Iodine-catalyzed thiolation of electron-rich aromatics using sulfonyl hydrazides as sulfenylation reagents

Article abstract of DOI:10.1039/c5ob02193f

Iodine-catalyzed thiolation of electron-rich aromatics, including substituted anisole, thioanisole, phenol, toluene, and naphthalene, using sulfonyl hydrazides as sulfenylation reagents was carried out. Sulfonothioates, the products of decomposition of sulfonyl hydrazides in the presence of iodine, are proposed as the major sulfenylation species in this transformation.

Full text of DOI:10.1039/c5ob02193f

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Iodine-Catalyzed Thiolation of Electron-Rich Aromatics Using
Sulfonyl Hydrazides as Sulfenylation Reagents
Xia Zhao,*a Tianjiao Li, a Lipeng Zhang, a and Kui Lu*b
Received 00th January 20xx,
Accepted 00th January 20xx
Iodine-catalyzed thiolation of electron-rich aromatics, including substituted anisole, thioanisole, phenol, toluene, and
naphthalene, using sulfonyl hydrazides as sulfenylation reagents was developed. Sulfonothioates, the products of
decomposition of sulfonyl hydrazides in the presence of iodine, are proposed as the major sulfenylation species in this
transformation.
DOI: 10.1039/x0xx00000x
www.rsc.org/
that DCE gave the best result (Table 1, Entry 5). Brønsted acids have
been reported to promote the decomposition of sulfonyl
hydrazides.5b However, when p-toluenesulfonic acid (TsOH) was
used as an additive, the yield was not improved (Table 1, Entry 6).
Introduction
To further optimize the reaction conditions, we varied the reactant
concentration and iodine catalyst loading, and found that changing
the reactant concentration had great effect on the reaction yield.
When the concentration of 2a was increased from 2.0 M to 6.7 M,
Carbon-sulfur (C─S) bond formaꢀon has emerged as a key step in
the syntheses of natural products, pharmaceuticals, and organic
materials.1 Significant research is being pursued on the
development of new C─S bond formaꢀon reacꢀons, with emphasis
on identifying new sulfenylation reagents.2 In the past two years,
sulfonyl hydrazides have been developed as environmentally
friendly sulfenylation reagents that are stable, readily accessible,
and odor-free.3 Following Tian’s report on indole sulfenylation
(Scheme 1),4 several research groups, including ours, have used
sulfonyl hydrazides for the thiolation of electron-rich heterocycles
such as benzofurans,5 pyrazolones,6 and imidazo[1,2-a]pyridines,7
as well as naphthols and naphthylamines.8 Although transition
R2
S
O
I2
R2
R2
S
NHNH2
R1
+
S
R1
+ R1
EtOH, 70 oC
N
H
N
N
O
H
H
R1
Ref. 4
R2
SAr
R1
R2
R1
O
O
O
Ar
S
NHNH2
R1
R2
SAr
R2
10
metal-catalyzed sulfenylation of arenes has been reported,9,
I2
I2
O
O
O
1,4-Dioxane
120 oC
1,4-Dioxane
120 oC
Ref. 5
Ref. 6
metal-free sulfenylation of electron-rich benzene and naphthalene
by sulfonyl hydrazides has not yet been reported. In this paper, we
report the iodine-catalyzed thiolation of substituted anisole,
thioanisole, phenol, toluene, and naphthalene using sulfonyl
hydrazides as sulfenylation reagents (Scheme 2).
O
OH
O
I2 / TsOH
R1
R1
S
N
N
R3
S
NHNH2
+
R3
i-PrOH, 120 oC
N
N
O
R2
N
R2
O
N
I2
Ar
R2
R2
S
NHNH2
R1
Ref. 7
Ref. 8
Ar
+
R1
N
EtOH, 70 oC
N
O
Results and discussion
S
R2
S
XH
+
O
S
I2
XH
R2
NHNH2
First, we treated anisole 1a with 4-methylbenzenesulfonohydrazide
2a using iodine as the catalyst in 1,4-dioxane at 120 °C and the
desired sulfenylation product 3aa was obtained in 28% yield (Table
1, Entry 1). To optimize the reaction conditions, we tested various
solvents such as 1,2-dichloroethane (DCE), ethanol (EtOH), toluene
and N,N-dimethylformamide (DMF) (Table 1, Entries 2-5) and found
THF, 100 oC
O
X = O, NH
Scheme 1 Sulfenylation of electron-rich heterocycles, naphthols,
and naphthylamines
S
R2
R1
O
S
I2
R1
R2
NHNH2
This work
+
DCE, 100 oC
O
R1 = H, OH, OMe, Me,
SMe, Br, Cl
Scheme 2 Sulfenylation of electron-rich benzenes and naphthalenes
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the yield increased from 70% to 79% (Table 1, Entries 5, 7, 8). Table 2 I2-catalyzed cross coupling with a series of anisoles and
However, further increase in the concentration led to diminished sulfonyl hydrazides.a
yield (Table 1, Entries 9, 10). We also found that decreasing the
catalyst loading from 0.2 equiv. to 0.1 equiv. did not have any
notable effect on the yield (Table 1, Entry 11). However, further
decreasing catalyst loading to 0.05 equiv. led to a lower yield (Table
1, Entry 12). This suggests that 0.1 equiv. of the iodine catalyst is
required for the optimal product yield. Finally, the equivalent
amount of 2a was examined: 1.2 equiv. of 2a was sufficient for the
reaction, giving 82% product yield (Table 1, Entries 11, 13-15). Thus,
the optimal reaction conditions were as follows: 1a, 2.0 mmol; 2a,
2.4 mmol; I2, 0.2 mmol; DCE, 0.3 mL; temperature, 120 °C.
