Synthesis of trifluoromethyl ethers and difluoro(methylthio)methyl ethers by the reaction of dithiocarbonates with IF5-pyridine-HF

Article abstract of DOI:10.1016/j.jfluchem.2015.04.016

Trifluoromethyl ether and difluoro(methylthio)methyl ether of phenols and aliphatic alcohols were selectively synthesized from the corresponding dithiocarbonates. When IF₅-pyridine-HF was used alone in the reaction of the dithiocarbonate, the difluoro(methylthio)methyl ether was selectively formed. On the other hand, by the additional use of Et₃N-6HF with IF₅-pyridine-HF, trifluoromethyl ether was formed selectively. Various functional groups such as ester, ether, amide, and acetonide could tolerate the reaction conditions, and various functionalized difluoro(methylthio)methyl ethers and trifluoromethyl ethers were synthesized.

Full text of DOI:10.1016/j.jfluchem.2015.04.016

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FLUOR-8554; No. of Pages 5
Journal of Fluorine Chemistry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of trifluoromethyl ethers and difluoro(methylthio)methyl
ethers by the reaction of dithiocarbonates with IF5-pyridine-HF
*
Toshiya Inoue, Chiaki Fuse, 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:
Trifluoromethyl ether and difluoro(methylthio)methyl ether of phenols and aliphatic alcohols were
selectively synthesized from the corresponding dithiocarbonates. When IF5-pyridine-HF was used alone
in the reaction of the dithiocarbonate, the difluoro(methylthio)methyl ether was selectively formed. On
the other hand, by the additional use of Et3N-6HF with IF5-pyridine-HF, trifluoromethyl ether was
formed selectively. Various functional groups such as ester, ether, amide, and acetonide could tolerate
the reaction conditions, and various functionalized difluoro(methylthio)methyl ethers and trifluor-
omethyl ethers were synthesized.
Received 16 February 2015
Received in revised form 20 April 2015
Accepted 27 April 2015
Available online xxx
Keywords:
Trifluoromethyl ether
Difluoro(methylthio)methyl ether
IF5-pyridine-HF
ß 2015 Elsevier B.V. All rights reserved.
1. Introduction
difluoro(methylthio)methyl ether 3a was obtained in 74% yield
(Entry 1 in Table 1). By performing the reaction for 3 h, the yield
Recently, bioactive compounds [1] and functional materials [2]
havinga trifluoromethoxy grouparebecomingimportant, andmany
methods for their synthesis have been developed [1–3]. Among
them, conversion from dithiocarbonateshas been frequently used to
synthesize the trifluoromethoxy group, because the starting
material can be easily prepared, and fluorine atoms can be
introduced under mild conditions using an oxidant such as NBS,
NIS, and DBH, and a fluorinating reagent such as pyridinium
poly(hydrogen fluoride) [4]. However, pyridinium poly(hydrogen
fluoride)istoxic, hygroscopic, and corrosiveliquid, and a specialcare
is required for its use. Furthermore, undesired side reaction such as
bromination of aromatic ring was observed during the reaction [4a
and d]. Therefore, more reliable and safer method for the conversion
of dithiocarbonates to trifluoromethyl ether was desired. Recently,
we reported an air-stable fluorinating reagent, IF5-pyridine-HF, and
its application to various fluorination reactions [5]. IF5-pyridine-HF
is a non-hygroscopic white solid, and special care is not required for
its use. Therefore, we applied IF5-pyridine-HF to the reaction with
dithiocarbonates of phenols and aliphatic alcohols (Scheme 1).
was increased to 87% (Entry 2). Neither further extension of the
reaction time nor additional use of IF5-pyridine-HF was effective in
improving the yield further (Entries 3 and 4). Under the employed
reaction conditions, the trifluoromethoxy compound 4a was not
formed at all. On the other hand, when the reaction was performed
using 2.0 eq of IF5-pyridine-HF in 1,2-dichloroethane at 60 8C for
24 h, 4a was formed in 5% yield with 32% of 3a (Entry 5). By
performing the reaction at 84 8C for 24 h, 4a was selectively formed
in moderate yield (Entry 6). The additional use of Et3N-6HF was
found to be effective to activate IF5-pyridine-HF, and by perform-
ing the reaction in a mixture of 5 eq of Et3N-6HF and 2.0 eq of IF5-
pyridine-HF at 60 8C for 15 h, 4a was obtained in 66% yield with 7%
of 3a (Entry 7). Finally, 4a was obtained in the highest yield by
performing the reaction in 1,2-dichloroethane at 60 8C for 9 h using
5 eq of Et3N-6HF and 2.0 eq of IF5-pyridine-HF (Entry 8).
