Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides

Article abstract of DOI:10.1021/acs.joc.6b01331

Herein, a copper-catalyzed 2,2,2-trifluoroethylthiolation reaction of aryl bromides and iodides with elemental sulfur, and 1,1,1-trifluoro-2-iodoethane is described. The reaction showed excellent functional group tolerance and allowed the synthesis of various substituted aryl 2,2,2-trifluoroethyl thioethers with good to excellent yields. This transformation constitutes a one-pot synthesis of 2,2,2-trifluoroethylthiolated compounds from inexpensive, readily available starting materials. Utility of the protocol was further demonstrated in the late-stage synthesis of the pirfenidone derivative. The copper thiolate species were prepared and proposed as key intermediates in the catalytic cycle.

Full text of DOI:10.1021/acs.joc.6b01331

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Note
Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides
Shouxiong Chen, Mengjia Zhang, Xuebin Liao, and Zhiqiang Weng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01331 • Publication Date (Web): 31 Jul 2016
Downloaded from http://pubs.acs.org on August 2, 2016
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Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides
Shouxiong Chen,† Mengjia Zhang,† Xuebin Liao,‡,* and Zhiqiang Weng†,*
† State Key Laboratory of Photocatalysis on Energy and Environment, College of
Chemistry, Fuzhou University, Fujian, China, 350108
‡ School of Pharmaceutical Sciences, Collaborative Innovation Center for Diagnosis
and Treatment of Infectious Diseases, Tsinghua University, Beijing, China, 100084
Corresponding authors. Tel.: +86 59122866121; fax: +86 59122866121
ABSTRACT:
Herein, a copper-catalyzed 2,2,2-trifluoroethylthiolation reaction of aryl
bromides and iodides with elemental sulfur, and 1,1,1-trifluoro-2-iodoethane
is described. The reaction showed excellent functional-group tolerance and
allowed the synthesis of various substituted aryl 2,2,2-trifluoroethyl
thioethers with good to excellent yields. This transformation constitutes a
one-pot synthesis of 2,2,2-trifluoroethylthiolated compounds from
inexpensive, readily available starting materials. Utility of the protocol was
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further demonstrated in the late-stage synthesis of the pirfenidone derivative.
The copper thiolate species were prepared and proposed as key intermediates
in the catalytic cycle.
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The physicochemical properties of organofluorine compounds has aroused the interest
of organic chemists, and extensive efforts have been dedicated to the synthesis of
fluorine-containing molecules.1-4 Among them, special interest has been focused on
the developing synthetic methods for the preparation of 2,2,2-trifluoroethyl thioethers.
The 2,2,2-trifluoroethylthio group (-SCH2CF3) is a key functionality in several
pharmaceutical and agrochemical compounds (Figure 1), which was used for
combating and controlling insects arachnids or nematodes in and on plants, and
animal pests, including arthropods.5-7 The introduction of -SCH2CF3 substituents
could significantly improve the physicochemical properties, and the metabolic
stability of organic molecules.
Figure 1. Patented 2,2,2-Trifluoroethylthio-Containg Bioactive Molecules.
To date, the methods for the installation of a 2,2,2-trifluoroethylthio group on an
aromatic ring have been only reported in several papers.8-14 The pioneering work with
the polar nucleophilic substitution of 1,1,1-trifluoro-2-iodoethane by sodium
thiophenoxide in methanol to 2,2,2-trifluoroethyl thioethers was achieved by Hine and
Ghirardell.15 However, -fluorine atoms disfavor SN2 reactivity of CF3CH2I.15,16 In
1998, Chen and co-workers reported the preparation of 2,2,2-trifluoroethylthiol
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derivatives in high yields through a SRN1 reactions of 2,2,2-trifluoroethyl halides with
thiolate ions under UV irradiation (Scheme 1).17 Unfortunately, these methods usually
rely on the use of malodorous thiols. In addition, these methods also often suffer from
narrow substrate scopes, which further limit the utility of these procedures in
synthetic applications. Thus, the development of an efficient method to access
2,2,2-trifluoroethyl thioethers is highly desirable. In particular, the utilization of aryl
halides18 and elemental sulfur19 involving the newly developed method is attractive
approach, because these starting materials are inexpensive, readily available, and
easily handled.
Scheme 1. Methods for the Synthesis of 2,2,2-Trifluoroethyl Thioethers
In 2009, Ma and co-workers elegantly demonstrated a CuI-catalyzed coupling of
aryl iodides, sulfur and alkyl halides under reductive conditions to afford aryl alkyl
thiol ethers in good to excellent yields.20 Inspired by their work and our previous
work,19-21 we became interested in whether similar reactions could occur employing
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CF3CH2I as fluorinated reagent to form 2,2,2-trifluoroethyl thioethers. Herein, we
report
our
findings
on
the
development
of
copper-catalyzed
2,2,2-trifluoroethylthiolation of aryl halides.
On the basis of our previous work on the synthesis of trifluoromethylthiolated
compounds from readily available reagents, such as elemental sulfur,21-23 we started
our investigation with a model reaction using 4-iodoanisole and CF3CH2I.
As described in Table 1, in the presence of CuI (0.1 equiv), phen (0.2 equiv), and
NaBH4 (3.0 equiv) in DMF at 85 C, 4-iodoanisole reacted with CF3CH2I (2.0 equiv)
and elemental sulfur (2.0 equiv) to afford the desired product
(4-methoxyphenyl)(2,2,2-trifluoroethyl)sulfane 2u in 88% NMR yield (Table 1, entry
1). Some factors affecting the 2,2,2-trifluoroethylthiolation reaction were also
investigated. Other copper catalysts only show modestly efficient or inefficient under
these conditions (Table 1, entries 2-9); no reaction occurred in the absence of copper
catalysts (Table 1, entry 10). This observation revealed the crucial role of copper for
this reaction. Of note, the use of Ma’s conditions20 for the synthesis of aryl alkyl thiol
ethers only led to a very low yield of 2u (Table 1, entry 11). A range of other diimine
and diamine ligands are ineffective (Table 1, entries 12 and 13). Interestingly, the use
of 5,5-dimethylcyclohexane-1,3-dione (dimedone) as ligand in DMF at 85 C gave
the product in comparable yield (82%, see Supporting Information) with phen (Table
1, entry 14). After different solvents were screened, DMF proved to be optimal, while
other solvents, such as DMSO, CH3CN, toluene, and THF resulted in the poor yields
(Table 1, entries 15-18). Interestingly, in the absence of NaBH4 no product 2u was
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detected (see Supporting Information). The role of NaBH4 was proposed to react with
CF3CH2I and S8 to form the HSCH2CF3 species.
