The direct thiolation of benzothiazole catalyzed by copper complex in superbase system

Article abstract of DOI:10.1055/s-0032-1316891

The copper-catalyzed direct thiolation of benzothiazole with iodobenzene and sulfur in superbase system under oxygen atmosphere is reported. The corresponding 2-thio-substituted benzothiazoles were formed in satisfactory yields. Georg Thieme Verlag KG Stu

Full text of DOI:10.1055/s-0032-1316891

PAPER
▌1247
paper
The Direct Thiolation of Benzothiazole Catalyzed by Copper Complex in
Superbase System
Direct Thiolation of Benzothiazole in Superbase System
Xiaowei Wang,a Yanjun Li,a Yu Yuan*a,b
a
College of Chemistry & Chemical Engineering, Yangzhou University, Jiangsu Province 225002, P. R. of China
b
Jiangsu Changqing Agrochemical Co., Ltd, Jiangsu Province 225218, P. R. of China
E-mail: yyuan@yzu.edu.cn
Received: 23.01.2013; Accepted after revision: 13.03.2013
Cu powder
(30 mol%)
Abstract: The copper-catalyzed direct thiolation of benzothiazole
with iodobenzene and sulfur in superbase system under oxygen at-
mosphere is reported. The corresponding 2-thio-substituted benzo-
thiazoles were formed in satisfactory yields.
S
N
I
R
S
N
our previous work
+
Key words: copper, C–H thiolation, superbase, benzothiazole,
cross coupling
R
R
S
Sulfur
S
CuI (30 mol%)
The formation of C–S bond represents a key step in the
synthesis of many molecules that are of biological, phar-
maceutical, and material interest.1 Among these thio com-
pounds, an increasing number of 2-thio-substituted
benzothiazoles have been designed and synthesized for
biological evaluation.2 Several methods have been devel-
oped for the synthesis of this type of compounds.3 Ma and
co-workers reported the synthesis of 2-thio-substituted
benzothiazoles in good yield via a domino condensation.3a
The cascade process has been developed for the prepara-
tion of these benzothiazoles directly from isothiocyanates
catalyzed by copper(I).3b,c Metal-catalyzed cross-coupling
reactions also have become a principal method for forma-
tion of these compounds.3d Usually, benzothiazole-2-thiol
was used as the substrate in the presence of copper salt as
the catalyst.3e–j The direct thiolation of benzothiazole cat-
alyzed by Lewis acids has been investigated extensive-
ly.3k–o Recently, we developed a copper powder-catalyzed
direct coupling reaction of heterocycles with aryl halides.4
Herein, we report a direct thiolation of benzothiazole with
iodobenzene and sulfur catalyzed by cuprous iodide in the
presence of 1,10-phenanthroline in DMSO in good to
moderate yields (Scheme 1).
N
this work
Scheme 1 Our research on coupling reactions between benzothia-
zole and iodobenzenes
(Table 1, entry 6). It was shown that the best choice of the
amount of KOH was 4 equivalents due to the efficiency in
the reaction. Different copper sources were investigated in
the reaction, such as Cu powder, Cu(OAc)2, and nano
CuO; only nano CuO could catalyze the reaction to pro-
vide a 30% yield of the product (Table 1, entries 7–9).
With the adjustment of the bases and solvents, the best
combination was found to be KOH and DMSO, which is
one type of superbase system used in the cross-coupling
reaction of thiols and iodobenzene5 (Table 1, entries 10–
13). When the catalyst amount of cuprous iodide was en-
hanced to 30 mol%, the reaction turned better under the
same conditions (Table 1, entry 14). Usually, the ligands
could promote the efficiency of the copper salts in the re-
actions, and it was found that the reaction yield was in-
creased to 87% when 1,10-phenanthroline (Figure 1) was
used as the ligand (Table 1, entries 15–19).
