Highly efficient synthesis of 2-mercaptobenzothiazole derivatives in water: Metal sulfide-disulfide dynamic interchange reaction

Article abstract of DOI:10.1039/c6gc03053j

A convenient and efficient method for the synthesis of 2-mercaptobenzothiazoles from disulfide and CS₂ mediated by a metal sulfide in water is described. This synthetic methodology could be used to prepare diverse 2-mercaptobenzothiazole derivatives in good to excellent yields. In this paper, the concept of metal sulfide-disulfide dynamic interchange reaction was put forward. Then the intermediates of the interchange reaction between NaHS and a disulfide were detected by LC-MS, which demonstrated that the S-S bond of the disulfide could be broken by the metal sulfide through the dynamic interchange reaction. In addition, NaHS was eventually transformed into sulfur S₈ by the dynamic interchange reaction. Moreover, the underlying mechanism of 2-mercaptobenzothiazole formation is proposed, in which NaHS not only acts as an S-S bond cleaving agent but also as an activator of CS₂. As a result, a novel synthetic route for the preparation of sulfur-containing heterocycles from a disulfide is developed.

Full text of DOI:10.1039/c6gc03053j

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Highly efficient synthesis of 2-mercaptobenzothiazole derivatives
in water: metal sulfide-disulfide dynamic interchange reaction
Received 00th January 20xx,
Accepted 00th January 20xx
Chunqing Lou, Ning Zhu,* Ronghua Fan, Hailong Hong, Limin Han, Jianbin Zhang and Quanling Suo
A convenient and efficient method for the synthesis of 2-mercaptobenzothiazoles from disulfide and CS2 mediated by
metal sulfide in water is described. This synthetic methodology could be used to prepare diverse 2-mercaptobenzothiazole
derivatives in good to excellent yields. In this paper, the concept of metal sulfide-disulfide dynamic interchange reaction
was put forward. Then the intermediates of the interchange reaction between NaHS and disulfde were detedted by LC-MS,
which demonstrated the S-S bond of disulfide could be broken by metal sulfide through the dynamic interchange reaction.
In addition, NaHS was eventually transformed into the sulfur S8 by the dynamic interchange reaction. Moreover, the
underlying mechanism of 2-mercaptobenzothiazole formation is proposed, in which NaHS not only acts as the S-S bond
cleaving agent but also as an activator of CS2. As a result, a novel synthetic route for the preparation of sulfur-containing
heterocycles from disulfide is developed.
DOI: 10.1039/x0xx00000x
www.rsc.org/
The MBTs prepared through the reactions of carbon disulfide
with aniline,5 o-haloaniline,6 o-aminothiophenols7 or disulfide8
have been widely reported (Scheme 1). However, each suffers
Introduction
2-Mercaptobenzothiazole and its derivatives (MBTs) are an
important class of heterocyclic compounds. In bioactive
properties,1 the MBTs are often used to prepare antimicrobial,
anti-inflammatory, anthelmintic and anti-tubercular drugs. In
industrial applications,2 MBTs are used as an accelerator in
rubber vulcanization3 and regarded as the promising ligands
for the metallic complexes that can be used as luminescent
materials.4 Thus, the study of synthetic methods for preparing
MBTs continues to be one of the most attractive areas in
synthetic chemistry.2
from various inherent drawbacks such as long reaction time,
high temperature, expensive and toxic solvent. Notably,
although the o-aminothiophenol was often used as raw
materials to prepare MBTs, most o-aminothiophenols
containing various substituted groups could not be prepared
easily and often spontaneously formed the corresponding
disulfides.9 Hence, an efficient method for synthesizing MBTs
from disulfide under mild condition is still highly desirable.
Disulfide is an important starting material and intermediate
for preparing sulfur-containing compounds.10 To utilize
disulfides as starting materials for the MBTs, the cleavage of S-
S bond is a key step in the construction of C-S bond. So far, the
sulfur-sulfur bond could be cleaved by nucleophilic,11 free
radical reagents10a, 10e and metal catalysts.12 However, due to
the inherent stability and kinetic inertness of disulfide, the
cleavage of S-S bond under mild conditions, especially in
water, is difficult.
