Article No : a11_349

Fluorine Compounds, Organic

GÜNTER SIEGEMUND, Hoechst Aktiengesellschaft, Frankfurt, Federal Republic
of Germany
WERNER SCHWERTFEGER, Hoechst Aktiengesellschaft, Frankfurt, Federal Republic
of Germany
ANDREW FEIRING, E. I. DuPont de Nemours & Co., Wilmington, Delaware,
United States
BRUCE SMART, E. I. DuPont de Nemours & Co., Wilmington, Delaware, United States
FRED BEHR, Minnesota Mining and Manufacturing Company, St. Paul,
Minnesota, United States
HERWARD VOGEL, Minnesota Mining and Manufacturing Company, St. Paul,
Minnesota, United States
BLAINE MCKUSICK, E. I. DuPont de Nemours & Co., Wilmington, Delaware,
United States

1. Introduction. . . . . . . . . . . . . . . . . . . . . . . 444 8. Fluorinated Carboxylic Acids and

2. Production Processes . . . . . . . . . . . . . . . . 445 Fluorinated Alkanesulfonic Acids . . . . . . 470
2.1. Substitution of Hydrogen. . . . . . . . . . . . . 445 8.1. Fluorinated Carboxylic Acids . . . . . . . . . 470
2.2. Halogen – Fluorine Exchange . . . . . . . . . 446 8.1.1. Fluorinated Acetic Acids . . . . . . . . . . . . . . 470
2.3. Synthesis from Fluorinated Synthons . . . 447 8.1.2. Long-Chain Perfluorocarboxylic Acids . . . . 470
2.4. Addition of Hydrogen Fluoride to 8.1.3. Fluorinated Dicarboxylic Acids . . . . . . . . . 472
Unsaturated Bonds . . . . . . . . . . . . . . . . . 447 8.1.4. Tetrafluoroethylene – Perfluorovinyl Ether
2.5. Miscellaneous Methods . . . . . . . . . . . . . . 447 Copolymers with Carboxylic Acid Groups . . 472
2.6. Purification and Analysis . . . . . . . . . . . . . 447 8.2. Fluorinated Alkanesulfonic Acids . . . . . . 472
3. Fluorinated Alkanes. . . . . . . . . . . . . . . . . 448 8.2.1. Perfluoroalkanesulfonic Acids . . . . . . . . . . 472
3.1. Fluoroalkanes and Perfluoroalkanes . . . . 448 8.2.2. Fluorinated Alkanedisulfonic Acids . . . . . . 473
3.2. Chlorofluoroalkanes. . . . . . . . . . . . . . . . . 452 8.2.3. Tetrafluoroethylene – Perfluorovinyl Ether
3.3. Bromofluoroalkanes. . . . . . . . . . . . . . . . . 456 Copolymers with Sulfonic Acid Groups . . . . 474
3.4. Iodofluoroalkanes. . . . . . . . . . . . . . . . . . . 457 9. Fluorinated Tertiary Amines . . . . . . . . . . 474
4. Fluorinated Olefins . . . . . . . . . . . . . . . . . 458 10. Aromatic Compounds with Fluorinated
4.2. Tetrafluoroethylene . . . . . . . . . . . . . . . . . 459 Side-Chains . . . . . . . . . . . . . . . . . . . . . . . 475
4.3. Hexafluoropropene . . . . . . . . . . . . . . . . . 460 10.1. Properties . . . . . . . . . . . . . . . . . . . . . . . . 475
4.4. 1,1-Difluoroethylene . . . . . . . . . . . . . . . . . 461 10.2. Production . . . . . . . . . . . . . . . . . . . . . . . . 476
4.5. Monofluoroethylene, Monofluoroethylene 461 10.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
4.6. 3,3,3-Trifluoropropene . . . . . . . . . . . . . . . 462 11. Ring-Fluorinated Aromatic, Heterocyclic,
4.7. 3,3,3-Trifluoro-2-(trifluoromethyl)- and Polycyclic Compounds . . . . . . . . . . . 477
prop-1-ene . . . . . . . . . . . . . . . . . . . . . . . . . 462 11.1. Mono- and Difluoroaromatic Compounds 478
4.8. Chlorofluoroolefins . . . . . . . . . . . . . . . . . 462 11.1.1. Properties . . . . . . . . . . . . . . . . . . . . . . . . . 478
5. Fluorinated Alcohols . . . . . . . . . . . . . . . . 463 11.1.2. Production. . . . . . . . . . . . . . . . . . . . . . . . . 478
6. Fluorinated Ethers . . . . . . . . . . . . . . . . . 464 11.1.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
6.1. Perfluoroethers . . . . . . . . . . . . . . . . . . . . 464 11.2. Highly Fluorinated Aromatic Compounds 481
6.1.1. Low Molecular Mass Perfluoroethers . . . . . 464 11.3. Perhaloaromatic Compounds. . . . . . . . . . 482
6.1.2. Perfluorinated Epoxides . . . . . . . . . . . . . . . 464 11.4. Fluorinated Heterocyclic and Polycyclic
6.1.3. High Molecular Mass Perfluoroethers . . . . . 465 Compounds . . . . . . . . . . . . . . . . . . . . . . . 483
6.2. Perfluorovinyl Ethers. . . . . . . . . . . . . . . . 465 11.4.1. Ring-Fluorinated Pyridines. . . . . . . . . . . . . 483
6.3. Partially Fluorinated Ethers . . . . . . . . . . 466 11.4.2. Trifluoromethylpyridines . . . . . . . . . . . . . . 483
7. Fluorinated Ketones and Aldehydes . . . . 466 11.4.3. Fluoropyrimidines . . . . . . . . . . . . . . . . . . . 483
7.1. Fluoro- and Chlorofluoroacetones . . . . . . 466 11.4.4. Fluorotriazines . . . . . . . . . . . . . . . . . . . . . 483
7.2. Perhaloacetaldehydes. . . . . . . . . . . . . . . . 468 11.4.5. Polycyclic Fluoroaromatic Compounds . . . . 484
7.3. Fluorinated 1,3-Diketones . . . . . . . . . . . . 469 12. Economic Aspects . . . . . . . . . . . . . . . . . . 484

2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

DOI: 10.1002/14356007.a11_349
444 Fluorine Compounds, Organic Vol. 15

13. Toxicology and Occupational Health . . . . 484 13.5. Fluorinated Carboxylic Acids . . . . . . . . . 486
13.1. Fluorinated Alkanes. . . . . . . . . . . . . . . . . 485 13.6. Other Classes. . . . . . . . . . . . . . . . . . . . . . 486
13.2. Fluorinated Olefins . . . . . . . . . . . . . . . . . 485 References . . . . . . . . . . . . . . . . . . . . . . . . 487
13.3. Fluorinated Alcohols . . . . . . . . . . . . . . . . 486
13.4. Fluorinated Ketones. . . . . . . . . . . . . . . . . 486

1. Introduction Fluorine attached to the ring of aromatic com-

pounds acts mainly as a para-directing substitu-
Organic fluorine compounds are characterized by ent, whereas perfluoroalkyl groups behave as
their carbon – fluorine bond. Fluorine can re- meta-directing substituents.
place any hydrogen atom in linear or cyclic Naturally, the influence of fluorine is greatest
organic molecules because the difference be- in highly fluorinated and perfluorinated com-
tween the van der Waals radii for hydrogen pounds. The fact that these compounds have a
(0.12 nm) and fluorine (0.14 nm) is small com- high thermal stability and chemical resistance
pared to that of other elements (e.g., chlorine and are physiologically inert makes them suitable
0.18 nm). Thus, as in hydrocarbon chemistry, for many applications for which hydrocarbons
organic fluorine chemistry deals with a great are not. Properties that are exploited commer-
variety of species. When all valences of a carbon cially include high thermal and chemical stabili-
chain are satisfied by fluorine, the zig-zag-shaped ty, low surface tension, and good dielectric prop-
carbon skeleton is twisted out of its plane in the erties, for example, in fluoropolymers, perfluori-
form of a helix. This situation allows the elec- nated oils and inert fluids.
tronegative fluorine substituents to envelop the Individual fluorine atoms or perfluoroalkyl
carbon skeleton completely and shield it from groups do not change the technical properties
chemical (especially nucleophilic) attack. Seve- of a hydrocarbon fundamentally. However, this
ral other properties of the carbon – fluorine bond is not the case with physiological properties. A
contribute to the fact that highly fluorinated fluorine atom in a bioactive material may sim-
alkanes are the most stable organic compounds. ulate a hydrogen atom, and although this does
These include low polarizability and high bond not prevent metabolic processes from occur-
energies, which increase with increasing substi- ring, the end products may be ineffective or
tution by fluorine (bond energies: C – F bond in toxic. Accordingly, such fluorine compounds
CH3F, 448 kJ/mol; C – H bond in CH4, 417 kJ/ are important in, for example, pesticides and
mol; C – Cl bond in CH3Cl, 326 kJ/mol; and pharmaceuticals.
C – F bond in CF4, 486 kJ/mol). A bibliography of the scientific literature of
The cumulative negative inductive effect of organofluorine chemistry was published in 1986
the fluorine in perfluoroalkyl groups may reverse [16]; commercial applications of fluorine pro-
the polarity of adjacent single bonds (e.g., in ducts are reviewed in [7], [17], and [18].
the pair H3C 3 I and F3C " I) or double bonds
(e.g.,CH3 Cdþ H ¼ Cd
H2 and CF3
Cd
H Nomenclature. Any organic fluorine com-
¼ Cdþ H2 ). Fluorine substitution changes the re- pound can be named according to the rules of the
activity of olefins and carbonyl compounds. International Union for Pure and Applied Chem-
Polyfluorinated olefins possess an electron-defi- istry (IUPAC) [19]. However, for highly fluori-
cient double bond, which reacts preferentially nated molecules with several carbon atoms, this
with nucleophiles. Carboxy groups are affected nomenclature can be confusing. Therefore, the
by the presence of an adjacent perfluoroalkyl term ‘‘perfluoro’’ may be used when all hydrogen
radical. In carboxylic acids, the acidity is atoms bonded to the carbon skeleton have been
markedly increased. In other carbonyl com- replaced by fluorine. The designation of hydro-
pounds, the reactivity is increased without any gen atoms belonging to functional groups (e.g.,
fundamental change in the chemistry of the CHO or COOH), of the functional groups them-
compound. Correspondingly, the basicity of selves, and of other substituents is not affected
amines is reduced by the introduction of fluorine. [19]. Examples are given in Table 1.
Vol. 15 Fluorine Compounds, Organic 445

Table 1. Nomenclature of organic fluorine compounds

Formula CAS IUPAC designation Perfluoro designation

registry no.

CF3CF3 [76-16-4] hexafluoroethane perfluoroethane, F-ethane

CF3CF2CF2CHO [375-02-0] Heptafluoro-n-butyraldehyde Perfluoro-n-butyraldehyde, F-n-butyraldehyde
CF3(CF2)6COOH [335-67-1] Pentadecafluoro-n-octanoic acid Perfluoro-n-octanoic acid, F-n-octanoic acid
CF3(CF2)2CHF2 [375-17-7] 1,1,1,2,2,3,3,4,4-Nonafluoro-n-butane 1H-Perfluoro-n-butane, 1-hydryl-F-n-butane
CF3(CF2)4CH2OH [423-46-1] 2,2,3,3,4,4,5,5,6,6,6-Undecafluoro-n-hexanol 1H,1H-Perfluoro-n-hexanol,
1,1-dihydroperfluoro-n-hexanol

In the case of highly fluorinated compounds 2. halogen – fluorine exchange with hydrogen
with few hydrogen atoms (1 – 4), the perfluoro fluoride, hydrogen fluoride-base complexes,
compound can be taken as the parent compound. or metal fluorides
The hydrogen atoms are named according to their 3. synthesis of higher molecular mass fluorine
number and position; the letter H or the prefix compounds from reactive fluorinated
hydryl (hydro) are used for hydrogen. The sym- synthons
bol F was approved by the American Chemical 4. addition of fluorine, hydrogen fluoride, or
Society as abbreviation for perfluoro [20]. reactive nonmetal fluorides to unsaturated
Historical Development. The pioneering bonds
work in organofluorine chemistry dates from
1835 to 1940 [21]. Controlled production of Only a few of the many possibilities in each
organic fluorine compounds was started in group have been developed commercially, with
1892 by exchanging halogen for fluorine in hy- varying degrees of success.
drocarbons, using antimony(III) fluoride. The
industrial phase began in 1929 in the United
States with the discovery of the nonflammable, 2.1. Substitution of Hydrogen
nontoxic refrigerants CCl3F and CCl2F2 [22]. In
Germany, commercial production of aromatic Fluorination with Elemental Fluorine [26],
fluorine compounds started in 1930. [27]. The action of elemental fluorine on organic
The first fluoropolymer, polychlorotrifluor- compounds normally leads to violent, mainly ex-
oethylene, was synthesized in 1934 in Germany, plosive, reactions. The substrate fragments into
followed by the discovery of polytetrafluoroethy- units with a varying degree of fluorination because
lene in 1938 in the United States. During World the heats of formation of the C – F bond (ca.
War II, thermally and chemically stable working 460 kJ/mol) and the H – F bond (566 kJ/mol) are
materials for the separation of uranium isotopes greater than the heat of formation of the C – C
were investigated by the United States Manhat- bond (ca. 348 kJ/mol).
tan Project [23]. After World War II, numerous Therefore, direct fluorinations must take place
novel applications were discovered. The devel- with strict control of the reaction and removal of
opment of new organic fluorine compounds with the heat generated. This may be achieved by
novel applications continues undiminished. dilution of the fluorine with inert gases (e.g.,
N2 or CO2), dilution of the organic substrates
with inert solvents [28], intensive mixing, and
2. Production Processes reduction of the temperature to as low as

150  C.
The four principal methods for the preparation of Direct fluorination can also be carried out in
organic fluorine compounds are as follows [1], the gas phase in a tubular reactor packed with
[2], [24], [25]: silver- or gold-plated copper turnings [29]. Spe-
cialized methods are based on LaMar fluorina-
1. substitution of hydrogen in hydrocarbons tion [26], aerosol fluorination [30], porous-tube
using fluorine, high-valency metal or nonmet- fluorination [31], and jet fluorination [32]; high
al fluorides, or electrochemical fluorination product selectivities are achieved at a laboratory
446 Fluorine Compounds, Organic Vol. 15

scale. Commercial operation remains to be halogenated compounds using hydrogen fluoride

developed. [42]:

Fluorination with Metal Fluorides [33].

Metal fluorides that can transfer fluorine to or-
ganic substrates by changing the oxidative state
of the metal, such as cobalt(III) fluoride (CoF3) Whether the process takes place with or with-
and silver(II) fluoride (AgF2), serve as fluorinat- out a catalyst depends on the reactivity of the
ing agents in an oxidizing fluorination. The spent chlorine atoms to be exchanged. With com-
metal fluoride is regenerated with elemental pounds containing several chlorine atoms of
fluorine. differing reactivity, selective fluorination can
be achieved by selecting suitable process
conditions.
Fluorinations without a catalyst such as

Fluorination and regeneration can be cyclical,

permitting a commercial operation.
are carried out in liquid, anhydrous hydrogen
Electrochemical Fluorination. The Simons fluoride at 100 – 150  C in pressure vessels
process [34], [35] is used commercially for the made of steel, alloy steels, or nickel. The process
production of perfluorinated compounds. Solu- can be carried out by batch (e.g., autoclave) or
tions of organic compounds (mainly carboxylic continuous methods (autoclaves in series or a
acids, sulfonic acids, and tertiary amines) are tubular reactor). In either case, the hydrogen
electrolyzed in anhydrous hydrogen fluoride in a chloride that is generated during fluorination is
single cell without intermediate formation of free removed from the reactor to maintain the desired
fluorine. Fluorination takes place at a nickel anode pressure.
by a free-radical mechanism at current densities of Most liquid-phase fluorinations, e.g., of CCl4,
10 – 20 mA/cm2 [36]. Selectivity decreases CHCl3, CCl3CCl3, CCl3CHCl2, or CCl3CH2Cl,
sharply as the number of carbons increases. are carried out in the presence of a catalyst [43] to
Volatile, hydrogen-containing compounds promote the exchange, which becomes increas-
(hydrocarbons and chlorohydrocarbons) can be ingly difficult as fluorination progresses. The
electrofluorinated on porous graphite anodes in main catalysts used are antimony(III) and anti-
KF-containing hydrogen fluoride in a process mony(V) halides with low volatility. Addition of
developed by Phillips Petroleum [37], [38], chlorine oxidizes the antimony to the pentavalent
[39] and now referred to as CAVE (Carbon Anode state.
Vapor Phase Electrochemical Fluorination), in In addition to the liquid-phase processes,
operation at 3 M [40]. The organic compound is many commercially important gas-phase fluor-
introduced into the cell through the anode. In the inations employ hydrogen fluoride [43]. The
pores of the anode, i.e., at the phase boundary, components in the gas phase are passed through
partial or complete exchange of the hydrogen, but a tubular reactor containing the catalyst. The
not the chlorine, takes place. To date this process composition of the product can be controlled
has been used only on a small scale. within wide limits by varying temperature, pres-
sure, residence time, catalyst, and the proportions
of the reactants. Various metal fluorides are
2.2. Halogen – Fluorine Exchange suitable catalysts, e.g., aluminum fluoride [44]
or basic chromium fluoride [45].
Exchange of chlorine with hydrogen fluo- For further processing of the mixture pro-
ride is used in many commercial processes both duced by gas- or liquid-phase fluorination, the
for the production of chlorofluoroalkanes and for following criteria should be satisfied [46]:
the side-chain fluorination of aromatic and N-
heterocyclic compounds [41]. The method in- 1. The hydrogen chloride generated should be
volves exchange of chlorine for fluorine in poly- separated in a pure form to permit further use.
Vol. 15 Fluorine Compounds, Organic 447

2. Unreacted hydrogen fluoride should be 2.4. Addition of Hydrogen Fluoride to

recovered. Unsaturated Bonds
3. Acid residues, water, and other impurities
must be removed from the product. Addition of hydrogen fluoride to alkenes and
alkynes takes place below 0  C with formation
Usually, the hydrogen chloride is separated of mono- or difluoroalkanes; ethylene and acety-
from the crude fluorination mixture by fractional lene are exceptions [24]. Ethyl fluoride is pro-
distillation. The bulk of the hydrogen fluoride duced from ethylene and hydrogen fluoride at
may then be separated from the residue. Further 90  C; catalytic processes have been developed
treatment includes washing to remove traces of for the addition of hydrogen fluoride to acetylene
acid, drying, and fractional distillation. to produce vinyl fluoride or 1,1-difluoroethane.
Unsymmetrical olefins obey Markovnikov’s rule.
Exchange of Chlorine with Nonoxidizing Chloroolefins can undergo chlorine – fluorine
Metal Fluorides [41]. Alkali fluorides, espe- exchange after addition of hydrogen fluoride.
cially potassium fluoride, are often used to Addition of hydrogen fluoride to the electron-
exchange chlorine in carboxylic acid chlorides, deficient double bond of perfluoroolefins can be
sulfonic acid chlorides, a-chlorocarboxylic acid performed using trialkylamine trishydrofluorides
derivatives (esters, amides, and nitriles), ali- at moderate temperatures [49].
phatic monochloro compounds, or activated
aromatic chloro compounds (Halex process)
[47]. 2.5. Miscellaneous Methods
The dry, finely powdered metal fluoride is
employed in a solvent-free process at 400 – Substitution of Amino Groups in Aromatic
600  C, e.g., with polychlorinated aromatic com- Compounds [50]. Introduction of one or two
pounds, or, in most other cases, in the presence of fluorine atoms into aromatic rings is carried out
a solvent. For slow reactions, polar, aprotic sol- commercially by diazotization of aromatic
vents are used. amines in anhydrous hydrogen fluoride with
solid sodium nitrite and decomposition of the
dissolved diazonium salt (see Section 11.1.2).
2.3. Synthesis from Fluorinated
Synthons Fluorination with Nonmetal Fluorides.
Reactions of nonmetal fluorides with certain sub-
The variety of organic fluorine compounds can strates are predominantly restricted to laboratory
be greatly increased by the use of easily accessi- operations. Sulfur tetrafluoride and the following
ble, low molecular mass fluoroalkanes and ole- compounds can be used for the controlled introduc-
fins to synthesize higher molecular mass pro- tion of fluorine into organic compounds: dialkyla-
ducts. Halofluoromethanes add to halogenated minosulfur(IV) fluorides (R2NSF3) [51–53],
ethylenes to form halogenated fluoropropanes fluoroalkylamines (e.g., 2-chloro-1,1,2-trifluor-
[48]. An industrially applied reaction is the ad- oethyldiethylamine or 1,1,2,3,3,3-hexafluoropro-
dition of iodopentafluoroethane to tetrafluor- pyldiethylamine), tetra-n-butylammonium fluoride,
oethylene yielding a homologous series of trialkylamine trishydrofluorides, nitrosyl fluoride,
long-chain 1-iodoperfluoroalkanes (see Section perchloryl fluoride, fluoroxyfluoroalkanes (e.g.,
3.4). The pyrolysis of chlorodifluoromethane is CF3OF) [54], xenon difluoride [55], or CH3COOF
the industrial source of tetrafluoroethylene, hex- [56]. They are of commercial value for the fluori-
afluoropropene, and the corresponding oligo- nation of complex organic compounds such as
mers and polymers (see Sections 4.2 and 4.3). pharmaceuticals.
These examples illustrate the importance of this
synthetic method, especially for the production
of organic fluorine compounds containing more 2.6. Purification and Analysis
than two carbon atoms where the above-men-
tioned fluorination methods fail to give high Impurities are usually removed from organic
yields of the desired products. fluorine compounds by fractional distillation,
448 Fluorine Compounds, Organic Vol. 15

fractional crystallization, or chromatographic This system does not allow isomerisms to be

methods. This does not apply to fluoropolymers expressed for ethane derivatives; for such cases, a
and high-boiling perfluorinated oils, which re- letter (a, b, . . . etc.) is added to isomers as their
quire special measures, i.e., the use of extremely asymmetry increases, e.g.,
pure starting materials.
CF2 Cl

