Eco-friendly synthesis of 2-substituted benzothiazoles catalyzed by silica sulfuric acid

Article abstract of DOI:10.1007/s11164-012-0739-y

2-Substituted benzothiazoles have been synthesized via one-pot reaction from aromatic aldehydes and o-aminothiophenol catalyzed by silica sulfuric acid in absolute methanol at room temperature. The remarkable advantages offered by this method are an envir

Full text of DOI:10.1007/s11164-012-0739-y

Res Chem Intermed (2013) 39:2077–2086
DOI 10.1007/s11164-012-0739-y
Eco-friendly synthesis of 2-substituted benzothiazoles
catalyzed by silica sulfuric acid
•
Guo Feng Chen Li Yan Zhang Hui Ming Jia
•
•
•
•
•
Bao Hua Chen Ji Tai Li Shu Xiang Wang
Guo Yi Bai
Received: 9 July 2012 / Accepted: 19 July 2012 / Published online: 3 August 2012
Ó Springer Science+Business Media B.V. 2012
Abstract 2-Substituted benzothiazoles have been synthesized via one-pot reaction
from aromatic aldehydes and o-aminothiophenol catalyzed by silica sulfuric acid in
absolute methanol at room temperature. The remarkable advantages offered by this
method are an environmentally friendly and reusable catalyst, a simple procedure,
mild conditions, short reaction times, and good to excellent yields of products.
Keywords Benzothiazoles ꢀ o-Aminothiophenol ꢀ Aldehydes ꢀ Silica sulfuric acid
Introduction
Benzothiazole and their derivatives are often found in heterocyclic compounds,
which exhibit a variety of biological activities [1, 2], such as a cathepsin S inhibitor
[3], an HIV reverse transcriptase inhibitor [4], an anticancer agent [5], and an
orexin-1 receptor antagonist [6]. They can also be used in industry as antioxidants,
vulcanization accelerators, and as a dopant in light-emitting organic electrolumi-
nescent devices [7–9]. Because of their importance, the synthesis of substituted
benzothiazoles has become a focus of synthetic organic chemistry. A number of
methods have been reported for the synthesis of benzothiazoles. One of the classic
methods for the synthesis of 2-aryl benzothiazoles is the condensation of o-
aminothiophenol with substituted nitriles [10], carboxylic acids [11–15], acyl
chlorides [16, 17], and esters [18]. Subsequently, because of the availability of a
G. F. Chen (&) ꢀ L. Y. Zhang ꢀ H. M. Jia ꢀ J. T. Li ꢀ S. X. Wang ꢀ G. Y. Bai
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental
Science, Hebei University, Wusi East Road No. 180, Baoding 071002, People’s Republic of China
e-mail: chenguofeng@hbu.edu.cn
B. H. Chen
College of Pharmaceutical Sciences, Hebei University, Baoding 071002,
People’s Republic of China
123

2078
G. F. Chen et al.
vast number of aldehydes, several improved protocols have been developed for the
synthesis of benzothiazoles via the condensation of o-aminothiophenol with
aldehydes. Various oxidative reagents, such as 4-methoxy-TEMPO [19], cetyltrim-
ethyl ammonium bromide [20], KAl(SO4)2ꢀ12H2O [21], H2O2/CAN [22], H2O2/HCl
[23], NaOAc [24], poly[4-diacetoxyiodo] styrene [25], Sc(OTf)3 [26], trichloroi-
socyanuric acid [27], I2 [28], HClO4/PANI [29], silica gel [30], PTSA [31],
activated carbon-molecular oxygen [32], ionic liquid [33], Bakers’ yeast [34], SDS
[35], glucose oxidase–peroxidase [36], P2O5 [37], Dowex 50W [38], Fe(HSO4)3
[39], etc., have all been used as oxidants in the reaction. However, many of these
methodologies are associated with one or more disadvantages such as expensive
reagents, drastic reaction conditions, low yields, tedious work-up procedures, and
co-occurrence of several side reactions. Therefore, a more effective and environ-
mentally friendly process is needed.