Table 1 Optimization of conditions for I2-catalyzed reaction of 1a
with 2a.a
I2
(eq.)
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.05
0.1
0.1
0.1
2a
(eq.)
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.2
1.1
1.0
Solvent
(mL)
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.3
0.2
0
0.3
0.3
0.3
0.3
0.3
Entry
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1,4-Dioxane
EtOH
Toluene
DMF
DCE
28
4
57
0
70
64b
75
79
72
70
77
27
82
77
72
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
Finally, to broaden the substrate scope of this transformation, we
tested other electron-rich aromatics using the optimized conditions.
The results are summarized in Table 3. Substituted toluene (4a and
4b), substituted phenol (4c and 4d), thioanisole (4e), naphthalene
(4f), and substituted naphthalene (4g-4i) underwent coupling with
various aryl sulfonyl hydrazides (2a-2c) to give the corresponding
mono- and di-sulfenylation products. In the case of substituted
toluenes, p-xylene afforded di-sulfenylation products 5aaa and
5acc, albeit in poor yields. Mesitylene resulted in the formation of
mono-thioethers 5ba, 5bb, and 5be in moderate to good yields. 4-
Methylphenol and 4-chlorophenol gave 2-sulfenylation products
5ca and 5da, respectively, while thioanisole gave the 4-sulfenylation
product 5ea in moderate to good yields. Moreover, when we used
naphthalene and 2-bromonaphthalene as substrates, the
corresponding 1, 4-disulfenylation products (5faa and 5iaa) were
DCE
DCE
a Reaction conditions: 1a (2.0 mmol), 2a (2.0-3.0 mmol), iodine (0.1-
0.4 mmol) solvent (0-1.0 mL). b TsOH (2.0 mmol) was added.
With the optimized conditions in hand, we extended the reaction
to a series of anisole and sulfonyl hydrazides; the results are
presented in Table 2. Most of the reactions afforded the
corresponding anisole thioethers in moderate to good yields. The
reaction of anisole proceeded as expected with meta-, ortho-, and
para-substituted aryl sulfonyl hydrazides, as well as with aryl
sulfonyl hydrazides with electron-withdrawing and electron-
donating groups, to give the corresponding mono-thioethers (3ab,
3ac, 3ad, and 3ae). However, aliphatic sulfonyl hydrazides such as
methanesulfonohydrazide 2f afforded the product in relatively low
yield. Notably, when an aryl sulfonyl hydrazide bearing a strong
electron-withdrawing group 2d and an ortho-substituted aryl
sulfonyl hydrazide 2e were used as substrates, decreasing the
reaction temperature to 100 °C increased the product yields. Next
the use of methoxy-substituted anisole in the reaction was
examined. 1,3-Dimethoxybenzene 1b and 1,3,5-trimethoxybenzene
1e afforded both the corresponding mono- and di-thioethers, while
1,4-dimethoxybenzene 1c and 1,2-dimethoxybenzene 1d gave only
the corresponding di-thioether.
obtained.
However,
1-methylnaphthalene
and
2-
methylnaphthalene gave only mono-sulfenylation products (5ga
and 5ha).
Although mechanisms for the sulfonyl hydrazide-based
sulfenylation have been proposed by many groups,3d, 3i, 4, 5b, the
actual sulfenylation species generated from sulfonyl hydrazides are
not very clear because the proposed sulfenylation intermediates
were unstable and could not be isolated and characterized.4 To
further understand the reaction mechanism and determine the
sulfenylation species produced, we investigated the decomposition
of 2a under the optimized reaction conditions, and obtained 1,2-di-
p-tolyldisulfane 6a and S-p-tolyl 4- methylbenzenesulfonothioate 7a
in 43% and 55% yields, respectively. Table 4 summarizes the results
2 | J. Name., 2012, 00, 1-3
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obtained when using 6a, 7a, and 4-methylbenzenesulfinic acid 8a, a
previously reported decomposition product of 2a,4 as well as the
A possible mechanism of this transformation, based on our
experimental observations and those reported in the literature,3d, 4
is proposed in Scheme 3. Sulfonyl hydrazide
2 ultimately
Table 3 I2-catalyzed sulfenylation of electron-rich aromatics with
decomposes into disulfide 6 and thiosulfonate 7. Two intermediates
are formed when iodine is used as the catalyst: sulfonyl diazene 9
and sulfinic acid 8. The key intermediate 7 reacts with electron-rich
aromatics 1 or 4 to produce the sulfenylation compound 8 as well
as products 3 or 5 when iodine or HI is added. Intermediate 8 then
reacts with 6 to yield 7 and thiophenol 10. The combination of 10
and 8 can be used as the sulfur source to convert substrates into
the sulfenylation products in the presence of iodine, as confirmed in
the following two experiments. 1) When 0.6 equiv. of 8a and 0.6
equiv. of 4-methylbenzenethiol 10a were used as the sulfur source,
in the presence of iodine and at 100 °C, the desired sulfenylation
product 3aa was obtained in 70 % yield. 2) When 10a was reacted
with benzenesulfinic acid 8a' instead of 8a as the sulfur source,
sulfenylation products 3aa and (4-methoxyphenyl)(phenyl)sulfane
3aa' were formed in 48% and 34% yield, respectively (Scheme 4).13
aryl sulfonyl hydrazides.a
S
R2
R1
O
S
O
2
I2 (0.1 equiv.)
