Table Of ContentSyntheses
of Fluoroorganic
Compounds
Edited by
I. L. Knunyants and G. G.Yakobson
Springer- ¥edag
Berlin Heidelberg New York Tokyo 1985
Professor I. L. Knunyants
t
Professor G. G. Yakobson
Institute of Organic Chemistry,
SU-630090 Novosibirsk
ISBN-13: 978-3-642-70209-9 e-ISBN-13: 978-3-642-70207-5
DOl: 10.1007/978-3-642-70207-5
Library of Congress Cataloging in Publication Data. Main entry under
title:
Syntheses of fluoroorganic compounds. Bibliography: p. Includes index.
1. Organofluoron compounds. 2. Chemistry, Organic-Synthesis.
I. Knunyants, Ivan Ludvigovich. II. Yakobson, G. G. (Georgi Gustavovich)
QD412.FIS95 1985 547'.02 84-26875
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Preface
Recently there has been a tremendous growth in the chemistry
of fluoroorganic compounds, which find wide applicatiori in
various fields of technique and are used to solve some basic
theoretical problems. The chemical properties of these compounds
are rather specific, as well as the methods for their preparation.
We realized that no good handbooks on the preparation offluoro
organic compounds were available, whereas the methods of pre
paration are scattered in numerous scientific papers and patents.
Even such a well-known publication as Organic Syntheses contains
just a few methods of preparation of fluoroorganic compounds.
As a consequence, not only for newcomers but even for specialists,
searching for simple and convenient methods for the preparation
of the required compounds is tedious.
To alleviate the problem, we undertook to prepare this book,
which presents detailed preparation methods of more than 300
flu oro organic compounds. Emphasis has been laid on syntheses
of polyfluorinated compounds, since they are of major interest
with respect to preparation and utility.
Preparation of fluoroorganic compounds is based both on the
classical methods of organic chemistry and on the specific ones,
which is due to the difficulty or even impossibility of the direct
introduction of fluorine into a definite position of organic mole
cule. Most organic compounds of fluorine are prepared by a suc
cession of conversions of a relatively small number of starting
compounds.
We attempted, on the one hand, to exemplify the synthetic
methods used in the chemistry of fluoroorganic compounds and,
on the other hand, to describe the preparation of compounds
that may be used as starting materials in further syntheses. The
preparation methods reported here may be reproduced in any
chemical laboratory. Accordingly, we have intentionally excluded
such methods as fluorination with elemental fluorine, electro
chemical fluorination and some others, which require special
equipment. Moreover, many such compounds as may be prepared
by these methods are commercially available at a reasonable
price.
This book is based on the two-volume Russian edition of Syn
theses of Fluoroorganic Compounds ("Sintezy Ftororganicheskih
Soedinenii", Khimia Publishers, Moscow), which covers more
VI
than 500 preparation methods of fluoroorganic compounds. The
present edition includes the preparation methods of compounds
that seemed to be the most interesting ones; these are complement
ed with some new preparations worked out in recent years at the
laboratories of the authors.
The book is divided into three sections: fluoroaliphatic com
pounds, fluoroaromatic compounds, and aromatic compounds
with fluorinated side chains. The preparations are arranged accord
ing to two principles. On the one hand, it seemed appropriate
to give first the preparation methods of fluorinated hydrocarbons,
then of compounds containing other halogens and, finally, of
compounds with various functional groups. On the other hand,
it appeared reasonable to give together compounds obtained by
similar procedures. Thus the preparation methods of some phenyl
containing compounds are included in the first section of the
book.
Every procedure is preceded by an enumeration of methods for
the preparation of the given compound. Only the principal ones,
although not exhaustively, are included.
Whenever identical procedures affording compounds of simi
lar structures are feasible, this is indicated after the procedure,
together with yields and constants for these compounds. All the
constants are given as they appear in References.
Since naming of polyfluoroorganic compounds does not strictly
follow the IUPAC nomenclature, the compounds included in the
book have widely accepted names, generally those used in the
cited papers.
Most preparations have been checked at the laboratories of
A. V. Fokin, I. L. Knunyants, L. M. Yagupolskii and G. G. Ya
kobson and modified, where necessary.
Syntheses of fluoroaliphatic compounds were compiled for
this publication by Dr. S. R. Sterlin, offluoroaromatic compounds
by Dr. G. G. Furin, and of aromatic compounds with fluorinated
side chain by Prof. L. M. Yagupolskii and Dr. Yu. A. Fialkov.
We would like to thank Mrs. L. G. Smolina for translating the
original into English and Dr. V. V. Bardin for checking refere.nces
and typing the manuscript in English. We also wish to make use
of this opportunity to express our deep gratitude to Mrs M. N.
Pastushenko, editor of Khimia Publishers, whose patience and
goodwill greatly promoted publication of Syntheses of Fluoro
organic Compounds in Russian.
I. L. Knunyants,
G. G. Yakobson.
Contents
Safety Measures ..................................... .
