An odorless, one-pot synthesis of nitroaryl thioethers via SNAr reactions through the in situ generation of S-alkylisothiouronium salts

Article abstract of DOI:10.1039/c4ra11490f

A newly developed C-S bond formation nucleophilic aromatic substitution (S_NAr) reaction in aqueous Triton X-100 (TX100) micelles has been disclosed. This chemistry, in which odorless, cheap and stable thiourea in place of thiols is used as the sulfur reagent, provides an efficient approach for the generation of nitroaryl thioethers, which are useful structural units of many bioactive molecules, rendering this methodology attractive to both synthetic and medicinal chemistry.

Full text of DOI:10.1039/c4ra11490f

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An odorless, one-pot synthesis of nitroaryl
thioethers via SNAr reactions through the in situ
generation of S-alkylisothiouronium salts†
Cite this: RSC Adv., 2014, 4, 59990
*
Guo-ping Lu and Chun Cai
A newly developed C–S bond formation nucleophilic aromatic substitution (SNAr) reaction in aqueous
Triton X-100 (TX100) micelles has been disclosed. This chemistry, in which odorless, cheap and stable
thiourea in place of thiols is used as the sulfur reagent, provides an efficient approach for the generation
of nitroaryl thioethers, which are useful structural units of many bioactive molecules, rendering this
methodology attractive to both synthetic and medicinal chemistry.
Received 30th September 2014
Accepted 28th October 2014
DOI: 10.1039/c4ra11490f
www.rsc.org/advances
thiols as the substrates in SNAr reactions for the generation of
thioethers.8 The sulfur nucleophiles (RSSiR3) prove to be a
Introduction
useful reagent for the construction of Caryl–S bonds due to their
ready availability, stability, reactivity and high tolerance of
various functionalities. However, the sulfur nucleophiles
(RSSiR3) pre-generated from thiols, are relatively high cost, and
the use of (potentially toxic) organic solvents is the norm.
Therefore, it will be interesting and signicant to develop a new
approach for the synthesis of thioethers via SNAr reactions in a
“green” solvent using cheap and odorless sulfur sources.
Recently, attempts are also made for the formation of C–S
bonds through the in situ generation of S-alkylisothiouronium
salts in place of thiols, which are formed by organic halides and
thiourea.9 Guided by the 12 principles of green chemistry,10 we
herein describe an odorless and efficient protocol for the
formation of nitroaryl thioethers, which constitute an impor-
tant class of pharmaceutical intermediates (Scheme 1),11 using
cheap and stable thiourea as the sulfur source in water.
The exploration of new protocols for C–S bond generation,
which can lead to the discovery of eco-friendly, cheap and more
efficient synthetic approaches for the preparation of biological,
pharmaceutical, and interesting organo-sulfur compounds has
attracted a great deal of attention.1 Typically, the formation of
C–S bonds, especially Caryl–S bonds can be mainly classied by
three routes: (1) the electrophilic substitution reactions2 of
activated aryl halides with arenethiols; (2) the transition-metal-
catalyzed coupling reactions;3 (3) the nucleophilic aromatic
substitution (SNAr) reactions.4
Despite the great advancements achieved in transition-
metal-catalyzed methods for C–S cross-couplings,1d,5 SNAr reac-
tions are still attractive strategies4,6 since they occur under
relatively mild conditions, more environmentally benign, and
no expensive noble metal catalysts or capricious ligands for
catalyst activation is required, all of which make them more
suitable for industrial production. Nevertheless, most of the
pioneering works in this eld have the drawback of using
malodorous and expensive thiols as starting materials. The
human olfactory system is extremely sensitive to thiols. For
example, tert-butyl thiol is added to natural gas to enable
detection of leaks, which can be smelled at levels of <1 part per
billion.7 Thiols are also air sensitive and can be readily oxidized
to disuldes by atmospheric oxygen. Because of their potent
stench and air sensitivity, the use of thiols as the substrates,
particularly on a large scale operation, is highly undesirable.