2. Results and discussion
When the dithiocarbonate of 4-isopropylphenol 2a was reacted
with 1.1 eq of IF5-pyridine-HF at room temperature for 50 min,
*
Corresponding author. Tel.: +81 11 7066556; fax: +81 11 7066556.
Scheme 1. Synthesis of trifluoromethyl ethers and difluoro(methylthio)methyl
E-mail address: shara@eng.hokudai.ac.jp (S. Hara).
ethers from alcohols or phenols.
http://dx.doi.org/10.1016/j.jfluchem.2015.04.016
0022-1139/ß 2015 Elsevier B.V. All rights reserved.
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Table 1
The reaction of dithiocarbonate 2a with IF5-pyridine-HFa
.
Entry
Additive (Additive/2a)
Solvent
Reaction conditions
Yield of 3a (%)b
Yield of 4a (%)b
1c
2c
3c
4d
5
none
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(CH2Cl)2
(CH2Cl)2
none
rt, 50 min
rt, 3 h
74
87
76
67
32
0
0
0
none
none
rt, 24 h
0
none
rt, 50 min
60 8C, 24 h
84 8C, 24 h
60 8C, 15 h
60 8C, 9 h
0
none
5
6
none
45
66
74
7
Et3N-6HF (5)
Et3N-6HF (5)
7
8
(CH2Cl)2
0
a
If otherwise not mentioned, 2.0 eq of IF5-pyridine-HF was used.
19F NMR yield based on 2a. Fluorobenzene was used as an internal standard.
1.1 eq of IF5-pyridine-HF was used.
b
c
d
1.5 eq of IF5-pyridine-HF was used.
The difluoro(methylthio)methyl ether and trifluoromethyl
difluoro(methylthio)methyl ether of aliphatic alcohols (3f–3j),
which are difficult to synthesize in reasonable yield by conven-
tional methods [4a and d], were also prepared from the
corresponding dithiocarbonates (2f–2j). On the other hand, the
trifluoromethyl ethers of phenols and alcohols were synthesized
from the corresponding dithiocarbonates by the reaction with IF5-
pyridine-HF and Et3N-6HF. Various functional groups such as ester
ether of various phenols and alcohols were synthesized from
the corresponding dithiocarbonate (Table 2). The difluoro(-
methylthio)methyl ether of phenols 3 were generally synthesized
by the reaction with IF5-pridine-HF at room temperature for 3 h.
However, when an electron withdrawing group was attached, a
longer reaction time was required (Entries
5 and 7). The
Table 2
Synthesis of difluoro(methylthio)methyl ethers 3 and trifluoromethyl ethers 4 from the corresponding dithiocarbonates 2 by the reaction with IF5-pyridine-HF
.
Entry
1
Substrate 2
Reaction time (h)
rt, 3 h
Methoda
A
Product
Yield (%)b
83(87)
3a
2c
3
2a
60 8C, 9 h
rt, 3 h
B
A
4a
3b
(74)
78
4
5
rt, 3 h
A
A
3c
64
68
rt, 24 h
3d
6c
7
2d
2e
60 8C, 24 h
rt, 24 h
B
A
4d
3e
(71)
54
8c
60 8C, 24 h
B
4e
55
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Table 2 (Continued )
Entry
9
Substrate 2
Reaction time (h)
rt, 3 h
Methoda
Product
Yield (%)b
(98)
A
3f
10
11
2f
rt, 2 h
rt, 3 h
B
A
4f
91
3g
(100)
10
11
2g
rt, 3 h
rt, 3 h
B
A
4g
3h
67
76
12
13
2h
2i
rt, 3 h
rt, 3 h
B
A
4h
3i
72
(100)
14d
15
rt, 3 h
B
A
4i
3j
77
0 8C, 24 h
(88)
16
17
2j
0 8C, 24 h
rt, 3 h
B
B
4j
53
50
4k
a
Method A: the reaction was carried out in CH2Cl2 using 1.1 eq of IF5-pyridine-HF. Method B: the reaction was carried out in CH2Cl2 using 2.0 eq of IF5-pyridine-HF and
5.0 eq of Et3N-6HF.
b
Isolation yield based on substrate. In parentheses, 19F NMR yield based on 2a, using fluorobenzene as an internal standard.
c
1,2-Dichloroethane was used as solvent.
d
1.0 eq of Et3N-6HF was used.
