The discovery of successful direct fluorination syntheses

283

Chapter 19 THE DISCOVERY OF SUCCESSFUL DIRECT FLUORINATION SYNTHESES: THREE ERAS OF ELEMENTAL FLUORINE REACTION CHEMISTRY

RICHARD J. LAGOW !

Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712-1167, USA

Eras defined

Our development of successful direct fluorination technology has passed through three distinct eras since 1963. The first era, which we shall call the Inception, comprises the years from 1964 through 1970, and was a period in which many novel organic and inorganic classes of fluorine compounds were prepared. However, the reactions proceeded on a long time scale (up to 7 days) and gave only two to five grams of product per run. Then came the Interim period in which great advances in capabilities and yields were made: it covered the years 1970 through 1992, and was an era when direct fluorination was done in ways that had much wider applications and capabilities. Reactions were performed using a number of different reactor styles and techniques. In this era, product yields normally fell in the 70-90% range, with product quantities per run ranging from five to forty grams. The third e r a - Renaissance (1992 to the present day) - saw the range of fluorinated inorganic, organometallic, and organic compounds capable of being prepared by our techniques increase markedly. Product yields mostly exceeded 98%, and early in this era the first commercial-scale direct fluorination technology was invented at Exfluor Research Corporation in Austin, TX, by me and my colleagues, Tom Bierschenk, Tim Juhlke and Hajimu Kawa. The Inception era

The strategy behind the early successful direct fluorination technology was generated by John L. Margrave and me at Rice University, Houston, Texas. Later, after I'd been appointed to the faculty of the Massachusetts Institute of Technology, we joined forces to describe that strategy in great detail in a 1979 review [ 1]. An important tactic was to heavily dilute fluorine with helium or nitrogen in the initial stages of a fluorination reaction, then gradually increase the fluorine concentration to bring the reaction to completion over several days. While this and other features of our work have been well documented [ 1-4], and now are widely understood, the circumstances surrounding the discovery of successful techniques for direct perfluorination of organic and organoelemental materials have not been discussed in detail previously. In fact, it all began with work on the fluorination of carbon itself. 1L.

N. VauquelinRegentsProfessorof Chemistryand Materials Science.

284 Graphite fluoride 2

In the spring of 1963 through the fall of 1964, I was a young undergraduate student at Rice University who loved to play American football and became part of a superb research group built up by Professor John L. Margrave (Fig. 19.1). Ever since junior high school I'd wanted to be a high-temperature/high-energy chemist, but in some classroom lectures delivered by Margrave I also became fascinated with the possibilities of making fluorine compounds. Margrave graciously accepted me as a fledgling researcher in his laboratory and, quite significantly (in the story of direct fluorination) I focused first on the synthesis of graphite fluoride, working with two postdoctoral fellows, James Wood and Ram Badachappe, to learn how to handle fluorine. Graphite fluoride had first been prepared in the 1930s by Ruff and later by the Rtidorffs and Palin and Wadsworth in the 1940s. At that time, perfluorinated (pure white) graphite fluoride had not been prepared. In Margrave's lab nearly white graphite fluoride had been obtained once or twice by fluorinating carbon at temperatures over 700 ~ but the success rate was low (about once in every 20 runs). By using electronic temperature controllers, I was able consistently to make twenty-gram quantities of snow-white superstoicheiometric graphite fluoride of composition CFI.12 [ 1]. This impressed most of Margrave's research staff, and we sent samples to the National Aeronautic and Space Administration who reported that it was an excellent lubricant and stable at high temperatures. Later, at the US Army's Fort Monmouth research centre, Dr Herbert Hunger established that it was a terrific material for high-performance lithium batteries. This battery technology later spread to the Eagle Pitcher Battery Company and widely across Japan. Margrave started MarChem Corporation and sold white CF1.12 graphite fluoride samples under the tradename CFX | for ten US dollars per gram. I built a high-temperature reactor capable of preparing twenty grams of this material per day (Fig. 19.2) and between classes and football practice, was able to earn about a hundred dollars per day under an agreement whereby Margrave split the profits with me. This enabled me to buy a new Buick when I collected my PhD degree in 1969 and left Rice to join the faculty at MIT. Why is this relevant? It so happens in the field of synthetic chemistry that John and I did not set out to solve the 'hundred-years-old' problem of how to control the reactions of elemental fluorine with organic compounds. Rather, there were questions about the structure of graphite fluoride, since it had proven impossible to get a single crystal structure of graphite fluoride itself. Proposals by several people, including the Rtidorffs and Lagow and Margrave, later on turned out to be correct. The first successful direct fluorinations of organic compounds involved work that I judged might produce lower-molecular-weight structural analogues of 'white' graphite fluoride, the objective being to produce a small-scale version of graphite fluoride so that a crystal structure could be obtained. The problem was that fluorine was reported to react vigorously and often explosively at or below room temperature with all hydrocarbons whereas graphite only begins to react with fluorine at 400 ~ The subtrates chosen were 2Graphite fluoride is a solid, layered, nonstoicheiometric perfluorocarbon of empirical formulaCFx, where 1.25, obtained by treating carbon with F2; the value of x defines the grade of material under discussion [5]. The snow-white variety, composition CF> 1.0, is sometimescalled superstoicheiometricpoly(carbon monofluoride); this is generally believed to have a lamellar structure of weakly-couplednongraphitic sheets constructed from an infinite array of trans-linked cyclohexane 'chairs', with each sp 2 carbon covalently bound to a fluorine atom [3, 5] and carbons on the edge of the sheet bound to two fluorine atoms.