Table 1. Optimization of 2,2,2-Trifluoroethylthiolation of 4-Iodoanisole.a
entry
[Cu]
ligand
solvent
yield (%) b
(10 mol%)
(20 mol%)
1
CuI
phen
phen
phen
phen
phen
phen
phen
phen
phen
phen
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
CH3CN
Toluene
THF
88
74
51
0
2
CuBr
CuCl
CuF2
Cu(TFA)2
Cu(OTf)2
Cu(MeCN)4PF6
CuCN
CuSCN
-
3
4
5
0
6
0
7
0
8
<1
<1
0
9
10
11
12
13
14
15
16
17
18
CuI
17
64
20
82
37
0
CuI
bpy
CuI
TMEDA
dimedone
phen
phen
phen
phen
CuI
CuI
CuI
CuI
trace
trace
CuI
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a
Reaction conditions: [Cu] (0.020 mmol), [ligand] (0.040 mmol), NaBH4 (0.60
mmol), 4-iodoanisole (0.20 mmol), S8 (0.40 mmol), CF3CH2I (0.40 mmol), solvent
(2.0 mL), 12 h, N2. Yields were determined by 19F NMR analysis of the crude
b
reaction mixture with PhOCF3 as internal standard. bpy = 2,2'-bipyridine, TMEDA =
tetramethylethylenediamine, dimedone = 5,5-dimethylcyclohexane-1,3-dione, DMF =
N,N-dimethylformamide, DMSO = dimethyl sulfoxide.
With the optimized conditions in hand, we studied the scope of the
2,2,2-trifluoroethylthiolation reaction with different aryl iodides and bromides. As
shown in Scheme 2, aryl iodides bearing either electron-neutral, electron-withdrawing,
or electron-donating groups at ortho-, meta-, and para-position on the aromatic ring,
afforded the corresponding products in good to excellent yields. Various functional
groups, such as nitro, ester, cyano, ketone, trifluoromethyl, trifluoromethoxy, and
methoxy were well tolerated. Notably, the 2,2,2-trifluoroethylthiolation reaction
proceeded smoothly with 1-chloro-4-iodobenzene and 1-fluoro-3-iodobenzene to give
the corresponding products 2v and 2w in 82% and 99% yields, respectively. This
feature could be quite useful to further introduce various substituents on the aromatic
ring to diversify new precursors to biologically active substances through different
types of transition metal-catalyzed cross-coupling reactions. Additionally,
1-iodonaphthalene and 3-iodo-9H-fluorene could also afford the corresponding
2,2,2-trifluoroethylthiolated products (2x and 2y) under standard conditions in very
good yields (91% and 83%, respectively).
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Scheme 2. Copper-Catalyzed Reductive 2,2,2-Trifluoroethylthiolation of Aryl
Halides. Reaction conditions: CuI (0.050 mmol), phen (0.10 mmol), NaBH4 (1.5
mmol), 1 (0.50 mmol), S8 (1.0 mmol), CF3CH2I (1.0 mmol), DMF (5.0 mL), 12-16 h,
N2. With aryl iodides at 85 C; with aryl bromides at 95 C, and
5,5-dimethylcyclohexane-1,3-dione was used instead of phen.
It is important to note that, the reactions occurred with aryl bromides to produce
aryl 2,2,2-trifluoroethyl thioethers 2a, 2f, 2j, 2lo proceeded smoothly with similar
yields and 2u in slightly lower yield compared with those obtained using
corresponding aryliodides as substrates, albeit at a slightly higher reaction
temperature of 95 C and the 5,5-dimethylcyclohexane-1,3-dione was chosen as the
ligand instead of phen. Interestingly, heteroaryl bromides and iodides, such as methyl
5-bromonicotinate, 5-bromoquinoline, 2-bromo-6-methoxybenzo[d]thiazole, and
3-iodothiophene-2-carboxylate could also be successfully used as the substrate,
affording the corresponding products 2aa, 2ab, 2ac, and 2ad in 89%, 61%, 76%, and
36% yields, respectively.
To assess the scalability of the protocol, the 2,2,2-trifluoroethylthiolation reaction
of 1-iodo-4-nitrobenzene was performed on a gram scale. The expected
2,2,2-trifluoroethylthiolated 2f was obtained in 89% yield, only slightly lower than the
yield achieved with the submillimolar scale reaction (Scheme 3).
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Scheme
3.
Scalability
of
the
2,2,2-Trifluoroethylthiolation
of
1-Iodo-4-nitrobenzene
To further demonstrate the synthetic application of this protocol, we have
undertaken the late-stage synthesis of the pirfenidone derivative, which has been
employed against fibrotic disorder.24 Under the optimized reaction conditions, the
2,2,2-trifluoroethylthiolation of 3 gave a 66% yield of CF3CH2S-containing
pirfenidone 4 (Scheme 4). This result indicates that the developed protocol could be
readily extended to other biologically active compounds.
Scheme 4. Late-stage 2,2,2-Trifluoroethylthiolation of Pirfenidone Derivative 3
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To shed light on mechanism, we initially tried to identify whether copper
thiolates species are involved in the reaction mechanism as in the copper mediated
Ullmann type of C-S cross-coupling of thiols with aryl halides.25,26 Thus, we started to
isolate the putative copper thiolate intermediates. The reaction of CuOt-Bu, phen, and
CF3CH2SH (prepared in situ from reaction of NaSH with CF3CH2I), in THF at r.t. for
20 min led to the isolation of [(phen)Cu(-SCH2CF3)]2 (5) in 83% yield (Scheme 5).
Alternatively, complex 5 was formed in 74% yield (19F NMR) from the reaction of
CuI and phen with CF3CH2I, in the presence of NaBH4 at 85 C for 12 h.
Scheme 5. Synthesis of [(phen)Cu(-SCH2CF3)]2 (5)
Subsequently, we evaluated the competence of this copper thiolate complex 5 to
be intermediates in the copper-catalyzed 2,2,2-trifluoroethylthiolation of aryl halides.