Fortunately, thiol-disulfide dynamic interchange reaction
was widely used to cleave disulfide in water in biochemistry.13
In addition, thiol-disulfide dynamic interchange reaction has
also been used to break disulfide bond to prepare sulfur-
containing heterocylcles in our previous work.8a However, the
thiol-disulfide dynamic interchange reaction requires high cost
organic base and thiols which have unpleasant smell.
Furthermore, this reaction also produces another disulfide
byproduct. To overcome this drawback, Teppema8b has
explored the method for the preparation of 2-
mercaptobenzothiozole from the reaction of 2,2’-
disulfanediyldianiline with CS2 in the presence of metal sulfide
in 1927. However, Teppema’s work did not show how the
Scheme 1 Synthesis of 2-mercaptobenzothiazole from CS2
Chemical Engineering College, Inner Mongolia University of Technology, Hohhot,
010051, P. R. China.
Email: zhuning2622@yahoo.com
† Electronic Supplementary Informaꢀon (ESI) available: The detailed mechanism,
LC-MS spectrometry, Crystallographic details of S8, NMR spectra. See
DOI: 10.1039/x0xx00000x
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metal sulfide broke S-S bond. Recently, our group had Table 1 Optimization of the reaction conditionsa
reported that sodium sulfide (Na2S) could cleave the disulfide
bond in the synthesis of 2-aryl substituted benzothiazoles.14
Nevertheless, the underlying mechanism of cleaving S-S bond
by metal sulfide is still unclear. Accordingly, exploring the
reaction mechanism of S-S bond cleavage is an important
Entry
Metal
T(°C)
Ratiob
Solvent
Yield
(%)d
research interest.
Herein, we envisioned the low-cost inorganic metal sulfide
could be used to replace organic thiols to render the metal
sulfide-disulfide dynamic interchange reaction. Therefore, the
preparation of MBTs is used as a model reaction to explore the
application of the dynamic interchange reaction between
metal sulfide and disulfide. Furthermore, the profound
function of metal sulfide in this reaction system has also been
investigated. To the best of our knowledge, it was the first
time to put forward and substantiate the mechanism of the
metal sulfide-disulfide dynamic interchange reaction, which
demonstrated how the S-S bond of disulfide was cleaved by
metal sulfide. As a result, the new mechanism of breaking
sulfide
1
Na2S
·
·
·
·
·
9H2O
90
80
50
25
80
80
80
80
80
80
80
80
80
80
1:0.5:4
1:0.5:4
1:0.5:4
1:0.5:4
1:0.5:4
1:0.5:4
1:0:4
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
86
88
75
40
77
93
39
90
73
69
85
95
82
91
2
Na2S
Na2S
Na2S
Na2S
9H2O
9H2O
9H2O
9H2O
3
4
5c
6
NaHS
-
7
8
NaHS
NaHS
NaHS
NaHS
NaHS
K2S
1:1:4
disulfide seems to provide
a novel synthetic route for
9
1:0.2:4
1:0.1:4
preparing the sulfur heterocycles from disulfide.
10
11
12
1:0.5:4 ethanol
Results and discussion
1:0.5:4
1:0.5:4
1:0.5:4
DMF
H2O
H2O
The metal sulfide was explored as a catalyst for the synthesis
of 2-mercaptobenzothiazole from the reaction of disulfide and 13
CS2. As indicated in Table 1, various parameters such as
14
CaS
different metal sulfides, temperature, solvent and the ratio of
disulfide to metal sulfide were screened to achieve the optimal
reaction conditions. Initially, various temperatures were tested
to carry out the reaction of 2,2’-disulfanediyldianiline (1a) and
CS2 mediated by sodium sulfide nonahydrate under inert
atmosphere in water. The highest yield of the desired product
2a was achieved at 80 °C (Entries 1-4). When sodium
hydrosulfide was used to replace the sodium sulfide
nonahydrate in this reaction, the yield of product 2a was
slightly increased (Entries 2 and 6). However, when metal
sulfide was not used in this reaction, product 2a was obtained
in only 39 % yield (Entry 7), which demonstrated that metal
sulfide was important in this reaction system. Then the
aReaction conditions: 1a (0.4 mmol), CS2 (1.6 mmol), metal
sulfide was added in indicated amount, and solvent (2.5 mL),
stirred under N2 atmosphere for 4 h. bRatio is the mole ratio of
1a: metal sulfide: CS2. cNo protected by N2. dIsolated yield
based on 1a after column chromatography.