Initially, treatment of benzothiazole (1a; 0.3 mmol), iodo-
benzene (2a; 0.5 mmol), and sulfur (0.6 mmol) with KOH
(4 equiv) and CuI (10 mol%) in DMSO at 130 °C under
air gave 2-phenylsulfanylbenzothiazole (3aa) in 15%
yield (Table 1, entry 1). Interestingly, the yield increased
to 40% when the atmosphere was changed to oxygen (Ta-
ble 1, entry 2), but no reaction was detected when argon
was used in the system (Table 1, entry 3). After decreasing
the amount of KOH, the yield of the product was dropped
(Table 1, entries 4, 5), whereas the yield increased a little
using 6 equivalents of KOH under the same conditions
N
N
N
N
L1
L2
O
N
O
N
O
O
O
N
N
L3
L4
L5
Figure 1 The ligands screened in the reaction
Next, the scope of the reaction with various substituted io-
dobenzenes 2 was evaluated with benzothiazoles 1 and
sulfur in DMSO at 130 °C under oxygen atmosphere in
SYNTHESIS 2013, 45, 1247–1255
Advanced online publication: 04.04.2013
DOI: 10.1055/s-0032-1316891; Art ID: SS-2013-H0072-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1248
X. Wang et al.
PAPER
Table 1 Optimization of Thiolation Conditionsa
I
S
S
N
S, [Cu], ligand
+
S
base, solvent
130° C
N
1a
2a
3aa
Entry
[Cu]
Ligand
Base
Solvent
Yield (%)b
1
2
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
Cu (0.1 equiv)
none
none
none
none
none
none
none
none
none
none
none
none
none
none
L1
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (3.0 equiv)
KOH (2.0 equiv)
KOH (6.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
K2CO3 (4.0 equiv)
Cs2CO3 (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
KOH (4.0 equiv)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
15c
40
3
n.r.d
30
4
5
26
6
44
7
20
8
Cu(OAc)2 (0.1 equiv)
nano CuO (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.1 equiv)
CuI (0.3 equiv)
CuI (0.3 equiv)
CuI (0.3 equiv)
CuI (0.3 equiv)
CuI (0.3 equiv)
CuI (0.3 equiv)
<10
30
9
10
11
12
13
14
15
16
17
18
19
n.r
n.r.
n.r.
n.r.
74
xylenes
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
87
L2
81
L3
48
L4
84
L5
79
a Reaction conditions: benzothiazole (0.3 mmol), iodobenzene (0.5 mmol), sulfur (0.6 mmol), base (1.2 mmol), [Cu] (0.1–0.3 equiv), ligand
(0.3 equiv), solvent (1.0 mL), 130 °C (oil bath temperature), stirred for 7 h under oxygen atmosphere.
b Isolated yield. n.r. = no reaction.
c Under air atmosphere.
d Under argon atmosphere.
the presence of 4 equivalents of KOH catalyzed by 30 The reaction yield dropped to 75% when the 2-iodonaph-
mol% CuI and 1,10-phenanthroline (Table 2). The corre- thalene instead of iodobenzene was used as substrate (Ta-
sponding products 3 were obtained in moderate to excel- ble 2, entry 14). Unfortunately, only 38% corresponding
lent yields (38–96%). In general, the thiolation reactions product was formed with the iodobenzene containing a tri-
of benzothiazole with para-substituted iodobenzenes fluoromethyl group (Table 2, entry 16). Moreover, bro-
were easier than those with ortho-substituted and meta- mobenzene could not react with benzothiazole under the
substituted iodobenzenes (Table 2, entries 2–7). It was conditions (Table 2, entry 17). The substituted benzothia-
shown that electron-donating substituent in iodobenzenes zole also could react well with iodobenzene and their de-
decreased the reaction yield slightly (Table 2, entry 8). rivatives under the optimal conditions (Table 2, entries
However, all halogen-substituted iodobenzenes could re- 18–22). Meanwhile, no product was detected when benz-
act with benzothiazole and sulfur smoothly in good yields oxazole was reacted with iodobenzene and sulfur in super-
(Table 2, entries 9–13); the best result was observed using base system (Table 2, entry 23).
4-fluroiodobenzene as the substrate (Table 2, entry 15).