CCl2 F ¼ CFC 113 ðR 113Þ
Quantitative determination of fluorine is pos-
sible in most cases by combustion and subse-
CF3

CCl3 ¼ CFC 113 a ðR 113 aÞ
quent analysis of the hydrogen fluoride generat-
ed. Wet chemical methods are used to determine The compound with the highest degree of
fluoride ions [57]. symmetry is not given a letter.
Because of the high volatility of organic fluo- A special isomer in the series of propane
rine compounds, purity can be readily deter- derivatives is designated by adding two letters
mined by gas chromatography. 19F-Nuclear mag- to the numbers derived from the standard rules
netic resonance spectroscopy is a valuable tool [60]. The first letter attached to the number refers
for determining the structure of organic fluorine to the central carbon atom, coding the total
compounds. Structure determinations, even of atomic mass of the two substituents attached
mixtures, are often easier using this method than (a ¼ CCl2, b ¼ CFCl, c ¼ CF2, d ¼ CHCl, e ¼
with 1H-NMR spectra due to the larger chemical CHF, f ¼ CH2). The second appended letter is
shifts of 19F-NMR spectra. The 19F signals can be derived from the symmetry rule applied to the
integrated and used for quantitative analysis [58]. two terminal carbon atoms combined to an imag-
inary ethane unit. This unit is then treated like an
ethane derivative with the difference that the
3. Fluorinated Alkanes letter a is given to the most symmetric combina-
tion. Examples for the codes of the isomeric
The hydrogen atoms of alkanes may be partially propane derivatives C3HCl2F5 are:
or totally replaced by fluorine. Partially fluori-
nated alkanes are hydrofluorocarbons (HFCs); CF3–CF2–CHCl2 HCFC 225 ca
fully fluorinated alkanes (perfluoroalkanes) are CF2Cl–CF2–CHFCl HCFC 225 cb
perfluorocarbons (PFCs). In chlorofluorocarbons CF3–CHCl–CF2Cl HCFC 225 da
(CFCs) and hydrochlorofluorocarbons (HCFCs), CF3–CHF–CFCl2 HCFC 225 eb.
the alkane hydrogens are replaced by both chlo-
rine and fluorine. Codes for the butane derivatives contain three
A special nomenclature [59] has been intro- letters appended to the numeral (e.g., CF3–CH2–
duced to identify smaller chain length fluoroalk- CF2–CH3 is coded as HFC 365 mfc [61]).
anes (up to four carbon atoms) used in refriger-
ants. It consists of a three-digit number combined
with various letters. The first figure of the three- 3.1. Fluoroalkanes and
digit number indicates the number of carbon Perfluoroalkanes
atoms minus one (for methane derivatives, the
figure 0 is omitted); the second figure indicates Properties. Monofluoroalkanes are at-
the number of the hydrogen atoms plus one; and tacked by bases and sometimes by heat; however,
the third figure indicates the number of fluorine chemical resistance increases with increasing
atoms. All other bonds are saturated with chlo- fluorine substitution, especially multiple substi-
rine. The letter R before the code number is an tution at the same carbon atom.
abbreviation for refrigerant; the letter C indicates Perfluoroalkanes have distinct properties
a cyclic compound. The complete number is [62], [63]. Their physical properties differ from
called the refrigerant number. The American those of the corresponding hydrocarbons: densi-
Society of Heating, Refrigerating, and Air Con- ties and viscosities are higher, whereas surface
ditioning Engineers (Atlanta, Georgia) ASH- tensions, refractive indices, and dielectric con-
RAE Standard 34 – 78 describes the method of stants are lower. At room temperature perfluor-
coding. The abbreviation F is sometimes used oalkanes are attacked only by sodium in liquid
and stands for fluorohydrocarbon. ammonia. At 400 – 500  C, they are degraded
Vol. 15 Fluorine Compounds, Organic 449

Table 2. Boiling points, melting points, and densities of fluoroalkanes and perfluoroalkanes

Compound CAS registry Formula Mr Refrigerant Code no. bp,  C mp,  C d4q , g/cm3
no. no. (q,  C)

Fluoromethane [593-53-3] CH3F 34.03 R 41 HFC 41
78.5
141.8 0.8428 (
60)

Difluoromethane [75-10-5] CH2F2 52.03 R 32 HFC 32
51.7
136 1.100 (20)
Trifluoromethane [75-46-7] CHF3 70.02 R 23 HFC 23
82.1
160 1.246 (
34)
Tetrafluoromethane [75-73-0] CF4 88.01 R 14 PFC 14
128
183.6 1.33 (
80)
Fluoroethane [353-36-6] CH3CH2F 48.06 R 161 HFC 161
37.1
143.2 0.8176 (
37)
1,2-Difluoroethane [624-72-6] CH2FCH2F 66.05 R 152 HFC 152 30.7 0.913 (19)
1,1-Difluoroethane [75-37-6] CH3CHF2 66.05 R 152a HFC 152a
24.7
117 0.966 (19)
1,1,2-Trifluoroethane [430-66-0] CHF2CH2F 84.04 R 143 HFC 143 5.0
84
1,1,1-Trifluoroethane [420-46-2] CH3CF3 84.04 R 143a HFC 143a
47.6
111 0.942 (30)
1,1,2,2-Tetrafluoroethane [359-35-3] CHF2CHF2 102.03 R 134 HFC 134
19.7
89
1,1,1,2-Tetrafluoroethane [811-97-2] CF3CH2F 102.03 R 134a HFC 134a
26.3
101 1.2078 (25)
Pentafluoroethane [354-33-6] CF3CHF2 120.03 R 125 HFC 125
48.5
103 1.250 (20)
Hexafluoroethane [76-16-4] CF3CF3 138.02 R 116 PFC 116
78.1
100.6 1.607 (
78)
1,1,2,2,3-Pentafluoropropane [679-86-7] CHF2CF2CH2F 134.05 R 245ca HFC 245ca 26
82
1,1,1,2,2-Pentafluoropropane [1814-88-6] CF3CF2CH3 134.05 R 245cb HFC 245cb
18
1,1,1,3,3-Pentafluoropropane [460-73-1] CF3CH2CHF2 134.05 R 245fa HFC 245fa 15.3 1.320 (25)
1,1,1,2,3,3,3-Heptafluorpropane [431-89-0] CF3CHFCF3 170.03 R 227ea HFC 227ea
16.5
131 1.394 (25)
Octafluoropropane [76-19-7] CF3CF2CF3 188.03 R 218 PFC 218
36.7
183 1.350 (20)

Octafluorocyclobutane [115-25-3] 200.04 RC 318 PFCC 318
6.06
40.7 1.5241 (20)

1,1,1,3,3-Pentafluoro-n-butane [406-58-6] CF3CH2CF2CH3 148.07 R 365mfc HFC 365mfc 40.2 1.264 (20)
Decafluoro-n-butane [355-25-9] CF3CF2CF2CF3 283.02 R 610
22
128.2 1.517 (20)

by alkali metals and silicon dioxide; the former fluoride or metal fluorides such as antimony
produce a metal fluoride and carbon, while the fluoride. Monohydroperfluoroalkanes can be ob-
latter produces silicon tetrafluoride and carbon tained by adding hydrogen fluoride to perfluor-
dioxide. Thermal decomposition starts above oalkenes (e.g., CF3–CHF–CF3, HFC 227 ea) or
800  C (compounds with tertiary carbon atoms by decarboxylation of perfluorocarboxylates in
above 600  C) with the formation of saturated the presence of proton donors. The novel com-
and unsaturated decomposition products and mercially interesting hydrofluorocarbons are
some carbon. In addition to their chemical and produced by processes, that have been developed
physical stability, perfluoroalkanes are charac- for the production of chlorofluorocarbons and
terized by nonflammability and physiological hydrofluorocarbons and optimized during the last
inertness. decades (see Section 3.2).
Whereas partially fluorinated alkanes dissolve Higher temperatures and higher hydrogen fluo-
in many common solvents, perfluoroalkanes ride : substrate ratios are necessary to achieve
have low solubility, which decreases with their complete replacement of all chlorine atoms in the
chain length. Only ethers, ketones, esters, chlor- starting chlorocompounds by fluorine. Both liquid-
ohydrocarbons, and chlorofluorocarbons have phase halogen exchange in the presence of catalysts
the power to dissolve perfluoroalkanes [62]. such as antimony(V) or tin(IV) chlorofluorides and
Boiling points, melting points, and densities of vapor phase reactions using solid-phase catalysts
fluoroalkanes and perfluoroalkanes are listed in based on chromium are employed. Preferred start-
Table 2. For other physical properties of HFCs, ing materials are chloroform for HFC 23 [45], [65],
see Table 3. Physical data for liquid perfluoralk- dichloromethane for HFC 32 [66] and 1,1,1-tri-
anes are given in Tables 4 and 5. chloroethane for HFC 143 a [67]. The conversion
of tetrachloroethylene to HFC 125 [68] and
Production. Mono- and difluoroalkanes can trichloroethylene to HFC 134 a [69] involves
be produced by addition of hydrogen fluoride to initial HF-addition across the double bond fol-
olefins or alkynes (e.g., CF2H–CH3, HFC 152 a). lowed by a series of chlorine – fluorine ex-
Another synthetic pathway is the exchange of change reactions. Vapor-phase hydrogenolysis
chlorine (or bromine) for fluorine using hydrogen of chlorofluorocarbons and hydrochlorofluoro-
450 Fluorine Compounds, Organic Vol. 15

Table 3. Physical properties of hydrofluorocarbons

Property CH2F2 CHF3 CHF2CH3 CF3CH3 CF3CH2F CF3CHF2 CF3CH2CHF2 CF3CHFCF3 CF3CH2CF2CH3

Critical temperature, C 78.2 26.3 113.3 73.6 101.1 66.3 154.1 101.8 187.7
Critical pressure, MPa 5.80 4.87 4.52 3.83 4.06 3.63 2.93 2.75
Critical density, g/cm3 0.527 0.365 0.434 0.515 0.517 0.582
Heat of evaporation 240.8 326.0 230.0 213.46 177.03 208.96 131.8
at bp, kJ/kg
Specific heat, 876
kJ/kg
1 K
1
Refractive index, nD 1.200 1.442 1.023 1.53 1.407 (25)
(
50) (
80) (
30) (
48.5)
Surface tension, N/cm 6.93  9.94  4.60  8.02  3.70 
10
5 10
5 10
5 10
5 10
5
Vapor pressure (kPa) at

120  C 5.9

100  C 31.5

80  C 113.9

60  C 314.0

40  C 177.3 712.0 141.7 52.0 148.4 32.4

20  C 405.8 1403.0 120.7 316.4 134.0 337.6 19.7 86.7 6.3

0 C 813.4 2504.3 264.2 620.2 293.0 670.6 53.6 196.2 18.8
20  C 1474.6 4184.3 513.4 1104.3 572.0 1204.6 123.8 390.2 46.7
40  C 2477.4 909.7 1831.5 1017.0 2008.1 251.8 702.9 100.9
60  C 3933.4 1501.0 2884.7 1681.0 463.5 1174.7 194.9
80  C 2344.1 2631.0 788.8 1857.2 344.6
100  C 3511.4 3970.0 1261.0 2824.6 567.3
120  C 1920.0 880.2
140  C 1300.2
Lower ignition limit 12.7 none 3.1 7.1 none none none none 3.5
(25  C), vol %,
Atmospheric lifetime, a 15.6 40.5 7.4 40 10.8
HGWP* (CFC 11 ¼ 1) 0.15 8.4 0.03 1.0 0.29 0.67 0.69
*
HGWP ¼ Halogen Global Warming Potential

carbons is also proposed for the production of a fluorine stream [72], [73]. This process is suitable
hydrofluorocarbons [70], [71]. for the production of perfluoroalkanes containing
Perfluoroalkanes can be produced by a variety of up to 20 carbon atoms. It affords better process
routes. Indirect fluorination of hydrocarbons with control and yields than the direct gas-phase fluori-
cobalt(III) fluoride or silver(II) fluoride is carried nation using dilute fluorine and a metal catalyst,
out in a steel or nickel tube with stirring. The especially for longer-chain compounds [74].
hydrocarbon vapors are passed at 150 – 450  C Fluoroalkanes and perfluoroalkanes can also
over the fluorinating agent, which is regenerated in be produced electrochemically by the Phillips

Table 4. Boiling points, melting points, and densities of liquid perfluorocarbons

Compound (also mixtures) CAS registry no. Molecular formula Mr Commercial designationa bp,  C pour point,  C d425 , g/cm3

F-pentanesb [678-26-2] C5F12 288 PP50 29
120 1.604

F-methylcyclopentanes C6F12 300 PP1C 48
70 1.707
F-hexanes [355-42-0] C6F14 338 PP1 57
90 1.682
F-methylcyclohexanes C7F14 350 PP2 76
30 1.778
F-decalin (cis/trans) [306-94-5] C10F18 462 PP5/PP6 142
8 1.917
F-perhydrofluorene C13F22 574 PP10 194
40 1.984
F-perhydrophenanthrene [306-91-2] C14F24 624 PP11 215
20 2.03
F-perhydrofluoranthene C16F26 686 PP24 244 0 2.052
F-cyclohexylmethyldecalin C17F30 774 PP25 260
10 2.049
a
Flutec notation (BNFL Fluorochemicals)
b
F ¼ perfluoro
Vol. 15 Fluorine Compounds, Organic 451

Table 5. Further physical properties of liquid perfluoroalkanes [64]

Property PP50 PP1C PP1 PP2 PP5/6 PP10 PP11 PP24 PP25

Critical temperature, C 148.7 180.8 177.9 212.8 292.0 357.2 377 388.7 400.4
Critical pressure, MPa 2.05 2.26 1.83 2.02 1.75 1.62 1.46 1.51 1.13
Critical volume, L/kg 1.626 1.567 1.582 1.522 1.521 1.59 1.58 1.606 1.574
Heat of evaporation 90.8 75.8 85.5 85.9 78.7 71 68 65.8 67.9
at bp, kJ/kg
Specific heat, kJ/kg
1 K
1 1.05 0.878 1.09 0.963 1.05 0.92 1.07 0.93 0.957
Refractive index, n20
D 1.283 1.2650 1.2509 1.2781 1.3130 1.3289 1.3348 1.3462 1.3376
Surface tension, N/cm 9.4  10
5 12.6  10
5 11.1  10
5 15.4  10
5 17.6  10
5 19.7  10
5 19  10
5 22.2  10
5
Viscosity (dynamic), 0.465 1.049 0.656 1.561 5.10 9.58 28.4 31.5 114.5
mPa  s
Vapor pressure (kPa) 8.62 3.68 2.94 1.41 0.09 < 0.01 < 0.01 < 0.01 < 0.01
at 25  C

Petroleum process or the electrochemical fluori- spheric level, leading to zero ozone depletion
nation of alcohols, amines, carboxylic acids, and potentials (ODP ¼ 0) and to reduced halogen
nitriles by the Simons process (see Section 2.1). global warming potentials (HGWPs). However,
Tetrafluoromethane (carbon tetrafluoride, depending on the structure of the HFCs this
CF4) can be produced by reaction of CCl2F2 or reduced stability can entail an increased flamma-
CCl3F and hydrogen fluoride in the gas phase bility and thus make safe handling more difficult.
[75] or by direct fluorination of carbon [76]. Therefore, alternatives to the CFCs need to retain
Hexafluoroethane (PFC 116) is often obtained the attractive properties of CFCs like low toxici-
as a byproduct in the production of CFC 115. ty, nonflammability, good thermodynamic prop-
Octafluoropropane (PFC 218) can be produced erties, and accessibility via economically and
by direct [77], electrochemical [78], or CoF3- ecologically viable manufacturing processes, but
fluorination [79] of commercially available avoid any adverse effect to the environment.
hexafluoropropene (see Section 4.3). Octafluor- In refrigeration and air-conditioning systems
ocyclobutane is obtained by dimerization of CFC 12 is replaced by HFC 134 a, HCFC 22 by
tetrafluoroethylene [80] or by passing 1,2-di- the azeotropic mixtures HFC 507 (HFC 125/
chloro-1,1,2,2-tetrafluoroethane, CClF2CClF2, HFC 143 a 1 : 1) or HFC 410 (HFC 32/HFC 125
over a nickel catalyst at 590  C [81]. 1 : 1) and CFC 13 by HFC 23. HFC 134 a and
HFC 227 ea can be used as propellants in medici-
Uses. Hydrofluorocarbons have been gaining nal aerosols instead of CFC 114. HFC 245 fa and
increasing commercial interest as substitutes for HFC 365 mfc are proposed as blowing agents for
chlorofluoro- and hydrochlorofluorocarbons since foams in replacing CFC 11, CFC 113 and
governmental regulations banned the worldwide HCFC 141 b [83]. Until now no HFC candidate
production and consumption of CFCs by 1996 and for replacement of CFC 11 and CFC 113 as sol-
introduced a specific timetable for the phase out of vents, degreasing agents, or cleaning agents for
HCFCs [82]. In contrast to CFCs hydrofluorocar- textiles or metal surfaces has been identified. In the
bons have no adverse effect on the ozone layer and period 1990 – 1995 159.5 x 103 t of HFC 134 a
only a low contribution to global warming (see have been produced [84].
below). The latter effect could be further minimized Gaseous perfluorocarbons (PFC 14, PFC 116,
by avoiding leakages in refrigeration and air-con- PFC 218) are used in plasma etching processes in
ditioning equipment and by refrigerant recycling. the microelectronic industry [85] and as gaseous
In all applications involving considerable emis- dielectrics. Liquid perfluorocarbons [64] serve
sions to the atmosphere, e.g., as propellants in as heat-transfer media in transformers and in
aerosols (except medicinal aerosols), in open cell capacitors, as lubricants and hydraulic fluids, or
foams, or in extruded foams CFCs will be replaced in vapor-phase soldering [86] and vapor-phase
by nonhalogenated compounds in the future. sterilization [64].
Due to the presence of hydrogen in the mole- Perfluoroalkanes, e.g., perfluorodecalin [306-
cule, the stability of HFCs is reduced. In the 94-5], are used in the production of blood sub-
atmosphere they are degraded below the strato- stitutes [87].
452 Fluorine Compounds, Organic Vol. 15

Trade Names. Hydrofluorocarbons substi- respect to the ozone balance and the greenhouse
tuting chlorofluorocarbons and hydrochloro- effect [89], [90] verified the adverse impact on
fluorocarbons are marketed worldwide under the stratospheric ozone layer and the significant
protected trade names. The individual product contributions to global warming due to the long
is characterized by the HFC code number fol- atmospheric lifetimes of the CFCs. In 1987, a
lowing the trade name. Some worldwide applied United Nations agreement, called the Montreal
trade names are: Protocol – revised in 1992 during the Copenha-
gen Intergovernmental Conference – set the
France
deadline for the phase out of CFCs in developed
Rhône-Poulenc Isceon countries. Since 1996 production and consump-
Elf Atochem Forane tion of CFCs are prohibited, except as intermedi-
Germany ates in the production of fluorine chemicals,
Hoechst Reclin
Solvay Solkane
especially fluoropolymers. For HCFCs with re-
United Kingdom duced atmospheric stabilities a timetable has
ICI Klea been introduced for their phase out. HCFCs are
Italy allowed to be used as drop-in alternatives for
Montefluos Algogrene
Japan
CFCs until suitable HFC substitutes (see Section
Asahi Glass Asahiflon 3.1) will have been developed, but no longer than
Daikin Daiflon until 2015 to 2030 [82].
United States High molecular mass chlorofluorocarbons, a
Allied Signal Genetron
DuPont Suva
small but significant class of CFCs will not be
Great Lakes Chemical FM affected by the ban.
3M 3M Brand
Properties. Chlorofluoroalkanes are char-
Perfluorocarbons are offered under trade acterized by high chemical and thermal stabili-
names such as Freon C-51–12; Perfluorokero- ties, which increase with their fluorine content.
sene FCX-329, FCX-330;Perfluorolube oil FCX- Low flammability (or nonflammability) and low
512, FCX-412 (DuPont); Flutec PP-1, PP-2, PP- toxicity are additional commercial advantages.
3, PP-9, etc. (BNFL Fluorochemicals), Multi- Most of these compounds have a pleasant, weak
fluor Inert Fluids (Air Products and Chemicals). odor; some are mild anesthetics [91].
Boiling points, freezing points, and densities
of formerly commercially important chloro-
3.2. Chlorofluoroalkanes fluoroalkanes are shown in Table 7; other phys-
ical properties are listed in Table 8. Physical
For more than 50 years chlorofluorocarbons and properties of some high molecular mass CFCs
hydrochlorofluorocarbons have been the most produced from chlorotrifluoroethylene are
important organic fluorine compounds commer- given in Table 9.
cially. The five products listed in Table 6 have
been by far the most important of these with Production. Commercial production of
regard to the field of applications and to the chlorofluoroalkanes employs halogen exchange,
amount produced [84]. with hydrogen fluoride in the liquid phase in the
The results of the investigation on postulated presence of a catalyst. The production scheme for
atmospheric changes caused by CFCs [88] with dichlorodifluoromethane shown in Figure 1 is
Table 6. Economically most important organic fluorine compounds

Compound Total production Maximum annual

through 1995, 106t production (year), 103 t

Trichlorofluoromethane (R 11, CFC 11) 8.62 382 (1987)

