Novel copper/PEG-400 catalyst systems for chemoselective S- and N-arylation of 2-mercaptobenzothiazole

Article abstract of DOI:10.1016/j.tet.2014.10.075

A novel approach for chemoselective S- and N-arylation of 2-mercaptobenzothiazole was developed by copper/PEG-400 catalyst systems. Copper source and reaction temperature play an important role in this protocol, selective S-arylation of 2-mercaptobenzothiazole was achieved by using CuI/PEG-400/50 °C catalyst system, while selective N-arylation was achieved with CuO/PEG-400/140 °C catalyst system. Both are compatible with a variety of aryl halides and selectively give the desired S- and N-arylation products in good to excellent yields, respectively.

Full text of DOI:10.1016/j.tet.2014.10.075

Accepted Manuscript
Novel copper/PEG-400 catalyst systems for chemoselective S- and N-arylation of 2-
mercaptobenzothiazole
Xiaokang Li, Tangjun Yuan, Yu Yang, Junmin Chen
PII:
S0040-4020(14)01540-3
10.1016/j.tet.2014.10.075
TET 26145
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 16 June 2014
Revised Date: 23 October 2014
Accepted Date: 30 October 2014
Please cite this article as: Li X, Yuan T, Yang Y, Chen J, Novel copper/PEG-400 catalyst systems for
chemoselective S- and N-arylation of 2-mercaptobenzothiazole, Tetrahedron (2014), doi: 10.1016/
j.tet.2014.10.075.
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Novel copper/PEG-400 catalyst systems for chemos lective S- and N- rylation
f 2-
Leave this area blank for abstract info.
mercaptobenzothiazole
a,b
a
a
a *
,
Xiaokang Li , Tangjun Yuan , Yu Yang, Junmin Chen
a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi
330022, China
bKey Laboratory of Organo-pharmaceutical Chemistry, Gannan Normal University, Ganzhou, Jiangxi
34100, China
E-mail: jxnuchenjm@163.com
Tel./fax: +86 0791 8812 0380
S
X
S
CuI (10% mmol),
NaOH (2.0 equiv)
CuO (10% mmol)
KOH (2.0 equiv)
S
N
N
S
N
+
SH
Ar
Ar
S
50-80°C, 24 h
PEG-400
Ar
140°C, 24 h
PEG-400
2a-l
3a-i
x = I; Br
1
18 examples
14 examples
74-93% yields
57-90% yields

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Novel copper/PEG-400 catalyst systems for chemoselective S- and N-arylation of 2-mercaptobenzothiazole
a,b
a
a
a *
,
Xiaokang Li , Tangjun Yuan , Yu Yang, Junmin Chen
a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022,
China
bKey Laboratory of Organo-pharmaceutical Chemistry, Gannan Normal University, Ganzhou, Jiangxi
34100, China
E-mail: jxnuchenjm@163.com
Tel./fax: +86 0791 8812 0380
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel approach for chemoselective S- and N-arylation of 2-
mercaptobenzothiazole was developed by copper/PEG-400 catalyst
systems. Copper source and reaction temperature play an important
Available online
role in this
protocol,
selective S-arylation of 2-
mercaptobenzothiazole was achieved by using CuI/PEG-400/50 °C
catalyst system, while selective N-arylation was achieved with CuO/
PEG-400/140 °C catalyst system. Both are compatible with a
variety of aryl halides and selectively give the desired S- and N-
arylation products in good to excellent yields, respectively.
Keywords:
Copper
Chemoselective
2-Mercaptobenzothiazole
PEG-400
2009 Elsevier Ltd. All rights reserved
.
1. Introduction
development of more effective catalyst systems for
transition-metal-catalyzed cross-coupling reactions,
the substrate scope and generality of these
processes has greatly improved.10 Furthermore,
many chemoselective C-O versus C-N11b,c and C-N
versus C-C10d coupling reactions in the same
substrates can be performed without the need to
employ protecting groups. For example, Buchwald
and workers reported sets of procedures for the Pd-
and Cu-catalyzed chemoselective arylation of
In the last decades, transition-metal-catalyzed
carbon-carbon
and
carbon-heteroatom bond
coupling reaction constitutes an important
methodology,1 which has vast applications in
pharmaceuticals, materials science as well as in the
synthesis of biologically active compounds.2-9
However, as for substrates with multiple
heteroatom sites capable of undergoing reaction,
the desirable coupling reaction compounds were
not frequently obtained. Recently, with the
aminobenzamides,11a
5-aminoindole,11a
4-(2-

2
Tetrahedron
11b
18
aminoethyl)aniline,11a
amino
alcohols, , anticancer agents.
Some therapeutic agents
ACCEPTED MANUSCRIPT
aminophenols11c and oxindoles.11d Recently, containing this core structure include potent heat
Buchwald have developed a catalyst-controlled shock protein-90 inhibitors19 and an inhibitor of
protocol for chemoselective N-arylations of 2- Cathepsin-D.20 They also act as antimicrobial
aminobenzimidazoles and related aminoazoles,
agents especially against Piricularia oryzae and
wherein selective N-arylation of the amino group Xanthomonasoryzae.21 Furthermore, 3-amino-
with a Pd-catalyzed method, while selective N- substituted mercaptobenzothiazoles such as 3-aryl-
arylation of azole nitrogen with a Cu-catalyzed 2-benzothiazolthions are a kind of important
procedure.12
organic intermediates22 and important redox-active
Although
transition-metal-catalyzed
compounds with broad chemical, material, and
chemoselective carbon-carbon versus carbon- biomedical applications. For example, 2,2'-azino-
heteroatom bond coupling reactions show some bis(3-ethylbenzothiazoline-6-sulphonic acid)
advantages, some specific ligands and different (ABTS) and its derivatives have been used as the
transition-metals were required, importantly, the electrochromic component in smart windows,23 as a
resulting chemoselectivities were generally low.13 chromogenic substrate in assays for enzymatic
On the other hand, the chemoselective C-N versus activity,24 and as a mediator for electron transfer in
C-S coupling reactions in the same substrates is a bioelectrocatalysis.25 Although 2-thio-substituted
relatively unexplored area and the N- and S- mercaptobenzothiazoles play an important role in
arylated products constitute a common structural
the field of pharmaceutical science, the available
motif in various potentially useful therapeutic synthetic methods for these compounds are very
agents and/or drug candidates.14 They have also limited. Two typical methods have generally been
been applied as building blocks for the preparation
of organic materials.15 Thus, it is desired to exploit mercaptobenzothiazoles. One by the nucleophilic
a simple and efficient catalyst system for attack of arylthiols with preformed 2-
chemoselective C-N versus C-S coupling reactions halobenzothiazoles and the second by
in the same substrates in view of green and nucleophilic attack of mercapto-benzothiazole upon
sustainable chemistry. haloarenes containing electron-withdrawing
The 1,3-benzothiazole derivatives are an substituents under strongly basic conditions.26
important class of molecules and are a common Alternatively, Wang developed a method for the
heterocyclic scaffold in biologically active and synthesis of 2-arylthiobenzothiazoles by the thio-
applied for the elaboration of 2-thio-substituted
a
a
medicinally significant compounds.16 Particularly,
arylation
of
benzothiazol-2-thiol
with
several 2-thio-substituted mercaptobenzothiazoles
diaryliodonium salts in an ioinic liquid
such as 2-arylthiobenzothiazoles have received [bmim]BF.27 Recent approaches have focused on
much attention due to their unique structure and its the use of transition-metal (Cu, Pd, and Fe)-
uses as radioactive amyloid imagining agents,17 and catalyzed, intermolecular, C-S bond formations for