substituted 2,2’-disulfanediyldianilines to provide the
corresponding MBTs, and the results are summarized in Table
2. We observed that the reaction could tolerate many
functional groups such as chloro, bromo, fluoro,
trifluoromethyl, methylsulfonyl, methoxy and methyl groups
(Entries 1-9). As shown, the disulfide bearing electron-
withdrawing or electron-donating groups could give the
influence of various ratios of NaHS on the yield of product 2a
was investigated (Entries 8-10 and 6), which showed that 0.5
equiv. of NaHS was the optimal ratio. Moreover, different
solvents were tested in the reaction system. Water was used
as environment friendly solvent in the following experiment,
although product 2a could be produced efficiently from the
reaction of 1a with CS2 in ethanol or DMF (Entries 11-12). In
addition, the yield of product 2a decreased when the 1a
reacted with CS2 in air (Entry 5), which may result from the
oxidation of intermediate 2-aminobenzenethiol (Scheme 2).
Furthermore, to test the efficiency of other metal sufides in
this reaction process, we found that K2S and CaS could also
promote the reaction of 1a and CS2 to form 2a in excellent
yields (Entries 13-14), which indicated all the water soluble
metal sulphides could render this reaction smoothly.
corresponding products
2 in moderate to excellent yields
under the optimal reaction conditions. Noteworthy, the
electron-donating groups on disulfide could promote the
reaction and produce higher yield of the corresponding
product. In contrast, the strong electron-withdrawing group
substituted disulfide (entry 5) could not react with CS2 in 10 h
completely and 35 % starting materials was recovered after
the reaction, which further demonstrated that the electron-
withdrawing groups impeded the reaction of disulfide with
CS2.
Based on the present experimental results and the
previously reported thiol-disulfide interchange reaction
mechanism,8a we proposed a mechanism for NaHS-disulfide
dynamic interchange reaction in Scheme 2 (the detailed
mechanism is shown in Scheme S1). Firstly, the S-S bond of
After established the optimum conditions (Table 1, entry 6),
the scope of the reaction was examined using diversely
2 | J. Name., 2012, 00, 1-3
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disulfide 1a is cleaved by the hydrosulfide ion (HS-) through the h. bIsolated yield based on substrate
ARTICLE
1
after column
dynamic interchange reaction, and the intermediates 2-
Table 2 Synthesis of 2-mercaptobenzothiazole derivativesa
chromatography.
aminobenzenethiolate B and persulfide C are formed
immediately. Simultaneously, the intermediate persulfide
C
continues to react with disulfide 1a by dynamic interchange
reaction to produce the intermediates 2-aminobenzenethiol
(
1
) and trisulfide (
further reacts with NaHS to afford the persulfide (2-
trisulfanylaniline ) and . According to this process, the
intermediates tetrasulfide ( ), pentasulfide ( ), hexasulfide,
heptasulfide ), octasulfide and nonasulfide would be
produced in this metal sulfide-disulfide interchange reaction
process. At last, the persulfide (2-nonasulfanylaniline ) could
cyclize intramolecularly to form 2-aminobenzenethiol ( ) and
2). The generated intermediate trisulfide (2)
D
B
Entry Substrate
1
Product
2
Time
(h)
Yield
(%)b
3
4
(
5
1
2b
4
76
E
1
2
3
2c
4
85
63
sulfur (S8). All the intermediates reach dynamic equilibrium in
the solution. When the electrophilic reagent was added into
2d
10
this solution, the intermediates 2-aminobenzenethiolate
B and
2-aminobenzenethiol (1) would decrease and the dynamic
4
5
6
2e
2f
10
10
8
65
50
71
equilibrium was broken. Eventually, the disulfide is totally
converted to the corresponding product by the nucleophilic
reaction of 2-aminobenzenethiolate
B or 2-aminobenzenethiol
(
1) with the electrophilic reagent in the presence of NaHS
which would be transformed into the elemental sulfur (S8).
