A novel method for introducing a polyfluoroalkyl group into aromatic compounds

Article abstract of DOI:10.1016/j.jfluchem.2011.06.006

Introduction of a polyfluoroalkyl group into aromatic compounds was achieved by Friedel-Crafts reaction using (1-chloro-1-hydroperfluoroalkyl) sulfides 1, and the subsequent desulfurizing-difluorination of the resulting product using IF₅/Et

Full text of DOI:10.1016/j.jfluchem.2011.06.006

Journal of Fluorine Chemistry 132 (2011) 579–586
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A novel method for introducing a polyfluoroalkyl group into aromatic compounds
*
Ryuhei Tahara, Tadahito Fukuhara, Shoji Hara
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Introduction of a polyfluoroalkyl group into aromatic compounds was achieved by Friedel-Crafts
reaction using (1-chloro-1-hydroperfluoroalkyl) sulfides 1, and the subsequent desulfurizing–
difluorination of the resulting product using IF5/Et3N-nHF. Perfluoroethyl, 1,1,2,2,3,3-hexafluoropropyl,
and 1,1,2,2,3,3,4,4,5,5-decafluoropentyl groups were introduced to various aromatic compounds by this
method. Selective perfluoroethylation of uracil at the 5-position was also performed.
ß 2011 Elsevier B.V. All rights reserved.
Received 9 May 2011
Received in revised form 2 June 2011
Accepted 7 June 2011
Available online 14 June 2011
Keywords:
Polyfluoroalkylation
Fluoro-Pummerer rearrangement
Desulfurizing–difluorination
IF5
5-(Perfluoroethyl)uracil
1. Introduction
substitution with a hydrogen atom and an alkylsulfanyl group [7].
As the perfluoroalkyl group in 2 is a strong electron-withdrawing
Introduction of a polyfluoroalkyl group into an aromatic
compound has been well studied [1] because the resulting
compounds exhibit remarkably different physical, chemical, and
biological properties [2]. Among the many methods available for
the polyfluoroalkylation of aromatic compounds, the electrophilic
method has an advantage over other methods: in a nucleophilic
method, an aromatic halide is required as a substrate, and in a free
radical method, regioselecitivity is low. On the other hand, in an
electrophilic polyfluoroalkylation, the polyfluoroalkyl group can
be introduced by substitution with a hydrogen atom under mild
conditions [3]. However, the electrophilic polyfluoroalkylation
method requires a special reagent, which is unstable and difficult
to prepare [2a,4]. Therefore, a more convenient method for the
introduction of a polyfluoroalkyl group into an aromatic com-
pound has been desired. Previously, Uneyama et al. reported that a
1-(phenylsulfanyl)-2,2,2-trifluoroethyl group can be introduced to
aromatic compounds by Friedel-Crafts reaction using (1-chloro-
2,2,2-trifluoroethyl) phenyl sulfide (1b, R = Ph, Rf = CF3) [5].
Various (1-chloro-1-hydroperfluoroalkyl) sulfides 1 can be pre-
pared from commercially available 1,1-dihydroperfluoroalkanols
[6], and they can be used for the reaction with aromatic compound
to synthesize (1-aryl-1-hydroperfluoroalkyl) sulfides 2. Recently,
we reported a desulfurizing–difluorination reaction of benzyl
sulfides having an electron-withdrawing group using IF5, where
two fluorine atoms were introduced to the benzyl position by
group, the desulfurizing–difluorination reaction can be applied to
2, and the polyfluoroalkyl group substituted aromatic compound 3
must be prepared from 2 (Scheme 1) [8].
2. Result and discussion
1-Chloro-2,2,2-trifluoroethyl hexyl sulfide 1a, 1-chloro-2,2,2-
trifluoroethyl phenyl sulfide 1b, 1-chloro-2,2,3,3-tetrafluoropro-
pyl hexyl sulfide 1c, and 1-chloro-2,2,3,3,4,4,5,5-octafluoropentyl
hexyl sulfide 1d were prepared from the corresponding poly-
fluoroalcohols [6], and used for the Friedel-Crafts reaction with
naphthalene in the presence of a Lewis acid (TiCl4 or SnCl4). The
alkylation occurred selectively at 1-position and 1-(1-hexylsul-
fanyl-2,2,2-trifluoroethyl)naphthalene 2a, 1-(1-phenylsulfanyl-
2,2,2-trifluoroethyl)naphthalene 2b, 1-(1-hexylsulfanyl-2,2,3,3-
tetrafluoropropyl)naphthalene 2g, and 1-(1-hexylsulfanyl-
2,2,3,3,4,4,5,5-octafluoropentyl)naphthalene 2h were obtained
in good yield as shown in Table 1 [9]. Similarly, in the reaction of
1a with p-xylene, p-dimethoxybenzene, octahydroanthracene,
and benzothiophene, the corresponding 1-(hexylsulfanyl)-2,2,2-
trifluoroethylated products 2c–f were obtained in good yields
(Table 1).
Next, the desulfurizing–difluorination of 1-(1-hexylsulfanyl-
2,2,2-trifluoroethyl)naphthalene 2a and 1-(1-phenylsulfanyl-
2,2,2-trifluoroethyl)naphthalene 2b was investigated for the
synthesis of 1-(perfluoroethyl)naphthalene 3a. When 2a was
subjected to the reaction with IF5, the expected 3a was obtained in
77% yield. However, 1-(1,2,2,2-tetrafluoroethyl)naphthalene 4a
was also formed in 14% yield (entry 1 in Table 2). When IF5/Et3N-
* Corresponding author.