DCE, 120 o
R1
R2
NHNH2
+
C
4
5
R = H, OH, SMe, Me, Br
Cl
S
S
S
S
S
S
Cl
OMe
5aaa, 26%c
5acc, 33%c
5ba, 78%b
5bb, 72%
Cl
S
O
S
S
S
S
OH
OH
Table 4. Reaction of anisole 1a with three decomposition products
of sulfonyl hydrazides 2a.a
5be, 56%
5ca, 78%b
5da, 55%
5ea, 43%b
S
S
S
Br
S
S
S
5faa, 47%c
5ga, 64%
5ha, 34%
5iaa, 13%c
a Reaction conditions: 1a-c (2.0 mmol), 2b-f (2.4 mmol), I2 (0.2 mmol), DCE (0.3 mL), 120 oC.
b The reaction was carried out in 100 oC.
Yield
(%)
0
19
42
Entry S source A S source B
Catalyst
Additive
c The yield was calculated using sulfonyl hydrazide as reference.
1
2
3
6a (0.6 eq.)
6a (0.6 eq.)
6a (0.6 eq.)
―
―
―
―
―
―
I2 (0.1 eq.)
I2 (0.1 eq.) H2O2 (1.5
eq.)
―
I2 (0.1 eq.)
―
results obtained with combinations of 6a/7a and 6a/8a as the
sulfenylation reagents in the reaction with 1a. We found that 6a did
not react with 1a to afford the desired 3aa product (Table 4, Entry
1), unless 0.1 equiv. of iodine (Table 4, Entries 2) was added.
Notably, when H2O2 was used as an additive to oxidize 6a to 7a, the
yield was improved from 19% to 42%, which suggests that 7a is a
more efficient sulfenylation reagent in this reaction (Table 4, Entry
3). Further, 7a could not be transformed into 3aa in the absence of
a catalyst or additive; however, when 0.1 equiv. of iodine was used
as a catalyst, 7a coupled with 1a to produce the desired product in
65% yield (Table 4, Entries 4, 5). Interestingly, HI, which is proposed
to be generated from the decomposition of sulfonyl hydrazide by
iodine,4 catalyzed the transformation of 7a to 3aa in 70% yield
(Table 4, Entry 6). Notably, when a combination of 0.3 equiv. 6a and
0.3 equiv. 7a was used for sulfenylation, an excellent product yield
of 87% was obtained (Table 4, Entry 7). It is known that 6a reacts
with 8a to produce 7a;11 hence, the combination of 6a and 8a was
tested as the sulfur source. When 0.6 equiv. of 6a was combined
with 0.1 equiv. of 8a, the desired product was obtained in 15% yield
in the absence of the iodine catalyst and in 31% yield in the
presence of the iodine catalyst (Table 4, Entries 8, 9). Notably,
increasing the loading of 8a led to an increase in the yields.
Additionally, 7a increased in amount during the reaction but
disappeared when the reaction was completed (Table 4; Entries 10,
11). Finally, when only 8a was used as the sulfenylation reagent,12
the desired products were obtained in 43% and 44% yield in the
presence of iodine and HI as the catalyst, respectively. (Table 4;
Entries 12, 13). Based on these data, we propose that 7a is the
major sulfenylation species in this reaction.
4
5
6
7a (0.6 eq.)
7a (0.6 eq.)
7a (0.6 eq.)
―
―
―
―
―
0
65
HI (0.1 eq.) 70
7
8
6a (0.3 eq.) 7a (0.3 eq.) I2 (0.1 eq.)
6a (0.6 eq.) 8a (0.1 eq.)
―
―
―
―
―
―
―
87
15
31
52
72
43
44
―
9
6a (0.6 eq.) 8a (0.1 eq.) I2 (0.1 eq.)
6a (0.6 eq.) 8a (0.2 eq.) I2 (0.1 eq.)
6a (0.6 eq.) 8a (0.3 eq.) I2 (0.1 eq.)
10
11
12
13
―
―
8a (1.2 eq.) I2 (0.1 eq.)
8a (1.2 eq.) HI (0.1 eq.)
a
Reaction conditions: 1a (1.0 mmol), S source (0.3-0.6 mmol),
iodine (0-0.1 mmol), additive (0-1.5 eq.), solvent (0.3 mL), 100 °C.
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Scheme 3 Proposed reaction pathway
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.3, 141.3, 136.1, 134.8,
129.8, 127.0, 125.5, 125.4, 122.6, 115.2, 55.4.
(4-methoxyphenyl)(4-(trifluoromethyl)phenyl)sulfane
After purification by silica gel column chromatography (PE : DCM =
OMe
O
OH
SH
S
OMe
(3ad)[2]
:
I2 (0.1 equiv.)
DCE, 100 o
+
+
C
S
100 : 1), compound 3ad was isolated as a white solid (131 mg, 23%
8a
0.6 equiv.
