General, practical and selective oxidation protocol for CF3s into CF3S(O) group

Article abstract of DOI:10.3390/molecules24071249

A simple and efficient protocol for the oxidation of trifluoromethyl, mono- and difluoromethyl sulfides to the corresponding sulfoxides without over-oxidation to sulfones, using TFPAA prepared in situ from trifluoroacetic acid and 15% H₂O₂ aqueous solution was developed. The methodology is suitable for a wide range of aromatic and aliphatic substrates in milligram and multigram scales.

Full text of DOI:10.3390/molecules24071249

molecules
Article
General, Practical and Selective Oxidation Protocol
for CF3S into CF3S(O) Group
Liubov V. Sokolenko 1, Raisa K. Orlova 1, Andrey A. Filatov 1, Yurii L. Yagupolskii 1,3,
* ,
Emmanuel Magnier 2,
*
, Bruce Pégot 2 and Patrick Diter 2
1
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmans’ka Str. 5, 02094 Kyiv,
Ukraine; sokolenko.liubov@gmail.com (L.V.S.); OrlovaRaisa@ukr.net (R.K.O.); filatov@ioch.kiev.ua (A.A.F.)
Bâtiment Lavoisier, Université de Versailles-Saint-Quentin, 45 avenue des Etats-Unis, 78035 Versailles,
France; bruce.pegot@uvsq.fr (B.P.); patrick.diter@uvsq.fr (P.D.)
2
3
Enamine Ltd, A. Matrosova str. 23, Kiev 01103, Ukraine
*
Correspondence: yagupolskii@ioch.kiev.ua (Y.L.Y.); emmanuel.magnier@uvsq.fr (E.M.);
Tel.: +38-044-559-0349 (Y.L.Y.); +33-013-925-4466 (E.M.)
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 14 March 2019; Accepted: 27 March 2019; Published: 30 March 2019
Abstract: A simple and efficient protocol for the oxidation of trifluoromethyl, mono- and
difluoromethyl sulfides to the corresponding sulfoxides without over-oxidation to sulfones, using
TFPAA prepared in situ from trifluoroacetic acid and 15% H2O2 aqueous solution was developed.
The methodology is suitable for a wide range of aromatic and aliphatic substrates in milligram and
multigram scales.
Keywords: trifluoromethylsulfides; trifluoromethylsulfoxides; oxidation; trifluoroperacetic acid;
dihydrogen peroxide
1. Introduction
The synthesis of trifluoromethylsulfinyl containing compounds is a recent trend in current
organic chemistry due to the practical significance of such compounds [
biological activity is promising. They are also key intermediates for trifluoromethyl-containing
sulfoximine synthesis and are excellent chiral auxiliaries [ ]. Synthetic approaches dedicated to
trifluoromethyl sulfoxides include (1) trifluoromethylation of the corresponding sulfinyl halides
or sulfinic esters using TMSCF3 [ ], (2) reaction of aromatic compounds with triflinate salts [ ],
1]. In particular, their
2–5
6
–
8
9
(3) rearrangement of aryl triflinates in the presence of AlCl3 [10], (4) trifluoromethanesulfinilation using
Langlois’ system (CF3SO2Na/POCl3) [11] or with 1-(trifluoromethylsulfinyl)-pyrrolidine-2,5-dione [12].
However, the most important and common method for the synthesis of trifluoromethylsulfoxides is
the oxidation of the corresponding trifluoromethylsulfides using various oxidants, mainly peroxyacids,
e.g. mCPBA [1]. It is noteworthy to mention that oxidation with mCPBA is sensitive to temperature.
As a result, over-oxidation frequently occurs and non-negligible amounts of trifluoromethylsulfone
are formed [13]. Furthermore, this reagent converts into m-chlorobenzoic acid, which is sometimes not
easy to separate from the sulfoxide. Oxidation of an aliphatic sulfide was also described with Oxone®
as oxidant [14]. Waste by-products formed during the oxidation reaction as well as the necessity to
use silica as a component of reaction medium cause difficulties in scaling up. Trifluoroperacetic acid
(TFPAA) was shown to be a convenient reagent for the oxidation of sulfides to sulfoxides, as it reacts
more rapidly at low temperature than other peroxy acids [15]. To the best of our knowledge, TFPAA has
not been widely applied to the oxidation of perfluoroalkyl sulfides and only a few articles [14
,16–21]
and patents [22 27] documented this procedure. TFPAA solution can be prepared from 30% H2O2 and
–
trifluoroacetic acid or 80–90% H2O2 and trifluoroacetic anhydride [28
,29]. On the basis of literature
Molecules 2019, 24, 1249; doi:10.3390/molecules24071249
www.mdpi.com/journal/molecules

Molecules 2019, 24, 1249
2 of 12
data and our experience in oxidation reactions of trifluoromethyl sulfides, the use of TFPAA, obtained
by both methods, has one common limitation as for mCPBA: over-oxidation readily occurs to form
difficult-to-separate mixtures of trifluoromethyl sulfide, trifluoromethyl sulfoxide, and trifluoromethyl
sulfone [17–19]. On the other hand, regarding the advantages of this method (easy to prepare and a
cheap reagent, trifluoroacetic acid as side product), we believed there was an urgent need to exploit it.
The description of a general and selective method of oxidation is especially important in the context of
an exponential growth of molecules bearing a SCF3 group [1].
Herein we propose an easy-to-handle and high-yielding procedure for the oxidation of alkyl
and aryl perfluoroalkyl sulfides to the corresponding sulfoxides without over-oxidation thanks to the
reappraisal of oxidation by TFPAA.
2. Results and Discussion
We postulated that a decrease in concentration, associated with a rigorous measurement of the
latter, could dramatically reduce the formation of unwanted sulfone. Indeed, the use of TFPAA
obtained in situ from trifluoroacetic acid and 15% H2O2 aqueous solution proved to be successful
(
see experimental part). This method was firstly applied to aryl trifluoromethyl sulfides
electrons donating and electron-withdrawing substituents in various positions on the aromatic ring
(Scheme 1, Table 1). Corresponding aryl trifluoromethyl sulfoxides were obtained in high yields
1 bearing both
2
whatever the nature of the substituents on the aromatic ring. In all experiments, the crude product
contained less than 7% of non-reacted trifluoromethyl sulfide; at the same time, trifluoromethyl sulfone
was detected in negligible amounts in only two reactions (Table 1, Entry 4, 10).
Scheme 1. Oxidation of aryl trifluoromethyl sulfides 1.
Table 1. Oxidation of aryl trifluoromethyl sulfides 1.
Molar ratio in Crude Product 1
Crude2
Yield, %
Isolated
Yield, %
Entry
Reagent
Product
1
2
ArSO2CF3
1
5
95
0
95
91
-
2
7
93
0
85
3
4
4
2
96
98
0
96
89
-
traces
86

