Halofluorination of alkenes with ionic liquid EMIMF(HF)2.3

Article abstract of DOI:10.1016/j.jfluchem.2003.11.015

Halofluorination of alkene by means of N-halosuccinimide and ionic liquid, 1-ethyl-3-methylimidazorium oligo hydrogenfluoride (EMIMF(HF)_2.3), was demonstrated. Various alkenes were converted into β-halo organofluorides in good yields after non-

Full text of DOI:10.1016/j.jfluchem.2003.11.015

Journal of Fluorine Chemistry 125 (2004) 455–458
Halofluorination of alkenes with ionic liquid EMIMF(HF)2.3
Hideaki Yoshinoa, Seijiro Matsubaraa,*, Koichiro Oshimaa, Kazuhiko Matsumotob,
Rika Hagiwarab, Yasuhiko Itob
aDepartment of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoutodaigaku-Katsura,
Nishikyo, Kyoto 615-8510, Japan
bDepartment of Fundamental Energy Science, Graduate School of Energy Science, Kyoto University,
Yoshida hon-machi, Sakyo, Kyoto 606-8501, Japan
Received 25 August 2003; received in revised form 25 November 2003; accepted 29 November 2003
Abstract
Halofluorination of alkene by means of N-halosuccinimide and ionic liquid, 1-ethyl-3-methylimidazorium oligo hydrogenfluoride
(EMIMF(HF)2.3), was demonstrated. Various alkenes were converted into b-halo organofluorides in good yields after non-aqueous
work-up.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Iodofluorination; Bromofluorination; Ionic liquid; Hydrogen fluoride
1. Introduction
2. Results and discussion
Halofluorination of alkenes has been a useful method to
incorporate fluorine atom into organic molecules, and the
obtained b-halo subunit is available for further reaction to
obtain various organofluoro compounds [1,2]. To prepare vic-
halofluoroalkanes, alkenes are reacted with halonium ion and
fluoride ion. As fluoride ion sources in these procedures,
elemental fluorine [3], hydrogen fluoride [4,5], HF-pyridine
(Olah’s reagent) [6,7], Et3N-3HF [8], silver fluoride [9],
potassium fluoride-poly(hydrogen fluoride) [10], and silicon
tetrafluoride [11] have been used. In these procedures, the
difficulties to handle these reagents should be taken care
because of their hazardous property and the occurrence of HF
at the aqueous work-up could not be avoided. Recently, ionic
liquid has been paid much attention because of the easiness in
handling and the possibility of non-aqueous work-up espe-
cially in the field of green chemistry and combinatorial
chemistry [12]. 1-Ethyl-3-methylimidazorium oligo hydro-
gen fluoride (EMIMF(HF)2.3), ionic liquid, which is stable
in air and moisture, might be used as fluoride ion source
ionic liquid. Herein, we wish to report halofluorination of
alkenes with combination of N-halosuccinimide and the ionic
liquid.
EMIMF(HF)2.3 was synthesized by a direct reaction of 1-
ethyl-3-methylimidazolium chloride and anhydrous hydro-
gen fluoride according to the reported procedure [13]. This
ionic liquid is stable against moisture and air. It consists of
1-ethyl-3-methylimidazorium cation and F(HF)2.3 anion, in
which a rapid exchange of HF between H2F3 and H3F4
occurs [13] (Fig. 1).
Reactions were carried out in polypropylene tall tubes that
are easy to handle for decantation in work-up process. To
a mixture of substrate dissolved in CH2Cl2 and ionic liquid,
N-iodosuccinimide (NIS) was added in several portions. The
reaction mixture gradually turned to be clear and yellow.
When the reaction was finished, hexane was added to the
reaction mixture. The resulting mixture became biphase.
Decantation of upper phase gave a hexane solution of the
produced b-halofluoride. After the solution was passed
through a short silica-gel column, it was concentrated under
reduced pressure (Scheme 1).