1a
10a
3aa
o
o
1
for 120 C), (308 mg, 54% for 100 C): Rf (PE : EA = 30 : 1) = 0.7; H
NMR (400 MHz, CDCl3): δ 7.47 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.4 Hz,
2H), 7.13 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 160.7, 114.8, 136.6, 127.2 (q, J =
32.0 Hz, 1C), 126.5, 125.6 (q, J = 4.0 Hz, 1C ), 124.2 (q, J = 270 Hz,
1C), 121.8, 115.4, 55.4.
1.0 equiv.
0.6 equiv.
70%
OMe
OMe
S
SH
O
OH
OMe
S
I2 (0.1 equiv.)
DCE, 100 o
+
+
+
C
S
(4-methoxyphenyl)(o-tolyl)sulfane (3ae)[3]: After purification by
silica gel column chromatography (PE : DCM = 100 : 1), compound
3ae was isolated as a colorless oil (264 mg, 57% for 120 oC), (305
8a'
0.6 equiv.
3aa'
34%
1a
10a
3aa
1.0 equiv.
0.6 equiv.
48%
1
mg, 66% for 100 oC): Rf (PE : EA = 30 : 1) = 0.68; H NMR (400 MHz,
CDCl3): δ 7.32 (dd, J = 6.8 Hz, 2.0Hz, 2H), 7.17 (d, J = 6.8 Hz, 1H),
7.03-7.11 (m, 2H), 6.98 (d, J = 6.8 Hz, 1H), 6.89 (dd, J = 6.8 Hz, 2.0Hz,
2H), 3.81 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
159.5, 137.01, 137.03, 134.5, 130.2, 129.1, 126.4, 126.1, 124.5,
115.0, 55.3, 20.3.
Scheme 4 Sulfenylation of anisole using 8a, 8a', and 10a as sulfur
sources
Experimental
(4-methoxyphenyl)(methyl)sulfane (3af)[17]: After purification by
silica gel column chromatography (PE : DCM = 100 : 1), compound
3af was isolated as a yellow oil (76 mg, 25%). Rf (PE : EA = 30 : 1) =
1) General methods and material
All solvents were distilled prior to use. Unless otherwise noted,
chemicals were used as received without further purification. For
chromatography, 200−300 mesh silica gel was employed. 1H and
13C{1H} NMR spectra were recorded at 400 MHz and 100 MHz
respectively. Chemical shifts are reported in ppm using
tetramethylsilane as internal standard. IR spectra were recorded in
wave numbers (cm−1) with a FT-IR spectrometer. HRMS was
performed on an FTMS mass instrument. Melting points are
reported as uncorrected.
1
0.72; H NMR (400 MHz, CDCl3): δ 7.27 (dd, J = 6.8 Hz, 2.0 Hz, 2H),
6.85 (d, J = 6.8 Hz, 2.0 Hz, 2H), 3.79 (s, 3H), 2.44 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 158.2, 130.2, 128.7, 114.6, 55.3, 18.0.
(2,4-dimethoxyphenyl)(p-tolyl)sulfane (3ba)[18]
:
(4,6-dimethoxy-1,3-phenylene)bis(p-tolylsulfane) (3baa): After
purification by silica gel column chromatography (PE : EA = 100 : 1),
compound 3ba and compound 3baa were isolated as a white solid
(310 mg, 60%) and as a white solid (205 mg, 27%) respectively. For
3ba: mp (melting point) = 69-70 oC; Rf (PE : EA = 30 : 1) = 0.4; IR
(film): 2942, 1594, 1490, 1463, 1303, 1209, 1162, 1075, 1031, 804
cm−1; 1H NMR (400 MHz, CDCl3): δ 7.24 (d, J = 8.4 Hz, 1H), 7.10 (d, J
= 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.51 (d, J = 2.4 Hz, 1H), 6.46
(dd, J = 8.4 Hz, 2.4 Hz, 1H), 3.82 (s, 6H), 2.29 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 161.3, 159.8, 135.7, 135.4, 133.4, 129.6, 129.0,
113.6, 105.3, 99.2, 55.9, 55.4, 21.0; HRMS (ESI, m/z): calcd for
C15H16O2S [M]+ 260.0866, found 260.0868, calcd for C15H16NaO2S
[M+Na]+ 283.0763, found 283.0765. For 3baa: mp (melting point) =
2) The synthesis and spectral data of the sulfenylation products
General Procedure: The I2-catalyzed reactions between electron-
rich aromatics 1a, 1b, 1d, 1e; 4a-i and sulfonyl hydrazides 2a-f
(Table 2, 3). Electron-rich aromatics (2.0 mmol), sulfonyl hydrazides
(2.4 mmol) and I2 (50.8 mg, 0.2 mmol) and DCE (0.3 mL) were mixed
in a sealed tube. The mixture was stirred at 120 oC or 100 oC until
electron-rich aromatics disappeared detected by TLC. Then, the
solvent was evaporated under reduced pressure and the residue
was purified by silica gel column chromatography to afford the pure
product.
o
111-112 C; Rf (PE : EA = 30 : 1) = 0.18; IR (film): 2923, 2842, 1576,
(4-methoxyphenyl)(p-tolyl)sulfane (3aa)[14]: After purification by
silica gel column chromatography (PE : DCM = 15 : 1, PE =
petroleum ether, DCM = CH2Cl2), compound 3aa was isolated as a
1491, 1365, 1274, 1207, 1028, 806 cm−1;1H NMR (400 MHz, CDCl3):
δ 7.15 (s, 1H), 7.09 (d, J = 8.4 Hz, 4H), 7.02 (d, J = 8.4 Hz, 4H), 6.52 (s,
1H), 3.88 (s, 6H), 2.30 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ
159.4, 138.3, 136.2, 132.1, 129.9, 129.7, 114.8, 96.1, 56.2, 21.0;
HRMS (ESI, m/z): calcd for C22H22O2S2 [M]+ 382.1056, found
382.1059, calcd for C22H22NaO2S2 [M+Na]+ 405.0953, found
405.0955.