Molecules 2019, 24, 1249
3 of 12
Table 1. Cont.
Molar ratio in Crude Product 1
Crude2
Yield, %
Isolated
Yield, %
Entry
Reagent
Product
1
2
ArSO2CF3
5
3
97
0
100
96
6
7
0
3
100
97
0
0
98
-
100
96
8
9
3
3
97
0
0
90
84
85
97 3
70 3
10
7
0
91
2
0
100
-
83
87
11
100
1
Composition of crude product on the basis of 19F NMR data; 2 Crude yield is the isolated yield of product after
removing the solvent before further purification; 3 Mixture of 2i and corresponding phenol in 85:15 molar ratio
(according to 19F NMR data).
In most cases the crude product needs no further purification. If needed, compounds
2 were
easily separated from impurities by standard methods (see experimental part for details). It should
be noted that during the oxidation of acylated phenol 1i partial hydrolysis occurred and the crude
product contained ~15% of o-trifluoromethylsulfinyl phenol, which we failed to separate from 2i by
column chromatography.
Oxidation of aliphatic sulfides also proved successful (Scheme 2, Table 2).
Scheme 2. Oxidation of alkyl trifluoromethyl sulfides 3.
The thioether 3a was oxidized by TFPAA in high yield (83%) in 24 h. This simple procedure
can be favorably compared to our previous method which employed Oxone® [14]. Compound 4b
was isolated in low yield, most probably due to the high solubility of the product in water. Attempts

Molecules 2019, 24, 1249
4 of 12
to separate 4b from 3b by distillation failed. Use of an acyl protective group (Table 2, Entry 3) led
to a higher yield of sulfoxide 4c. In this case, as well as in the previous one, a small amount (<3%)
of trifluoromethyl sulfone was detected in the reaction mixture and the crude product. As in the
experiment with acylated phenol 1i (Table 1, Entry 9), product 4c contains ~15% of the corresponding
alcohol (Table 2, Entry 3), which we failed to separate from the ester by distillation. Oxidation of
sulfide 3d by 15% H2O2 solution in TFA proceeded with 90% conversion. The use of H2O2 in excess
(1.1 equiv.) led to the same results and the sulfone was not observed in this reaction mixture. Two other
examples demonstrated the efficiency of this transformation (entries 6–7).
Table 2. Oxidation of alkyl trifluoromethyl sulfides 3.
Molar ratio in Crude Product 1
Crude2
Yield, %
Isolated
Yield, %
Entry
Reagent
Product
3
4
AlkSO2CF3
1
2
3
4
5
6
4
96
0
-
-
83
15 3
54 4
60 5
60
11
0
89
97 4
90
traces
3
-
10
4
0
-
96
0
traces
1
63
-
13
0
87
85
7
99
-
85
1
Composition of crude product on the basis of 19F NMR data; 2 Crude yield is the isolated yield of product after
3
4
removing the solvent before further purification; Contains ~11 % of starting sulfide 3b
;
Mixture of 4c and
corresponding alcohol 4b in 85:15 molar ratio (according to 19F NMR data); 5 Use of 10% excess of H2O2 lead to the
same results.
To show the scope of our oxidation procedure a number of sulfides bearing difluoromethyl 5a–c,
bromodifluoromethyl 5e, dichlorofluoromethyl 5f, and 1,1,2,2-tetrafluoro-2-((1,2,4-triazol)-1-yl)-ethyl
5d groups were converted into sulfoxides (Scheme 3,Table 3).
Scheme 3. Oxidation of fluoromethyl and difluoromethyl sulfides 5.
As it is evident from Table 3, all compounds 6a
–f were obtained in high yields and the crude
products were pure enough to be used without further purification. The oxidation of 5a was strongly
exothermic and the reaction was complete within 4 h at room temperature yielding pure sulfoxide 6a
,
which contained neither difluoromethyl sulfide 5a nor difluoromethyl sulfone. If this reaction was

Molecules 2019, 24, 1249
5 of 12
◦ ◦
15 C for 6 h, with further stirring at ~10 C for 20 h, the crude product contained ~2%
of unreacted sulfide 5a.
performed at
−
Table 3. Oxidation of fluoromethyl and difluoromethyl sulfides 5.
Molar ratio in Crude Product 1
Isolated
Yield, %
Crude2Yield, %
Entry
Reagent
Product
5
6
ArSO2RF
70 3
1
0
100
0
-
2
3
4
4
96
96
0
0
80
75
-
-
4
5
5
3
95
96
0
1
95
-
92
91
6
0
100
0
-
69
1
Composition of crude product on the basis of 19F NMR data; 2 Crude yield is the isolated yield of product after
removing the solvent before further purification; 3 Reaction time 4 h.
It should be emphasized that the oxidation reactions of sulfides
a 0.05 to 50 g scale.
The application of this method to heterocyclic thioethers is highly challenging, as demonstrated
by the two following preliminary results. Thus, 2-trifluoromethylsulfenyl-5-acetylamino-pyridine
was oxidized to sulfoxide with low conversion after seven days stirring, and we failed to separate
1, 3, and 5 could be performed on
7
8
the product from the starting sulfide (Scheme 4). A study devoted to the oxidation of heterocyclic
substrates is needed but falls outside the scope of the present study.
Scheme 4. Oxidation of heterocyclic trifluoromethyl sulfides.
3. Materials and Methods
3.1. General Information
The purification of products by column chromatography (CC) was performed on Silica gel,
1
70–230 mesh 60A (Aldrich, Saint Louis, MI, USA) or by preparative TLC chromatography. H NMR