Results of iodofluorination of alkenes are summarized in
Table 1. The iodofluorination products of various alkenes,
aliphatic, cyclic, and aryl alkenes were obtained in good
yields and with high regioselectivity. As shown in entries
3 and 4, the reaction proceeded with anti-manner. When
1-fluoro-2-iodo-1-phenylpropane, prepared from (E)-
1-phenylpropene, was treated with DBU at room tempera-
ture, dehydroiodination occurred to give (E)-1-fluoro-
* Corresponding author. Tel.: þ81-75-383-2441; fax: þ81-75-383-2438.
E-mail address: matsubar@mc.kyoto-u.ac.jp (S. Matsubara).
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2003.11.015

456
H. Yoshino et al. / Journal of Fluorine Chemistry 125 (2004) 455–458
Table 2
HF
F
HF
F(HF)2.3
N
Bromofluorination of alkenes
HF
F
N
FH HF
HF
Entry
1
Alkene
Time (h) Product
3
Yield (%)
86a
Fig. 1. EMIMF(HF)2.3
.
2
1
90
NIS (2 eq.), EMIMF(HF)2.3
CH2Cl2, r. t.
R
F
I
R
3
4
1
1
90
95
Scheme 1.
1-phenylpropene stereospecifically (Scheme 2) as reported
by Schlosser [14,15].
Bromofluorination of olefines also proceeded under the
same conditions using N-bromosuccinimide (NBS) instead
of NIS. Results are summarized in Table 2. vic-Bromo-
fluoroalkanes were also obtained in good yields. Chloro-
fluorination was also examined by N-chlorosuccinimide, but
resulted in low yields in spite of longer reaction time
(Scheme 3).
In summary, we demonstrated halofluorination of alkenes
with mild and safe fluorinating reagent EMIMF(HF)2.3
which makes the non-aqueous work-up possible.
5
6
7
1
1
1
81
87
93
a 1-Fluoro-2-bromo-decane was also obtained in 9% yield.
3. Experimental
Table 1
Iodofluorination of alkenes
Reagents were purchased from Wako Chemical, Inc. or
Tokyo Kasei, and used without further purification. Reac-
tions were monitored by thin-layer chromatography using
25 mm E. Merck silica-gel plates (Silica Gel F254). Silica-
gel was purchased from Kanto Chemical Co. The polypro-
pylene tube used was a centrifuge tube (15 ml) with a screw
cap, and is available from Corning. NMR spectra were
recorded on a Varian Gemini 300 or Mercury 2000 in CDCl3.
EMIMF(HF)2.3 was prepared according to the literature
[13].
Entry
1
Alkene
Time (h) Product
3
Yield (%)
80a
2
3
36
1
64b
91
4
5
1
1
95
98
3.1. General procedure for halofluorination
In a 15 ml polypropylene tube, CH2Cl2 (500 ml) solution
of alkene (1 mmol) and EMIMF(HF)2.3 (600 ml) were placed
and stirred with magnetic stirrer vigorously. To this reaction
mixture, N-halosuccinimide (2 mmol) was added in several
portions at room temperature. When the reaction finished,
hexane (1 ml) was added and the whole was stirred vigor-
ously. The stirring was stopped, the mixture was separated
into two phases. The upper layer was collected by decanta-
tion. This extraction with hexane was repeated twice more.
The combined hexane layers were passed through a short
silica-gel column (1 cm) to obtain crude product. The crude
product was purified by a short silica-gel column chromato-
graphy. Yield was determined by 19F NMR in comparison
with internal standard.
6
7
8
1
1
1
70
88
78
a 1-Fluoro-2-iodo-undecane was also obtained in 2% yield.
b 1 mmol of NIS was used. Thirty percent of starting material was
remained.

H. Yoshino et al. / Journal of Fluorine Chemistry 125 (2004) 455–458
457
F
F
NIS, EMIMF(HF)2.3
CH2Cl2, r. t.
