276 Proc. Jpn. Acad., Ser. B 85 (2009) [Vol. 85,
Review Overview on the history of organo uorine chemistry from the viewpoint of material industry
By Takashi OKAZOE 1,†
(Communicated by Hitosi NOZAKI, M.J.A.)
Abstract: Fluorine (from ‘‘le uor’’, meaning ‘‘to ow’’) is a second row element of Group 17 in the periodic table. When bound to carbon it forms the strongest bond in organic chemistry to give organo uorine compounds. The scienti c eld treating them, organo uorine chemistry, started before elemental uorine itself was isolated. Applying the fruits in academia, industrial organo- uorine chemistry has developed over 80 years via dramatic changes during World War II. Nowa- days, it provides various materials essential for our society. Recently, it utilizes elemental uorine itself as a reagent for the introduction of uorine atoms to organic molecules in leading-edge indus- tries. This paper overviews the historical development of organo uorine chemistry especially from the viewpoint of material industry.
Keywords: organo uorine chemistry, uorine, uorination
who prepared methyl uoride from dimethyl sulfate Introduction|Incunabula of organo uorine (Eq. 2). chemistry Alexander Borodin (1833{1887), who is well- ½2 known as a composer in classical music, is said to have made the rst organo uorine compound.1) More Formation of an aryl carbon{ uorine (C-F) precisely, he carried out the rst nucleophilic replace- bond was rst carried out through diazo uorination ment of a di erent halogen atom by uoride (Eq. 1) by Schmitt et al. in 1870 (though the characteriza- and reported the results in 1862.2)–4) This was the tion was wrong), then by Lenz in 1877 (Eq. 3).4) rst example of synthesis of an organo uorine com- pound by halogen exchange, which is now broadly used in uorine chemistry and especially in uoro- ½3 chemical industry for the introduction of uorine atoms into organic molecules. Borodin was a promis- Mineral uorides were recognized and used as ing young chemist, and became a professor of chem- early as 16th century. In 17th century, it was already istry in 1864. known that glass was etched when it was exposed to a new acid generated from uorspar and sulfuric acid.5) The generated acid was called hydro uoric ½1 acid and was characterized by Scheele in 1771.5),6) Then it was eventually realized that hydro uoric acid contained a previously unknown element, uo- Actual rst synthesis of an organo uorine com- rine. Although organo uorine compounds were pre- 4) pound was reported by Dumas et al. in 1835, pared in mid 19th century, elemental uorine itself was not isolated at that time. 1 Asahi Glass Co., Ltd., Tokyo, Japan. After continuous e orts by a great number of † Correspondence should be addressed: T. Okazoe, Asahi Glass Co., Ltd., 1-12-1, Yuraku-cho, Chiyoda-ku, Tokyo 100-8405, chemists, elemental uorine was nally isolated in Japan (e-mail: [email protected]). 1886 by Moissan, who electrolyzed a melt mixture doi: 10.2183/pjab.85.276 62009 The Japan Academy No. 8] Overview of organo uorine chemistry 277 of potassium hydrogen di uoride and hydrogen on uorine chemistry in academic eld are also avail- uoride.5),7) able.21)–27) Because of hazards and dif culties in handling Chloro uorocarbons|First industrial highly reactive and corrosive reagents, organo uo- application rine chemistry remained relatively undeveloped until 1920’s. In 1928, General Motors Corporation, manufac- In 1926, carbon tetra uoride was rst isolated turers of refrigerators, appointed McNary, Midgley from the product of the reaction of uorine with and Henne to the task of nding inert refrigerants. wood charcoal by French chemists, Lebeau and Until then, available conventional refrigerants had Damiens,8) and was fully characterized 4 years later serious drawbacks: some were ammable, others like 9) by Ru . SO2 were corrosive and toxic, and still others like 6) In 1927, Schiemann found an aromatic uorina- NH3 combined all three hazards. Midgley et al. tion methodology:10) diazonium salts of aromatic studied on a fundamental basis, plotting trends of amines were rst prepared, and then decomposed in toxicity, ammability, and boiling point on a peri- the presence of uoroboric acid to give uorinated odic chart of the element. He concluded that desired aromatic compounds (Eq. 4). This reaction was im- boiling range of 0 Cto 40 C might be achieved by proved and is still used even now for the manufac- uoroaliphatic compounds. At rst, carbon tetra- ture of uoroaromatic compounds. uoride (CF4) seemed appropriate because its boiling point was reported by Moissan as 15 C28) (though this was incorrect).4) However, feeling that the syn-