Dichlorodifluoromethane (R 12, CFC 12) 11.28 425 (1987)
Chlorodifluoromethane (R 22, HCFC 22) 3.85 243 (1995)
1,2,2-Trichloro-1,1,2-trifluoroethane (R 113, CFC 113) 2.97 251 (1989)
1,2-Dichloro-1,1,2,2-tetrafluoroethane (R 114, CFC 114) 0.51 19 (1986)
Vol. 15 Fluorine Compounds, Organic 453

Table 7. Boiling points, melting points, and densities of chlorofluoroalkanes

Compound CAS Formula Mr Refrigerant Code no. bp, mp, d4q ,

 
registry no. number C C g/cm3 (q,  C)

Trichlorofluoromethane [75-69-4] CCl3F 137.38 R 11 CFC 11 23.7
111 1.490 (20)

Dichlorodifluoromethane [75-71-8] CCl2F2 120.93 R 12 CFC 12
29.8
155 1.328 (20)
Chlorotrifluoromethane [75-72-9] CClF3 104.47 R 13 CFC 13
81.1
181 0.924 (20)
Dichlorofluoromethane [75-43-4] CHCl2F 102.93 R 21 HCFC 21 8.9
135 1.366 (20)
Chlorodifluoromethane [75-45-6] CHClF2 86.48 R 22 HCFC 22
40.8
160 1.213 (20)
Tetrachloro-1,2-difluoroethane [76-12-0] CCl2FCCl2F 203.85 R 112 CFC 112 92 27.4 1.634 (30)
Tetrachloro-1,1-difluoroethane [76-11-9] CClF2CCl3 203.85 R 112 a CFC 112 a 91.5 40.8 1.649 (20)
1,1,2-Trichlorotrifluoroethane [76-13-1] CCl2FCClF2 187.39 R 113 CFC 113 47.7
33 1.582 (20)
1,1,1-Trichlorotrifluoroethane [354-58-5] CF3CCl3 187.39 R 113 a CFC 113 a 45.9 14 1.579 (20)
1,2-Dichlorotetrafluoroethane [76-14-2] CClF2CClF2 170.94 R 114 CFC 114 3.8
94 1.473 (20)
1,1-Dichlorotetrafluoroethane [374-07-2] CF3CCl2F 170.94 R 114 a CFC 114 a
2
56.6 1.478 (21)
Chloropentafluoroethane [76-15-3] CF3CClF2 154.48 R 115 CFC 115
38
106 1.291 (25)
1,1,2-Trichloro-2,2-difluoroethane [354-21-2] CClF2CHCl2 169.39 R 122 HCFC 122 71.9
140 1.544 (25)
1,1-Dichlor-2,2,2-trifluoroethane [306-83-2] CF3CHCl2 152.94 R 123 HCFC 123 28.7
107 1.475 (15)
1-Chloro-1,2,2,2-tetrafluoroethane [2837-89-0] CF3CHClF 136.48 R 124 HCFC 124
12
199 1.364(25)
1,2-Dichloro-1,1-difluoroethane [1649-08-7] CClF2CH2Cl 134.94 R 132 b HCFC 132 b 46.8
101.2 1.4163 (20)
1-Chloro-2,2,2-trifluoroethane [75-88-7] CF3CH2Cl 118.49 R 133 a HCFC 133 a 6.9
101 1.389 (0)
1,1-Dichloro-1-fluoroethane [1717-00-6] CCl2FCH3 116.95 R 141 b HCFC 141 b 32
103.5 1.250 (10)
1-Chloro-1,1-difluoroethane [75-68-3] CClF2CH3 100.49 R 142 b HCFC 142 b
9.2
130.8 1.120 (25)
1,1-Dichloro-2,2,3,3,3- [422-56-0] CF3CF2CHCl2 202.9 R 22 5ca HCFC 225 51.1
94 1.550 (25)
pentafluoropropane ca
1,3-Dichloro-1,2,2,3,3- [507-55-1] CClF2CF2CHClF 202.9 HCFC 56.1
97 1.560 (25)
pentafluoropropane 225 cb

typical [93]: of chlorine to convert it to the catalytically active

Sb(V) form.
CCl4 þ2 HF!CCl2 F2 þ2 HCl
The crude product is fractionally distilled
under pressure (0.6 – 0.8 MPa). The lower-
A steam-heated steel autoclave (a) lined with boiling fraction contains some chlorotrifluoro-
stainless steel (V2A) serves as the reactor. The methane and most of the dichlorodifluorometh-
seals are made from aluminum or copper. The ane (yield 90 % based on carbon tetrachloride,
autoclave (capacity 2 – 5 m3) is filled with 80 % based on hydrogen fluoride). The higher-
500 kg of hydrogen fluoride, 1540 kg of carbon boiling fraction consists of trichlorofluoromethane
tetrachloride, 220 kg of antimony(III) chloride, (5 – 10 % based on carbon tetrachloride), which
and 20 kg of chlorine, and the mixture is heated can be recycled. The distilled product is passed
to 100  C. After ca. 2 h and an increase in through a caustic filter (s). Steel bottles, pressure
pressure to ca. 3 MPa, the fluorination products vessels, tank cars, and tank trucks are used for
with lower boiling points are removed together transport.
with the hydrogen chloride that is generated and More recently developed exchange processes
some hydrogen fluoride; higher-boiling products are carried out continuously in the gas phase at
in the exit gases are condensed and recycled. The 100 – 400  C, using catalysts based on chromi-
low-boiling fraction is first washed with water in um [45], aluminum [44], or iron [94]. Starting
a tower (e) lined with poly(vinyl chloride) and materials, which include carbon tetrachloride,
packed with graphite; it is then washed with chloroform, tetrachloroethylene, and trichloro-
caustic in a tower (f) filled with porcelain pack- ethylene, are passed over the catalyst with excess
ing. After being washed to neutrality, the product hydrogen fluoride and, where necessary, chlo-
is dried in a tower (i) containing concentrated rine. Further processing follows the same prin-
sulfuric acid, compressed to a liquid, and fed into ciples as in the liquid-phase process.
an intermediate storage tank (m). Each batch In the Montedison chlorofluorination process,
takes ca. 24 h to process. The antimony catalyst reaction of C1- and C2-hydrocarbons with chlo-
remains in the reactor and is regenerated before rine and hydrogen fluoride takes place in a single
each subsequent batch by adding a small amount step in a fluidized-bed reactor. A suitable catalyst
454 Fluorine Compounds, Organic Vol. 15

Table 8. Physical properties of chlorofluoroalkanes [92]

Property CCl3F CCl2F2 CClF3 CHClF2 CCl2FCClF2 CClF2CClF2 CF3CHCl2 CF3CHClF CCl2FCH3 CClF2CH3

Critical temperature, 198.0 112.0 28.8 96.0 214.1 145.7 185 122.2 210.3 137.1

C
Critical pressure, 4.40 4.21 3.86 4.94 3.41 3.27 3.79 3.57 4.64 4.12
MPa
Critical density, 0.548 0.558 0.581 0.525 0.576 0.578
g/cm3
Heat of evaporation 182.16 166.88 148.50 234.12 145.70 139.42 174.17 167.9 223.15 223.15
at bp, kJ/kg
Specific heat at
101.3 kPa,
J kg
1 K
1 871 854 850 1088 946 971 1017.4 1130 1155.6 1297.9
Refractive index, 1.384 1.285 1.263 1.252 1.355 1.290 1.3322 (15) 1.3600 (10)
n26:5
D
Surface tension, 1910
5 910
5 910
5 1910
5 1310
5 1910
5
N/cm
Solubility in water,
g/100 g
at 0  C 0.0036 0.0025 0.0019 0.060 0.0036 0.0026
at 30  C 0.013 0.0125 0.0065 0.15 0.013 0.011 0.39 1.71 0.021 0.14
(25  C) (25  C) (25  C) (25  C)
Dielectric strength
at 101.3 kPa,
23  C, nitrogen ¼ 1 3.1 2.4 1.4 1.3 2.6 (39.2 kPa) 2.8
Dielectric constant
liquid at 25  C* 2.5 2.1 2.3 6.6 2.6 2.2
(
30  C)
vapor (t,  C) 1.0019 1.0016 1.0013 1.0035 1.0024 (27.5) 1.0021 7.9 (20  C)
(26) (29) (29) (25.4) (26.8)
Vapor pressure
(kPa) at

120  C 6.96

100  C 1.18 33.14

80  C 6.12 109.8

60  C 22.7 282.5 3.6

40  C 5.1 64.3 607 13.0

20  C 15.7 151.0 1146 246 5.08 37.0
0 C 40.2 308.7 1969 500 14.79 87.9 28
20  C 89.0 566.9 3177 917 36.4 182 65
40  C 176 958.5 1549 78.3 340 184 (50  C)
60  C 316 1518.7 2459 151.3 583
80  C 528 2284.7 268.0 935
100  C 830 3297.5 442.2 1423
120  C 1242 2083
140  C 1785 2964
Atmospheric 55 116 15.8 110 220 1.71 7.0 10.8 22.4
lifetime, a
ODP 1.00 1.00 0.055 1.07 0.80 0.02 0.022 0.11 0.065
HGWP (CFC11 ¼ 1) 1.00 3.00 0.33 1.6 7.1 0.02 0.11 0.14 0.41
*
Except where otherwise stated.

Table 9. Physical data of high molecular mass CFCs with the structure is a combination of aluminum chloride and other
Cl(CF2CFCl)nCl
metals [95–97]:
n¼ 2 3 4 5

Mr 304 420.5 537 653.5

bp,  C 136 205 255 300
Density, d437:8 1.713 1.808 1.865 1.902
Viscosity (dynamic), 1.35 3.4 10.8 48.9 Commercial production of chlorofluoroalk-
mPa  s (37.8  C)
anes is also possible by the electrochemical
Vol. 15 Fluorine Compounds, Organic 455

Figure 1. Manufacture of dichlorodifluoromethane (R 12) by fluorination of carbon tetrachloride in the liquid phase
a) Autoclave; b) Reflux condenser; c) Separator; d) Pressure valve; e) Wash column (water); f) Wash column (NaOH); g) Pump
for NaOH; h) Gasometer; i) Wash column (H2SO4); j) Pump for H2SO4; k) Compressor; l) Condenser; m) Receiver for crude
product; n) Distillation pot; o) Dephlegmator; p) Condenser; q) Forerun receiver; r) Tank for pure product; s) Caustic filter

fluorination process developed by Phillips Petro- the area of refrigerants, where R 11, R 12, R 13,
leum (see Section 2.1). R 22, R 113, R 114, R 115, and the chlorine-free
High molecular mass chlorofluoroalkanes are compounds R 23 and RC 318 were preferred. Of
produced by fluorination with chlorine trifluoride the drop-in alternatives to CFCs HCFC 22 is the
[98], [99]. most important compound, used as refrigerant
Other important processes for production of (annual production in 1995 243  103 t [84]),
high molecular mass CFCs are based on the followed by HCFC 141 b (113  103 t in 1995
telomerization of chlorotrifluoroethylene (see [84]) and HCFC 142 b (38  103 t in 1995 [84])
Section 4.8) with carbon tetrachloride [100] or used as blowing agents for closed cell foams. For
CFC 113 [101] as telogens. Stabilization and HFCs as alternatives see Section 3.1.
end-group fluorination are achieved using cobalt Chlorofluoroalkanes, especially R 11 and
trifluoride as fluorinating agent [102], [103]. R 113, were also employed as solvents and de-
greasing and cleaning agents for textiles;
Specifications. Chlorofluoroalkanes (and HCFC 22, CFC 113, and HCFC 142 b will be
also the alternative HCFCs and HFCs) produced important intermediates for the production of
on an industrial scale are subject to stringent fluoroolefins also in the future.
standards. Impurities must not exceed the fol- Higher molecular mass perchlorofluoroalk-
lowing limits (vol %): anes are used as oils, greases, and waxes, as
lubricants, hydraulic fluids, damping oils, heat-
transfer media, impregnating agents, and plasti-
cizers. Oligomers of chlorotrifluoroethylene
acids 0
moisture < 0.001 have achieved special importance in this area
higher-boiling fractions < 0.05 [104].
other gases 2
Trade Names. Chlorofluoroalkanes were
Uses. Up to the ban in the USA in 1978 sold worldwide under protected trade names; the
chlorofluoroalkanes had been used mainly as refrigerant numbers describing the chemical
aerosol propellants and as spraying and foam composition (see Table 7) are included to specify
blowing agents (R 11, R 12, R 114). Further individual compounds. Some of the trade names
important applications up to 1996 had been in that were applied worldwide are:
456 Fluorine Compounds, Organic Vol. 15

Halon 1301 denotes CF3Br; Halon 1211 is

Australia
CF2ClBr; and Halon 2402 denotes CF2BrCF2Br).
Australian Fluorine Chemicals Isceon
Czechoslovakia Bromofluorocarbons (BFCs) and hydrobro-
Slovek Pro Chemickov Ledon mofluorocarbons (HBFCs) are involved in the
Federal Republic of Germany depletion of stratospheric ozone and global
Hoechst Frigen
warming like the CFCs and HCFCs; however
Kali-Chemie Kaltron
France the contributions of the bromine-containing
Rhône-Poulenc Flugene compounds are distinctly higher. Therefore, the
Ugine Kuhlmann Forane 1992 Copenhagen meeting agreed to phase out
German Democratic Republic
the production of BFCs and HBFCs by 1994,
Volkseigener Betrieb Chemiewerk Nunchritz Fridohna
Volkseigener Betrieb Fluorwerke Dohna Frigedohn with the exception of Halon for some essential
Italy fire-fighting applications. HFC 125 and
Montedison Algofrene HCFC 123 (DuPont) or HFC 227 ea (Great
Japan
Lakes) are announced as alternatives though they
Asahi Glass Asahiflon
Daikin Kogyo Daiflon are significantly less efficient as fire extinguish-
Mitsui Fluorochemicals Flon ing agents than the BFC Halons
North America
Allied Chemical Genetron
Properties. Fully halogenated compounds
DuPont Freon
Kaiser Chemicals Kaiser with a high fluorine content have excellent ther-
Pennwalt Isotron mal stability; they are nonflammable and some
Racon Racon (e.g., CF3Br) are physiologically inert [92]. At high
Union Carbide Ucon
temperature, thermal cleavage of the C – Br bond
Soviet Union
Khladon into radicals occurs, which is responsible for the
Eskimon utility of some of these compounds in extinguish-
The Netherlands ing fires (! Fire Extinguishing Agents) [105].
AKZO FCC
Their chemical stability is slightly lower than that
United Kingdom
ICI Arcton of the corresponding chlorofluoroalkanes. Howev-
Imperial Smelting Corporation Isceon er, as with the chlorofluoroalkanes, stability in-
creases with the fluorine : bromine ratio. Some
Trade names of higher molecular mass chloro- compounds have a marked anesthetic effect
fluoroalkanes include Florubes (ICI), Fluorolube [91]. Physical properties are listed in Table 10.
oils, Fluorolube greases (Hooker Industrial Che-
micals Division), Halocarbon oils, greases, and Production. Bromofluoromethanes are ob-
waxes (Halocarbon Products), Kel-F oils, greases, tained by bromination of a stream of the appropri-
and waxes (3M), and Voltalef (Atochem). ate fluoromethane [106] or chlorofluoromethane
[107] at 300 – 600  C. Ethane derivatives can also
be obtained by thermal bromination [108] or by
3.3. Bromofluoroalkanes addition of bromine or hydrogen bromide [109] to
fluoroolefins. In some cases hydrogen bromide can
Bromofluoro compounds of practical importance be used to exchange a chlorine atom in a chloro-
are found mainly in the methane and ethane series. fluoroalkane for a bromine atom [110]. Iodine –
In the refrigerant (R) numbering system for bromine exchange in a fluoroiodoalkane can be
bromofluoroalkanes, the corresponding chloro- effected with bromine [111].
fluoroalkanes are taken as the basic structures (see
also Section 3); the substitution of chlorine by Uses. The lower-boiling compounds CBrF3
bromine is expressed by the addition of B1, B2, (R 13B1; Halon 1301) and CBrClF2 (R 12B1;
etc. For example, bromotrifluoromethane is de- Halon 1211) had been used as fire extinguishing
noted as R 13B1 and 1,2-dibromotetrafluoroethane agents. Producers were Atochem, ICI, and Solvay
as R 114B2. In fire-fighting applications the Halon in Europe, DuPont and Great Lakes in the USA
numbering system is used, specifying the number and Asahi Glass, Daikin, and Nippon Halon in
of carbon, fluorine, chlorine, and bromine atoms in Japan. The total worldwide Halon production was
the molecules when reading from left to right (e.g., estimated to be 25  103 t in 1986.
Vol. 15 Fluorine Compounds, Organic 457

Table 10. Boiling points, melting points, and densities of bromofluoroalkanes

Compound CAS Formula Mr Halon no. bp, mp, d 4q, g/m3 ODP Atmospheric
 
registry no. C C (q, C) R 11 ¼ 1 lifetime,a

Tribromofluoromethane [353-54-8] CBr3F 270.76 1103 106
74.5 2.7648 (20)

Dibromodifluoromethane [75-61-6] CBr2F2 209.84 1202 24.5
110 2.3063 (15)
Dibromochlorofluoromethane [353-55-9] CBr2ClF 226.30 1112 80
Bromotrifluoromethane [75-63-8] CBrF3 148.93 1301
57.8
168 1.58 (21) 16 67
Bromochlorodifluoromethane [353-59-3] CBrClF2 165.38 1211
4
160.5 1.850 (15) 4 19
Bromodifluoromethane [1511-62-2] CHBrF2 130.92 1201
15.5
145 1.825 (20) 1.4 5.6
1,2-Dibromotetrafluoroethane [124-73-2] CBrF2CBrF2 259.85 2402 47.5
110.4 2.18 (20) 6
1-Bromo-2-chloro-1,1,2- [354-06-3] CHClFCBrF2 197.40 2311 a 51.7 1.864 (20)
trifluoroethane
2-Bromo-2-chloro-1,1,1- [151-67-7] CF3CHBrCl 197.40 2311 50.2 1.861 (25)
trifluoroethane

Perfluoro-1-bromo-n-octane [423-55-2] is Properties. In contrast to chloro- and bro-

physiologically inert and is useful as an X-ray mofluoroalkanes, iodofluoroalkanes readily un-
contrast agent, especially for lung examinations dergo chemical reactions [24, Chap. 6], reacting
[112]. With its low surface tension it penetrates preferentially by homolytic cleavage of the C – I
small spaces and evenly wets healthy lung tissue. bond.
2-Bromo-2-chloro-1,1,1-trifluoroethane [151- The radical intermediates CnF2nþ1. and I . can
67-7], also known as halothane, has been used add to double bonds; thus, reaction with ethylene
worldwide since 1956 as an effective, nonflam- yields 1H,1H,2H,2H-1-iodoperfluoroalkanes,
mable inhalation anesthetic (! Anesthetics, which are commercially important intermediates
General). It is commonly produced by the ICI [114]:
process:
Cn F2nþ1 IþCH2 ¼ CH2 !Cn F2nþ1 CH2 CH2 I

Control of the reaction between iodofluor-

or the Hoechst process [43, pp. 208 – 210]: oalkanes and fluoroolefins, especially tetrafluor-
oethylene, can result in oligomerization (telo-
merization) of the olefin [115]:
CF3 Iþn CF2 ¼ CF2 !CF3 ðCF2 CF2 Þn I
As alternatives for halothane a series of
fluorinated ethers (containing in addition hydro-
gen and chlorine atoms or exclusively hydrogen This reaction is employed commercially and
atoms) have been developed, that retain or even is initiated by free radicals, UV irradiation, or
surmount the desirable properties of halothane heat [116].
as inhalation anesthetic [113]. However, also Iodofluoroalkanes also form organometallic
these compounds have an adverse effect on the compounds, some of which are useful intermedi-
ozone layer. ates, e.g., for Grignard reactions [117].
Iodoperfluoroalkanes cannot be used as alky-
lating agents and their applications are therefore
Trade Names. Fluothane (ICI), Halothane limited. However, derivatives of the FITS-type
‘‘HOECHST’’ (Hoechst). reagent are alkylating agents [118]:

3.4. Iodofluoroalkanes

Iodofluoroalkanes have become important inter-

mediates in the commercial production of com- Physical constants of some iodofluoroalkanes
pounds containing a perfluorinated moiety. are shown in Table 11.
458 Fluorine Compounds, Organic Vol. 15

Table 11. Boiling points, melting points, and densities of iodoperfluoroalkanes

Compound CAS registry no. Formula Mr bp,  C mp,  C d4 q, g/cm3 (q,  C)

Trifluoroiodomethane [2314-97-8] CF3I 195.9
22.5 2.3608 (
32)

Pentafluoroiodoethane [354-64-3] CF3CF2I 245.9 12.5
92 2.0850 (20)
Perfluoro-1-iodopropane [27636-85-7] CF3(CF2)2I 295.9 41.2
95 2.0626 (20)
Perfluoro-2-iodopropane [677-69-0] CF3CFICF3 295.9 38
Perfluoro-1-iodo-n-butane [423-39-2] CF3(CF2)3I 345.9 67
88 2.07 (15)
Perfluoro-1-iodo-n-pentane [638-79-9] CF3(CF2)4I 395.9 94.4
50 2.0349 (27.8)
Perfluoro-1-iodo-n-hexane [355-43-1] CF3(CF2)5I 445.9 117
45 2.06 (20)
Perfluoro-1-iodo-n-heptane [335-58-0] CF3(CF2)6I 495.9 137 – 138
Perfluoro-1-iodo-n-octane [507-63-1] CF3(CF2)7I 545.9 163 20.8 2.008 (25)
Perfluoro-1-iodo-n-decane [423-62-1] CF3(CF2)9I 645.9 195 – 200 65.5 1.940 (70)
1,2-Diiodotetrafluoroethane [354-65-4] CF2ICF2I 353.8 112 2.629 (25)
1,4-Diiodooctafluoro-n-butane [375-50-8] I(CF2)4I 453.8 150
9.0 2.4739 (27)