Recently, silica sulfuric acid has attracted a great deal of attention due to its
unique properties and potential applications in organic synthesis. It is a good proton
source in terms of convenience, cheapness, easy production, insolubility to all
organic solvents and can be selected as an excellent candidate for sulfuric acid or
chlorosulfonic acid replacement in organic reactions [40]. As reported in previous
papers, silica sulfuric acid has been used as an efficient catalyst in a number of
organic reactions with the advantage that it is reusable and has minimal
environmental impact [41–46]. Considering the above points and in continuation
of our work on the synthesis of heterocyclic compounds [47, 48], we report here a
green, mild, and practical method for the synthesis of 2-substituted benzothiazoles
from o-aminothiophenol and aldehydes at room temperature (Scheme 1).
Results and discussion
To examine the effect of reaction conditions on the synthesis of title compounds, the
condensation of o-aminothiophenol (1) and benzaldehyde (2a) was selected as the
model reaction. The results are summarized in Table 1.
In the studies regarding the effect of temperature and solvents, the above reaction
was conducted in the presence of silica sulfuric acid with various solvents such as
EtOH, CH3COOC2H5, CH2Cl2, CH3CN, THF, CHCl3, and CH3OH at room or
reflux temperature. The results indicated that the solvents and temperature had a
significant effect on the product yield (Table 1). In general, non-polar solvents such
as ethyl acetate afforded low yields either at room or reflux temperature. The best
conversion was observed when the reaction was performed in CH3OH at room
temperature. The yield of 2-phenylbenzothiazole (3a) was 85.2 % at rt (Entry 7)
SH
S
SiO2-OSO3H
CH3OH, r.t.
R
+
RCHO
N
NH2
1
2(a-r)
3(a-r)
Scheme 1 Synthesis of 2-substituted benzothiazoles
123

Eco-friendly synthesis
2079
Table 1 The effect of solvent and temperature on the synthesis of 2-phenylbenzothiazole (3a)
Entry
Solvent
Time (h)
Amount
of catalyst
(mg)
Isolated yield (%)
A
B
1
C2H5OH
CH3COOC2H5
CH3CN
CH2Cl2
THF
2
2
2
2
2
2
2
2
2
2
2
2
2
200
200
200
200
200
200
200
150
100
50
74.9
73.7
84.6
77.4
72.0
63.9
64.4
73.9
2
60.1
67.5
77.9
76.4
81.8
85.2
75.6
85.7
68.2
50.0
75.9a
73.5b
3
4
5
6
CHCl3
7
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
8
9
10
11
12
13
0
200
100
Reaction conditions: o-aminothiophenol (1.0 mmol), benzaldehyde (1.0 mmol), solvent (5 mL)
A reflux, B stirred at room temperature
a
Under ultrasound
b
Operated in nitrogen atmosphere
while at reflux temperature the reaction can be completed in 64.4 % yield (Entry 7)
within the same reaction time. So, we chose room temperature as the reaction
temperature. Moreover, we found that the yields were obviously affected by the
amount of silica sulfuric acid. When 200, 150, 100, 50, and 0 mg of silica sulfuric
acid were used, the yields were 85.2, 75.6, 85.7, 68.2, and 50.0 %, respectively
(Table 1, Entries 7–11). Therefore, 100 mg silica sulfuric acid was sufficient;
however, utilizing 200 mg of silica sulfuric acid did not significantly increase the
yield. In addition, in the absence of catalyst, the reaction gave an unsatisfactory
yield of 2-phenylbenzothiazole (3a) (Table 1, Entry 11). The above results showed
that silica sulfuric acid was essential for high yield, and the best results were
obtained when the reaction was carried out with 100 mg silica sulfuric acid at room
temperature. We also observed the effect of ultrasound irradiation on the reaction.
3a was obtained in 75.9 % yield under ultrasound irradiation at 25–30 °C (Table 1,
Entry 12). When the reaction was run under a nitrogen atmosphere, 2-phen-
ylbenzothiazole (3a) was obtained in 73.5 % yield (Table 1, Entry 13). These
results suggest that oxygen played an oxidant role in this reaction.
Recyclability of the catalyst was also investigated. After completion of the
reaction of o-aminothiophenol (1) and benzaldehyde (2a), the catalyst was separated
by filtration, thoroughly washed with ethyl acetate, and dried at room temperature
for 4 h. The recovered catalyst was then added to fresh substrates under the same
experimental conditions for three runs, our observations revealing that as the
number of the recycle of catalyst increases the activity decreases (Table 2).