In order to eliminate these problems, Xu Q. et al. have
employed trialkylsilyl sulfur nucleophiles (RSSiR3) instead of
Chemical Engineering College, Nanjing University of Science & Technology, Nanjing,
Jiangsu 210094, P. R. China. E-mail: glu@njust.edu.cn
† Electronic supplementary information (ESI) available: More experimental
entails, characterization data and copies of 1H NMR, 13C NMR spectra of all
products. See DOI: 10.1039/c4ra11490f
Scheme
intermediates.
1
Examples of nitroaryl thioether pharmaceutical
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electron-withdrawing groups (such as –CN, –COOEt) also failed
to apply in the protocol. Increasing of temperature and the use
of a strong base (NaOH) were required to achieve the SNAr
reaction using secondary benzyl halide ((1-bromoethyl)
benzene) as the substrate (3g). Strong bases (such as NaOH,
KOH) could afford better yields than K2CO3 when less active
organic halides (such as allylic and alkyl halides) were employed
(3h–k). It may be explained that S-allyl and S-alkyl iso-
thiouronium salts have lower nucleophilicity than S-benzyliso-
thiouronium salts, which make them more prone to form by-
products (diallyl or dialkyl thioethers) than to react with nitro-
benzene uorides.
Likewise, a variety of nitrobenzene uorides could also react
with thiourea and benzyl chlorides to generate the nitroaryl
thioethers in water (Scheme 3). Because only benzene uorides
containing nitro group in the ortho or para position can form
the Meisenheimer complex,13 3-nitrobenezne uorides and 2-
uoropryrine failed to produce the desired thioethers (3u, 3v).
The electronic effects play a crucial role on the transformation.
Normally, electron-donating groups on nitrobenzene uorides
would inhibit the SNAr reaction. In order to show the possibility
for large-scale operation, we also scaled up the reaction to 20
mmol, and the reaction proceeded well with 94% yield of the
desired product 3w.
Results and discussion
With our interest in the reaction in water,12 a test experiment
was performed for the synthesis of 3a from 1a, 2a and thiourea
in water at 80 ꢀC for 48 h. To our delight, a moderate yield (79%)
of 3a was obtained (Table 1, entry 1), but the result was not
satisfactory when the reaction was carried out at lower
temperature (50 ꢀC) (entry 2). To improve the poor yield, several
surfactants were added in water to form micelles.
As expected, the use of surfactants clearly promotes the
reaction (entries 3–8),9a–f and the transformation can occur even
at room temperature (entries 6–9). A Triton X-100 (TX100)
aqueous solution provided higher yield than most organic
solvents except DMF (entries 6, 9–13). Considering the potential
toxicity and tedious work-up procedures of DMF, TX100
aqueous micelles proved to be a better choice for the process.
We also screened different bases (entries 6, 13–16), and K2CO3
emerged as the best selection (entry 6).
With the optimized conditions in hand, various organic
halides were chosen to establish the scope and generality of the
protocol (Scheme 2). Benzyl halides containing electron-
withdrawing or electron-donating groups reacted well to
produce the corresponding thioethers at 50 ꢀC with excellent
yields (3a–f, 3m). 2-Nitrobenzene chloride was also utilized in
the reaction successfully, but only moderate yield (55%) of the
product 3a was obtained even under harsher conditions.
However, no reaction took place when 2-nitroaryl bromides and
iodides were employed. Other aryl uorides containing
The nitro group on the benzene ring serves as an interme-
diate for a common multitude of transformations into other
important functional groups (such as –NH2, –OH, –F, –H).
Therefore, this methodology was applied to a two-step synthesis
of the aminoaryl thioether 6 (Scheme 4). It can react with sali-
cylaldehyde to produce Schiff base 7, which is a potential anti-
bacterial agent.14 In addition, we can construct 2-phenyl
Table 1 Optimization of the reaction conditionsa
benzothiazoles from 2-(benzylthio)aniline
6 via an iron-
catalyzed oxidative process using di-tert-butyl peroxide (DTBP)
as the oxidant, which may be a robust method for the synthesis
of substituted benzothiazoles.