Fluoroaliphatic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
G. G. Belenki, A. V. Fokin, D. S. Rondarev, R. M. Ryazanova,
S. V. Sokolov, S. R. Sterlin, A. N. Voronkov, Yu. V. Zeifman
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 103
Fluoroaromatic Compounds ............................ 109
G. G. Furin, G. F. Grebenshchikova, A. Yu. Lvova, V. M. Vlasov,
G. G. Yakobson
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225
Aromatic Compounds with Fluorinated Sid Chains ........ 233
Yu. A. Fialkov, L. M. Yagupolski
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 286
Subject Index ........................................ 291
Formula Index ....................................... 297
Safety Measures
Some syntheses described in the book involve toxic and dangerous compounds.
The safety measures for handling them are generally included in the corresponding
procedures. However, such compounds as hydrogen fluoride, sulphur tetrafluoride,
tetrafluoroethylene and perfluoroisobutene are used in many syntheses, therefore
it seemed reasonable to consider the safety measures pertaining to these chemicals,
and first-aid treatment of injuries, in a separate chapter to avoid repetitions. These
measures are to be perused before starting work with the above-mentioned compounds.
Hydrogen Fluoride
Hydrogen fluoride is a colourless liquid fuming in air Mp -83°C, bp 19.5 °C,
critical temperature 230°C, critical pressure 66.2 atm, density 1.00 (0 0C).
Anhydrous HF may be handled in a steel, polyethylene or polytetrafluoroethylene
vessel. Even diluted HF in contact with the skin produces painful and slowly healing
wounds. Its vapours are irritant to the respiratory passage and mucous membranes.
It is therefore imperative to protect the hands with undamaged rubber gloves (pre
ferably made of synthetic rubber), to shield the face with a protective shield of trans
parent plastic, the body with a rubber or plastic apron, and the feet with rubber boots.
In small laboratory experiments at least the face shield and rubber gloves must be
used. It is advisable to test the gloves for leakages from time to time. Even an insig
nificant leak in the glove may cause serious trouble. Work with anhydrous hydrogen
fluoride must be carried out under efficient hoods or in strongly ventilated rooms
since its vapours attack the lungs and the mucous membranes, especially those of
the eyes.
Anhydrous hydrogen fluoride reacts violently, almost explosively, with water.
Disposal of spent HF must therefore be carried out with caution and with protective
devices against splattering. Smaller amounts are disposed of by evaporating in the
draft of a hood, or by pouring into a sink and flushing rapidly with a strong stream
of water, larger amounts by treatment with a lime slurry.
When the skin is stained with anhydrous hydrogen fluoride, the spot must be imme
diately washed with large amounts of water. Immersion of the burnt spot in ice-cold
saturated solution of magnesium sulfate or in ice-cold aqueous ethanol for about an
hour is recommended to retard the passage of the fluoride ion through the tissues.
In this respect, ice-cold aqueous or alcoholic solutions of high-molecular-weight
quaternary ammonium compounds (Hyamine, Phemorol, Zephirane, etc.) are even
better because of their bactericidal effects (2 g of Hyamine 1622 in 1 liter of distilled
water is recommended).
Finally a paste is applied, prepared by mixing 20 % of magnesium sulphate, 6 % of
magnesium oxide, 18 %o f glycerol, 55 %o f water, and 1 % of procaine hydrochloride,
2 Safety Measures
or by mixing 3 parts of magnesium oxide, 4 parts of mineral oil, and II parts of white
vaseline. Even a simple slurry of magnesium oxide in glycerol slightly diluted with a
small amount of water (to reduce the viscosity) is satisfactory. More extensive burns
should be treated by subcutaneous injections of calcium gluconate solution.
Eyes affected by hydrogen fluoride should be washed long enough with luke warm
water, then with a 2 % solution of sodium bicarbonate, and finally exposed for a
quarter of an hour to the action of 2~ 3 drops of a 0.5 % solution of pantocaine. Oint
ments are not recommended [I].
Sulphur Tetrafluoride
Sulphur tetrafluoride is a colourless gas with a heavy smell. Np -124 DC, bp -40.4 DC,
critical temperature 90 DC, density 1. 92 (-73 QC), vapour pressure 12 atm at 25°C.
Sulphur tetrafluoride is easily hydrolysed, forming hydrogen fluoride and thionyl
fluoride. It is unreactive with sulphur, mercury and rubber and does not affect tho
roughly dried glassware. Sulphur tetrafluoride should be stored in steel cylinders with
steel valves. Copper and brass valves in contact with SF get destroyed.
4
The toxic effect of sulphur tetrafluoride is similar to that of difluorophosgene and
about twice as strong as that of phosgene. It is enhanced by HF, released when SF4
has been inhaled or has been in contact with skin, therefore skin should be protected,
work should be done under a good hood and a gas mask should be worn.
The first-aid treatment of poisoning is the same as of difluorophosgene poisoning
(see. p. 60). ARTIFICIAL RESPIRATION IS FORBIDDEN! The injured person
should be hospitalized without delay.
Tetrafluoroethylene
Tetrafluoroethylene is a colourless gas. Mp -142.5 DC, bp -76.3 DC, critical tempe
rature 33.3 DC, density 1.533 (-80 QC). Tetrafluoroethylene is explosive under pres
sure, therefore syntheses should be conducted only in autoclave provided with anti
explosion diaphragms or in armed boxes.