123

2080
G. F. Chen et al.
Table 2 Synthesis of 2-phenylbenzothiazole (3a) with recovered catalyst
Cycle
Fresh
85.7
First
78.5
Second
74.8
Third
72.3
Yield (%)a
a
Isolated yield
Under the optimized reaction conditions, a range of 2-substituted benzothiazoles
3a–r was synthesized catalyzed by silica sulfuric acid at room temperature. The
results are summarized in Table 3. Most products described here have been
previously reported in the literature [11–39]. As shown in Table 3, the condensation
of o-aminothiophenol with a series of aromatic aldehydes afforded 2-substituted
benzothiazoles in excellent yields catalyzed by silica sulfuric acid in absolute
methanol. The reaction proceeded very cleanly at room temperature and no
undesirable side reactions were observed. Aromatic aldehydes bearing an electron-
withdrawing functionality, such as a nitro group, showed obviously weaker
reactivity than those containing electron-neutral or electron-donating groups. No
corresponding product was obtained when the substrate was 2-nitrobenzaldehyde or
2,4-dinitrobenzaldehyde (Table 3, Entries 19, 20) in this experiment.
Table 3 The synthesis of 2-substituted benzothiazoles derivatives catalyzed by silica sulfuric acid
Entry
R
Product
Time (h)
Yielda (%)
mp (°C) [lit]
1
C6H5
3a
3b
3c
3d
3e
3f
2.6
4.2
3.2
1.6
1.8
4.3
1.6
2.3
0.7
2.0
2.7
3.7
2.3
3.2
2.8
3.9
2.0
3.0
4.8b
5.0b
85.7
73.8
78.5
80.4
76.8
89.5
82.2
89.2
73.8
13.2
82.8
33.4
79.8
60.8
92.0
95.1
81.9
70.9
116–117 (112–114) [21]
81–83 (81–82) [1]
2
2-ClC6H4
3
2-OHC6H4
130–134 (129–131) [28]
110–112 (120–122) [20]
116–120 (114–115) [21]
232–238 (231) [35]
4
2-CH3OC6H4
4-ClC6H4
5
6
4-OHC6H4
7
4-CH3OC6H4
4-CH3C6H4
4-(Me)2NC6H3
4-NO2C6H4
3-ClC6H4
3g
3h
3i
122–124 (121) [35]
8
82–86 (83) [21]
9
184–186 (173) [35]
10
11
12
13
14
15
16
17
18
19
20
a
3j
236–241 (231–232) [20]
97–100 (94–95) [29]
194–197 (185–186) [16]
180–183 (162–164) [38]
170–173 (162–163) [39]
122–124 (118–120) [2]
151–152 (144–145) [1]
126–128 (125–127) [20]
107–108 (106) [35]
3k
3l
3-NO2C6H4
4-OH-3-MeOC6H3
2-OH-3-MeOC6H3
3,4-Cl2C6H3
2,4-Cl2C6H3
3,4-OCH2OC6H3
2-Furyl
3m
3n
3o
3p
3q
3r
–
2-NO2C6H4
2,4-(NO2)2C6H3
–
Isolated yield
b
No reaction
123

Eco-friendly synthesis
2081
According to the method catalyzed by 4-methoxy-TEMPO in presence of oxygen
[19], the time and yield of 3a were 9 h and 80 %, respectively, heating at 120 °C in
xylene for the condensation of o-aminothiophenol and benzaldehyde, while the
present procedure gave 85.7 % yield within 2 h (Table 3, Entry 1) at room
temperature. In the reaction catalyzed by Bakers’ yeast in DCM [34], 3h was
obtained in 67 % yield at room temperature for 24 h, whereas the present procedure
afforded 3h in 89.2 % yield within 2.3 h at room temperature (Table 3, Entry 8).
Encouraged by these results, the condensation of furfuraldehyde (2r) and o-
aminothiophenol (1) was also examined to extend the scope of this method, 2-(2-
furanyl)benzothiazole (3r) was obtained in moderate yields(70.9 %) within 3.0 h
(Table 3, Entry 18).
Conclusion
In conclusion, we have found an efficient and practical procedure for the preparation
of 2-substituted benzothiazoles catalyzed by silica sulfuric acid at room temper-
ature. Compared to the classical method, the remarkable advantages offered by this
are milder conditions, shorter reaction times, higher yields, non-corrosive, non-
polluting, and employing a reusable catalyst. The cheapness and availability of the
reagents, and the simple procedure and work-up make this method attractive for
large-scale operations.