DBU
I
CH2Cl2, r. t.
E / Z = > 99:1
85%
95%
Scheme 2.
NBS (2 eq.), EMIMF(HF)2.3
CH2Cl2, r. t.
R
F
Br
3.8. 1-(1-Fluoro-2-iodo-ethyl)-4-methyl-benzene
R
1H NMR (300 MHz, CDCl3): d 7.28–7.15 (m, 4H) 5.52
(ddd, J ¼ 45:3, 18.6, 6.3 Hz, 1H), 3.55–3.40 (m, 2H), 2.37
(s, 3H). 13C NMR (75 MHz, CDCl3): d 139.3, 135.1 (d,
J ¼ 20:5 Hz), 129.6, 125.8 (d, J ¼ 6:2 Hz), 93.4 (d,
J ¼ 175:5 Hz), 21.7, 7.9 (d, J ¼ 28:8 Hz). 19F NMR
(282 MHz, CDCl3): d ꢀ164.6 (ddd, J ¼ 45:4, 23.7,
15.8 Hz). Anal. Calcd for C9H10FI: C, 40.93; H, 3.82.
Found: C, 40.66; H, 3.69.
Scheme 3.
3.2. 2-Fluoro-1-iodo-undecane
1H NMR (300 MHz, CDCl3): d 4.41 (ddt, J ¼ 48:0, 10.8,
1.5 Hz, 1H), 3.31 (ddd, J ¼ 20:1, 5.7, 2.1 Hz, 2H), 1.80–
1.65 (m, 2H), 1.45–1.20 (m, 16H), 0.88 (t, J ¼ 6:9 Hz, 3H).
19F NMR (282 MHz, CDCl3): d ꢀ170.6 (m).
3.9. Erythro-(1-fluoro-2-iodo-propyl)-benzene
3.3. 2-Fluoro-1-iodo-2-methyl-dodecane
1H NMR (300 MHz, CDCl3): d 7.39–7.13 (m, 5H), 5.53
(dd, J ¼ 46:5, 6.0 Hz, 1H), 4.49–4.34 (m, 2H) 1.91
(d, J ¼ 6:9 Hz, 3H). 19F NMR (282 MHz, CDCl3): d
ꢀ172.3 (dd, J ¼ 46:5, 17.2 Hz).
1H NMR (300 MHz, CDCl3): d 3.34 (d, J ¼ 16:8 Hz, 2H),
1.83–1.72 (m, 2H), 1.49 (d, J ¼ 21:0 Hz, 3H), 1.40–1.20 (m,
16H), 0.88 (t, J ¼ 6:9 Hz, 3H). 19F NMR (282 MHz,
CDCl3): d ꢀ140.0 (m).
3.10. (E)-1-fluoro-1-phenyl-1-propene
3.4. 1-Fluoro-2-iodo-cyclohexane
To
a
solution of (1-fluoro-2-iodo-propyl)-benzene
(0.5 mmol) in CH2Cl2 (5 ml) was added DBU (0.15 g,
1 mmol) at room temperature. The reaction mixture was
stirred for 12 h at ambient temperature, and then quenched
with sat. NH4Claq and extracted with hexane three times.
The combined organic layers were dried over Na2SO4, and
evaporated. The crude was purified with a silica-gel column
chromatography. 1H NMR (300 MHz, CDCl3): d 7.50–7.35
(m, 5H), 5.47 (dq, J ¼ 22:5, 7.5 Hz, 1H), 1.80 (dd, J ¼ 7:5,
2.7 Hz, 3H). 19F NMR (282 MHz, CDCl3): d ꢀ102.6
(dq, J ¼ 22:5, 2.7 Hz).