thesis of CF4 would be dif cult, they decided to se- ½4 lect CCl2F2 as their rst choice and prepared sample by the reaction of CCl4 and SbF3, a synthesis origi- Another important synthesis of uoroaromatic nally reported by Swarts.4) Midgley gave a dramatic compounds, nucleophilic halogen exchange from Cl introduction of the new refrigerant by lling his to F using KF (Eq. 5), was reported by Gottlieb in lungs and extinguishing a light candle at a meeting 1936.4),11) This was the rst example of halogen ex- of American Chemical Society in 1930.4),29) change method used in the uoroarene synthesis. In the meantime, General Motors had ap- proached E. I. du Pont de Nemours & Company (DuPont) with a proposal to manufacture this prod- uct.6) The original work was soon supplemented by ½5 development studies for the practical production on a commercial scale (Eq. 7).4),6),30)
Aromatic compounds with uorinated side chain ½7 was reported by Swarts in 1898 for the rst time.4),12) Benzotrichloride was found to react rapidly with
SbF3 (Eq. 6). In 1930, a joint corporation, Kinetic Chemicals Inc., was formed by the two companies. By early ½6 1931, the new product, trademarked Freon2-12, was being produced in commercial quantities. Applica- This conversion from aromatic {CCl3 to {CF3 tion of the new compound was successful, and by was later achieved with HF and reported in the end of 1931, Kinetic Chemicals had expanded its 13),14) 1930’s. facilities, and begun manufacture of anhydrous hy- Reactions above formed the basis of industrial dro uoric acid, a basic raw material (Eq. 8).6) application. The present overview treats mainly the history of material industry in organo uorine chemis- ½8 try. Pharmaceutical and agrochemical applications are discussed brie y. Detail surveys of them have Expansion during the next few years was contin- been provided by several reviews.15)–20) Review books uous, and the product line was expanded as early 278 T. OKAZOE [Vol. 85,
2 as 1932 to include Freon -11 (CCl3F) as well polymer nowadays, it was not the rst of the 2 2 as Freon -113 (CClF2CCl2F) and Freon -114 uoroplastics to be prepared. The rst one was (CClF2CClF2), two of the polychloro uoroethane poly(chlorotri uoroethylene), PCTFE, the polymer derivatives (Eq. 9).4),6),30)–33) of chlorotri uoroethylene (CTFE), which was ob- tained by the dechlorination of Freon2-113 (Eq. 12)31),32) on an experimental scale as early as 1934.35),36) [9]
In 1935, this reaction was improved and em- ployed for the synthesis of chloro uoromethanes, the uorinated derivatives of chloroform (Eq. 10).6) [12]
Development during World War II [10] At that time, uoropolymers were so expensive to produce that all believed they would never nd First uoroplastics a market. Their features were striking in ful lling 2 One of these, Freon -22 (CHClF2), soon gained the requirements of the gaseous di usion process of wide acceptance. This compound later became very the Manhattan project at Columbia University in important as the precursor of tetra uoroethylene New York City during World War II and the uoro- (TFE). At that time, however, TFE was synthesized polymers were rst used as materials that could tol- by dechlorination of Freon2-114 with zinc (Eq. erate uorine or its derivative uranium hexa uoride 4),31),32) 37) 11). (UF6). Even after the isolation of uorine by Moissan in 1886, the dif culties in research using uorine dis- couraged most chemists, and it was not until World [11] War II when development was undertaken. The rst large-scale production of uorine was carried out for In 1938, a DuPont chemist Plunkett, who was the atomic bomb Manhattan project which needed working with new chloro uorocarbon gases relating UF6 as a gaseous carrier of uranium to separate the 2 to Freon refrigerants, discovered polytetra uoro- 235U and 238U isotopes of