Experimental
Apparatus, materials and measurements
All chemicals were obtained from commercial suppliers and were used without
further purification, and melting points were uncorrected. Silica sulfuric acid was
1
obtained according to the method reported in the literature [42]. The H NMR
(600 MHz) and 13C NMR (150 MHz) spectra were recorded on a Bruker AVANCE
III 600 spectrometer using TMS as internal standard and DMSO-d6 or CDCl3 as
solvent.
General procedure for synthesis of 2-substituted benzothiazoles
Aromatic aldehydes (2, 1.0 mmol) and o-aminothiophenol (1, 1.0 mmol) were
dissolved in absolute methanol (5 mL) in a 25-mL round bottomed flask. Silica
sulfuric acid (100 mg) was then added and the mixture was stirred in oil bath at
room temperature for a period time as indicated in Tables 1, 2, and 3 (reaction was
continued until aromatic aldehydes disappeared as indicated by TLC). The reactant
was dissolved in ethyl acetate. The catalyst was removed by filtration and washed
with ethyl acetate. The solvent was evaporated under reduced pressure. The crude
product was subjected to column chromatography on silica gel (200–300 mesh) and
eluted with petroleum ether or the mixture of petroleum ether and ethyl acetate.
123

2082
G. F. Chen et al.
All the products are known compounds and were identified by spectroscopic data
(1H NMR, 13C NMR) and comparison of their physical properties (melt point) with
the literature.
2-Phenylbenzothiazole (3a)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.11–8.14 (m, 3H, ArH),
7.93 (d, J = 8.0 Hz, 1H, ArH), 7.51–7.54 (m, 4H, ArH), 7.42 (t, J = 8.0 Hz, 1H,
ArH); 13C NMR (CDCl3, 150 MHz): dC 168.1, 154.2, 135.1, 133.6, 131.0, 129.0,
127.6, 126.34, 125.2, 123.3, 121.6.
2-(2-Chlorophenyl)benzothiazole (3b)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 8.23–8.26 (m, 1H, ArH), 8.17 (d,
J = 8.1 Hz, 1H, ArH), 7.98 (d, J = 8.0 Hz, 1H, ArH), 7.55–7.58 (m, 2H, ArH),
7.43–7.48 (m, 3H, ArH); 13C NMR (CDCl3, 150 MHz): dC 164.2, 152.5, 136.1,
132.8, 132.3, 131.8, 131.2, 130.8, 127.1, 126.3, 125.5, 123.5, 121.4.
2-(2-Hydroxyphenyl)benzothiazole (3c)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 12.55 (s, 1H, OH), 8.00 (d, 1H,
J = 8.0 Hz, ArH), 7.91 (d, 1H, J = 7.9 Hz, ArH), 7.71 (dd, 1H, J1 = 7.9 Hz,
J2 = 1.1 Hz, ArH), 7.51–7.54 (m, 1H, ArH), 7.40–7.44 (m, 2H, ArH), 7.14 (dd, 1H,
J1 = 8.3 Hz, J2 = 0.8 Hz, ArH), 6.97–6.99 (m, 1H, ArH); 13C NMR (CDCl3,
150 MHz): dC 169.4, 158.0, 151.9, 132.7, 132.6, 128.4, 126.7, 126.7, 125.5, 122.2,
121.5, 119.5, 117.9, 116.8.
2-(2-Methoxyphenyl)benzothiazole (3d)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.58 (dd, 1H, J1 = 7.8 Hz,
J2 = 1.6 Hz, ArH), 8.14 (d, J = 8.2 Hz, 1H, ArH), 7.96 (d, J = 7.9 Hz, 1H, ArH),
7.47–7.54 (m, 2H, ArH), 7.40 (t, J = 7.3 Hz, 1H, ArH), 7.17 (t, J = 7.4 Hz, 1H,
ArH), 7.08 (d, J = 8.3 Hz, 1H, ArH), 4.07 (s, 3H, CH3); 13C NMR (CDCl3,
150 MHz): dC 163.1, 157.3, 152.2, 136.2, 131.8, 129.6, 125.9, 124.6, 122.8, 122.4,
121.2, 111.7, 55.7.
2-(4-Chlorophenyl)benzothiazole (3e)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 8.09 (d, J = 8.1 Hz, 1H, ArH),
8.05 (d, J = 8.5 Hz, 2H, ArH), 7.92 (d, J = 8.0 Hz, 1H, ArH), 7.51–7.54 (m, 1H,
ArH), 7.49 (d, 1H, J = 8.6 Hz, ArH), 7.41–7.44 (m, 1H, ArH); 13C NMR (CDCl3,
150 MHz): dC 166.6, 154.1, 137.1, 135.1, 132.1, 129.3, 128.7, 126.5, 125.4, 123.3,
121.7.