0 < x <~ca.

285

Fig. 19.1. The author (right) and Professor John L. Margrave: No one could have had a better Research Advisor.

Fig. 19.2. Multi-tray high-temperature reactor for preparing graphite fluoride.

286 the polynuclear aromatic hydrocarbons coronene and ovalene. The literature contained no reports on reactions involving the interior carbons of such polynuclear hydrocarbons; electrophilic substitution of peripheral hydrogen was known, of course. A 3/4" thick glass-encased reactor with stout plates of nickel at the top and bottom was on hand in Margrave's lab to use as an observation vessel when fluorine bomb calorimetrists had trouble achieving the complete combustion of compounds in fluorine; this way they could observe what it took to achieve their objective.

Coronene

Ovalene

I crafted a 3" by 3" tray out of nickel foil, placed about one gram of finely powdered coronene on this handmade 'boat' and placed it in the observation reactor so that just what happened when elemental fluorine contacted the hydrocarbon could be clearly seen. (The manifold that we used to deliver and control the fluorine is shown in Fig. 19.2.) As I cracked open the heavy autoclave valves slightly on the fluorine line, a flame about an inch high was observed in the reaction vessel. This flame disappeared when the valve was turned off after a short delay. Incredibly, even with pure fluorine, if the pulses were short one could reignite the reaction for several short spurts of fluorination. The material in the centre of the sample of bright orange coronene powder charred and became black in colour, but surprisingly around the edges of the sample, there appeared to be a white ash. When I tried lower concentrations of fluorine in the ballast-tube fluorine source, the amount of white ash increased. Actually, I thought that the reaction flame was rather tame. Since I was looking tbr a white solid comparable to graphite fluoride, I carefully used a spatula to separate the 'ashes' from the obviously decomposed centre section of the coronene sample and measured their infrared spectrum. You can image my delight when a strong C-F stretching absorption appeared at 1200 cm - I . Moving next to Margrave's time-of-flight mass spectrometer, the white product was found volatile enough to obtain a nice spectrum which contained a molecular ion corresponding to perfluoroperhydrocoronene as well as an [MF] + peak. Later that day, I fluorinated ovalene (a burnt orange powder) and found again that all the aromatic systems were saturated with fluorine and all the hydrogen replaced, according to the results of MS and IR analyses. From this work, I quickly concluded that if such a result could be obtained just by controlling the fluorine supply manually with a fairly coarse valve of the type used, then even greater success would surely be achieved if one could carefully measure and monitor as well as control the supply of elemental fluorine. At the time I had no real idea what the consequences would be; although later just what goes on in a simple elemental fluorine reaction was explained in detail [ 1,2]. No careful calculations of the thermodynamics and kinetics of fluorine's reactions with hydrocarbons were available to guide me in those early days in Margrave's l a b - just instinct and curiosity? Obviously, the central regions of