Production. Iodofluoroalkanes can be Properties. The chemical behavior of fluor-

produced by heating the silver salts of the per- oolefins [126] is governed by the number of
fluorocarboxylic acids with iodine [119] or the vinylic fluorine atoms. In contrast to their hydro-
corresponding sodium salts with iodine in di- carbon analogues, fluoroolefins are attacked by
methylformamide [120]. Of commercial impor- electrophiles only with difficulty [127], which
tance is the production of pentafluoroiodoethane increases with the degree of fluorination. How-
(CF3CF2I) by reaction of tetrafluoroethylene with a ever, fluoroolefins react readily with nucleo-
mixture of iodine pentafluoride and iodine [121]: philes [128], [129], because as the number of
vinylic fluorine atoms increases, the p-electron
5 CF2 ¼ CF2 þIF5 þ2 I2 !5 CF3 CF2 I
system of the double bond is destabilized. Ther-
modynamic calculations have shown that the
Heptafluoro-2-iodopropane (CF3CFICF3) is strength of the C – C p-bond in tetrafluoroethy-
obtained similarly from hexafluoropropene. lene
The higher homologues CnF2nþ1I (n ¼ 4 – 12) . .
CF2 ¼ CF2 CF2

CF2
are produced commercially by reaction of the lower
members with tetrafluoroethylene (telomerization). is only ca. 160 kJ/mol as opposed to 241 kJ/mol
a,w-Diiodoperfluoroalkanes are obtained in ethylene [130]. In unsymmetrically substitut-
from tetrafluoroethylene and iodine [122]: ed fluoroolefins, the nucleophile attacks the
carbon atom that is made strongly positive by
the neighboring fluorine atoms and is shielded
only weakly (sp2 hybridization). The reactivity
of fluoroolefins toward nucleophiles increases
Uses. 1-Iodoperfluoroalkanes and as follows:
1H,1H,2H,2H-1-iodoperfluoroalkanes are inter-
CF2 ¼ CF2 < CF2 ¼ CF

CF3 < CF2 ¼ CðCF3 Þ2
mediates in the production of surfactants and
textile finishes [123]. Perfluorocarboxylic acids,
especially perfluorooctanoic acid, are obtained Fluoroolefins are slightly to highly toxic and
from perfluoroiodoalkanes [124], and perfluori- must be handled with care. The toxicity of fluo-
nated dicarboxylic acids are obtained from a,w- rinated olefins is apparently proportional to their
diiodoperfluoroalkanes [125]. reactivity toward nucleophiles [131]. Perfluoroi-
sobutene, CF2¼C(CF3)2 [382-21-8], for exam-
ple, is far more toxic than its lower homologues.
4. Fluorinated Olefins Physical properties of commercial fluoro- and
chlorofluoroolefins are given in Table 12.
The commercial importance of fluoro- and chlor- Fluoroolefins also differ from hydrogen-con-
ofluoroolefins lies in the production of fluorinat- taining olefins in their marked tendency to un-
ed plastics and inert fluids. dergo cycloaddition [132].
Vol. 15 Fluorine Compounds, Organic 459

Table 12. Physical properties of fluoroolefins and chlorofluoroolefins

Property Tetrafluoro- Hexafluoro- 1,1-Difluoro- Fluoro- Chlorotri- 3,3,3-Tri-

ethylene propene ethylene ethylene fluoroethylene fluoro-
prop-1-ene
[116-14-3] [116-15-4] [75-38-7] [75-02-5] [359-29-5] [677-21-4]

Mr 100.02 150.02 64.03 46.04 116.47 96.05

bp,  C
75.6
29.4
82
72.2
28.36
27
mp,  C
142.5
156.2
144
160.5
158.2
d4q, g/cm3 (q,  C) 1.519 (
76.3) 1.292 (
29.4) 0.617 (23.6) 0.775 (
30) 1.51 (
40)
Critical temperature,  C 33.3 86.2 30.1 54.7 105.8 107
Critical pressure, MPa 3.82 2.75 4.29 5.43 3.93 4.14
Critical density, g/cm3 0.58 0.417 0.320 0.55
Heat of evaporation, 16 821 (
75.6) 20 100 (
29) 13 189 (
40) 13 494 (
20) 20 893 (
28.4)
J/mol (t,  C)

Production. Fluoroolefins are produced by (see Section 4.3) and the highly toxic perfluor-
dehalogenation of chlorofluoro-, bromofluoro-, oisobutene are formed [139].
or iodofluoroalkanes with zinc and alcohol, by
dehydrohalogenation of hydrogen-containing Production. Many commercial processes
haloalkanes with alcoholic alkali, or by heating. for the production of tetrafluoroethylene are
Other common methods include addition of hy- known, e.g., reaction of tetrafluoromethane in
drogen halides to alkynes, decarboxylation of an electric arc [140], dechlorination of CF2Cl

fluorocarboxylic acid salts, and pyrolysis of CF2Cl with a metal [141], and thermal decom-
fluorohydrocarbons [133–135]. position of trifluoroacetic acid [142]:
2 CF3 COOH!CF2 ¼ CF2 þ2 HFþ2 CO2
4.2. Tetrafluoroethylene
The two principal commercial methods are
Properties. Tetrafluoroethylene (TFE), per- pyrolysis of trifluoromethane [143]:
fluoroethylene, CF2¼CF2, a colorless, odorless
gas, is flammable in oxygen, producing tetra-
fluoromethane and carbon dioxide. For physical
properties, see Table 12. At low temperature in and pyrolysis of chlorodifluoromethane [144]:
the presence of oxygen, explosive peroxides are
formed [136], [137]. Tetrafluoroethylene must be
handled with great care since, even in the absence
of oxygen, it can decompose explosively into
carbon and tetrafluoromethane under pressure In the second method (Fig. 2), the chlorodi-
above
20  C (DH ¼
276 kJ/mol at fluoromethane gas is passed at atmospheric or
298 K). If the polymerization to polytetrafluor- reduced pressure through a heated platinum,
oethylene (PTFE) (DH ¼
172 kJ/mol at silver, or carbon tubular reactor (a). The 28 %
298 K) is uncontrolled, a more strongly exother- conversion obtained under these conditions is
mic decomposition reaction can occur. Polymer- low (yield, 83 %), but can be increased to ca.
ization inhibitors include dipentene [138-86-3], 65 % with the same yield by adding steam [145].
a-pinene [80-56-8], which are added to liquid In modification of this method, chlorodifluoro-
tetrafluoroethylene during purification and stor- methane is treated with superheated steam at ca.
age (at
30  C) [138]. In the United States, the 700  C, which results in a conversion rate of
transportation of liquid TFE containing stabili- 60 – 80 % and a selectivity of 84 – 93 % [146].
zers is permitted. The pyrolysis gas is washed with water (b) to cool
In the gas phase at ca. 300 – 500  C, tetra- it and to remove HCl. After being washed with
fluoroethylene dimerizes to perfluorocyclobu- caustic soda (c) and dried with concentrated
tane [139]. Above 600  C, hexafluoropropylene sulfuric acid (d), the crude product can be stored
460 Fluorine Compounds, Organic Vol. 15

Figure 2. Flow sheet for tetrafluoroethylene production

a) Pyrolysis reactor; b) Quench column (water); c) Wash column (NaOH); d) Drier (conc. H2SO4); e) Intermediate storage tank
for crude tetrafluoroethylene; f) Fractionation column for low-boiling constituents; g) Product distillation column;
h) Tetrafluoroethylene storage tank; i) Fractionation column

in liquid or gaseous form (e). It is a complex Polytetrafluoroethylene [9002-84-0], (PTFE)

mixture from which tetrafluoroethylene is sepa- is a homopolymer sold under the trade names
rated by distillation in the presence of dipentene Algoflon (Montefluos), Fluon (ICI), Halon (Al-
or a similar stabilizer to prevent polymerization. lied Chemical), Hostaflon TFE (Hoechst), Teflon
An overhead fraction containing inert gases and PTFE (DuPont), Fluon (Asahi Glass), and Poly-
trifluoromethane is obtained in a low-boiling flon TFE (Daikin). Copolymers with fluorinated
fractionation column (f) before isolating pure or fluorine-free olefins or vinyl ethers are also
TFE (column g). commercially available.
The higher-boiling fractions are processed (i)
to recover unreacted CHCl2F and to isolate
hexafluoropropene, a byproduct. Extractants 4.3. Hexafluoropropene
such as methanol are added because of the
formation of azeotropes during distillation Properties. Hexafluoropropene (HFP),
[147]. Methanol also reacts with the toxic CF3CF¼CF2, a colorless, odorless gas, is non-
perfluoroisobutene, (CF3)2C¼CF2, to give an flammable in air at room temperature. For physi-
addition product. cal properties, see Table 12. It exhibits no special
tendency toward radical homopolymerization
Uses. Currently, tetrafluoroethylene is the [149], but like other fluoroolefins, it reacts readi-
most important fluoroolefin; it is used mainly for ly with nucleophiles [128], [129].
the production of fluoropolymers (! Fluoropo- Liquid hexafluoropropene has unlimited stor-
lymers, Organic). It reacts with perfluoronitro- age life under pressure at room temperature in
soalkanes to produce so-called nitroso rubbers steel containers, even without stabilizers. In
[148]. Tetrafluoroethylene is also used in the many countries the liquid can be transported in
production of low molecular mass compounds steel cylinders or tank cars. Hexafluoropropene is
and intermediates, e.g., for the manufacture of toxic (LC50 3000 ppm) and can decompose ther-
iodoperfluoroalkanes (see Section 3.4). mally to form highly toxic perfluoroisobutene.
Vol. 15 Fluorine Compounds, Organic 461

Production. Hexafluoropropene is pro- Vinylidene fluoride is transported as a liquid

duced commercially by temperature-controlled in steel cylinders without stabilizers.
pyrolysis of chlorodifluoromethane (cf. produc-
tion of tetrafluoroethylene, see Section 4.2) Uses. 1,1-Difluoroethylene is the starting
[150]. Hexafluoropropene can also be obtained material for the commercially important homo-
from tetrafluoroethylene by heating at normal or polymer poly(vinylidene fluoride) [24937-79-9],
reduced pressure, preferably in the presence of an (PVDF) (! Fluoropolymers, Organic, Section
inert gas (e.g., CO2) or water vapor [151]: 2.8.).

Trade Names (PVDF). Kynar (Atochem

USA), Florafon (Atochem), Solef (Solvay), Neo-
flon (Daikin), KF (Kureha Chem.), Vidar
Uses. An important application of hexa- (S€uddeutsche Kalkstickstoffwerke). Worldwide
fluoropropene is the production of copolymers, annual production (1988): 7.4  103 t.
e.g., with tetrafluoroethylene or 1,1-difluoroethy- The copolymer with hexafluoropropene [116-
lene (! Fluoropolymers, Organic, Section 2.3., 15-4] is marketed as Viton (DuPont) and Fluorel
! Fluoropolymers, Organic, Section 3.2.). The (3M).
versatile epoxide, hexafluoropropylene oxide
[428-59-1] (see Section 6.1.2), can be obtained
from hexafluoropropene by oxidation. 4.5. Monofluoroethylene,
Monofluoroethylene
4.4. 1,1-Difluoroethylene
vinyl fluoride (VF), CH2¼CHF, is a colorless,
vinylidene fluoride (VDF) CH2¼CF2, is a com- highly flammable gas; up to 0.2 % of polymeri-
mercially important, partially fluorinated olefin. zation inhibitors are added for stabilization dur-
It is a colorless, flammable gas that undergoes ing transport and storage. For physical proper-
homopolymerization and copolymerization. For ties, see Table 12.
physical properties, see Table 12.
Production. In the past, vinyl fluoride was
Production. Currently, three basic methods produced by dehydrofluorination of 1,1-difluor-
are used for the commercial production of vinyl- oethane [75-37-6], obtained in two steps by
idene fluoride: addition of hydrogen fluoride to acetylene [24,
p. 59 – 66], [156]:
1. Dechlorination of 1,2-dichloro-1,1-difluor-
oethane [1649-08-7], R 132 b in the gas
phase and on a metal catalyst [142], [152]:

However, with mercury catalysts, vinyl fluo-

ride can be produced directly from acetylene and
hydrogen fluoride [24, p. 59 – 66], [157]:
2. Dehydrochlorination of 1-chloro-1,1-difluor-
oethane [75-68-3], R 142 b [144], [153]:

The dehydrochlorination of 1-chloro-1-fluor-

In the presence of steam the temperature can oethane [1615-75-4], CHClFCH3, and 1-chloro-
be reduced to 500 – 650  C [154]. 2-fluoroethane [762-50-5], CH2FCH2Cl, are also
3. Dehydrofluorination of 1,1,1-trifluoroethane utilized commercially [158].
[420-46-2], R 143 a [155]:
Uses. The main use of monofluoroethylene
is in the production of poly(vinyl fluoride)
[24981-14-4] (PVF) (! Fluoropolymers, Organic,
462 Fluorine Compounds, Organic Vol. 15

Section 2.8., ! Fluoropolymers, Organic, Section

2.9.).

Trade Names (PVF). Tedlar (DuPont),

Dalbon (Diamond Shamrock, USA). Worldwide
annual production (1988): 1.6  103 t

Acetic anhydride can be used with hexafluor-

4.6. 3,3,3-Trifluoropropene
oacetone instead of ketene. The multistep reac-
tion takes place in a single operation in a copper
3,3,3-Trifluoropropene, CF3CH¼CH2 (TFP), is
reactor above 300  C [167]. Presumably, pro-
produced almost exclusively by fluorination and
cesses based on the highly toxic perfluoroisobu-
dehalogenation of 1,1,1,3-tetrachloropropane
tene are designed to remove it as a harmful
[1070-78-6] (TCP), CCl3CH2CH2Cl. With sodi-
byproduct of tetrafluoroethylene or hexafluoro-
um fluoride at 400 – 475  C, trifluoropropene is
propene production.
obtained in a single step, involving chlorine –
Hexafluoroisobutene is used for the produc-
fluorine exchange and dehydrochlorination
tion of fluoropolymers. The trade name of the
[159]. Using hydrogen fluoride and oxygen, the
copolymer [34149-71-8] with vinylidene fluo-
reaction can be carried out at 300  C over a
ride is CM-X (Ausimont) [168].
chromium fluoride catalyst [160]. Liquid-phase
fluorination of 1,1,1,3-tetrachloropropane with
hydrogen fluoride in the presence of an antimony 4.8. Chlorofluoroolefins
catalyst yields 1,1,1-trifluoro-3-chloropropane,
CF3CH2CH2Cl, which gives 3,3,3-trifluoropro- Among the numerous known chlorofluoroolefins
pene when treated with a base [161]. The con- [134], [134], 1,1-dichloro-2,2-difluoroethylene
version is effected in a single operation with a [79-35-6] has some importance as a starting
mixture of hydrogen fluoride and a tertiary amine material in the production of methoxyflurane
[162]. [76-38-0], an inhalation anesthetic. However,
chlorotrifluoroethylene is the most important
member of this class.

Chlorotrifluoroethylene [359-29-5]
A multistep synthesis starts from vinylidene (CTFE), CF2¼CFCl, a colorless, flammable gas,
fluoride (CF2¼CH2) [163]. is less reactive than tetrafluoroethylene. For
physical properties, see Table 12. Although
Uses. The main use of trifluoropropene is in chlorotrifluoroethylene is more stable than tetra-
the production of fluorine-containing silicones fluoroethylene, stabilizers such as tributylamine
used in hydraulic fluids [159], [164]. are used during transportation and storage in steel
cylinders [169]. Chlorotrifluoroethylene is toxic.

4.7. 3,3,3-Trifluoro-2-(trifluoromethyl)- Production. Chlorotrifluoroethylene is pro-

prop-1-ene duced commercially by dechlorination of 1,1,2-
trichloro-1,2,2-trifluoroethane [76-13-1], (R 113)
3,3,3-Trifluoro-1-(trifluoromethyl)prop-1-ene with zinc in methanol [170]:
[382-10-5], hexafluoroisobutene, (HFIB),
(CF3)2C¼CH2, is a colorless, toxic gas (4-h LC50
1700 ppm) with a bp of 14.1  C at 101.3 kPa. A
number of processes for its production have been An alternative route is dechlorination in the
described; the most important use hexafluoroa- gas phase, e.g., on an aluminum fluoride – nickel
cetone [165] or perfluoroisobutene [166] as the phosphate catalyst; this catalyst is highly stable
starting material. [171].
Vol. 15 Fluorine Compounds, Organic 463

Uses. Chlorotrifluoroethylene is a starting Table 13. pKa values of alcohols [178]

material for homopolymers and copolymers Alcohol R¼H R¼F
(PCTFE) (! Fluoropolymers, Organic, Section
2.6., ! Fluoropolymers, Organic, Section 2.7.). CR3CH2OH 15.9 12.8
(CR3)2CHOH 17.1 9.3
In addition, chlorotrifluoroethylene is an inter- (CR3)3COH 19.2 5.4
mediate in the production of the inhalation anes-
thetic halothane. (2-Chloro-1,1,2-trifluor-
oethyl)-diethylamine [357-83-5], ClFHCCF2N trifluoroethanol [75-89-8], bp 73.6  C, and
(C2H5)2 (an addition product of chlorotrifluor- 1,1,1,3,3,3-hexafluoro-2-propanol [920-66-1],
oethylene with diethylamine), is used as a fluori- bp 58.2  C, have achieved commercial impor-
nating agent to replace hydroxyl groups in ster- tance. The former is prepared by catalytic hydro-
oids and carbohydrates with fluorine [54], [172]. genation of trifluoroacetamide [179], trifluoroa-
Another use of chlorotrifluoroethylene is in tel- cetyl chloride [180], or trifluoroacetic acid esters
omerization with carbon tetrachloride or chloro- [181], or by reduction of trifluoroacetic acid with
form. The products are stabilized with fluorine or metal hydrides [182]. Similar processes are used
CoF3 and are used as inert fluids, hydraulic fluids, to prepare the latter from hexafluoroacetone
or lubricants [104], [173]. [183]. Because of their strong tendency to form
hydrogen bonds, the fluorinated alcohols form
Trade Names (PCTFE). Aclon (Allied- stable complexes with hydrogen bond acceptors
Signal), Daiflon (Daikin), Kel-F (3M), Voltalef and are excellent solvents for polar polymers
(Atochem). Worldwide annual production [184]. Ethers derived from these alcohols are
(1988): 103 t. used as inhalation anesthetics (see Section
6.3). 2-Aryl-1,1,1,3,3,3-hexafluoro-2-propanols
are prepared by alkylation of aromatic com-
5. Fluorinated Alcohols [174] pounds with hexafluoroacetone [185]. Tertiary
diols, e.g., 1,3-bis(2-hydroxyhexafluoro-2-pro-
Primary and secondary alcohols that have fluorine pyl) benzene [802-93-7] are used to prepare
and hydroxyl groups on the same carbon atom are fluoroepoxy resins [186].
unstable, and readily lose hydrogen fluoride to
form carbonyl compounds. Primary and second-
ary perfluoroalkoxides, however, can be prepared
in polar solvents under aprotic conditions from
carbonyl compounds and a source of ionic fluo-
ride [175]; typical counterions are alkali-metal, Long-Chain Fluoroalcohols. The unique
tetraalkylammonium, or tris(dialkylamino)sulfo- hydro- and oleophobic properties of long per-
nium cations. The perfluoroalkoxides are moder- fluoroalkyl chains lead to many applications of
ately nucleophilic and are used in situ to prepare long-chain fluoroalcohols and their derivatives
compounds containing perfluoroalkoxy groups as surfactants, antisoilants, and surface-treat-
(see Section 6.3). Tris(dialkylamino)sulfonium ment agents [187]. Structures can be repre-
perfluoroalkoxides are unusually stable and, in sented by,
some cases, have been isolated as crystalline
solids [176]. Tertiary perfluoro alcohols, e.g.,
perfluoro-tert-butanol (1,1,1,3,3,3-hexafluoro-2- where X is typically F, H, or CH3, n is 6 – 12,
trifluoromethyl-2-propanol) [2378-02-1] [177] and m is 1 or 2. The most important compounds
and alcohols containing CH2 groups between the are the 1H,1H-perfluoroalcohols (X ¼ F, m ¼
fluorinated segment and the OH group are also 1), prepared by reduction of the corresponding
stable. Fluorinated alcohols are more acidic than perfluorinated carboxylic acids [188], and the
their nonfluorinated analogues because fluorine is 1H,1H,2H,2H-perfluoroalcohols (X ¼ F, m ¼
highly electronegative (see Table 13) [178]. 2); the latter are prepared by treatment of the
corresponding 1-iodo-1H,1H,2H,2H-perfluor-
Short-Chain Fluoroalcohols. Of the short- oalkanes with oleum [189]. Alcohols of the
chain fluorinated alcohols (C2– C4), only 2,2,2- formula H(CF2)nCH2OH, where n is an even
464 Fluorine Compounds, Organic Vol. 15

number, are prepared by telomerization of tet- partially fluorinated or nonfluorinated ethers by

rafluoroethylene with methanol [190]. fluorination with cobalt fluoride or elemental
For use as soil-repellent finishes, the long- fluorine under carefully controlled conditions
chain fluoroalcohols are converted into deriva- [195].
tives to adjust the hydrophobicity, solubility in
aqueous and organic solutions, surface retention, Trade Names. Fluorinert liquids (3M) and
and stability for each specific application. These Galden fluorinated fluids (Montedison).
derivatives include esters, phosphates, carboxy-
lates, and polyoxyethylenes. Polymeric alcohols
are prepared by esterification with (meth)acry- 6.1.2. Perfluorinated Epoxides
loyl chloride, followed by polymerization.
In contrast to other perfluorinated cyclic ethers,
Trade Names. Teflon, Zepel, and Zonyl ring strain in perfluorinated epoxides results in
(DuPont), Scotchgard (3M), and Oleophobal high reactivity, making them versatile precursors
(Chemische Fabrik Pfersee, Ciba-Geigy). to other fluorinated compounds [196]. The most
important is hexafluoropropylene oxide [428-59-
1] (HFPO), trifluoro(trifluoromethyl)oxirane
6. Fluorinated Ethers [191] [197]. It is prepared from hexafluoropropene by
reaction with elemental oxygen [198], by elec-
6.1. Perfluoroethers trochemical oxidation [199], or by reaction with
hypochlorites [200] or hydrogen peroxide [201]
Perfluorinated ethers are less basic than their in alkaline media.
hydrogen-containing analogues [192]. The satu- Hexafluoropropylene oxide (bp
27.4  C) is
rated aliphatic and cycloaliphatic perfluoroethers stable at room temperature, but decomposes
are noncombustible, and, with the exception of above 150  C to form trifluoroacetyl fluoride and
the perfluorinated epoxides, display high chemi- difluorocarbene [202]. In the presence of strong
cal and thermal stability. Other properties of the Brønsted or Lewis acids, such as alumina or
stable ethers, such as a large difference between aluminum chloride, HFPO undergoes catalytic
the melting and boiling points at ambient pres- rearrangement to hexafluoroacetone, constitut-
sure, and a low pour point, surface tension, and ing a convenient synthesis of this compound
dielectric constant, are the basis of applications [203]. Most significantly, HFPO reacts readily
such as dielectric and heat-exchange fluids in, for with nucleophiles. Attack usually occurs at the
example, high power transformers. Higher mo- central carbon atom [204], resulting in formation
lecular mass perfluoroethers are used as lubri- of an acid fluoride by loss of a fluoride ion from
cants and hydraulic fluids in extreme service the intermediate perfluoroalkoxide, which can
conditions, i.e., at high temperature and/or in a react further with HFPO to form higher oligo-
corrosive environment. mers. Acid fluorides are precursors to the com-
mercially important perfluorovinyl ethers and
higher molecular mass perfluoroethers.
6.1.1. Low Molecular Mass
Perfluoroethers