E-mail address: shara@eng.hokudai.ac.jp (S. Hara).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.06.006

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R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
next step, 5 was converted to 3a by the substitution of the
alkylsulfanyl group with a fluoride (desulfurizing–fluorination
reaction). In path 2, the desulfurizing–fluorination reaction
initially took place to afford 4a. The reaction of 2a mainly
proceeded though path 1 and 3a was formed as a main product.
When a less reactive IF5/Et3N-nHF was used as a fluorination
reagent, the reaction predominantly proceeded through path 1 and
3a was formed selectively (entries 1–3 in Table 2). On the other
hand, in the reaction of 2b, because of the higher leaving ability of
the phenylsulfanyl group, the reaction proceeded through path 2 to
afford 4a selectively (entries 5 and 6).
From various (1-aryl-2,2,2-trifluoroethyl) hexyl sulfides 2a and
2c–f, the corresponding perfluoroethylated aromatic compounds
3a and 3c–f were obtained with good selectivity (100–90%) by
desulfurizing–difluorination reaction using IF5/Et3N-nHF, as
shown in Table 3. Similarly, 1-(1,1,2,2,3,3-hexafluoropropyl) and
1-(1,1,2,2,3,3,4,4,5,5-decafluoropentyl)naphthalene 3g–h were
selectively formed by the reaction of the corresponding sulfides
2g–h with IF5/Et3N-HF.
Fluorine-containing pyrimidine derivatives including uracils
and nucleosides are potent antitumor and antiviral agents [11],
and much effort has gone into the synthesis of 5-(trifluoromethy-
l)uracil derivatives [12]. However, there are few reports on the
synthesis of their perfluoroethyl derivatives. Therefore, we used
Scheme 1. Polyfluoroalkylation of aromatic compounds.
3HF was used instead of IF5 to prevent the formation of 4a [10], the
yield of 4a was reduced to 8% (entry 2). Finally, 3a was selectively
obtained using IF5/Et3N-2HF (entry 3). On the other hand, in the
reaction of 2b with IF5, the decomposition of 2b took place under
the same conditions, and neither 3a nor 4a was obtained in
reasonable yield (entry 4). In the reaction of 2b with IF5/Et3N-3HF,
4a was selectively obtained in good yield without the formation of
3a (entries 5 and 6). Consequently, the perfluoroethyl or the
1,2,2,2-tetrafluoroethyl group can be selectively introduced to 1-
position of naphthalene using 1a or 1b.
our method for the synthesis of
a 5-(perfluoroethyl)uracil
The difference in the reactivities of 2a and 2b can be explained
from leaving ability of the alkylsulfanyl group (Scheme 2): in path
1, substitution of hydrogen with a fluoride (Fluoro-Pummerer
reaction) initially took place to afford tetrafluoro-sulfide 5. In the
derivative. The Friedel-Crafts reaction of 1a with uracil or
N-protected uracil was unsuccessful, and the expected 5-(2,2,2-
trifluoro-1-(hexylsulfanyl)ethyl)uracil 7 was not obtained. There-
fore, 7 was prepared by the reaction of uracil with trifluoroace-
Table 1
Friedel-Crafts reaction of aromatic compounds with sulfide 1.a
Aromatic compound
Reagent
Reaction time (h)
Product
Yield (%)b
10
84 (1-:2- = 98:2)
20
77 (1-:2- = 96:4)
1a
15
71
1a
12
80
1a
15
78

R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
581
Table 1 (Continued )
Aromatic compound
Reagent
Reaction time (h)
Product
Yield (%)b
1a
15
77c (3-:2- = 77:23)
82 (1-:2- = 96:4)
85d,e (1-:2- = 96:4)
15
3
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2, using 1.5 eq of TiCl4 and 2 eq of ArH.
Isolated yield based on 1 used. In parentheses, isomer ratio.
1.2 eq of SnCl4 was used Lewis-acid.
b
c
d
e
1.0 eq of SnCl4 was used.
5.0 eq of naphthalene was used.
taldehyde ethyl hemiacetal [13], and the subsequent reaction of
used for the reaction with 2i, the formation of 3i, and 5-{1,2,2,2-
tetrafluoro-1-(hexylsulfanyl)ethyl}uracil (the Fluoro-Pummerer
rearrangement product), and the absence of 5-(tetrafluoroethy-
l)uracil were confirmed from 19F NMR analysis of the reaction
mixture after 24 h at room temperature. Under these conditions,
the desulfurizing–fluorination reaction is slow and is the rate-
determining step. The desulfurizing–fluorination step was accel-
the resulting product with hexanethiol (Scheme 3) [14]. The
nitrogen atom at 1-position in 7 was protected with a tosyl group
to afford 1-tosyl-5-{2,2,2-trifluoro-1-(hexylsulfanyl)ethyl}uracil
2i. In the reaction of 2i with IF5, the expected 5-(perfluoroethy-
l)uracil 3i was obtained in 54% yield with 3% of 5-(1,2,2,2-
tetrafluoroethyl)uracil. On the other hand, when IF5/Et3N-3HF was
Scheme 2. Reaction mechanism of desulfurizing-difluorination and -monofluorination.

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R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
Table 2
Desulfurizing–difluorination reaction of 2a and 2b.a
.
Entry
Substrate
Reagent
Condition
Yield (%)b
3a
4a
1
2
3
4
5
6
2a (R =Hex)
IF5
0 8C, 13 h
0 8C, 8 h
rt, 65 h
77
14
2a
IF5/Et3N-3HF
IF5/Et3N-2HF
IF5
IF5/Et3N-3HFc
IF5/Et3N-3HFc
86
8
2a
98 (80)
0
2b (R = ph)
0 8C, 13 h
0 8C, 60 h
rt, 18 h
0
0
0
3
2b
2b
68
92 (80)
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 using 1.5 eq of IF5 reagent.