Molecules 2019, 24, 1249
6 of 12
spectra were recorded at 500 MHz with Bruker AVANCE DRX 500 instrument, or at 200 MHz or
300 MHz with Bruker AC-200 or AC-300, or at 400 MHz with Varian UNITY–Plus 400 spectrometer.
19F NMR spectra were recorded on Varian UNITY–Plus 400 spectrometer at 376.5 MHz or at 470 MHz
with Bruker AVANCE DRX 500 instrument or at 188 MHz with Bruker AC-200 (Bruker, Billerica,
MA, USA). Chemical shifts are given in ppm relative to Me4Si and CCl3F, respectively, as internal
or external standards. 13C NMR-spectra (proton decoupled) were recorded on a Bruker AVANCE
DRX 500 instrument at 125.7 MHz, or on Varian UNITY–Plus 400 spectrometer at 100.6 MHz, or at
75 or 50 MHz with Bruker AC-300 or AC-200. IR spectra were recorded with a Vertex 70 (Bruker)
instrument (in KBr tablet). Melting points were determined in open capillaries using SMP3 instrument
(Stuart Scientific Bibby Sterlin Ltd, Stone, Staffordshire, UK). Elemental analysis was performed in the
Analytical Laboratory of the Institute of Organic Chemistry, NAS of Ukraine, Kyiv.
In all experiments trifluoroacetic acid from Sigma-Aldrich, 99% (CAS 76-05-1) was used.
Difluoromethyl sulfides 5a
synthesized as was described in the article [31]. Fluoromethylsulfides 1k
according to the described procedures [32 34]. Trifluoromethylsulfides 1a
–
c
were synthesized by standard method [30]. Compound 5d was
3f,g, and 5e,f were prepared
3a , and were
,
–
–
j
,
–
e,
7
9
purchased from Enamine Ltd (www.enamine.net).
3.2. Important Information
It is critical to know the exact concentration of H2O2 used in order to avoid over dosage of
reagent that led to over oxidation. A solution of 15% H2O2 (mass concentration) was prepared from
commercial ~30–35% H2O2 solution by dilution with water ~1:1 w/w. The concentration of H2O2
solution was measured using densimetry or titration (see Supplementary Materials).
3.3. General Procedure for Oxidation of Polyfluoroalkyl Sulfides to Polyfluoroalkyl Sulfoxides
To the solution of sulfide 1, 3, or 5 (10 mmol) in CF3COOH (15–20 mL) 15 mass% aqueous
solution of H2O2 (containing 10 mmol of H2O2) was added dropwise very slowly (during 40–90 min)
at room temperature. Reaction is strongly exothermic; H2O2 was added at such a rate that the
, 3f,g,
temperature was kept in the range 25–28 ◦C inside the flask (20 ◦C for compounds 1k and 0 ◦C
for compounds 5e,f). Reaction mixture was stirred overnight at r.t. (for compound 3d − 96 h,
for 7–7 days), poured into water, neutralized with solid NaHCO3 to pH=6–7, then extracted with ether
or ethyl acetate (4 × 30 mL). Compounds 2k
,
4f,g, and 6e,f were extracted with dichloromethane
20 mL),
before neutralizing the TFA with NaHCO3. The organic phase was washed with water (4
×
dried with MgSO4 or Na2SO4. Solvent was removed at atmospheric pressure for low-boiling liquids
or on a rotary evaporator for solids or high-boiling liquids. Crude product was analyzed by NMR and
purified if necessary.
Phenyl Trifluoromethyl sulfoxide 2a
400 MHz):
= 7.56–7.63 (m, 3H, Ar-H), 7.75–7.77 (m, 2H, Ar-H). 19F NMR (DMSO-d6, 376.5 MHz):
−76.6 (s). Compound 1a was oxidized on a 50 g scale (in 70 mL of CF3COOH) with the same yield.
[13,35,
36]. Colorless liquid; yield 1.8 g (95%). 1H NMR (CDCl3,
δ
δ =
N-(4-((Trifluoromethyl)sulfinyl)phenyl)acetamide 2b 37 38]. Crude product was purified by column
chromatography, eluent CH2Cl2 (Rf = 0), then methyl-tert-butyl ether (Rf = 0.6). Pale yellow solid;
yield 2.1 g (85 %); m.p. 140–141 ◦C (Lit. 141–142 ◦C). 1H NMR (DMSO-d6, 500 MHz):
= 2.10 (s, 3H,
CH3), 7.80 (d, 3JH-H = 8 Hz, 2H, Ar-H), 7.90 (d, 3JH-H = 8 Hz, 2H, Ar-H), 10.41 (s, 1H, NH). 19F NMR
(DMSO-d6, 376.5 MHz):
75.2 (s). 13C NMR (DMSO-d6, 125.7 MHz): = 24.5, 119.8, 125.2 (q, 1JC-F
[ ,
δ
δ
=
−
δ
= 335.6 Hz, CF3), 127.6, 128.2, 144.8, 169.6. Compound 1b was also oxidized on a 10 g scale (in 30 mL
of CF3COOH) with the same yield.
N-(3-((Trifluoromethyl)sulfinyl)phenyl)acetamide 2c
(Lit. 104.5–105.5 ◦C). 1H NMR (DMSO-d6, 500 MHz):
Ar-H), 7.61 (t, 3JH-H = 8 Hz, 1H, Ar-H), 7.85 (d, 3JH-H = 8 Hz, 1H, Ar-H), 8.24 (s, 1H, Ar-H), 10.38 (s, 1H,
[
37]. White solid; yield 2.4 g (96%); m.p. 101–102 ◦C
= 2.08 (s, 3H, CH3), 7.49 (d,3JH-H = 8 Hz, 1H,
δ