3
ACCEPTED MANUSCRIPT
the synthesis of 2-(arylthio)-1,3-benzothiazoles
under milder conditions with better efficiency and decrease to 38% (Table 1, entry 2). Further
selectivity.28 Additionally, Patel developed a single
decreasing the temperature to 100 °C and 80 °C, the
catalytic system for two sequential intra- and yields of the S-arylation coupling reaction was
intermolecular S-arylations leading to a direct increased to 51% and 78%, respectively (Table 1,
synthesis of 2-arylthiobenzothiazoles from entries 3 and 4). However, under the same
with 46% yield, while the yield of 3a was
dithiocarbamates.29 However, specific ligand and conditions, lowering of the reaction temperature (50
transition metal were needed for obtaining high °C) led to low conversion. Gratifyingly, the yield of
yields. Furthermore, to the best of our knowledge, S-arylation product was increased to 89% through
the
synthesis
of
3-animo-substituted
longer reaction time to 24 h, only small amounts of
N-arylation product was detected (Table 1, entry 5).
mercaptobenzothiazoles has not so far been
reported. In a continuation of our endeavors to When the reaction was carried out using different
develop copper-catalyzed carbon-heteroatom bonds copper salts such as CuCl2, CuSO4, and CuO,
cross-coupling reactions in PEG-400,30 we, herein, affording the S-arylation and N-arylation products
report
a
novel Cu-catalyzed chemoselective in very low yields (Table 1, entries 6-8). Then,
condition for S- or N-arylation of unprotected 2- various bases were also screened at the above same
mercaptobenzothiazole with aryl halides using
different copper salts, bases, and varied
temperatures.
reaction condition, moderate yield was obtained
using KOH as base (Table 1, entry 9), while K3PO4,
K2CO3 or NaOAc as bases afforded the S- and N-
arylation products in lower yields (table 1, entries
2. Results and discussion
The optimization of the reaction conditions was 10-12).
carried out with 2-mercaptobenzothiazole 1 and Table 1: Reaction optimization
S
N
iodobenzene as model substrates using different
I
S
2a
S
copper sources and bases at varied temperatures in
[Cu], base
or
SH
+
N
S
N
temp., 15-24h
PEG-400
Table 1. Initially, the reaction was conducted under
the action of 10 mol % of CuI, and two equivalent
of NaOH in PEG-400 at 140 °C. It was found that
most of the 2-mercaptobenzothiazole was
consumed after 15 h. Unexpectedly, the desired
product of the S-arylation coupling reaction, 2a,
was obtained in only 41% yield, together with the
corresponding N-arylation product, 3a (47% yield
on the basis of 1 used, Table 1, entry 1). To our
delight, decreasing the temperature of the coupling
reaction to 120 °C resulted the S-arylation product
S
1
3a
Entry
[Cu]
base
Temp
(ꢀ)
140
120
100
80
Yieldb(%)
a
1
2
3
4
5
6
7
CuI
CuI
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
2a/41, 3a/47
2a/46, 3a/38
2a/51, 3a/29
2a/78, 3a/11
2a/89, 3a/7
2a/<5, 3a/3
2a/15, 3a/6
CuI
CuI
CuI
50
50
50
CuCl2
CuSO4

4
Tetrahedron
ACCEPTED MANUSCRIPT
Next, we firstly explored the scope of the Cu-
8
9
CuO
CuI
NaOH
KOH
50
50
2a/16, 3a/10
2a/68, 3a/19
2a+3a /<5
catalyzed chemoselective S-arylation of 2-
mercaptobenzothiazole using 10 mol% CuI, 200
mol% NaOH as the base, and PEG-400 as the
solvent at temperatures 50 °C for 24h. Our catalytic
system efficiently promotes highly chemoselective
S-arylation cross-coupling reactions between 2-
mercaptobenzothiazole and aryl halides with either
10
11
12
13
14
15
16
17
CuI
K3PO4
K2CO3
NaOAc
KOH
50
CuI
50
2a+3a /<5
CuI
50
2a+3a /<5
CuI
140
140
140
140
140
2a/12, 3a/61
2a/16, 3a/81
2a/13, 3a/15
2a/19, 3a/12
2a/11, 3a/8
CuO
CuCl2
Cu(NO3)2
Cu2SO4
KOH
KOH
KOH
KOH
electron-donating
or
electron-withdrawing
a
2-Mercaptobenzothiazole (1.0 mmol), iodobenzene (1.1
substituents, thus giving the corresponding S-
arylation products in 74-93 % yields upon isolation
(Table 2, entries 1-18). Particularly interesting was
that ortho-substituted aryl iodides provided better
yields than para- and meta- substituted aryl halides
(Table 2, entries 2 vs 5; 10 vs 12 or 13),
presumably because of the steric effect on S-
arylation. A heterocyclic compound, such as 2-
iodothiophene, could also afford the corresponding
S-arylation products in 89% yield (Table 2, entry
7). However, some electron-deficient aryl bromides
such as p-fluoro bromobenzene, p-chloro
bromobenzene, and o-chloro bromobenzene
exhibited relatively weak reactivity and also gave
relatively good yields by increasing reaction
temperature to 80 ꢀ (Table 2, entries15-17).
Remarkably, 2-bromo naphthalene also proved to
be good substrate in the reaction, giving the desired
product in satisfactory yield (Table 2, entry 18). It
was worth mentioning that the process showed
good functional group compatibility (Table 2,
entries15-17).
mmol), copper salt (10 mol%), base (2.0 mmol), PEG-400
(2.0 mL), entries 1-4 for 15 h, others for 24h.
b
Yield of isolated product based on 2-
mercaptobenzothiazole, average of two runs.
Finally, by a systematic variation of the reaction
parameters we establish CuI/PEG-400/50 °C an
effective catalytic system for chemoselective S-
arylation of 2-mercaptobenzothiazole.
Then, we turned our attention to finding
conditions for the selective formation of the N-
arylation product. Obviously, higher reaction
temperature was of great benefit to the N-arylation.
Unexpectedly, switching the base to KOH provided
an improved yield (Table 1, entries 1 vs 13). Thus,
we selected KOH as the base at 140 °C in the
following studies. The effect of the copper salts on
this reaction was evaluated, we found that copper
salt also plays a crucial role for this coupling
reaction, as is evident from CuO affording 81%
yield (Table 1, entries 14), while a moderate yield
was observed in the case of CuI, and a relatively
low yield was observed when CuCl2, Cu(NO3)2 or
Cu2SO4 were employed (Table 1, entries 15-17).
Finally, we established that CuO/KOH/140 °C was
an effective catalytic system for chemoselective N-
arylation of 2-mercaptobenzothiazole.
Table 2 Scope of the Cu-catalyzed S-arylation of 2-
mercaptobenzothiazol