19F NMR yield based on 2 used. In parentheses, isolated yield.
0.75 eq of IF5/Et3N-3HF was used.
b
c
Scheme 3. Introduction of a perfluoroethyl group at 5-position of Uracil.
Table 3
The desulfurizing–fluorination reaction of 2.a
Substrate
Reagent
Condition
rt, 65 h
Product (ratio)
Yield (%)b
80 (99)
2a
IF5/Et3N-2HF
2b
IF5/Et3N-3HF
rt, 18 h
80 (92)c
2c
IF5/Et3N-3HF
rt, 60 h
80

R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
583
Table 3 (Continued )
Substrate
Reagent
Condition
rt, 37 h
Product (ratio)
Yield (%)b
2d
IF5/Et3N-HF
86
2e
IF5/Et3N-2HF
rt, 70 h
75
2f
IF5/Et3N-HF
rt, 50 h
79
2g
IF5/Et3N-HF
rt, 32 h
86
2h
IF5/Et3N-HF
rt, 24 h
83
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 using 1.5 eq of IF5 reagent.
Isolated yield based on 2 used. In parentheses, 19F NMR yield.
0.75 eq of IF5/Et3N-3HF was used.
b
c
erated by the addition of IF5 to the reaction mixture, and 3i was
obtained in 61% yield in 48 h (Scheme 3).
referred to TMS (1H, 13C) and CFCl3 (19F), respectively. The EI-high-
resolution massspectra weremeasured ona JEOLJMS-700TZ. IF5 ina
stainless-steel cylinder was supplied by Asahi Glass Co., Ltd. IF5 was
transferred through a TeflonTM tube into a TeflonTM FEP bottle from
the cylinder under an N2 atmosphere. IF5 was transferred quickly
from the bottle to the reaction vessel made of Teflon TM FEP in open
air. IF5/5CH2Cl2 and IF5/Et3N-3HF were prepared as described
previously [10]. IF5 decomposes in air emitting HF fume, and,
therefore, it should be carefully handled in a bench hood with
rubber-gloved hands. 2,2,3,3-Tetrafluoropropanol and 2,2,3,3,4,
4,5,5-octafluoropentanol were donated from Daikin Industries,
Ltd. (1-Chloro-2,2,2-trifluoroethyl) hexyl sulfide 1a, (1-chloro-
2,2,2-trifluoroethyl) phenyl sulfide 1b, (1-chloro-2,2,3,3-tetrafluor-
opropyl) hexyl sulfide 1c, and (1-chloro-2,2,3,3,4,4,5,5-octafluor-
opentyl)hexyl sulfide 1d were prepared from 2,2,2-trifluoroethanol,
2,2,3,3-tetrafluoropropanol, and 2,2,3,3,4,4,5,5-octafluoropentanol,
respectively, according to the reported procedure [6].
3. Conclusion
Perfluoroethyl, hexafluoropropyl, and decafluoropentyl groups
can be introduced to various aromatic compounds by Friedel-
Crafts reaction with (1-chloro-1-hydroperfluoro)alkyl sulfides 1,
and the subsequent desulfurizing–difluorination of the resulting
product with IF5/Et3N-nHF. As the starting sulfides 1 can be
prepared from commercially available polyfluoro-alcohols, our
method is useful for introducing various polyfluoro-alkyl groups
into aromatic compounds. In order to demonstrate the usefulness
of our method, 5-(perfluoroethyl)uracil was synthesized.
4. Experimental
4.1. General
4.2. Friedel-Crafts reaction of aromatic compounds with 1
The melting points were measured with a Yanagimoto micro
melting-point apparatus. The IR spectra were recorded using a
JASCO FT/IR-410. The 1H NMR (400 MHz) spectra, 19F NMR
(376 MHz) spectra, and 13C NMR (100 MHz) were recorded in
4.2.1. 1-{2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl}naphthalene (2a)
To a CH2Cl2 solution (20 mL) of naphthalene (1.28 g, 10 mmol)
and 1a (1.18 g, 5 mmol) was added TiCl4 (1.44 g, 7.5 mmol) under
N2 atmosphere at 0 8C. The mixture was stirred at room
CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, d, is

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R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
temperature for 10 h and then 3 M aqueous HCl (10 mL) was
added. After stirring for 30 min, the mixture was extracted with
CH2Cl2 (30 mL Â 3). The combined organic phase was dried over
MgSO4 and concentrated under reduced pressure. Purification by
column chromatography (silica gel/hexane:benzene = 50:1) gave
2a (1.37 g) in 84% yield (containing ca. 2% of 2-substituted isomer).
Pure 2a is obtainable by careful column chromatography. Oil: IR
4.2.7. 1-{2,2,3,3-Tetrafluoro-1-(hexylsulfanyl)propyl}naphthalene
(2g)
Oil: IR (neat) 2929, 1227, 1115, 1041 cmÀ1. 1H NMR
d 0.82 (3H,
t, J = 6.7 Hz), 1.14–1.26 (6H, m), 1.45–1.54 (2H, m), 2.50–2.63 (2H,
m), 5.17 (1H, t, J = 15.2 Hz), 5.97 (1H, tt, J = 54.4, 5.2 Hz), 7.51–7.61
(3H, m), 7.86–7.92 (3H, m), 8.00 (1H, d, J = 8.9 Hz). 13C NMR
d
13.9,
2
1
22.4, 28.2, 29.0, 31.2, 32.8, 44.2 (t, JC–F = 22.9 Hz), 109.5 (tt, JC–
2
1
2
(neat) 2929, 1251, 1149, 1105 cmÀ1
.