To further demonstrate the potential of this methodology,
aniline 9 was synthesized by a tandem reaction in water, fol-
lowed by the iron-catalyzed oxidative procedure to afford
GW610 10 (an antitumor agent) with 71% total yield (Scheme
5).15 Compared with the typical approach,16 our work provided
higher yield (71% vs. 39%), in fewer steps (2 vs. 4), under more
environmental friendly conditions. Moreover, some hazardous
and toxic reagents (such as Br2 and NH4SCN) were avoided in
this protocol.
1,4-Benzothiazine derivatives are well-known to display
diverse biological activities in vivo and in vitro. For example, 13
prepared from 12, is a pharmaceutically active compound
exhibiting ion channel antagonistic activity (Scheme 6).17 Thus,
the attempts for this protocol to be used for the synthesis of 11,
which could be transform to 1,4-benzothiazine 12 via a cycli-
zation reaction, was also realized to explore the applications of
this chemistry in organic synthesis.
Entry
Solvent
T (ꢀC)
Base
Yieldb (%)
1
2
3
4
5
6
7
8
H2O
H2O
80
50
50
50
50
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
t-BuONa
NEt3
79c
22
>99
54
>99
72
71
57
38
36
0
88
51
49
66
63
2 wt% TX100d/H2O
2 wt% SDSe/H2O
2 wt% CTABf/H2O
2 wt% TX100/H2O
2 wt% CTAB/H2O
2 wt% Brij35g/H2O
EtOH
9
10
11
12
13
14
15
16
MeCN
Hexane
DMF
2 wt% TX100/H2O
2 wt% TX100/H2O
2 wt% TX100/H2O
2 wt% TX100/H2O
NaOH
a
In addition, we also focused on investigating the ratio of
Reaction conditions: 1a 0.50 mmol, thiourea 1.50 mmol, 2a 0.75
b
c
mmol, base 1.5 mmol, solvent 1 mL, 16 h. GC yields. The reaction nitrobenzene uoride 1, thiourea and organic halides 2 to
time is 48 h. t-Octylphenoxypolyethoxyethanol. Sodium dodecyl
sulphate. Cetyltrimethylammonium bromide. Polyoxyethyleneglycol
dodecyl ether.
d
e
further optimize the reaction conditions, making the protocol
more environmentally friendly. Taking the reaction of 1a, 2a
and thiourea as an example, different ratios of 1a : 2a : thiourea
f
g
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Scheme 2 The SNAr reactions of 2-nitrobenzene fluoride 1a, thiourea and organic haildes 2.a,b a Reaction conditions: 1a 0.50 mmol, thiourea
1.50 mmol, 2 0.75 mmol, base 1.5 mmol, 2 wt% TX100/H2O 1 mL. b Isolated yields. c Reaction conditions: 2-nitrobenzene chloride 0.50 mmol,
thiourea 1.50 mmol, 2a 0.75 mmol, KOH 1.5 mmol, 2 wt% TX100/H2O 1 mL, 80 ꢀC, 24 h.
Scheme 3 The SNAr reactions of nitrobenzene fluorides 1, thiourea and benzyl chlorides 2.a,b a Reaction conditions: 1a 0.50 mmol, thiourea 1.50
mmol, 2 0.75 mmol, base 1.5 mmol, 2 wt% TX100/H2O 1 mL. b Isolated yields. c The scale of the reaction is 20 mmol.
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Scheme 4 Transformation of 6 prepared by a one-pot, two-step process in water.
Scheme 5 The synthesis of an antitumor agent GW610 10.