The low molecular mass perfluoroethers are usu-

ally prepared by electrochemical fluorination of
aliphatic ethers, alcohols, or carboxylic acids
[193]. Typical empirical formulas are C6F12O,
C7F14O, and C8F16O; these ethers often consist of where X ¼ nucleophile, e.g., fluoride ion.
isomer mixtures. Compound FC-75 [11072-16- Both tetrafluoroethylene oxide [694-17-7]
5] (3M), mostly perfluorobutyltetrahydrofurans, (TFEO), also called tetrafluorooxirane [205], and
is a useful solvent that has been explored as an epoxides of longer chain-length perfluoroolefins
oxygen-transport agent in artificial blood [194]. [206] are known; however, the former is unstable
Perfluorinated ethers can also be prepared from at room temperature and rearranges to form
Vol. 15 Fluorine Compounds, Organic 465

trifluoroacetyl fluoride, whereas the latter are alkoxide generated in situ, or of other nucleo-
prepared from inaccessible perfluoroolefins. On- philes with HFPO. The resulting acid fluorides
ly HFPO has achieved commercial significance are converted to acid salts, which lose carbon
because it is used for the synthesis of hexafluor- dioxide and metal fluoride when heated in an
oacetone (see Hexafluoroacetone), high molecu- aprotic environment. For example, HFPO is
lar mass perfluoroethers, Section 6.1.3, and fluo- treated with cesium trifluoromethoxide (from
rinated vinyl ethers (Section 6.2). cesium fluoride and carbonyl fluoride). Hydroly-
sis and decarboxylation of the resulting acid
fluoride gives perfluoro(methyl vinyl ether)
6.1.3. High Molecular Mass [1187-93-5].
Perfluoroethers

High molecular mass perfluorinated ethers are

prepared by fluoride-catalyzed oligomerization
of HFPO [207]. The resulting terminal acid
fluoride group is removed by hydrolysis and
This compound is a comonomer with tetrafluor-
decarboxylative fluorination with elemental fluo-
oethylene in a perfluorinated elastomer [211].
rine. Chemically inert ethers are produced which
Perfluoro(propyl vinyl ether) [1623-05-8],
have the formula,
CF3CF2CF2OCF¼CF2, prepared from the dimer
of HFPO [212], is copolymerized with tetrafluor-
oethylene to a melt-processable perfluoroplastic.
Perfluorovinyl ethers containing specific
functional groups and usually two or more moles
These ethers are obtained in various molecu-
of hexafluoropropylene oxide are prepared in a
lar mass and viscosity ranges by controlling
similar fashion. These compounds have the struc-
oligomerization conditions or by partial distilla-
ture RO(C3F6O)CF¼CF2; they are used as func-
tion of the oligomeric mixture. In an alternative
tional groups in perfluoroelastomers which can
method [208], perfluorinated olefins (e.g., tetra-
undergo a crosslinking reaction, i.e., cure-site
fluoroethylene or hexafluoropropene) react pho-
monomers (R ¼ CF2CF2CN or pentafluorophe-
tochemically with oxygen to form oligomeric
nyl) [213] and as monomers that provide the ionic
perfluoroethers with terminal acid fluoride
groups in perfluorinated ion-exchange resins
groups and peroxide bonds [209]. These end
(R ¼ CF2CF2SO2F, CF2CF2CF2CO2CH3, or
groups and the unstable peroxide linkages are
CF2CF2CO2CH3) [214]. Synthesis of the sulfo-
eliminated by fluorination. Perfluoroethers with
nyl fluoride-substituted vinyl ether is illustrative.
molecular masses of ca. 500 – 6000 are used as
Reaction of tetrafluoroethylene with sulfur triox-
inert fluids, lubricants, and hydraulic fluids in
ide gives a sultone, which rearranges to fluoro-
applications that require resistance to high tem-
sulfonyldifluoroacetyl fluoride. The anion
perature or strongly corrosive environments.
formed after addition of fluoride ion to this acid
fluoride gives a 2 : 1 adduct with HFPO [215].
Trade Names. Krytox (DuPont), Aflunox
Pyrolysis of the sodium salt over sodium carbon-
(SCM Specialty Chemicals), and Fomblin
ate gives the functional monomer [216].
(Montedison).

6.2. Perfluorovinyl Ethers

Perfluorovinyl ethers are comonomers used in

the preparation of melt-processable perfluoro-
plastics, fluorinated elastomers, and perfluoro-
polymers containing functional groups [210] (!
Fluoropolymers, Organic, Section 3.3.). The
ethers are synthesized by reaction of a fluorinated
466 Fluorine Compounds, Organic Vol. 15

Perfluorovinyl ethers can also be prepared by

deiodofluorination of iodine-containing ethers,
XRfCF2OCF2CF2I, where X is hydrogen, halo-
gen, CO2R, CONR2, SO2F, or PO(OR)2 (R ¼
alkyl) and Rf is a perfluoroalkyl group. Initially, The flammability behavior of the compound is
an organometallic derivative of the iodide is not significantly better than that of nonfluori-
formed by reaction with metals, such as Mg, Cu, nated anesthetics, and it behaves as a mutagen
Zn, Sn, or Sb. Heating in the absence of a proton in the Ames test [226]; therefore, the compound
source affords the vinyl ethers [217]. is not currently produced commercially.
2-Chloro-1-(difluoromethoxy)-1,1,2-trifluoro-
ethane [13838-16-9] [trade name: Ethrane (Ana-
6.3. Partially Fluorinated Ethers quest)], which is nonflammable, is prepared by
successive chlorination and fluorination of the
Partially fluorinated ethers are synthesized by hydrocarbon ether [227]. 1-Chloro-1-(difluoro-
several methods. Fluoroalkyl alkyl or fluoroalkyl methoxy)-2,2,2-trifluoroethane [26675-46-7]
aryl ethers are prepared from alkoxides or phen- [trade name: Forane (Anaquest)] is prepared in a
oxides and fluoroolefins [218]; for example, similar fashion [228]. Other possible anesthetics
1,1,2,2-tetrafluoro-1-methoxyethane [425-88-7] include 2,2-dichloro-1,1-difluoro-1-methox-
is prepared from tetrafluoroethylene and sodium yethane [76-38-0] [229] and 1,1,1,3,3,3-hexa-
methoxide – methanol. Higher perfluoroolefins fluoro-2-(fluoromethoxy)propane [28523-86-6]
can also be employed [219]. The methyl ethers [230].
are valuable intermediates, which can be con-
verted to acid fluorides with sulfur trioxide [220]
or other Lewis acids [221]. Primary and second- 7. Fluorinated Ketones and
ary perfluorinated alkoxides (see Chap. 5) are not Aldehydes
sufficiently nucleophilic to react with fluorinated
or nonfluorinated olefins. However, they react The carbonyl groups in partially or perfluorinated
with a variety of olefins in the presence of halo- ketones and aldehydes are electron deficient
gen to give ethers [222], e.g., owing to the inductive effect of the highly elec-
tronegative fluorine atom. Compared with their
hydrocarbon counterparts, fluorinated ketones
and aldehydes are, consequently, much more
reactive toward nucleophilic reagents. Stable
Perfluoroalkoxides react with benzyl halides addition compounds with water, alcohols, and
to give perfluoroalkyl benzyl ethers [223]. amines are commonly formed. By contrast, fluo-
In contrast to the physiological inertness of rinated ketones and aldehydes are relatively un-
perfluoroethers, some partially fluorinated ethers reactive toward electrophilic reagents. An ex-
act as inhalation anesthetics. Many cyclic and treme case is hexafluoroacetone, which is not
acyclic ethers containing varying amounts of protonated by the FSO3H – SbF5 superacid
fluorine, hydrogen, and sometimes other halo- [231].
gens have been evaluated as anesthetics in search A wide variety of fluoroalkyl ketones and
of the ideal combination of potency, volatility, aldehydes has been synthesized, often by special
lack of short- and long-term toxicity, and non- methods that are unique to polyfluorinated com-
flammability [224]. Some ethers have achieved pounds [232]. Of the many known examples, a
clinical significance (! Anesthetics, General, few fluorinated acetones, aldehydes, and 1,3-
Section 2.5.). diketones are of practical importance.
The first fluorinated ether anesthetic to be
introduced clinically was2,2,2-trifluoro-1-viny-
loxyethane [406-90-6] [trade name: Fluromar 7.1. Fluoro- and Chlorofluoroacetones
(Anaquest)] [225]. It is prepared by addition of
2 mol of trifluoroethanol to acetylene, followed Several fluoro- and chlorofluoroacetones (propa-
by thermolysis: nones) are listed in Table 14. Hexafluoroacetone
Vol. 15 Fluorine Compounds, Organic 467

Table 14. Molecular masses and boiling points of fluoro- and chlorofluoropropanones

Name CAS Formula Mr bp,  C

registry no. (101.3 kPa)

1,1,1-Trifluoro-2-propanone [421-50-1] CF3COCH3 112.05 21.5 – 22.5

1,1,3,3-Tetrafluoro-2-propanone [360-52-1] CHF2COCHF2 130.05 58
1,1,1,3,3,3-Hexafluoro-2-propanone [684-16-2] CF3COCF3 166.03
27.4
1-Chloro-1,1,3,3,3-pentafluoro-2-propanone [79-53-8] CClF2COCF3 182.48 7.8
1,3-Dichloro-1,1,3,3-tetrafluoro-2-propanone [127-21-9] CClF2COCClF2 198.93 45.2
1,1,3-Trichloro-1,3,3-trifluoro-2-propanone [79-52-7] CCl2FCOCClF2 215.38 84.5
1,1,3,3-Tetrachloro-1,3-difluoro-2-propanone [79-51-6] CCl2FCOCCl2F 231.83 123.9
1,1,1,3,3-Pentachloro-3-fluoro-2-propanone [2378-08-7] CCl3COCCl2F 248.28 163.7
1,1,1,3,3,3-Hexachloro-2-propanone [116-16-5] CCl3COCCl3 264.73 203.6

and, to a lesser extent, chloropentafluoroacetone plete exchange of chlorine in hexachloroacetone,

and sym-dichlorotetrafluoroacetone are commer- using hydrogen fluoride and a Cr3þ or Cr5þ
cially important. Hexafluoroacetone is manufac- catalyst [234], [235], [237]. Their properties and
tured by DuPont in the United States and by chemical reactivities are similar to those of hex-
Hoechst in the Federal Republic of Germany. afluoroacetone [238]. Like hexafluoroacetone,
The two chlorofluoroacetones were made in pi- chloropentafluoroacetone and sym-dichlorotetra-
lot-plant quantities by Allied in the 1960s [233], fluoroacetone form stable, acidic hydrates and
but their production has been discontinued. hemiacetals, e.g., CClF2COCF3 3 H2O [34202-
28-3], bp 105  C, and CClF2COCClF2 2 H2O
Hexafluoroacetone, 1,1,1,3,3,3-hexafluoro- [34202-29-4], bp 106  C. The hydrates are pow-
2-propanone, is made industrially by the vapor- erful solvents for acetal resins and various polar
phase reaction of hexachloroacetone with hydro- polymers [239], [240]. These chlorofluoroace-
gen fluoride in the presence of a chromium tones and some of their derivatives possess her-
catalyst [234], [235]. The rearrangement of hex- bicidal or fungicidal activity [241–243] and are
afluoropropylene oxide induced by Lewis acids useful intermediates for synthesizing repellants
[203] is an attractive new route that avoids the for textile fibers [244], [245], specialty polycar-
highly toxic sym-dichlorotetrafluoro- and chlor- bonates [246], [247], and inhalation anesthetics
opentafluoroacetones. A convenient laboratory [248].
synthesis uses hexafluoropropylene as a starting
material [236]: 1,1,1-Trifluoro-2-propanone can be pre-
pared in quantitative yield by the acid hydro-
lysis of ethyl trifluoroacetoacetate, the ethyl
ester of 4,4,4-trifluoro-3-oxobutanoic acid
[372-31-6], which is made by the alkali-pro-
moted condensation of ethyl trifluoroacetate
with ethyl acetate [249]. 1,1,1-Trifluoro-2-pro-
panone is easily made in the laboratory by the
Hexafluoroacetone is used mainly for the reaction of trifluoroacetic acid with methyl-
manufacture of the solvent hexafluoro-2-propa- magnesium iodide [250]. Its aryl hydrazone
nol and high-performance fluoropolymers. For derivatives show nematocidal and acaricidal
the properties, chemistry, and uses of hexafluor- activity [251].
oacetone, see ! Acetone.
1,1,3,3-Tetrafluoro-2-propanone is made
Chloropentafluoroacetone, 1-chloro- by the acid hydrolysis of the ethyl ester
1,1,3,3,3-pentafluoro-2-propanone [trade name: of 2,2,4,4-tetrafluoro-3-oxobutanoic acid,
5FK (Allied)] and sym-dichlorotetrafluoroace- CHF2COCF2 CO2C2H5 [249]. The ketone is used
tone, 1,3-dichloro-1,1,3,3-tetrafluoro-2-propa- as an intermediate in the synthesis of inhalation
none (4FK, Allied) can be made by the incom- anesthetics [252], [253].
468 Fluorine Compounds, Organic Vol. 15

Table 15. Molecular mass and boiling points of perchlorofluoroacetaldehydes

Name Formula Mr CAS registry no. bp,  C (101.3 kPa)

Trichloroacetaldehyde CCl3CHO 147.38 [75-87-6] 97.8

Dichlorofluoroacetaldehyde CCl2FCHO 130.93 [63034-44-6] 56
Chlorodifluoroacetaldehyde CClF2CHO 114.48 [811-96-1] 17.8
Trifluoroacetaldehyde CF3CHO 98.03 [75-90-1]
18 to
19a
*
At 99.7 kPa

7.2. Perhaloacetaldehydes fluoride) to give free trifluoroacetaldehyde. Hydro-

lysis of the inhalation anesthetic Halothane,
Perchlorfluoroacetaldehydes. Some phys- CF3CHBrCl, by a mixture of 65 % oleum, mercu-
ical properties of the perchlorofluoroacetalde- ric oxide, and silver oxide also produces trifluor-
hydes are shown in Table 15. Their chemical oacetaldehyde in high yield [257].
reactivities are similar to those of the per- Trifluoroacetaldehyde is commercially avail-
chlorofluoroacetones. able as its hydrate or methyl and ethyl hemiace-
Chlorodifluoroacetaldehyde and dichloro- tals, which liberate the pure aldehyde in polypho-
fluoroacetaldehyde can be prepared by the lithium sphoric acid at 150 – 180  C. A Hoechst process
aluminum hydride reduction of the corresponding for the manufacture of its hemiacetals involves
methyl chlorofluoroacetates [254], [255]. treating the product from the gas-phase fluorina-
tion of chloral with tetraalkoxyl silanes, or with
Trifluoroacetaldehyde (fluoral) and some alcohols and silicon tetrachloride. This process
of its derivatives have found practical importance avoids the need to isolate or handle free trifluor-
as monomers and intermediates for biologically oacetaldehyde [258], [259].
active compounds.

Properties. Trifluoroacetaldehyde is a col-

orless gas at ambient temperature and pressure.
Like hexafluoroacetone, it reacts with water to
form a stable, solid hydrate – 1,1-dihydroxy-
2,2,2-trifluoroethane [421-53-4], CF3CH(OH)2, Uses of Perhaloacetaldehydes. Certain
mp 69 – 70  C. It reacts in a manner similar to oximes [260] and hydrazones [251] of trifluor-
hexafluoroacetone with alcohols to give stable oacetaldehyde have insecticidal or acaricidal
hemiacetals: 2,2,2-trifluoro-1-methoxyethanol activity. Its hemiacetal, 2,2,2-trifluoro-1-meth-
[431-46-9], CF3CH(OH)OCH3, bp 96 – oxyethanol, has been used as a starting material
96.5  C; and 2,2,2-trifluoro-1-ethoxyethanol for the preparation of fluoroether inhalation an-
[433-27-2], CF3CH(OH)OC2H5, bp 104 – esthetics [261] (see Section 6.3), including iso-
105  C (99.3 kPa). Unlike hexafluoroacetone, it flurane, CF3CHClOCHF2 [262], and its isomer
readily homopolymerizes upon cationic, anionic, CF3CHFOCHClF [263], [264].
or free-radical initiation [254], [255]. The stereoregularity of perchlorofluoroacetal-
dehyde polymerizations has been an area of
Production. Several laboratory syntheses of active research, although no commercial uses of
trifluoroacetaldehyde have been developed, in- the polymers have yet appeared.
cluding reduction of trifluoroacetic acid and its Trifluoroacetaldehyde can be homopolymer-
alkyl esters, trifluoroacetic anhydride, and trifluor- ized to give insoluble crystalline, or soluble,
oacetyl chloride [256]. Trifluoroacetaldehyde can amorphous, polyoxymethylene polymers de-
be manufactured on a large scale by the reaction of pending upon the polymerization conditions
trichloroacetaldehyde (chloral) with hydrogen [254], [255]. This is in contrast with trichloroa-
fluoride in the presence of chromium catalysts cetaldehyde which can only be polymerized to
[235]. The product is a CF3CHO  HF complex, a crystalline, apparently isotactic polymer.
bp 38  C (133.3 kPa), which requires treatment Copolymers of perhaloacetaldehydes have been
with a hydrogen fluoride acceptor (e.g., sodium prepared [254], [255].
Vol. 15 Fluorine Compounds, Organic 469

7.3. Fluorinated 1,3-Diketones dione [123-54-6], CH3COCH2COCH3 (pKa ¼

8.9), CF3COCH2COCH3 (pKa ¼ 6.7), and
Fluorinated 1,3-diketones in which the two car- CF3COCH2COCF3 (pKa ¼ 4.6) [267]. Fluori-
bonyl groups are separated by a methylene or nated 1,3-diketones have a high enolic content,
methine group form complexes with a wide typically 92 – 100 %, in comparison with ca.
variety of metal ions. This property is the basis 80 % for 1,3-pentanedione. Their enolic protons
of their utility in chromatographic analysis of can be readily replaced by metals or metal salts to
metals, laser technology, NMR spectroscopy, form 1,3-diketonates of the type
and hydrometallurgical separations. The proper-
ties, preparation, and uses of fluorinated 1,3-
diketones and theirmetal complexes have been
extensively reviewed [265–267].

Properties and Production. Some physical

properties of the industrially important fluorinat-
ed 1,3-diketones are shown in Table 16. These Fluorinated 1,3-diketones form hydrates with
compounds are considerably more acidic than water and hemiketals with shorter alcohols. They
their nonfluorinated analogues, i.e., 1,3-pentane- are usually obtained by a Claisen condensation of

Table 16. Molecular masses and boiling points of fluorinated 1,3-diketones

Name CAS Formula Mr bp,  C (kPa)

registry no.

1,1,1-Trifluoro-2,4- [367-57-7] CF3COCH2COCH3 154.09 105 – 107 (101.3)

pentanedione
1,1,1,5,5,5-Hexafluoro- [1522-22-1] CF3COCH2COCF3 208.06 70 – 71 (101.3)
2,4-pentanedione
1,1,1-Trifluoro-5,5-di- [22767-90-4] CF3COCH2COC(CH3)3 196.17 138 – 141 (101.3)
methyl-2,4-hexanedione
1,1,1,2,2,3,3-Hepta- [17587-22-3] CF3CF2CF2COCH2COC(CH3)3 296.19 46 – 47 (0.67)
fluoro-7,7-dimethyl-4,6-
octanedione
4,4,4-Trifluoro-1-phenyl- [326-06-7] 216.16 224 (101.3)a
1,3-butanedione

4,4,4-Trifluoro-1-(2-thie- [326-91-0] 222.18 96 – 98 (1.07)b

nyl)-1,3-butanedione

3-(Trifluoroacetyl)cam- [51800-98-7] 248.25 100 – 101 (2.13)

phor, 1,7,7-trimethyl-3-
(trifluoroacetyl)-bicyclo
[2.2.1]heptan-2-one

3-(Heptafluorobutyryl) [51800-99-8] 348.26 60 – 70 (0.03)

camphor, 3-
(2,2,3,3,4,4,4-hepta-
fluoro-1-oxo-butyl)-bicy-
clo[2.2.1]heptan-2-one

a
mp 38 – 40  C.
b
mp 42 – 43  C.
470 Fluorine Compounds, Organic Vol. 15

a fluorinated carboxylic acid ester with a ketone, acid (2.66), difluoroacetic acid (1.24), and tri-
using a strong base such as a sodium alkoxide or fluoroacetic acid (0.23) compared to the pKa of
sodium hydride. 4.74 for acetic acid [270].