1H NMR
d
0.84 (3H, t,
F = 251.8 Hz, JC–F = 33.7 Hz), 116.9 (tt, JC–F = 254.1 Hz, JC–
J = 7.0 Hz), 1.18–1.35 (6H, m), 1.48–1.61 (2H, m), 2.64–2.76 (2H,
F = 25.3 Hz), 122.1. 125.4, 125.9, 126.9, 128.0, 129.2, 129.3,
m), 5.19 (1H, brs), 7.48–7.60 (3H, m), 7.62–8.05 (4H, m). 13C NMR
d
129.9, 131.5, 133.7. 19F NMR
d
À119.58 to À119.64 (2F, m),
À138.30 (2F, ddt, J = 297.3, 53.7, 7.2 Hz). HRMS (EI) calcd. for
C
19H22F4S (M+) 358.13783, found 358.13732.
2
13.9, 22.4, 28.3, 28.9, 31.2, 33.1, 46.3 (q, JC–F = 29.3 Hz), 122.2,
125.2, 125.9 (2C), 126.5 (q, JC–F = 279.4 Hz), 126.8, 129.2, 129.3,
1
129.5, 131.1, 133.8. 19F NMR
d
À67.54 (3F, s). HRMS (EI) calcd. for
C
18H21F3S (M+) 326.13161, found 326.13105.
4.2.8. 1-{2,2,3,3,4,4,5,5-Octafluoro-1-
(hexylsulfanyl)pentyl}naphthalene (2h)
Oil: IR (neat) 2930, 1172, 1130 cmÀ1 1H NMR
. d 0.82 (3H, t,
4.2.2. 1-{2,2,2-Trifluoro-1-(phenlsulfanyl)ethyl}naphthalene (2b)
Oil: IR (neat) 3062, 1248, 1105 cmÀ1 1H NMR
5.45 (1H, q,
J = 7.8 Hz), 7.24–7.32 (3H, m), 7.41–7.65 (6H, m), 7.85–8.00 (3H, m).
13C NMR 50.8 (q, 2JC–F = 29.2 Hz), 122.2, 125.2, 125.9, 126.1 (q, 1JC–
F = 280.4 Hz), 126.8, 127.0, 128.8 (2C), 129.1 (2C), 129.2 (2C), 129.4,
.
d
J = 6.8 Hz), 1.16–1.32 (6H, m), 1.46–1.57 (2H, m), 2.55–2.67 (2H,
m), 5.36 (1H, dd, J = 17.9, 12.9 Hz), 5.97 (1H, tt, J = 52.1, 5.5 Hz),
d
7.49–7.61 (3H, m), 7.82–7.99 (4H, m). 13C NMR
d 13.8, 22.4, 28.2,
29.0, 31.2, 33.4, 44.2 (t, 2JC–F = 23.2 Hz), 104.8–120.3 (4C, m), 121.7,
130.9, 132.7, 133.8, 134.0. 19F NMR
d
À67.16 (3F, d, J = 6.2 Hz). HRMS
125.3, 125.8, 127.0, 128.0, 129.2, 129.3, 129.7, 131.1, 133.7. 19F
(EI) calcd. for C18H13F3S (M+) 318.06901, found 318.06848.
NMR
d
À108.60 (1F, dt, J = 276.7, 13.8 Hz), À120.84 (1F, d,
J = 274.9 Hz), À122.67 to À121.64 (2F, m), À130.49 to À130.62
(2F, m), À136.83 to À138.73 (2F, m). HRMS (EI) calcd. for C21H22F8S
(M+) 458.13145, found 458.13161.
4.2.3. 2-{2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl}-1,4-
dimethylbenzene (2c)
Oil: IR (neat) 2928, 1255, 1147, 1111 cmÀ1. 1H NMR
d 0.87 (3H,
t, J = 6.9 Hz), 1.20–1.39 (6H, m), 1.50–1.63 (2H, m), 2.32 (3H, s),
2.35 (3H, s), 2.60–2.72 (2H, m), 4.50 (1H, q, J = 8.5 Hz), 7.02–7.08
4.2.9. 1-(Perfluoroethyl)naphthalene (3a)
IF5/Et3N-2HF (0.75 mmol) was prepared in situ by the addition
of Et3N (25.3 mg, 0.25 mmol) to a mixture of IF5/5CH2Cl2 (0.16 g,
0.25 mmol), IF5/Et3N-3HF (190 mg, 0.5 mmol), and CH2Cl2 (0.5 mL)
at 0 8C in Teflon PFA bottle. To the resulting CH2Cl2 solution of IF5/
Et3N-2HF (0.75 mmol), a CH2Cl2 solution (2.5 mL) of 2a (164 mg,
0.5 mmol) was added at 0 8C and the mixture was stirred at room
temperature for 65 h. The mixture was poured into saturated
aqueous NaHCO3 (30 mL) and extracted with ether (30 mL Â 3).
The combined organic phase was washed with aqueous Na2S2O3,
dried over MgSO4, and concentrated under reduced pressure.
Purification by column chromatography (silica gel/hexa-
ne:CH2Cl2 = 50:1) gave 3a (100 mg) in 80% yield. Oil: IR (neat)
(2H, m), 7.26–7.27 (1H, m). 13C NMR
d
14.0, 19.2, 21.0, 22.5, 28.3,
29.1, 31.3, 33.1, 47.2 (q, 2JC–F = 31.5 Hz), 126.5 (q, 1JC–F = 279.6 Hz),
128.8, 129.3, 130.4, 131.9, 132.9, 136.1. 19F NMR
J = 7.1 Hz). HRMS (EI) calcd. for C16H23F3S (M+) 304.14726, found
d
À68.11 (3F, d,
304.14684.