1H NMR (300 MHz, CDCl3): d 4.52 (ddt, J ¼ 47:7, 8.7,
4.5 Hz, 1H), 4.16–4.06 (m, 1H), 2.44–2.30 (m, 1H), 2.28–
2.13 (m, 1H), 2.02–1.78 (m, 2H), 1.66–1.54 (m, 2H),
1.50–1.24 (m, 2H). 19F NMR (282 MHz, CDCl3): d
ꢀ159.5 (m).
3.5. 1-Fluoro-2-iodo-1-methyl-cyclohexane
1H NMR (300 MHz, CDCl3): d 4.37 (dt, J ¼ 8:1, 4.2 Hz,
1H), 2.30–2.08 (m, 2H), 2.00–1.87 (m, 1H), 1.82–1.62 (m,
3H), 1.56 (d, J ¼ 22:2 Hz, 3H), 1.54–1.40 (m, 2H). 19F
NMR (282 MHz, CDCl3): d ꢀ132.4 (m).
3.11. 1-Bromo-2-fluoro-dodecane
1H NMR (300 MHz, CDCl3): d 4.62 (dddt, J ¼ 48:6, 7.5,
5.4, 5.4 Hz, 1H), 3.51 (ddd, J ¼ 19:8, 10.8, 5.4 Hz, 2H),
1.77–1.64 (m, 2H), 1.49–1.26 (m, 16H), 0.88 (t, J ¼ 6:8 Hz,
3H). 19F NMR (282 MHz, CDCl3): d ꢀ178.0 (dddt,
J ¼ 48:6, 27.0, 19.8, 19.8 Hz).
3.6. (1-Fluoro-2-iodo-ethyl)-benzene
1H NMR (300 MHz, CDCl3): d 7.50–7.30 (m, 5H), 5.53
(ddd, J ¼ 46:5, 7.2, 4.8 Hz, 1H), 3.55–3.41 (m, 2H). 19F
NMR (282 MHz, CDCl3): d ꢀ166.4 (ddd, J ¼ 46:5, 23.7,
17.8 Hz).
3.12. 1-Bromo-2-fluoro-2-methyl-dodecane
3.7. (1-Fluoro-2-iodo-1-methyl-ethyl)-benzene
1H NMR (300 MHz, CDCl3): d 3.46 (d, J ¼ 15:9 Hz, 2H),
1.80–1.71 (m, 2H), 1.46 (d, J ¼ 21:3 Hz, 3H), 1.39-1.26 (m,
16H), 0.88 (t, J ¼ 7:2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d 95.0 (d, J ¼ 171:5 Hz), 38.3 (dd, J ¼ 41:2, 25.6 Hz), 32.0,
29.8, 29.7, 29.6, 29.5, 29.4, 23.6, 23.6, 23.5, 23.4, 23.3, 22.8.
1H NMR (300 MHz, CDCl3): d 7.50–7.30 (m, 5H), 3.59
(d, J ¼ 20:4 Hz, 2H), 1.86 (d, J ¼ 21:6 Hz, 3H). 19F NMR
(282 MHz, CDCl3): d ꢀ142.4 (tq, J ¼ 21:6, 20.4 Hz).

458
H. Yoshino et al. / Journal of Fluorine Chemistry 125 (2004) 455–458
19F NMR (282 MHz, CDCl3): d ꢀ144.9 (m). Anal. Calcd
for C13H26FBr: C, 55.52; H, 9.32. Found: C, 55.59;
H, 9.13.
(s, 3H). 19F NMR (282 MHz, CDCl3): d ꢀ172.3 (ddd,
J ¼ 46:8, 25.9, 18.9 Hz).
3.13. 1-Bromo-2-fluoro-cyclohexane
Acknowledgements
1H NMR (300 MHz, CDCl3): d 4.48 (ddt, J ¼ 48:0, 8.4,
4.5 Hz, 1H), 4.07–3.97 (m, 1H), 2.35–2.17 (m, 2H), 1.89–
1.62 (m, 4H), 1.42–1.31 (m, 2H). 19F NMR (282 MHz,
CDCl3): d ꢀ167.4 (dm, J ¼ 48:0 Hz).
