A simple and eco-friendly process catalyzed by montmorillonite K-10, with air as oxidant, for synthesis of 2-substituted benzothiazoles

Article abstract of DOI:10.1007/s11164-014-1619-4

Simple and eco-friendly synthesis of 2-substituted benzothiazoles is described. The reaction is performed in absolute ethanol at room temperature, using a catalytic amount of montmorillonite K-10, and with continuous bubbling of air as oxidant. Simplicity

Full text of DOI:10.1007/s11164-014-1619-4

Res Chem Intermed
DOI 10.1007/s11164-014-1619-4
A simple and eco-friendly process catalyzed
by montmorillonite K-10, with air as oxidant,
for synthesis of 2-substituted benzothiazoles
•
Guo Feng Chen Nan Xiao Jing Sen Yang
•
•
•
Hong Yang Li Bao Hua Chen Li Fen Han
•
Received: 30 December 2013 / Accepted: 13 March 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract Simple and eco-friendly synthesis of 2-substituted benzothiazoles is
described. The reaction is performed in absolute ethanol at room temperature, using
a catalytic amount of montmorillonite K-10, and with continuous bubbling of air as
oxidant. Simplicity, ease of handling of the system, an environmentally friendly and
reusable catalyst, a plentiful, inexpensive, and safe oxidant, and mild conditions are
the main advantages of this procedure.
Keywords Benzothiazoles Á o-Aminothiophenol Á Aromatic aldehydes Á
Montmorillonite K-10 Á Air oxidation
Introduction
Benzothiazole and its derivatives have been attracting increasing interest because of
their biological and pharmaceutical activity. Applications in drug discovery are
based on their antitumor [1–4], antimicrobial [5], and antiviral [6] activity. They are
also used in the production of antioxidants, vulcanization accelerators, and organic
Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1619-4)
contains supplementary material, which is available to authorized users.
G. F. Chen (&) Á N. Xiao Á J. S. Yang Á H. Y. Li
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; chenguofeng@hbu.cn
B. H. Chen
College of Pharmaceutical Sciences, Hebei University, Baoding 071002,
People’s Republic of China
L. F. Han
Shijiazhuang Shuanglian Fertilizer Co., Ltd., Shijiazhuang 050200, People’s Republic of China
123