4.2.4. 2-{2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl}-1,4-
dimethoxybenzene (2d)
Oil: IR (neat) 2931, 1503, 1236 cmÀ1 1H NMR
. d 0.87 (3H, t,
J = 7.0 Hz), 1.23–1.39 (6H, m), 1.54–1.62 (2H, m), 2.59–2.72 (2H,
m), 3.77 (3H, s), 3.82 (3H, s), 4.92–4.98 (1H, q, J = 8.8 Hz), 6.844 (2H,
brs), 7.03 (1H, s). 13C NMR
d
14.0, 22.4, 28.3, 29.0, 31.3, 33.1, 43.3 (q,
3059, 1133 cmÀ1
. d 7.52–7.62 (3H, m), 7.83 (1H, d,
1H NMR
2JC–F = 30.5 Hz), 55.7, 56.3, 111.9, 114.8, 114.9, 123.4, 126.3 (q, 1JC–
J = 7.3 Hz), 7.92 (1H, d, J = 8.3 Hz), 8.04 (1H, J = 8.2 Hz), 8.24 (1H, d,
F = 279.4 Hz), 150.8, 153.6. 19F NMR
HRMS (EI) calcd. for C16H23F3O2S (M+) 336.13708, found
336.13645.
d
À68.48 (3F, d, J = 8.9 Hz).
J = 8.3 Hz). 13C NMR
d 115.3 (tq, JC–F = 255.3 Hz, JC–F = 39.4 Hz),
1
2
119.7 (tq, 2JC–F = 39.3 Hz, 1JC–F = 287.0 Hz), 124.2 (t, 2JC–F = 21.7 Hz),
124.3, 124.7–124.8 (m), 126.4, 127.4 (t, 3JC–F = 9.5 Hz), 127.6 129.0,
129.9, 133.3, 134.1. 19F NMR
[15] À83.8 (3F, s), À108.9 (2F, s)).
d
À83.97 (3F, s), À108.90 (2F, s) (lit.
4.2.5. 9-{2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl}-1,2,3,4,5,6,7,8-
octahydroanthracene (2e)
Oil: IR (neat) 2930, 1250, 1146, 1102 cmÀ1. 1H NMR
d
0.88 (3H,
4.2.10. 1-(1,2,2,2-Tetrafluoroethyl)naphthalene (4a)
t, J = 6.7 Hz), 1.25–1.43 (6H, m), 1.54–1.89 (10H, m), 2.68–2.94
Oil: IR (neat) 3059, 1359, 1274, 1185, 1140 cmÀ1. 1H NMR
d 6.42
(10H, m), 4.77 (1H, q, J = 10.0 Hz), 6.84 (1H, s). 13C NMR
d
14.0, 21.9,
(1H, dq, J = 43.5, 5.8 Hz), 7.26–7.62 (3H, m), 7.77 (1H, d, J = 7.2 Hz),
3
1
2
22.3, 22.5 (2C), 23.9, 27.7, 27.8 (q, JC–F = 3.5 Hz), 28.4, 29.3, 29.4,
30.2, 31.3, 35.8, 47.2 (q, 2JC–F = 30.7 Hz), 127.0 (q, 1JC–F = 281.4 Hz),
7.92–7.98 (3H, m). 13C NMR
d 85.8 (dq, JC–F = 185.7 Hz, JC–
1
2
F = 35.0 Hz), 122.5, 122.9 (dq, JC–F = 282.3 Hz, JC–F = 29.5 Hz),
130.6 (2C), 132.6, 134.9, 136.5, 136.7. 19F NMR
d
À65.70 (3F, d,
125.0, 126.0 (d, JC–F = 18.3 Hz), 126.1, 126.3 (d, JC–F = 10.5 Hz),
2
3
J = 9.0 Hz). HRMS (EI) calcd. for C22H32F3S (M++1) 385.21768, found
127.2, 129.1, 130.6 (d, JC–F = 3.8 Hz), 131.1 (d, JC–F = 1.9 Hz),
133.6. 19F NMR
3
4
385.21366.
d
À78.09 (3F, dd, J = 12.5, 5.4 Hz), À195.1 (1F, dq,
J = 43.0, 12.6 Hz) (lit. [16] À77.9 (3F, dd, J = 13, 6 Hz), À194.9 (1F,
4.2.6. 3-(2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl)benzo[b]thiophene
dq, J = 44, 13 Hz)).
(2f)
Oil. IR (neat) 2928, 1253, 1150, 1108 cmÀ1. 1H NMR
d
0.84 (3H, t,
4.2.11. 2-(Perfluoroethyl)-1,4-dimethylbenzene (3c)
J = 6.6 Hz), 1.18–1.34 (6H, m), 1.44–1.59 (2H, m), 2.53–2.60 (1H,
m), 2.67–2.74 (1H, m), 4.73 (1H, q, J = 8.4 Hz), 7.39–7.47 (2H, m),
Oil: IR (neat) 2931, 1207, 1187 cmÀ1. 1H NMR
d
2.36 (3H, s), 2.43
(3H, t, J = 3.0 Hz), 7.14–7.31 (3H, m). 13C NMR
d 19.7–19.8 (m), 20.7,
115.0 (tq, JC–F = 254.2 Hz, JC–F = 38.2 Hz), 119.7 (tq, JC–
F = 40.1 Hz, JC–F = 286.1), 126.6 (t, JC–F = 21.7 Hz), 128.5 (t, JC–
1
2
2
7.56 (1H, s), 7.87 (2H, dd, J = 15.1, 8.5 Hz). 13C NMR
d
13.9, 22.4,
2
1
2
3
28.3, 28.9, 31.2, 32.5, 45.5 (q, JC–F = 30.8 Hz), 121.6, 122.9, 124.4,
124.8, 126.0, 126.1 (q, JC–F = 279.7 Hz), 127.1, 137.3, 139.9. 19F
1
3
F = 8.6 Hz), 132.4, 132.5, 134.7 (t, JC–F = 2.2 Hz), 135.8. 19F NMR
d
NMR
d
À68.27 (3F, d, J = 9.0 Hz). HRMS (EI) calcd. for C16H19F3S2
À84.86 (3F, s), À110.94 (2F, s), (lit. [17] À84.72 (3F, s), À110.78
(M+) 332.08803, found 332.08739.
