyl protecting group

CVD

Chemical vapor deposition

cVHP

Chicken villin headpiece subdomain

DABCO

Diazabicyclooctane

DAM

Di(

p

-anisyl)methyl protecting group

DAST

N

,

N

-Diethylamino sulfur trifluoride

DBH

1,3-Dibromo-5,5-dimethylhydantoin

DBPO

Dibenzoyl peroxide

DEAD

Diethyl azodicarboxylate

DCC

Dicyclohexylcarbodiimide

DCEH

Dicarboxyethoxyhydrazine

DEC

N

,

N

-Diethylcarbamoyl protecting group

DFI

2,2-Difluoro-1,3-dimethylimidazolidine

DFT

Density functional theory

DIP-Cl

β-Chlorodiisopinocampheylborane

DMAc

N

,

N

-Dimethylacetamide

DMAP

4-(

N

,

N

-Dimethylamino)pyridine

DME

1,2-Dimethoxyethane

DMF

N

,

N

-Dimethylformamide

DMS

Dimethyl sulfide

DMSO

Dimethyl sulfoxide

DSM

Dynamic scattering mode

DTBP

Di-

tert

-butyl peroxide

dTMP

Deoxythymidine monophosphate

dUMP

Deoxyuridine monophosphate

ECF

Electrochemical fluorination

ED

Effective dose

EPSP

5-Enolpyruvylshikimate-3-phosphate

ETFE

Poly(ethylene-

co

-tetrafluoroethylene)

FAR

α-Fluorinated alkylamine reagents

FDA

Fluorodeoxyadenosine

FDG

Fluorodeoxyglucose

FET

Field effect transistor

FFS

Fringe field switching

FITS

Perfluoroalkyl phenyl iodonium trifluoromethylsulfonate reagents

FRPSG

Fluorous reversed-phase silica gel

FSPE

Fluorous solid-phase extraction

F-TEDA

N

-Fluoro-

N

′-chloromethyldiazoniabicyclooctane reagents

GWP

Global warming potential

HFCF

Hydrofluorocarbon

HFC

Hydrofluorocarbon

HFP

Hexafluoropropene

HMG

+

Hexamethylguanidinium cation

HMPA

Hexamethylphosphoric acid triamide

HSAB

Hard and soft acids and bases (Pearson concept)

IPS

In-plane switching

ITO

Indium tin oxide

LC

1. Liquid crystal

2. Lethal concentration

LCD

Liquid crystal display

LD

Lethal dose

LDA

Lithium diisopropylamide

MCPBA

m

-Chloroperbenzoic acid

MEM

Methoxyethoxymethyl protecting group

MOM

Methoxymethyl protecting group

MOST

Morpholino sulfur trifluoride

MVA

Multi-domain vertical alignment

NAD

+

/NADH

Nicotinamide adenine dinucleotide, oxidized/reduced form

NADP

+

/NADPH

Nicotinamide adenine dinucleotide phosphate, oxidized/reduced form

NBS

N

-Bromosuccinimide

NCS

N

-Chlorosuccinimide

NE

Norepinephrine

NFPy

N

-Fluoropyridinium tetrafluoroborate

NFTh

N

-Fluoro-

o

-benzenedisulfonimide

NIS

N

-Iodosuccinimide

NLO

Nonlinear optics

NMP

N

-Methylpyrrolidone

NPSP

N

-Phenylselenylphthalimide

OD

Ornithine decarboxylase

ODP

Ozone-depleting potential

OFET

Organic field effect transistor

OLED

Organic light-emitting diode

OPV

Organic photovoltaics

OTFT

Organic thin-film transistor

PCH

Phenylcyclohexane

PCTFE

Polychlorotrifluoroethylene

PDA

Personal digital assistant

PET

1. Positron emission tomography

2. Poly(ethylene terephthlate)

PFA

Perfluoropolyether

PFC

Perfluorocarbon

PFMC

Perfluoro(methylcyclohexane)

PFOA

Perfluorooctanoic acid

PFOB

Perfluoro-

n

-octyl bromide

PFOS

Perfluorooctylsulfonic acid

phen

Phenanthroline

PI

Polyimide

PIDA

Phenyliodonium diacetate

pip

+

1,1,2,2,6,6-Hexamethylpiperidinium cation

PLP

Pyridoxal phosphate

PNP

Purine nucleoside phosphorylase

PPVE

Poly(heptafluoropropyl trifluorovinyl ether)