123

Eco-friendly synthesis
2083
2-(4-Hydroxyphenyl)benzothiazole (3f)
1
Brown crystals, H NMR (DMSO-d6, 600 MHz): dH 10.25 (s, 1H, OH), 8.07 (d,
J = 7.9 Hz, 1H, ArH), 7.98 (d, J = 8.1 Hz, 1H, ArH), 7.94 (d, J = 8.5 Hz, 2H,
ArH), 7.49–7.51 (m, 1H, ArH), 7.39–7.41 (m, 1H, ArH), 6.94–6.96 (m, 2H, ArH);
13C NMR (DMSO-d6, 150 MHz): dC 167.9, 161.0, 160.8, 154.2, 134.6, 129.5,
126.9, 125.4, 124.6, 122.8, 122.6, 116.6, 116.5.
2-(4-Methoxyphenyl)benzothiazole (3g)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.06–8.07 (m, 3H, ArH),
7.90 (d, J = 8.0 Hz, 1H, ArH), 7.48–7.51 (m, 1H, ArH), 7.37–7.39 (m, 1H, ArH),
7.02–7.03 (m, 2H, ArH), 3.91 (s, 3H, OCH3); 13C NMR (CDCl3, 150 MHz): dC
167.9, 161.9, 154.2, 134.9, 129.1, 126.5, 126.2, 124.80, 122.8, 121.5, 114.4, 55.5.
2-(4-Methylphenyl)benzothiazole (3h)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 8.10 (d, J = 7.9 Hz, 1H, ArH),
8.02 (d, J = 8.2 Hz, 2H, ArH), 7.91 (d, J = 8.0 Hz, 1H, ArH), 7.50–7.53 (m, 1H,
ArH), 7.38–7.41 (m, 1H, ArH), 7.32 (d, J = 7.9 Hz, 2H, ArH), 2.45 (s, 3H, CH3);
13C NMR (CDCl3, 150 MHz): dC 168.3, 154.2, 141.5, 134.9, 131.0, 129.7, 127.5,
125.02, 126.3, 123.1, 121.6, 21.5.
2-(4-N,N-dimethylphenyl)benzothiazole (3i)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.02 (d, 1H, J = 8.0 Hz,
ArH), 7.98–8.00 (m, 2H, ArH), 7.86 (d, 1H, J = 8.4 Hz, ArH), 7.45–7.48 (m, 1H,
ArH), 7.32–7.34 (m, 1H, ArH), 6.75–6.78 (m, 2H), 3.07 (s, 6H, CH3); 13C NMR
(CDCl3, 150 MHz): dC 168.8, 154.4, 152.2, 134.6, 128.9, 126.0, 124.2, 122.3,
121.4, 111.7, 40.2.
2-(4-Nitrophenyl) benzothiazole (3j)
1
Yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.38 (d, J = 8.6 Hz, 2H, ArH),
8.30 (d, J = 8.7 Hz, 2H, ArH), 8.16 (d, J = 8.2 Hz, 1H, ArH), 7.98 (d, J = 7.9 Hz,
1H, ArH), 7.58 (t, J = 7.4 Hz, 1H, ArH), 7.49 (t, J = 7.4 Hz, 1H); 13C NMR
(CDCl3, 150 MHz): dC 164.8, 154.1, 149.1, 139.2, 135.5, 128.2, 126.9, 126.2,
124.3, 123.9, 121.8.
2-(3-Chlorophenyl)benzothiazole (3k)
White crystals, 1H NMR (CDCl3, 600 MHz): dH 8.14 (t, 1H, J = 1.8 Hz ArH), 8.11
(d, 1H, J = 8.2 Hz, ArH), 7.96–7.97 (m, 1H, ArH), 7.93 (d, 1H, J = 8.4 Hz, ArH),
7.52–7.55 (m, 1H, ArH), 7.47–7.49 (m, 1H, ArH), 7.42–7.45 (m, 2H, ArH); 13C
NMR (CDCl3, 150 MHz): dC 166.3, 154.0, 135.3, 135.2, 135.1, 130.9, 130.2, 127.4,
126.5, 125.7, 125.6, 123.5, 121.7.