(1/1/1.5, 1/1.2/1.5, 1/1.2/2, 1/1.5/2) were used in the reaction, in the reaction mixture to produce a thiolate moiety 14 and
respectively. The reactions were performed at 50 ꢀC for 8 h, and urea.9a–f Because 3-nitrobenzene uorides and aryl uorides,
the corresponding yields were 74%, 85%, 91% and 90%, containing other electron-withdrawing groups (such as –CN,
respectively, indicating that the ratio of 1a, 2a and thiourea –COOEt) failed to provide the desired products in the protocol,
could be reduced to 1/1.2/2 without signicant change in yield. and no regioisomeric products was found during the reaction,
Finally, a proposed mechanism for the reaction was also we believe the SNAr reaction in water is an addition–elimina-
illustrated in Scheme 7. This reaction proceeds by the in situ tion mechanism.13 The generated 14, which is a synthetic
generation of a S-alkylisothiouronium salt which is hydrolyzed equivalent of thiol and an odorless moiety, reacts with 2 to
Scheme 6 The synthesis of 1,4-benzothiazine 12 by this protocol.
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Scheme 7 A proposed mechanism for the SNAr reactions by the in situ generation of S-alkylisothiouronium salts in water.
form hydrogen-bonded Meisenheimer complex at rst, fol- mixture of organic halide 1 0.75 mmol, nitroaryl uoride 2 0.50
lowed by elimination and rearrangement processes to yield the mmol, thiourea 1.50 mmol and base 1.50 mmol in 2 wt%
nal thioethers. It should be noted that hydrogen bonding aqueous Triton X-100 solution (1.0 mL) was stirred at 40–80 ꢀC
between one H2O molecule and the Meisenheimer complex for 8–24 h. Upon completion, the reaction mixture was diluted
may generate a six-membered ring structure like 15 and 16, with EtOAc (4.0 mL), ltered through a bed of silica gel layered
which may enhance the leaving ability of the F group to over Celite. The volatiles were removed in vacuo to afford the
increase the reaction rate.13
crude product. The extent of conversions was determined by
The catalytic effects of TX100 micelles in the reaction GC. Sometimes, further column chromatography on silica gel
could be explained from two points of view. In the TX100 affords the pure desired product 3.
aqueous micelles, according to substrates polarity, they were
buried in the hydrophobic cores. On one hand, due to the
huge interfacial area in micelles, the base could be in contact
with substrates sufficiently. On the other hand, micelle
droplets formed by TX100 with substrates were hydrophobic
enough to exclude Fꢁ and urea,18 making it easy to form the
product. Thus, the reaction occurred more easily in a micelle,
specially, with respect to it functioning as a micro- or
nanoreactor.19
General procedure for the synthesis of anilines 6, 9 and 11 via
a two-step one-pot process
A mixture of organic halide 0.75 mmol, aryl uoride 0.5 mmol,
thiourea 1.5 mmol and NEt3 (K2CO3 for 11) 1.5 mmol in 2 wt%
aqueous Triton X-100 solution (1.0 mL) was stirred at 50 ꢀC
(80 ꢀC for 11) for 8–24 h. Upon completion of the reaction, zinc
power 2.5 mmol and AcOH 2.5 mmol were employed in aqueous
medium, and the mixture was allowed to stir at room temper-
ature for another 8 h. Then, the reaction mixture was diluted
with EtOAc (4.0 mL) and ltered through a bed of silica gel
layered over Celite. The volatiles were removed in vacuo to afford
the crude product. The extent of conversions was determined by
GC. Further column chromatography on silica gel afforded the
pure desired product.
Conclusions
In summary, we have developed a one-pot, odorless method
for the synthesis of nitroaryl thioethers by the SNAr reaction
using thiourea as the sulfur source. The nonionic surfactant
Triton X-100, which self-assembles in water to form micelles,
proves to enhance the reaction remarkably. The novel proce-
dure is free of organic solvents and foul-smelling thiols during
these reactions, and workup entails only an in-ask extraction
with a minimal amount of a single, recoverable organic
solvent, making it more environmentally friendly and suitable
for large-scale operations. Additionally, 2-nitroaryl thioethers
can also be transformed to corresponding 2-aminoaryl thio-
ethers by a one-pot tandem process in water, which are
versatile precursors to convert benzothiazoles and 1,4-benzo-
thiazine derivatives.