(4e, 4i), amide (4h), and acetonide (4k) could tolerate the reaction
conditions, and introduction of the trifluoromethoxy group to
various substrates is possible by using this method. The
trifluoromethyl ether of sec-alcohol is difficult to synthesize by
conventional methods [4b, d and h], because of instability of the
starting dithiocarbonate under acidic conditions. The trifluoro-
methyl ether of 4-tert-butylcyclohexanol 4j was synthesized from
the corresponding dithiocarbonate 2j in a reasonable yield by
performing the reaction using 5 eq of Et3N-6HF and 2.0 eq of IF5-
pyridine-HF at 0 8C for 24 h (Entry 16).
Trifluoromethoxy group substituted bi(cyclohexane) deriva-
tives are expected as a novel liquid crystalline material, and 1-(4-
propylcyclohexyl)-4-trifluoromethoxycyclohexane 4l was previ-
ously prepared from the corresponding dithiocarbonate 2l by using
NBS and 70% HF/pyridine in 40% yield [4e]. As our method is
applicable to the synthesis of the trifluoromethyl ether of sec-
alcohol, IF5-pyridine-HF/Et3N-6HF was used in the reaction with 2l,
and 4l was obtained in 65% isolated yield from 2l (Scheme 2).
3. Conclusion
We showed that an air-stable fluorination reagent, IF5-
pyridine-HF, can be used for the selective synthesis of various
difluoro(methylthio)methyl ethers and trifluoromethyl ethers of
phenols and alcohols from the corresponding dithiocarbonates. The
present method has some advantages over the previously reported
methods. IF5-pyridine-HF is easy to use and special care is not
required, and can be used for the synthesis of the difluoro(-
methylthio)methyl ethers and trifluoromethyl ethers which were
difficult to synthesize previously. Furthermore, undesired side
reaction such as halogenation of aromatic ring was not observed
during the reaction. We also used the reagent for the synthesis of the
trifluoromethyl ether of 40-propyl-[1,10-bi(cyclohexan)]-4-ol, which
is expected to be a new ionic liquid material.
4. Experimental
4.1. General
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
Scheme 2. Synthesis of 1-(4-propylcyclohexyl)-4-trifluoromethoxycyclohexane 4l.
CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, d, is
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referred to TMS (1H, 13C) and CFCl3 (19F), respectively. The EI-high-
resolution mass spectra were measured on a JEOL JMS-700TZ. IF5 in
a cyclinder was supplied by Daikin industries, Ltd. Anhydrous HF in
a cyclider was purchaed from Stella Chemifa Corporation. IF5-
pyridine-HF is air-stable and non-hygroscopic white solid. The
reaction using IF5-pyridine-HF can be carried out in glass vessel,
but use of Teflon or polyethylene vessel is recommended. It was
prepared from IF5 and pyridine-HF by the previously reported
method [5]. Dithiocarbonates 2 were prepared from the corre-
sponding phenols or alcohols 1, according to the literature [4d].
154.2, 131.4 (2C), 129.9 (t, 1JC–F = 295.0 Hz), 128.1, 120.8 (2C), 61.3,
14.4, 12.5; HRMS (EI) calcd for C11H12F2O3S 262.04750, found
262.04700.