Molecules 2019, 24, 1249
7 of 12
NH). 19F NMR (DMSO-d6, 376.5 MHz):
δ
=
−
74.8 (s). 13C NMR (DMSO-d6, 125.7 MHz):
δ
= 24.0, 115.1,
120.2, 123.6, 124.7 (q, 1JC-F = 335.6 Hz, CF3), 130.2, 135.8, 140.7, 168.9.
N-(2-((Trifluoromethyl)sulfinyl)phenyl)acetamide 2d
.
Crude product was purified by column
◦
chromatography, eluent methyl-tert-butyl ether (Rf = 0.6). White solid; yield 2.1 g (86%); m.p. 68–69 C.
IR (KBr): 3295, 3103, 2999, 2765, 2387, 2310, 2116, 1685, 1586, 1512, 1474, 1431, 1377, 1304, 1266, 1180,
1136, 1074, 1044, 1007, 889, 853, 776, 670, 603, 576, 549, 522, 476, 455, 431 cm−1 1H NMR (CDCl3,
.
500 MHz):
7.61 (t, 3JH-H = 7.5 Hz, 1H, Ar-H), 8.55 (d, 3JH-H = 7.5 Hz, 1H, Ar-H), 10.00 (s, 1H, NH). 19F NMR (CDCl3,
376.5 MHz):
= -72.3 (s). 13C NMR (CDCl3, 125.7 MHz): = 24.9, 118.1, 123.0, 123.6, 125.4 (q, 1JC-F
δ
= 2.17 (s, 3H, CH3), 7.20 (t, 3JH-H = 7.5 Hz, 1H, Ar-H), 7.39 (d, 3JH-H = 7.5 Hz, 1H, Ar-H),
δ
δ
=
337 Hz, CF3), 128.5, 135.1, 142.2, 168.9. Anal. Calcd for C9H8F3NO2S: C, 43.03; H, 3.21; N, 5.58. Found:
C, 43.00; H, 3.18; N, 5.57.
1-Fluoro-4-((trifluoromethyl)sulfinyl)benzene 2e [9]. Crude product contains 97 mol% of 2e and 3 mol% of
starting sulfide, which may be removed in vacuum (1 mBar) to give pure sulfoxide 2e. Light yellow
1
liquid; yield 1.9 g (96%). H NMR (CDCl3, 400 MHz):
δ
= 7.25–7.29 (m, 2H, Ar-H), 7.76–7.80 (m, 2H,
Ar-H). 19F NMR (DMSO-d6, 376.5 MHz):
δ
=
−
75.7 (s, 3F, CF3),
−
104.8 (s, 1F, Ar-F). 13C NMR (CDCl3,
100.6 MHz):
δ
= 117.2 (d, 2JC-F = 22 Hz), 124.6 (q, 1JC-F = 335 Hz, CF3), 128.5 (d, 3JC-F = 9 Hz), 131.1,
166.0, (d, 1JC-F = 254.5 Hz, C-F). Compound 1e was oxidized on a 50 g scale (in 70 mL of CF3COOH)
with the same yield.
1-Fluoro-2-((trifluoromethyl)sulfinyl)benzene 2f. White solid; yield 2.0 g (98%); m.p. 44–45 ◦C. IR (KBr):
3094, 2124, 1986, 1948, 1820, 1724, 1633, 1598, 1474, 1449, 1261, 1141, 955, 867, 823, 762, 706, 673, 579,
1
544, 490, 459, 430 cm−1. H NMR (CDCl3, 400 MHz):
δ
= 7.19–7.23 (m, 1H, Ar-H), 7.42–7.46 (m, 1H,
75.9 (s,
= 116.4 (d, 2JC-F = 20 Hz), 123.5 (dq,
Ar-H), 7.61–7.67 (m, 1H, Ar-H), 7.94–7.98 (m, 1H, Ar-H). 19F NMR (CDCl3, 376.5 MHz):
3F, CF3),
114.5 (s, 1F, Ar-F). 13C NMR (CDCl3, 125.7 MHz):
3JC-F = 15 Hz, 4JC-F 2.5 Hz), 124.9 (qd, 1JC-F = 335.5 Hz, 4JC-F = 3.8 Hz, CF3),125.6 (d, 4JC-F = 3.8 Hz),
127.2, 135.5 (d, 3JC-F = 7.5 Hz), 159.7 (d, 1JC-F = 252.7 Hz, C-F). Anal. Calcd for C7H4F4OS: C, 39.63; H,
1.90; S, 15.11. Found: C, 39.62; H, 1.91; S, 15.11.
δ
=
−
−
δ
1-Bromo-4-((trifluoromethyl)sulfinyl)benzene 2g
mol% of starting sulfide, which may be removed by washing with pentane to give pure product 2g
White solid; yield 2.6 g (96%); m.p. 57–58 ◦C (Lit. 56–57 ◦C). 1H NMR (CDCl3, 500 MHz):
= 7.66
[30,38]. Crude product contains 97 mol% of 2g and 3
.
δ
3
3
(d, JH-H = 8.5 Hz, 2H, Ar-H), 7.75 (d, JH-H = 8.5 Hz, 2H, Ar-H). 19F NMR (CDCl3, 470 MHz):
δ =
−74.4 (s). 13C NMR (CDCl3, 125.7 MHz): δ = 124.4 (q, 1JC-F = 335.6 Hz, CF3), 127.3, 128.6, 133.0, 134.7.
Compound 1g was oxidized on a 15 g scale (in 35 mL of CF3COOH) with the same yield.
2-((Trifluoromethyl)sulfinyl)-acetophenone 2h. Crude product contains 97 mol% of 2h and 3 mol% of
starting sulfide, which may be removed by washing with pentane to give pure product 2h. Pale yellow
solid; yield 2 g (85 %); m.p. 97–98 ◦C. IR (KBr): 3080, 2968, 1675, 1585, 1468, 1438, 1359, 1280, 1187,
1
1130, 1073, 961, 885, 772, 663, 602, 571, 483, 434 cm−1. H NMR (CDCl3, 400 MHz):
δ = 2.68 (s, 3H,
CH3), 7.74 (t, 3JH-H= 7 Hz, 1H, Ar-H), 7.88 (t, J = 7 Hz, 1H, Ar-H), 8.04 (d, 3JH-H = 7 Hz, 1H, Ar-H), 8.36
(d, 3JH-H= 7 Hz, 1H, Ar-H). 19F NMR (CDCl3, 376.5 MHz): 70.0 (s). 13C NMR (CDCl3, 100.6 MHz):
= 26.2, 125.1 (q, 1JC-F = 340 Hz, CF3), 126.0, 131.0, 132.4, 134.2, 135.4, 140.3, 198.3. Anal. Calcd for
δ
=
−
δ
C9H7F3O2S: C, 45.76; H, 2.99; S, 13.57. Found: C, 45.78; H, 3.01; S, 13.60.
2-((Trifluoromethyl)sulfinyl)phenyl acetate 2i. Crude product was purified by column chromatography,
eluent hexane-methyl-tert-butyl ether, 2:1 (Rf = 0.5), but the product contains ~15% of the corresponding
1
phenol. Pale yellow oil; yield 1.8 g (70 %). H NMR (CDCl3, 500 MHz):
δ = 2.33 (s, 3H, CH3), 7.05 (d,
3JH-H = 8 Hz, 1H, Ar-H), 7.53 (t, 3JH-H = 8 Hz, 1H, Ar-H), 7.68 (t, 3JH-H = 8 Hz, 1H, Ar-H), 8.03 (d, 3JH-H
= 8 Hz, 1H, Ar-H). 19F NMR (CDCl3, 470 MHz): 73.5 (s). 13C NMR (CDCl3, 125.7 MHz):
= 20.5,
123.4, 124.9 (q, 1JC-F = 336 Hz, CF3), 126.8, 127.0, 127.8, 134.5, 148.6, 167.8.
δ
=
−
δ