287 the coronene and ovalene samples had become charred, crosslinked and decomposed. In retrospect, the fluorinated white powders obtained contained at least fifty percent of 'polymeric' (crosslinked) material as well as saturated perfluorinated analogues of the aromatic substrates. My search for F2 control devices led me to one of my colleagues, Romy Bautista who told me about new Monel mass flowmeters that worked electronically with a flow-cooling transducer. Margrave had one on order at the time, and I ordered a second one. Initially, though, I controlled fluorine flow with Monel needle valves and found that passage of mixtures of fluorine and helium for 24 hours over finely-powdered coronene or ovalene contained in a long nickel boat inside a nickel tube reactor (fitted with Teflon | O-tings) converted all of the so coloured hydrocarbons to snow-white fluorocarbon materials with

no charring whatsoever.t My mind now turned to fluorinations ofpossible commercial significance. It did not take long to focus in that regard on the fluorination of finely-powdered polyethylene. In the same nickel apparatus, and using a continuous flow system starting with a 100% helium atmosphere then gradually increases the concentration of fluorine from 0 to 100%, I was able to prepare a perfluorinated polyethylene powder. When this new material was placed on a hot plate, I could clearly see that the high-temperature properties and inertness (to oxidation in air) were such that there was no doubt that is was perfluorocarbon in nature. At the time, the price of polytetrafluoroethylene was around $6.50 a pound, so what a bonanza, I thought, if one could make that same material with fluorine at $3.00 a pound and polyethylene at 30 cents a pound. (Later, it became clear that although the fluorinated polyethylene had all of the thermal and physical properties one associates with DuPont's Teflon | it was crosslinked and possessed other disadvantages.) I moved next to the fluorination of polyethylene bottles and vials. Surface fluorination gave them Teflon-like properties at a much lower price, and news of this was covered by C&EN in January 1970 [6]. Representatives of Air Products and Chemicals as well as Eddie Hedeya of Union Carbide really paid attention. The Rice University patent attorneys did not do a good job in protecting our intellectual property (they were oilfield attorneys), and both companies initiated work on the fluorination of plastic bottles. Air Products called their process 'Airopak', and Union Carbide labeled their technique the 'Linde Process' without licensing the Rice University patents. Margrave called the Rice University process the 'Fluorokote' technique. Margrave continued to suggest further research in the area, and I found samples (organic and inorganic) on my desk labelled 'Let's fluorinate this and see what happens. JLM'. So even though I continued to spend a lot of time playing football, I also kept four fluorination reactors running around the clock in my California-style hood, even on weekends. There were two things that I loved to do, one was synthetic chemistry and the other was making tackles and sacking quarterbacks (Fig. 19.3). Although our direct fluorination advance first came to light worldwide in C & E News in 1970 [6], it had been reported verbally in the US at a major meeting. In the winter of 1969 Professor Margrave had announced that he had scheduled the first public lecture on this discovery at a fluorine conference at Marquette University, and wanted me, at 21 years of age, to stand in for him as he had a conflict. To help with this task, he gave me a copy of Harry Emel6us's new book The Chemistry of Fluorine and Its Compounds (Academic Press, 1969) to read on the planes connecting to Marquette. Earlier in the fall of 1969, I had been interviewed for a faculty opening at MIT and presented a lecture on our breakthrough