The stoichiometric reaction of complex 5 with 4-iodoanisole in DMF at 85 C for 12
h produced the expected product 2u in 99% NMR yield (Eqn 1). The catalytic activity
of copper thiolate species towards 2,2,2-trifluoroethylthiolation was then investigated
by conducting the reaction of 4-iodoanisole with CF3CH2I and elemental sulfur in the
presence of 5 (5 mol%), phen (10 mol %), and NaBH4 in DMF at 90 C for 18 h.
Complex 5 was found to be an equally active catalyst and the reaction afforded the
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desired product 2u in 99% yield with a rate constant of 1.0110-3 s-1 (Eqn 2). These
results provide support for the possible role of 5 as an intermediate in the catalytic
cycle of 2,2,2-trifluoroethylthiolation reaction.
Alternatively, the copper(I) thiophenolato complex could also be involved in the
reaction.20,26 Indeed, the reaction of [(phen)Cu(-SC6H4-p-OMe)]2 (6) with 2 equiv of
CF3CH2I in DMF at 85 C for 12 h provided the desired product 2u in only 32%
NMR yield (Eqn 3). However, the catalytic 2,2,2-trifluoroethylthiolation of
4-iodoanisole with CF3CH2I and elemental sulfur catalyzed by 6 (5 mol%) furnished
the desired product 3u in 84% yield (Eqn 4). These results indicate that 6 may also
serve as an intermediate in the catalytic cycle of reaction.
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Subsequently, the copper-catalyzed 2,2,2-trifluoroethylthiolation of 4-iodoanisole
was
performed
in
the
presence
of
radical
scavengers
like
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Under the optimized reaction
conditions, the desired product 2u was isolated in good yield (Scheme 6). The
addition of TEMPO had no apparent effect on the 2,2,2-trifluoroethylthiolation
reaction, indicating that radical intermediate may not be involved in this process.
Scheme 6. Inhibition Experiment with TEMPO
Based on the above studies,
a
plausible mechanism of the
2,2,2-trifluoroethylthiolation reaction is provided in Scheme 7 based on the
experimental observations. The LnCuI may follow one of two pathways: the reaction
with CF3CH2I and elemental sulphur in the presence of NaBH4 may form complex 5,
which upon oxidative addition with aryl iodides generates intermediate I.
Subsequently, intermediate I undergoes reductive elimination to afford the desired
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2,2,2-trifluoroethylthiolated product and re-generates LnCuI (Pathway A). Another
plausible sequence (pathway B) may occur by the reaction of LnCuI with aryl iodides
and elemental sulphur under reductive conditions20 to form the copper(I)
thiophenolato complex 6,26 which upon oxidative addition with CF3CH2I produces
intermediate II. The subsequent reductive elimination of II gives the desired product
ArSCH2CF3 and generates LnCuI (Pathway B).
Scheme 7. Proposed Reaction Mechanism
To further distinguish which pathway is favoured pathway, a cross-over
experiment was carried out. The reaction of 5 with 4-iodoanisole-d3 reacted faster
than that of 6 with CF3CH2I (Scheme 8). These results clearly demonstrate that the
Pathway A involving the formation of 5 probably is favored during the catalytic
cycles although we could not rule out Pathway B.
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Scheme 8. Cross Over Experiments
In summary, the 2,2,2-trifluoroethylthiolation reaction of aryl bromides and
iodides with elemental sulfur, and 1,1,1-trifluoro-2-iodoethane was achieved by
copper catalysis. This method offers a new strategy to selectively construct aryl
2,2,2-trifluoroethyl thioethers in good to excellent yield from readily available,
inexpensive reagents. Moreover, these reactions are operationally simple, scalable and
compatible with varied functional groups. These aryl 2,2,2-trifluoroethyl thioethers
constitute a group of synthetically demanding and medicinally important compounds.
Mechanistic studies indicate that the copper thiolate species 5 may be involved as key
intermediates of the catalytic cycle.
EXPERIMENTAL SECTION
General Methods: All manipulations were carried out under an inert atmosphere
using a nitrogen-filled glovebox or standard Schlenk techniques. All glassware was
oven or flame dried immediately prior to use. Solvents were freshly dried and
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degassed according to the procedures in Purification of Laboratory Chemicals prior to
use. Deuterated solvents were purchased commercially, and were degassed and stored
over activated 4 Å molecular sieves. 5-iodo-2H-[1,2'-bipyridin]-2-one (3)27 was
prepared according to the published procedures. All other reagents were obtained
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from commercial sources and used without further purification. The H, 19F and
13C{1H}NMR spectra were recorded at 400, 376, and 101 MHz, respectively. 19F
NMR chemical shifts were determined relative to CFCl3 as outside standard and low
field is positive. Mass spectrometry was performed on GC/MS spectrometer under
electron impact (EI) ionization technique. HRMS data were recorded on a GC-TOF
instrument using EI technique.
General procedure A (for the copper-catalyzed 2,2,2-trifluoroethylthiolation
reaction of aryl iodides): In a dry-box, CuI (9.5 mg, 0.050 mmol), phen (18 mg, 0.10
mmol), NaBH4 (57 mg, 1.5 mmol), S8 (32 mg, 1.0 mmol), CF3CH2I (98.5 µL, 1.0
mmol), aryl iodides (0.50 mmol), and 5.0 mL DMF were added to a oven-dried 25
mL test tube with Teflon screw cap. The tube was sealed and the solution was placed
into a preheated 85 C oil bath for 12 h. The tube was removed from the oil bath and
cooled to r.t. The reaction mixture was filtered through a layer of Celite, eluted with
diethyl ether. Water (5.0 mL) was added to the mixture at 0 °C. The resulting mixture
was extracted by ethyl ether (10 mL × 3), and the combined organic layers was
washed with water (10 mL × 3), and then dried over magnesium sulfate. The solvent
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was removed by rotary evaporation in ice bath and the resulting product was purified
by column chromatography on silica gel with pentane/Et2O.
General procedure B (for the copper-catalyzed 2,2,2-trifluoroethylthiolation
reaction of aryl bromides): In a dry-box, CuI (9.5 mg, 0.050 mmol),
5,5-dimethylcyclohexane-1,3-dione (14 mg, 0.10 mmol), NaBH4 (57 mg, 1.5 mmol),
S8 (32 mg, 1 mmol), ICH2CF3 (98.5 µL, 1.0 mmol), aryl bromides 0.50 mmol), and
5.0 mL DMF were added to a oven-dried 25 mL test tube with Teflon screw cap. The
tube was sealed and the solution was placed into a preheated 95 C oil bath for 12 h.