To verify the metal sulfide-disulfide interchange reaction
mechanism and clarify the special role of sodium hydrosulfide,
we investigated the reaction product by mixing disulfide and
sodium hydrosulfide in ethanol at room temperature. After
stirring for 20 minutes, the reaction products were
characterized by high performance liquid chromatography
mass spectrometry (LC-MS). As illustrated in Fig. 1 (The original
spectrometry is shown in Fig. S1), the reaction of disulfide with
2g
7
2h
10
86
8
9
2i
2j
4
90
89
10
aReaction conditions:
mmol) and H2O (2.5 mL), stirred under N2 atmosphere for 4-10
1 (0.4 mmol), NaHS (0.2 mmol), CS2 (1.6
sodium hydrosulfide generated
a
major product 2-
aminobenzenethiol (1) and a small amount of
Scheme 2 Proposed mechanism of NaHS-disulfide interchange reaction
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confirmed our proposed mechanism of metal sulfide-disulfide
interchange reaction.
To shed light on the other functions of NaHS, several
controlled experiments were carried out. As shown in
Scheme 3, when 2-aminobenzenethiol reacted with carbon
disulfide under optimum conditions in the absence of NaHS,
(5)
408.70
248.95
(2)
280.85
(1)
126.00
product 2a was formed only in 37
% yield, which
(3)
312.85
demonstrated that NaHS had other roles besides cleaving S-S
bond of disulfide (Eqs. 1 and 2). After the addition of NaHS, 2-
aminobenzenethiol can be transformed into the desired
(4)344.80
8.0
9.0
a
product 2a in 77
%
yield (Eq. 3). Obviously, 2-
aminobenzenethiol cannot react with NaHS to produce 2a
(Eq. 4) and a new peak (236.5 ppm) was presented in the
13CNMR spectra after mixing the NaHS and CS2 in the
deuterated DMF (Fig. S3), which suggested that NaHS could
also activate carbon disulfide besides cleaving the disulfide
(S-S) bond. However, the yield of 2a from the reaction of 2-
aminobenzenethiol (Eq. 3) was still lower than from the
reaction of disulfide (Eq. 1). From the mechanism of NaHS-
disulfide interchange reaction (Scheme 2), we found that half
b
c
2.5
5.0
7.5
10.0
min
Fig. 1 (a) LC-MS analysis of the reaction between disulfide 1a
and NaHS after 20 min in ethanol at room temperature
(Molecular weight was shown below the molecular
structure.), (b) The LC chromatogram of disulfide 1a, and (c)
the LC chromatogram of 2-aminobenzenethiol.
intermediate products such as trisulfide (
), and even smaller amount of pentasulfide (
heptasulfide ( ), which demonstrated that the metal sulfide-
2) and tetrasulfide
(
3
4
) and
5
disulfide interchange reaction could take place easily. These
identified intermediates supported our proposed mechanism
(Scheme 2). However, persulfide (C, D and E) could not be
directly detected by the LC-MS because of their instability.15
After the reaction of disulfide 1a with CS2 catalyzed by
NaHS completed, a byproduct was isolated by column
chromatography eluted by petroleum ether only. The
byproduct was crystalized and analyzed by single crystal X-ray
diffraction. The crystal structure (Fig. S2 in SI) indicated the
byproduct was the expected sulfur S8, which further
Scheme 3 Controlled Experiments
Scheme 4 The proposed mechanism for the reaction of 1a with CS2 mediated NaHS
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In summary, we have developed an efficient synthetic
method for preparing 2-mercaptobenthiazole derivatives
using dynamic interchange reaction between disulfide and
metal sulfide in water. Commercially available and easily
handled metal sulfide and water were used in this synthetic
route. Moreover, the NaHS-disulfide dynamic interchange
reaction has firstly been demonstrated and the role of NaHS
in activating CS2 has also been proposed in this model
reaction.