Synthesis 2013, 45, 1247–1255
© Georg Thieme Verlag Stuttgart · New York

PAPER
Direct Thiolation of Benzothiazole in Superbase System
1249
Table 2 Synthesis of 2-Thio-Substituted Benzothiazoles via CuI-Catalyzed Direct C–H Thiolation of Benzothiazoles in Superbase Systema
X
S
Z
S, CuI, 1,10-phen
S
R1
+
KOH, DMSO
130 °C, O2
N
R1
N
R2
2
1
R2
Z = S, O
X = Br, I
3
Entry
1
Heterocycles
ArX
2a
Product
Yield (%)b
S
N
I
S
S
87
N
1a
3aa
3ab
3ac
S
N
I
S
2
3
1a
1a
71
84
2b
S
N
I
S
2c
S
N
S
I
4
1a
88
2d
3ad
3ae
3af
S
N
I
S
S
S
OMe
5
6
1a
1a
54
77
OMe
2e
S
N
MeO
I
OMe
2f
S
N
I
7
1a
1a
85
78
MeO
OMe
2g
3ag
3ah
S
N
S
I
8
EtO
OEt
2h
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1247–1255

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X. Wang et al.
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Table 2 Synthesis of 2-Thio-Substituted Benzothiazoles via CuI-Catalyzed Direct C–H Thiolation of Benzothiazoles in Superbase Systema
(continued)
X
S
Z
S, CuI, 1,10-phen
S
R1
+
KOH, DMSO
130 °C, O2
N
R1
N
R2
2
1
R2
Z = S, O
X = Br, I
3
Entry
9
Heterocycles
ArX
Product
Yield (%)b
S
N
I
S
S
S
Cl
1a
90
Cl
2i
3ai
3aj
S
N
Cl
I
10
11
1a
1a
95
91
Cl
2j
S
N
I
Cl
Cl
2k
3ak
S
N
S
I
12
1a
87
Br
Br
Cl
2l
3al
S
N
Cl
S
I
13
14
1a
1a
94
75
Cl
Cl
2m
3am
3an
S
N
I
S
2n
S
N
S
I
15
1a
96
F
F
2o
3ao
Synthesis 2013, 45, 1247–1255
© Georg Thieme Verlag Stuttgart · New York

PAPER
Direct Thiolation of Benzothiazole in Superbase System
1251
Table 2 Synthesis of 2-Thio-Substituted Benzothiazoles via CuI-Catalyzed Direct C–H Thiolation of Benzothiazoles in Superbase Systema
(continued)
X
S
Z
S, CuI, 1,10-phen
S
R1
+
KOH, DMSO
130 °C, O2
N
R1
N
R2
2
1
R2
Z = S, O
X = Br, I
3
Entry
16
Heterocycles
ArX
Product
Yield (%)b
S
N
F3C
I
S
S
1a
38
CF3
2p
2q
2a
3ap
S
N
17
18
19
20
21
1a
0
Br
3aq
O2N
S
I
O2N
S
S
N
N
41
54
83
70
1b
3ba
Cl
S
N
S
N
I
S
S
S
S
Cl
2a
1c
3ca
Cl
S
N
I
Cl
1c
1c
Cl
2i
3ci
S
N
Cl
I
Cl
Cl
2j
3cj
S
N
I
Cl
22
1c
88
F
F
2o
3co
O
N
I
O
S
23
0
N
1d
2a
3da
a Reaction conditions: benzothiazole (0.3 mmol), iodobenzene (0.5 mmol), sulfur (0.6 mmol), CuI (0.09 mmol), 1,10-phenanthroline (0.09
mmol), KOH (1.2 mmol), DMSO (1.0 mL), 130 °C, stirred for 7 h under oxygen atmosphere.
b Isolated yield.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1247–1255

1252
X. Wang et al.
PAPER
IR (KBr): 3060, 1582, 1457, 1424, 1307, 1263, 1080, 1015, 752
cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.74 (d,
J = 7.1 Hz, 2 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.49 (dd, J = 16.2, 7.4
Hz, 3 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.27 (t, J = 7.5 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 168.53, 152.92, 134.57, 134.30,
129.41, 129.00, 128.89, 125.14, 123.31, 120.96, 119.76.