Financial support by Grant-in-Aid from the Ministry of
Education, Science, Sports, and Culture is acknowledged.
Financial support by Chugai Pharmaceutical Co. Ltd. is also
acknowledged.
3.14. 2-Bromo-1-fluoro-1-methyl-cyclohexane
References
1H NMR (300 MHz, CDCl3): d 4.20 (dt, J ¼ 7:2, 3.9 Hz,
1H), 2.35–1.25 (m, 8H), 1.51 (d, J ¼ 22:4, 3H). 19F NMR
(282 MHz, CDCl3): d ꢀ137.0 (m).
[1] C.M. Sharts, W.A. Sheppard, Org. React. 21 (1974) 125–406.
[2] T. Hiyama, Organofluorine Compounds, Springer-Verlag, New York,
2000.
[3] S. Rozen, M. Brand, J. Org. Chem. 50 (1985) 3342–3348.
´
[4] A. Bowers, L.C. Iban˜ez, E. Denot, R. Becerra, J. Am. Chem. Soc. 82
3.15. 2-Bromo-1-fluoro-1-phenyl-ethane
(1960) 4001–4007.
1H NMR (300 MHz, CDCl3): d 7.51–7.35 (m, 5H), 5.50
(ddd, J ¼ 46:8, 7.2, 4.2 Hz, 1H), 3.64–3.43 (m, 2H). 19F
NMR (282 MHz, CDCl3): d –174.1 (ddd, J ¼ 46:8, 23.7,
16.5 Hz).
[5] A. Bowers, E. Denot, R. Becerra, J. Am. Chem. Soc. 82 (1960)
4007–4012.
[6] G.A. Olah, J.T. Welch, Y.D. Vankar, M. Nojima, I. Kerebe, J.A. Olah,
J. Org. Chem. 44 (1979) 3872–3881.
[7] D.Y. Chi, M.R. Kilbourn, J.A. Katzenellenbogen, M.J. Welch, J. Org.
Chem. 52 (1987) 658–664.
3.16. (2-Bromo-1-fluoro-1-methyl-ethyl)-benzene
[8] G. Alvernhe, A. Lawrent, G. Haufe. Synthesis (1987) 562–564.
[9] L.D. Hall, J.F. Manville, Can. J. Chem. 51 (1973) 2902–2913.
[10] M. Tamura, M. Shibakami, A. Sekiya, Synthesis (1995) 515–517.
[11] M. Shimizu, Y. Nakahara, H. Yoshioka, J. Chem. Soc., Chem.
Commun. (1989) 1881–1882.
1H NMR (300 MHz, CDCl3): d 7.43–7.32 (m, 5H), 3.73–
3.60 (m, 2H), 1.84 (d, J ¼ 22:2 Hz, 3H). 19F NMR
(282 MHz, CDCl3): d ꢀ147.5 (ddq, J ¼ 22:2, 22.2,
18.4 Hz).
[12] C.C. Tzschucke, C. Markert, W. Bannwarth, S. Roller, A. Hebel, R.
Haag, Angew. Chem. Int. Ed. 41 (2002) 3964–4000.
[13] R. Hagiwara, T. Hirashige, T. Tsuda, Y. Ito, J. Electrochem. Soc. 149
(2002) D1–D6.
3.17. 1-(2-Bromo-1-fluoro-ethyl)-4-methyl-benzene
[14] H. Suga, T. Hamatani, Y. Guggisberg, M. Schlosser, Tetrahedron 46
(1990) 4255–4260.
1H NMR (300 MHz, CDCl3): d 7.38–7.18 (m, 4H), 5.57
(ddd, J ¼ 46:8, 8.1, 4.2 Hz, 1H), 3.75–3.53 (m, 2H), 2.37
[15] M. Kuroboshi, T. Hiyama, Bull. Chem. Soc. Jpn. 68 (1995)
1799–1805.