Molecules 2019, 24, 1249
8 of 12
2,4-Dinitro-1-((trifluoromethyl)sulfinyl)benzene 2j
.
Crude product was purified by column
chromatography, eluent hexane-methyl-tert-butyl ether, 5:1 (Rf = 0.2). Pale yellow solid; yield 2.4 g
(83%), m.p. 85–87 ◦C. IR (KBr): 3110, 3039, 2883, 1611, 1544, 1347, 1224, 1186, 1134, 1074, 917, 896, 860,
1
835, 742, 678, 602, 574, 531, 496, 439 cm−1. H NMR (DMSO-d6, 500 MHz):
δ
= 8.46 (d, 3JH-H = 8 Hz,
68.5
= 121.0, 125.7 (q, 1JC-F = 342 Hz, CF3), 128.8, 130.4, 142.1, 146.9,
1H, Ar-H), 8.92 (d,3JH-H = 8 Hz, 1H, Ar-H), 8.97 (s, 1H, Ar-H). 19F NMR (CDCl3, 376.5 MHz):
(s). 13C NMR (DMSO-d6, 125.7 MHz):
δ
=
−
δ
150.8. Anal. Calcd for C7H3F3N2O5S: C, 29.59; H, 1.06; N, 9.86; S, 11.28. Found: C, 29.58; H, 1.05; N,
9.87; S, 11.29.
2-((Trifluoromethyl)sulfinyl)naphthalene 2k. Product was purified by column chromatography, eluent
Et2O-petroleum ether, 1:9 (Rf = 0.6). Pale yellow liquid; yield 1.4 g (87%). IR (KBr): 2940, 1171, 1126,
1
1073, 813, 744,639 cm−1. H NMR (300 MHz, CDCl3):
δ
= 7.53–7.67 (m, 2H, Ar-H), 7.75 (d, 3JH-H
=
F
8.6 Hz, 1H, Ar-H), 7.85–7.96 (m, 2H, Ar-H), 7.99 (d, 3JH-H = 8.7 Hz, 1H, Ar-H), 8.31 (s, 1H, Ar-H). 19
NMR (188 MHz, CDCl3):
74.5 (s). 13C NMR (75 MHz, CDCl3):
δ
=
−
δ
= 120.4, 124.9 (q, 1JC-F = 335 Hz,
CF3), 127.7, 127.8, 128.2, 128.8, 129.0, 129.9, 132.4, 132.5, 132.6, 135.5. HRMS: calcd. for C11H7F3SONa
267.0063; found 267.0067 [M − Na]+ (δ = −1.5).
1-Chloro-2-((trifluoromethyl)sulfinyl)ethane 4a
[
14]. Product was purified by distillation. Colorless
1
liquid; yield 1.5 g (83%); b.p. 68–70 ◦C (10 Torr). H NMR (CDCl3, 400 MHz):
δ
= 3.21–3.24 (m, 1H,
73.6 (s).
CH2), 3.43–3.48 (m, 1H, CH2), 3.95–4.00 (m, 2H, CH2). 19F NMR (CDCl3, 376.5 MHz):
Compound 3a was oxidized on a 15 g scale (in 35 mL of CF3COOH) with the same yield.
δ
=
−
2-(Trifluoromethyl)sulfinyl-ethanol 4b. Crude product was purified by distillation, but the product
◦
contains 11% of starting sulfide. Colorless liquid; yield 0.25 g (15%); b.p. 108–110 C (10 Torr). IR (KBr):
3417, 2893, 1396, 1293, 1174, 1138, 1047, 1004, 946, 844, 749, 645, 563, 442 cm−1 1H NMR (CDCl3,
.
500 MHz):
δ
= 3.02–3.20 (m, 2H, CH2), 3.67 (s, 1H, OH), 4.09–4.13 (m, 2H, CH2). 19F NMR (CDCl3,
470 MHz): δ = −73.6 (s). 13C NMR (CDCl3, 125.7 MHz): δ = 51.2, 54.4, 125.5 (q, 1JC-F = 332 Hz, CF3).
2-((Trifluoromethyl)sulfinyl)ethyl acetate 4c. Crude product was purified by distillation, but the product
◦
contains 15% of the corresponding alcohol. Colorless liquid; yield 1.1 g (54%); b.p. 100–102 C (10 Torr).
1H NMR (CDCl3, 500 MHz):
NMR (CDCl3, 470 MHz):
1JC-F = 333 Hz, CF3), 170.3.
δ
= 2.10 (s, 3H, CH3), 3.20–3.33 (m, 2H, CH2), 4.47–4.64 (m, 2H, CH2). 19F
−
δ
=
73.7 (s). 13C NMR (CDCl3, 125.7 MHz):
δ = 20.4, 48.2, 55.9, 125.3 (q,
Methyl 2-((trifluoromethyl)sulfinyl)acetate 4d
[
16]. Product was purified by distillation. Colorless liquid;
= 3.79 (s, 3H, CH3), 3.87 (d, 2JH-H
◦
1
yield 1.1 g (60%); b.p. 90 C (10 Torr). H NMR (CDCl3, 500 MHz):
δ
= 15 Hz, 1H, CH2), 3.94 (d, 2JH-H = 15 Hz, 1H, CH2). 19F NMR (CDCl3, 376.5 MHz):
δ
=
−
73.8 (s). 13C
NMR (CDCl3, 125.7 MHz): δ = 53.5, 53.6, 125.1 (q, 1JC-F = 334.5 Hz, CF3), 164.2.
Methyl 3-((trifluoromethyl)sulfinyl)propanoate 4e. Product was purified by distillation. Colorless liquid;
yield 1.25 g (60%); b.p. 96–98 ◦C (10 Torr). IR (KBr): 2959, 1735, 1440, 1367, 1173, 1136, 1074, 980, 828,
1
746, 661, 564, 450 cm−1. H NMR (CDCl3, 400 MHz):
δ
= 2.77–2.97 (m, 2H, CH2), 3.17–3.27 (m, 2H,
CH2), 3.72 (s, 3H, CH3). 19F NMR (CDCl3, 376.5 MHz):
= 25.6, 43.2 (q, 3JC-F = 2.5 Hz, CH2-S(O)CF3), 52.4, 125.4 (q, 1JC-F = 334.5 Hz, CF3), 170.8. Anal. Calcd
δ
=
−
74.2 (s). 13C NMR (CDCl3, 125.7 MHz):
δ
for C5H7F3O3S: C, 29,42; H, 3,46; S, 15.70. Found: C, 29.43; H, 3.44; S, 15.72.
7-((Trifluoromethyl)sulfinyl)heptanenitrile 4f. Compound 3f was oxidized on a 0.12 g scale. Product
was purified by preparative TLC chromatography, eluent Et2O-petroleum ether, 1:9 (Rf = 0.1). Pale
1
yellow liquid; yield 0.11 g (85%). IR (KBr): 2936, 2864, 2239, 1171, 1143, 1080 cm−1. H NMR (CDCl3,
300 MHz):
3JH-H = 6.9 Hz, 2H, CH2), 2.73–2.90 (m, 1H, CH), 2.93–3.11 (m, 1H, CH). 19F NMR (CDCl3, 188 MHz):
74.1 (s). 13C NMR (CDCl3, 75 MHz): = 17.0, 21.5, 24.9, 27.8, 28.1, 48.2, 119.5, 125.3 (q, 1JC-F = 333
Hz, CF3). HRMS: calcd. for C8H12NF3SONa 250.0477; found 250.0489 [M − Na]+ (δ = 0.4).
δ = 1.40–1.56 (m, 4H, CH2 -CH2), 1.56–1.76 (m, 2H, CH2), 1.74–1.92 (m, 2H, CH2), 2.31 (t,
δ
=
−
δ