288

Fig. 19.3. Dick Lagow (left) and George Schulgen -outstanding Rice Owls players in 1966 (the Rice Owls lost to the US National Champions 27 to 24 when UCLA kicked a field goal in the last three seconds; Lagow made 22 tackles in the game).

in elemental fluorine chemistry. This was followed two weeks later by an interview at UC Berkeley where I met the distinguished inorganic fluorine chemist, Neil Bartlett. I was offered the post at Berkeley on the spot, and a week and a half later A1 Cotton called to offer me an assistant professorship at M I T - which I accepted. A1 Cotton and Neil Bartlett have become life-long friends of mine. I remember meeting Darryl DesMarteau for the first time at Marquette. He was given a standing ovation before his talk as he was coming back from an accident in Cady's laboratory which had left him with only one natural arm. I have never seen anybody 'less handicapped' than Darryl. He is a strong fearless person with no mental scars and has become one of the world's best fluorine chemists. Also lauded with a standing ovation at the meeting was Jean'ne Shreeve, who had succeeded in being the first person to prepare tetrafluorourea, a synthetic target for many from 1965 through the mid-1970s, when defense programmes were in search of novel propellants and oxidizers. I'd realized before going to Marquette that what had been tersely presented in C&EN was controversial and provided little proof that our discovery was indeed real. Margrave warned me not to discuss direct fluorination in too much detail or the patents which Rice University had applied for could be jeopardized. At the end of my lecture there was quite a lengthy question-and-answer session with members of the fluorocarbon hierarchy, who were unconvinced. That great gentleman and eminent fluorine chemist George Cady stood up and asked: 'Are you are saying that you can take naphthalene and convert it with el-

~<~

289

emental fluorine to perfluorodecalin and obtain a 60% yield?' 'Yes', I replied. 'Will you take your chalk then and show me on the board exactly how you do this?', he continued. Although Cady was his usual gracious self, he was obviously unconvinced when I gave more detail, while explaining that my instructions were not to give complete descriptions of the apparatus and techniques. A year later, at the first Winter Fluorine Conference (St. Petersburg, Florida), I was invited to sit at Paul Tarrant's table, and so became aware of his great sense of humour (I already knew of Paul Tarrant's great chemistry). Midway into the meal, and after telling a lot of jokes and being extremely friendly, Paul leaned over and said, 'Organic compounds bum in elemental fluorine, don't they?' I thought carefully for several moments then answered, 'Paul, it really depends on how you do it' (which was a pretty good retort for a twenty-three year old). Seriously, fluorine chemists are some of the nicest people in the world, and over the years I have formed a great affection for these wonderful people. As this era closed, we had proven that finely powdered hydrocarbon solids can be converted to fluorocarbon analogues using controlled elemental fluorine as a reagent [4, 7]. The reaction times were often long (sometimes five to seven days in length) and scales were small (usually 1-2 g), but products hardly dreamed of previously had been made and characterized. The game was on.

The Interim period In 1969, I moved to MIT and rapidly built up a fluorine laboratory; this marked the beginning of the second era of direct fluorination synthesis with elemental fluorine in which the research goals changed. At this time, of course, it was necessary to raise research money, and in this regard, people in the Air Force funding system made major contributions to the work. First in line was the fluorine chemist, Dr Christ Tamborski, who strongly believed in direct fluorination and the potential of direct fluorination. The other key person was Dr Tony Matuszko of the Air Force Office of Scientific Research in Washington. At this stage, it was not in general possible to successfully fluorinate volatile samples or liquid materials. More importantly, the fluorination of volatile hydrocarbons, particularly those containing oxygen, had not been attempted except in a very cursory and exploratory way at Rice. Tamborski invited me to visit Wright-Patterson Air Force Base and the US Materials Laboratory in Dayton, Ohio. He then asked if my group would focus on producing oxygencontaining compounds, particularly perfluoropolyethers. Tamborski wanted to know if it was possible for us to preserve carbon-oxygen bonds at all. I informed him that we did not know for certain but we thought we could succeed. We had some ideas that might facilitate that result, and we were certainly anxious to try. Tamborski arranged for a $50000 per year grant and told me that if we were able to convert oxygen-containing hydrocarbon compounds to perfluorocarbon analogues he would double this amount in the second year. In 1969 and 1970, this was a lot of research money. Most of the oxygen-containing organic substrates in which the Air Force was immediately interested were volatile liquids. Obviously a new reactor system or set of systems would have to be designed. The way to proceed was with frozen liquids, but of course, even our freeze dried liquids in a powder form would have offered problems because only the surfaces would have been fluorinated.

