Novel fluorination reagent: IF5/Et3N-3HF

Article abstract of DOI:10.1246/cl.2001.222

IF₅ in Et₃N-3HF was found to be a stable, non-hazardous, easy to handle, and inexpensive reagent that enables effective and selective fluorination of organic compounds under mild conditions.

Full text of DOI:10.1246/cl.2001.222

222
Chemistry Letters 2001
Novel Fluorination Reagent: IF5 / Et3N–3HF
Norihiko Yoneda* and Tsuyoshi Fukuhara
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
(Received December 13, 2000; CL-001116)
IF5 in Et3N–3HF was found to be a stable, non-hazardous,
pared by adding a substrate (1.0 mmol) dissolved in a solvent (2
mL) to 1.2 mmol of IF5 / Et3N–3HF with 4 mL of a solvent at
room temperature. D) The same procedure as C) except at –78
°C.
easy to handle, and inexpensive reagent that enables effective
and selective fluorination of organic compounds under mild
conditions.
A wide variety of reagents have been developed for intro-
ducing fluorine into organic compounds over the last 50 years1
with several halogen fluorides such as ClF3 and BrF3 so on.2,3
However, iodine fluorides (IFn; n=1, 3 and 5), except for IF,
have hardly been employed in organic fluorination reactions,
because of their hazardousness, instability and high reactivity.3
We describe here for the first time an efficient and convenient
fluorination reagent, called IF5 / Et3N–3HF, (IF5 in Et3N–3HF
solution), which is non-hazardous, easy to handle and inexpen-
sive,4 and selectively fluorinates organic compounds under mild
conditions.
IF5 itself is a hazardous chemical (bp 100.5 °C, mp 9.4 °C,
vapor pressure: 2190 Pa at 21 °C)5 and is very sensitive to
moisture. IF5 / Et3N–3HF (IF5:Et3N:HF = 1:1:3 molar ratio),6
on the other hand, is not sensitive to moisture and has a low
vapor pressure7 of 270 Pa at 21 °C. 19F NMR spectra of IF5,
IF5 / HF, and IF5 / Et3N–3HF solutions are shown in Figure 1.
It is well known that IF5 has two kinds of fluorine atoms: Fa
and Fb (1:4).8 These can be clearly assigned because of their
distinct NMR shifts as shown in a and b of Figure 1. In the 19
F
NMR spectrum of IF5 / Et3N–3HF, however, the two signals for
Fa and Fb become extinct and a new chemical shift emerges at
–53.1 ppm (broad s). On the other hand, the chemical shift is
divided into two broad signals at 7.5 ppm and –160 ppm with
integration ratio of 1:1 at low temperatures (–40 °C). Judging
from these results, IF5 in Et3N–3HF solution is thought to form
a novel complex. The structure of the complex has not been
confirmed yet. Further investigations are necessary to clarify
the structure of IF5 / Et3N–3HF.
Fluorination of organic compounds has been carried out
according to the following procedures (A, B, C, and D). A) In a
15-mL PFA9-made reactor equipped with a reflux condenser
and/or a cold trap, 1.2 mmol of IF5 / Et3N–3HF (0.46 g, ca. 0.27
mL) was added together with 4 mL of solvent. A substrates
(1.0 mmol) was then added and the mixture was allowed to
stand with stirring at the desired temperature and time. The
reaction mixture was then quenched, neutralized with aqueous
NaHCO3, and washed with 10% sodium thiosulfate. The prod-
ucts were extracted with ether, isolated by column chromatog-
raphy (silica gel / hexane–ether), and identified by conventional
spectroscopic methods. B) In a 100 mL PFA-made reactor
equipped with a reflux condenser and/or a cold trap, a substrate
(1.0 mmol) dissolved in 20 mL of solvent was added to 1.2
mmol of IF5 / Et3N–3HF in 20 mL of solvent at room tempera-
ture for 1 h, and then allowed to stand with stirring at the