Uses. The 1,3-diketones RCOCH2COR0 (R ¼ Production. Trifluoroacetic acid has been

CF3, n-C3F7 and R0 ¼ t-C4H9, CF3) that form prepared by the electrochemical fluorination of
volatile, thermally and hydrolytically stable com- acetyl chloride or acetic anhydride in anhydrous
plexes are useful for liquid or gas chromatographic hydrogen fluoride using the Simons process (Sec-
analysis of metals. These diketones, especially tion 2.1) followed by hydrolysis of the resulting
1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octa- trifluoroacetyl fluoride. The yield is excellent
nedione are widely used for the extraction of metal (> 90 %) [271], [272]. The Phillips Petroleum
ions from aqueous solutions at variable pH [268]. electrochemical process (Section 2.1) employs
4,4,4-Trifluoromethyl- 1-(2-thienyl)-1,3-bu- acetyl fluoride as feed to produce trifluoroacetyl
tanedione is especially suited for the analysis of fluoride along with mono and difluoroacetyl fluo-
uranium and other radioactive elements. The ride [273]. Sulfur trioxide treatment of CF3CCl3,
tetrakis-chelates of 4,4,4-trifluoro-1-phenyl- obtained by isomerization of Freon 113,
1,3-butanedione with rare-earth elements are CF2ClCFCl2, yields CF3COCl [274]. The acid is
potential laser materials. purified by hydrolysis of the acyl halide with
The paramagnetic lanthanide complexes of alkali, followed by acidification and distillation.
heptafluoro-7,7-dimethyl-4,6-octanedione have
gained considerable importance as NMR shift Uses. Most uses of fluorinated acetic acids
reagents for simplifying the interpretation of are confined to trifluoroacetic acid, its anhydride,
complex NMR spectra [269]; the europium com- and its derivative, 1,1,1-trifluoroethanol. Mono-
plex is the most widely used. fluoroacetic acid derivatives (salts, esters,
amides, and alcohols) are toxic because they are
metabolized to fluorocitric acid which inhibits
respiration (see Section 13.5) [275]. w-Fluoro
acids of the formula F(CH2)nCOOH, where n is
an odd number, are extremely toxic, because of
degradation in vivo to monofluoroacetic acid and
The chiral-shift reagents derived from 3-hep- finally to fluorocitric acid [275]. Sodium mono-
tafluorobutyryl-(þ)- or -(
)-camphor and 3-tri- fluoroacetate has been used as a rodenticide, but
fluoroacetyl-(þ)- or -(
)-camphor are very use- is now banned.
ful for the NMR assay of enantiomeric purity in
solution [269].
8.1.2. Long-Chain Perfluorocarboxylic
Acids

Properties. The boiling points and densities

of straight-chain perfluorocarboxylic acids are
shown in Table 17.

Production. Long-chain perfluorocarbo-

8. Fluorinated Carboxylic Acids and xylic acids are prepared by the Simons electro-
Fluorinated Alkanesulfonic Acids chemical fluorination (see Section 2.1.) of the
corresponding acyl halide:
8.1. Fluorinated Carboxylic Acids

8.1.1. Fluorinated Acetic Acids

The acids are obtained by hydrolysis of the
Fluorination increases the strength of acetic acid perfluoroacyl fluoride, followed by distillation.
as seen in the pKa values of monofluoroacetic Some carbon – carbon bond scission occurs to
Vol. 15 Fluorine Compounds, Organic 471

Table 17. Boiling points and densities of perfluorocarboxylic acids

Acid CAS registry no. Formula bp,  C (kPa) d420 , g/cm3

Perfluoroacetic [76-05-1] CF3CO2H 72.4 1.489

Perfluoropropionic [422-64-0] C2F5CO2H 96 1.561
Perfluorobutyric [375-22-4] C3F7CO2H 120 1.651
Perfluorovaleric [2706-90-3] C4F9CO2H 130
Perfluorocaproic [307-24-4] C5F11CO2H 157 1.762
Perfluoroheptanoic [375-85-9] C6F13CO2H 175 1.792
Perfluorocaprylic [335-67-1] C7F15CO2H 189
Perfluorononanoic [375-95-1] C8F17CO2H 110 (2.1)
Perfluorocapric [335-76-2] C9F19CO2H 121 (2.0
Perfluoroundecanoic [2058-94-8] C10F21CO2H 245
Perfluorododecanoic [307-55-1] C11F23CO2H 270

form lower homologous acids along with inert Polyfluoroalkoxyacyl fluorides of the type
fluorocarbons and cyclic ethers. The acid yield
decreases with increasing chain length; for ex-
ample, perfluorobutyric acid yields are ca. 36 %
compared to ca. 20 % for the industrially impor- are prepared by the addition of perfluoroacyl
tant perfluorooctanoic acid [271], [272]. Trifluor- fluorides and hexafluoropropylene oxide cata-
oacetic acid is also prepared by the Phillips lyzed by alkali-metal fluorides [281]. Acids,
electrochemical method, employing a KF  HF salts, or esters are obtained by hydrolysis, neu-
molten salt electrolyte [273]. Acids with higher tralization, or esterification, respectively.
boiling points are not easily or efficiently pre- Addition reactions of perfluorodiacyl fluor-
pared by the Phillips process. ides with hexafluoropropylene oxide [282] give
Perfluorocarboxylic acids are also prepared ether-containing diacyl fluorides, such as
by nonelectrochemical methods. Treatment of
perfluoroalkyl iodides (RfI) with sulfur trioxide
[276] or chlorosulfonic acid [277] gives the
carboxylic acid in good yield. Another method
employs fuming sulfuric acid (oleum) [278]. where n is usually 2 – 4, and at least two units are
Another process involves the preparation of per- derived from hexafluoropropylene oxide (i.e.,
fluorotetrahydroalkyl iodides, RfCH2CH2I, ob- m  2) [282]. The addition reaction may occur
tained by the free-radical addition of ethylene to at one or both acyl groups of the starting diacyl
perfluoroalkyl iodides, followed by dehydroio- fluoride. Selectivity can be maintained by esteri-
dination and oxidation by dichromate [279] or fying one of the acyl fluoride groups. Thus,
ozonolysis [280]: CH3OCO(CF2)2COF, prepared by addition of
methanol to perfluoro-g-butyrolactone or per-
fluorosuccinyl fluoride, reacts with hexafluoro-
propylene oxide to give ester acyl fluorides of the
formula

This process produces carboxylic acids hav-

ing one more carbon atom than the starting
perfluoroalkyl iodide, in contrast to the electro-
chemical and oleum routes, which produce [283], [284]. The acyl halides are converted to
acids containing the same number of carbon acids or salts by hydrolysis or neutralization,
atoms as the original acyl halide or telomeric respectively.
iodide. In all processes utilizing fluorinated
iodine-containing telomers, it is important to Uses. Long-chain perfluoroalkanecarboxylic
find uses for the telomers and to recover the acids and their salts are surface-active chemicals
expensive iodine. (surfactants), which greatly reduce the surface
472 Fluorine Compounds, Organic Vol. 15

tension (surface energy) of water, aqueous solu- 8.1.4. Tetrafluoroethylene – Perfluorovinyl

tions, and organic liquids even at low concentra- Ether Copolymers with Carboxylic Acid
tions. These acids (C6– C12) and derivatives are Groups
used as wetting, dispersing, emulsifying, and
foaming agents. Ion-exchange membranes, used in fuel cells and
Ammonium perfluorooctanoate (FC-143, chloralkali production, are copolymers of tetra-
3M) is used as an emulsifier in the polymerization fluoroethylene and perfluorovinyl ethers that
of fluorinated monomers, especially tetrafluor- contain esters or other acid precursor groups
oethylene. It has exceptional chemical stability [287]. These membranes have excellent thermal
and lowers the surface tension of water to ca. and chemical resistance to hot concentrated
3 mN  m at 0.5 wt %. In contrast with hydrocar- alkali (up to 40 %).
bon emulsifiers, ammonium perfluorooctanoate
does not interfere with the emulsion polymeriza- Production. The vinyl ethers are prepared
tion of tetrafluoroethylene. by the reaction of hexafluoropropylene oxide and
methyl-3-fluorocarbonyl perfluoropropionate
Trade Names. Fluorad FC-26, 126, 143 [285], followed by pyrolysis to give:,
(3M), Fluorowet CP (Hoechst), RM 350, 370
(Rimar), and Surflon S-111P (Asahi Glass).

Copolymerization with tetrafluoroethylene

8.1.3. Fluorinated Dicarboxylic Acids
followed by saponification produces a polymer
with terminal carboxylic acid groups.
Properties. The boiling points and densities
of perfluorodicarboxylic acids are shown in Ta-
Trade Names. Flemion (Asahi Glass), Na-
ble 18.
fion (DuPont), Neosepta (Tokuyama Soda), and
Aciplex (Asahi Chemical).
Production. a,w-Perfluoroalkanedicarbo-
xylic acids are prepared by the electrochemical
method, followed by hydrolysis, acidification, 8.2. Fluorinated Alkanesulfonic Acids
and extraction. Other methods include the oxi-
dation of the appropriate chlorofluoroolefin or 8.2.1. Perfluoroalkanesulfonic Acids
perfluoroolefin. Perfluoroglutaric acid is pre-
pared from hexachlorocyclopentadiene by halo- Properties. The first member of the series,
gen exchange, followed by oxidation and acidi- trifluoromethanesulfonic acid, was reported in
fication [285]. Perfluoroadipic acid is prepared 1954 [288]. Perfluoroalkanesulfonic acids are
by an analogous method from hexachloroben- among the strongest acids known. Conductivity
zene [286]. The cyclic anhydrides from perfluor- measurements in acetic acid show that the acid
osuccinic and perfluoroglutaric acid are prepared strength of trifluoromethanesulfonic acid is com-
by dehydration of the acids with phosphorus parable to that of fluorosulfonic and perchloric
pentoxide. They are used to prepare the corre- acids [289]. Boiling points are listed in Table 19.
sponding alcohols by reduction. Because of their ability to lower surface energy,

Table 18. Physical properties of perfluorodicarboxylic acids

Acid CAS registry no. Formula mp,  C bp,  C (kPa)

Perfluoromalonic [1514-85-8] CF2(CO2H)2 117 – 118

Perfluorosuccinic [377-38-8] (CF2)2(CO2H)2 86 – 87 150 (2.0)
Perfluoroglutaric [376-73-8] (CF2)3(CO2H)2 88 134 – 138 (0.4)
Perfluoroadipic [336-08-3] (CF2)4(CO2H)2 132 – 134 138 (0.5)
Perfluorosuberic [678-45-5] (CF2)6(CO2H)2 154 – 158
Vol. 15 Fluorine Compounds, Organic 473

Table 19. Boiling points of perfluoroalkanesulfonic acids agents [292], [293]. The higher homologues
Acid Formula CAS registry no. 
bp, C (kPa)
exhibit good surfactant properties; the deriva-
tives of perfluorohexanesulfonyl fluoride are
CF3SO3H [1493-13-6] 60 (0.4) employed in fire extinguishing formulations.
C2F5SO3H [354-88-1] 81 (0.29)
n-C4F9SO3H [59933-66-3] 76 – 84 (0.13)
Useful derivatives containing the sulfonamido
n-C5F11SO3H [3872-25-1] 110 (0.67)* group can be prepared by reaction of the sulfonyl
n-C6F13SO3H [355-46-4] 95 (0.46) fluoride with a diamine, followed by quaterniza-
n-C8F17SO3H [1763-23-1] 133 (0.8) tion with alkylating agents such as methyl iodide
* n-C5F11SO3H  H2O
to give a cationic surfactant. As an example,
reaction of perfluorohexanesulfonyl fluoride
the longer-chain perfluoroalkanesulfonic acids with 3-dimethylaminopropylamine gives
and sulfonyl fluoride derivatives have found
utility as surface-active agents and water repel-
lents and for antisoiling treatment of textiles and
fabrics. The properties related to the low surface energy
of the perfluorooctanesulfonyl fluoride,
Production. Perfluoroalkanesulfonyl fluor- C8F17SO2F, are utilized in many derivatives. These
ides are usually made by the Simons electro- derivatives include alcohols and their acrylate and
chemical fluorination process (see Section 2.1), methacrylate esters; they are used as comonomers
in which a hydrocarbon sulfonyl fluoride is elec- in polymers that impart oil-, water-, and soil-
trolyzed in anhydrous hydrogen fluoride at nickel repellent properties to porous substrates such as
electrodes: paper and textiles [294], [295]. A typical reaction
sequence for the synthesis of a perfluoroalkane-
sulfonamide acrylate monomer is shown below:

The electrochemical yield is excellent for the

first member of the series and decreases progres-
sively with the increasing length of the carbon
chain; the yield for octanesulfonyl fluoride is ca.
40 % [271], [290]. Alkaline hydrolysis of per-
fluoroalkanesulfonyl fluorides gives the corre-
sponding salts, which when acidified and dis-
tilled from concentrated sulfuric acid yield the Perfluoroalkanesulfonamido alcohols are also
anhydrous sulfonic acids [288]. used as mold-release agents. Esterification with
A nonelectrochemical method for the prepa- phosphoric acid gives phosphate ester salts of the
ration of trifluoromethanesulfonic acid deriva- type
tives is shown below:

which are useful oil repellents for paper products

Alkaline hydrolysis, followed by acidification [296].
of the sulfonate salt, gives the acid [291].
Trade Names. Paper Treatment FC-807,
Uses. Short-chain perfluoroalkanesulfonyl 808 (3M), Textile Treatment Dic-Guard (Dai-
fluorides are used to prepare sulfonamides, which nippon Ink), and Scotchgard (3M).
are employed as plant growth regulators and
herbicides. Trifluoromethanesulfonic acid is
used as an esterification catalyst (FC-24, 3M), 8.2.2. Fluorinated Alkanedisulfonic Acids
and the lithium salt has been investigated as a fuel
cell and battery electrolyte (FC-124, 3M). Per- a,w-Perfluoroalkanedisulfonyl fluorides are
fluorobutanesulfonate salts are used as antistatic prepared by the electrochemical fluorination of
474 Fluorine Compounds, Organic Vol. 15

hydrocarbon disulfonyl fluorides. The corre- followed by copolymerization with tetrafluor-

sponding acids are prepared by alkaline hydro- oethylene gives polymers with fluorosulfonyl
lysis of the fluoride and acidification, or by side chains, which are hydrolyzed to sulfonate
aqueous permanganate oxidation of the disul- group side-chains [307].
fone, CH3SO2(CF2CF2)nSO2CH3 [297]. Distilla-
tion of the acids from phosphorus pentoxide
yields the cyclic anhydrides [298]. 9. Fluorinated Tertiary Amines
Physical Properties. Relative to their mo-
8.2.3. Tetrafluoroethylene – Perfluorovinyl lecular mass, perfluoroalkyl-tert-amines, like the
Ether Copolymers with Sulfonic Acid perfluoroethers, have low boiling points and low
Groups freezing or pour points, as shown in Table 20.
Low polarity and weak intermolecular forces are
Ion-exchange membranes are prepared by the responsible for other unusually low values for
copolymerization of tetrafluoroethylene with properties such as viscosity, solubility, heat of
perfluorovinyl ethers containing sulfonyl halide vaporization, refractive index, dielectric con-
groups, followed by hydrolysis to yield sulfonic stant, and surface tension [308]. Some perfluor-
acids. These membranes have excellent chemical obis(dialkylaminoalkyl) ethers have even lower
and thermal properties similar to those of ion- pour points and liquid ranges as broad as 250  C.
exchange membranes with terminal carboxylic These ethers exhibit increased internal flexibility
acid groups (see Section 8.1.4) [299–301]. through the combined effect of the nitrogen and
oxygen atoms [311].
Production. These ethers are prepared by
the condensation of hexafluoropropylene oxide Chemical Properties. Perfluorinated tert-
with fluorosulfonyldifluoroacetyl fluoride, amines are chemically inert and thermally stable
FSO2CF2COF, which is prepared from C2F4 and [308], [312]. The electron-withdrawing nature of
SO3, followed by isomerization [302], [303]. the perfluoroalkyl substituents deprives the ni-
Condensation of hexafluoropropylene oxide with trogen atom of its basic character and reactivity.
g-fluorosulfonylperfluoroalkyl carbonyl fluor- Fluorinated tert-amines do not form salts or
ides, FSO2(CF2)nCOF (prepared by electro- complexes with strong acids and are not attacked
chemical fluorination of the respective aliphatic by most oxidizing or reducing agents. With
sulfone [304], [305]) gives perfluoroether fluor- aluminum chloride they form chlorinated imines
osulfonyl acyl fluorides, e.g., [306] [313]. Because of their nonpolar nature, fluori-
nated tert-amines are poor solvents and are im-
miscible with water and alcohols [308]. Gases
such as oxygen, nitrogen, and carbon dioxide
have unusually high solubility in perfluorinated
Subsequent conversion to the vinyl ether
tert-amines. For example, perfluorotributyla-
mine dissolves 40 vol % of oxygen at ambient
conditions and has been used in artificial blood as
an effective oxygen-transport medium [313].

Table 20. Physical properties of fluorinated tert-amines [308–310]

Compound CAS registry no. Formula Mr bp,  C Pour point,  C d425

Perfluorotrimethylamine [432-03-1] N(CF3)3 221
11

Perfluorotriethylamine [359-70-6] N(C2F5)3 371 69 1.74
Perfluorotripropylamine [338-83-0] N(C3F7)3 521 130
52 1.82
Perfluorotributylamine [311-89-7] N(C4F9)3 671 178
50 1.88
Perfluorotriamylamine [338-84-1] N(C5F11)3 821 215
25 1.93
Perfluorotrihexylamine [432-08-6] N(C6F13)3 971 256 33* 1.90**
*
Freezing point.
** 35
d4
Vol. 15 Fluorine Compounds, Organic 475

Production. Electrochemical fluorination The perfluoroalkyl substituents of aromatic com-

via the Simons process (see Section 2.1) is the pounds are meta-directing; this influence can, of
preferred route to fluorinated tertiary alkyla- cause, be overcome by a stronger ortho- or para-
mines. The hydrogen atoms are completely re- directing substituent. These compounds are usu-
placed by fluorine atoms. Perfluorotributyla- ally prepared from iodoperfluoroalkanes and ha-
mine, for example, is synthesized as follows:, logenated aromatic compounds in the presence of
a copper catalyst [315–317]. Except for the ben-
zotrifluorides, aromatic compounds with fluori-
nated side-chains have only scientific interest
The crude product contains a significant [318]. Araliphatic compounds with one or two
amount of perfluorinated isomers and cleavage trifluoromethyl substituents on the benzene ring
products because of molecular rearrangement gained commercial importance in the early 1930s
during electrolysis; it is purified by fractional for two reasons: 1) the recognition of the advan-
distillation and treatment with base. tageous properties of aromatic dyes with CF3
substituents, and 2) the development of an eco-
Uses. The combination of unusual physical nomical production process [4]. Since then, their
and chemical properties, excellent dielectric importance in the production of dyes, pharma-
properties, nonflammability, and lack of toxicity ceuticals, and pesticides has increased.
make the perfluorinated tert-amines useful for
many fluid applications that involve direct con-
tact with sensitive materials [308], [313]. The 10.1. Properties
electronic industry relies heavily on these fluids
in reliability testing of electronic components, as The physical properties of benzotrifluorides are
direct-contact coolants for integrated circuits, shown in Table 21.
and as heating media in vapor-phase reflow If no other substituents are present in the
soldering. Perfluorinated tributylamine, triamy- benzene ring, the trifluoromethyl group is ther-
lamine, and trihexylamine are the main consti- mally stable up to 350  C and resistant to bases
tuents of Fluorinert electronic liquids FC-43, FC- up to 130  C. It is inert toward reducing agents
70, and FC-71 (3M). [319], [320] and inhibits oxidation of the benzene
Information on the preparation and utility of ring. However, in the presence of aluminum
other nitrogen-containing fluoroaliphatic com- chloride the trifluoromethyl group undergoes
pounds can be found in the general references chlorolysis to produce a trichloromethyl group
[1–15]. [321], and acid hydrolysis forms a carboxy group
[322]. Substituents such as amino or hydroxyl
groups destabilize the trifluoromethyl group
10. Aromatic Compounds with [323].
Fluorinated Side-Chains The characteristic reaction of benzotrifluor-
ides is electrophilic substitution of the benzene
The first aromatic compound with a fluorinated ring; chlorination and nitration are commercially
side-chain, benzotrifluoride [98-08-8], trifluoro- important. Chlorination of benzotrifluoride at
methylbenzene, was synthesized in 1898 [314]. 65  C with FeCl3 as a catalyst yields 83 %

Table 21. Physical properties of benzotrifluorides

Compound CAS registry Empirical Mr bp,  C d4 q (q,  C) nDq (q,  C)

number formula

Benzotrifluoride [98-08-8] C7H5F3 146.11 102.03 1.188 (20) 1.4114 (25)