uranium. Uranium tetra- 34) ethylene (PTFE). When Plunkett was preparing uoride (UF4), which was prepared from uranium di- for an experiment with TFE and attempted to oxide (UO2) and hydrogen uoride (HF), was con- 6),37),38) pump the gaseous TFE into hydrochloric acid to verted to UF6 by reaction with uorine. chlorinate it, he observed that nothing was coming Using uorine chemistry, atomic bombs were con- out. He weighed the cylinder and it was the same as structed and exploded over Hiroshima and Nagasaki, before. Plunkett then cut the cylinder open and dis- Japan.37) 4) covered a waxy substance formed inside. After UF6 was almost as reactive as elemental uo- studying the powder, he found the substance to be rine. In order to use it in a gas-di usion plant, a heat resistant and chemically inert, and to have very wide range of materials which would not react with low surface friction so that most other substances UF6 remained to be developed. These would include would not adhere to it. Plunkett realized that the relatively low molecular weight liquids for coolants; exact combination of pressure and cold temperature, higher molecular weight materials for lubricants; along with the age of the gas in a cylinder, had al- and polymers that could be fabricated into gaskets, lowed the TFE gas molecules to polymerize to give valve packings and tubing.6),37) In 1937 and more this product PTFE with such potentially useful char- extensively in 1939, preparative methods and pro- acteristics. Chemists and engineers in the Central perties of liquid uorocarbons were disclosed by Research Department of DuPont investigated the Simons and Block.39) In 1940, the possibility of use substance further. of uorocarbons as sealants and coolants and as
Although PTFE is the best known uoro- materials that are directly exposed to UF6 was sug- No. 8] Overview of organo uorine chemistry 279
uoroacyl uorides, per uoroalkanesulfonyl uorides, and per uorinated amines.47),48) Among them, per- uoroacyl uorides led to the development of 3M’s Scotchgard2, textile nishes.47) It works as an water and oil repellent agent. Scheme 1. Fluorination with CoF3. Per uoroalkyl iodides, which are synthesized by the telomerization method (Eq. 13) reported by Has- zeldine around 1950,49)–51) are utilized for the same gested by Simons. A 2 mL sample of liquid uoro- purpose. carbon was sent from Simons to Urey at Columbia University and tested to show that it had the desired properties.40) The problem was preparation of uoro- carbons on a large scale. Several methods were sub- ½13 sequently developed. The rst major process was a catalytic uorina- Further process development on CoF uorina- tion process using uorine. However, it was found ex- 3 tion after Manhattan project was carried out at ISC tremely dif cult to extend this process to large-scale Chemicals Limited,52),53) and led to production of low production.40) 2 molecular weight uorocarbon uids (Flutec )later. Another and principal method was the metallic The rst commercial products of PTFE were uoride process, which employs cobalt tri uoride sold under the ‘Te on’ tradename by DuPont in (CoF ), in particular.41) Fowler developed this pro- 2 3 1948.4) Te on has become a familiar household cess42),43) based on the method reported by Ru .44),45) name, recognized worldwide for the superior non- The uorides can only be prepared by uorinating stick properties associated with its use as a coating the metal or low valent metal salt, with elemental on cookware and as a soil and stain repellant for fab- uorine. Ru et al. demonstrated that metal uorides rics and textile products. of higher oxidation state were powerful uorinating The monomer TFE is manufactured by the agents and utilized them to prepare a number of method developed in Manhattan project,37),54) uorocarbons (Scheme 1). 