(2F, s)).

R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
585
4.2.12. 2-(Perfluoroethyl)-1,4-dimethoxybenzene (3d)
Oil: IR (neat) 2958, 2842, 1057, 1200 cmÀ1. 1H NMR
s), 3.82 (3H, s), 6.94-6.97 (1H, m), 7.04–7.05 (2H, m). 13C NMR
55.8, 56.6, 113.4 (tq, 1JC–F = 255.6 Hz, 2JC–F = 39.3 Hz), 114.1 (t, 3JC–
129.0, 130.2, 133.2, 134.1. 19F NMR
d
À106.09 (2F, t, J = 7.5 Hz),
d
3.79 (3H,
À129.34 to À129.38 (2F, m), À137.00 to À137.21 (2F, m). HRMS
d
(EI) calcd. for C13H8F6 (M+) 278.05302, found 278.05256.
2
1
F = 9.0 Hz), 114.2, 117.4 (t, JC–F = 16.1 Hz), 118.5, 119.4 (qt, JC–
4.2.19. 1-(1,1,2,2,3,3,4,4,5,5-Decafluoropentyl)naphthalene (3h)
F = 296.6, 2JC–F = 39.1 Hz), 152.4 (t, 3JC–F = 2.9 Hz), 153.2. 19F NMR
d
Oil: IR (neat) 1516, 1188, 1132 cmÀ1
.
1H NMR
d
6.06 (1H, tt,
J = 52.6, 5.3 Hz), 7.54–7.63 (3H, m), 7.83 (1H, d, J = 7.5 Hz), 7.93
(1H, d, J = 9.5 Hz), 8.06 (1H, d, J = 8.2 Hz), 8.23 (1H, d, J = 8.5 Hz). 13
NMR
104.9–120.9 (5C, m), 124.2, 124.7 (t, 2JC–F = 21.9 Hz), 124.8–
125.0 (m), 126.4, 127.6, 128.0 (t, 3JC–F = 9.9 Hz), 129.0, 130.3, 133.4,
134.1. 19F NMR
À84.4 (3F, s), À112.5 (2F, s). HRMS (EI) calcd. for C10H9F5O2 (M+)
256.05227, found 256.05179.
C
d
4.2.13. 2-(1,2,2,2-Tetrafluoroethyl)-1,4-dimethoxybenzene (4d)
Oil: IR (neat) 2958, 2842, 1506, 1226, 1184 cmÀ1. 1H NMR
d
3.79
(3H, s), 3.82 (3H, s), 6.14 (1H, dt, J = 43.8, 6.1 Hz), 6.87 (1H, d,
J = 9.0 Hz), 6.96 (1H, dd, J = 9.1, 3.2 Hz), 7.07 (1H, d, J = 2.8 Hz). 13
NMR
55.6, 56.0, 82.9 (dq, 1JC–F = 182.1 Hz, 2JC–F = 35.6 Hz), 122.6
d
À105.12 (2F, t, J = 6.6 Hz), À120.99 (2F, s),
À123.64 (2F, s), À130.38 (2F, s), À137.66 (2F, dm, J = 51.9 Hz).
C
HRMS (EI) calcd. for C15H8F10 (M+) 378.04663, found 378.04593.
d
2
1
(dq, JC–F = 30.6 Hz, JC–F = 281.3 Hz), 112.0, 113.3 (d,
F = 7.6 Hz), 116.7 (d, JC–F = 1.9 Hz), 119.5 (d, JC–F = 20.0 Hz),
151.4 (d, JC–F = 5.5 Hz), 153.7. 19F NMR
J = 13.4, 6.3 Hz), À198.77 (1F, dq, J = 43.8, 12.4 Hz). HRMS (EI)
J
3JC–
4.2.20. 5-(2,2,2-Trifluoro-1-hydroxyethyl)uracil (6)
4
2
5-(2,2,2-Trifluoro-1-hydroxyethyl)uracil 6 was prepared by the
modification of the reported procedure [13]. A mixture of uracil
(3.37 g, 30 mmol) and trifluoroacetaldehyde ethyl hemiacetal
(containing 10% EtOH) in DMF (18 mL) was stirred at 120 8C for
15 h. After cooling to room temperature, the mixture was poured
into saturated aqueous NH4Cl (30 mL) and extracted with AcOEt
(20 mL Â 3). The combined organic phase was dried over MgSO4
and concentrated under reduced pressure. The remained solid was
washed with acetone to give 6 (5.23 g, 83%) which was used for the
next step without further purification.
3
d
À79.31 (3F, dd,
calcd. for C10H10F4O2 (M+) 238.06169, found 238.06115.