a
Scheme 5 A gram-scale reaction of 1a and CS2
aReaction conditions: 2,2'-disulfanediyldianiline (5.0 mmol,
1.0 equiv.), sodium hydrosulfide (1.5 mmol, 0.3 equiv.), CS2
(15 mmol, 3.0 equiv.), H2O (25 mL), 80 °C, and stirred in a
stainless steel autoclave reactor for 10 h; the yields of
product and byproducts (S8) are calculated based on the
theoretical amount.
Experimental section
General Procedures
of the disulfide was converted into 2-aminobenzenethiol (
and the other half was transformed into 2-
aminobenzenethiolate by NaHS. It is possible that the
1)
All reagents were used without further purification, which
were purchased from Aladdin and Alfa. Most of the reactions
were performed in a Wattecs parallel reactor. Reactions were
monitored by TLC. Column chromatography separations were
carried out on silica gel (200-300 mesh). Melting points were
measured with SGC X-4 microscopic melting point meter used
uncorrected. Molecular weights were determined by mass
B
intermediate 2-aminobenzenethiolate reacted with CS2 more
easily than 2-aminobenzenethiol. To verify our idea, the
experiment of 2-aminobenzenethiol reacted with CS2 under
2eq. NaOH (Eq. 5) was carried out and the excellent yield of
target product was obtained, which demonstrated that 2-
aminobenzenethiolate could react with CS2 more easily than
2-aminobenzenethiol.
spectrometry. The H and 13C NMR spectra were obtained in
1
CDCl3 or DMSO-d6 on an Agilent 500 MHz DD2 spectrometer
and referenced to the residual deuterated solvent or TMS.
The NMR results were processed using MestReNova
software.
Based on the S-S bond cleavage process by metal sulfide-
disulfide interchange reaction, the reaction mechanism of
disulfide and CS2 mediated by NaHS is proposed. Firstly, one
equivalent NaHS reacted with one equivalent disulfide to
produce one equivalent 2-aminobenzenethiol and one
General Procedure for Synthesis of 2-Mercapbenzothiazole
Derivatives (2a-2j).
equivalent
2-aminobenzenethiolate
B
.
Then
2-
2,2’-Disulfanediyldianiline or its corresponding derivatives
aminobenzenethiol and 2-aminobenzenethiolate reacted
with CS2 to produce 2-mercaptobenzothiazole by nucleophilic
addition and cyclization reaction. Notably, H2S was formed
from the reaction of 2-aminobenzenethiol and CS2, while
hydrosulfide ion (HS-) was formed from the reaction of 2-
(0.4 mmol), metal sulfide (0.2 mmol NaHS, Na2S·9H2O, K2S or
CaS) in H2O (2.5 mL) were put into a reaction tube of parallel
reactor (Wattecs). The reaction mixture was stirred at 80 °C
under N2 atmosphere for the indicated time until the starting
material was consumed completely as monitored by TLC and
LC-MS analysis. The reaction mixture was acidified by dilute
hydrochloric acid (3 mol/L) and extracted with CH2Cl2 or
EtOAc. The organic layers were dried over anhydrous MgSO4.
After filtering to remove the MgSO4, the solvent was
removed under reduced pressure. The crude product was
purified by column chromatography through a silica-gel
column to afford the byproduct sulfur S8 eluted by petroleum
ether and the desired products eluted by CH2Cl2 or EtOAc.