123

2084
G. F. Chen et al.
2-(3-Nitrophenyl)benzothiazole (3l)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.93 (s, 1H, ArH), 8.42 (d,
J = 7.7 Hz, 1H, ArH), 8.34 (dd, 1H, J1 = 8.1 Hz, J2 = 1.3 Hz, ArH), 8.13 (d,
J = 8.2 Hz, 1H, ArH), 7.96 (d, J = 8.0 Hz, 1H, ArH), 7.70 (t, J = 7.9 Hz, 1H,
ArH), 7.56 (t, J = 7.5 Hz, 1H, ArH), 7.47 (t, J = 7.6 Hz, 1H, ArH); 13C NMR
(CDCl3, 150 MHz): dC 164.9, 153.9, 148.8, 135.3, 135.2, 133.0, 130.1, 126.8,
126.0, 125.1, 123.7, 122.3, 121.8.
2-(3-Methoxy-4-hydroxyphenyl)benzothiazole (3m)
Brown crystals, 1H NMR (CDCl3, 600 MHz): dH 9.85 (s, 1H, OH), 8.06 (d,
J = 8.2 Hz, 1H, ArH), 7.89 (d, J = 7.9 Hz, 1H, ArH), 7.75 (d, J = 1.8 Hz, 1H,
ArH), 7.56 (dd, 1H, J1 = 8.2 Hz, J2 = 1.9 Hz, ArH), 7.48–7.51 (m,1H, ArH),
7.37–7.39 (m, 1H, ArH), 7.03 (d, J = 8.2 Hz, 1H, ArH), 4.00 (s, 3H, CH3); 13C
NMR (CDCl3, 150 MHz): dC 168.2, 154.0, 148.6, 147.0, 134.8, 126.3, 126.2, 124.9,
122.7, 122.0, 121.5, 114.8, 109.3, 56.2.
2-(2-Hydroxy-4-methoxyphenyl)benzothiazole (3n)
Brown crystals, 1H NMR (CDCl3, 600 MHz): dH 9.85 (s, 1H, OH), 8.06 (d,
J = 8.1 Hz, 1H, ArH), 7.89 (d, J = 7.9 Hz, 1H, ArH), 7.75 (d, J = 1.4 Hz, 1H,
ArH), 7.56 (dd, 1H, J1 = 8.2 Hz, J2 = 1.7 Hz, ArH), 7.49 (t, J = 7.6 Hz, 1H,
ArH), 7.38 (t, J = 7.6 Hz, 1H, ArH), 7.03 (d, J = 8.2 Hz, 1H, ArH), 3.99 (s, 3H,
CH3); 13C NMR (CDCl3, 150 MHz): dC 168.2, 154.0, 148.6, 147.0, 134.8, 126.3,
126.2, 124.9, 122.7, 122.0, 121.5, 114.8, 109.3, 56.2.
2-(3,4-Dichlorophenyl)benzothiazole (3o)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 8.23 (d, J = 2.1 Hz, 1H, ArH),
8.09 (d, J = 8.2 Hz, 1H, ArH), 7.93(d, J = 7.9 Hz, 1H, ArH), 7.90 (dd, 1H,
J1 = 8.3 Hz, J2 = 2.0 Hz, ArH), 7.57 (d, J = 8.3 Hz, 1H, ArH), 7.52–7.55 (m, 1H,
ArH), 7.43–7.45 (m, 1H, ArH); 13C NMR (CDCl3, 150 MHz): dC 165.0, 154.0,
135.1, 133.5, 131.0, 129.0, 126.7, 126.5, 125.7, 123.5, 121.7.
2-(2,4-Dichlorophenyl)benzothiazole (3p)
1
White crystals, H NMR (CDCl3, 600 MHz): dH 8.26 (d, J = 8.5 Hz, 1H, ArH),
8.15 (d, J = 8.2 Hz, 1H, ArH), 7.97 (d, J = 8.0 Hz, 1H, ArH), 7.55–7.58 (m, 2H,
ArH), 7.45–7.48 (m, 1H, ArH), 7.42 (dd, 1H, J1 = 8.5 Hz, J2 = 2.0 Hz, ArH); 13
C
NMR (CDCl3, 150 MHz): dC 163.0, 152.4, 136.6, 136.1, 133.3, 132.5, 130.8, 130.6,
127.6, 126.5, 125.7, 123.5, 121.4.