5
ACCXEPTED MANUSCRIPT
CuI(10% mmol)
NaOH (200% mmol)
S
S
N
Ar
S
Ar
SH +
50-80°C, 24 h
PEG-400
N
2a-l
1
x = I; Br
Entrya
1
ArX
Product
Yield b(%)
89
S
S
N
I
2a
2
3
4
I
H C
3
S
S
N
86
91
87
CH
32b
I
H3CO
S
S
N
OCH
CH3
3 2c
H C
3
I
S
S
N
2d
2e
OCH
I
3
5
H CO
3
93
S
N
S
6
7
8
I
F
S
82
89
85
S
F 2f
2g
N
S
I
S
S
S
N
Br
S
N
S
2a
9
S
N
87
87
91
S
CH
Br
H C
3
32b
10
11
S
S
OCH
Br
H3CO
3 2c
N
CH
H C
3
3
S
S
Br
N
2d
12
OCH3
H CO
3
89
S
S
Br
N
2h

6
Tetrahedron
ACCEPTED MANUSCRIPT
13
14
H CO
OCH
3
3
91
90
S
S
N
Br
2e
CH
CH
H3C
3
S
N
S
Br
3
2i
H3C
F
15c
16c
17c,
S
80
84
85
F 2f
S
Br
Br
N
S
N
Cl 2j
S
Cl
Cl
Cl
S
S
Br
N
2k
2l
18c
Br
74
S
N
S
a Reaction condiction: 2-mercaptobenzothiazole (1.0 mmol), aryl halide (1.1 mmol), NaOH (2.0 mmol), CuI (10 mol%),
PEG-400 (2.0 mL), 50 ꢀ, 24 h under N2.
b Yield of isolated product based on 2-mercaptobenzothiazole, average of two runs.
c Reaction temperature at 80 ꢀ,24 h.
The scope of the Cu-catalyzed N-selective
arylation was also investigated using 10 mol%
CuO, 200 mol% KOH as the base, and PEG-400 as
the solvent at temperatures 140 °C (Table 3). In
these reactions, we found that reactions of 2-
mercaptobenzothiazole with a variety of electron-
neutral, and -rich aryl halides generally underwent
N-arylation in excellent yields and with high levels
of chemoselectivity (Table 3, entries 1-9).
However, bromonaphthalenes as substrates gave
only moderate yields (58%, 57%, respectively
Table 3, entries 10-11). Electron-deficient aryl
halides, such as p-fluoroiodobenzene, p-
fluorobromobenzene, and p-chlorobromobenzene
afforded good yields (Table 3, entries 12-13), o-
chlorobramobenzene also gave the N-arylation
product in high yield.
Table 3 Scope of the Cu-catalyzed N-arylation of 2-mercaptobenzothiazole
S
CuO (10%mmol)
KOH (200%mmol)
X
S
N
S
N
+
SH
Ar
140°C, 24 h
PEG-400
Ar
1
3a-i

7
Entrya
1
ArX
Product
Yield b(%)
85
ACCEPTED MANUSCRIPT
S
S
I
N
3a
2
3
S
S
H3CO
I
N
81
80
OCH3
3b
S
S
N
H C
I
3
CH3
S
3c
4
5
S
H3C
N
81
87
I
CH3
3d
S
S
N
F
I
F
3e
3a
6
7
S
S
Br
N
90
81
S
N
S
Br
H3C
CH3
3c
8
H C
3
86
Br

8
Tetrahedron
ACCEPTED MANUSCRIPT
S
S
N
CH3
3d
9
S
N
S
H CO
Br
3
83
58
OCH3
3b
10
S
Br
S
N
3e
3f
11
12
S
Br
S
N
57
73
S
N
S
Br
F
F
S
3g
13
14
S
N
Br
Cl
86
80
Cl
3h
S
Cl
S
N
Cl
Br
3i
a Reaction condiction: 2-mercaptobenzothiazole (1.0 mmol), aryl halide (1.1 mmol), KOH (2.0 mmol),
CuO (10 mol%), PEG-400 (2.0 mL), 140 ,24 h under N2.
b Yield of isolated product based on 2-mercaptobenzothiazole, average of two runs.
ꢀ
mercaptobenzothiazole
by
copper/PEG-400
3. Conclusions
We have developed a novel approach for
chemoselective S- and N-arylation of 2-
catalyst systems. Copper source and reaction
temperature play an important role in this protocol,

9
ACCEPTED MANUSCRIPT
selective S-arylation of 2-mercaptobenzothiazole
was achieved by using CuI/PEG-400/50 °C catalyst
system, while selective N-arylation was achieved
with CuO/PEG-400/140 °C catalyst system. Both
are compatible with a variety of aryl halides and
selectively give the desired S- or N-arylation
products in good to excellent yields. Application of
this protocol for other coupling reactions involving
chemoselective S- versus N-arylation and a
detailed mechanistic study are currently under
investigation.
117.17, 115.37. IR (KBr): 3057, 1581, 1458,
1433, 1311, 1235, 1019, 1004, 753 cm-1. HR
EIMS: 243.0153 m/z (calcd for C13H9NS2:
243.0156).
4.1.2. 2-(p-Tolylthio)benzo[d]thiazole (2b).
S
S
CH3
N
1
White solid, M.p. 71-72 °C. H NMR (400MHz,
CDCl3): δ 7.45 (d, J = 8.0 Hz, 1H), 7.25-7.19 (m,
1H), 7.02 (t, J = 7.6 Hz, 4H), 6.78-6.72 (m, 2H),
2.28 (s, 3H); 13C NMR (100MHz, DMSO-d6): δ
169.26, 150.41, 136.97, 135.43, 133.37, 131.15,
130.14, 127.54, 117.13, 115.31, 113.44, 20.93. IR
(KBr): 3064, 2912, 1595, 1426, 1315, 1239, 817,
761 cm-1. HR EIMS: 257.0326 m/z (calcd for
C14H11NS2: 257.0333).
4. Experimental section
4.1. General Procedure A: Cu-catalyzed S-
arylation of 2-mercaptobenzothiazole
A flask equipped a magnetic stirring bar was
charged with 2-mercaptobenzothiazole (1.0 mmol),
aryl halide (1.1 mmol), CuI (0.1 mmol), NaOH (2
mmol) and PEG-400 (2 ml). The reaction mixture
was stirred under a nitrogen atmosphere at 50 °C
for 24 h. The reaction mixture was cooled to room
temperature, diluted with Et2O, washed with brine
and dried over MgSO4. Silica gel (1.0 g) was added
to the mixture and the mixture was concentrated in
vacuo. The silica gel-adsorbed product was
purified through flash chromatography with
petroleum ether/ethyl acetate as eluent to give the
desired S-arylation products.
4.1.3.
2-(4-Methoxyphenylthio)benzo[d]thiazole
(2c).
S
N
S
OCH3
White solid, M.p. 61-63 °C. 1H NMR (400 MHz,
CDCl3): δ 7.84 (d, J = 8.4Hz, 1H), 7.66-7.61 (m,
3H), 7.37 (d, J = 8.0 Hz, 1H), 7.25-7.23 (m, 1H),
7.00-6.98 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H); 13C
NMR (100MHz, CDCl3): δ 171.81, 161.74, 154.22,
137.57, 135.47, 126.10, 124.09, 121.79, 120.76,
120.26, 115.54, 55.49. IR (KBr): 3056, 2922, 1589,
1496, 1453, 1425, 1252, 1003, 833, 758 cm-1. HR
EIMS: 273.0338 m/z (calcd for C14H11NOS2:
273.0341).
4.1.1. 2-(Phenylthio)benzo[d]thiazole (2a)
S
S
N
4.1.4.
2-(3-Methylphenylthio)benzo[d]thiazole
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ
(2d).
7.46 (d, J = 8.0 Hz, 1H), 7.26-7.20 (m, 3H), 7.13-
7.07 (m, 3H), 6.80-6.74 (m, 2H). 13C NMR (100
MHz, DMSO-d6): δ 169.39, 150.84, 137.39,
131.81, 131.44, 129.50, 128.28, 126.73, 125.83,
CH
3
S
N
S
1
White solid, M.p. 87-91°C; H NMR (400 MHz,
CDCl3): δ 7.43 (d, J = 7.6 Hz, 1H), 7.22 (d, J = 7.6