2-Chlorobenzotrifluoride [88-16-4] C7H4ClF3 180.56 152.5 1.367 (20) 1.4550 (20)
4-Chlorobenzotrifluoride [98-56-6] C7H4ClF3 180.56 140 1.35 (15) 1.4444 (25)
2,4-Dichlorobenzotrifluoride [320-60-5] C7H3Cl2F3 215.0 117 – 118 1.377 (20) 1.4802 (20)
1,3-Bis(trifluoromethyl)benzene [402-31-3] C8H4F6 214.11 116.1 1.379 (25) 1.3791 (20)
1,4-Bis(trifluoromethyl)benzene [433-19-2] C8H4F6 214.11 117.1 1.381 (25) 1.3792 (20)
3-Trifluoromethylbenzoyl fluoride [328-99-4] C8H4F4O 192.11 159 – 163 1.4350 (20)
476 Fluorine Compounds, Organic Vol. 15

3-chlorobenzotrifluoride [98-15-7] [324]; chlo-

rination of 4-chlorobenzotrifluoride gives 3,4-
dichlorobenzotrifluoride [328-84-7]. Nitration of
benzotrifluoride results in a 6 : 3 : 91 mixture of
2-nitro- [384-22-5], 4-nitro- [402-54-0], and 3- This reaction can be carried out as a batch
nitrobenzotrifluoride [98-46-4] [325]. Other process in autoclaves or continuously in a series
commercially important nitrations are the con- of autoclaves [329] (Fig. 3) or tubular reactors
version of 2-chlorobenzotrifluoride [88-16-4] to [330]. Typical conditions for the production of
2-chloro-5-nitrobenzotrifluoride [777-37-7] and benzotrifluoride are a temperature of 80 –
the conversion of 4-chlorobenzotrifluoride to 110  C, pressure of 1.2 – 1.4 MPa, and a molar
yield 99 % 4-chloro-3-nitrobenzotrifluoride ratio of HF : benzotrichloride of 4 : 1. A yield of
[121-17-5] or 4-chloro-3,5-dinitrobenzotrifluor- 70 % is obtained within 3 – 4 h [331]. In contin-
ide [393-75-9] [326]. These derivatives are re- uous processing, a yield of over 90 % is obtained
duced to amines or are further processed. in a nickel flow tube with a residence time of 1 h
at 90 – 130  C and at 3 – 5 MPa [332]. Yields
are increased by using additives such as hexam-
10.2. Production ethylenetetraamine [333] or by employing chlo-
rine – fluorine exchange in the gas phase in the
Benzotrifluorides are prepared on a laboratory presence of a transition metal – aluminum oxide
scale by the reaction of aromatic compounds with catalyst [334]. Corrosion is reduced by lowering
iodotrifluoromethane [315]; by the reaction of the reaction temperature (< 60  C) and adding
aromatic carboxylic acids and their derivatives iron or iron compounds [335], [336].
with sulfur tetrafluoride [51–53]; or by chlo- This method is used to produce benzotrifluoride,
rine – fluorine exchange in trichloromethyl aro- 2-chlorobenzotrifluoride, 4-chlorobenzotrifluor-
matic compounds with metal fluorides [327]. ide, 2,4-dichlorobenzotrifluoride, 1,3-bis(trifluoro-
In the commercial process, known since 1931, methyl)benzene, 1,4-bis(trifluoromethyl)benzene,
chlorine is exchanged for fluorine with use of 3-(trifluoromethyl)benzoyl fluoride, and 4-(tri-
anhydrous hydrogen fluoride in the presence or fluoromethyl)benzoyl fluoride [368-94-5] from the
absence of catalyst [328]: corresponding trichloromethyl compounds.

Figure 3. Production of benzotrifluorides in a series of autoclaves [329]

a) Reactor; b) Pressure distillation column; c) Separator; d) Product distillation column; e) Product storage tank
Vol. 15 Fluorine Compounds, Organic 477

The trifluoromethyl group can also be intro- sant fluoxetine [54910-89-3], the muscle relaxant
duced into aromatic compounds by the Friedel – flumetramide [7125-73-7], the appetite depres-
Crafts reaction with carbon tetrachloride in the sants fenfluramine [458-24-2] and fludorex
presence of hydrogen fluoride [337]. [15221-81-5], and the tranquilizers trifluproma-
zine [146-54-3] and fluphenazine [69-23-8].
Bendroflumethiazide [73-48-3] is an effective
diuretic and antihypertensive agent.

Pesticides. Benzotrifluorides are also im-

portant in the production of pesticides [342]. The
key intermediate, 4-chloro-3,5-dinitrobenzotri-
fluoride [393-75-9], is obtained by dinitration of
4-chlorobenzotrifluoride. Reaction with second-
10.3. Uses ary amines gives trifluralin [1582-09-8], proflur-
alin [26399-36-0], and benfluralin [1861-40-1].
Benzotrifluoride and 4-chlorobenzotrifluoride 4-Chlorobenzotrifluoride and 3,4-dichlo-roben-
are key intermediates for the synthesis of dyes, zotrifluoride are intermediates for herbicides
pharmaceuticals, and pesticides. with a diphenyl ether structure – fluorodifen
[15457-05-3] and acifluorfen [50594-66-6] and
Dyes. Trifluoromethyl aromatic compounds the insecticide fluvalinate [69409-94-5]. 3-Ami-
were first used in dyes [4] and are still important nobenzotrifluoride [98-16-8] is obtained from
intermediates for azo, anthraquinone, and triphe- benzotrifluoride by nitration and hydrogenation.
nylmethane dyes. The strongly electronegative It is used to make the selective herbicide fluo-
trifluoromethyl group improves color clarity and meturon [2164-17-2] or is used as a component of
fastness to light and washing; it also shifts light the herbicide norflurazon [27314-13-2].
absorption to the visible and ultraviolet ranges.
Some of these dye intermediates [338] for the
production of anthraquinone and azo dyes
(Naphtol AS, Hoechst AG) and azo pigments
11. Ring-Fluorinated Aromatic,
are still used, especially for polyesters and poly- Heterocyclic, and Polycyclic
amides. These compounds include 2-aminoben- Compounds
zotrifluoride [88-17-5] for C.I. Pigment Yellow
154 [63661-02-9]; 3-amino-4-chlorobenzotri- The compounds discussed in this chapter contain
fluoride [121-50-6] for C.I. Pigment Orange 60 one or more fluorine atoms that are directly
[68399-99-5]; 3-(trifluoromethyl)benzoyl fluo- attached to aromatic, heterocyclic, or polycyclic
ride for Indanthren Blue CLB [6492-78-0] rings. Unlike chlorination and bromination,
(BASF) as well as 2-amino-5-chlorobenzotri- fluorination with elemental fluorine is rarely
fluoride [445-03-4], 3,5-bis(trifluoromethyl)ani- employed for their production because its vio-
line [328-74-5], and 3-amino-4-ethylsulfonyl- lence produces many side reactions (ring-open-
benzotrifluoride [382-85-4]. ing, coupling, polymerization, and charring).
Therefore, indirect methods are used, distribut-
Pharmaceuticals. The trifluoromethyl sub- ing the reaction enthalpy over several controlla-
stituent is highly lipophilic; it increases the lipid ble steps [318].
solubility of pharmaceuticals and thus acceler- Diazonium salts are suitable for introducing
ates their absorption and transport in a living up to three fluorine atoms per ring. Chlorine –
organism [339], [340]. In some cases, introduc- fluorine exchange (halogen exchange, Halex pro-
tion of the CF3 group also increases drug effec- cess) with alkali – metal fluorides is suitable in
tiveness and reduces undesirable side effects; cases where activating substituents are present.
therefore, benzotrifluorides are used in the Ring-fluorinated aromatic, heterocyclic, and
synthesis of many pharmaceuticals [341]. These polycyclic compounds are predominantly used
include the analgesics flufenamic acid [530-78- as intermediates for pharmaceuticals, pesti-
9] and niflumic acid [4394-00-7], the antidepres- cides, dyes and other products. The exceptional
478 Fluorine Compounds, Organic Vol. 15

properties of fluorinated cyclic compounds (bio- The reactivity of fluorine in benzene deriva-
activity spectrum, effectiveness, and solublity) tives depends on the nature of the other ring
justify the higher production costs compared to substituents. Nucleophilic substitution occurs
those of fluorine-free compounds. only where activating groups (e.g. nitro) are
present in the ortho or para position. In other
cases, e.g., with 1-bromo-4-fluorobenzene [460-
11.1. Mono- and Difluoroaromatic 00-4], the carbon – fluorine bond is stronger;
Compounds hydrolysis gives 4-fluorophenol [371-41-5]
[344], [345].
Research on ring-substituted aromatic fluorine
compounds began in 1870. The fluorine atom
attached to the benzene ring is strongly electro- 11.1.2. Production
negative; it preferentially directs new substitu-
ents into the para position and rarely, if ever, into Among the published processes for the produc-
the ortho position [343]. Important aspects, es- tion of mono- or difluoroaromatic compounds,
pecially for biological applications, are (1) the ring fluorination with dilute fluorine or fluorinat-
influence of the strongly electronegative fluorine ing agents such as xenon difluoride [346–349]
substituent on adjacent groups, (2) its participa- does not follow a clear course (i.e., without side
tion in the resonance system of the aromatic reactions) and has no commercial value. Fluor-
compound by returning electron density, and obenzene itself can be prepared by pyrolysis of
(3) the simulation of hydrogen or hydroxy sub- chlorodifluoromethane or chlorotrifluoroethy-
stituents that is due to the similarity in space lene in the presence of cyclodipentadiene at
requirements and has led to the synthesis of a 300 – 800  C [350] and by anodic fluorination
series of monofluoro aromatic enzyme inhibitors. of benzene with tetraethylammonium fluoride in
The varying lability of the carbon – fluorine acetonitrile [351]. Promising methods are the
bond in mono- and difluoro aromatic compounds decarbonylation of benzoyl fluorides in the pres-
has been exploited to prepare indicators and ence of tris(triphenylphosphine)rhodium(I) chlo-
analytical reagents, especially for biogenic and ride in boiling xylene [352] and the thermal
metabolic studies. decarboxylation of aryl fluoroformates [353].

Diazotization. Aromatic compounds con-

11.1.1. Properties taining one or two fluorine substituents are pro-
duced commercially by diazotization of aromatic
Replacement of aromatic hydrogen by fluorine amines and decomposition of the resulting dia-
has only a minor effect on boiling points. Density zonium fluorides [318], [354]. In one process,
increases, whereas refractive index and surface aromatic amines are diazotized with dry sodium
tension decrease. Physical constants are shown in nitrite in anhydrous hydrogen fluoride at 0 –
Table 22. 20  C [355] (see Fig.4).

Table 22. Physical properties of ring-fluorinated aromatic compounds

Compound CAS registry Empirical Mr bp,  C d4 q (q,  C) nDq (q,  C)

number formula (101.3 kPa)

Fluorobenzene [462-06-6] C6H5F 96.1 84.7 1.083 (25) 1.4629 (25)

2-Fluorotoluene [95-52-3] C7H7F 110.13 113 – 114 1.003 (21) 1.4727 (20)
3-Fluorotoluene [352-70-5] C7H7F 110.13 115 0.991 (25) 1.4691 (20)
4-Fluorotoluene [352-32-9] C7H7F 110.13 116 0.991 (25) 1.4688 (20)
4,40 -Difluorodiphenylmethane [457-68-1] C13H10F2 204.22 263.5* 1.145 (20) 1.5362 (20)
1,3-Difluorobenzene [372-18-9] C6H4F2 114.09 82 – 83 1.1572 (20) 1.4410 (20)
1,4-Difluorobenzene [540-36-3] C6H4F2 114.09 88 – 89 1.176 (20) 1.4421 (20)
*
At 100.5 kPa
Vol. 15 Fluorine Compounds, Organic 479

Figure 4. Production of fluoroaromatics by the HF diazotization – dediazoniation method [354]

a) Diazotation reactor; b) Dediazoniation vessel; c) Condenser; d) Separator; e) Distillation column; f) HF purification column;
g) Product storage tank

The temperature is increased to 30 – 120  C, This thermal decomposition must be strictly

and the formed diazonium fluorides decompose controlled, especially when nitro substituents are
to form fluoroaromatic compounds. A yield of present, to avoid an explosion. Diazonium tetra-
over 90 % of mono- and difluorinated com- fluoroborates usually decompose at a higher
pounds is obtainable. Yields of ca. 81 % are temperature than the corresponding diazonium
reported for batch operations on a 1-t scale. fluorides. The Balz – Schiemann process has
In a continuous process the three exothermic rarely been used on a large scale because of the
steps are controlled by separation; i.e., hydro- difficulties in handling diazonium tetrafluorobo-
fluorination of the aromatic amine, diazotization, rates. However, it is convenient as a laboratory
and thermal decomposition [356]. This permits process because it does not require specialized
safe operation on a large scale. Diazotization apparatus. A plant of several 100 t/a has been
with nitrosyl chloride [357] and nitrosyl fluo- reported [361].
ride – HF complexes [358] is also possible. Pro- A large number of fluoroaromatic compounds
blems associated with these processes are hydro- have been produced by using the two diazotiza-
gen fluoride recovery and waste gas treatment. tion routes described [327], [362]. Those of
In another method (Balz – Schiemann reac- commercial interest include fluorobenzene from
tion), water-insoluble diazonium fluoroborates aniline; 2-, 3-, and 4-fluorotoluene from the appro-
are prepared by diazotization of aromatic amines priate toluidines; 4,40 -difluorodiphenylmethane
with sodium nitrite in the presence of 40 % from 4,40 -diaminodiphenylmethane; 1,3-difluoro-
fluoroboric acid or sodium or ammonium tetra- benzene from m-phenylenediamine; and 1,4-di-
fluoroborate in HCl [327], [359]. After filtration fluorobenzene from p-phenylenediamine.
the diazonium salts are dried and thermolyzed The reaction sequence of nitration, reduction,
[360] (Fig. 5): diazotization, and thermal decomposition can be
480 Fluorine Compounds, Organic Vol. 15

Figure 5. Production of fluoroarmatics by the Balz – Schiemann method

a) Stirred diazotization reactor; b) Storage for 50 % HBF4; c) Filter; d) Drier; e) Mixer; f) Dediazoniation reactor; g) Condenser;
h) Separation column; i) Product distillation column; k) Product storage tank

repeated to introduce up to four fluorine atoms

into the benzene ring.

Chlorine – Fluorine Exchange. Of similar

commercial importance to diazotization is the
replacement of activated chlorine atoms with the
aid of alkali-metal fluorides [318], [354]. The
usual activating groups are ortho and para nitro, Phase-transfer catalysts are sometimes used
cyano, and trifluoromethyl groups [363]. Apro- [364]. The effectiveness of the fluoride source
tic – polar solvents are preferred, such as di- decreases in the order CsF > KF > NaF > LiF.
methylformamide, dimethylacetamide, dimethyl In commercial batch or semicontinuous
sulfoxide, N-methyl-2-pyrrolidone, and tetrahy- operations, the Halex process (Fig. 6), potassium
drothiophene-1,1-dioxide (sulfolane). fluoride and the activated chloroaromatic compound

Figure 6. Flow sheet of the Halex process for the manufacture of fluoronitrobenzene [363]
a) Reactor; b) Distillation column; c) Condenser; d) Drier; e) Product distillation column; f) Product storage tank; g) Condenser
for off-gas
Vol. 15 Fluorine Compounds, Organic 481

are thoroughly mixed (1 : 1) with a large volume of benzuron [35367-38-5] (made from 2,6-difluor-
an aprotic solvent (dimethyl sulfoxide or sulfolane) obenzonitrile), the herbicides flamprop [58677-
and are heated to 150 – 250  C [363], [365]. The 63-3] and fluoronitrofen [13738-63-1], and the
reaction is 90 % complete within 48 h. Removal of fungicides nuarimol [63284-71-9] and flurimid
KCl and distillation of the product present no [41205-21-4].
difficulty, but efficient solvent recovery is important 4,40 -Difluorobenzophenone [345-92-6], a
to reduce costs. starting material for aromatic polycondensates,
Cost is also reduced by regenerating the potas- is produced by oxidation of 4,40 -difluorodiphe-
sium fluoride by treating the KCl with HF [366]. nylmethane, which is obtained by diazotization
The Halex process has the clear advantage of of the corresponding diamine. 4,40 -Difluoroben-
readily accessible raw materials, simplicity of a zophenone undergoes polycondensation with hy-
single-step procedure, and structural specificity. droquinone, yielding a polyetherether ketone
Certain products are accessible in no other way. (PEEK) resin, a thermoplastic. 4-Fluoroaniline
The following commercially important inter- [371-40-4], 4-fluorobenzaldehyde [459-57-4],
mediates are obtained by the Halex process: 1- and 4-fluorobenzoic acid [456-22-4] are inter-
fluoro-2-nitrobenzene [1493-27-2] and 1-fluoro- mediates for liquid crystal polymers [369].
4-nitrobenzene [350-46-9] from the correspond- Aromatic compounds with reactive fluorine
ing chloronitrobenzenes;1-chloro-2-fluoro-5-ni- substituents are used for the characterization of
trobenzene [350-30-1] from 1,2-dichloro-4-ni- amino acids (Sanger’s reagent, 1-fluoro-2,4-di-
trobenzene;1-chloro-4-fluoro-3-nitrobenzene nitrobenzene [70-34-8]), the immobilization of
[345-18-6] from 1,4-dichloro-2-nitrobenzene;1- enzymes (4-fluoro-3-nitrophenylazide [28166-
fluoro-2,4-dinitrobenzene [70-34-8] from 1- 06-5]), and peptide cross-linkage (1,5-difluoro-
chloro-2,4-dinitrobenzene;5-fluoro-2-nitroben- 2,4-dinitrobenzene [327-92-4]).
zotrifluoride [393-09-9] from 5-chloro-2-nitro- Aromatic fluorine compounds have been de-
benzotrifluoride [118-83-2]; 1,3-difluoro-4-ni- veloped for medical applications, such as 19F-
trobenzene [446-35-5] from 1,3-dichloro-4-ni- magnetic resonance imaging (MRI) and in 18F-
trobenzene; and 2,6-difluorobenzonitrile [1897- positron emission tomography (PET) [370].
52-5] from 2,6-dichlorobenzonitrile. These inter-
mediates are mostly used for substituted anilines
and compounds with carbonyl and carboxy 11.2. Highly Fluorinated Aromatic
functions. Compounds

Compounds in which an aromatic ring is substi-

11.1.3. Uses tuted by three to five fluorine atoms have little
commercial importance. 1,2,4-Trifluoroben-
Fluorobenzene, difluorobenzenes, and their de- zene [367-23-7], bp 88  C, and 1,3,5-trifluoro-
rivatives are used widely in the synthesis of benzene [372-38-3], bp 75.5  C, are produced
pharmaceuticals and pesticides, and as fine che- by the Balz – Schiemann reaction (see Section
micals. Fluoroaromatics have played a special 11.1.2) from 2,4-difluoroaniline [367-25-9] and
role in the development of drugs that act on the 3,5-difluoroaniline [372-39-4], respectively.
central nervous system [367]. The increase in 1,3,5-Tricyano-2,4,6-trifluorobenzene [3638-
lipid solubility due to fluorine atoms facilitates 97-9], mp 148 – 150  C, is used as an interme-
the absorption and transport of drugs through the diate for pesticides; it is obtained by chlorine –
blood – brain barrier into the central nervous fluorine exchange from 1,3,5-tricyano-2,4,6-tri-
system. chlorobenzene [371].
Fluorobenzene derivatives are used in neuro- 1,2,3,5-Tetrafluorobenzene [2367-82-0], bp
leptics such as haloperidol [52-86-8], tranquili- 83  C, is obtained by the Balz – Schiemann
zers such as fluspirilene [1841-19-6], sedatives reaction from 2,3,5-trifluoroaniline [363-80-4],
such as flurazepam [17617-23-1], and antide- and 1,2,4,5-tetrafluorobenzene [327-54-8], bp
pressants such as fluroxamin [54739-18-3]. 90  C, from 2,4,5-trifluoroaniline [57491-45-
Pesticidal [342] and fungicidal fluorobenzene 9]. 1,2,3,4-Tetrafluorobenzene [551-62-2], bp
derivatives [368] include the insecticide diflu- 95  C, pentafluorobenzene [363-72-4], bp
482 Fluorine Compounds, Organic Vol. 15

85  C, and hexafluorobenzene are produced by The CoF2 formed in this reaction is fluorinated
the CoF3 method (see Section 11.3). to CoF3 with elemental fluorine, and reused. The
The Halex process (Section 11.1.2) is used organic products are heated with an alkali-metal
commercially to produce 1,4-dicyano-2,3,5,6- hydroxide to form a mixture of polyfluorocyclo-
tetrafluorobenzene [1835-49-0], mp 197 – hexenes and polyfluorocyclohexadienes. These
199  C, from the corresponding tetrachloro de- products are aromatized by passage over iron or
rivative [372]. This compound is used as a iron compounds at 400 – 600  C to give hexa-
monomer for thermostable polymers. fluorobenzene, pentafluorobenzene, and tetra-
fluorobenzenes. Octafluorotoluene [434-64-0]
and the three perfluoroxylenes are also obtained
11.3. Perhaloaromatic Compounds by this method.
The disadvantages of this process are the
Hexafluorobenzene [392-56-3], bp 80.3  C, has technological difficulties and the low utilization
been thoroughly investigated [373]. Nucleophilic of fluorine, of which a large part is converted to
substitution produces pentafluoroaromatic com- hydrogen fluoride and alkali-metal fluorides. As
pounds such as a consequence, aromatic fluorine compounds
containing other halogens are currently produced
bromopentafluorobenzene [344-04-7], bp by the Halex method (Section 11.1.2). Reaction
135.6  C of hexachlorobenzene [365] with potassium fluo-
pentafluorophenol [771-56-2], bp 117 – 118  C ride at 450  C and 1.03 MPa gives a yield of
pentafluoroaniline [771-60-8], bp 153  C 21 % hexafluorobenzene together with chloro-
pentafluorobenzene [771-61-9], bp 143  C pentafluorobenzene [344-07-0] (20 %), 1,3-di-
pentafluorotoluene [771-56-2], bp 117  C chloro-2,4,5,6-tetrafluorobenzene [1198-61-4]
pentafluorobenzaldehyde [653-37-2], bp 164 – (14 %), and 1,3,5-trichloro-2,4,6-trifluoroben-
166  C zene [319-88-0] (12 %).
pentafluorobenzoic acid [602-94-8], bp 220  C

Production. Hexafluorobenzene was first

produced in 1955 by pyrolysis of tribromofluor- The yield of hexafluorobenzene can be in-
omethane [353-54-8] in a platinum tube at creased by recycling the other products for fur-
640  C under atmospheric pressure [374]:, ther reaction with potassium fluoride. A yield of
42 % hexafluorobenzene is obtained from chlor-
opentafluorobenzene with the more reactive, but
more expensive, cesium fluoride [377].
Of greater commercial interest is the pyrolysis Hexachlorobenzene reacts with KF in aprotic
of an equimolar mixture of dichlorofluoro- solvents such as dimethylformamide, dimethyl
methane [75-43-40] and chlorofluoromethane sulfoxide, N-methyl-2-pyrrolidone, and sulfo-
[593-70-4] at 600 – 800  C [375]: lane to give not hexafluorobenzene, but the
above-mentioned mixed products. The reaction
temperature is 150 – 250  C and the residence
time 5 – 36 h. Detailed discussions of the pro-
For many years a commercial multistep pro- cess are given in [363], [365].
cess employed CoF3 as the fluorinating agent
[376]. For example, at 150  C benzene gives a Uses. Hexafluorobenzene has been investi-
mixture of cyclohexanes containing 8 – 11 fluo- gated as an inhalation anesthetic in veterinary
rine atoms. medicine [378] and as a working fluid in Ran-
kine-cycle engines for temperatures above
350  C [379]. Derivatives such as pentafluoro-
benzaldehyde or pentafluorophenyl dimethylsi-
lyl ether are used in the chromatographic analysis
of steroids [380] and catecholamines [381], and
as intermediates for the production of liquid
Vol. 15 Fluorine Compounds, Organic 483

crystal polymers [382]. Pentafluorophenoxy per- mixtures with hexafluorobenzene is used as the
fluorovinyl ethers are cross-linking comonomers working fluid in Rankine-cycle engines up to
for perfluorinated elastomers [383]. 382  C [379].