123

Eco-friendly synthesis
2085
2-(30,40-Methylenedioxyphenyl)benzothiazole (3q)
1
Light yellow crystals, H NMR (CDCl3, 600 MHz): dH 8.05 (d, J = 8.1 Hz, 1H,
ArH), 7.88 (d, J = 7.9 Hz, 1H, ArH), 7.61–7.64 (m, 2H, ArH), 7.48–7.51 (m, 1H,
ArH), 7.37–7.40 (m, 1H, ArH), 6.92 (d, J = 8.0 Hz, 1H, ArH), 6.07 (s, 2H, CH2);
13C NMR (CDCl3, 150 MHz): dC 167.6, 154.0, 150.1, 148.4, 134.8, 128.0, 126.3,
125.0, 122.9, 122.5, 121.5, 108.7, 107.5, 101.7.
2-(2-Furanyl)benzothiazole (3r)
1
Brown crystals, H NMR (CDCl3, 600 MHz): dH 8.08 (d, J = 8.2 Hz, 1H, ArH),
7.90 (d, J = 7.9 Hz, 1H, ArH), 7.62 (s, 1H, FuranH), 7.51 (t, J = 7.3 Hz, 1H, ArH),
7.40 (t, J = 7.3 Hz, 1H, ArH), 7.22 (d, J = 2.8 Hz, 1H, FuranH), 6.61 (d,
J = 1.5 Hz, 1H, FuranH); 13C NMR (CDCl3, 150 MHz): dC 157.6, 153.7, 148.8,
144.7, 134.3, 126.5, 125.2, 123.1, 121.6, 112.5, 111.5.
Acknowledgments The project was supported by Natural Science Foundation of Hebei Province
(B2011201072) and Foundation of Hebei University (2009-163).
References
1. V.Z. Shirinian, S.Yu. Melkova, L.I. Belen’kii, M.M. Krayushkin, Russ. Chem. Bull. 49, 1859 (2000)
2. D.Q. Shi, S.F. Rong, G.L. Dou, Synth. Commun. 40, 2302 (2010)
3. D.C. Tully, H. Liu, P.B. Alper, A.K. Chatterjee, R. Epple, M.J. Roberts, J.A. Williams, K.T. Nguyen,
D.H. Woodmansee, C. Tumanut, J. Li, G. Spraggon, J. Chang, T. Tuntland, J.L. Harris, D.S. Ka-
ranewsky, Bioorg. Med. Chem. Lett. 16, 1975 (2006)
4. J.A. Grobler, G. Dornadula, M.R. Rice, A.L. Simcoe, D.J. Hazuda, M.D. Miller, J. Biol. Chem. 282,
8005 (2007)
5. J. Easmon, G. Prstinger, K.S. Thies, G. Heinisch, J. Hofmann, J. Med. Chem. 49, 6343 (2006)
6. K. Rasmussen, M.A. Hsu, Y. Yang, Neuropsychopharmacology 32, 786 (2007)
7. S.C. Debnath, D.K. Basu, J. Appl. Polym. Sci. 52, 597 (1994)
8. C.P. Ye, N.G. Wang, H.Q. Jia, X.J. Xu, Chin. J. Appl. Chem. 19, 1008 (2002)
9. A. Heynderickx, R. Guglielmetti, R. Dubest, J. Aubard, A. Samat, Synthesis 1112 (2003)
10. R.H. Tale, Org. Lett. 4, 1641 (2002)
11. M. Terashima, M. Ishii, Y. Kanaoka, Synthesis 484 (1982)
12. S. Mourtas, D. Gatos, K. Barlos, Tetrahedron Lett. 42, 2201 (2001)
13. A.K. Chakraborti, C. Selvam, G. Kaur, S. Bhagat, Synlett 851 (2004)
14. C.P. Chen, Y.J. Chen, Tetrahedron Lett. 45, 113 (2004)
15. J.A. Seijas, M.P. Vazquez-Tato, M.R. Carballido-Reboredo, J. Crecente-Campo, L. Romar-Lopez,
Synlett 313 (2007)
16. I.R. Laskar, T.M. Chen, Chem. Mater. 16, 111 (2004)
17. R.N. Nadaf, S.A. Siddiqui, T. Daniel, R.J. Lahoti, K.V. Srinivasan, J. Mol. Catal. A: Chem 214, 155
(2004)
18. H. Matsushita, S.H. Lee, M. Joung, B. Clapham, K.D. Janda, Tetrahedron Lett. 45, 313 (2004)
19. Y.X. Chen, L.F. Qian, W. Zhang, B. Han, Angew. Chem. Int. Ed. 47, 9330 (2008)
20. X.L. Yang, C.M. Xu, S.M. Lin, J.X. Chen, J.C. Ding, H.Y. Wu, W.K. Su, J. Braz. Chem. Soc. 21, 37
(2010)
21. S.S. Pawar, D.V. Dekhane, M.S. Shingare, S.N. Thore, Aust. J. Chem. 61, 905 (2008)
22. K. Bahrami, M.M. Khodaei, F. Naali, J. Org. Chem. 73, 6835 (2008)
23. H.Y. Guo, J.C. Li, Y.L. Shang, Chin. Chem. Lett. 20, 1408 (2009)
24. M. Okimoto, T. Yoshida, M. Hoshi, K. Hattori, M. Komata, K. Tomozawa, T. Chiba, Heterocycles
75, 35 (2008)
123