4.2.6. 1-[Difluoro(methylthio)methoxy]decane (3f)
IR (neat) 2926, 2855, 1179, 1074, 1035, 1006, 445 cmꢁ1 1H
;
NMR
d
3.91 (t, J = 4.0 Hz, 2H), 2.30 (s, 3H), 1.69–1.62 (m, 2H), 1.37–
—50.53 (s, 2F); 13
1.27 (m, 14H), 0.88 (t, J = 6.9 Hz, 3H); 19F NMR
d
C
NMR
d
130.2 (t, 1JC–F = 293.0 Hz), 66.4 (t, 3JC–F = 4.0 Hz), 31.9, 29.5,
29.5, 29.3, 29.2, 29.0, 25.7, 22.7, 14.1, 12.2 (t, 3JC–F = 2.0 Hz); HRMS
(EI) calcd for C12H24F2OS 254.15159, found 254.15166.
4.1.1. Preparation of Et3N-6HF
Anhydrous HF (10 g, 0.5 mole) was collected in a Teflon bottle
from a cylider. The anhydrous HF in the Teflon bottle was cooled to
0 8C and freshly distilled Et3N (8.42 g, 0.083 mole) was added
slowly. As it is highly exothermal, slow and careful additon of Et3N
is required. After the addition, the mixture was stirred for 30 min.
The resulting clear solution of Et3N-6HF was used without further
purification and kept in the Teflon bottle with a screw cap.
Anhydrous HF is highly hazadrous and should be handled with
rubber gloves in a bench hood.
4.2.7. 3-[Difluoro(methylthio)methoxy]-1-phenylpropane (3g)
IR (neat) 2936, 1177, 1029, 756 cmꢁ1; 1H NMR
d 7.32–7.19 (m,
5H), 3.93 (t, J = 6.4 Hz, 2H), 2.73 (t, J = 7.6 Hz, 2H), 2.31 (s, 3H), 2.02–
1.95 (m, 2H); 19F NMR
NMR
d
—50.61 (s, 2F) (lit. [4d]—50.51 (s)); 13C
1
d
149.9, 141.1, 128.6 (4C), 126.2 (t, JC–F = 230.9 Hz), 65.6 (t,
3JC–F = 4.4 Hz), 32.0, 30.8, 12.4; HRMS (EI) calcd for C11H14F2OS
232.07334, found 232.07291.
4.2.8. N-2-[difluoro(methylthio)methoxy]ethylphthalimide (3h)
White solid. Mp 48.0–50.9 8C; IR (KBr) 2968, 1772, 1714 (C55O),
4.2. Reaction of dithiocarbonate with IF5-pyridine-HF
1395, 1198, 1082, 978 cmꢁ1 1H NMR
; d 7.89–7.85 (m, 2H), 7.76–
7.73 (m, 2H), 4.18 (t, J = 5.7 Hz, 2H), 3.99 (t, J = 5.7 Hz, 2H), 2.25 (s,
4.2.1. 1-Isopropyl-4-[difluoro(methylthio)methoxy]benzene (3a)
To a CH2Cl2 solution (2 mL) of 2a (113 mg, 0.5 mmol) was added
IF5-pyridine-HF (193 mg, 0.6 mmol) at room temperature, and the
mixture was stirred at room temperature for 3 h. The resulting
dark red solution was poured into water (20 mL) and extracted
with CH2Cl2 (20 mL ꢀ 3). The combined organic layer was washed
with aq NaHCO3 and aq Na2S2O3, and dried over MgSO4. After
concentration under reduced pressure, 3a was isolated in 83% yield
by column chromatography (silica gel/hexane); IR (neat) 2291,
3H); 19F NMR
d
—51.26 (s, 2F); 13C NMR
d
167.8 (2C), 134.1 (2C),
1
3
131.8 (2C), 130.1 (t, JC–F = 292.0 Hz), 123.3 (2C), 62.9 (t, JC–
F = 4.4 Hz), 37.1, 12.2; HRMS (ESI) calcd for C12H11F2NO3SNa
(M+ + Na) 310.03250 found 310.03200.