2 namely by the pyrolysis of Freon -22 (Eq. 14). Prod- Treatment of a hydrocarbon with CoF at 3 uct TFE is accompanied by hexa uoropropylene 400 C gives a product where all the hydrogen atoms (HFP) when pyrolysis was carried out with steam are replaced by uorine. Cobalt di uoride (CoF )is 2 and alumina (Eq. 15).55),56) HFP is also obtained by co-produced but is converted with elemental uorine pyrolysis of TFE at 850 C.55) to cobalt tri uoride. An entirely di erent approach was also carried out: the electrochemical uorination (ECF) process ½14 for producing uorocarbons. ECF was invented by Simons,46) but was not reported until 1949 for secu- rity reasons associated with the Manhattan project. Civilian use of wartime technology After World War II, Minnesota Mining and Manufacturing Company (3M) acquired the technol- ½15 ogy of ECF and improved it to a pilot plant level as early as 1947.47) The rst commercial plant for the production of uorocarbons was put into operation in 1951.47) Further study of ECF was carried out after After World War II, PCTFE, or Kel-F2, was the launch of uorocarbons, and product line was marketed by M. W. Kellogg. It became generally extended to production of uorocarbon derivatives available in the early 1950’s and was taken over by possessing functional groups: per uoroethers, per- 3M in 1957.36) 280 T. OKAZOE [Vol. 85,
Scheme 2. Synthesis of partially- uorinated ethylene monomers.
In addition to per uorinated homopolymer, TFE/HFP copolymer ( uorinated ethylene/propy- Functionalized uoropolymers lene copolymer: FEP) was studied during the Man- On the other hand, it was dif cult to copolymer- hattan project36) and commercialized in 1959 by Du- ize TFE with per uorinated monomers other than Pont.57) PTFE is characterized by high melting HFP. However, per uorinated vinyl ethers were point, high thermal stability, insolubility, and chem- found to react with TFE to give copolymers.58),59) ical inertness. However, it cannot be processed by Thus, per uoroalkoxycopolymer (PFA) was syn- conventional melt techniques. This dif culty was thesized and commercialized in 1972 by DuPont.57) overcome by FEP. The monomer, per uorinated propyl vinyl ether (PPVE) is synthesized from hexa uoropropylene Partially- uorinated polymers oxide (HFPO)60) as shown in Scheme 3.48),61) Polymers with partially- uorinated monomers, Before PFA was manufactured, HFPO was used that is, PVdF (poly(vinylidene uoride)) was devel- as a monomer for anion polymerization in the pre- oped in DuPont in 1948 and commercialized in paration of per uoropolyether (PFPE) uids, which 1950.57) Poly(vinyl uoride) (PVF) was also studied was developed by DuPont and commercialized as and launched in 1960’s.36) Their lms are important Krytox2.62)–64) Direct photo-oxidation of HFP or in industry, while PVdF is mainly used for water- TFE was also developed for this purpose by Monte- resistant coating. The monomers are produced by a dison (Fomblin2).63)–65) The products PFPE uids, route shown in Scheme 2. which were commercialized in 1960’s, have high The majority of commercial homopolymers chemical and thermal stability and excellent physical nowadays are produced from only four monomers properties as lubricants which are highly reliable discussed above: tetra uoroethylene (TFE), chloro- under very severe conditions. tri uoroethylene (CTFE), vinyl uoride (VF), and In 1960’s, NASA used fuel cell for space explora- vinylidene uoride (VdF). Per uorinated polymers tion project including Gemini and Apollo. Na on2, are prepared by a free-radical polymerization reac- membranes made of a per uorinated sulfonic acid tion in water or in a uorinated solvent. ionomer, was rst employed as a separator in the Copolymerization of these monomers with hy- fuel cell. It is made of the polymer prepared by co- drocarbon monomers were studied world-wide and polymerization of TFE and the functional per uoro- commercialized in 1970’s. vinyl ether, which is derived from HFPO as shown in Ethylene/TFE copolymer (ETFE): 1972 by Du- Scheme 4.56) Pont and Asahi Glass independently.57) TFE/propylene copolymer (TFE-P) A as2: 1975 Organo uorine chemistry in minimization of by Asahi Glass.57) environmental impact ETFE is mainly used for insulation of electric In the late 1960’s, the chemical business came cable, and also provides tough and exible lm which up against environmental issues. The sea around is used for architectural area. TFE-P is one of uoro- Kyushu, Japan, turned out to be the site of an out- elastomers as well as VdF-HFP copolymers. break of Minamata Disease, said to be one of the No. 8] Overview of organo uorine chemistry 281
Scheme 3. Synthesis of PPVE.