290

C~,-O-CH,CH,-O-CH~-O-CH,~-TII"C CF,-O-CFtC~-O-CF, C~-O-CF,, , , , , , CH"~ CHz-.-~O

r2

/CFz"~ CF2-- 0

o/- c.,..c./

o'--cF,- cF,/

(40%)

Scheme 19.1.

,CH3 ,CH3 H3C- , C ~ C - C H 3 CH3 CH 3

F2/He ~ -78~

C,F3 C,F3 F3C-C,~ C , -CF 3 CF 3 CF3 H

F2/He

_

-78 ~

"-

F F

,

~

F

F

Scheme 19.2.

In the first days of the Lagow laboratory and throughout the next few years the key contributors were Dr Norma Maraschin, who was my first graduate student at MIT, Dr Ed Liu, and Dr James Adcock, who joined after receiving a PhD at the University of Texas at Austin. Various trials brought us the concept of the cryogenic 4- and 8-zone reactors [6] (Fig. 19.4) in which liquids and volatile materials were distilled slowly through lowtemperature gradients until they became perfluorinated and then collected downstream. The Lagow research group with Jim Adcock at the bench was very successful in preserving carbon-oxygen bonds using this technique [8-10] (e.g. Scheme 19.1); he was such a talented chemist that I've always said 'having him on a project increased the yield by ten to fifteen percent'. Other new achievements included the synthesis of structurally unusual fluorocarbons by Norma Maraschin [11, 12] (e.g. Scheme 19.2) and the successful fluorination of metal alkyls by Ed Liu [13]. Products were still made on only a two gram scale but the work was noteworthy because the synthetic achievements were, in general, unprecedented. Christ Tamborski was very proud of the success achieved with oxygen-containing organic compounds, particularly in the field of ethers. He wanted us to proceed with higher molecular weight materials, but at that time (1972) the basic research part of the military budget was cut so badly that the Wright-Patterson people decided to suspend support for academic chemistry. However, Tamborski was such a strong ally that he convinced Dr Anthony Matuszko to accept an AFOSR proposal on the same fluorination topic, so at least the Air Force Office was able to send me thirty-five thousand dollars. This was the first new grant that AFOSR had given to anyone for two years (since the end of the Sputnik funding era). Primary credit for the successes we enjoyed in the Interim period will always be due to Tony Matuszko and (with great appreciation) to Dr Don Ball, who was director of the Air Force Office of Scientific Research Chemistry Division. Tony was the best programme officer that my group has encountered in thirty years of chemistry. Matuszko took a lot of pride in what he supported, and he was a strong supporter of direct fluori-

