A mild ring opening fluorination of epoxide with ionic liquid 1-ethyl-3-methylimidazorium oligo hydrogenfluoride (EMIMF(HF) 2.3)

Article abstract of DOI:10.1016/j.jfluchem.2004.02.002

Ring opening fluorination of epoxides with hydrogen fluoride in ionic liquid 1-ethyl-3-methylimidazorium oligo hydrogenfluoride EMIMF(HF)_2.3 was demonstrated. This ionic liquid released hydrogen fluoride graduately to make mild conditions witho

Full text of DOI:10.1016/j.jfluchem.2004.02.002

Journal of Fluorine Chemistry 125 (2004) 1127–1129
A mild ring opening fluorination of epoxide with ionic liquid
1-ethyl-3-methylimidazorium oligo hydrogenfluoride (EMIMF(HF)2.3)
Hideaki Yoshinoa, Kenichi Nomuraa, 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 13 January 2004; received in revised form 3 February 2004; accepted 4 February 2004
Available online 30 April 2004
Abstract
Ring opening fluorination of epoxides with hydrogen fluoride in ionic liquid 1-ethyl-3-methylimidazorium oligo hydrogenfluoride
EMIMF(HF)2.3 was demonstrated. This ionic liquid released hydrogen fluoride graduately to make mild conditions without oligomerization
of epoxides.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Fluorohydrin; Epoxide ring opening; Hydrogen fluoride; Ionic liquid
1. Introduction
temperature to obtain 2-fluoro-2-phenyl-ethanol (2a) in
72% yield (Scheme 1). The reaction mixture is biphase
which consist of CH2Cl2 phase and ionic liquid phases.
In order to increase the rate of releasing hydrogen fluoride
into CH2Cl2 phase, methanol was added as an additive. The
addition of proton source will carry fluoride ion from ionic
liquid like phase transfer catalyst. 2-Fluoro-2-phenyl-etha-
nol (2a) was sole product and the region isomer 1-fluoro-2-
Ring opening fluorination of epoxide has been a conve-
nient method for preparation of fluorohydrin [1]. The direct
way may be treatment of epoxides with anhydrous hydrogen
fluoride [2,3], but in some cases, it has a drawback due to its
toxicity and difficulty for handle. Alternative fluorine
sources have been employed successfully to avoid this
problem. HF-amine complex [4–6], potassium dihydrogen
trifluoride or potassium hydrogen difluoride [7–9], silicon
tetrafluoride [10], titanium tetrafluoride [11], tetrabutylam-
monium dihydrogen trifluoride [12], were reported as effec-
tive reagents for ring opening fluorination of epoxide. In a
previous paper [13], we reported halofluorination of alkenes
in the presence of ionic liquid 1-ethyl-3-methylimidazorium
oligo hydrogenfluoride EMIMF(HF)2.3 (Fig. 1) [15] and
proved that this ionic liquid was available as fluoride ion
source with easy-handling. In this paper, we wish to report
ring opening fluorination of epoxides with the ionic liquid as
hydrogen fluoride source.
1
phenyl-2-ethanol was not detected by H and 19F NMR in
the obtained crude product. As shown in entry 2 of Table 1,
when catalytic amount of methanol was added, the yield was
improved. The use of methanol as a solvent instead of
CH2Cl2 accelerated the consumption of epoxide, but for-
mation of 2-methoxy-2-phenyl ethanol which was arisen
from attack of methoxide anion was predominant (entry 4).
Ring opening fluorination of various epoxide with
EMIMF(HF)2.3 and methanol catalyst are summarized in
Table 2. In all cases, regioselectivity was high. Aryl and
cyclic epoxides were converted to fluorohydrins in moderate
yield (entry 1–4). Mono-alkyl substituted epoxide resulted
in recovery of the starting material (entry 8). These results
indicated that stabilization effect of carbocation which was
formed by epoxide ring opening at the intermediate played
an important role (Scheme 2).
2. Results and discussion
Styrene oxide (1a) in CH2Cl2 was added EMIMF(HF)2.3
at room temperature and stirred vigorously at ambient
If epoxides react with aqueous hydrogen fluoride in
methanol solution, epoxides were consumed rapidly, but
oligomerization occurred and no flurohydrin was obtained.
This ionic liquid generated hydrogen fluoride to organic
* 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 # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.02.002