Scheme 4. Synthesis of a monomer for ion-exchange membrane. worst cases of mercury poisoning in history. This in- side chain. The manufacturing process is shown in cident caused deep concern about chemical produc- Scheme 5.68) tion processes. In 1968, Japanese government an- The electrolysis process with ion-exchange mem- nounced its consensus that ‘‘Minamata Disease was brane electrolysis method became common in com- caused by industrial waste water containing organic mercial applications in 1984, and further improved mercury.’’ Restrictions were later placed on the use to employ sulfonate-carboxylate laminated polymer of inorganic mercury as well for electrochemical pro- membrane eventually achieving 100% proliferation duction of caustic soda (NaOH). One of the candi- in Japan and 51% worldwide (as of 2007). Moreover, dates for new mercury-free approach was the ‘‘ion- the energy consumption of electrolysis processes was exchange membrane electrolysis method’’. The key dramatically reduced by developing an advanced was a central membrane that allow only speci c ions electrode. to pass through. When sodium chloride (NaCl) is Common plastics are made from a variety of or- electrolyzed to produce sodium hydroxide (NaOH), ganic materials, but the use of these materials should a violent situation to the membrane with strong al- be minimized for reducing environmental burden. kali occurs. Only a membrane made from uoropoly- One way is to ensure products last longer. For exam- mer could withstand this reaction. ple, for outdoor coating products that are exposed to The ion-exchange membrane Na on2 for fuel outdoor environment, durable uorinated materials cell was applied to this purpose.56) Performance of are used. Lumi on2, the rst solvent-soluble uo- Na on2 was not high enough, however, and a ropolymer for coatings, was developed by Asahi per uorinated carboxylate polymer membrane was Glass,57) which is the material for anti-corrosive coat- required to obtain a higher concentration of caustic ing of various structures such as bridges. It is soda. Flemion2(Asahi Glass, Japan) were developed made of CTFE/non- uorinated vinyl ether copoly- as such an ion exchange membrane,66) and commer- mer.56),69) Although conventional coating materials cially produced since 1978.56),67) without uorine last a few more than 10 years at The per uorinated carboxylic acid membrane best, Lumi on2 lasts up to 30 or 40 years. The added consists of a copolymer of TFE and per uorinated uorinated structure enabled to create surprisingly vinyl ether, which has a carboxylic acid group in the durable coating materials. 282 T. OKAZOE [Vol. 85,
Scheme 5. Synthesis of a monomer for per uorinated carboxylic acid membrane.