G. F. Chen et al.
optoelectronic materials [7–9]. In recent years, because of their importance in
bioorganic and medicinal chemistry, numerous methods have been developed for
synthesis of benzothiazole and its derivatives. Among these, the most commonly
used method involves condensation of o-aminothiophenol with substituted nitriles
[10], carboxylic acids [11–14], acyl chlorides [15, 16], or esters [17]. These reactions
are often accomplished under drastic reaction conditions. Aldehydes have recently
become very popular starting materials for synthesis of 2-substituted benzothiazoles,
because of their ready availability, low cost, relatively low toxicity and ease of
transformation into a wide variety of functional groups. Several oxidants, for
example 4-methoxy-TEMPO [18], H2O2/CAN [19], H2O2/HCl [20], poly(4-diacet-
oxyiodo)styrene [21], Sc(OTf)3 [22], trichloroisocyanuric acid [23], I2 [24], HClO4/
PANI [25], activated carbon–molecular oxygen [26], bakers’ yeast [27], glucose
oxidase–peroxidase [28], and Fe(HSO4)3 [29], among others, have been used in the
cyclocondensation of o-aminothiophenol and aldehydes. Other methods include
cyclization of thioformanilides [30, 31], copper-catalyzed coupling of 2-haloanilides
with metal sulfides [32], palladium-catalyzed Suzuki biaryl coupling of 2-halo-
benzothiazole with arylboronic acids [33, 34], and coupling of benzothiazoles with
aryl bromides [35]. We have recently reported the preparation of 2-substituted
benzothiazoles promoted by FeCl3–montmorillonite K-10 or silica–sulfuric acid [36,
37]. However, despite the merits of these procedures, many have one or more
disadvantages, for example harsh reaction conditions, requirement for excess
reagents or catalysts, prolonged reaction time, low yields of products, tedious work
up procedures, and non-reusability of the catalysts. Development of a more efficient,
convenient, and environmentally friendly methods for synthesis of 2-substituted
benzothiazoles is, thus, still an important experimental challenge for chemists.
Environmentally friendly or ‘‘green’’ chemistry is becoming increasingly important
in modern organic synthesis. This requires us to avoid the use of toxic and/or hazardous
solventsandreagents, preferablyeliminate the formation ofwaste, minimize the energy
requirement, and utilizerenewable raw materials where possible. Airandcommercially
available montmorillonite K-10 are materials that can fulfill these requirements.
Montmorillonite K-10 has been widely used in synthetic organic chemistry because it
is non-toxic, inexpensive, air and water-compatible, highly effective under mild
reaction conditions, non-corrosive, and recyclable; use and work-up procedures are
also convenient [38–42]. Recently, use of air as an oxidant has attracted much attention
because it is inexpensive, readily available, simple to use, non-toxic, and safe [43–45].
As a part of our continuing attempts to develop green synthetic routes for
biologically important heterocycles [44], we report here the use of montmorillonite
K-10 as a reusable catalyst and continuous bubbling of air as oxidant for synthesis
of 2-substituted benzothiazoles by condensation of o-aminothiophenol and a variety
of aldehydes (Scheme 1).
Results and discussion
We have previously reported that synthesis of 2-substituted benzimidazoles in
absolute ethanol at room temperature can be promoted by continuous bubbling of air
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A simple and eco-friendly process catalyzed by montmorillonite K-10
NH2
N
S
Montmorillonite K-10
+
R
RCHO
air, EtOH, r.t.
H
S
1
2(a-r)
3(a-r)
Scheme 1 Synthesis of 2-substituted benzimidazoles
[45]. In continuation of our interest in the use of air in useful synthetic methods, we
attempted to synthesize 2-substituted benzothiazoles from o-aminothiophenol and
aldehydes with use of air to improve the efficiency of the reaction. Initially,
synthesis of 2-phenylbenzothiazole (3a) from benzaldehyde (2a) and o-aminothio-
phenol (1) was performed as model reaction. The results are listed in Table 1. The
model reaction yielded 65.8 % 3a after 10 h with continuous bubbling of air as
oxidant, at room temperature, with stirring (Table 1, Entry 1). Similar results were
observed in the presence of Na2SO4 and MgSO4 (Table 1, Entries 2, 3). I2 was also
used as promoter in the model reaction under the same conditions, and 3a was
obtained in 79.6 % yield after 10 h at 25–30 °C in absolute ethanol (Table 1, Entry
4). The poor yield of 3a inspired us to investigate this transformation further. When
montmorillonite K-10 (25 mg) was added to the system as catalyst, the yield of 3a
was increased to 84.0 % (Table 1, Entry 5). Thus, montmorillonite K-10 has a
definitive catalytic effect on benzothiazole formation. When 50, 75, and 100 mg
montmorillonite K-10 were used, the yields were 80.4, 81.7 and 81.5 %,
respectively (Table 1, Entries 6–8). From this, we concluded that 25 mg of
montmorillonite K-10 was the optimum amount of catalyst for this reaction.
Post-treatment in this method is simple. After completion of the reaction (as
indicated by TLC), the mixture was filtered and the ethanol was removed under
reduced pressure to afford the crude product. The corresponding benzothiazoles
were obtained by silica gel chromatography with petroleum ether or a mixture of
petroleum ether and ethyl acetate as eluent.
To study the scope and limitations of this new procedure, a variety of aldehydes
with electron-donating or electron-withdrawing groups were investigated. The
results are listed in Table 2. A variety of substituents, for example p-methyl, o-
chloro, o-methoxy, and m-chloro gave excellent yields ([80 %). The highest yield
was obtained with m-chlorobenzaldehyde as starting material (Table 2, Entry 11).
For p-hydroxy, 2,4-dichloro, 4-dimethylamino, o-hydroxy, 3-nitro, and 4-nitro as
substituents, however, yields were \40 %. Of all aldehydes, 4-dimethylamino-
benzaldehyde gave the lowest yield (17.6 %).
The procedure is, moreover, also applicable to heterocyclic aldehydes, for
example furfural (2q), which produced the corresponding 2-(2-furanyl)benzothia-
zole (3q) smoothly in moderate yield (73.5 %) within 35 h (Table 2, Entry 18).
Under the same reaction conditions, none of the desired products were obtained
when aliphatic aldehydes, for example n-butyraldehyde and n-heptaldehyde, were
used as substrates (Table 2, Entries 21, 22). The product was probably destabilized
because the resulting benzothiazole cannot form a conjugated plane. The same
123