The tube was removed from the oil bath and cooled to r.t. The reaction mixture was
filtered through a layer of Celite, eluted with diethyl ether. Water (5.0 mL) was added
to the mixture at 0 °C. The resulting mixture was extracted by ethyl ether (10 mL × 3),
and the combined organic layers was washed with water (10 mL × 3), and then dried
over magnesium sulfate. The solvent was removed by rotary evaporation in ice bath
and the resulting product was purified by column chromatography on silica gel with
pentane/Et2O.
p-Tolyl(2,2,2-trifluoroethyl)sulfane (2a). According to general procedure A,
obtained in 81 % yield (83 mg) as a yellow oil. According to general procedure B,
obtained in 71 % yield (73 mg). Rf (n-pentane) = 0.73. 1H NMR (400 MHz, CDCl3) δ
7.43 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H), 3.42 (q, J = 9.8 Hz, 2H), 2.38 (s,
3H). 19F NMR (376 MHz, CDCl3) δ -66.4 (t, J = 9.8 Hz, 3F). 13C{1H}NMR (101 MHz,
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CDCl3) δ 138.5 (s), 132.6 (s), 131.1 (s), 130.1 (s), 125.5 (q, J = 276.3 Hz), 38.7 (q, J
= 32.4 Hz), 21.1 (s). IR (KBr): ν 2928, 1680, 1607, 1581, 1305, 1242, 1081, 870, 592
cm-1. GC-MS m/z 206 (M+). HRMS (EI) m/z: calcd. for C9H9SF3: 206.0377; found:
206.0383.
(3,5-Dimethylphenyl)(2,2,2-trifluoroethyl)sulfane (2b). According to general
procedure A, obtained as a yellow oil in 93% yield (102 mg). Rf (n-pentane) = 0.59.
1H NMR (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.13 (s, 1H), 6.96 (d, J = 8.0 Hz, 1H),
3.46 (q, J = 9.3 Hz, 2H), 2.33 (s, 3H), 2.29 (s, 3H). 19F NMR (376 MHz, CDCl3) δ
-66.4 (t, J = 9.3 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 139.0 (s), 133.2 (s),
129.8 (s), 129.2 (s), 125.4 (q, J = 277.8 Hz), 38.0 (q, J = 32.5 Hz), 21.2 (s). IR (KBr):
ν 2934, 1682, 1601, 1581, 1379, 1271, 1125, 848, 546 cm-1. GC-MS m/z 220 (M+).
HRMS (EI) m/z: calcd. for C10H11SF3: 220.0534; found: 220.0537.
(4-(tert-Butyl)phenyl)(2,2,2-trifluoroethyl)sulfane (2c). According to general
procedure A, obtained as a yellow oil in 71% yield (88 mg). Rf (n-pentane) = 0.86. 1H
NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.2, Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 3.46 (q,
J = 9.7 Hz, 2H), 1.37 (d, J = 1.4 Hz, 9H). 19F NMR (376 MHz, CDCl3) δ -66.3 (t, J =
9.7 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 151.6 (s), 132.1 (s), 130.2 (s), 126.3
(s), 125.5 (q, J = 276.4 Hz), 38.5 (q, J = 32.5 Hz), 34.6 (s), 31.2 (s). IR (KBr): ν 2965,
2870, 1490, 1399, 1364, 1306, 1268, 1119, 1014, 828, 556 cm-1. GC-MS m/z 248
(M+). HRMS (EI) m/z: calcd. for C12H15SF3: 248.0847; found: 248.0839.
[1,1'-Biphenyl]-4-yl(2,2,2-trifluoroethyl)sulfane (2d). According to general
procedure A, obtained as a white solid in 75% yield (101 mg). Rf (n-pentane) = 0.41.
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M.p: 74-75 °C . 1H NMR (400 MHz, CDCl3) δ 7.66 – 7.56 (m, 7H), 7.49 (t, J = 7.2 Hz,
1H), 7.44 – 7.36 (m, 1H), 3.51 (q, J = 9.5 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ
-66.2 (t, J = 9.5 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 141.1 (s), 140.1 (s),
132.6 (s), 132.2 (s), 129.5 (s), 128.9 (s), 127.9 (s), 127.7 (s), 127.1 (s), 125.4 (q, J =
276.5 Hz), 38.2 (q, J = 32.6 Hz). IR (KBr): ν 2927, 1680, 1479, 1398, 1308, 1243,
1127, 1007, 833, 698 cm-1. GC-MS m/z 268 (M+). HRMS (EI) m/z: calcd. for
C14H11SF3: 268.0534; found: 268.0527.
[1,1'-Biphenyl]-2-yl(2,2,2-trifluoroethyl)sulfane (2e). According to general
procedure A, obtained as a yellow oil in 97% yield (130 mg). Rf (n-pentane) = 0.50.
1H NMR (400 MHz, CDCl3) δ 7.65 – 7.57 (m, 1H), 7.51 – 7.42 (m, 5H), 7.37 (m, 3H),
3.18 (q, J = 9.7 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -65.9 (t, J = 9.7 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 144.0 (s), 140.3 (s), 131.9 (s), 131.7 (s), 130.8 (s),
129.4 (s), 128.2 (s), 127.9 (s), 127.7 (s), 125.3 (q, J = 277.8 Hz), 36.8 (q, J = 32.5 Hz).
IR (KBr): ν 2928, 1681, 1586, 1596, 1463, 1307, 1270, 1125, 1039, 840, 650 cm-1.
GC-MS m/z 268 (M+). HRMS (EI) m/z: calcd. for C14H11SF3: 268.0534; found:
268.0531.
(4-Nitrophenyl)(2,2,2-trifluoroethyl)sulfane (2f). According to general
procedure A, obtained as a yellow oil in 99% yield (117 mg). According to general
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procedure B, obtained in 96% yield (114 mg). Rf (n-pentane:ether=10:1) = 0.48. H
NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 3.63 (q,
J = 9.3 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.1 (t, J = 9.3 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 146.5 (s), 143.2 (s), 128.8 (s), 124.9 (q, J = 276.7
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Hz), 124.2 (s), 35.8 (q, J = 33.8 Hz). IR (KBr): ν 2925, 2854, 1635, 1582, 1518, 1341,
1242, 1131, 853, 682 cm-1. GC-MS m/z 237 (M+). HRMS (EI) m/z: calcd. for
C8H6SNO2F3: 237.0071; found: 237.0067.