1
pale yellow oil (379 mg, 82%): Rf (PE : EA = 30 : 1) = 0.63; H NMR
(400 MHz, CDCl3): δ 7.36 (dd, J = 6.8 Hz, 2.0 Hz, 2H), 7.13 (dd, J = 6.8
Hz, 2.0 Hz, 2H), 7.06 (d, J = 6.8 Hz, 2H), 6.87 (dd, J = 6.8 Hz, 2.0 Hz,
2H), 3.80 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
159.4, 136.1, 134.3, 129.7, 129.4, 125.6, 114.8, 55.3, 21.0.
(2,5-dimethoxy-1,4-phenylene)bis(p-tolylsulfane) (3caa): 1c (276
mg, 2.0 mmol), 2a (893 mg, 4.8 mmol) and I2 (50.8 mg, 0.2 mmol)
and DCE (0.3 mL) were mixed in a sealed tube. The mixture was
stirred at 120 oC until 1c disappeared detected by TLC. Then, the
solvent was evaporated under reduced pressure and the residue
was purified by silica gel column chromatography (PE : CH2Cl2 = 5 :
1) to get compound 3caa (264 mg, 35%) as a white solid: mp
(melting point) = 162-163 oC; Rf (PE : EA = 30 : 1) = 0.43; IR (film):
bis(4-methoxyphenyl)sulfane (3ab)[15]: After purification by silica
gel column chromatography (PE:DCM = 5:1), compound 3ab was
isolated as a pale yellow oil (404 mg, 82%): Rf (PE : EA = 30 : 1) =
1
0.48; H NMR (400 MHz, CDCl3): δ 7.28 (dd, J = 6.8 Hz, 2.0 Hz, 4H),
6.84 (dd, J = 6.8 Hz, 2.0 Hz, 4H), 3.79 (s, 6H); 13C{1H} NMR (100 MHz,
CDCl3): δ 158.9, 132.7, 127.4, 114.7, 55.3.
(3-chlorophenyl)(4-methoxyphenyl)sulfane
(3ac)[16]
:
After
2952, 1490, 1438, 1365, 1205, 1037, 812, 777 cm−1 1H NMR (400
;
purification by silica gel column chromatography (PE : DCM = 100 :
1), compound 3ac was isolated as a pale yellow oil (378 mg, 75%): Rf
(PE : EA = 30 : 1) = 0.6; 1H NMR (400 MHz, CDCl3): δ 7.43 (dd, J = 6.8
Hz, 2.0 Hz, 2H), 7.12-7.15 (m, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.07 (s,
1H), 7.00 (d, J = 8.0 Hz, 1H), 6.92 (dd, J = 6.8 Hz, 2.0 Hz, 2H), 3.84 (s,
MHz, CDCl3): δ 7.28 (d, J = 8.0 Hz, 4H), 7.14 (d, J = 8.0 Hz, 4H), 6.57
(s, 2H), 3.64 (s, 6H), 2.35 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ
151.5, 137.6, 132.1, 130.2, 130.3, 124.3, 113.8, 56.5, 21.1; HRMS
(ESI, m/z): calcd for C22H23O2S2 [M+H]+ 383.1134, found 383.1141,
calcd for C22H22NaO2S2 [M+Na]+ 405.0953, found 405.0958.
4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5OB02193F
Journal Name
(4,5-dimethoxy-1,2-phenylene)bis(p-tolylsulfane) (3da): After mesityl(o-tolyl)sulfane (5be)[20]
ARTICLE
:
After purification by silica gel
purification by silica gel column chromatography (PE : EA = 50 :1), column chromatography (PE), compound 5be was isolated as a pale
compound 3da was isolated as a pale yellow solid (380 mg, 83%):
yellow oil (271 mg, 56%)： Rf (PE) = 0.85; IR (film): 2921, 1588,
o
1
1466, 1377, 1045, 851, 745 cm−1; H NMR (400 MHz, CDCl3): δ 7.12
mp (melting point) = 99-100 C; Rf (PE : EA = 30 : 1) = 0.2; IR (film):
1
2930, 1489, 1436, 1252, 1207, 1178, 1035, 806 cm−1; H NMR (400
(d, J = 6.8 Hz, 1H), 7.02 (s, 2H), 6.90-6.99 (m, 2H), 6.39 (dd, J = 8.0
Hz, 1.2 Hz, 1H), 2.43 (s, 3H), 2.35 (s, 6H), 2.32 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 143.8, 139.1, 137.4, 134.6, 129.9, 129.3, 127.0,
126.4, 124.2, 124.0, 21.6. 21.1, 20.0; HRMS (ESI, m/z): calcd for
C16H19S [M+H]+ 243.1202, found 243.1207.