Molecules 2019, 24, 1249
9 of 12
1-Fluoro-4-(((trifluoromethyl)sulfinyl)methyl)benzene 4g
[39]. Compound 3g was oxidized on a 0.05 g
scale. Product was purified by preparative TLC chromatography, eluent Et2O-petroleum ether, 1:9 (Rf
◦
◦
= 0.3). Pale yellow solid; yield 0.041 g (85%); m.p. 80 C (Lit. 81–82 C). IR (KBr): 2983, 2927, 1600, 1507,
1243, 1178, 1139, 1050, 1011, 842, 745 cm−1. H NMR (CDCl3, 300 MHz):
δ =
= 4.20 (AB syst., 2JH-H
1
13.2 Hz, 2H, CH2), 7.11 (t, 3JH-H = 3JH-F= 8.4 Hz, 2H, Ar-H), 7.35 (dd, 3JH-H = 8.4 Hz, 4JH-F = 5.3 Hz, 2H,
Ar-H). 19F NMR (CDCl3, 188 MHz): 112.25(m, 1F, Ar-F). 13C NMR (CDCl3,
73.11 (s, 3F, CF3),
75 MHz):
= 54.7 (q, 3JC-F = 3.1 Hz), 116.5 (d, 2JC-F = 21.9 Hz), 123.3 (d, 4JC-F = 3.3 Hz), 125.3 (q, 1JC-F
335.0 Hz, CF3), 132.3 (d, 3JC-F = 8.5 Hz), 163.4 (d, 1JC-F = 249.3 Hz, C-F).
δ
=
−
−
δ
=
1
((Difluoromethyl)sulfinyl)benzene 6a
[
40]. Colorless liquid; yield 1.2 g (70%); b.p. 130 ◦C (10 Torr). H
NMR (CDCl3, 400 MHz):
δ
= 6.02 (t, 2JH-F = 55.6 Hz, 1H, CHF2), 7.55-7.60 (m, 3H, Ar-H), 7.69–7.71 (m,
2H, Ar-H). 19F {H} NMR (CDCl3, 376.5 MHz):
δ
=
−
119.4 (d, 2JF-F = 260 Hz, 1F, CHF2), -120.2 (d, 2JF-F
δ
= 120.8 (dd, 1JC-F= 288 Hz, 287 Hz, CHF2), 125.4,
= 260 Hz, 1F, CHF2). 13C NMR (CDCl3, 100.6 MHz):
129.5, 132.8, 136.6 (t, 3JC-F = 4 Hz).
N-(4-((Difluoromethyl)sulfinyl)phenyl)acetamide 6b
166–167 C (Lit. 170–171 C). H NMR (DMSO-d6, 500 MHz):
[
30]. Pale yellow solid; yield 1.9 g (80%); m.p.
◦
◦
1
2
δ
= 2.09 (s, 3H, CH3), 6.89 (t, JH-F
= 54 Hz, 1H, CHF2), 7.70 (d, 3JH-H = 8 Hz, 2H, Ar-H), 7.85 (d, 3JH-H = 8 Hz, 2H, Ar-H), 10.34 (s, 1H,
NH). 19F NMR (DMSO-d6, 376.5 MHz): = -121.4 (dd, 2JF-F = 257 Hz, 2JH-F = 54 Hz, 1F, CHF2), -125.5
(dd, 2JF-F = 257 Hz, 2JH-F = 54 Hz, 1F, CHF2). 19F {H} NMR (CDCl3, 376.5 MHz): 121.5 (d, 2JF-F
= 257 Hz, 1F, CHF2), -123.3 (d, 2JF-F = 257 Hz, 1F, CHF2). 13C NMR (DMSO-d6, 125.7 MHz):
= 24.6,
119.8, 120.6 (t, 1JC-F = 292 Hz, CHF2), 120.9 (t, 1JC-F = 280 Hz, CHF2), 127.2, 127.3, 129.9, 143.8, 169.5.
δ
δ
=
−
δ
1-((Difluoromethyl)sulfinyl)-4-nitrobenzene 6c
30]. Pale yellow solid; yield 1.7 g (75%); m.p. 84–85 ◦C
(Lit. 81–83 ◦C). 1H NMR (DMSO-d6, 500 MHz): = 7.08 (t, 2JH-F = 56 Hz, 1H, CHF2), 8.04 (d, 3JH-H
6.5 Hz, 2H, Ar-H), 8.46 (d, 3JH-H = 6.5 Hz, 2H, Ar-H). 19F NMR (DMSO-d6, 376.5 MHz):
120.8 (dd,
2JF-F = 254 Hz, 2JH-F = 56 Hz, 1F, CHF2), -125.9 (dd, 2JF-F = 254 Hz, 2JH-F = 56 Hz, 1F, CHF2). 19F {H}
NMR (DMSO-d6, 376.5 MHz):
120.8 (d, 2JF-F = 254 Hz, 1F, CHF2), 125.9 (d, 2JF-F = 254 Hz, 1F,
CHF2). 13C NMR (DMSO-d6, 125.7 MHz): = 120.4 (t, 1JC-F = 284 Hz, CHF2), 120.6 (t, 1JC-F = 287 Hz,
CHF2), 124.7, 124.9, 127.4, 127.5, 133.9, 144.3, 150.4.
[
δ
=
δ
=
−
δ
=
−
−
δ
(1,1,2,2-Tetrafluoro-2-((1,2,4-triazol)-1-yl)-ethyl)-sulfinylbenzene 6d. Crude product was purified by
column chromatography, eluent CH2Cl2, then methyl-tert-butyl ether (Rf = 0.7). Pale yellow solid;
yield 2.7 g (92%); m.p. 77–78 ◦C. IR (KBr): 3105, 2872, 1819, 1688, 1582, 1512, 1477, 1453, 1403, 1378,
1
1294, 1262, 1221, 1191, 1140, 1111, 1070, 981, 903, 830, 756, 691, 667, 629, 591, 514, 482, 449 cm−1. H
NMR (CDCl3, 500 MHz):
(s, 1H, Het-H). 19F NMR (CDCl3, 376.5 MHz):
226 Hz, 1F, CF2),
112.5 (d, 2JF-F = 237 Hz, 1F, CF2), 124.3 (d, 2JF-F = 237 Hz, 1F, CF2). 13C NMR (CDCl3,
125.7 MHz):
δ
= 7.56–7.65 (m, 3H, Ar-H), 7.77 (d, 2H, Ar-H), 8.15 (s, 1H, Het-H), 8.59
δ
=
−
94.0 (d, 2JF-F = 226 Hz, 1F, CF2), 94.6 (d, 2JF-F
−
=
−
δ
= 113.0 (tt, 1JC-F = 271 Hz, 2JC-F = 31 Hz, CF2), 116.9 (ddt, 1JC-F = 318 Hz, 1JC-F = 308 Hz,
2JC-F 38 Hz, CF2), 126.7, 129.5, 133.8, 135.0, 143.4, 154.1. Anal. Calcd for C12H12F4N3OS: C, 44.72; H,
3.75; N, 13.04; S, 9.95. Found: C, 44.74; H, 3.76; N, 13.02; S, 9.98.
((Bromodifluoromethyl)sulfinyl)benzene 6e [41]. Compound 5e was oxidized only on a 50 mmol scale.
Crude product was purified by column chromatography, eluent petroleum ether-diethyl ether, 8:2 (Rf
1
= 0.6). Yellow oil; yield 8.1 g (91%). IR (KBr):1443, 1114, 1073, 1056, 854, 827, 742, 687 cm−1. H NMR
(CDCl3, 200 MHz):
δ
= 7.52 (m, 3H, ArH), 7.72 (m, 2H, ArH). 19F NMR (CDCl3, 188 MHz):
δ
= -53.49
and -55.56 (2F, CF2Br, syst. AB 2JC-F = 145 Hz). 13C NMR (CDCl3, 50 MHz):
355 Hz, 350.5Hz), 129.1, 133.4, 136.7 (dd, 3JC-F = 3 Hz, 1 Hz).
δ
= 126.2, 128.4 (dd, 1JC-F
=
((Dichlorofluoromethyl)sulfinyl)benzene 6f [42]. Compound 5f was oxidized only on a 50 mmol scale.
Crude product was purified by column chromatography, eluent petroleum ether-diethyl ether, 8:2 (Rf
1
= 0.5). Yellow oil; yield 10.6 g (69%). IR (KBr): 1445, 1104, 1061, 840, 792, 744, 684 cm−1. H NMR
(CDCl3, 200 MHz):
δ
= 7.61 (m, 3H, Ar-H), 7.82 (m, 2H, Ar-H). 19F NMR (CDCl3, 188 MHz):
δ
=
−
62.8