4.2.9. Butyl 5-[difluoro(methylthio)methoxy]pentanoate (3i)
IR (neat) 2960, 1735 (C55O), 1154 cmꢁ1 1H NMR
; d 4.08 (t,
J = 6.6 Hz, 2H), 3.93 (t, J = 6.0 Hz, 2H), 2.35 (t, J = 7.0 Hz, 2H), 2.30 (s,
3H), 1.78–1.69 (m, 4H), 1.65–1.58 (m, 2H), 1.43–1.33 (m, 2H), 0.94
1507, 1199, 1135, 1053 434 cmꢁ1; 1H NMR
d
7.20 (d, J = 8.6 Hz, 2H),
(t, J = 7.6 Hz, 3H); 19F NMR
d
—50.81 (s, 2F); 13C NMR
3
d
173.4, 130.3
1
7.12 (d, J = 8.4 Hz, 2H), 2.96–2.85 (m, 1H), 2.38 (s, 3H), 1.24 (d,
(t, JC–F = 290.8 Hz), 65.8 (t, JC–F = 4.4 Hz), 64.4, 33.8, 30.7, 28.5,
21.4, 19.2, 13.8, 12.3; HRMS (FTMS) calcd for C11H20F2O3SNa
293.09930, found 293.09970.
J = 8.0 Hz, 6H); 19F NMR
129.8 (t, JC–F = 294.0 Hz), 127.3 (2C), 121.3 (2C), 33.5, 24.0 (2C),
12.4 (t, 3JC–F = 2.0 Hz); HRMS (EI) calcd for C11H14F2OS 232.07330,
found 232.07350.
d
—46.74 (s, 2F); 13C NMR
d
148.5, 146.6,
1
4.2.10. 1-tert-Butyl-4-[difluoro(methylthio)methoxy]cyclohexane
(3j)
4.2.2. 1-Methoxy-4-[difluoro(methylthio)methoxy]benzene (3b)
IR (neat) 2952, 1200, 1077 cmꢁ1
;
1H NMR
d
4.17–4.12 (m, 1H),
2.31 (s, 3H), 2.08 (d, J = 9.1 Hz, 2H), 1.81 (d, J = 11.0 Hz, 2H), 1.43–
1.40 (m, 2H), 1.09 -1.00 (m, 3H), 0.85 (s, 9H); 19F NMR
—47.29 (s,
IR (neat) 1507, 1193, 1143, 1034, 478 cmꢁ1; 1H NMR
d
7.13 (d,
J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.73 (s, 3H); 19
F
d
NMR
d
—46.35 (s, 2F) (lit. [4d]—46.84 (s)); 13C NMR
d
157.5, 144.0,
2F); 13C NMR 130.2(t, 1JC–F = 291.3 Hz), 77.5 (t, 3JC–F = 3.2 Hz), 46.7,
d
129.9 (t, 1JC–F = 291.6 Hz), 122.8 (2C), 114.3 (2C), 55.5, 12.3 (t, 3JC–
33.4 (2C), 32.3, 27.6 (3C), 25.6 (2C), 12.4 (t, 3JC–F = 2.5 Hz); MS (EI) m/
z 41 (40), 56 (22), 57 (100), 67 (27), 81 (28), 94 (20), 123 (11), 138 (5).
F = 3.0 Hz).
4.2.3. 4-[Difluoro(methylthio)methoxy]-1,10-biphenyl (3c)
4.2.11. 1-Isopropyl-4-(trifluoromethoxy)benzene (4a)
White solid. Mp 29.3–30.8 8C; IR (KBr) 1487, 1134, 1086, 1039,
To IF5-pyridine-HF (321 mg, 1.0 mmol) in dichloroethane
(2 mL), were added Et3N-6HF (553 mg, 2.5 mmol) and 2a
(113 mg, 0.5 mmol) successively at room temperature. The
mixture was stirred at 60 8C for 9 h. The resulting dark red
solution was poured into water (20 mL) and extracted with CH2Cl2
(20 mL ꢀ 3). The combined organic layer was washed with aq
NaHCO3 and aq Na2S2O3, and dried over MgSO4. The yield of 4a was
determined to be 74% by 19F NMR using fluorobenzene as an
internal standard. Pure 4a was obtained by column chromatogra-
756 cmꢁ1
;
1H NMR
d
7.58–7.55 (m, 4H), 7.44 (d, J = 8.0 Hz, 2H),
7.37–7.34 (m, 1H), 7.23 (d, J = 12.0 Hz, 2H), 2.40 (s, 3H); 19F NMR
d
—46.72 (s, 2F) (lit. [4d]—47.91 (s)); 13C NMR
d 150.0, 140.0, 139.1,
129.9 (t, 1JC–F = 292.5 Hz), 128.8 (2C), 128.1 (2C), 127.4, 127.0 (2C),
3
121.7 (2C), 12.4 (t, JC–F = 3.0 Hz).