1128
H. Yoshino et al. / Journal of Fluorine Chemistry 125 (2004) 1127–1129
Scheme 1.
Scheme 2.
Fig. 1. EMlMF(HF)2.3
.
phase graduately and effectively that concentration of
hydrogen fluoride was kept appropriate, which realized mild
fluorination condition.
Table 1
Ring opening fluorination of styrene oxide
In summary, we demonstrated ring-opening fluorination
of epoxide with mild and safe fluorinating reagent
EMIMF(HF)2.3 which makes the non-aqueous work-up
possible.
Entry
Solvent
Time (h)
2a (%)
3a (%)
1
2
3
4
CH2Cl2
24
16
12
4
72
81
74
4
–
CH2Cl2/0.1 eq. MeOH
CH2Cl2/1.0 eq. MeOH
MeOH
–
17
75
3. Experimental
Reagents were purchased from Wako, Tokyo Kasei, or
Aldrich, and used without further purification. Epoxides
were prepared by oxidation of olefines with mCPBA or
addition of (bromometyl) lithium to carbonyl compounds
[14]. Reactions were monitored by thin-layer chromatogra-
phy using 25 mm E. Merck silica-gel plates (Silica Gel
Table 2
Ring opening fluorination of various epoxides
Entry Epoxide
Time
(h)
Product
Yield
(%)
F
O
OH
1
2
16
16
16
6
81
F254). Silica-gel was purchased from Kanto Chemical Co.
1a
The polypropylene 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
[15].
2a
F
O
OH
74
1b
2b
F
O
3
4
5
6
55
1c
OH
2c
2d
3.1. General procedure for ring opening fluorination
of epoxides
F
O
65
1d
OH
In a 15 mm polypropylene tube, epoxide (1 mmol),
CH2Cl2 (500 ml), and methanol (4 ml) were placed. Ionic
liquid EMIMF(HF)2.3 (600 ml) was added to the mixture at
room temperature, and stirred. When the reaction finished,
ethyl acetate (1 ml) was added and the whole was stirred
vigorously. The stirring was stopped, the mixture was
separated into two phases. The upper layer was collected
by decantation. This extraction with ethyl acetate was
repeated twice more. The crude product was purified by a
short silica-gel column chromatography. Yield was deter-
mined by 19F NMR in comparison with internal standard.
F
O
OH
n-C H
24
24
37a
28b
n-C H
8
17
8
17
1e
2e
F
O
HO
n-C H
n-C H
8
17
8
17
1f
2f
n-C H
4
HO
9
O
7c
0d
n-C H
4
9
7
8
48
n-C H
1g
4
9
n-C H
F
4
9
2g
O
120
–
n-C H
8
17
1h
a 50% of starting material was recovered.
b 47% of starting material was recovered.
c 83% of starting material was recovered.
d Starting material was only recovered.
3.1.1. 2-Fluoro-2-phenyl-ethanol (2a)
1H NMR (300 MHz, CDCl3): d 7.41–7.34 (m, 5H), 5.57
(ddd, J ¼ 3:0, 7.5, 48.3 Hz, 1H), 4.01–3.76 (m, 2H), 2.02

H. Yoshino et al. / Journal of Fluorine Chemistry 125 (2004) 1127–1129
1129
(bs, 1H). 19F NMR (282 MHz, CDCl3): d ꢀ186.8 (ddd,
J ¼ 48:6, 29.6, 17.8 Hz).
(t, J ¼ 7:2 Hz, 6H). 13C NMR (75 MHz, CDCl3): d 96.6
(d, J ¼ 167:9 Hz), 73.0 (d, J ¼ 21:6 Hz), 31.4, 29.2
(d, J ¼ 20:7 Hz), 28.0, 27.6, 22.7, 22.6, 14.1, 14.0.
19F NMR (282 MHz, CDCl3): d ꢀ190.8 (m). Anal. Calcd
for C10H21FO: C, 68.14; H, 12.01. Found: C, 68.21; H,
11.72.
3.1.2. 2-Fluoro-2-phenyl-propan-1-ol (2b)
1H NMR (300 MHz, CDCl3): d 7.40–7.32 (m, 5H), 3.92–
3.69 (m, 2H), 1.83 (bs, 1H), 1.75 (d, J ¼ 22:5 Hz, 3H). 19
NMR (282 MHz, CDCl3): d ꢀ157.2 (m).
F
3.1.3. 2-Fluorocyclohexane-1-ol (2c)
Acknowledgements
1H NMR (300 MHz, CDCl3): d 4.21 (dm, J ¼ 51:3 Hz,
1H), 3.67–3.57 (m, 1H), 2.45 (bs, 1H), 2.13–1.99 (m, 2H),
1.77–1.69 (m, 2H), 1.51–1.20 (m, 4H). 19F NMR (282 MHz,
CDCl3): d ꢀ181.4 (d, J ¼ 51:3 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.
3.1.4. 2-Fluoro-2-methyl-cyclohexanol (2d)
1H NMR (300 MHz, CDCl3): d 3.76–3.67 (m, 1H), 2.17
(bs, 1H), 1.94–1.21 (m, 11H). 19F NMR (282 MHz, CDCl3):
d ꢀ142.0 (m).
References
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