Molecules 2019, 24, 1249
10 of 12
(s). 13C NMR (CDCl3, 50 MHz):
(d, 3JC-F = 1.5 Hz).
δ
= 126.9 (d, 1JC-F = 340 Hz), 126.9 (d, 4JC-F = 1.5 Hz), 128.9, 133.5, 137.4
N-(6-((Trifluoromethyl)sulfinyl)pyridin-3-yl)acetamide
8
.
Crude product was purified by column
chromatography, eluent ethyl acetate (Rf = 0.5) to give compound
8
with 80 % purity (contains
= 2.12 (s,
1
~20% of starting sulfide). Yellow solid; yield 0.75 g (~30%). H NMR (DMSO-d6, 400 MHz):
δ
3H, CH3), 8.02 (d, 3JH-H = 8.8 Hz, 1H, Het-H), 8.41 (d, 3JH-H = 8.8 Hz, 1H, Het-H), 10.6 (s, 1H, NH), 8.88
(s, 1H, Het-H). 19F {H} NMR (DMSO-d6, 376.5 MHz):
δ
=
−
72.7 (s). 13C NMR (CDCl3, 125.7 MHz):
δ =
24.4, 122.5, 125.3 (q, 1JC-F = 338 Hz, CF3), 127.9, 139.8, 141.3, 149.3, 170.1.
4. Conclusions
In summary, a simple, convenient, and high-yielding procedure for the oxidation of fluoroalkyl
sulfides to fluoroalkyl sulfoxides was developed. It was shown that the new protocol is suitable for
a wide range of aliphatic and aromatic substrates on a milligram and multigram scales. In almost
all cases, over-oxidation did not occur, and the crude products contained only a small quantity of
starting sulfides.
Supplementary Materials: The following are available online: titration of H2O2 solution, NMRs and IRs of the
new synthesized compounds.
Author Contributions: Y.L.Y. conceived idea of the article; L.V.S., R.K.O., A.F., B.P., P.D. performed the
experiments; L.V.S. wrote the paper, Y.L.Y. and E.M. reviewed and edited the manuscript. All authors read
and approved the final manuscript.
Acknowledgments: We thank Enamine Ltd (www.enamine.net) and CNRS for generous support of our research.
We thank Karen Wright for the improvement of the English Manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Xu, X.-H.; Matsuzaki, K.; Shibata, N. Synthetic Methods for Compounds Having CF3-S Units on Carbon by
Trifluoromethylation, Trifluoromethylthiolation, Triflylation, and Related Reactions. Chem. Rev. 2015, 115,
731–764. [CrossRef] [PubMed]
2.
3.
4.
5.
6.
Bizet, V.; Kowalczyk, R.; Bolm, C. Fluorinated sulfoximines: Syntheses, properties and applications.
Chem. Soc. Rev. 2014, 43, 2426–2438. [CrossRef]
Shen, X.; Hu, J. Fluorinated Sulfoximines: Preparation, Reactions and Applications. Eur. J. Org. Chem. 2014
,
4437–4451. [CrossRef]
Barthelemy, A.L.; Magnier, E. Recent trends in perfluorinated sulfoximines. C. R. Chim. 2018, 21, 711–722.
[CrossRef]
Batisse, C.; Panossian, A.; Hanquet, G.; Leroux, F. Access towards enantiopure α,α-difluoromethyl alcohols
by means of sulfoxides as traceless chiral auxiliaries. Chem. Comm. 2018, 54, 10423–10426. [CrossRef]
Movchun, V.N.; Kolomeitsev, A.A.; Yagupolskii, Y.L. Nucleophilic trifluoromethylation of organic substrates
using (trifluoromethyl)trimethylsilane in the presence of a fluoride anion II. A convenient route to
aryltrifluoromethyl-sulfides, -sulfoxides and -sulfones. J. Fluorine. Chem. 1995, 70, 255–257. [CrossRef]
Patel, N.R.; Kirchmeier, R.L. Trifluoromethylation and pentafluorophenylation of sulfur and carbon centers
using (trifluoromethyl)- and (pentafluorophenyl)trimethylsilane. Inorg. Chem. 1992, 31, 2537–2540.
[CrossRef]
Singh, R.P.; Cao, G.; Kirchmeier, R.L.; Shreeve, J.M. Cesium Fluoride Catalyzed Trifluoromethylation of
Esters, Aldehydes, and Ketones with (Trifluoromethyl)trimethylsilane. J. Org. Chem. 1999, 64, 2873–2876.
[CrossRef] [PubMed]
7.
8.
9.
Wakselman, C.; Tordeux, M.; Freslon, C.; Saint-Jalmes, L. Aryltrifluoromethylsulfoxides: Sulfinylation of
Aromatics by Triflinate Salts in Acid Medium. Synlett 2001, 4, 550–552. [CrossRef]
10. Chen, X.; Tordeux, M.; Desmurs, J.-R.; Wakselman, C. Thia-Fries rearrangement of aryl triflinates to
trifluoromethanesulfinylphenols. J. Fluor. Chem. 2003, 123, 51–56. [CrossRef]