4.2.4. 1-Bromo-4-[difluoro(methylthio)methoxy]benzene (3d)
IR (neat) 1484, 1200, 1143, 1067, 1012, 445 cmꢁ1
;
1H NMR
d
—
7.50–7.46 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H), 2.73 (s, 3H); 19F NMR
d
phy (silica gel/hexane); IR (neat) 2963, 1256, 1212 cmꢁ1; 1H NMR
7.23 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 2.95–2.85 (m, 1H),
d
47.16 (s, 2F) (lit. [4d]—46.96 (s)); 13C NMR
d
149.6 (t, 3JC–F = 2 Hz),
132.5 (2C), 129.7 (t, 1JC–F = 298.0 Hz), 123.2 (2C), 119.2, 12.3 (t, 3JC–
1.24 (d, J = 6.8 Hz, 6H); 19F NMR —58.53 (s, 3F); 13C NMR
d d 147.7,
F = 3.0 Hz).
147.3, 127.8 (2C), 121.0 (2C), 120.7 (q, 1JC–F = 257.7 Hz), 33.7, 24.1
(2C); HRMS (EI) calcd for C10H11F3O 204.07620, found 204.07606.
4.2.5. Ethyl 4-[difluoro(methylthio)methoxy]benzoate (3e)
IR (neat) 2983, 1720 (C55O), 1606, 1505 cmꢁ1; 1H NMR
d
8.07–
8.05 (m, 2H), 7.27–7.25 (m, 2H), 4.38 (q, J = 7.3 Hz, 2H), 2.38 (s, 3H),
1.39 (t, J = 7.2 Hz, 3H); 19F NMR —46.94 (s, 2F); 13C NMR
165.8,
4.2.12. 1-Bromo-4-(trifluoromethoxy)benzene (4d)
IR (neat) 2961, 1743, 1380, 1227 cmꢁ1
;
1H NMR
d
7.52
d
d
(d, J = 9.2 Hz, 2H), 7.10 (d, J = 9.2 Hz, 2H); 19F NMR
d—58.70
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(s, 3F) (lit. [4d]—58.63 (s)); 13C NMR
120.4 (q, JC–F = 257.7 Hz), 120.3.
d
148.4, 133.1 (2C), 122.9 (2C),
J = 5.5 Hz, 1H), 4.62 (dd, J = 2.4, 8.0 Hz, 1H), 4.35 (dd, J = 2.4, 5.2 Hz,
1H), 4.25 (dd, J = 1.8, 8.0 Hz, 1H), 4.15–4.02 (m, 3H), 1.54 (s, 3H),
1
1.43 (s, 3H), 1.34 (s, 6H); 19F NMR —61.45 (s, 3F); 13C NMR
d d 121.8
4.2.13. Ethyl 4-(trifluoromethoxy)benzoate (4e)
(q, 1JC–F = 256.0 Hz), 109.9, 109.0, 96.3, 70.7, 70.5, 66.1, 66.0, 65.9,
26.1, 26.0, 25.0, 24.5; HRMS (ESI) calcd for C13H19O6F3Na (M+ + Na)
351.10259 found 351.10262.
IR (neat) 2986, 1721 (C55O), 1259, 1169, 1105 cmꢁ1; 1H NMR
d
8.10 (d, J = 9.2 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 4.39 (q, J = 7.2 Hz,
2H), 1.40 (t, J = 7.2 Hz, 3H); 19F NMR
—58.23 (s, 3F) (lit. [6]ꢁ58.1);
13C NMR
165.5, 152.7, 131.6 (2C), 129.0, 120.4 (q, JC–
d
1
d
4.2.20. 4-Propyl-40-(trifluoromethoxy)-1,10-bi(cyclohexane) (4l)
White solid. Mp 28.8–29.2 8C (lit. [4e] 30.8–31.1 8C); IR (KBr)
F = 260.0 Hz), 120.3 (2C), 61.4, 14.3.