PTC

Phase transfer catalysis

PTFE

Polytetrafluoroethylene (Teflon

TM

)

PVDF

Poly(vinylidene difluoride)

PVPHF

Poly(vinylpyridine) hydrofluoride

P3DT

Poly(3-dodecylthiophene)

QM/MM

Quantum mechanics/molecular mechanics

QSAR

Quantitative structure–activity relationships

SAH

S

-Adenosylhomocysteine hydrolase

SAM

1.

S

-Adenosylmethionine

2. Self-assembled monolayer

SBAH

Sodium bis(methoxyethoxy)aluminum hydride

scCO

2

Supercritical carbon dioxide

SFC

Supercritical fluid chromatography

SET

Single electrton transfer

SFM

Superfluorinated material

SPE

Solid-phase extraction

STN

Super-twisted nematic

TADDOL

α,α,α′,α′-Tetraaryl-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol

TAS

+

Tris(dimethylamino)sulfonium cation

TASF

Tris(dimethylamino)sulfonium difluorotrimethylsiliconate, (Me

2

N)

3

S

+

Me

3

SiF

2

−

TBAF

Tetrabutylammonium fluoride

TBDMS

tert

-Butyldimethylsilyl protecting group

TBS

See TBDMS

TBTU

O

-(Benzotriazol-1-yl)-

N

,

N

,

N

′,

N

′-tetramethyluronium tetrafluoroborate

TDAE

Tetrakis(dimethylamino)ethylene

TEMPO

2,2,6,6-Tetramethylpiperidine-

N

-oxide

TFT

Thin film transistor

THF

1. Tetrahydrofuran

2. Tetrahydrofolate coenzyme

THP

Tetrahydropyranyl protecting group

TIPS

Triisopropylsilyl protecting group

TLC

Thin-layer chromatography

TMS

Trimethylsilyl protecting group

TN

Twisted nematic

TPP

Triphenylphosphine

TPPO

Triphenylphosphine oxide

TR

Trypanothione reductase

VHR

Voltage holding ratio

ZPE

Zero point energy

1

Introduction

1.1 Why Organofluorine Chemistry?

Fluorine is the element of extremes, and many fluorinated organic compounds exhibit extreme and sometimes even bizarre behavior. A large number of polymers, liquid crystals, and other advanced materials owe their unique property profile to the influence of fluorinated structures.

Fluoroorganic compounds are almost completely foreign to the biosphere. No central biological processes rely on fluorinated metabolites. Many modern pharmaceuticals and agrochemicals, on the other hand, contain at least one fluorine atom, which usually has a very specific function. Perfluoroalkanes, especially, can be regarded as “orthogonal” to life – they can assume a purely physical function, for example, oxygen transport, but are foreign to the living system to such an extent that they are not recognized and are completely ignored by the body.

Although fluorine itself is the most reactive of all elements, some fluoroorganic compounds have chemical inertness like that of the noble gases. They sometimes cause ecological problems not because of their reactivity but because of the lack of it, making them persistent in Nature on a geological time scale.

All these points render fluoroorganic chemistry a highly unusual and fascinating field [1–14], providing surprises and intellectual stimulation in the whole range of chemistry-related sciences, including theoretical, synthetic, and biomedical chemistry and materials science.

1.2 History

Because of the hazardous character of hydrofluoric acid and the difficult access to elemental fluorine itself, the development of organofluorine chemistry and the practical use of fluoroorganic compounds started relatively late in the nineteenth century (Table 1.1). The real breakthrough was the first synthesis of elemental fluorine by Henri Moissan in 1886 [15], but the first defined fluoroorganic compound, benzoyl fluoride, had already been prepared and described by the Russian chemist, physician, and composer Alexander Borodin in 1863 [16].

Table 1.1 Dates and historical key events in the development of fluoroorganic chemistry.

Time

Key event

1764

First synthesis of hydrofluoric acid from fluorspar and sulfuric acid by A. S. Marggraf, repeated in 1771 by C. Scheele