Molecules 2019, 24, 1249
11 of 12
11. Billard, T.; Greiner, A.; Langlois, B.R. A new equivalent of the CF3S(O)+ cation. Synthesis of
trifluoromethanesulfinates and trifluoromethanesulfinamides. Tetrahedron 1999, 55, 7243–7250. [CrossRef]
12. Romanenko, V.D.; Thoumazet, C.; Lavallo, V.; Tham, F.S.; Bertrand, G. Synthesis and
reactivity of a stable crystalline diastereomerically pure trifluoromethanesulfinic acid derivative:
(S)-( )-1-trifluoromethylsulfinyl-(R)-4-phenyloxazolidin-2-one. Chem. Commun. 2003, 14, 1680–1681.
−
[CrossRef]
13. Yang, J.-J.; Kirchmeier, R.L.; Shreeve, J.M. New Electrophilic Trifluoromethylating Agents. J. Org. Chem. 1998
,
63, 2656–2660. [CrossRef] [PubMed]
14. Sokolenko, L.V.; Maletina, I.I.; Yagupolskii, L.M.; Yagupolskii, Yu. L. A Convenient and Efficient Synthesis
of Trifluoromethyl Vinyl Sulfoxide and its Reactivity in Addition Reactions. Synlett 2010, 14, 2075–2078.
[CrossRef]
15. Venier, C.G.; Squires, T.G.; Chen, Y.-Y.; Hussmann, G.P.; Shei, J.C.; Smith, B.F. Peroxytrifluoroacetic acid
oxidation of sulfides to sulfoxides and sulfones. J. Org. Chem. 1982, 47, 3773–3774. [CrossRef]
16. Sokolenko, L.V.; Yagupolskii, Yu. L.; Kumanetska, L.S.; Marrot, J.; Magnier, E.; Lipetskij, V.O.; Kalinin, I.V.
CF3S(O)n-Containing Enaminones as Precursors for syntheses of Pyrimidine-4(3H)-ones. Tetrahedron Lett.
2017, 58, 1308–1311. [CrossRef]
17. Tang, R.-Y.; Zhong, P.; Lin, Q.-L. A convenient conversion of pyrazolyl disulfide to sulfides by sodium
dithionite and synthesis of sulfoxides. J. Fluorine. Chem. 2006, 127, 948–953. [CrossRef]
18. Scribner, R.M. Some New Sulfonyl- and Trifluoromethylthio-p-benzoquinones. Their Reactions,
Polarographic Reduction Potentials, and π Acid Strengths. J. Org. Chem. 1966, 31, 3671–3682. [CrossRef]
19. Pazenok, S.V.; Kondratenko, N.V.; Popov, V.I.; Troitskaya, V.I.; Il’chenko, A.Y.; Al’perovich, M.A.;
Yagupolskii, L.M. Indo- and benzindocyanine dyes with fluorine-containing substituents. Chemistry of
Heterocyclic Compounds 1983, 19, 1182–1187. [CrossRef]
20. Magnier, E.; Tordeux, M.; Goumont, R.; Magder, K.; Wakselman, C. Perfluoroalkylation of 2-mercaptoethanol
as a key step for a new synthesis of perfluoroalkyl vinyl sulfides, sulfoxides and sulfones. J. Fluorine. Chem.
2003, 124, 55–59. [CrossRef]
21. Moise, J.; Goumont, R.; Magnier, E.; Wakselman, C. Synthesis of Fluoroalkyl Vinyl Sulfoxides and their Use
in Diels-Alder Reactions. Synthesis 2004, 14, 2297–2302. [CrossRef]
22. Meng, C.Q.; Le Hir de Fallois, L.P.; Lee, H.I.; Zhan, X.; Labrosse, J.R.; Mulhauser, M. Processes for the
Preparation of 1-Aryl-5-Alkyl Pyrazole Compounds. U.S. Patent 2013/281710, 24 October 2013.
23. Lee, H.I.; Le Hir de Fallois, L.P.; Timmons, Ph.R.; Cawthorne, W.G.; de Leon, A.P. 1-Aryl-5-Alkyl Pyrazole
Derivative Compounds, Processes of Making and Methods of Using Thereof. U.S. Patent 2008/031902,
7 February 2008.
24. Chou, D.T.; Knauf, W.; Maier, M.; Malaska, M.J.; Mcintyre, D.; Lochhaas, F.; Huber, S. K Pesticidal Agents on
the Basis of 1-Aryl-Aminopyrrol. WO Patent 2006/000315, 5 January 2006.
25. Wu, T.-T.; Sinodis, D.N.; Timmons, P.R.; Powell, G.S.; Chou, D.T.; Newsome, P.W.; Hall, L.S. Pesticidal
1-Arylimidazoles. U.S. Patent 5223525, 29 June 1993.
26. Hatton, L.R.; Buntain, I.G.; Hawkins, D.W.; Parnell, E.W.; Pearson, C.J.; Roberts, D.A. Derivatives of
N-phenylpyrazoles. U.S. Patent 5232940, 3 August 1993.
27. Huang, J.; Lowder, P.D.; Ray, N.C.; Hawkins, D.W. Pesticidal 1-Arylpyrazole Derivatives. U.S. Patent 5817688,
6 October 1998.
28. Caster, K.C.; Rao, A.S.; Mohan, H.R. Trifluoroperacetic acid. In Handbook of Reagents for Organic Synthesis.
Fluorine-Containing Reagents; Paquette, L.A., Ed.; Wiley: Chichester, England, 2007; pp. 619–624.
29. Emmons, W.D. Peroxytrifluoroacetic Acid. I. The Oxidation of Nitrosamines to Nitramines1. J. Am. Chem. Soc.
1954, 76, 3468–3470. [CrossRef]
30. Sedova, L.N.; Gandel’sman, L.Z.; Alekseeva, L.A.; Yagupol’skii, L.M. Derivatives of phenyldifluoromethyl
sulfide, sulfoxide, and sulfone. Zh. Obshch. Khim. 1969, 39, 2057–2062.
31. Petko, K.I.; Sokolenko, T.M.; Bezdudny, A.V.; Yagupolskii, L.M. N-(2-Bromotetrafluoroethyl) derivatives of
five-membered nitrogen-containing heterocycles. J. Fluorine. Chem. 2005, 126, 1342–1346. [CrossRef]
32. Anselmi, E.; Blazejewski, J.-C.; Tordeux, M.; Wakselman, C. Perfluoroalkylation of aliphatic thiols in the
presence of sodium hydroxymethanesulfinate. J. Fluorine Chem. 2000, 105, 41–44. [CrossRef]

Molecules 2019, 24, 1249
12 of 12
33. Anselmi, E.; Simon, C.; Marrot, J.; Bernardelli, P.; Schio, L.; Pégot, B.; Magnier, E. Ionic Liquids for Fast and
Solvent-Free Nucleophilic Trifluoromethylthiolation of Alkyl Halides and Alcohols. Eur. J. Org. Chem. 2017
2017, 6319–6326. [CrossRef]
,
34. Pégot, B.; Urban, C.; Bourne, A.; Le, T.-N.; Bouvet, S.; Marrot, J.; Diter, P.; Magnier, E. Difluoromethyl and
Chlorofluoromethyl Sulfoximines: Synthesis and Evaluation as Electrophilic Perfluoroalkylating Reagents.
Eur. J. Org. Chem. 2015, 2015, 3069–3075. [CrossRef]
35. Bzhezovsky, V.M.; Penkovsky, V.V.; Rozhenko, A.B.; Iksanova, S.V.; Kondratenko, N.V.; Yagupolskii, L.M.
Multinuclear NMR spectroscopy and semi-empirical MNDO-PM3 quantum chemical investigations of the
compounds C6H5XY (X=S, SO, SO2; Y=CF3, CH3). J. Fluor. Chem. 1994, 69, 41–49. [CrossRef]
36. Tordeux, M.; Magnier, E.; Guidotti, J.; Diter, P.; Wakselman, C. 29/28, 30/28Silicon, 34/32sulfur and
80/77selenium isotope-induced fluorine chemical shifts through two bonds. Magn. Reson. Chem. 2004
42, 700–703. [CrossRef] [PubMed]
,
37. Yagupol’skii, L.M.; Marenets, M.S.; Kondratenko, N.V. The orienting action of trifluoromethyl sulfoxide
group. Zh. Obshch. Khim. 1965, 62, 377, Chem. Abstr. 1965, 62, 14551a.
38. Yagupol’skii, L.M.; Troitskaya, V.I.; Gruz, B.E.; Kondratenko, N.V. Cyanine dyes containing fluorine. XII.
Cyanine dyes from derivatives of 5-trifluoromethylthio-2-methylbenzimidazole. Zh. Obshch. Khim. 1966, 64,
1644–1650, Chem. Abstr. 1966, 64, 3731c.
39. Orda, V.V.; Yagupol’skii, L.M.; Bystrov, V.F.; Stepanyants, A.U. Transmission of inductive effect of substituents
SCF3, SOCF3, and SO2CF3, through a methylene group. Zh. Obshch. Khim. 1965, 63, 1628–1636, Chem. Abstr.
1965, 63, 17861c.
40. Surya Prakash, G.K.; Weber, C.; Chacko, S.; Olah, G.A. New Electrophilic Difluoromethylating Reagent.
Org. Lett. 2007, 9, 1863–1866. [CrossRef] [PubMed]
41. Burton, D.; Wiemers, D.M. Synthesis of bromodifluoromethyl phenyl sulfide, sulfoxide and sulfone.
J. Fluorine Chem. 1981, 18, 573–582. [CrossRef]
42. Saikia, A.K.; Tsuboi, S. Chemistry of Trichlorofluoromethane: Synthesis of Chlorofluoromethyl Phenyl
Sulfone and Fluoromethyl Phenyl Sulfone and some of Their Reactions. J. Org. Chem. 2001, 66, 643–647.
[CrossRef] [PubMed]
Sample Availability: Samples of the compounds 1–6 are available from the corresponding authors.
©
2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).