MHz, CDCl3): δ 7.19 (d, J = 8.0 Hz, 4H), 7.10 (d, J = 8.0 Hz, 4H), 6.77
(s, 2H), 3.71 (s, 6H), 2.32 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ
148.9, 136.8, 132.4, 130.6, 129.9, 129.2, 115.5, 56.0, 21.1; HRMS
(ESI, m/z): calcd for C22H23O2S2 [M+H]+ 383.1134, found 383.1141,
calcd for C22H22NaO2S2 [M+Na]+ 405.0953, found 405.0959.
4-methyl-2-(p-tolylthio)phenol (5ca)[21]: After purification by silica
gel column chromatography (PE : DCM = 15 : 1), compound 5ca was
isolated as a colorless oil (363 mg, 78%)： Rf (PE : EA = 30 : 1) = 0.5;
1H NMR (400 MHz, CDCl3): δ 7.31 (d, J = 2.0 Hz, 1H), 7.14 (dd, J = 8.4
Hz, 2.0 Hz, 1H), 6.99-7.05 (m, 4H), 6.94 (d, J = 8.4 Hz, 1H), 6.35 (s,
1H), 2.28 (s, 3H), 2.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
154.9, 136.6, 136.2, 132.7, 132.4, 130.4, 129.9, 127.5, 116.7, 115.2,
20.9, 20.3.
p-tolyl(2,4,6-trimethoxyphenyl)sulfane (3ea) [21]
:
(2,4,6-trimethoxy-1,3-phenylene)bis(p-tolylsulfane) (3eaa): After
purification by silica gel column chromatography (PE : EA = 50 : 1),
compound 3ea and 3eaa were isolated as a white solid (354 mg,
61%) and as a white solid (113 mg, 14%) respectively. For 3ea: Rf
(PE : EA = 20 : 1) = 0.23; mp (melting point) = 120-121 oC; IR (film):
1580, 1490, 1226, 1206, 1161, 1123, 804, 739 cm−1 1H NMR (400
;
MHz, CDCl3): δ 6.93-6.98 (m, 4H), 6.21 (s, 2H), 3.86 (s, 3H), 3.80 (s,
6H), 2.25 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.7, 162.5,
135.0, 134.1, 129.2, 126.0, 99.4, 91.2, 56.3, 55.4, 20.8; HRMS (ESI,
m/z): calcd for C16H19O3S [M+H]+ 291.1049, found 291.1050, calcd
for C16H18NaO3S [M+Na]+ 313.0869, found 313.0871. For 3eaa: Rf
(PE : EA = 20 : 1) = 0.17; mp (melting point) = 142-144 oC; IR (film):
4-chloro-2-(p-tolylthio)phenol (5da): After purification by silica gel
column chromatography (PE : EA = 200 : 1), compound 5da was
isolated as a yellow oil (275 mg, 55%)： Rf (PE : EA = 30 : 1) = 0.3; IR
(film): 3418, 1491, 1468, 1275, 1190, 820, 803, 725 cm−1 1H NMR
;
(400 MHz, CDCl3): δ 7.48 (d, J = 2.4 Hz, 1H), 7.28 (dd, J = 8.8 Hz, 2.4
Hz, 1H), 7.04-7.09 (m, 4H), 6.97 (d, J = 8.8 Hz, 1H), 6.45 (s, 1H), 2.29
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.6, 137.0, 135.3, 131.7,
131.0, 130.2, 128.3, 125.4, 119.3, 116.6, 20.9; HRMS (ESI, m/z):
calcd for C13H12ClOS [M+H]+ 251.0292, found 251.0296.
1
2928, 1571, 1491, 1369, 1212, 1116, 1097, 803 cm−1; H NMR (400
MHz, CDCl3): δ 6.99 (s, 8H), 6.41 (s, 1H), 3.86 (s, 6H), 3.76 (s, 3H),
2.26 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.9, 163.3, 134.7,
134.6, 129.4, 126.6, 107.5, 92.5, 62.2, 56.3, 20.8; HRMS (ESI, m/z):
calcd for C23H25O3S2 [M+H]+ 413.1240, found 413.1245, calcd for
C23H24NaO3S2 [M+Na]+ 435.1059, found 435.1063.
1-methoxy-4-(4-(methylthio)phenylthio)benzene (5ea)[22]
:
After
purification by silica gel column chromatography (PE : DCM = 5 : 1),
compound 5ea was isolated as a pale yellow solid (224 mg, 43%)：
mp (melting point) = 41-43 oC; Rf (PE : EA = 30 : 1) = 0.6; IR (film):
(2,5-dimethyl-1,4-phenylene)bis(p-tolylsulfane) (5aaa)[19]
:
After
1
2920, 1591, 1493, 1476, 1246, 1172, 1106, 1031, 828, 808 cm−1; H
purification by silica gel column chromatography (PE), compound
5aaa was isolated as a white solid (110 mg, 26%): Rf (PE) = 0.55; mp
(melting point) = 114-116 oC; IR (film): 2924, 1489, 1467, 1445,
NMR (400 MHz, CDCl3): δ 7.37 (dd, J = 6.8 Hz, 2.0 Hz, 1H), 7.11-7.16
(m, 4H), 6.88 (dd, J = 6.8 Hz, 2.0 Hz, 2H), 3.81 (s, 3H), 2.45 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 159.6, 136.3, 134.7, 134.6, 129.4,
127.4, 124.9, 114.9, 55.3, 16.1; HRMS (ESI, m/z): calcd for C14H15OS2
[M+H]+ 263.0559, found 263.0565.