291

Fig. 19.4. The first 4-zone cryogenicfluorine reactors and reaction system. nation. Throughout the years, Tamborski stayed a strong proponent of direct fluorination (he was right! - as revealed by progress during the early years of the Exfluor Research Corporation [ 14]). During the first part of the Interim era and extending into the second part, there were still a good number of fluorine chemists who did not believe that our fluorination techniques worked. Some actually thought that we were faking the results and simply fabricating spectra of the unusual new compounds we reported. It is fun to be a source of controversy and have achievements doubted: one receives a lot of invitations to speak and is often challenged. I have been quoted as saying, 'If one makes controversial and substantial breakthroughs and is proven right, then there is a lot of fun to be had in the process'; however, I suspect that it might not be much fun at all to be in that position and be proven incorrect. In the second phase of the Interim period, the leading researchers in my laboratory were PhD students, Hsu-Nan Huang, Todd Milsna, Win-Huey Lin and Robert Aikman. This was the era of the disk reactor, and amelioration of reactions with many new ether and polyether structures by scavenging HF with potassium fluoride or sodium fluoride to preserve these structures. The quantity of product was increased to the eight-to-ten grams range, and a very wide range of new classes of organometallic, inorganic and organofluorine compounds were prepared.

The Renaissance period From the inception of the Lagow Laboratory in 1969 in the Department of Chemistry at the Massachusetts Institute of Technology, direct fluorinations were normally conducted

292 on a five to twenty gram scale, and it was still not clear that it would be possible to scale up any of the reactions to commercial proportions. During this period over two thousand new organofluorine compounds and perfluorinated organometallic compounds were generated in the academic laboratories, first at MIT and then (post 1976) at The University of Texas at Austin. Leaders in the Lagow academic laboratory during the Renaissance phase were Dr Joel Kampa, Dr Han-Chao Wei, and Dr Tzuhn-Yaun Lin, and graduate students Ryan Callahan, Cameron Youngstrom, Dr Kuansen Sung and Dr Koichi Murata. They were major factors in our success. It is very significant, however, that one of the new concepts enabling high-volume production and scale-up of direct fluorination came from an experiment done 'just for fun' in our laboratory several years previously. In 1982, my first University of Texas student, Robert Aikman, and I tried using a CFC solvent at - 9 0 ~ to moderate the direct fluorination of hexamethyltungsten, a compound first made in about 1974 by Geoff Wilkinson and his co-workers. Despite the weakness of the carbon-tungsten bonds in W(CH3)6 (probably in the 20-35 kcal mo1-1 range), the yield of hexakis(trifluoromethyl)tungsten was about 50% (Scheme 19.3) when carried out in the reactor depicted in Fig. 19.5. (Note that this solution-phase reactor was very different from the reactors later developed by myself, Dr Thomas Bierschenk, Dr Timothy Juhlke and Dr Hajimu Kawa for use in the Lagow-Exfluor Process.) Wilkinson's new compound was more stable when complexed with triethylphosphine; Aikman's new perfluoroalkyltungsten counterpart was stable while uncomplexed in chlorofluorocarbon solvents but found to be even more stable when complexed with this phosphine. Aikman and I found it amazing that 20-35 kcal C - W bonds were surviving collisions with F2 to such an extent when the overall reaction leading to the conversion of just one C--H bond to C--F is more than 100 kcal exothermic. The intellectual picture that emerged from this finding is that the entire energy generated does not go into vibrational excitation of the tungsten-carbon bonds when a hydrogen attached to carbon in an entity RH is replaced in two steps by fluorine (RH + F. ~ R. + HF; R. + F2 ~ RF + F.). Hence, about half of the substrate species survived the 36 step free-radical conversion W(CH3)6 W(CF3)6, in which each of the 18 two-part CH ~ CF stages generates something of the order of 103 kcal mo1-1 of energy. Therefore the equilibrium constant (K) for this reaction is often greater than 1012l Note that with the Lagow-Aikman reactor there was no continuous addition of substrate, the reactant was highly diluted, and the reaction was conducted on only about a half-gram scale. However, this experiment taught us that one needs to have rapid vibrational relaxation in reactions between F2 and hydrocarbon moieties, and that cold 'inert' solvents efficiently promote such relaxation. Initiation of radical chain fluorination at low temperatures can be ascribed to molecule-induced homolysis of molecular fluorine, RH + F2 ~ R. + HF + F., which is spontaneous at room temperature although the enthalpy is slightly positive (for RH = CH4:AG298 = - 5 . 8 kcal mo1-1 and A H = 3.9 kcal mo1-1). Studies by researchers such as Dick Bernstein (UCLA), Doug McDonald (University of Illinois) and Dick Zare (Stanford) have revealed that the activation energy for abstraction of hydrogen atom from an alkane by molecular fluorine in the gas phase ranges from zero to 'as high as' 1 cal (not kcal) mo1-1 [4]. This reaction is one of the fastest chemical reactions known. Details of the design and operation of very successful lab-scale solution-phase fluorination reactors created in my academic laboratory at the University of Texas can be found