The reaction mechanism was proposed according to some
related reactions reported in literature.6 Firstly iodoben-
zene was readily transformed to diphenyl disulfide under
superbase conditions in the presence of sulfur.5a The prod-
uct could be detected clearly by GC. At the same time, the
deprotonation of benzothiazole by KOH occurs at the C-2
position, followed by cupration via transmetalation. Then
the copper species (A) reacted with diphenyl disulfide to
form the product and the copper species (B), which could
be oxidized by oxygen to copper(II) complex (C).6a The
intermediate (C) could react with benzothiazole to gener-
ate the complex (D), which was converted to the product
after the reductive elimination. Meanwhile, copper(0) was
oxygenated to copper(I) to finish the catalytic cycle
(Scheme 2).
MS (EI): m/z = 243 [M]+.
2-o-Tolylsulfanylbenzothiazole (3ab)
Yield: 54.8 mg (71%); yellow oil.
IR (KBr): 2963, 1580, 1512, 1455, 1419, 1261, 1019, 801, 699
cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.87 (d, J = 8.2 Hz, 1 H), 7.74 (d,
J = 7.7 Hz, 1 H), 7.63 (d, J = 7.9 Hz, 1 H), 7.45 (t, J = 7.1 Hz, 1 H),
7.42–7.37 (m, 2 H), 7.31 (t, J = 7.4 Hz, 1 H), 7.25 (t, J = 7.2 Hz, 1
H), 2.52 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 169.90, 154.16, 143.22, 137.07,
135.49, 131.43, 131.23, 129.23, 127.41, 126.09, 124.12, 121.82,
120.74, 20.87.
MS (EI): m/z = 257 [M]+.
HRMS (ESI): m/z calcd for C14H11NS2 ([M + H]+): 258.0408;
ArH, KOH
O2, I–
KI, H2O
CuI
Cu
Ar-Cu (A)
ArSPh
KOH
PhSSPh
ArSPh
+
S
ArI
DMSO
ArCuSPh (D)
KI, H2O
ArH, KOH
found: 258.0406.
2-m-Tolylsulfanylbenzothiazole (3ac)
Yield: 64.8 mg (84%); yellow oil.
PhSCu (B)
PhSCuI
(C)
IR (KBr): 2963, 1580, 1512, 1458, 1425, 1262, 1086, 1018, 799,
752 cm–1.
I–, O2
1H NMR (600 MHz, CDCl3): δ = 7.88 (d, J = 8.2 Hz, 1 H), 7.66 (d,
J = 7.9 Hz, 1 H), 7.59–7.50 (m, 2 H), 7.39 (dt, J = 21.3, 7.6 Hz, 2
H), 7.32 (d, J = 7.6 Hz, 1 H), 7.27 (t, J = 7.5 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 169.93, 153.98, 139.96, 135.83,
135.59, 132.33, 131.26, 129.70, 129.67, 126.11, 124.26, 121.95,
120.75, 21.25.
MS (EI): m/z = 257 [M]+.
HRMS (ESI): m/z calcd for C14H11NS2 ([M + H]+): 258.0410;
Scheme 2 Plausible catalytic cycle of the thiolation
In conclusion, we have developed a new approach to pre-
pare 2-thio-substituted benzothiazoles 3 starting from
benzothiazoles 1, iodobenzenes 2, and sulfur in high
yields. The C–H bond of benzothiazole and their deriva-
tives was activated directly in the catalytic system. The di-
sulfide was formed in situ under superbase conditions,
which can be considered as an environmentally benign
process.
found: 258.0406.
2-p-Tolylsulfanylbenzothiazole (3ad)3b
Yield: 67.8 mg (71%); yellow oil.