10
Tetrahedron
-1
ACCEPTED MANUSCRIPT
Hz, 1H), 7.103 (t, J = 7.6 Hz, 2H), 6.93 (d, J =
746 cm . HR EIMS: 261.0144. m/z (calcd for
7.6 Hz, 1H), 6.84 (d, J = 11.2 Hz, 1H), 6.82 (d, J =
7.6 Hz, 1H), 6.75 (t, J1 = 7.6 Hz, J2 = 6.8 Hz, 1H),
2.27 (s, 3H); 13C NMR (100 MHz, DMSO-d6): δ
169.02, 150.66, 138.77, 137.31, 136.93, 131.40,
129.34, 127.44, 126.70, 124.04, 117.15, 115.34,
112.63, 21.42. IR (KBr): 3454.60, 2925.87,
1570.31, 1426.05, 1158.26, 1076.87, 950.90,
859.14, 754.50, 546.46. HR EIMS: 257.0328 m/z
(calcd for C14H11NS2: 257.0333).
C13H9FNS2 261.0156).
4.1.7. 2-(2-thiophenylthio)benzo[d]thiazole (2g).
S
S
S
N
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ
7.31-7.29 (m, 2H), 7.19-7.18 (m, 2H), 6.96-6.91
(m, 3H); 13C NMR (100 MHz, DMSO-d6): δ
169.36, 149.11, 134.57, 134.24, 132.82, 130.49,
130.14, 128.21, 117.15, 117.03, 115.42. IR (KBr):
3058, 2947, 1590, 1423, 1237, 813, 754 cm-1. HR
EIMS: 249.3746 m/z (calcd for C11H7NS3:
249.3750).
4.1.5.
2-(2-Methoxyphenylthio)benzo[d]thiazole
(2e).
H CO
3
S
N
S
4.1.8.
2-(3-Methoxyphenylthio)benzo[d]thiazole
1
Colorless liquid, H NMR (400 MHz, CDCl3): δ
7.47 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H),
7.11-7.10 (m, 1H), 6.87-6.77 (m, 4H), 6.66 (d, J =
8.0 Hz, 1H), 3.94 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): δ 169.46, 155.85, 151.10, 137.67,
131.48, 126.60, 126.05, 125.16, 121.47, 117.32,
115.25, 111.36, 111.30, 56.17. IR (KBr): 3061,
2954, 1590, 1428, 1239, 812, 765 cm-1. HR EIMS:
273.0337 m/z (calcd for C14H11NOS2: 273.0341).
(2h).
OCH3
S
N
S
1
Yellow liquid, H NMR (400MHz, CDCl3): δ 7.45
(d, J = 8.0 Hz, 1H), 7.25-7.22 (m, 1H), 7.15-7.11
(m, 1H), 6.79-6.73 (m, 2H), 6.67-6.64 (m, 3H),
3.72 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
160.09, 148.90, 138.29, 137.52, 131.22, 129.81,
118.78, 118.73, 115.37, 114.16, 112.10, 111.03,
55.18. IR (KBr): 3468, 3369, 3063, 2936, 2834,
1609, 1589, 1478, 1247, 1042, 751 cm-1. HR
EIMS: 273.0338 m/z (calcd for C14H11NOS2:
273.0341).
4.1.6. 2-(4-fluorophenylthio)benzo[d]thiazole (2f).
S
S
F
N
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 8.06
(d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.85
(d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.54-
7.47 (m, 1H), 7.45-7.38 (m, 2H), 7.36-7.34 (m,
1H); 13C NMR (100 MHz, DMSO-d6): δ 168.71,
162.26, 159.84, 150.55, 137.10, 132.51, 131.46,
129.34, 117.19, 116.63, 115.42. IR (KBr): 3056,
2923, 1582, 1457, 1433, 1258, 1104, 1015, 813,
4.1.9. 2-(3,5-Dimethylphenylthio)benzo[d]thiazole
(2i).
CH3
S
S
N
CH3
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ
7.45-7.43 (m, 1H), 7.23 (d, J = 12.0 Hz, 1H), 6.79-
6.72 (m, 5H), 2.22 (s, 6H); 13C NMR (100 MHz;