293

F2/He

W(CH3)6

CFCI3, -90 ~

W(CF3) s -50% yield

PEt3 ,.~_ W(CF3)s.PEt3 CFCl 3

Scheme 19.3.

Fig. 19.5. Solution-phase reactor used to prepare W(CF3) 6.

Fig. 19.6. Exfluor's talented staff-(left to right) Tim Juhlke, Tom Bierschenk, Hajimu Kawa and the author (far right) was very fortunate to have them.

294 in a recent review [4]. These have been used by Dr Han-Chao Wei to prepare, for example, the unique perfluorinated crown ethers 1-4 [4, 15]. = F2F2F, F2~. F ~ ~ O / ~o/~r2 F2 _ F~o ' ~,F~ I'/~..~ F2 F2~ ~"~F2

g,

F~o

O~F~

~,_~ F~

_~F~ ~

F2~-Zo /

o~...J,F~

F2F~O 2 /0

F2F~/I

0 ~ _ F2 - \ F2 0 ~x~F2

0

o-%F

0

F2

"7 F2q,o

_.,,,,'F2 O.--.J

0

F2~O~.__jO~ ,~ F2 F2 1:2 F2

(1)

(2)

F2

.o

F2 ~'~

2F~-/'~_./N.J= F2 " F2 F2 F2 F2 '-2

~\_

F2 F2 ~ 0 / ~ 0 , ~

F2 1:2 F2~O'~F2

F2

o~o I I

F2~,.,..,u.., I O'~F2F2X'~0~ F2

/F~ o:,

.u,_./ ,., )F2

F2

F2

F2 F2 F 2 ~ 0 1 ~ I F2

o_ o

F~'o

o--"/- ~'~---o

-P

/ | F2 F2 / Y Fzt~,10-~'J F2 F21~,,o~,J F2

F2

(3)

(4)

Liquid-phase direct fluorination technology has been developed further at the Exfluor research Corporation of Austin (Texas) in collaboration with two of my former graduate (PhD) students Dr Tom Bierschenk (University of Texas at Austin), Tim Juhlke (MIT) - both hired in 1982 - and Dr Hajimu Kawa (Tokyo Institute of Technology), who came in 1984. These talented people (Fig. 19.6) teamed up with me to generate the Lagow-Exfluor elemental fluorine process which is described in several US patents [16]. The procedure involved enabled extremely high yields of perfluorinated products to be achieved (often 95-99%) on a kilogram to multi-ton scale. Products sold by Exfluor include CFa(CFE)xCOEH (x = 9, 10, 12, 14, 16), HOEC(CF2)xCO2H (x = 4, 6, 8, 10), CF3(CF2)sBr, and Br(CF2)8Br [4]. For the records, I founded 'Exfluor' in 1987; it was funded primarily by Federal government research contracts and its goal was to develop direct fluorination technology. Exfluor Research Corporation uses it commercial-scale fluorination reactors to produce extraordinarily pure fluorocarbons that are especially suitable as new biomedical and biomaterials since they are often orders of magnitude purer than those obtainable via other routes. Our procedures often produce only a single compound containing virtually no hydrogen and without complications arising from the occurrence of crosslinking during the fluorination. For example, some of the perfluoroethers synthesized contain residual hydrogen in concentrations below 3 parts per billion; to put that in perspective, in polytetrafluoroethylene made from tetrafluoroethylene monomer, the hydrogen content is several parts per million.