1H NMR and 13C NMR spectra were recorded on Bruker Avance
600 and Bruker Avance 400 spectrometer in CDCl3 with TMS as an
internal standard. IR spectra were recorded on a Bruker Tensor 27
FT-IR spectrophotometer using KBr pellets. GC-MS was per-
formed on a Finnigan Trace DSQ chromatograph. High-resolution
mass spectra were obtained on UHR-TOF MAXis. Petroleum ether
(PE) used refers to the fraction boiling in the 60–90 °C range.
IR (KBr): 2961, 2860, 1574, 1456, 1424, 1261, 1019, 803, 736
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.70–
7.57 (m, 3 H), 7.41 (t, J = 7.7 Hz, 1 H), 7.31 (d, J = 7.9 Hz, 2 H),
7.28 (t, J = 3.7 Hz, 1 H), 2.46 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.79, 159.95, 154.05, 137.40,
135.63, 132.68, 125.95, 124.04, 121.83, 121.52, 120.66, 117.87,
111.99, 56.05.
Thiolation of Benzothiazole; 2-Phenylsulfanylbenzothiazole
(3aa);3a Typical Procedure
MS (EI): m/z = 257 [M]+.
Sulfur (19.2 mg, 0.6 mmol), CuI (17.2 mg, 0.09 mmol), 1,10-phen-
anthroline monohydrate (17.8 mg, 0.09 mmol), and KOH (67.2 mg,
1.2 mmol) were added to a solution of DMSO (1.0 mL) charged
with iodobenzene (2a; 102 mg, 0.5 mmol) and benzothiazole (1a;
41 mg, 0.3 mmol) under oxygen atmosphere. The reaction mixture
was stirred at 130 °C for 7 h. The progress of the reaction was mon-
itored by TLC (EtOAc–PE, 1:20). After completion of the reaction,
the mixture was partitioned between H2O (5 mL) and EtOAc (10
mL). The organic and aqueous layers were then separated, and the
aqueous layer was extracted with EtOAc (3 × 8 mL). The combined
organic extracts were dried (Na2SO4), then the solvent was removed
in vacuo, and the remaining residue was purified by silica gel col-
umn chromatography (eluent: EtOAc–PE, 1:30) to afford 3aa as a
yellow oil; yield: 63.5 mg (87%).
2-o-Methoxyphenylsulfanylbenzothiazole (3ae)7
Yield: 44.3 mg (54%); yellow oil.
IR (KBr): 2963, 1661, 1609, 1530, 1476, 1448, 1261, 1063, 1024,
800, 747, 685 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.87 (d, J = 8.1 Hz, 1 H), 7.70 (dd,
J = 7.5, 1.6 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.52 (td, J = 8.1, 1.7
Hz, 1 H), 7.43–7.35 (m, 1 H), 7.25 (dd, J = 11.1, 4.1 Hz, 1 H), 7.05
(t, J = 7.9 Hz, 2 H), 3.86 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.90, 154.16, 143.22, 137.07,
135.49, 131.43, 131.23, 129.23, 127.41, 126.09, 124.12, 121.82,
120.74, 20.87.
MS (EI): m/z = 273 [M]+.
Synthesis 2013, 45, 1247–1255
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Direct Thiolation of Benzothiazole in Superbase System
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2-m-Methoxyphenylsulfanylbenzothiazole (3af)
Yield: 63.1 mg (77%); yellow oil.
2-p-Chlorophenylsulfanylbenzothiazole (3ak)3o
Yield: 75.6 mg (91%); yellow oil.
IR (KBr): 2963, 1583, 1458, 1423, 1260, 1094, 1020, 801, 691
cm–1.
IR (KBr): 2963, 1572, 1460, 1424, 1261, 1091, 1017, 802, 696
cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.67 (d,
J = 8.0 Hz, 1 H), 7.45–7.36 (m, 2 H), 7.32 (d, J = 7.6 Hz, 1 H), 7.28
(d, J = 7.1 Hz, 2 H), 7.05 (dd, J = 8.2, 2.4 Hz, 1 H), 3.84 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 169.33, 160.40, 153.92, 135.64,
130.91, 130.66, 127.30, 126.15, 124.37, 122.02, 120.80, 120.04,
116.63, 55.50.