The hazard may be minimized by heating the charged autoclave during 16 h, at
20D~25 DC, shaking it the while, with subsequent heating to the required temperature.
The experience of one of the authors of the book who worked many years in the
laboratory and a pilot plant shows that in flow systems tetrafluoroethylene may be
used without any additional safety measures. But it should be kept in mind that the
pyrolysis of that compound may yield, among other products, toxic perfluoroiso
butene in small amounts.
Perfluoroisobutene
For the physical properties of perfluoroisobutene see p. 9. Perfluoroisobutene is
highly toxic. Its toxic activity is comparable to that of phosgene. Work with this
compound should be conducted only under a efficient hood. When poisoned by per
fluoroisobutene, one should inhale ethanol vapours till easy respiration is restored.
References
1. Hudlicky, M.: Chemistry of Fluorine Compounds. New Yark etc. John Wiley & Sons, 1976,
p. 13-14
Fluoroaliphatic Compounds
G. G. Belenki, A. V. Fokin, D. S. Rondarev, R. M. Ryazanova, S. V. Sokolov,
S. R. Sterlin, A. N. Voronkov, Yu. V. Zeifman
2-Iodoheptafluoropropane
MW296
2-Iodoheptafluoropropane is a low-boiling volatile colourless liquid; when exposed
to light, assumes a rosy colour. Bp 40 DC, n~O 1.3237 [1].
Method of Preparation
2-Iodoheptafluoropropane is obtained in the reaction of perfluoropropylene with
iodine and potassium iodine in acetonitrile (63 % yield) [2], or by the reaction of
perfluoropropylene with iodine and iodine pentafluoride (77 % yield) [1].
Procedure (I]
In a 250-ml steel autoclave are placed 15 g (0.065 mol) of iodine pentafluoride, 30 g
(0.24 mol) of finely powdered iodine and 2 or 3 ml of SbFs' The autoclave is cooled
with liquid nitrogen, evacuated and 50 g (0.3 mol) of perf lu orop ropylene is condensed
into it; then it is heated in a tilting furnace at 150°C during 10 h, whereupon it is
cooled to room temperature. The contents are poured onto ice, the organic layer is
separated and washed with aqueous solution of NaHC03, with two portions of 25 %
aqueous KOH and with water, then dried over PzOs and distilled.
The yield of perfluoroisopropyl iodide is 70 g (80 %); bp 40 DC, n~O 1.323·7.
1-Fluorobutane
CH3-CHz-CHz-CH1F
C H F MW76
4 9
l-Fluorobutane is a low-boiling liquid. Bp 31.5 °Cj73l mm Hg; n~o 1.3410 [3].
4 Fluoroaliphatic Compounds
Method of Preparation
I-Fluorobutane is obtained by the reaction of I-bromobutane with HgF2 [4], or by
the reaction of n-butyl alcohol with (2-chloro-l, 1, 2-trifluoroethyl)diethylamine
(75 % yield) [3].
Procedure [3]
(C2HS)2NH n-C4HgOH
CF 2=CFCI ) CHFCI-CF 2-N(C2Hsh •
CH3(CH2hCH2F
(2-Chloro-l,J ,2-tr(fluoroethyl) diethylamine. In a Drechsel bottle cooled to _5°
to -10 DC is placed 40 g (0.56 mol) of diethylamine, then 70 g (0.6 mol) of thoroughly
dried chlorotrifluoroethylene is bubbled through it during 10 h. The reaction is
distilled in vacuum. The yield of (chlorotrifluoroethyl)diethyl amine is 70 g (66 %) ;
bp 320_33 °Cj6 mm Hg.
I-Fluorobutane. In a three-necked flask provided with a stirrer, a dropping funnel,
and a Wurtz column connected to a downward Liebig condenser, is placed 37.8 g
(0.2 mol) of (chlorotrifluoroethyl)diethylamine, to which is added dropwise 14.8 g
(0.2 mol) of n-butyl alcohol. The reaction proceeds with evolution of heat; I-fluoro
butane formed in the reaction distils off from the flask. The product is washed with ice
water, dried over CaCl2 and distilled. The yield of I-fluorobutane is 10.1 g (75 %);
bp 3f.5 °Cj731 mm Hg; n~o 1.3410.
1-Fluorohexane
CH3-CH2-CH2-CH2-CH2-CH2F
C6H13F MW 104
I-Fluorohexane is a colourless liquid. Bp 91.1 °Cj755 mm Hg [4], 910-93.5 °C [5];
nbo 1.3748; d.~o 0.8002 [4].
Method of Preparation
I-Fluorohexane is a colourless liquid. Bp 91.1 °Cj755 mm Hg [4], 91 °-93.5 °C [5];
fluoride in the absence of solvents (20 %y ield) [6], or in a diethylene glycol- ethylene
glycol mixture (54 % yield) [5].
Procedure [5]
In a I-I three-necked flask provided with a stirrer, a dropping funnel, and a fractionat
ing column (300 mm long) carrying a reflux condensing head, are placed 116 g (2 mol)