The Reaction Process of 2,2'-Disulfanediyldianiline and NaHS
Detected by LC-MS
aminobenzenethiolate
B
and CS2. The formed HS- and H2S
could also cleave S-S bond of disulfide. Therefore, a catalytic
amount of NaHS could promote the reaction of disulfide with
CS2 smoothly.
To test the reaction’s practical utility, a gram-scale reaction
was carried out by using 2,2’-disulfanediyldianiline 1a (5
mmol) under optimum conditions. After the reaction was
completed, the crude product was separated by simple
filtration. The pure target product and byproduct sulfur (S8)
were obtained in excellent yield through column
chromatography of the filtrate cake (Scheme 5).
2,2'-Disulfanediyldianiline (0.2 mmol), NaHS (0.4 mmol) in
CH3CH2OH (2.5 mL) were put into a reaction tube of parallel
reactor (Wattecs). The reaction mixture was stirred at room
temperature for 20 min and analyzed by LC-MS. The LC-MS
results are shown in Fig. 1 and Fig. S1.
Conclusions
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The Reaction Procedure of 2-Aminobenzenethiol and CS2
procedure affording the product as a white solid. Elute by
CH2Cl2, Yield: 102 mg, 63% yield. Mp: 199-200 °C; MS (EI):
2-Aminobenzenethiol (1 mmol), CS2 (1.2 mmol), in the
presence or absence of NaHS (0.25 mmol) in H2O (2.5 mL)
were put into a stainless steel autoclave reactor. The reaction
mixture was stirred at 80 °C for 4 hours. The reaction mixture
was acidified by dilute hydrochloric acid (3 mol/L) and
extracted with CH2Cl2 or EtOAc. The organic layers were dried
over anhydrous MgSO4. After filtering to remove MgSO4, the
solvent was removed under reduced pressure. The crude
product was purified by column chromatography through a
silica-gel column to afford the desired products in 37.4 %
yield (63 mg) in the absence of NaHS or 77 % yield (129 mg)
in the presence of NaHS (0.25 mmol) eluted by CH2Cl2.
The Reaction Procedure of 2-Aminobenzenethiol and CS2 in the
presence of NaOH
1
m/z 200.9 [C7H4ClNS2], calcd. [M] 201.0. H NMR (500 MHz,
DMSO-d6, TMS): δ (ppm) 13.84 (brs, 1H), 7.72 (d, 1H, J = 8.5
Hz), 7.35 (dd, 1H, J1 =8.5 Hz, J2 = 2.0 Hz), 7.28 (d, 1H, J = 2.0
Hz). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm) 190.80,
142.14, 131.68, 128.15, 123.95, 123.13, 111.84.
4-fluorobenzo[d]thiazole-2-thiol 2e18: 6,6'-disulfanediylbis(2-
fluoroaniline) was reacted according to the general
procedure affording the product as a white solid. Elute by
CH2Cl2, Yield: 96 mg, 65% yield. Mp: 190-192 °C; MS (EI): m/z
184.9 [C7H4FNS2], calcd. [M] 185.2. 1H NMR (500 MHz, DMSO-
d6, TMS): δ (ppm) 14.22 (brs, 1H), 7.53-7.52 (m, 1H), 7.31-
7.24 (m, 2H). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm)
190.60, 146.77 (d, 1C, J = 247.0 Hz), 131.61 (d, 1C, J = 12.0
Hz), 129.49 (d, 1C, J = 60.0 Hz), 124.95 (d, 1C, J = 25.5 Hz),
117.67 (d, 1C, J = 15.0 Hz), 113.11 (d, 1C, J = 66.0 Hz).
2-Aminobenzenethiol (1 mmol), CS2 (1.2 mmol), and NaOH (2
mmol) in H2O (2.5 mL) were put into a stainless steel
autoclave reactor. The reaction mixture was stirred at 80 °C
for 4 hours. The reaction mixture was acidified by dilute
hydrochloric acid (3 mol/L) and extracted with CH2Cl2 or
EtOAc. The organic layers were dried over anhydrous MgSO4.