2086
G. F. Chen et al.
25. A. Kumar, R.A. Maurya, P. Ahmad, J. Comb. Chem. 11, 198 (2009)
26. T. Itoh, K. Nagata, H. Ishikawa, A. Ohsawa, Heterocycles 62, 197 (2004)
27. H.L. Xiao, J.X. Chen, M.C. Liu, D.J. Zhu, J.C. Ding, H.Y. Wu, Chem. Lett. 38, 170 (2009)
28. Y. Li, Y.L. Wang, J.Y. Wang, Chem. Lett. 35, 460 (2006)
29. M. Abdollahi-Alibeik, S. Poorirani, Phosphorus Sulfur Silicon Relat. Elem. 184, 3182 (2009)
30. M. Kodomari, Y. Tamaru, T. Aoyama, Synth. Commun. 34, 3029 (2004)
31. N. Azizi, A.K. Amiri, R. Baghi, M. Bolourtchian, M.M. Hashemi, Monatsh. Chem. 140, 1471 (2009)
32. Y. Kawashita, J. Yanagi, T. Fujii, M. Hayashi, Bull. Chem. Soc. Jpn. 82, 482 (2009)
33. B.C. Ranu, R. Jana, S.S. Dey, Chem. Lett. 33, 274 (2004)
34. U.R. Pratap, J.R. Mali, D.V. Jawale, R.A. Mane, Tetrahedron Lett. 50, 1352 (2009)
35. K. Bahrami, M.M. Khodaei, A. Nejatia, Green Chem. 12, 1237 (2010)
36. A. Kumar, S. Sharma, R.A. Maurya, Tetrahedron Lett. 51, 6224 (2010)
37. S.V. Nalage, S.V. Bhosale, D.S. Bhosale, W.N. Jadhav, Chin. Chem. Lett. 21, 790 (2010)
38. C. Mukhopadhyay, A. Datta, J. Heterocycl. Chem. 46, 91 (2009)
39. H. Eshghi, M. Rahimizadeh, A. Shiri, P. Sedaghat, Bull. Korean Chem. Soc. 33, 515 (2012)
40. K.S. Niralwad, B.B. Shingate, M.S. Shingare, Bull. Korean Chem. Soc. 31, 981 (2010)
41. G.A. Olah, R. Molhotra, S.C. Narang, J. Org. Chem. 43, 4628 (1978)
42. M.A. Zolfigol, Tetrahedron 57, 9509 (2001)
43. T.S. Jin, H.X. Wang, K.F. Wang, T.S. Li, Synth. Commun. 34, 2993 (2004)
44. L.F. Xiao, J.J. Peng, C.G. Xia, Chin. Chem. Lett. 17, 617 (2006)
45. J.T. Li, X.T. Meng, B. Bai, M.X. Sun, Ultrason. Sonochem. 17, 14 (2010)
46. J.T. Li, X.T. Meng, L. Liu, G.F. Chen, Chin. J. Org. Chem. 31, 733 (2011)
47. J.T. Li, G.F. Chen, S.X. Wang, H. Lin, T.S. Li, Aust. J. Chem. 58, 231 (2005)
48. G.F. Chen, X.Y. Dong, F.Z. Meng, B.H. Chen, J.T. Li, S.X. Wang, G.Y. Bai, Lett. Org. Chem. 8, 464
(2011)
123