(2-Methyl-4-nitrophenyl)(2,2,2-trifluoroethyl)sulfane (2g). According to
general procedure A, obtained as a yellow oil in 99% yield (124 mg). Rf
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(n-pentane:ether=10:1) = 0.61. H NMR (400 MHz, CDCl3) δ 8.08 – 8.02 (m, 2H),
7.46 (d, J = 9.2 Hz, 1H), 3.63 (q, J = 9.4 Hz, 2H), 2.50 (s, 3H). 19F NMR (376 MHz,
CDCl3) δ -66.2 (t, J = 9.4 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 149.5 (s),
136.0 (s), 135.4 (s), 133.6 (s), 132.9 (s), 127.5 (s), 125.1 (q, J = 277.8 Hz), 37.8 (q, J
= 33.3 Hz), 20.2 (s). IR (KBr): ν 2934, 1609, 1525, 1449, 1310, 1243, 1129, 1082,
799, 637 cm-1. GC-MS m/z 251 (M+). HRMS (EI) m/z: calcd. for C9H8SNO2F3:
251.0228; found: 251.0226.
(3-Nitrophenyl)(2,2,2-trifluoroethyl)sulfane (2h). According to general
procedure A, obtained as a yellow oil in 85% yield (101 mg). Rf
(n-pentane:ether=10:1) = 0.42. 1H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 8.18 (d, J
= 8.2 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 3.56 (q, J = 9.4 Hz,
2H). 19F NMR (376 MHz, CDCl3) δ -66.2 (t, J = 9.4 Hz, 3F). 13C{1H}NMR (101 MHz,
CDCl3) δ 136.8 (s), 136.2 (s), 130.1 (s), 125.5 (s), 125.0 (q, J = 277.8 Hz), 122.8 (s),
37.4 (q, J = 33.3 Hz). IR (KBr): ν 2940, 1591, 1481, 1427, 1308, 1245, 1268, 1126,
1043, 861, 687 cm-1. GC-MS m/z 237 (M+). HRMS (EI) m/z: calcd. for C8H6SNO2F3:
237.0071; found: 237.0069.
Ethyl 4-((2,2,2-trifluoroethyl)thio)benzoate (2i). According to general
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procedure A, obtained as a yellow oil in 99% yield (131 mg). Rf
(n-pentane:ether=10:1) = 0.44. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.4 Hz, 2H),
7.47 (d, J = 7.4 Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H), 3.55 (q, J = 9.5 Hz, 2H), 1.40 (t, J =
7.0 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -66.2 (t, J = 9.5 Hz, 3F). 13C{1H}NMR
(101 MHz, CDCl3) δ 165.9 (s), 139.9 (s), 130.4 (d, J = 3.0 Hz), 130.2 (s), 129.3 (s),
129.2 (s), 125.1 (q, J = 277.6 Hz), 61.2 (s), 36.4 (q, J = 33.3 Hz), 14.3 (s). IR (KBr): ν
2985, 1711, 1595, 1477, 1368, 1272, 1106, 1017, 843, 637 cm-1. GC-MS m/z 264
(M+). HRMS (EI) m/z: calcd. for C11H11SO2F3: 264.0432; found: 264.0430.
Methyl 4-((2,2,2-trifluoroethyl)thio)benzoate (2j). According to general
procedure B, obtained as a yellow oil in 76% yield (95 mg). Rf (n-pentane:ether=10:1)
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= 0.41. H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.9 Hz, 2H), 7.48 (d, J = 8.0 Hz,
2H), 3.94 (s, 3H), 3.56 (q, J = 9.5 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.2 (t, J
= 9.5 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 166.4 (s), 140.0 (s), 130.3 (s),
129.1 (s), 129.0 (s), 125.1 (q, J = 277.6 Hz), 52.3 (s), 36.4 (q, J = 33.4 Hz). IR (KBr):
ν 2953, 1718, 1596, 1492, 1436, 1308, 1242, 1116, 1015, 842 ,691 cm-1. GC-MS
m/z 250 (M+). HRMS (EI) m/z: calcd. for C10H9SO2F3: 250.0275; found: 250.0269.
Methyl 3-((2,2,2-trifluoroethyl)thio)benzoate (2k). According to general
procedure A, obtained as a yellow oil in 95% yield (125 mg). Rf
(n-pentane:ether=10:1) = 0.41. 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.99 (d, J
= 7.8 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 3.95 (s, 3H), 3.50 (q,
J = 9.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.3 (t, J = 9.6 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 166.2 (s), 135.9 (s), 134.4 (s), 132.4 (s), 131.3 (s),
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129.3 (s), 129.1 (s), 125.2 (q, J = 267.5 Hz), 52.4 (s), 37.8 (q, J = 33.0 Hz). IR (KBr):
ν 2953, 1720, 1601, 1523, 1422, 1356, 1245, 1116, 1017, 842 ,637 cm-1. GC-MS m/z
250 (M+). HRMS (EI) m/z: calcd. for C10H9SO2F3: 250.0275; found: 250.0271.
Methyl 2-((2,2,2-trifluoroethyl)thio)benzoate (2l). According to general
procedure A, obtained as a yellow oil in 88% yield (110 mg). According to general
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procedure B, obtained in 83% yield (104 mg). Rf (n-pentane:ether=10:1) = 0.31. H
NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.6 Hz, 1H), 7.59 – 7.42 (m, 2H), 7.36 – 7.29
(m, 1H), 3.96 (s, 3H), 3.60 (q, J = 9.7 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -65.2 (t,
J = 9.7 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 166.9 (s), 137.1 (s), 132.5 (s),
131.2 (s), 130.0 (s), 128.4 (s), 126.1 (s), 125.4 (q, J = 277.7 Hz), 52.4 (s), 35.8 (q, J =
32.5 Hz). IR (KBr): ν 2953, 1713, 1589, 1466, 1435, 1310, 1255, 1126, 1060, 963,
692 cm-1. GC-MS m/z 250 (M+). HRMS (EI) m/z: calcd. for C10H9SO2F3: 250.0275;
found: 250.0269.