After filtering to remove MgSO4, the solvent was removed
under reduced pressure. The crude product was purified by
column chromatography through a silica-gel column to afford
the desired products in 90 % yield (151.2 mg) eluted by
CH2Cl2.
5-(trifluoromethyl)benzo[d]thiazole-2-thiol
disulfanediylbis(3-(trifluoromethyl)aniline)
2f16
was
:
6,6'-
reacted
according to the general procedure affording the product as a
white solid. Elute by CH2Cl2, Yield: 94 mg, 50% yield. Mp: 205-
1
207 °C; MS (EI): m/z 234.9 [C8H4F3NS2], calcd. [M] 235.0. H
NMR (500 MHz, DMSO-d6, TMS): δ (ppm) 14.03 (brs, 1H),
7.95 (d, 1H, J = 8.5 Hz), 7.64-7.63 (m, 1H), 7.49 (d, 1H, J =1.5
Hz). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm) 190.95,
141.38, 133.99 (d, 1C, J = 1.3 Hz), 127.54 (q, 1C, J = 32.0 Hz),
123.83 (q, 1C, J = 270.0 Hz), 122.94, 120.44 (q, 1C, J = 3.8 Hz),
108.53 (q, 1C, J = 4.0 Hz).
6-(methylsulfonyl)benzo[d]thiazole-2-thiol
disulfanediylbis(4-(methylsulfonyl)aniline)
2g19
was
:
2,2'-
Characterization data for all products
2-mercaptobenzothiazole 2a16: 2,2'-disulfanediyldianiline was
reacted according to the general procedure affording the
product as a white solid. Elute by CH2Cl2, Yield: 124 mg, 93%
yield. Mp: 182-183 °C; MS (EI): m/z 167.1 [C7H5NS2], calcd.
[M] 167.0. 1H NMR (500 MHz, DMSO-d6, TMS): δ (ppm) 13.75
(brs, 1H), 7.69 (d, 1H, J = 9.0 Hz), 7.41-7.38 (m, 1H), 7.32-7.27
(m, 2H). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm) 189.69,
141.13, 129.22, 127.03, 124.08, 121.66, 112.30.
reacted
according to the general procedure affording the product as a
white solid. Elute by CH2Cl2, Yield: 134 mg, 71% yield. Mp:
243-244 °C; MS (EI): m/z 245.0 [C8H7NO2S3], calcd. [M] 245.3.
1H NMR (500 MHz, DMSO-d6, TMS): δ (ppm) 14.12 (brs, 1H),
8.33 (d, 1H, J = 2.0 Hz), 7.92 (dd, 1H, J1 =8.5 Hz, J2 = 2.0 Hz),
7.47 (d, 1H, J = 8.5 Hz), 3.22 (brs, 3H). 13C NMR (125 MHz,
DMSO-d6, TMS): δ (ppm) 192.02, 144.71, 136.13, 130.01,
126.21, 121.36, 112.53, 43.80.
6-chlorobenzo[d]thiazole-2-thiol 2b17: 2,2'-disulfanediylbis(4-
chloroaniline) was reacted according to the general
procedure affording the product as a white solid. Elute by
CH2Cl2, Yield: 122 mg, 76% yield. Mp: 239-241 °C; MS (EI):
4-methylbenzo[d]thiazole-2-thiol 2h20: 6,6'-disulfanediylbis(2-
methylaniline) was reacted according to the general
procedure affording the product as a white solid. Elute by
CH2Cl2, Yield: 124 mg, 86% yield. Mp: 191-193 °C; MS (EI):
m/z 181.1 [C8H7NS2], calcd. [M] 181.0. 1H NMR (500 MHz,
DMSO-d6, TMS): δ (ppm) 13.57 (brs, 1H), 7.51-7.48 (m, 1H),
7.20 (s, 1H), 7.19 (s, 1H), 2.45 (s, 3H). 13C NMR (125 MHz,
DMSO-d6, TMS): δ (ppm) 190.04, 140.12, 128.94, 128.12,
124.06, 122.50, 118.86, 17.44.