11
ACCEPTED MANUSCRIPT
CDCl3): δ 148.70, 138.67, 137.27, 136.21, 130.87,
127.54, 124.38, 128.66, 115.33, 114.81, 21.27. HR
EIMS: 271.0481 m/z (calcd for C15H13NS2:
271.0489).
8.0 Hz, 1H), 7.51-7.47 (m, 2H), 7.41-7.37 (m,
2H), 7.28-7.21 (m, 2H), 6.81-6.76 (m, 2H); 13C
NMR
(100 MHz, CDCl3): δ 148.90, 137.47, 134.26,
133.84, 131.62, 131.25, 128.70, 127.78, 127.07,
126.60, 125.48, 125.19, 124.41, 118.85, 115.51,
114.35. IR (KBr): 3468, 3371, 3053, 1607, 1479,
1448, 1309, 1063, 851, 813, 747. cm-1. HR EIMS:
293.0327 m/z (calcd for C17H11NS2: 293.0334).
4.2. General Procedure B: Cu-catalyzed N-
arylation of 2-mercaptobenzothiazole
4.1.10.
2-(4-Chlorophenylthio)benzo[d]thiazole
(2j).
S
S
Cl
N
1
Brown liquid, H NMR (400 MHz, CDCl3): δ 7.44
(d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.27-
7.17 (m, 2H), 7.01-6.91 (m, 2H), 6.80-6.74 (m,
2H); 13C NMR (100 MHz, DMSO-d6): δ 169.32,
150.84, 137.45, 136.41, 131.81, 130.36, 129.39,
128.28, 117.21, 115.49, 111.70. IR (KBr): 3470,
3370, 2924, 1608, 1574, 1474, 1309, 1091, 1010,
814, 750 cm-1. HR EIMS: 276.9782 m/z (calcd for
C13H8ClNS2:276.9786).
A flask equipped a magnetic stirring bar was
charged with 2-mercaptobenzothiazole (1.0 mmol),
aryl halide (1.1 mmol), CuO (0.1 mmol), KOH (2
mmol) and PEG-400 (2 ml). The reaction mixture
was stirred under a nitrogen atmosphere at 140 °C
for 24 h. The reaction mixture was cooled to room
temperature, diluted with Et2O, washed with brine
and dried over MgSO4. Silica gel (1.0 g) was added
to the mixture and the mixture was concentrated in
vacuo. The silica gel-adsorbed product was
purified through flash chromatography with
petroleum ether/ethyl acetate as eluent to give the
desired N-arylation products.
4.1.11.
2-(2-Chlorophenylthio)benzo[d]thiazole
(2k).
Cl
S
S
N
1
Brown liquid, H NMR (400 MHz, CDCl3): δ 7.46
(d, J = 12.0 Hz, 1H), 7.35-7.26 (m, 2H), 7.06-7.04
(m, 2H), 6.83-6.78 (m, 2H), 6.65-6.62 (m, 1H); 13C
NMR (100 MHz, DMSO-d6): δ 168.95, 151.31,
137.83, 136.33, 132.21, 130.25, 129.96, 128.07,
126.76, 126.35, 117.45, 115.58, 109.99. IR (KBr):
3485, 3375, 2931, 1607, 1556, 1476, 1301, 1090,
1015, 812, 786, 753 cm-1. HR EIMS: 276.9783 m/z
(calcd for C13H8ClNS2:276.9786).
4.2.1. 3-Phenyl-3H-benzothiazole-2-thione(3a).
S
S
N
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ
7.37-7.33 (m, 4H), 7.31-7.29 (m, 3H), 7.27-7.23
(m, 2H); 13C NMR (100 MHz, DMSO-d6): δ
169.31, 153.87, 135.69, 135.32, 131.38, 130.77,
129.34, 126.89, 124.97, 122.18, 121.87. IR (KBr):
3061, 2924, 2854, 1581, 1476, 1440, 1377, 1081,
4.1.12.
2-(2-Naphthalenylthio)benzo[d]thiazole
(2l).
S
S
N
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 7.75-
7.72 (m, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.63 (d, J =

12
Tetrahedron
-1
S
ACCEPTED MANUSCRIPT
1024, 737, 689, 516. cm . HR EIMS: 243.0152
S
N
m/z (calcd for C13H9NS2: 243.0156).
4.2.2. 3-(4-Methoxy-phenyl)-3H-benzothiazole-2-thione
(3b).
CH3
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.45
(d, J = 8.4 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.10
(d, J = 7.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 2H), 6.87
(d, J = 8.4 Hz, 1H), 6.80-6.76 (m, 2H), 2.27 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 148.66,
138.84, 137.38, 136.50, 131.02, 128.88, 127.20,
126.43, 123.63, 118.78, 115.42, 114.67, 75.88,
21.42. IR (KBr): 3468, 3370, 1609, 1449, 1082,
953, 864, 564, 519. cm-1. HR EIMS: 257.0324 m/z
(calcd for C14H11NS2: 257.0333).
S
S
N
OCH
3
1
White solid, M.p. 57-59ꢀ; H NMR (400 MHz,
CDCl3): δ 7.85 (d, J = 8.0 Hz, 1H), 7.67-7.61 (m,
3H), 7.40-7.36 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H),
6.70 (d, J = 8.0 Hz, 2H), 3.87 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 172.01, 161.73, 154.20,
137.63, 135.41, 126.12, 124.09, 121.76, 120.77,
120.18, 115.54, 55.51. IR (KBr): 3445, 2458, 1642,
1567, 1426, 1161, 1070, 951, 861, 547. cm-1. HR
EIMS: 273.0336 m/z (calcd for C14H11NOS2:
273.0341).
4.2.5.
3-Naphthalen-2-yl-3H-benzothiazole-2-thione
(3e)
S
N
S
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ
4.2.3. 3-p-Tolyl-3H-benzothiazole-2-thione(3c).
7.76-7.62 (m, 3H), 7.51-7.36 (m, 4H), 7.28-7.21
S
S
N
13
(m, 2H), 6.80-6.76 (m, 2H); C NMR (100 MHz,
DMSO-d6): δ 170.45, 150.76, 137.30, 137.24,
134.74, 133.75, 131.58, 129.03, 128.09, 127.24,
127.18, 125.98, 125.63, 124.59, 117.24, 115.48,
112.40. IR (KBr): 3057, 1456, 1425, 1310, 1238,
1020, 1007, 771, 755, 726, 665, 477. cm-1. HR
EIMS: 293.0325 m/z (calcd for C17H11NS2:
293.0334).
CH
3
1
White solid, M.p. 49-50ꢀ; H NMR (400 MHz,
CDCl3): δ 7.44 (d, J = 7.6 Hz, 1H), 7.22 (m, 1H),
7.027 (dd, J = 8.4 Hz, 8Hz, 4H), 6.77 (t, J = 8.0
Hz, 2H), 2.28 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): δ 170.30, 153.98, 141.68, 135.91,
135.24, 131.45, 126.87, 125.74, 124.84, 122.17,
121.17, 21.33. IR (KBr): 3450, 2952, 2451, 1567,
1447, 1160, 951, 860, 547, 521. cm-1. HR EIMS:
257.0325 m/z (calcd for C14H11NS2: 257.0333).
4.2.4. 3-m-Tolyl-3H-benzothiazole-2-thione(3d)
4.2.6.
3-Naphthalen-1-yl-3H-benzothiazole-2-thione
(3f)
S
N
S
Yellow liquid, 1H NMR (400 MHz, CDCl3): δ 8.34
(d, J = 8.0 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.74-