1
1087, 1012, 805 cm−1; H NMR (400 MHz, CDCl3): δ 7.16 (d, J = 8.0
Hz, 4H), 7.11 (d, J = 8.0 Hz, 4H), 7.03 (s, 2H), 2.33 (s, 6H), 2.24 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3): δ 137.0, 136.8, 133.9, 133.1,
131.5, 130.7, 130.0, 21.1, 19.9; HRMS (ESI, m/z): calcd for C22H23S2
[M+H]+ 351.1236, found 351.1232.
1,4-bis(p-tolylthio)naphthalene (5faa)[9]: After purification by silica
gel column chromatography (PE), compound 5faa was isolated as a
white solid (209 mg, 47%)： Rf (PE) = 0.48; 1H NMR (400 MHz,
CDCl3): δ 8.40 (dd, J = 6.8 Hz, 3.2 Hz, 2H), 7.55 (dd, J = 6.8 Hz, 3.2 Hz,
2H), 7.30 (s, 2H), 7.21 (d, J = 8.0 Hz, 4H), 7.10 (d, J = 8.0 Hz, 4H), 2.32
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 137.2, 133.4, 133.0, 131.4,
131.1, 130.1, 129.5, 127.0, 125.7, 21.1.
(2,5-dimethyl-1,4-phenylene)bis((3-chlorophenyl)sulfane) (5acc):
After purification by silica gel column chromatography (PE),
compound 5acc was isolated as a white solid (153 mg, 33%)： Rf
(PE) = 0.76; mp (melting point) = 71-72 oC; IR (film): 2918, 1576,
1460, 1081, 774, 678 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.23 (s, 2H),
7.15-7.22 (m, 6H), 7.06 (d, J = 8.0 Hz, 2H), 2.28 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3): δ 138.8, 138.2, 135.4, 135.0, 132.9, 130.2, 128.7,
127.2, 126.5, 20.0； HRMS (ESI, m/z): calcd for C20H17Cl2S2 [M+H]+
391.0143, found 391.0149.
(4-methylnaphthalen-1-yl)(p-tolyl)sulfane (5ga): After purification
by silica gel column chromatography (PE), compound 5ga was
isolated as a yellow oil (340 mg, 64%)： Rf (PE) = 0.67; IR (film):
mesityl(p-tolyl)sulfane (5ba)[10]
: After purification by silica gel
2919, 1491, 1378, 1088, 829, 804, 757 cm−1 1H NMR (400 MHz,
;
column chromatography (PE : DCM = 100 : 1), compound 5ba was
isolated as a white solid (378 mg, 78%)： Rf (PE) = 0.8; 1H NMR (400
MHz, CDCl3): δ 6.99 (s, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0
Hz, 2H), 2.38 (s, 6H), 2.31 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 143.6, 139.0, 134.8, 134.2, 129.6, 129.3, 127.5,
125.7, 21.7, 21.1, 20.8.
CDCl3): δ 8.43 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 8.02 (dd, J = 7.6 Hz, 2.0 Hz,
1H), 7.50-7.56 (m, 3H), 7.26 (d, J = 7.6 Hz, 1H), 7.07-7.09 (m, 2H),
7.01 (d, J = 8.0 Hz, 2H), 2.70 (s, 3H), 2.27 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 135.9, 135.6, 133.63, 133.56, 133.4, 132.2, 129.8,
129.6, 129.1, 126.7, 126.4, 126.3, 126.1, 124.7, 20.9, 19.5; HRMS
(ESI, m/z): calcd for C18H16S [M]+ 264.0967, found 264.0971, calcd
for C18H17S [M+H]+ 265.1046, found 265.1049.
mesityl(4-methoxyphenyl)sulfane (5bb)[9]
: After purification by
silica gel column chromatography (PE), compound 5bb was isolated
as a pale yellow solid (371mg, 72%). Rf (PE) = 0.35; 1H NMR (400
MHz, CDCl3): δ 6.98 (s, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.74 (d, J = 8.8
Hz, 2H), 3.74 (s, 3H), 2.39 (s, 6H), 2.30 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 157.4, 143.4, 138.9, 129.2, 129.0, 128.3, 127.6,
114.6, 55.3, 21.8, 21.1.
(2-methylnaphthalen-1-yl)(p-tolyl)sulfane (5ha): After purification
by silica gel column chromatography (PE), compound 5ha was
isolated as a yellow oil (180 mg, 34%): Rf (PE) = 0.75; IR (film): 2920,
1491, 1085, 1016, 803, 775, 742 cm−1; 1H NMR (400 MHz, CDCl3): δ
8.56 (d, J = 8.0 Hz, 1H), 7.82-7.85 (m, 2H), 7.42-7.51 (m, 3H), 6.94 (d,
J = 8.0 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H), 2.65 (s, 3H), 2.23 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 142.7, 135.8, 134.6, 134.5, 132.9,
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C5OB02193F
ARTICLE
Journal Name
129.8, 129.6, 128.9, 128.2, 127.6, 127.1, 126.3, 125.4, 22.2, 20.8;
HRMS (ESI, m/z): calcd for C18H16S [M]+ 264.0967, found 264.0972,
calcd for C18H17S [M+H]+ 265.1046, found 265.1049.