1
m/z 200.9 [C7H4ClNS2], calcd. [M] 201.0. H NMR (500 MHz,
DMSO-d6, TMS): δ (ppm) 13.86 (brs, 1H), 7.86 (d, 1H, J = 2.0
Hz), 7.44 (dd, 1H, J1 = 8.5 Hz, J2 = 2.0 Hz), 7.28 (d, 1H, J = 8.5
Hz). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm) 190.05,
140.13, 130.94, 128.47, 127.16, 121.33, 113.38.
6-bromobenzo[d]thiazole-2-thiol 2c17: 2,2'-disulfanediylbis(4-
bromoaniline) was reacted according to the general
procedure affording the product as a white solid. Elute by
CH2Cl2, Yield: 167 mg, 85% yield. Mp: 265-266 °C; MS (EI):
6-methoxybenzo[d]thiazole-2-thiol
2i1b
:
2,2'-
disulfanediylbis(4-methoxyaniline) was reacted according to
the general procedure affording the product as a white solid.
Elute by CH2Cl2, Yield: 142 mg, 90% yield. Mp: 203-204 °C; MS
(EI): m/z 197.0 [C8H7NOS2], calcd. [M] 197.0. 1H NMR (500
MHz, DMSO-d6, TMS): δ (ppm) 13.61 (brs, 1H), 7.35 (d, 1H, J =
2.5 Hz), 7.22 (d, 1H, J = 9.0 Hz), 6.99 (dd, 1H, J1 = 8.5 Hz, J2 =
2.5 Hz), 3.77 (s, 3H). 13C NMR (125 MHz, DMSO-d6, TMS): δ
(ppm) 188.24, 156.51, 135.08, 130.58, 114.68, 112.95,
105.81, 55.59.
1
m/z 244.9 [C7H4BrNS2], calcd. [M] 244.9. H NMR (500 MHz,
DMSO-d6, TMS): δ (ppm) 13.86 (brs, 1H), 7.98 (d, 1H, J = 2.0
Hz), 7.56 (dd, 1H, J1 = 8.5 Hz, J2 = 2.0 Hz), 7.22 (d, 1H, J = 8.5
Hz). 13C NMR (125 MHz, DMSO-d6, TMS): δ (ppm) 189.94,
140.58, 131.39, 129.84, 124.04, 116.21, 113.78.
5-chlorobenzo[d]thiazole-2-thiol 2d18: 6,6'-disulfanediylbis(3-
chloroaniline) was reacted according to the general
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C6GC03053J
Journal Name
ARTICLE
6-methylbenzo[d]thiazole-2-thiol 2j16: 2,2'-disulfanediylbis(4-
methylaniline) was reacted according to the general
procedure affording the product as a white solid. Elute by
CH2Cl2: EtOAc= 30:1, Yield: 129 mg, 89% yield. Mp: 179-181
Green Chem., 2012, 14, 2066-2070; (c) E. T. Ayodele, A. A.
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1
°C; MS (EI): m/z 181.1 [C8H7NS2], calcd. [M] 181.0. H NMR
(500 MHz, CDCl3, TMS): δ (ppm) 11.76 (brs, 1H), 7.27 (s, 1H),
7.23 (d, 1H, J =8.0 Hz), 7.18-7.16 (m, 1H), 2.40 (brs, 3H). 13C
NMR (125 MHz, CDCl3, TMS): δ (ppm) 190.23, 138.14, 134.90,
130.13, 128.29, 121.36, 111.91, 21.24.
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Acknowledgements
The authors gratefully acknowledge the financial support
provided by the National Natural Science Foundation of China
(21362019), Natural Science Foundation of Inner Mongolia
Autonomous Region of China (2016MS0207) and CAS “Light
of West China” Program.
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DOI: 10.1039/C6GC03053J
Table of Contents
A convenient and efficient method for the synthesis of 2-mercaptobenzothiazoles from disulfide
and CS2 was performed by dynamic interchange reaction between disulfide and metal sulfide in
water.