295

Epilogue Way back in the late '60s, John Margrave and I realized immediately that we had made a substantial and perhaps very important discovery. In retrospect, however, I could not have predicted the breadth of the impact direct fluorination has had on synthetic capabilities in organofluorine and fluoro-organoelemental areas. I certainly learned a lot from John, and I have been very fortunate, first at MIT and then at the University of Texas and at Exfluor, to have been able to surround myself with excellent young chemists. I've always done my best to encourage them to think for themselves, to be innovative, and to try to do things that many would expect to fail. Even though direct fluorination isn't the answer to every synthetic challenge, it looks now that it will become the most broadly applicable general synthetic technique utilized by organofluorine chemists (both in the laboratory and on a commercial scale) during the next century.

Acknowledgement Fluorine chemistry at the University of Texas is funded by the US National Science Foundation (CHE 9972888).

References 1 R.J. Lagow and J. L. Margrave, 'Direct Fluorination: A New Approach to Fluorine Chemistry', Prog. Inorg. Chem., 26 (1979) 161. 2 R.J. Lagow, 'High-Yield Reactions of Elemental Fluorine', in R. E. Banks, D. W. A. Sharp and J. C. Tatlow (eds.), Fluorine: The Fist Hundred Years (1886-1986), Elsevier Sequoia, Lausanne and New York, 1986, pp. 321-325. 3 R.J. Lagow, 'Direct Fluorination', in M. Howe-Grant (ed.), Fluorine Chemistry: A Comprehensive Treatment, John Wiley, New York, 1995, pp. 242-259. (Reprinted from the Kirk-Othmer Encyclopaedia of Chemical Technology.) 4 R. J. Lagow, in Organofluorine Compounds (Methods of Organic Chemistry: Houben We3,1), Georg Thieme Verlag, Stuttgart, Vol. E10a, 1999, pp. 188-193 ('Reactions of Fluorine with Solids'), pp. 194-201 ('Reactions of Fluorine in the Presence of Solvents'). 5 N. Watanabe and T. Nakajima, 'Graphite Fluoride', in R. E. Banks (ed.), Preparation, Properties and Industrial Application of Organofluorine Compounds, John Wiley, New York, 1982, pp. 297-322. 6 Chemical & Engineering News, 48, No. 2 (January 12) (1970) 41-42. 7 R.J. Lagow and J. L. Margrave, 'Direct Fluorination of Organic and Inorganic Substances', Proc. Natl. Acad. Sci., 67 (1970) 4, 8A. 8 J. L. Adcock and R. J. Lagow, 'The Synthesis of the Perfluoroethers, Perfluoroglyme and Perfluorodiglyme by Direct Fluorination', J. Org. Chem., 38 (1973) 3617. 9 J.L. Adcock and R. J. Lagow, 'The Synthesis of Perfluoro-1,4-dioxane, Perfluoro(ethyl acetate)and Perfluoropivaloyl Fluoride by Direct Fluorination', J. Am. Chem. Soc., 96 (1974) 7588. 10 J. L. Adcock, R. A. Beh and R. J. Lagow, 'Successful Direct Fluorination of Oxygen-Containing Hydrocarbons', J. Org. Chem., 40 (1975) 3271. 11 R.J. Lagow and N. J. Maraschin, 'The Successful Fluorination of Neopentane: A Challenge Met by Direct Fluorination', Inorg. Chem., 12 (1973) 1459. 12 N. J. Maraschin, B. D. Catsikis, L. H. Davis, G. Jarvinen and R. J. Lagow, 'The Synthesis of Structurally Unusual Fluorocarbons by Direct Fluorination', J. Am. Chem. Soc., 97 (1975) 513. 13 E.K.S. Liu and R. J. Lagow, J. Organometal. Chem., 145 (1978) 161; Chem. Commun., (I977) 450; Inorg. Chem., (1978) 618 E.

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