The procedure for the synthesis of 7
A mixture of 6 0.50 mmol and salicylaldehyde 0.50 mmol in
ethanol (1.0 mL) was stirred at room temperature for 30 min.
The solution was then kept undisturbed for 6 hours at room
temperature. The yellow crystalline product 7 that formed was
ltered off, washed several times with ethanol and dried in
vacuum.
The procedure for the synthesis of 8 and 10
A mixture of 6 or 9 0.50 mmol, FeBr2 0.05 mmol and DTBP 2.00
ꢀ
mmol in toluene was stirred at 110 C for 16 h. Upon comple-
Experimental section
tion, the reaction mixture was diluted with EtOAc (4.0 mL) and
General procedures for the synthesis of nitroaryl thioethers ltered through a bed of silica gel layered over Celite. The
from organic halides, thiourea and aryl uorides in water: a volatiles were removed in vacuo to afford the crude product. The
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extent of conversions was determined by GC. Further column
chromatography on silica gel afforded the pure desired product
8 or 10.
(3,4-Dimethoxybenzyl)(2-nitrophenyl)sulfane 3m. Light
yellow solid, mp: 96–98 ꢀC. 1H NMR (CDCl3, 500 MHz) d 3.87 (s,
6H), 4.16 (s, 2H), 6.79–6.84 (d, J ¼ 8.0 Hz, 1H), 6.93–6.96 (m,
2H), 7.24–7.27 (m, 1H), 7.45–7.54 (m, 2H), 8.19 (d, J ¼ 8.5 Hz,
1H). 13C NMR (CDCl3, 125 MHz) d 37.7, 56.0 (2C), 111.4, 112.2,
121.5, 124.9, 126.1, 127.2, 127.3, 133.6, 137.9, 146.1, 148.8,
149.3. MS (ESI) m/z: 305 [M+]. Anal. Calcd for C15H15NO4S: C,
59.00%; H, 4.95%, N, 4.59%. Found: C, 59.32; H, 4.56%; N,
4.97%.
The procedure for the synthesis of 12
A mixture of 11 0.50 mmol, NaI 0.60 mmol and K2CO3 1.00
mmol in DMF (1 mL) was stirred at 90 ꢀC for 16 h. Upon
completion, the reaction mixture was diluted with EtOAc (10.0
mL), and washed by water (10 ꢂ 3 mL). The collected organic
phase is ltered through a bed of silica gel layered over Celite,
and removed in vacuo to afford the product 12.
Benzyl(5-uoro-2-nitrophenyl)sulfane 3p. Light yellow solid,
1
ꢀ
mp: 74–76 C. H NMR (CDCl3, 500 MHz) d 4.17 (s, 2H), 6.91–
6.94 (m, 1H), 7.14–7.16 (dd, J ¼ 9.5, 2.0 Hz, 1H), 7.30–7.44 (m,
5H), 8.28-8.31 (dd, J ¼ 9.0, 5.5 Hz, 1H). 13C NMR (CDCl3, 125
MHz) d 36.7, 110.9–111.1 (d, J ¼ 24 Hz, 1C), 112.2–112.5 (d, J ¼
28 Hz, 1C), 127.0, 128.0, 128.1, 133.2, 140.6, 141.1, 163.2–165.2
(d, J ¼ 258 Hz, 1C). MS (ESI) m/z: 263 [M+]. Anal. Calcd for
Characterization data for unknown compounds
(4-Fluorobenzyl)(2-nitrophenyl)sulfane 3d. Light yellow
solid, mp: 78–80 ꢀC. 1H NMR (CDCl43, 500 MHz) d 4.17 (s, 2H),
7.01–7.04 (t, J ¼ 8.5 Hz, 2H), 7.25–7.28 (m, 1H), 7.36–7.43 (m,
3H), 7.51–7.54 (m, 1H), 8.20 (d, J ¼ 8.5 Hz, 1H). 13C NMR (CDCl3,
125 MHz) d 35.9, 114.8 (d, J ¼ 21 Hz, 1C), 124.0, 125.1, 126.1,
129.6, 129.7, 132.5, 136.3, 145.1, 160.3–162.3 (d, J ¼ 245 Hz, 1C).