13
Brown liquid, H NMR (400 MHz, CDCl3): δ
1
ACCEPTED MANUSCRIPT
7.38 (m, 5H), 7.26 (d, J = 8.0 Hz,2H), 6.94 (d, J =
7.2 Hz, 1H), 6.79 (s, 2H); 13C NMR (100 MHz,
DMSO-d6): δ 169.34, 153.82, 137.03, 137.02,
135.35, 134.72, 133.99, 132.93, 129.51, 128.71,
127.56, 126.86, 126.14, 125.14, 124.87, 122.16,
121.82. IR (KBr): 3121, 2982, 1659, 1454, 1315,
1285, 1007, 852, 756, 716, 582, 516, 455. cm-1. HR
EIMS: 293.0325 m/z (calcd for C17H11NS2:
293.0334).
7.50-7.43 (m, 1H), 7.43-7.23 (m, 1H), 7.18 (d, J =
8.8 Hz, 2H), 6.70 (d, J = 8.4 Hz, 2H), 6.81-6.75
(m, 2H); 13C NMR (100 MHz, CDCl3): δ148.76,
137.46, 135.45, 131.46, 131.25, 129.09, 127.67,
118.90, 115.51, 113.86. IR (KBr): 3470, 3372,
3065, 1608, 1475, 1447, 1309, 1092, 1011, 814,
750, 553, 482. cm-1. HR EIMS: 276.9781 m/z
(calcd for C13H8ClNS2:276.9786).
4.2.7. 3-(4-Fluoro-phenyl)-3H-benzothiazole-2-thione
(3g)
4.2.9. 3-(2-Chloro-phenyl)-3H-benzothiazole-2-thione
(3i)
S
S
N
S
S
N
Cl
F
1
Brown liquid, H NMR (400 MHz, CDCl3): δ
1
White solid, M.p. 98-100ꢀ; H NMR (400 MHz,
7.460 (d, J = 7.6 Hz, 1H), 7.35-7.26 (m, 2H), 7.06-
CDCl3): δ 8.05 (d, J = 8.4 Hz, 2H), 8.84 (d, J = 7.6
Hz, 2H), 7.53-7.49 (m, 2H), 7.434-7.40 (m, 2H);
13C NMR (100 MHz, DMSO-d6): δ 169.76, 150.84,
137.45, 136.41, 131.81, 130.35, 139.39, 128.28,
117.20, 115.49, 111.69. IR (KBr): 3444, 1642,
1566, 1428, 1410, 1159, 1074, 991, 952, 861, 755,
547, 520. cm-1. HR EIMS: 261.0141. m/z (calcd for
C13H9FNS2 261.0156).
7.03 (m, 2H), 6.86-6.79 (m, 2H), 6.65-6.62 (m,
13
1H); C NMR (100 MHz, DMSO-d6): δ 170.16,
151.32, 137.84, 136.35, 132.21, 130.27, 129.93,
128.05, 126.74, 126.36, 117.46, 115.59, 110.02. IR
(KBr): 3468, 3371, 3061, 1609, 1574, 1479, 1449,
1431, 1309, 1252, 1115, 1032, 747, 660. cm-1. HR
EIMS:
276.9784
m/z
(calcd
for
C13H8ClNS2:276.9786).
4.2.8. 3-(4-Chloro-phenyl)-3H-benzothiazole-2-thione
Acknowledgements
(3h)
We are grateful for the financial support of
Educational Commission of Jiangxi Province,
China (No GJJ13246), and Science and
Technology Planning Project of Jiangxi Province,
China (20121BBG70015 and 20122BAB213012).
S
S
N
Cl
2 Martin R.; Buchwald, S. L.; Acc. Chem. Res.
2008, 41, 1461.
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ACCEPTED MANUSCRIPT
Novel copper/PEG-400 catalyst systems for chemoselective S- and N-arylation of
2-mercaptobenzothiazole
Xiao-kang Lia,b, Xiao-meng Zhoua, Tang-jun yuana, Yu Yanga, Jun-min Chena,*
a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi
330022, PR China
bKey Laboratory of Organo-pharmaceutical Chemistry, Gannan Normal University, Ganzhou,
Jiangxi 34100, PR China
E-mail: jxnuchenjm@163.com
Table of contents
General Information……………………………………………………………….…. 2
General Procedure A: Cu-catalyzed S-arylation of 2-mercaptobenzothiazole………..2
General Procedure B: Cu-catalyzed N-arylation of 2-mercaptobenzothiazole………..2
Identification Data and Spectra……………………...………………..……..……..3-30
References…………………………………………………..………..………………30
1

ACCEPTED MANUSCRIPT
General information
All reactions were carried out under an Ar atmosphere using a standard Schlenk tube
techniques. All reagents and solvents PEG-400 were purchased from Alfa, Acros,
Aldrich or TCI, and used without further purification. Flash chromatography was
performed on silca gel (silca gel, 200-300 mesh).1H NMR and13C NMR spectra were
recorded on Bruker 400 MHz and Bruker 100 MHz spectrometers with CDCl3 or
DMSO-d6 as the solvent. Mass spectra were determined on a Finnigan 8230 mass
spectrometer. Melting points were determined on an XT-4 electrothermal
Micro-melting-point apparatus.
General Procedure A: Cu-catalyzed S-arylation of 2-mercaptobenzothiazole
A flask equipped a magnetic stirring bar was charged with 2-mercaptobenzothiazole
(1 mmol), aryl halide (1.1 mmol), CuI (0.1 mmol), NaOH (2 mmol) and PEG-400 (2
ml). The reaction mixture was stirred under a nitrogen atmosphere at 50 °C for 24 h.
The reaction mixture was cooled to room temperature, diluted with Et2O, washed with
brine and dried over MgSO4. Silica gel (1.0 g) was added to the mixture and the
mixture was concentrated in vacuo. The Silica gel-adsorbed product was purified
through flash chromatography with petroleum ether/ethyl acetate as eluent to give
2a-l.
General Procedure B: Cu-catalyzed N-arylation of 2-mercaptobenzothiazole
A flask equipped a magnetic stirring bar was charged with 2-mercaptobenzothiazole
(1 mmol), aryl halide (1.1 mmol), CuO (0.1 mmol), KOH (2 mmol) and PEG-400 (2
ml). The reaction mixture was stirred under a nitrogen atmosphere at 140 °C for 24 h.
The reaction mixture was cooled to room temperature, diluted with Et2O, washed with
brine and dried over MgSO4. Silica gel (1.0 g) was added to the mixture and the
mixture was concentrated in vacuo. The Silica gel-adsorbed product was purified
through flash chromatography with petroleum ether/ethyl acetate as eluent to give
3a-i.
2