11.4. Fluorinated Heterocyclic and 11.4.2. Trifluoromethylpyridines

Polycyclic Compounds
2-Trifluoromethyl- [368-48-9], 3-trifluoro-
Fluorinated pyridines, pyrimidines, and triazines methyl- [3796-23-4], and 4-trifluoromethylpyr-
are heterocycles with commercial importance. idine [3796-24-5] can be obtained by the reaction
Only some representative polycyclic fluorine of picolinic, nicotinic, or isonicotinic acid, re-
compounds are discussed as examples. spectively, with sulfur tetrafluoride [394]. Com-
mercial processes use side-chain chlorination of
the methylpyridines followed by chlorine – fluo-
11.4.1. Ring-Fluorinated Pyridines rine exchange with antimony chlorofluorides or
anhydrous hydrogen fluoride [395]. 2-Chloro-5-
Introduction of fluorine into the pyridine ring trifluoromethylpyridine, bp 190  C, is produced
reduces the basicity of the latter [384]. 2-Fluor- commercially from 2-chloro-5-trichloromethyl-
opyridine [372-48-5], bp 126  C (100.4 kPa), has pyridine and hydrogen fluoride at 180 – 200  C
a labile fluorine substituent. It is produced in 74 % and at a pressure of 3 – 4.5 MPa. It is an inter-
yield by reaction of 2-chloropyridine with potas- mediate for the synthesis of the selective herbi-
sium bifluoride at 315  C in 4 h [385]. 3-Fluor- cide fluazifop [69335-91-7], [396].
opyridine [372-47-4], bp 105 – 107  C
(100.3 kPa), is produced in 50 % yield from 3-
aminopyridine using the Balz – Schiemann pro- 11.4.3. Fluoropyrimidines
cess (see Diazotization). 4-Fluoropyridine [694-
52-0], bp 108  C (100 kPa) is produced in 54 % Certain fluoropyrimidines have gained commer-
yield by diazotization of 4-aminopyridine in an- cial importance [397]. 5-Fluoropyrimidines are
hydrous hydrogen fluoride [386]. employed in cancer chemotherapy; their bio-
2,4-Difluoropyridine [34941-90-7], bp 104 – chemistry and pharmacology have been inten-
105  C, is obtained by the Halex process (see sively studied [398]. 5-Fluorouracil [51-21-8] is
Chlorine – Fluorine Exchange) from 2,4-di- obtained in a 80 – 92 % yield by the fluorination
chloropyridine and potassium fluoride in sulfo- of 2,4-dihydroxypyrimidine with fluorine or tri-
lane [387]. 2,6-Difluoropyridine [1513-65-1], bp fluoromethyl hypofluorite [399], [400].
124.5  C (99.1 kPa), is obtained by the reaction 5-Chloro-2,4,6-trifluoropyrimidine [697-83-
of 2,6-dichloropyridine with potassium fluoride 6], bp 114.5  C (100 kPa), is produced commer-
in the absence of solvent. The yield is 80 % after cially from 2,4,5,6-tetrachloropyrimidine by
18 h at 400  C [388]. chlorine – fluorine exchange, using sodium fluo-
For pentafluoropyridine [700-16-3], bp 83  C, ride at 300  C [401] or anhydrous hydrogen
the preferred method is the reaction of pentachlor- fluoride in the liquid phase [402] or gas phase
opyridine with KF at 480 – 500  C; the yield is [403].
83 % [389]. Nucleophilic substitution reactions The 5-chloro-2,4-difluoropyrimidinyl radical
have been thoroughly investigated [390]. acts as the reactive group in reactive dyes [397]
for cellulose and cotton fibers such as Levafix EA
Uses. Fluoropyridines are intermediates for (Bayer) and Drimarene K (Sandoz) and for wool,
pesticides. For example, 2-fluoro-4-hydroxypyr- e.g., Verofix (Bayer) and Drimalene (Sandoz).
idine [22282-69-5] is a precursor of 2-fluoro-3,5-
dihalo-4-hydroxypyridine herbicides [391]; 2-
fluoro-6-hydroxypyridine [55758-32-2] is used 11.4.4. Fluorotriazines
for insecticides and nematocides [392] and vari-
ous derivatives of fluorinated pentahalogenpyr- 2,4,6-Trifluoro-1,3,5-triazine [675-14-9], bp
idine herbicides [393]. Pentafluoropyridine in 72.4  C (101.7 kPa), is produced commercially
484 Fluorine Compounds, Organic Vol. 15

from 2,4,6-trichloro-1,3,5-triazine (cyanuric dyes. The main producers in Western Europe are
chloride) with either anhydrous hydrogen fluo- Bayer AG, Ciba-Geigy, ICI, and Sandoz.
ride [404] or sodium fluoride in sulfolane [405]. Fluorobenzene and its derivatives are pro-
It is used to manufacture reactive dyes by reac- duced in Western Europe by AlliedSignal –
tion between one or two fluorine substituents Riedel-de-Ha€en (production capacity 1600 t/a),
with amino groups of chromophores; the remain- Zeneca (2000 – 2500 t/a), Rhône-Poulenc
ing fluorine binds to the fiber [406]. The reactive (1000 t/a), MitEni (1000 t/a) in Europe, DuPont
intermediates can be synthesized e.g., from the (1400 t/a), Mallinckrodt (1200 t/a) in the USA
corresponding 6-substituted 2,4-dichlorotria- and Asahi Glass (1000 t/a) in Japan. Fluoroni-
zines and an alkali-metal fluoride or by reaction trobenzenes and fluoroanilines are produced by
of cyanuric fluoride with anilines or phenols in the Halex process by Hoechst, MitEni, Rhône-
organic solvents [406], [407]. Like the pyrimi- Poulenc, Asahi Glass, and others. The total ca-
dine reactive dyes, the fluorotriazines are used on pacity for fluoroaromatic intermediates is esti-
cellulose, polyesters, polyamides, and wool mated to be several thousand tons per year.
[397]. See also ! Reactive Dyes.
13. Toxicology and Occupational
11.4.5. Polycyclic Fluoroaromatic Health
Compounds
With few exceptions, organic fluorine com-
Polycyclic fluoroaromatic compounds are pounds are physiologically inert and display
used as intermediates for the production of insignificant toxicity. This is a consequence of
pharmaceuticals. the chemical stability of the carbon – fluorine
4-Fluoro- [324-74-3] and 4,40 -difluorobiphe- bond and the increased stability of hydrogen and
nyl [398-23-2] are obtained by diazotization halogen bonds attached to a fluorinated carbon
from the corresponding amines in yields of up atom. Low toxicity is an important factor in many
to 80 % [408]. Other biphenyl derivatives are applications of these compounds.
prepared from fluorobenzenes. The analgesic The difference in toxicity between a chloro or
diflunisal [22494-42-4] is produced from 2,4- bromo compound and the corresponding fluoro
difluoroaniline [367-25-9] by diazotization and compound is often striking. Thus, carbon tetra-
coupling with salicylic acid. The anti-inflamma- chloride [56-23-5] is a powerful liver and kidney
tory drugsflurbiprofen [5104-49-4] and fluprofen toxin and a weak carcinogen, as reflected in its
[17692-38-5] are prepared from 2-fluoroaniline TLV of 5 ppm. However, the product obtained
[348-54-9]. by replacing one chlorine atom with fluorine,
The anti-inflammatory drug sulindac [38194- trichlorofluoromethane [75-69-4], has no ad-
50-2] is a monofluorinated indole-3-acetic acid. verse effects on the liver, kidney, or other organs,
and no carcinogenic effects on animals exposed
to high concentrations for a lifetime; the TLV is
12. Economic Aspects 1000 ppm. Another example is the chemical
warfare agent mustard gas, S(CH2CH2Cl)2
The compounds discussed in Chapters 10 and 11 [505-60-2], which is a strong alkylating agent
are not produced in large quantities and often and notorious vesicant. The fluoro analog, bis(2-
command high prices. 4-Chlorobenzotrifluoride, fluoroethyl) sulfide [373-25-1], is chemically
3,4-dichlorobenzotrifluoride, 3-trifluoromethyl- and physiologically inert, with no vesicant prop-
phenyl isocyanate, and benzotrifluoride are pro- erties [409].
duced in the United States by Occidental Chemi- The few highly toxic organofluorine com-
cal, in Western Europe by Hoechst, Rhône-Pou- pounds usually have easily replaceable fluorine
lenc, MitEni and Dow-Elanco, and in Japan by atoms. Examples are diisopropyl fluoropho-
Daikin. The worldwide production capacity is ca. sphate [55-91-4], a potent cholinesterase inhibi-
35 000 – 40 000 t/a. tor, and perfluoroisobutylene [382-21-8], which
Heterocyclic fluorine compounds have eco- causes pulmonary edema at low concentrations.
nomic importance in the production of reactive Sodium fluoroacetate [62-74-8], a potent roden-
Vol. 15 Fluorine Compounds, Organic 485

ticide, is an exception; it does not liberate fluo- ly more toxic, whereas 1,2-dichloro-1,1,2,2-tet-
rine, but interferes with metabolism by mimick- rafluoroethane [76-14-2] is slightly less toxic.
ing acetic acid. However, for all three a TLV of 1000 ppm is
judged to provide an adequate margin of safety.
On the other hand, 1,1,1,2-tetrachloro-2,2-di-
13.1. Fluorinated Alkanes fluoroethane [76-11-9] and 1,1,2,2-tetrachloro-
1,2-difluoroethane [76-12-0] cause liver and lung
Fluoroalkanes [410], [411]. Perfluoroalk- damage to rats subjected to repeated exposure at
anes have very low toxicity. Thus, rats exposed 1000 ppm; therefore, a TLV of 500 ppm is re-
to an 80 : 20 mixture of perfluorocyclobutane commended for these compounds. These data
[115-25-3] and oxygen for 4 h survived with no indicate that the toxicity of chlorofluorocarbons
ill effects. Likewise, no ill effects were seen in tends to increase with the chlorine : fluorine ratio
four species of animals exposed to a 10 % con- and the number of carbon atoms.
centration in air 6 h/d for 90 d. Partially fluori- Although the toxicity of most chlorofluor-
nated alkanes have similarly low toxicity, as oalkanes bearing hydrogen (chlorofluorohydro-
shown by similar experiments with difluoro- carbons) is also low, it tends to be higher than that
methane [75-10-5] and1,1-difluoroethane [75- of the closely related chlorofluorocarbons. The
37-6]. difference is usually slight, as in the case of 2-
chloro-1,1,1,2-tetrafluoroethane [2837-89-0],
Chlorofluoroalkanes are more toxic than which is a slightly stronger cardiac sensitizer
the corresponding fluoroalkanes; nevertheless, than 1,2-dichloro-1,1,2,2-tetrafluoroethane, but
most chlorofluoroalkanes have low toxicity is otherwise similar to it in toxic properties.
[410–412]. High concentrations (10 – 50 % in Chlorodifluoromethane [75-45-6] is similar in
air) of many of them, like lower concentrations of toxicity to dichlorodifluoromethane in most re-
many hydrocarbon and chlorohydrocarbon sol- spects, and has the same TLV of 1000 ppm. At
vents, can cause cardiac sensitization, i.e., sen- 50 000 ppm it has a weak carcinogenic effect in
sitization of the heart to the body’s adrenalin. male rats, but not at lower concentrations or in
This can lead to cardiac arrhythmia (heartbeat mice or female rats; therefore, this is considered
irregularity) and sometimes cardiac arrest. of no practical significance [415].
Deaths have been caused by ‘‘aerosol sniffing’’. The toxicity of dichlorofluoromethane [75-
The toxicity of dichlorodifluoromethane [75- 43-4] is more like that of chloroform than of
71-8] has been thoroughly investigated. Rats dichlorodifluoromethane or chlorotrifluoro-
survived a 6-h exposure to an 80 % mixture with methane [75-72-9], especially with respect to
oxygen. Five species of animals continuously injury on repeated exposure; its TLV, 10 ppm,
exposed to 810 ppm for 90 d showed no effects is low for a chlorofluoroalkane.
except for slight liver damage in guinea pigs.
Rats and dogs showed no significant health ef- Bromofluoroalkanes, some of which are
fects when fed a diet containing 0.3 % for 2 years. fire extinguishing agents and anesthetics, are
Teratogenic and reproductive tests in rats were more toxic than the corresponding chlorofluor-
also negative. Repeated exposure caused little or oalkanes, but generally are low in toxicity com-
no irritation to rat skin or the rabbit eye. In a pared to other fire extinguishing agents and
screening test, dogs injected with adrenalin anesthetics [409], [413]. Trifluorobromo-
showed cardiac sensitization on exposure to methane [75-63-8] produced no adverse effects
50 000 ppm in air, but not to 25 000. On the on dogs and rats exposed to 23 000 ppm 6 h/d,
basis of animal data and human experience, a 5 d/week, for 18 weeks; its TLV is 1000 ppm
TLV of 1000 ppm has been selected to provide [413].
an ample margin of safety against cardiac sensi-
tization and other injury [413]. The MAK is also
1000 ppm [414]. 13.2. Fluorinated Olefins
Compared to dichlorodifluoromethane, tri-
chlorofluoromethane [75-69-4] and 1,1,2-tri- Most fluorinated olefins have halogen atoms of
chloro-1,2,2-trifluoroethane [76-13-1] are slight- low reactivity and a correspondingly low-to-
486 Fluorine Compounds, Organic Vol. 15

Table 23. Toxicities of fluorinated olefins* fluoroacetone and three fully halogenated chlor-
Compound CAS Lethal conc.,
ofluoroketones indicated moderate acute toxicity
registry no. ppm [416].
Vinyl fluoride [75-02-5] > 800 000 (ALC)**
Vinylidene fluoride [75-38-7] > 800 000 (ALC)**
Tetrafluoroethylene [116-14-3] 40 000 (LC50) 13.5. Fluorinated Carboxylic Acids
Hexafluoropropene [116-15-4] 3 000 (LC50)
Chlorotrifluoroethylene [79-38-9] 1 000 (LC50) Fluoroacetic acid [144-49-0] is highly toxic to
*
Inhalation by rats, 4-h exposure. mammals; its sodium salt is an effective, but
**
Approximate lethal concentration. indiscriminate, rodenticide; in rats the LD50 of
the salt is only 1.7 mg/kg [413]. In contrast,
moderate toxicity [409], [412]. The toxicities of difluoroacetic acid [381-73-7] and perfluoroalk-
the five most common members of the class, anoic acids have low acute toxicity.
typical in these respects, are shown in Table 23. The unusually high toxicity of fluoroacetic
In perfluoroisobutylene and 2,3-dichloro- acid compared to the more highly fluorinated
1,1,1,4,4,4-hexafluoro-2-butene [303-04-8], ha- acids is due to its unique ability to interfere
logens are readily displaced by nucleophilic with the citric acid cycle, the oxidation path-
reactants; thus, these two compounds exhibit way used for energy production from amino
high acute toxicity. Perfluoroisobutene, with a acids, fatty acids, and carbohydrates. Fluoroa-
LC50 of 0.5 ppm, acts much like phosgene in cetic acid enters the cycle at the same site as
causing death by pulmonary edema. However, acetic acid and is converted to fluorocitric acid
perfluoroisobutene is ca. 10 times as toxic as [387-89-1] analogously to the conversion of
phosgene, so exposure to it must be carefully acetic acid to citric acid. The fluorocitric acid
avoided. Pyrolysis of tetrafluoroethylene or its inhibits aconitase, a key enzyme for the break-
polymers above 400  C is one of its sources. down of citric acid, with the result that the
citric acid concentration soon rises to lethal
levels [417].
13.3. Fluorinated Alcohols Substances that yield fluoroacetic acid on
biochemical oxidation, such as straight-chain,
2-Fluoroethanol [371-62-0] has a high acute even-numbered, w-fluoro alcohols or alkanoic
toxicity (LD50 10 mg/kg), a consequence of its acids, are also very toxic.
ready biological oxidation to fluoroacetic acid
(see Section 13.6). Thus, contact with the skin
and inhalation of vapors must be avoided. The di- 13.6. Other Classes
and trifluoroethanols ([359-13-7] and [75-89-8],
respectively) have relatively low acute toxicity, Simple perfluoroethers, and the oily oligomers of
similar to the corresponding acetic acids [412]. hexafluoropropylene oxide with modified end
The acute toxicity of 1,1,1,3,3,3-hexafluoro-2- groups, have the low toxicity expected from their
propanol [920-66-1] is also low, but the sub- chemical inertness. Hexafluoropropylene oxide
stance is a strong skin and eye irritant. itself, a reactive substance, is moderately toxic to
rats (4-h LC50, 3700 ppm) [418]. Several partial-
ly fluorinated ethers are used as anesthetics, e.g.,
13.4. Fluorinated Ketones Enflurane [13838-16-9], F2CHOCF2CHFCl, and
Methoxyflurane [76-38-0], CH3OCF2CHCl2.
In 90-d inhalation studies in animals, hexafluor- Their toxicity is low compared to that of most
oacetone [684-16-2] caused severe damage to anesthetics (! Anesthetics, General).
kidneys and other organs at 12 ppm, moderate Perfluorinated tertiary aliphatic amines are
damage at 1 ppm, and no damage at 0.1 ppm. inert both chemically and biologically. This is
Repeated skin exposure led to testicular damage illustrated by perfluorotripropylamine [338-83-
in rats. These data and plant experience led to 0]; in emulsion with perfluorodecalin [306-94-5],
selection of a TLV of 0.1 ppm, with a warning it has shown promise as a blood substitute in
against skin exposure [413]. Studies of hexa- clinical trials [419].
Vol. 15 Fluorine Compounds, Organic 487

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184 Hoechst, DE 1 017 782, 1957 (P. Schlack). M. Good- 205 DuPont, US 3 125 599, 1964 (J. L. Warnell).
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218 D. C. England, L. R. Melby, M. A. Dietrich, R. V. 251 Commonwealth Scientific and Industrial Research Or-
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227 Air Reduction Co., GB 1 138 406, 1969 (R. C. Terrell). 263 Hoechst, DE-OS 2 361 058, 1975 (G. Siegemund, R.
228 Air Reduction Co., US 3 535 425, 1970 (R. C. Terrell). Muschaweck).
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246 Allied, NL-A 6 407 623, 1965 (E. E. Gilbert, J. A. Otto). 280 Asahi Glass, US 4 138 417, 1979 (H. Ukihashi, T.
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285 A. L. Henne, W. J. Zimmersheid, J. Am. Chem. Soc. 69 pp. 45 – 80; M. Le Blanc, J. E. Riess, R. E. Banks
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299 DuPont, US 3 301 893, 1967 (R. Putnam, W. Nicoll 324 Hooker Chemical, US 3 234 292, 1966 (St. Robota, E.
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300 S. Torrey (ed.): Membrane and Ultrafiltration Technol- 325 R. J. Albers, E. C. Kooyman, Rec. Trav. Chim. Pays Bas
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308 ‘‘Fluorinert Electronic Liquids,’’ Product Manual, 3M 333 Hoechst, DE 1 965 782, 1969 (H. Hermann, H.
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309 R. N. Haszeldine, Research (London) 3 (1950) 430. R. 334 Hooker Chem. Corp., DE-AS 1 543 015, 1965 (St.
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343 W. A. Sheppard, C. M. Sharts: Organic Fluorine Chem- 370 R. Filler, J. Fluorine Chem. 33 (1986) 361.
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