2925, 1297, 1125 cmꢁ1
;
1H NMR
d
4.07 (tt, J = 4.8, 10.8 Hz, 1H),
2.11–2.07 (m, 2H), 1.81–1.67 (m, 6H), 1.44–0.82 (m, 19H), 0.87
(t, J = 7.4 Hz, 3H); 19F NMR
—58.12 (s, 3F) (lit. [4e]—58.0 (s,
3F)); 13C NMR 121.8 (q, 1JC–F = 254.8 Hz), 78.7, 42.7, 42.0, 37.9,
4.2.14. 1-(Trifluoromethoxy)decane (4f)
IR (neat) 1724, 1442, 1281 cmꢁ1
;
1H NMR
d
3.95 (t, J = 6.6 Hz,
d
2H), 1.72–1.65 (m, 2H), 1.45–1.12 (m, 14H), 0.83 (t, J = 7.0 Hz 3H);
d
19F NMR
d
—61.23 (s, 3F) (lit. [4d]—61.14 (s)); 13C NMR
d
121.9 (q,
37.7, 33.6 (2C), 32.9 (2C), 32.4, 30.3 (2C), 28.0 (2C), 26.8, 22.9,
14.3; HRMS (EI) calcd for C18H31OF3 320.23270 found
320.23274.
1JC–F = 255.0 Hz), 67.7 (d, 3JC–F = 2.9 Hz), 32.0, 29.7, 29.6, 29.5, 29.2,
28.9, 25.6, 22.8, 14.2.
4.2.15. 3-(Trifluoromethoxy)-1-phenylpropane (4g)
Acknowledgment
IR (neat) 2927, 2857, 1467, 1408, 1275, 1141 cmꢁ1 1H NMR
; d
7.32–7.28 (m, 2H), 7.21–7.18 (m, 3H), 3.96 (t, J = 6.4 Hz, 2H), 2.73 (t,
J = 8.4 Hz, 2H), 2.04–1.97 (m, 2H); 19F NMR
—61.23 (s, 3F) (lit.
We are grateful to Daikin industries, Ltd. for their donation
of IF5.
d
[7]—60.3); 13C NMR
d140.7, 128.7, 128.6 (2C), 126.3 (2C), 121.9 (q,
3
1JC–F = 254.8 Hz), 66.6 (q, JC–F = 3.8 Hz), 31.7, 30.4.
References
4.2.16. N-2-(trifluoromethoxy)ethylphthalimide (4h)
[1] F.R. Leroux, B. Manteau, J.-P. Vors, S. Pazenok, Beilstein J. Org. Chem. 4 (2008) 1–15.
[2] (a) T. Hiyama, in: H. Yamamoto (Ed.), Organofluorine Compounds, Springer-Ver-
lag, Heidelberg, 2000, pp. 197–211;
White solid. Mp 70.0–72.0 8C (lit. [4g] 77.0–77.4 8C); IR (KBr)
1775, 1716 (C55O), 1392, 1225 cmꢁ1
;
1H NMR
d
7.91–7.87 (m, 2H),
7.78–7.72 (m, 1H), 4.23 (t, J = 6.0 Hz, 2H), 4.02 (t, J = 5.2 Hz, 2H); 19F
NMR 168.0 (2C), 134.4 (2C),
—61.6 (s, 3F) (lit. [4g]—61.4); 13C NMR
(b) M. Kuroboshi, K. Kanie, T. Hiyama, Adv. Synth. Catal. 343 (2001) 233–250;
(c) P. Kirsh, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004, pp.
215–237.
d
d
1
3
131.9 (2C), 123.7 (2C), 121.6 (q, JC–F = 256.8 Hz), 64.0 (q, JC–
[3] As for the recent reviews of synthesis of the trifluoromethoxy group, see:
(a) MA. McClinton, D.A. McClinton, Tetrahedron 48 (1992) 6555–6666;
(b) T. Umemoto, Chem. Rev. 96 (1996) 1757–1777;
F = 2.9 Hz).