ACCEPTED MANUSCRIPT
2-(Phenylthio)benzo[d]thiazole (2a) [1]
S
S
N
Yellow liquid, 1 H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.0 Hz, 1H), 7.26-7.20 (m,
3H), 7.13-7.07 (m, 3H), 6.80-6.74 (m, 2H). 13C NMR (100 MHz, DMSO-d6): δ
169.39, 150.84, 137.39, 131.81, 131.44, 129.50, 128.28, 126.73, 125.83, 117.17,
115.37. IR (KBr): 3057, 1581, 1458, 1433, 1311, 1235, 1019, 1004, 753 cm-1. HR
EIMS: 243.0153 m/z (calcd for C13H9NS2: 243.0156).
2-(p-Tolylthio)benzo[d]thiazole (2b) [1]
S
S
CH
3
N
1
White solid, M.p. 71-72 °C. H NMR (400MHz, CDCl3): δ 7.45 (d, J = 8.0 Hz, 1H),
7.25-7.19 (m, 1H), 7.02 (t, J = 7.6 Hz, 4H), 6.78-6.72 (m, 2H), 2.28 (s, 3H); 13C NMR
(100MHz, DMSO-d6): δ 169.26, 150.41, 136.97, 135.43, 133.37, 131.15, 130.14,
127.54, 117.13, 115.31, 113.44, 20.93. IR (KBr): 3064, 2912, 1595, 1426, 1315, 1239,
817, 761 cm-1. HR EIMS: 257.0326 m/z (calcd for C14H11NS2: 257.0333).
2-(4-Methoxyphenylthio)benzo[d]thiazole (2c) [1]
S
S
OCH
3
N
White solid, M.p. 61–63 °C. 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4Hz, 1H),
7.66-7.61 (m, 3H), 7.37 (d, J = 8.0 Hz, 1H), 7.25-7.23 (m, 1H), 7.00-6.98 (d, J = 8.8
Hz, 2H), 3.86 (s, 3H); 13C NMR (100MHz, CDCl3): δ 171.81, 161.74, 154.22, 137.57,
135.47, 126.10, 124.09, 121.79, 120.76, 120.26, 115.54, 55.49. IR (KBr): 3056, 2922,
1589, 1496, 1453, 1425, 1252, 1003, 833, 758 cm-1. HR EIMS: 273.0338 m/z (calcd
for C14H11NOS2: 273.0341).
2-(3-Methylphenylthio)benzo[d]thiazole (2d) [1]
CH3
S
S
N
1
White solid, M.p. 87-91°C ; H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 7.6 Hz, 1H),
7.22 (d, J = 7.6 Hz, 1H), 7.103 (t, J = 7.6 Hz, 2H), 6.93 (d, J = 7.6 Hz, 1H), 6.84 (d, J
= 11.2 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 6.75 (t, J1 = 7.6 Hz, J2 = 6.8 Hz, 1H), 2.27 (s,
3H); 13C NMR (100 MHz, DMSO-d6): δ 169.02, 150.66, 138.77, 137.31, 136.93,
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ACCEPTED MANUSCRIPT
131.40, 129.34, 127.44, 126.70, 124.04, 117.15, 115.34, 112.63, 21.42. IR (KBr):
3454.60, 2925.87, 1570.31, 1426.05, 1158.26, 1076.87, 950.90, 859.14, 754.50,
546.46. HR EIMS: 257.0328 m/z (calcd for C14H11NS2: 257.0333).
2-(2-Methoxyphenylthio)benzo[d]thiazole (2e) [2]
H3CO
S
S
N
Colorless liquid, 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J = 8.0 Hz, 1H), 7.26 (d, J =
8.0 Hz, 2H), 7.11-7.10 (m, 1H), 6.87-6.77 (m, 4H), 6.66 (d, J = 8.0 Hz, 1H), 3.94 (s,
3H); 13C NMR (100 MHz, DMSO-d6): δ 169.46, 155.85, 151.10, 137.67, 131.48,
126.60, 126.05, 125.16, 121.47, 117.32, 115.25, 111.36, 111.30, 56.17. IR (KBr):
3061, 2954, 1590, 1428, 1239, 812, 765 cm-1. HR EIMS: 273.0337 m/z (calcd for
C14H11NOS2: 273.0341).
2-(4-fluorophenylthio)benzo[d]thiazole (2f). [3]
S
S
F
N
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.0 Hz, 1H), 7.94 (d, J =
8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.54-7.47 (m, 1H),
7.45-7.38 (m, 2H), 7.36-7.34 (m, 1H); 13C NMR (100 MHz, DMSO-d6): δ 168.71,
162.26, 159.84, 150.55, 137.10, 132.51, 131.46, 129.34, 117.19, 116.63, 115.42. IR
(KBr): 3056, 2923, 1582, 1457, 1433, 1258, 1104, 1015, 813, 746 cm-1. HR EIMS:
261.0144. m/z (calcd for C13H9FNS2 261.0156).
2-(2-thiophenylthio)benzo[d]thiazole (2g).
S
S
S
N
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.31-7.29 (m, 2H), 7.19-7.18 (m, 2H),
6.96-6.91 (m, 3H); 13C NMR (100 MHz, DMSO-d6): δ 169.36, 149.11, 134.57,
134.24, 132.82, 130.49, 130.14, 128.21, 117.15, 117.03, 115.42. IR (KBr): 3058, 2947,
1590, 1423, 1237, 813, 754 cm-1. HR EIMS: 249.3746 m/z (calcd for C11H7NS3:
249.3750).
2-(3-Methoxyphenylthio)benzo[d]thiazole (2h) [2]
4