MS (ESI) m/z: 263 [M+]. Anal. Calcd for C13H10FNO2S: C, 59.30;
H, 3.83%, N, 5.32%. Found: C, 59.51; H, 4.21%; N, 5.12%.
(2-Fluorobenzyl)(2-nitrophenyl)sulfane 3e. Light yellow
C
13H10NO2S: C, 59.30%; H, 3.83%, N, 5.32%. Found: C, 59.08;
H, 4.12%; N, 5.26%.
(3,4-Dimethoxybenzyl)(5-uoro-2-nitrophenyl)sulfane
3w.
1
ꢀ
Light yellow solid, mp: 92–94 C. H NMR (CDCl3, 500 MHz) d
3.97 (s, 6H), 4.25 (s, 2H), 6.91 (d, J ¼ 8.0 Hz, 1H), 7.02–7.03 (m,
2H), 7.36–7.40 (m, 1H), 7.52–7.55 (dd, J ¼ 9.0, 5.0 Hz, 1H), 7.98–
8.01 (dd, J ¼ 8.5, 3.0 Hz, 1H). 13C NMR (CDCl3, 125 MHz) d 37.0,
54.9 (2C), 110.3, 111.0, 112.0–112.2 (d, J ¼ 26 Hz, 1C), 120.1,
120.2–120.4 (d, J ¼ 25 Hz, 1C), 126.1, 128.3, 131.7, 145.7, 147.8,
148.3, 157.4–159.4 (d, J ¼ 248 Hz, 1C). MS (ESI) m/z: 323 [M+].
Anal. Calcd for C15H14FNO4S: C, 55.72%; H, 4.36%, N, 4.33%.
Found: C, 56.01; H, 3.97%; N, 4.14%.
1
ꢀ
solid, mp: 71–73 C. H NMR (CDCl3, 500 MHz) d 4.24 (s, 2H),
7.06–7.13 (m, 2H), 7.26–7.30 (m, 2H), 7.42–7.47 (m, 2H), 7.53–
7.56 (t, J ¼ 7.5 Hz, 1H), 8.20 (d, J ¼ 8.5 Hz, 1H). 13C NMR (CDCl3,
125 MHz) d 29.3, 114.6 (d, J ¼ 22 Hz, 1C), 121.3 (d, J ¼ 14 Hz, 1C),
123.5, 124.0, 125.1, 126.1, 128.6, 128.7, 130.0, 132.6, 136.2,
145.1, 159.0–160.9 (d, J ¼ 246 Hz, 1C). MS (ESI) m/z: 263 [M+].
Anal. Calcd for C13H10FNO2S: C, 59.30; H, 3.83%, N, 5.32%.
Found: C, 59.28; H, 3.60%; N, 5.44%.
2-(3,4-Dimethoxybenzylthio)-4-uoroaniline 9. Light yellow
oil. 1H NMR (CDCl3, 500 MHz) d 3.69 (s, 3H), 3.72 (s, 2H), 3.76 (s,
3H), 4.42 (s, 2H), 6.23–6.27 (m, 1H), 6.31–6.33 (dd, J ¼ 10.5, 2.5
Hz, 1H), 6.51 (d, J ¼ 1.5 Hz, 1H), 6.58–6.60 (dd, J ¼ 8.0, 1.0 Hz,
1H), 6.67 (d, J ¼ 8.0 Hz, 1H), 7.04–7.07 (m, 1H). 13C NMR (CDCl3,
125 MHz) d 39.6, 55.7, 55.9, 101.1–101.3 (d, J ¼ 25 Hz, 1C),
105.1–105.2 (d, J ¼ 21 Hz, 1C), 111.2, 112.2–112.3 (d, J ¼ 23 Hz,
1C), 121.1, 130.9, 138.7, 138.8, 150.6–150.7 (d, J ¼ 10 Hz, 1C),
163.4–165.4 (d, J ¼ 244 Hz, 1C). MS (ESI) m/z: 293 [M+]. Anal.