4-((2,2,2-Trifluoroethyl)thio)benzonitrile (2m). According to general procedure
A, obtained as a yellow oil in 90% yield (97 mg). According to general procedure B,
obtained in 85% yield (92 mg). Rf (n-pentane:ether=10:1) = 0.22. 1H NMR (400 MHz,
CDCl3) δ 7.62 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 7.8 Hz, 2H), 3.58 (q, J = 9.4 Hz, 2H).
19F NMR (376 MHz, CDCl3) δ -66.1 (t, J = 9.4 Hz, 3F). 13C{1H}NMR (101 MHz,
CDCl3) δ 140.8 (s), 132.6 (s), 129.3 (s), 125.0 (q, J = 276.7 Hz), 118.3 (s), 110.7 (s),
36.0 (q, J = 33.7 Hz). IR (KBr): ν 2921, 2229, 1594, 1487, 1400, 1315, 1241, 1129,
1016, 823, 637, 545 cm-1. GC-MS m/z 217 (M+). HRMS (EI) m/z: calcd. for
C9H6SNF3: 217.0175; found: 217.0173.
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2-((2,2,2-Trifluoroethyl)thio)benzonitrile (2n). According to general procedure
B, obtained as a yellow oil in 82% yield (89 mg). Rf (n-pentane:ether=10:1) = 0.32. 1H
NMR (400 MHz, CDCl3) δ 7.77 – 7.65 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.45 (t, J =
7.8 Hz, 1H), 3.58 (q, J = 9.4 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.1 (t, J = 9.4
Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 137.2 (s), 134.1 (s), 133.8 (s), 133.3 (s),
128.8 (s), 125.0 (q, J = 277.7 Hz), 116.8 (s), 116.6 (s), 37.5 (q, J = 33.3 Hz). IR
(KBr): ν 2928, 2227, 1675, 1586, 1467, 1312, 1242, 1128, 1084, 840, 637 cm-1.
GC-MS m/z 217 (M+). HRMS (EI) m/z: calcd. for C9H6SNF3: 217.0169; found:
217.0173.
1-(4-((2,2,2-Trifluoroethyl)thio)phenyl)ethanone (2o). According to general
procedure A, obtained as a yellow oil in 78% yield (91 mg). According to general
procedure B, obtained as a yellow oil in 85% yield (100 mg). Rf
(n-pentane:ether=10:1) = 0.14. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.8 Hz, 2H),
7.50 (d, J = 7.8 Hz, 2H), 3.58 (q, J = 9.7 Hz, 2H), 2.62 (s, 3H). 19F NMR (376 MHz,
CDCl3) δ -66.2 (t, J = 9.5 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 197.1 (s),
140.4 (s), 135.7 (s), 129.1 (s), 129.0 (s), 125.0 (q, J = 277.7 Hz), 36.2 (q, J = 33.5 Hz),
26.6 (s). IR (KBr): ν 2933, 1682, 1591, 1560, 1359, 1264, 1131, 957, 821, 590 cm-1.
GC-MS m/z 234 (M+). HRMS (EI) m/z: calcd. for C10H11SOF3 (M++2H): 236.0483;
found: 236.0480.
1-(3-((2,2,2-Trifluoroethyl)thio)phenyl)ethanone (2p). According to general
procedure A, obtained as a yellow oil in 97% yield (113 mg). Rf
(n-pentane:ether=10:1) = 0.13. 1H NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.40 (d, J
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= 6.8 Hz, 1H), 7.37 – 7.30 (m, 2H), 3.47 (q, J = 9.6 Hz, 2H), 1.49 (d, J = 6.3 Hz, 3H).
19F NMR (376 MHz, CDCl3) δ -66.3 (t, J = 9.6 Hz, 3F). 13C{1H}NMR (101 MHz,
CDCl3) δ 147.1 (s), 133.9 (s), 130.5 (s), 129.4 (s), 128.6 (s), 125.1 (s), 125.4 (q, J =
277.5 Hz), 69.9 (s), 37.9 (q, J = 32.7 Hz), 25.3 (s). IR (KBr): ν 2976, 1593, 1473,
1411, 1306, 1242, 1076, 791, 700, 532 cm-1. GC-MS m/z 234 (M+). HRMS (EI) m/z:
calcd. for C10H9SOF3: 234.0326; found: 234.0317.
(2,2,2-Trifluoroethyl)(4-(trifluoromethyl)phenyl)sulfane (2q). According to
general procedure A, obtained as a white oil in 84% yield (110 mg). Rf (n-pentane) =
0.75. 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H),
3.54 (q, J = 9.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -62.7 (s, 3F), -66.2 (t, J = 9.6
Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 138.7 (q, J = 1.6 Hz), 130.2 (s), 129.7 (q,
J = 32.9 Hz), 126.1 (q, J = 3.8 Hz), 125.2 (s), 125.1 (q, J = 277.6 Hz), 122.5 (s), 36.8
(q, J = 33.4 Hz). IR (KBr): ν 2934, 1609, 1506, 1402, 1327, 1240, 1131, 1015, 832,
595 cm-1. GC-MS m/z 260 (M+). HRMS (EI) m/z: calcd. for C9H6SF6: 260.0094;
found: 260.0097.
(2,2,2-Trifluoroethyl)(4-(trifluoromethyl)phenyl)sulfane (2r). According to
general procedure A, obtained as a yellow oil in 81% yield (112 mg). Rf (n-pentane) =
0.64. 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H),
3.45 (q, J = 9.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -57.9 (s, 3F), -66.3 (t, J = 9.6
Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 149.2 (q, J = 1.9 Hz), 133.7 (s), 132.2 (s),
125.2 (q, J = 276.4 Hz), 121.7 (q, J = 1.0 Hz), 120.4 (q, J = 258.8 Hz), 38.3 (q, J =
32.9 Hz). IR (KBr): ν 2944, 1491, 1445, 1384, 1257, 1208, 1046, 856, 545 cm-1.
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GC-MS m/z 276 (M+). HRMS (EI) m/z: calcd. for C9H6SOF6: 276.0044; found:
276.0050.
(2-Methoxyphenyl)(2,2,2-trifluoroethyl)sulfane (2s). According to general
procedure A, obtained as a yellow oil in 62% yield (69 mg). Rf (n-pentane) = 0.45. 1H
NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.00 –
6.90 (m, 2H), 3.95 (s, 3H), 3.48 (q, J = 9.8 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ
-66.0 (t, J = 9.8 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 158.7 (s), 134.1 (s),
130.1 (s), 125.6 (q, J = 276.5 Hz), 121.1 (s), 120.5 (s), 111.0 (s), 55.8 (s), 35.6 (q, J =
32.3 Hz). IR (KBr): ν 2939, 1583, 1478, 1434, 1307, 1240, 1081, 1024, 841, 638
cm-1. GC-MS m/z 222 (M+). HRMS (EI) m/z: calcd. for C9H9SOF3: 222.0326;
found: 222.0330.