ACCEPTED MANUSCRIPT
OCH3
S
N
S
Yellow liquid, 1H NMR (400MHz, CDCl3): δ 7.45 (d, J = 8.0 Hz, 1H), 7.25-7.22 (m,
1H), 7.15-7.11 (m, 1H), 6.79-6.73 (m, 2H), 6.67-6.64 (m, 3H), 3.72 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 160.09, 148.90, 138.29, 137.52, 131.22, 129.81, 118.78,
118.73, 115.37,114.16, 112.10,111.03,55.18. IR (KBr): 3468, 3369, 3063, 2936, 2834,
1609, 1589, 1478, 1247, 1042, 751 cm-1. HR EIMS: 273.0338 m/z (calcd for
C14H11NOS2: 273.0341).
2-(3,5-Dimethylphenylthio)benzo[d]thiazole (2i) [2]
CH
3
S
N
S
CH
3
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.45-7.43 (m, 1H), 7.23 (d, J = 12.0
Hz, 1H), 6.79-6.72 (m, 5H), 2.22 (s, 6H); 13C NMR (100 MHz; CDCl3): δ 148.70,
138.67, 137.27, 136.21, 130.87, 127.54, 124.38, 128.66, 115.33, 114.81, 21.27. IR
(KBr): 3452.58, 2924.82, 1570.51, 1425.83, 1075.82, 954.95, 757.84, 525.82. HR
EIMS: 271.0481 m/z (calcd for C15H13NS2: 271.0489).
2-(4-Chlorophenylthio)benzo[d]thiazole (2j) [2]
S
S
Cl
N
1
Brown liquid, H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 8.0 Hz, 1H), 7.35 (d, J =
8.0 Hz, 1H), 7.27-7.17 (m, 2H), 7.01-6.91 (m, 2H), 6.80-6.74 (m, 2H); 13C NMR (100
MHz, DMSO-d6): δ 169.32, 150.84, 137.45, 136.41, 131.81, 130.36, 129.39, 128.28,
117.21, 115.49, 111.70. IR (KBr): 3470, 3370, 2924, 1608, 1574, 1474, 1309, 1091,
1010, 814, 750 cm-1. HR EIMS: 276.9782 m/z (calcd for C13H8ClNS2:276.9786).
2-(2-Chlorophenylthio)benzo[d]thiazole (2k) [2]
Cl
S
S
N
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 12.0 Hz, 1H), 7.35-7.26 (m,
13
2H), 7.06-7.04 (m, 2H), 6.83-6.78 (m, 2H), 6.65-6.62 (m, 1H); C NMR (100 MHz,
DMSO-d6): δ 168.95, 151.31, 137.83, 136.33, 132.21, 130.25, 129.96, 128.07,
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ACCEPTED MANUSCRIPT
126.76, 126.35, 117.45, 115.58, 109.99. IR (KBr): 3485, 3375, 2931, 1607, 1556,
1476, 1301, 1090, 1015, 812, 786, 753 cm-1. HR EIMS: 276.9783 m/z (calcd for
C13H8ClNS2:276.9786).
2-(2-Naphthalenylthio)benzo[d]thiazole (2l) [2]
S
S
N
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 7.75-7.72 (m, 1H), 7.69 (d, J = 8.0 Hz,
1H), 7.63 (d, J = 8.0 Hz, 1H), 7.51-7.47 (m, 2H), 7.41-7.37 (m, 2H), 7.28-7.21 (m,
2H), 6.81-6.76 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 148.90, 137.47, 134.26,
133.84, 131.62, 131.25, 128.70, 127.78, 127.07, 126.60, 125.48, 125.19, 124.41,
118.85, 115.51, 114.35. IR (KBr): 3468, 3371, 3053, 1607, 1479, 1448, 1309, 1063,
851, 813, 747. cm-1. HR EIMS: 293.0327 m/z (calcd for C17H11NS2: 293.0334).
3-Phenyl-3H-benzothiazole-2-thione (3a)
S
S
N
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.37-7.33 (m, 4H), 7.31-7.29 (m, 3H),
7.27-7.23 (m, 2H); 13C NMR (100 MHz, DMSO-d6): δ 169.31, 153.87, 135.69,
135.32, 131.38, 130.77, 129.34, 126.89, 124.97, 122.18, 121.87. IR (KBr): 3061,
2924, 2854, 1581, 1476, 1440, 1377, 1081, 1024, 737, 689, 516. cm-1. HR EIMS:
243.0152 m/z (calcd for C13H9NS2: 243.0156).
3-(4-Methoxy-phenyl)-3H-benzothiazole-2-thione (3b)
S
S
N
OCH
3
1
White solid, M.p. 57-59℃; H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.0 Hz, 1H),
7.67-7.61 (m, 3H), 7.40-7.36 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 8.0 Hz,
13
2H), 3.87 (s, 3H); C NMR (100 MHz, CDCl3): δ 172.01, 161.73, 154.20, 137.63,
135.41, 126.12, 124.09, 121.76, 120.77, 120.18, 115.54, 55.51. IR (KBr): 3445, 2458,
1642, 1567, 1426, 1161, 1070, 951, 861, 547. cm-1. HR EIMS: 273.0336 m/z (calcd
for C14H11NOS2: 273.0341).
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ACCEPTED MANUSCRIPT
3-p-Tolyl-3H-benzothiazole-2-thione (3c)
S
S
N
CH
3
1
White solid, M.p. 49-50℃; H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 7.6 Hz, 1H),
7.22 (m, 1H), 7.027 (dd, J = 8.4 Hz, 8Hz, 4H), 6.77 (t, J = 8.0 Hz, 2H), 2.28 (s, 3H);
13C NMR (100 MHz, DMSO-d6): δ 170.30, 153.98, 141.68, 135.91, 135.24, 131.45,
126.87, 125.74, 124.84, 122.17, 121.17, 21.33. IR (KBr): 3450, 2952, 2451, 1567,
1447, 1160, 951, 860, 547, 521. cm-1. HR EIMS: 257.0325 m/z (calcd for C14H11NS2:
257.0333).
3-m-Tolyl-3H-benzothiazole-2-thione (8d)
S
S
N
CH3
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 8.4 Hz, 1H), 7.24 (d, J =
8.4 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 2H), 6.87 (d, J = 8.4 Hz,
1H), 6.80-6.76 (m, 2H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.66, 138.84,
137.38, 136.50, 131.02, 128.88, 127.20, 126.43, 123.63, 118.78, 115.42, 114.67,
75.88, 21.42. IR (KBr): 3468, 3370, 1609, 1449, 1082, 953, 864, 564, 519. cm-1. HR
EIMS: 257.0324 m/z (calcd for C14H11NS2: 257.0333).
3-Naphthalen-2-yl-3H-benzothiazole-2-thione (3e)
S
S
N
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 7.76-7.62 (m, 3H), 7.51-7.36 (m, 4H),
13
7.28-7.21 (m, 2H), 6.80-6.76 (m, 2H); C NMR (100 MHz, DMSO-d6): δ 170.45,
150.76, 137.30, 137.24, 134.74, 133.75, 131.58, 129.03, 128.09, 127.24, 127.18,
125.98, 125.63, 124.59, 117.24, 115.48, 112.40. IR (KBr): 3057, 1456, 1425, 1310,
1238, 1020, 1007, 771, 755, 726, 665, 477. cm-1. HR EIMS: 293.0325 m/z (calcd for
C17H11NS2: 293.0334).
3-Naphthalen-1-yl-3H-benzothiazole-2-thione (3f)
7

ACCEPTED MANUSCRIPT
S
N
S
1
Yellow liquid, H NMR (400 MHz, CDCl3): δ 8.34 (d, J = 8.0 Hz, 1H), 7.83 (d, J =
7.2 Hz, 1H), 7.74-7.38 (m, 5H), 7.26 (d, J = 8.0 Hz,2H), 6.94 (d, J = 7.2 Hz, 1H), 6.79
(s, 2H); 13C NMR (100 MHz, DMSO-d6): δ 169.34, 153.82, 137.03, 137.02, 135.35,
134.72, 133.99, 132.93, 129.51, 128.71, 127.56, 126.86, 126.14, 125.14, 124.87,
122.16, 121.82. IR (KBr): 3121, 2982, 1659, 1454, 1315, 1285, 1007, 852, 756, 716,
582, 516, 455. cm-1. HR EIMS: 293.0325 m/z (calcd for C17H11NS2: 293.0334).
3-(4-Fluoro-phenyl)-3H-benzothiazole-2-thione (3g)
S
S
N
F
White solid, M.p. 98-100℃; 1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.4 Hz, 2H),
8.84 (d, J = 7.6 Hz, 2H), 7.53-7.49 (m, 2H), 7.434-7.40 (m, 2H); 13C NMR (100 MHz,
DMSO-d6): δ 169.76, 150.84, 137.45, 136.41, 131.81, 130.35, 139.39, 128.28, 117.20,
115.49, 111.69. IR (KBr): 3444, 1642, 1566, 1428, 1410, 1159, 1074, 991, 952, 861,
755, 547, 520. cm-1. HR EIMS: 261.0141. m/z (calcd for C13H9FNS2 261.0156).
3-(4-Chloro-phenyl)-3H-benzothiazole-2-thione (3h)
S
S
N
Cl
1
Brown liquid, H NMR (400 MHz, CDCl3): δ 7.50-7.43 (m, 1H), 7.43-7.23 (m, 1H),
7.18 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.4 Hz, 2H), 6.81-6.75 (m, 2H); 13C NMR (100
MHz, CDCl3): δ 148.56, 137.43, 135.40, 131.43, 131.27, 129.09, 127.71, 119.01,
115.59, 114.02. IR (KBr): 3470, 3372, 3065, 1608, 1475, 1447, 1309, 1092, 1011, 814,
750, 553, 482. cm-1. HR EIMS: 276.9781 m/z (calcd for C13H8ClNS2:276.9786).
3-(2-Chloro-phenyl)-3H-benzothiazole-2-thione (3i)
S
S
N
Cl
8

ACCEPTED MANUSCRIPT
Brown liquid, 1H NMR (400 MHz, CDCl3): δ 7.460 (d, J = 7.6 Hz, 1H), 7.35-7.26 (m,
13
2H), 7.06-7.03 (m, 2H), 6.86-6.79 (m, 2H), 6.65-6.62 (m, 1H); C NMR (100 MHz,
DMSO-d6): δ 170.16, 151.32, 137.84, 136.35, 132.21, 130.27, 129.93, 128.05,
126.74, 126.36, 117.46, 115.59, 110.02. IR (KBr): 3468, 3371, 3061, 1609, 1574,
1479, 1449, 1431, 1309, 1252, 1115, 1032, 747, 660. cm-1. HR EIMS: 276.9784 m/z
(calcd for C13H8ClNS2:276.9786).
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13