Wang, F.-L. Yang and S.-K. Tian, Adv. Synth. Catal.
2015, 357, 928. (e) K. Xu, V. Khakyzadeh, T. Bury and B. Breit, J.
Am. Chem. Soc. 2014, 136, 16124. (f) J. Zhang, Y. Shao, H. Wang,
Q. Luo, J. Chen, D. Xu and X. Wan, Org. Lett. 2014, 16, 3312. (g)
(6-bromonaphthalene-1,4-diyl)bis(p-tolylsulfane) (5iaa): After
purification by silica gel column chromatography (PE), compound
5iaa was isolated as a pale yellow oil (71 mg, 13%): Rf (PE) = 0.46; IR
S. Guo, W. He, J. Xiang and Y. Yuan, Chem. Commun. 2014, 50
,
8578. (h) F.-L. Yang, F.-X. Wang, T.-T. Wang, Y.-J. Wang and S.-K.
Tian, Chem. Commun. 2014, 50, 2111. (i) R. Singh, D. S.
Raghuvanshi and K. N. Singh, Org. Lett. 2013, 15, 4202. (j) N.
Singh, R. Singh, D. S. Raghuvanshi and K. N. Singh, Org. Lett.
2013, 15, 5874. (k) X. Li, X. Xu, P. Hu, X. Xiao and C. Zhou, J. Org.
Chem. 2013, 78, 7343.
(film): 2923, 1594, 1491, 1329, 987, 826, 807 cm−1 1H NMR (400
;
MHz, CDCl3): δ 8.59 (d, J = 2.0 Hz, 1H), 8.26 (d, J = 9.2 Hz, 1H), 7.61
(dd, J = 9.2Hz, 2.0 Hz, 1H), 7.28 (s, 2H), 7.23 (dd, J = 6.4 Hz, 2.0 Hz,
2H), 7.19 (dd, J = 6.4 Hz, 2.0 Hz, 2H), 7.09-7.13 (m, 4H), 2.33 (s, 3H),
2.32 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 137.6, 137.5, 134.3,
133.6, 133.0, 131.6, 131.5, 131.2, 131.0, 130.7, 130.4, 130.3,
130.22, 130.17, 129.8, 128.0, 127.6, 121.7, 21.09, 21.07; HRMS (ESI,
m/z): calcd for C24H20BrS2 [M+H]+ 451.0184, found 451.0188.
4 F.-L. Yang and S.-K. Tian, Angew. Chem., Int. Ed. 2013, 52
,
4929.
5 X. Zhao, L. Zhang, X. Lu, T. Li and K. Lu, J. Org. Chem. 2015, 80,
2918.
Conclusions
6 (a) J. Sun, J.-K. Qiu, Y.-L. Zhu, C. Guo, W.-J. Hao, B. Jiang and S.-
J. Tu, J. Org. Chem. 2015, 80, 8217. (b) X. Zhao, L. Zhang, T. Li, G.
Liu, H. Wang and K. Lu, Chem. Commun. 2014, 50, 13121.
7 A. Hajra, A. K. Bagdi, S. Mitra and M. Ghosh, Org. Biomol.
Chem. 2015, 13, 3314.
In conclusion, we developed an efficient iodine-catalyzed cross-
coupling reaction of sulfonyl hydrazides with electron-rich
aromatics, including substituted anisole, thioanisole, phenol,
toluene, and naphthalene, via direct C─H funcꢀonalizaꢀon. This
study not only broadened the scope of sulfenylation reactions with
sulfonyl hydrazides as reagents from electron-rich heterocycles to
general electron-rich aromatics, but also demonstrated that
sulfonothioates were the major sulfenylation species in this
transformation.
8 X. Kang, R. Yan, G. Yu, X. Pang, X. Liu, X. Li, L. Xiang and G.
Huang, J. Org. Chem. 2014, 79, 10605.
9 P. Saravanan and P. Anbarasan, Org. Lett. 2014, 16, 848.
10 X. Li, Y. Xu, W. Wu, C. Jiang, C. Qi and H. Jiang, Chem. - Eur. J.
2014, 20, 7911.
11 S. Oae, T. Takata and Y. H. Kim, Tetrahedron, 1981, 37, 37.
12 C.-R. Liu and L.-H. Ding, Org. Biomol. Chem. 2015, 13, 2251.
13 Because 3aa and 3aa' could not be separated by silica gel
column chromatography, the yield was calculated by NMR.
14 A. Martin, D. Nelson, S. Meiries, A. Slawin and S. Nolan, Eur. J.
Org. Chem. 2014, 3127.
Acknowledgements
The authors sincerely thank the financial support from
National Science Foundation of China (Grants 21202119,
21202118, 21572158).
15 D. J. C. Prasad and G. Sekar, Org. Lett. 2011, 13, 1008.
16 S. Saba, J. Rafique and A. Braga, Adv. Synth. Catal. 2015, 357,
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Notes and references
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6 | J. Name., 2012, 00, 1-3
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