MS (EI): m/z = 273 [M]+.
HRMS (ESI): m/z calcd for C14H11NOS2 ([M + H]+): 274.0355;
1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.67 (dd,
J = 11.3, 8.3 Hz, 3 H), 7.49–7.36 (m, 3 H), 7.29 (t, J = 7.6 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 168.20, 153.82, 136.91, 136.36,
135.59, 130.13, 128.46, 126.27, 124.55, 122.11, 120.84.
MS (EI): m/z = 277 [M]+.
2-p-Bromophenylsulfanylbenzothiazole (3al)3o
Yield: 83.8 mg (87%); yellow oil.
IR (KBr): 2963, 1573, 1456, 1423, 1262, 1016, 803, 696 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.80 (d,
J = 8.2 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.63–7.56 (m, 2 H), 7.43
(dd, J = 18.1, 8.0 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 1 H).
found: 274.0355.
2-p-Methoxyphenylsulfanylbenzothiazole (3ag)3a
Yield: 69.6 mg (85%); yellow oil.
IR (KBr): 2961, 1586, 1493, 1457, 1425, 1294, 1251, 1014, 828,
755 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.86 (d, J = 8.2 Hz, 1 H), 7.65 (dd,
J = 18.8, 8.3 Hz, 3 H), 7.39 (t, J = 7.4 Hz, 1 H), 7.24 (t, J = 7.6 Hz,
1 H), 7.00 (d, J = 8.7 Hz, 2 H), 3.98–3.80 (m, 3 H).
13C NMR (150 MHz, CDCl3): δ = 167.91, 139.07, 136.48, 136.44,
135.62, 133.11, 130.01, 129.15, 126.29, 125.11, 124.60, 122.15,
120.86.
MS (EI): m/z = 321 [M]+.
13C NMR (150 MHz, CDCl3): δ = 170.79, 160.72, 153.20, 136.55,
134.45, 125.07, 123.06, 120.79, 119.72, 119.28, 114.51, 54.46.
2-(2,4-Dichlorophenylsulfanyl)benzothiazole (3am)
Yield: 83.8 mg (94%); yellow oil.
MS (EI): m/z = 273 [M]+.
IR (KBr): 2963, 1567, 1454, 1424, 1261, 1096, 1020, 806, 758
cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 1 H), 7.74–
7.70 (m, 2 H), 7.59 (d, J = 2.1 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 1 H),
7.36–7.30 (m, 2 H).
13C NMR (150 MHz, CDCl3): δ = 165.65, 153.73, 139.62, 137.43,
137.32, 135.83, 130.67, 128.29, 128.25, 126.33, 124.80, 122.34,
120.94.
MS (EI): m/z = 310 [M]+.
HRMS (ESI): m/z calcd for C13H7Cl2NS2 ([M + H]+): 311.9471;
2-p-Ethoxyphenylsulfanylbenzothiazole (3ah)
Yield: 67.2 mg (78%); yellow oil.
IR (KBr): 2964, 1591, 1456, 1423, 1260, 1092, 1022, 800, 664
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.73 (d, J = 8.1 Hz, 1 H), 7.51 (dd,
J = 8.1, 5.9 Hz, 3 H), 7.25 (dd, J = 11.3, 4.1 Hz, 1 H), 7.15–7.08 (m,
1 H), 6.86 (d, J = 8.7 Hz, 2 H), 3.97 (q, J = 7.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 161.12, 154.18, 137.54, 135.42,
126.04, 124.02, 121.74, 120.70, 119.97, 115.95.
found: 311.9470.
MS (EI): m/z = 287 [M]+.
HRMS (ESI): m/z calcd for C15H13NOS2 ([M + H]+): 288.0511;
2-(1-Naphthylsulfanyl)benzothiazole (3an)
Yield: 65.9 mg (75%); yellow oil.
found: 288.0511.