(3-Methoxyphenyl)(2,2,2-trifluoroethyl)sulfane (2t). According to general
procedure A, obtained as a yellow oil in 93% yield (103 mg). Rf (n-pentane) = 0.47.
1H NMR (400 MHz, CDCl3) δ 7.33 – 7.22 (m, 1H), 7.13 – 7.00 (m, 2H), 6.86 (d, J =
8.2 Hz, 1H), 3.84 (s, 3H), 3.48 (q, J = 9.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ
-66.3 (t, J = 9.6 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 159.9 (s), 134.9 (s),
130.1 (s), 125.3 (q, J = 276.4 Hz), 123.6 (s), 116.8 (s), 113.7 (s), 55.4 (s), 37.9 (q, J =
32.8 Hz). IR (KBr): ν 2940, 1591, 1577, 1481, 1427, 1308, 1245, 1126, 1043, 993,
774 cm-1. GC-MS m/z 222 (M+). HRMS (EI) m/z: calcd. for C9H9SOF3: 222.0326;
found: 222.0329.
(4-Methoxyphenyl)(2,2,2-trifluoroethyl)sulfane (2u). According to general
procedure A, obtained as a yellow oil in 84% yield (93 mg). According to general
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procedure B, obtained in 60% yield (67 mg). Rf (n-pentane) = 0.60. H NMR (400
MHz, CDCl3) δ 7.51 (d, J = 7.5 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 3.83 (s, 3H), 3.34
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(q, J = 9.8 Hz, 2H). F NMR (376 MHz, CDCl3) δ -66.3 (t, J = 9.8 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 160.2 (s), 135.4 (s), 132.8 (s), 132.7 (s), 125.5 (q,
J = 276.5 Hz), 124.0 (s), 114.8 (s), 55.4 (s), 39.6 (q, J = 32.0 Hz). IR (KBr): ν 2926,
1598, 1493, 1411, 1307, 1241, 1123, 1018, 841, 502 cm-1. GC-MS m/z 222 (M+).
HRMS (EI) m/z: calcd. for C9H9SOF3: 222.0326; found: 222.0323.
(4-Chlorophenyl)(2,2,2-trifluoroethyl)sulfane (2v). According to general
procedure A, obtained as a yellow oil in 82% yield (93 mg). Rf (n-pentane) = 0.61. 1H
NMR (400 MHz, CDCl3) δ 7.46 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 3.43 (q,
J = 9.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.3 (t, J = 9.6 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 166.4 (s), 140.0 (s), 130.3 (s), 129.1 (s), 128.9 (s),
125.1 (q, J = 276.7 Hz), 52.3 (s), 36.4 (q, J = 33.4 Hz). IR (KBr): ν 2927, 1574, 1477,
1390, 1309, 1242, 1094, 1013, 820, 500 cm-1. GC-MS m/z 226 (M+). HRMS (EI)
m/z: calcd. for C8H6SClF3: 225.9831; found: 225.9837.
(3-Fluorophenyl)(2,2,2-trifluoroethyl)sulfane (2w). According to general
procedure A, obtained as a yellow oil in 99% yield (104 mg). Rf (n-pentane) = 0.65.
1H NMR (400 MHz, CDCl3) δ 7.40 – 7.25 (m, 2H), 7.21 (d, J = 9.0 Hz, 1H), 7.02 (t, J
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= 8.4 Hz, 1H), 3.49 (q, J = 9.6 Hz, 2H). F NMR (376 MHz, CDCl3) δ -66.3 (t, J =
9.6 Hz, 3F), -111.4 - -111.5 (m, 1F). 13C{1H}NMR (101 MHz, CDCl3) δ 163.9 (s),
161.4 (s), 135.8 (d, J = 7.9 Hz), 130.6 (d, J = 8.5 Hz), 126.8 (d, J = 3.0 Hz), 125.2 (q,
J = 276.4 Hz), 118.1 (d, J = 22.3 Hz), 37.6 (q, J = 33.1 Hz). IR (KBr): ν 2927, 2855,
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1598, 1580, 1475, 1310, 1263, 1128, 881, 520 cm-1. GC-MS m/z 210 (M+). HRMS
(EI) m/z: calcd. for C8H6SF4: 210.0126; found: 210.0125.
Naphthalen-1-yl(2,2,2-trifluoroethyl)sulfane (2x). According to general
procedure A, obtained as a yellow oil in 91% yield (110 mg). Rf (n-pentane) = 0.63.
1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.5 Hz, 1H), 7.97 – 7.84 (m, 3H), 7.67 (t, J
= 7.3 Hz, 1H), 7.59 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 3.49 (q, J = 9.7 Hz,
2H). 19F NMR (376 MHz, CDCl3) δ -66.0 (t, J = 9.7 Hz, 3F). 13C{1H}NMR (101 MHz,
CDCl3) δ 134.3 (s), 133.6 (s), 133.3 (s), 130.4 (s), 130.0 (s), 128.9 (s), 129.19 –
127.70 (m), 127.3 (s), 126.5 (s), 125.7 (s), 125.4 (q, J = 279.8 Hz), 125.2 (s), 38.1 (q,
J = 32.4 Hz). IR (KBr): ν 3057, 1503, 1411, 1380, 1306, 1242, 1124, 973, 840, 649
cm-1. GC-MS m/z 242 (M+). HRMS (EI) m/z: calcd. for C12H9SF3: 242.0377; found:
242.0373.
(9H-fluoren-3-yl)(2,2,2-trifluoroethyl)sulfane (2y). According to general
procedure A, obtained as a white solid in 83% yield (116 mg). Rf (n-pentane) = 0.43.