4.2.14. 9-(Perfluoroethyl)-1,2,3,4,5,6,7,8-octahydroanthracene (3e)
Oil: IR (neat) 2937, 1200, 1146, 1033 cmÀ1. 1H NMR
d
1.71–1.72
(8H, m), 2.73–2.83 (8H, m), 6.98 (1H, s). 13C NMR
d 21.87 (2C), 23.1
(2C, t, JC–F = 1.9 Hz), 27.3–27.5 (2C, m), 30.0 (2C), 117.0 (tq, JC–
F = 256.5 Hz, JC–F = 39.1 Hz), 121.6 (qt, JC–F = 288.0 Hz, JC–
F = 39.1 Hz), 124.8 (t, JC–F = 19.8 Hz), 133.9, 136.4 (2C), 137.0
3
1
2
1
2
2
3
(2C, t, JC–F = 2.6 Hz). 19F NMR
d
À83.61 (3F, t, J = 3.5 Hz), À99.65
4.2.21. 5-(2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl)uracil (7)
A mixture of crude 6 (5.23 g, 25 mmol) and hexanethiol (10 mL)
in DMF (8 mL) was stirred under reflux for 48 h. After cooling to
room temperature, volatile part was removed under reduced
pressure. Purification by column chromatography (silica gel/
hexane:acetone = 3:1) gave 7 (3.22 g) in 54% yield.
(2F, s). HRMS (EI) calcd. for C16H17F5 (M+) 304.12504, found
304.12414.
4.2.15. 9-(1,2,2,2-Tetrafluoroethyl)-1,2,3,4,5,6,7,8-
octahydroanthracene (4e)
Oil: IR (neat) 2935, 1274, 1180, 1138 cmÀ1. 1H NMR
d
1.68–1.83
(8H, m), 2.74 (8H, brs), 6.16 (1H, dt, J = 36.5, 7.5 Hz), 6.92 (1H, s).
4.2.22. 5-(2,2,2-Trifluoro-1-(hexylsulfanyl)ethyl)-1-tosyluracil (2i)
To a CH3CN solution (5 mL) of 7 (467 mg, 1.5 mmol) was added
N,O-bis(trimethylsilyl)acetamide (610 mg, 3 mmol) at room tem-
perature under N2 atmosphere. The mixture was stirred under
reflux for 1 h, and then cooled to 0 8C. To the mixture, TsCl (574 mg,
3 mmol) was added and the mixture was stirred under reflux for
24 h. After cooling to room temperature, a volatile part was
removed under reduced pressure. Purification by column chro-
matography (silica gel/hexane:acetone = 3:1) gave 2i (390 mg,
0.84 mmol) in 56% yield. White solid. Mp 120–121 8C. IR (KBr)
13C NMR
d 22.3 (2C), 23.2 (2C), 26.5–26.6 (2C), 29.8 (2C), 87.2 (dq,
2
2
1JC–F = 187.2, JC–F = 35.3 Hz), 123.5 (dq, JC–F = 28.7 Hz, 283.4 Hz),
3
125.5 (2C, d, JC–F = 16.5 Hz), 129.6, 132.5 (2C), 135.6. 19F NMR
d
À75.39 (3F, dd, J = 13.4, 7.2 Hz), À196.47 (1F, dq, J = 43.9, 13.4 Hz),
HRMS (EI) calcd. for C16H18F4 (M+) 286.13446, found 286.13371.
4.2.16. 3-(Perfluoroethyl)benzo[b]thiophene (3f)
Oil: IR (neat) 3112, 1332, 1202 cmÀ1. 1H NMR
d 7.42–7.49 (2H,
1
2
m), 7.90–7.98 (3H, m). 13C NMR
d
112.9 (tq, JC–F = 252.7 Hz, JC–
F = 40.1 Hz), 119.2 (qt, 1JC–F = 286.4, 2JC–F = 39.1 Hz), 122.7, 123.2 (t,
3060, 2931, 2857, 1738, 1685, 1261, 1194 cmÀ1 1H NMR
. d 0.89
3JC–F = 2.6 Hz), 124.1 (t, JC–F = 26.4 Hz), 125.2, 125.3, 130.8 (t, JC–
F = 17.6 Hz), 135.1, 140.4. 19F NMR
(3H, t, J = 6.7 Hz), 1.28–1.42 (6H, m), 1.58–1.66 (2H, m), 2.48 (3H,
s), 2.68–2.80 (2H, m), 4.56 (1H, q, J = 8.4 Hz), 7.40 (2H, d, J = 8.2 Hz),
2
3
d
À84.80 (3F, s), À110.83 (2F, s).
HRMS (EI) calcd. for C10H5F5S (M+) 252.00321, found 252.00271.
7.96 (2H, d, J = 8.5 Hz), 8.27 (1H, s), 8.47 (1H, s). 13C NMR
d
13.9,
2
21.8, 22.4, 28.2, 28.9, 31.2, 33.8, 41.5 (q, JC–F = 31.7 Hz), 110.4,
1
4.2.17. 3-(1,2,2,2-Tetrafluoroethyl)benzo[b]thiophene (4f)
125.4 (q, JC–F = 279.2 Hz), 129.8 (2C), 129.9 (2C), 132.4, 137.3,
Oil: IR (neat) 3086, 1278, 1187, 1147 cmÀ1. 1H NMR
d
6.00 (1H,
dq, J = 44.0 Hz, J = 6.1 Hz), 7.40–7.48 (2H, m), 7.74 (1H, d,
J = 1.7 Hz), 7.85 (1H, d, J = 7.8 Hz), 7.90–7.92 (1H, m). 13C NMR
146.5, 147.2, 161.7. 19F NMR
d
À69.31 (3F, d, J = 8.1 Hz). HRMS (EI)
calcd. for C19H23F3N2O4S2 (M+) 464.10513, found 464.10639.
d
1
2
2
85.0 (dq, JC–F = 185.0 Hz, JC–F = 36.2 Hz), 122.0, 122.3 (dq, JC–
4.2.23. 5-(Perfluoroethyl)-1-tosyluracil (3i)
1
3
F = 29.4 Hz, JC–F = 281.3 Hz), 122.9, 124.9, 125.1, 125.2 (d, JC–
F = 21.2 Hz), 128.6 (d, 3JC–F = 7.9 Hz), 136.6 (d, 3JC–F = 6.0 Hz), 140.2.