Calcd for C15H16FNO2S: C, 61.41%; H, 5.50%, N, 4.77%. Found:
C, 61.13; H, 5.22%; N, 4.38%.
(2-Nitrophenyl)(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecauorooctyl)-
sulfane 3j. Light yellow oil 1H NMR (CDCl3, 500 MHz) d 2.46 (m,
2H), 3.22–3.25 (m, 2H), 7.34–7.37 (m, 1H), 7.41 (d, J ¼ 8.0 Hz,
1H), 7.63–7.66 (m, 1H), 8.24–8.26 (m, 1H). 13C NMR (CDCl3, 125
MHz) d 22.1, 29.2–29.5 (m), 49.9, 124.4, 125.2, 125.4, 132.9,
134.4, 145.6. 19F NMR (CDCl3, 470 MHz) d ꢁ126.1, ꢁ123.3,
ꢁ122.8, ꢁ121.8, ꢁ114.2, ꢁ80.8. MS (ESI) m/z: 501 [M+]. Anal.
Calcd for C14H8F13NO2S: C, 33.55; H, 1.61%, N, 2.79%. Found:
C, 33.19; H, 1.94%; N, 3.13%.
Heptyl(2-nitrophenyl)sulfane 3k. Light yellow oil. 1H NMR
(CDCl3, 500 MHz) d 0.87–0.90 (t, J ¼ 7.0 Hz, 3H), 1.28–1.37 (m,
6H), 1.45–1.50 (m, 2H), 1.71–1.77 (m, 2H), 2.94–2.97 (t, J ¼ 7.5
Hz, 2H), 7.23–7.26 (m, 1H), 7.40 (d, J ¼ 8.0 Hz, 1H), 7.53–7.55
(m, 1H), 8.19–8.21 (m, 1H). 13C NMR (CDCl3, 125 MHz) d 13.0,
21.6, 26.9, 27.9, 28.1, 30.7, 31.4, 123.3, 125.1, 125.6, 132.3, 137.3,
145.1. MS (ESI) m/z: 253 [M+]. Anal. Calcd for C13H19NO2S: C,
61.63; H, 7.56%, N, 5.53%. Found: C, 61.59; H, 7.87%; N, 5.14%.
(Cyclohexylmethyl)(2-nitrophenyl)sulfane 3l. Light yellow
Notes and references
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42, 5400; (b) T. Kondo and T.-a. Mitsudo, Chem. Rev., 2000,
100, 3205; (c) H. Liu and X. Jiang, Chem.–Asian J., 2013, 8,
2546; (d) F. Pan and Z.-J. Shi, ACS Catal., 2013, 4, 280; (e)
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1
oil. H NMR (CDCl3, 500 MHz) d 0.97–1.05 (m, 2H), 1.10–1.23
(m, 3H), 1.57–1.69 (m, 4H), 1.87–1.90 (m, 2H), 2.76 (d, J ¼ 8.5
Hz, 2H), 7.14–7.17 (t, J ¼ 7.5 Hz, 1H), 7.32 (d, J ¼ 8.0 Hz, 1H),
7.45–7.48 (t, J ¼ 8.0 Hz, 1H), 8.11 (d, J ¼ 8.0 Hz, 1H). 13C NMR
(CDCl3, 125 MHz) d 25.0, 25.2, 32.2, 35.8, 38.7, 123.2, 125.1,
125.7, 132.3, 137.6, 145.2. MS (ESI) m/z: 251 [M+]. Anal. Calcd for
C
13H17NO2S: C, 62.12%; H, 6.82%, N, 5.57%. Found: C, 61.91;
H, 6.56%; N, 5.38%.
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