M.p: 69-72 °C . 1H NMR (400 MHz, CDCl3) δ 7.84 – 7.69 (m, 3H), 7.62 – 7.53 (t, J =
8.1 Hz, 2H), 7.47 – 7.32 (m, 2H), 3.92 (s, 2H), 3.51 (q, J = 9.7 Hz, 2H). 19F NMR
(376 MHz, CDCl3) δ -66.2 (t, J = 9.7 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ
144.3 (s), 143.3 (s), 142.1 (s), 140.7 (s), 131.5 (s), 131.1 (s), 129.1 (s), 127.3 (s),
127.0 (s), 125.5 (q, J = 276.5 Hz), 125.2 (s), 120.5 (s), 120.2 (s), 38.8 (q, J = 32.4 Hz),
36.8 (s). IR (KBr): ν 3065, 2896, 1465, 1450, 1407, 1306, 1241, 1120, 953, 828, 581
cm-1. GC-MS m/z 280 (M+). HRMS (EI) m/z: calcd. for C15H11SF3: 280.0534;
found: 280.0533.
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Methyl 5-((2,2,2-trifluoroethyl)thio)nicotinate (2aa). According to general
procedure B, obtained as a yellow oil in 89% yield (117 mg). Rf (n-pentane:ether=5:1)
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= 0.40. H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.3 Hz, 1H), 7.70 (t, J = 7.5 Hz,
1H), 7.47 – 7.35 (m, 1H), 4.14 (q, J = 9.9 Hz, 2H), 4.00 (s, 3H). 19F NMR (376 MHz,
CDCl3) δ -66.5 (t, J = 9.9 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 165.2 (s),
155.5 (s), 147.7 (s), 137.4 (s), 125.8 (s), 125.3 (q, J = 277.0 Hz), 122.1 (s), 52.9 (s),
31.2 (q, J = 33.7 Hz). IR (KBr): ν 2999, 2953, 1730, 1580, 1446, 1429, 1308, 1245,
1132, 977, 844 cm-1. GC-MS m/z 251 (M+). HRMS (EI) m/z: calcd. for C9H8SNO2F3:
251.0228; found: 251.0233.
5-((2,2,2-Trifluoroethyl)thio)quinoline (2ab). According to general procedure B,
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obtained as a yellow oil in 61% yield (74 mg). Rf (n-pentane:ether=5:1) = 0.29. H
NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 8.36 (s, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.95 –
7.72 (m, 2H), 7.62 (t, J = 7.5 Hz, 1H), 3.53 (q, J = 9.5 Hz, 2H). 19F NMR (376 MHz,
CDCl3) δ -66.2 (t, J = 9.5 Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 152.9 (s),
147.3 (s), 139.8 (s), 130.4 (s), 130.0 (s), 129.4 (s), 128.8 – 127.2 (m), 127.6 (d, J = 4.8
Hz), 125.2 (q, J = 277.8 Hz), 123.8 (s), 38.3 (q, J = 32.8 Hz). IR (KBr): ν 2976, 1620,
1567, 1488, 1382, 1272, 1130, 1046, 888, 547 cm-1. GC-MS m/z 242 (M+-H).
HRMS (EI) m/z: calcd. for C11H8SNF3: 243.0330; found: 243.0331.
6-Methoxy-2-((2,2,2-trifluoroethyl)thio)benzo[d]thiazole (2ac). According to
general procedure B, obtained as a white solid in 76% yield (106 mg). Rf
(n-pentane:ether=10:1) = 0.68. M.p: 70-71 °C . 1H NMR (400 MHz, CDCl3) δ 7.81 (d,
J = 8.9 Hz, 1H), 7.25 (d, J = 2.5 Hz, 1H), 7.06 (dd, J = 8.9, 2.6 Hz, 1H), 4.12 (q, J =
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9.7 Hz, 2H), 3.87 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -66.4 (t, J = 9.7 Hz, 3F).
13C{1H}NMR (101 MHz, CDCl3) δ 159.4 (s), 157.5 (s), 147.1 (s), 137.1 (s), 124.8 (q,
J = 276.4 Hz), 122.4 (s), 115.3 (s), 104.1 (s), 55.8 (s), 34.6 (q, J = 34.3 Hz). IR (KBr):
ν 2954, 1602, 1560, 1480, 1309, 1224, 1135, 1002, 831, 649 cm-1. GC-MS m/z 280
(M++H). HRMS (EI) m/z: calcd. for C10H8S2NOF3: 278.9999; found: 278.9993.
Methyl 3-((2,2,2-trifluoroethyl)thio)thiophene-2-carboxylate (2ad). According
to general procedure A, obtained as a yellow solid in 36% yield (46 mg). Rf
(n-pentane:ether=10:1) = 0.43. M.p: 73-75 °C . 1H NMR (400 MHz, CDCl3) δ 7.55 (d,
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J = 5.3 Hz, 1H), 7.08 (d, J = 5.3 Hz, 1H), 3.92 (s, 3H), 3.64 (q, J = 9.6 Hz, 2H). F
NMR (376 MHz, CDCl3) δ -65.8 (t, J = 9.6 Hz). 13C{1H}NMR (101 MHz, CDCl3) δ
162.1 (s), 139.6 (s), 131.2 (s), 127.7 (q, J = 1.6 Hz), 125.3 (s), 125.1 (q, J = 276.7 Hz),
52.2 (s), 35.9 (q, J = 33.4 Hz). IR (KBr): ν 3096, 2949, 2360, 1686, 1493, 1442, 1401,
1267, 1134, 1075, 896, 767, 636 cm-1. GC-MS m/z 256 (M+-H). HRMS (EI) m/z:
calcd. for C8H7S2O2F3: 255.9840; found: 255.9842.
5-((2,2,2-Trifluoroethyl)thio)-2H-[1,2'-bipyridin]-2-one (4). According to
general procedure A, obtained as a yellow oil in 66% yield (94 mg). Rf
(n-pentane:ether=1:1) = 0.23. 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 4.6 Hz, 1H),
8.25 (s, 1H), 7.97 – 7.82 (m, 2H), 7.52 (d, J = 9.6 Hz, 1H), 7.37 (s, 1H), 6.63 (d, J =
9.5 Hz, 1H), 3.29 (q, J = 9.7 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.1 (t, J = 9.7
Hz, 3F). 13C{1H}NMR (101 MHz, CDCl3) δ 161.1 (s), 151.0 (s), 149.1 (s), 145.4 (s),
142.3 (s), 138.0 (s), 125.3 (q, J = 276.5 Hz), 123.6 (s), 122.5 (s), 121.2 (s), 110.0 (s),
39.3 (q, J = 32.1 Hz). IR (KBr): ν 3394, 2973, 1667, 1597, 1525, 1435, 1308, 1269,
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