To IF5/Et3N-3HF (250 mg, 0.65 mmol) in Teflon PFA bottle was
added a CH2Cl2 solution (3 mL) of 2i (198.5 mg, 0.43 mmol) at 0 8C
and the mixture was stirred at room temperature for 24 h
(complete consumption of 3 was confirmed from NMR analysis).
To the reaction mixture, IF5/5CH2Cl2 (280 mg, 0.43 mmol) was
added and the mixture was stirred at room temperature for
another 24 h. Then, the mixture was poured into saturated
aqueous NaHCO3 (20 mL) and extracted with ether (30 mL Â 3).
The combined organic layer was washed with saturated aqueous
Na2S2O3 (20 mL), dried over MgSO4, and concentrated under
reduced pressure. Purification by column chromatography (silica
gel/hexane:acetone = 3:1) gave 3i (101 mg) in 61% yield. White
19F NMR
d
À78.21 (3F, dd, J = 13.4 Hz, 6.2 Hz), À192.95 (1F, dq,
J = 43.8 Hz, J = 13.5 Hz). HRMS (EI) calcd. for C10H6F4S (M+)
234.01263, found 234.01224.
4.2.18. 1-(1,1,2,2,3,3-Hexafluoropropyl)naphthalene (3g)
Oil: IR (neat) 3059, 1516, 1133 cmÀ1
.
1H NMR
d
6.15 (1H, tt,
J = 52.2, 5.5 Hz), 7.26–7.62 (3H, m), 7.80 (1H, d, J = 7.3 Hz), 7.91
(1H, d, J = 6.8 Hz), 8.05 (1H, J = 8.2 Hz), 8.24 (1H, d, J = 8.0 Hz). 13
NMR
105.8 (tt, 1JC–F = 252.9 Hz, 2JC–F = 15.8 Hz), 110.7–114.1 (m),
C
d
1
2
2
117.8 (tt, JC–F = 254.1 Hz, JC–F = 33.0 Hz), 124.2, 124.8 (t, JC–
F = 21.7 Hz), 124.9–125.1 (m), 126.3, 127.5, 127.6 (t, 3JC–F = 9.8 Hz),
solid. Mp 211–212 8C. IR (KBr) 3437, 1709, 1205, 1179 cmÀ1 1H
.

586
R. Tahara et al. / Journal of Fluorine Chemistry 132 (2011) 579–586
[4] T. Hiyama, in: H. Yamamoto (Ed.), Organofluorine Compounds, Springer, Heidel-
NMR (acetone-d6) d 2.47 (3H, s), 7.51 (2H, d, J = 8.4 Hz), 8.04 (2H, d,
berg, 2000, pp. 111–118.
J = 8.5 Hz), 8.54 (1H, s), 10.82 (1H, brs). 13C NMR (acetone-d6)
d
[5] (a) K. Uneyama, M. Momota, Tetrahedron Lett. 30 (1989) 2265–2266;
(b) K. Uneyama, M. Momota, K. Hayashida, T. Itoh, J. Org. Chem. 55 (1990)
5364–5368.
2
1
2
21.6, 104.8 (t, JC–F = 23.8 Hz), 112.8 (tq, JC–F = 255.6 Hz, JC–
F = 41.0 Hz), 119.7 (qt, JC–F = 286.1, JC–F = 39.1 Hz), 130.6 (2C),
1
2
[6] (a) T. Nakai, K. Tanaka, H. Setoi, N. Ishikawa, Bull. Chem. Soc. Jpn. 50 (1977)
3069–3070;
2
130.8 (2C), 133.6, 142.2 (t, JC–F = 10.4 Hz), 147.1, 148.1, 158.8 (t,
3JC–F = 1.8 Hz). 19F NMR (acetone-d6)
d
À81.91 (3F, s), À111.94 (2F,
(b) Y.G. Shermolovich, V.M. Timoshenko, R.Y. Musyanovich, M.I. Povolotsky, V.V.
Pirozhenko, L.N. Markovsky, Heteroat. Chem. 9 (1998) 151–154.
[7] T. Fukuhara, S. Hara, Synlett (2009) 198–200.
s). HRMS (EI) calcd. for C13H8F5N2O4S (M+À1) 383.01304, found
383.01329.
[8] As for the preparation of polyfluoroalkyl group substituted aromatic compounds
by desulfurizing–fluorination reaction, see: M. Kuroboshi, T. Hiyama, J. Fluorine
Chem. 69 (1994) 127–128.
[9] In these reactions, 2–4% of 2-alkylated isomers were also formed which are
separable by column chromatography.
Acknowledgments
We are grateful to Asahi Glass Co., Ltd., and Daikin Industries,
Ltd., for their donation of IF5 and, 2,2,3,3-tetrafluoropropanol and
2,2,3,3,4,4,5,5-octafluoropentanol, respectively.
[10] Addition of Et3N-nHF to IF5 can reduce its reactivity, see: T. Fukuhara, S. Hara, J.
Org. Chem. 75 (2010) 7393–7399.
[11] J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
[12] (a) T. Lin, Y. Gao, J. Med. Chem. 26 (1983) 598–601;
(b) Y. Tanabe, N. Matsuo, N. Ohno, J. Org. Chem. 53 (1988) 4582–4585;
(c) J. Yamashita, H. Matsumoto, K. Kobayashi, K. Noguchi, M. Yasumoto, T. Ueda,
Chem. Pharm. Bull. 37 (1989) 2287–2292;
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