desired temperature and time. C) The reaction mixture was pre-
The results obtained are listed in Table 1. The correspon-
ding organo-fluorine compounds were obtained in satisfactory
yields except for olefins, although the present conditions for
fluorination does not give the optimum results.
Fluorinative ring-opening of epoxides and transformation
of alcohols to alkyl fluorides are known to occur by reacting
with amine–HF such as pyridine–9HF,10 but, with the inevitable
formation of some by-products together with tarry matter
because of the high acidity of the reagents used. In addition,
although tertiary and secondary alcohols are readily fluorinated
in pyridine–HF, transformation of primary alcohol to the corre-
sponding RF hardly takes place in the presence of such amine-
HF reagents. It should be noted that Et3N–3HF itself can not
initiate the fluorination of all substrates listed in Table 1. In the
absence of Et3N–3HF, inevitable violent reaction of IF5 takes
place to give the considerable amount of undesirable tarry like,
sometimes, carbonized mater. And selective fluorination can
be accomplished by the reaction using IF5 only in the presence
of Et3N–3HF under mild conditions. However, the mechanism
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
223
has not been clarified yet. The active species in IF5 /
Et3N–3HF, reaction mechanism, and scope of this novel fluori-
nation reagent are under investigation.
In conclusion, we have successfully developed an efficient,
convenient and novel selective fluorination reagent, IF5 /
Et3N–3HF, for organic compounds. We believe this novel fluo-
rination reagent may open up a new field in the synthesis of
varieties of organofluorine compounds.
The authors would like to acknowledge Daikin Industrial
Co., Ltd., for providing IF5 and financial support. Thanks are
also due to Mitsubishi Kagaku Co., Ltd., JEMCO Co., Ltd., and
Asahi Denka Co., Ltd., for financial support.
References and Notes
1
S. D. Taylor, C. C. Kotoris, and G. Hum, Tetrahedron, 55,
12431 (1999).
2
a) “New Fluorinating Agents in Organic Synthesis,” ed. by
L. German and S. Zemskov, Springer-Verlag Tokyo
(1989). b) Y. Katsuhara and D. DesMarteau, J. Am. Chem.
Soc., 102, 2681 (1980).
3
4
a) S. Rozen and M. Brand, J. Org. Chem., 50, 3342 (1980).
b) “The Merck Index,” 12th ed., Merck & Co., Inc.,
Whitehouse Station, NJ (1996) p.861.
a) IF5 is industrially produced for the production of surfac-
tant and textile chemicals. H. C. Fielding, “Organofluorine
Chemicals and Their Industrial Applications,” ed. by R. E.
Banks, Ellis Harwood Publishers, Chichester (1979), Chap.
11. b) M. Schmeisser, P. Sartoi, and D. Naumann, Chem.
Ber., 103, 880 (1970).
5
6
a) E. W. Osborne, F. Schreiner, and H. Selig, J. Chem.
Phys., 54, 3790 (1971). b) M. T. Rogers, J. L. Speirs, H. B.
Thompson, and M. B. Panish, J. Am. Chem. Soc., 76, 4843
(1954).
A prescribed amount of Et3N–3HF was pipetted into
50–100 mmol of IF5 in a 30-mL PFA9 bottle without cool-
ing since the temperature did not rise appreciably. Thus,
any particular precautionary measures are not necessary for
the preparation of IF5 / 3HF–Et3N. This reagent can be
stored in PFA bottle for several months on a laboratory
table without any particular caution and without any deteri-
oration of fluorination activity.
7
8
9
Vapor pressure measurement of IF5 / 3HF–Et3N was carried
out according to the technique described in ref 5b.
R. D.Burbank and G. R. Jones, Inorg. Chem., 13, 1071
(1974).
Tetrafluoroethylene-perfluoroalkylvinyl-ether co-polymer.
10 N. Yoneda, Tetrahedron, 47, 5329 (1991).