The outstanding resistance to violent chemicals CFC-113 was selected from thousands of candidate in ion-exchange membranes and the excellent weath- materials, then actually synthesized by modi ed erability are derived from high stability of C-F Prins reaction of TFE and CHCl2F (HCFC-21) (Eq. bonds. Any oxidants or chemicals hardly attack the 16).72)–74) uorine-substituted carbons. However, this stability was back red in chloro- uorocarbons (CFCs). Studies have shown that in the deep blue sky, CFCs and other substances re- ½16 leased into the atmosphere are causing damage to the ozone layer.70) In 1985, an ozone hole was discov- Thus, organo uorine chemistry plays important ered over the South Pole. CFCs are so stable sub- roles in minimization of environmental impact and in stances that they moved far into the upper atmo- production of various materials for industrial use sphere, causing the destruction of the ozone layer. such as thermoplastics, elastomers, membranes, tex- Carbon{chlorine bond cleavage of CFCs by UV light tile nishes, coatings. generates radical species, which cause ozone deple- tion, whereas C-F bonds are stable even in the Pharmaceuticals, agrochemicals and stratosphere. It was therefore necessary to nd alter- ne chemicals native CFCs that possess carbon-hydrogen bonds, Fluorine is the most electronegative element in which are cleaved before they reach the stratosphere. the periodic table. When bound to carbon, it forms CFCs had three main applications: Refrigerants the strongest bonds in organic chemistry. This makes for air conditioners and refrigerators, blowing agents introduction of uorine attractive for the develop- for urethane foaming, and precision equipment clean- ment of material science. Although highly polarized, ing agents. Refrigerant CFC-12 (the same compound the C-F bond gains stability from the resultant elec- 2 75) as Freon -12: CCl2F2) was replaced by HFC-134a trostatic attraction between C and F atoms. Ap- (CF3CH2F), and blowing agent CFC-11 (CCl3F) plication to materials is mostly based on the proper- was substituted by HCFC-141b (CH3CCl2F) and ties derived from the uorine-carbon bonds, which 71) then HFC-245fa (CF3CH2CHF2). However, there are hardly attacked by any oxidants or chemicals were no alternatives for cleaning agents CFC-113 since C-F bonds tolerate various conditions. There-
(CCl2FCClF2). fore, normal metabolism in a living body is easily in- The alternative material for CFC-113 was hibited as well (block e ect) by such strong bonds. developed by Asahi Glass (HCFC-225ca and cb: On the other hand, the van der Waals radius of ASAHIKLIN2 AK-225). The innovative develop- uorine is similar to that of hydrogen. Accordingly, ment was assisted by not only conventional experi- organo uorine compounds are similar in steric size mental chemistry but computer chemistry tech- to non- uorinated ones but quite di erent in elec- nologies and the most appropriate alternative to tronic nature. As a living body can not sterically dis- No. 8] Overview of organo uorine chemistry 283 tinguish uorinated molecules from the correspond- rination of benzene again using uorine diluted with ing non- uorinated one, uorinated molecules are in- nitrogen. The explosion was avoided, though they corporated into metabolic sequences in a manner obtained only tarry products.82),85) Beckmuller at- similar to that of non- uorinated one (mimic e ect). tempted the uorination of several aromatic com- However, since the C-F bond in the uorinated mole- pounds with uorine, but also obtained only tars cule resists the metabolism common with the parent with high uorine content.82),86) compound due to opposite polarization, the normal During World War II, the rst sample of metabolism in a living body is inhibited to cause var- uorocarbons, found to be inert towards UF6, had ious biological e ects. This makes uorine substitu- been made by direct reaction between carbon and tion attractive for invention of pharmaceuticals and elemental uorine catalyzed by mercury.37) In 1941, agrochemicals.15),16) Bigelow and Fukuhara reported that direct uorina- There are many applications. For examples, tion of benzene with elemental uorine in the vapor inhalation anesthetics15) are synthesized by classical phase over copper gauze catalyst gave per uoro- 30)–32) 37),87) halogen exchange reactions. Aryl-CF3 contain- cyclohexane with only moderate degradation. ing herbicides16)–18) are synthesized using a halogen This method looked promising for Manhattan proj- exchange reaction originated in 1930’s (Eq. 6).13),14) ect, and was investigated in detail. Although yields Non-steroidal anti-in ammatory drugs (NSAIDs),15),16) were improved up to 58% of per uorocyclohexane 19),20) 18) anti-bacterial agents and insecticides are syn- from benzene, CoF3 method was found more suitable thesized by Balz-Schiemann reaction (Eq. 4)10) or to preparation of various uorocarbons.37) aromatic halogen exchange (HALEX) reaction (Eq. After World War II, in order to modify the high 5).11) The HALEX reaction is extensively performed reactivity of uorine, the vapor-phase uorination on a commercial scale to produce aromatic interme- (‘‘Jet uorination’’) apparatus for direct uorination diate building blocks of low uorine content for func- was developed by Bigelow and coworkers.88) Jet tional materials such as liquid crystals (LCs). uorination seems to be a method of choice for