(c) F. Leroux, P. Jeschke, M. Schlosser, Chem. Rev. 105 (2005) 827–856;
(d) M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 44 (2005) 214–231;
(e) S. Rozen, Adv. Synth. Catal. 352 (2010) 2691–2702;
(f) P. Chen, G. Liu, Synthesis 45 (2013) 2919–2939;
4.2.17. Butyl 5-(trifluoromethoxy)pentanoate (4i)
IR (neat) 2964, 1737 (C55O), 1273, 1142 cmꢁ1; 1H NMR
d 4.08 (t,
J = 7.0 Hz, 2H), 3.99–3.96 (m, 2H), 2.37–2.34 (m, 2H), 1.78–1.73 (m,
(g) M.G. Campbell, T. Ritter, Org. Process. Res. Dev. 18 (2014) 474–480.
[4] (a) M. Kuroboshi, K. Suzuki, T. Hiyama, Tetrahedron Lett. 33 (1992) 4173–4176;
(b) K. Kanie, Y. Tanaka, M. Shimizu, M. Kuroboshi, T. Hiyama, Chem. Commun.
(1997) 309–310;
4H), 1.65–1.57 (m, 2H), 1.43–1.33 (m, 2H), 0.938 (t, J = 7.6 Hz, 3H);
1
19F NMR
d
—61.40 (s, 3F); 13C NMR
d
173.3, 121.8 (q, JC–
3
F = 255.0 Hz), 67.0 (d, JC–F = 2.9 Hz), 64.5, 33.7, 30.8, 28.2, 21.1,
19.3, 13.8; HRMS (EI) calcd for C10H18F3O3 (M+ + H) 243.12026,
found 243.12050.
(c) I. Ben-David, D. Rechavi, E. Mishani, S. Rozen, J. Fluorine Chem. 97 (1999)
75–78;
(d) K. Kanie, Y. Tanaka, K. Suzuki, M. Kuroboshi, T. Hiyama, Bull. Chem. Soc. Jpn.
73 (2000) 471–484;
(e) K. Kanie, S. Takehara, T. Hiyama, Bull. Chem. Soc. Jpn. 73 (2000) 1875–1892;
(f) C.E. Raab, D.C. Dean, D.G. Melillo, J. Labelled Cpd. Radiopharm. 44 (2001)
815–829;
4.2.18. 1-tert-Butyl-4-(trifluoromethoxy)cyclohexane (4j)
IR (neat) 2955, 1288, 1214, 1133 cmꢁ1; 1H NMR
d 4.11–4.04 (m,
1H), 2.12 (d, J = 10.8 Hz, 2H), 1.84 (d, J = 12.0 Hz, 2H), 1.49–1.39 (m,
(g) J.-C. Blazejewski, E. Anselmi, C. Wakselman, J. Org. Chem. 66 (2001) 1061–
1063;
(h) Y. Carcenac, M. Tordeux, C. Wakselman, P. Diter, New J. Chem. 30 (2006)
447–457.
2H), 1.11–0.99 (m, 3H), 0.86 (s, 9H); 19F NMR
d
—58.14 (s, 3F); 13
C
1
NMR
d
121.8 (q, JC–F = 254.9 Hz), 78.7, 46.8, 33.0 (2C), 32.4,
27.7(3C), 25.5 (2C); MS (EI) m/z 123(18), 81(23), 69 (21), 67 (18), 57
(100), 56 (84), 41 (67).
[5] (a) S. Hara, M. Monoi, R. Umemura, C. Fuse, Tetrahedron 68 (2012) 10145–10150;
(b) M. Kunigami, S. Hara, J. Fluorine Chem. 167 (2014) 101–104.
[6] C. Huang, T. Liang, S. Harada, E. Lee, T. Ritter, J. Am. Chem. Soc. 133 (2011) 13308–
13310.
[7] R. Koller, K. Stanek, D. Stolz, R. Aardoom, K. Niedermann, A. Togni, Angew. Chem.
Int. Ed. 48 (2009) 4332–4336.
4.2.19. 1,2:3,4-Di-O-isopropylidene-6-O-trifluoromethyl-
galactopyranose (4k)
a-D-
[8] G.L. Trainor, J. Carbohydr. Chem. 4 (1985) 545–563.
White solid. Mp. 53.0–56.0 8C (lit. [8] 53.5–55.5 8C); IR (KBr)
2997, 1218, 1146, 1065, 1005, 871 cmꢁ1 1H NMR
5.54 (d,
;
d
Please cite this article in press as: T. Inoue, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.04.016