IR (KBr): 2957, 2923, 2860, 1567, 1502, 1457, 1425, 1376, 1263,
1013, 800, 763, 727, 668 cm–1.
1H NMR (600 MHz, CDCl3): δ = 8.50 (dd, J = 6.1, 3.5 Hz, 1 H),
8.12–8.05 (m, 2 H), 7.94 (dd, J = 6.0, 3.4 Hz, 1 H), 7.89 (d, J = 8.2
Hz, 1 H), 7.59–7.55 (m, 3 H), 7.53 (d, J = 8.0 Hz, 1 H), 7.39 (t, J =
7.6 Hz, 1 H), 7.21 (t, J = 7.6 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 169.95, 153.94, 136.34, 135.60,
134.54, 134.34, 132.13, 128.76, 127.88, 126.93, 126.06, 125.90,
125.52, 124.13, 121.84, 120.71.
2-o-Chlorophenylsulfanylbenzothiazole (3ai)7
Yield: 74.8 mg (90%); yellow oil.
IR (KBr): 2963, 1571, 1454, 1419, 1261, 1014, 800, 699 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.91 (d, J = 8.2 Hz, 1 H), 7.80 (d,
J = 7.7 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H),
7.44 (dt, J = 12.6, 7.6 Hz, 2 H), 7.36 (t, J = 7.6 Hz, 1 H), 7.30 (t, J =
7.5 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 166.79, 153.84, 138.96, 136.97,
135.84, 131.69, 131.03, 129.65, 127.92, 126.21, 124.58, 122.24,
120.87.
MS (EI): m/z = 293 [M]+.
HRMS (ESI): m/z calcd for C17H11NS2 ([M + H]+): 294.0407;
MS (EI): m/z = 277 [M]+.
found: 293.0406.
2-m-Chlorophenylsulfanylbenzothiazole (3aj)3b
Yield: 79.8 mg (96%); yellow oil.
2-p-Fluorophenylsulfanylbenzothiazole (3ao)
Yield: 75.2 mg (96%); yellow oil.
IR (KBr): 2963, 1573, 1457, 1424, 1261, 1094, 1016, 800, 727
cm–1.
IR (KBr): 2963, 1588, 1489, 1458, 1424, 1261, 1092, 1020, 800,
756 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.91 (d, J = 8.2 Hz, 1 H), 7.77–
7.67 (m, 2 H), 7.61 (d, J = 7.7 Hz, 1 H), 7.49–7.38 (m, 3 H), 7.31 (t,
J = 7.6 Hz, 1 H).
1H NMR (300 MHz, CDCl3): δ = 7.87 (d, J = 8.1 Hz, 1 H), 7.73 (dd,
J = 8.8, 5.2 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 1 H), 7.45–7.37 (m, 1 H),
7.31–7.27 (m, 1 H), 7.18 (t, J = 8.6 Hz, 2 H).
13C NMR (150 MHz, CDCl3): δ = 167.26, 153.74, 135.73, 135.38,
134.40, 132.80, 131.95, 130.80, 130.38, 126.31, 124.70, 122.25,
120.89.
13C NMR (100 MHz, CDCl3): δ = 164.22 (d, J = 250.5 Hz), 153.94
(s), 137.72 (d, J = 8.7 Hz), 135.51 (s), 126.24 (s), 125.19 (d, J = 3.2
Hz), 124.42 (s), 122.01 (s), 120.81 (s), 117.32 (s), 117.10 (s).
MS (EI): m/z = 277 [M]+.
MS (EI): m/z = 261 [M]+.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1247–1255

1254
X. Wang et al.
PAPER
HRMS (ESI): m/z calcd for C13H8FNS2 ([M + H]+): 262.0154;
found: 262.0155.
13C NMR (150 MHz, CDCl3): δ = 170.00, 154.54, 135.47, 134.72,
133.76, 133.12, 132.34, 131.21, 130.92, 130.74, 125.01, 121.94,
121.50.
MS (EI): m/z = 311 [M]+.