pre- More sophisticated syntheses are carried out paration of low-molecular-weight uorocarbons. It for manufacturing LCs particularly for thin lm was used on a semi-technical scale for production transistor-liquid crystal display (TFT-LCD),76),77) of per uoropropane, which is used as a dry (plasma) transparent uorinated resin such as Cytop278) for etchant in microelectronics industry.48) plastic optical ber (POF)79) and for semi-conductor In 1970, the low temperature gradient uorina- manufacturing process,80) and a new lubricant, which tion (‘‘LaMar uorination’’) technique was devel- is synthesized by application of direct uorination, oped by Lagow and Margrave.89),90) In the LaMar for a hard disc drive (HDD).81) uorination process, substrates are condensed at low temperature into a tube packed with copper turnings Direct uorination with elemental uorine through which uorine, initially highly diluted in Elemental uorine was rst prepared in small either helium or nitrogen, is passed. The concen- quantities by Henri Moissan in 1886 by electrolysis tration of uorine and the reaction temperature are of anhydrous hydrogen uoride.5),7) Moissan himself slowly increased over a period of several days to per- was the rst to carry out the reactions between neat mit per uorination. This batch process requires rela- uorine and several organic compounds. However, tively long reaction times to obtain per uorinated only decomposed products resulted and, occasion- material. ally, explosions occurred.82) Some years later, Adcock invented a ow ver- In the early 20th century, it was very dif cult sion, an aerosol uorination process.91) The principle to control the reactions with uorine because of the is that substrates are absorbed onto the surface of violence in nature. For example, in 1929, Bancroft ne sodium uoride particles in a uorination appa- and Jones reported explosions during attempted ratus, into which uorine is introduced and the appa- uorination of benzene and toluene with molecular ratus is warmed and UV irradiated to complete uorine.83),84) However, dilution of uorine by inert per uorination. This process has an advantage that gases such as nitrogen came to allow the reactions it is a continuous ow method and the control of re- with uorine to be carried out safely and ef ciently. action parameters are easier. In 1931, Bancroft and Wherty tried the uo- In 1980’s, Scherer, Yamanouchi, and Ono dis- 284 T. OKAZOE [Vol. 85,
Scheme 6. Synthesis of PPVE from a non- uorinated dichloroethyl ether.
Scheme 7. The PERFECT method for synthesis of per uorinated vinyl ethers.
closed a practical liquid-phase direct per uorina- concentration of uorine radicals that ensure per uo- tion method through study on arti cial blood sub- rination of substrates. stitutes.84),92) The method is quite characteristic in The Ex uor-Lagow elemental uorine process i) inverse addition of a substrate into an inert liquid can give products of the liquid-phase uorination saturated F2 gas, ii) undiluted 100% uorine gas is process in high yields. However, reaction solvents used, and iii) UV irradiation. In fact, in the liquid- are limited to now-regulated CFCs, particularly for phase direct uorination process, the reactant is in- direct uorination of substrates which contain func- jected at a very slow constant rate into an inert tional group(s) in the structure because of solubility uorocarbon solvent saturated by uorine. It is problem. pointed out to be very important that a large excess Partially uorinated substrates are more stable of F2 relative to hydrogen atoms to be replaced in a towards the uorination process, since solubility in- substrate should be maintained. This method is, creases, and presence of a poly uoroalkyl group signi- however, only suitable for the per uorination of sub- cantly lowers the oxidation potential of the sub- strates, such as partially uorinated ethers and strates. Consequently, per uorinated compounds are amines, both soluble in a per uorocarbon solvent generally produced in higher yields than the corre- and can withstand such vigorous reaction conditions. sponding non- uorinated compounds. This method Almost the same time, Ex uor Corporation was applied to preparation of per uoro ethers.94),95) claimed that various ethers and esters are per- Considering these results, it is suggested that uorinated without UV irradiation (Ex uor-Lagow direct uorination method had almost reached an method).90),93) Their methods are based on the essen- adequate standard level for monomer synthesis in tial idea of inverse addition of substrates into an industry. inert liquid dissolving uorine gas. The Ex uor- Combination of direct uorination and Lagow method involves slow addition of both a organic synthesis hydrocarbon substrate and uorine in excess into a vigorously stirred chloro uorocarbon (CFC) or a Okazoe et al. attempted at the direct appli- per uorinated inert solvent. If required, the reaction cation of Ex uor-Lagow method to the synthesis of is accelerated by adding a small quantity of a highly the monomer PPVE for per uoroalkoxy copolymer reactive hydrocarbon such as benzene, which reacts (PFA) (Scheme 6). However, it was found hard to spontaneously with uorine to produce a very high reproduce the results.96) In some cases, vapor phase No. 8] Overview of organo uorine chemistry 285
Scheme 8. The PERFECT method for synthesis of various per uorinated acyl uorides.