HRMS (ESI): m/z calcd for C13H7Cl2NS2 ([M + H]+): 311.9481;
2-m-Trifluoromethylphenylsulfanylbenzothiazole (3ap)3i
Yield: 35.5 mg (38%); yellow oil.
IR (KBr): 2963, 1457, 1418, 1322, 1261, 1098, 1021, 800, 695
cm–1.
found: 311.9470.
1H NMR (300 MHz, CDCl3): δ = 8.00 (s, 1 H), 7.91 (d, J = 8.0 Hz,
2 H), 7.73 (dd, J = 10.4, 8.2 Hz, 2 H), 7.60 (t, J = 7.8 Hz, 1 H), 7.48–
7.39 (m, 1 H), 7.35–7.27 (m, 1 H).
13C NMR (150 MHz, CDCl3): δ = 166.70 (s), 153.65 (s), 137.91 (s),
135.64 (s), 132.25 (q, J = 32.6 Hz), 131.57 (s), 131.34 (d, J = 4.8
Hz), 130.28 (s), 126.87 (d, J = 3.6 Hz), 126.39 (s), 124.82 (s),
123.38 (q, J = 271.8 Hz), 122.27 (s), 120.94 (s).
5-Chloro-2-p-fluorophenylsulfanylbenzothiazole (3co)
Yield: 78.1 mg (88%), yellow solid; mp 95–96 °C.
IR (KBr): 3057, 2964, 2928, 1583, 1542, 1484, 1451, 1422, 1290,
1261, 1221, 1148, 1671, 1012, 896, 802, 514 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.73 (dd, J = 8.3, 5.3
Hz, 2 H), 7.55 (d, J = 8.5 Hz, 1 H), 7.24 (d, J = 8.5 Hz, 1 H), 7.19
(t, J = 8.4 Hz, 2 H).
13C NMR (150 MHz, CDCl3): δ = 171.92 (s), 164.30 (d, J = 251.0
Hz), 154.72 (s), 137.88 (d, J = 8.85 Hz), 133.58 (s), 132.22 (s),
124.71 (s), 124.58 (d, J = 3.60 Hz), 121.72 (s), 121.41 (s), 117.39
(s), 117.25 (s).
MS (EI): m/z = 311 [M]+.
6-Nitro-2-phenylsulfanylbenzothiazole (3ba)3a
Yield: 35.5 mg (41%); yellow solid; mp 87–88 °C.
IR (KBr): 3058, 2963, 2924, 1571, 1517, 1470, 1332, 1263, 1047,
1017, 817, 745 cm–1.
1H NMR (600 MHz, CDCl3): δ = 8.55 (d, J = 2.0 Hz, 1 H), 8.27 (dd,
J = 9.0, 2.1 Hz, 1 H), 7.90 (d, J = 9.0 Hz, 1 H), 7.77 (d, J = 7.4 Hz,
2 H), 7.59 (d, J = 7.4 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 2 H).
MS (EI): m/z = 295 [M]+.
HRMS (ESI): m/z calcd for C13H7ClFNS2 ([M + H]+): 295.9779;
found: 295.9765.
13C NMR (150 MHz, CDCl3): δ = 177.59, 157.82, 144.13, 135.75,
135.56, 131.33, 130.33, 128.53, 121.92, 121.71, 121.18, 117.35,
117.15.
Acknowledgment
This work was supported by the Priority Academic Program Deve-
lopment of Jiangsu Higher Education Institutions.
MS (EI): m/z = 288 [M]+.
5-Chloro-2-phenylsulfanylbenzothiazole (3ca)
Supporting Information for this article is available online at
Yield: 45.3 mg (54%); yellow solid; mp 87–88 °C.
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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IR (KBr): 3061, 2963, 1582, 1544, 1451, 1424, 1069, 1008, 860,
802, 751, 689, 607 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.65 (d, J = 7.6 Hz,
2 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.15–7.12
(m, 1 H).
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found: 311.9470.
5-Chloro-2-m-chlorophenylsulfanylbenzothiazole (3cj)
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1012, 881, 805, 670 cm–1.
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1247–1255