Scheme 9. The PERFECT method for synthesis of monomers for carboxylic acid membrane. reaction partly took place due to high volatility of counterpart alcohol and an available per uoroacyl substrate and led to an explosion. In order to solve uoride (Scheme 8).97) this problem, they have developed an entirely new The PERFECT method was applied to the syn- method that involves combination of direct uorina- thesis of per uorinated diacyl uorides, which are tion and organic synthesis, perf luorination of esteri- used for the carboxylic acid type ion exchange mem- ed compounds followed by thermolysis, abbreviated brane (Scheme 9).98) Non- uorinated diols are em- as PERFECT (Scheme 7).96) By employing partially- ployed as the substrates. uorinated ester of high-molecular weight, the dan- Synthesis of monomers for per uoalkanesulfonic gerous vapor-phase reactions can be suppressed and acid type membrane was achieved through direct solubility of substrates in a solvent used in the uorination of the substrate which possesses a sul- liquid-phase uorination can be much improved. fonyl group at the end (Scheme 10).99) This contrasts sharply to that of non- uorinated com- The application of the PERFECT method to pounds. Thus, available per uoro(alkoxyalkanoyl) non- uorinated secondary alcohols as a starting ma- uorides such as per uoro(2-propoxypropionyl) uo- terial (Scheme 11) enabled to synthesize per uori- ride can be multiplied by use of the hydrocarbon nated ketones.100) A precursor poly uoro ketone for counterpart alcohols and uorine gas as raw mate- uoropolymer resists for 157 nm microlithography rials (Scheme 7). was synthesized.100) Subsequently, the possibility of the PERFECT Recently, the PERFECT method was success- method was extended to synthesis of more general fully applied to polymers as substrates81) and pro- per uoroacyl uorides. In the case that the desired vides manufacturing process of the new lubricant for per uoro(alkoxyalkanoyl) uoride is not readily HDD. available, it can be obtained from its hydrocarbon The PERFECT process can provide with tailor- 286 T. OKAZOE [Vol. 85,
Scheme 10. The PERFECT method for synthesis of monomers for per uorosulfonic acid membrane.
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Pro le
Takashi Okazoe was born in Sapporo in 1961. He received his B. of Eng. and M. of Eng. from Kyoto University under the direction of Professor Hitosi Nozaki in 1985 and Professor Kiitiro Utimoto in 1987, respectively. He joined Asahi Glass Co., Ltd. as a researcher at Research Center in 1987 and started study of uorinated pharmaceu- tical intermediates and ingredients. There he was promoted to Group Leader in uorinated materials eld in 1999. In 2006, he moved to the head o ice of AGC Chem- icals, Asahi Glass Co., Ltd. and engaged in planning of research and development strategy. He received Technology Award from the Society of Synthetic Organic Chem- istry, Japan in 2006, and was awarded the Doctorate degree from Kyoto University in 2009. He is the inventor of over 100 patents as well as the author of academic papers. His current research interests are organo uorine chemistry and industrial synthetic methodology which minimize environmental impact for sustainable society.