G. F. Chen et al.
Table 1 Optimization of the conditions for synthesis of 2-phenylbenzothiazole (3a)a
Entry
Catalyst
Solvent
Time (h)
Isolated yield (%)b
1
2
3
4
5
6
7
8
a
None
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
10
10
10
10
10
10
10
10
63.8
71.0
64.5
79.6
84.0
80.4
81.7
81.5
Na2SO4 (25 mg)
MgSO4 (25 mg)
I2 (25 mg)
Montmorillonite K-10 (25 mg)
Montmorillonite K-10 (50 mg)
Montmorillonite K-10 (75 mg)
Montmorillonite K-10 (100 mg)
Standard conditions: o-aminothiophenol (1.0 mmol), benzaldehyde (1.0 mmol), absolute ethanol
(10 mL), continuous bubbling of air, room temp
b
Isolated yield after silica gel column chromatography
Table 2 Synthesis of 2-substituted benzothiazole derivatives
Entry
R
Product
Time (h)
Isolated yield (%)
m.p. (°C) (lit)
1
C6H5
3a
3a
3b
3c
3d
3e
3f
10
10
15
12
40
40
14
17
28
13
9
84.0
77.0a
55.2
83.9
23.8
47.1
17.6
81.3
85.3
38.3
88.3
31.5
64.3
37.1
47.1
48.1
53.2
73.5
19.4
–
113–115 (112–113) [24]
2
C6H5
3
4-ClC6H4
118–120 (116–117) [25]
84–86 (83–85) [24]
226–228 (230–234) [36]
123–124 (120–122) [24]
172–175 (169–170) [25]
82–84 (80–82) [36]
104–106 (110–112) [36]
134–136(129–131) [24]
99–100 (94–95) [25]
186–188 (183–185) [24]
123-124 (123-124) [36]
146–149 (150–152) [36]
176–178 (180–182) [36]
160–161 (162–163) [29]
126–128 (129–130) [36]
98–100 (102–104) [24]
232–234 (235) [26]
–
4
4-CH3C6H4
4-OHC6H4
5
6
4-CH3OC6H4
4-(Me)2NC6H4
2-ClC6H4
7
8
3g
3h
3i
9
2-CH3OC6H4
2-OHC6H4
10
11
12
13
14
15
16
17
18
19
20
21
22
a
3-ClC6H4
3j
3-NO2C6H4
3,4-Cl2C6H3
2,4-Cl2C6H3
4-OH-3-MeOC6H3
2-OH-3-MeOC6H3
3,4-OCH2OC6H3
2-Furyl
3k
3l
40
55
31
40
38
39
35
28
40b
15b
15b
3m
3n
3o
3p
3q
3r
4-NO2C6H4
2,4-(NO2)2C6H3
CH3CH2CH2
CH3(CH2)5
–
–
–
–
The reaction was carried out on a 20 mmol scale
b
No reaction
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A simple and eco-friendly process catalyzed by montmorillonite K-10
Table 3 Synthesis of 2-phenylbenzothiazole (3a) with recovered montmorillonite K-10
Number of cycles
Isolated yield (%)
Fresh
84.0
Recycle I
79.5
Recycle II
75.5
Recycle III
75.4
Recycle IV
74.0
HS
N
Montmorillonite K-10
air, EtOH, r.t.
H2N
S
H
O
1
2a
3a
K-10
[O2]
-H2O
SH
S
N
H
N
I
II
Scheme 2 Proposed mechanism for the synthesis of 2-phenylbenzothiazole (3a)
situation was found when 2,4-dinitrobenzaldehyde was used as substrate (Table 2,
Entry 20).
Recovery and reusability of the catalyst are among the most important features of
this procedure. After completion of the reaction of 1 and 2a, the catalyst was
separated by simple filtration, washed successively with absolute ethanol to remove
remaining organic compounds, dried at 120 °C for 1 h, and re-used. Recovered
catalyst was reused for four consecutive runs under the same experimental
conditions as for the initial run, and furnished the corresponding benzothiazole with
isolated yields of 79.5, 75.5, 75.4 and 74.0 % (Table 3). These experimental results
reveal that the catalyst can be reused accompanied by appreciable loss of its
activity.
Montmorillonite K-10 has been widely used as an acidic catalyst for a variety of
organic reactions because of its Brønsted and Lewis acidity [40, 41]. The
mechanism proposed for synthesis of 2-phenylbenzothiazole catalyzed by mont-
morillonite K-10 with air as oxidant is shown in Scheme 2. First, the carbonyl
oxygen of benzaldehyde is activated by the acid sites of montmorillonite K-10 and
subsequently condenses with o-aminothiophenol to form a Schiff base of type (I) as
intermediate. Intermediate (I) is converted to a five-membered ring intermediate (II)
in either a sequential or concerted manner. Finally, elimination of hydrogen from
intermediate (II), with air as oxidant, affords 2-phenylbenzothiazole (3a).
Finally, to show the potential of our procedure for large-scale synthesis of these
heterocycles, condensation of 1 with 2a was conducted on the 20 mmol scale, by
123

G. F. Chen et al.
use of the montmorillonite K-10–air system at room temperature. The reaction
proceeded smoothly and the isolated yield of 3a was 77.0 %, slightly less than that
obtained on the smaller scale under these mild conditions.
Conclusion
In summary, a facile and green method catalyzed by montmorillonite K-10 at room
temperature, with continuous bubbling of air as oxidant, has been developed for
synthesis of 2-substituted benzothiazoles. Compared with methods reported
previously, this procedure features mild reaction conditions, a practically inex-
haustible oxidant, and easy separation and reuse of the catalyst. Also, the
montmorillonite K-10–air system is inexpensive, safe, and environmentally benign.
Experimental
Apparatus, materials, and measurements
Unless otherwise specified, materials were purchased from commercial suppliers
and used without further purification. Montmorillonite K-10 from Sigma–Aldrich
was used without pretreatment. Before use in reactions, solvents were dried and
freshly distilled by use of standard literature procedures. Reactions were monitored
by use of thin-layer chromatography (TLC) on silica gel F254 plates. Melting points
are uncorrected. 1H NMR (600 MHz) spectra were recorded at room temperature on
a Bruker Avance III 600 spectrometer with CDCl3 or DMSO-d6 as solvent and
tetramethylsilane (TMS) as internal standard.
General procedure for synthesis of 2-substituted benzothiazoles
Aldehyde (2, 1.0 mmol) and o-aminothiophenol (1, 1.0 mmol) were mixed in
absolute ethanol (10 mL) in a 50-mL three-necked flask equipped with a water-
cooled condenser and a gas inlet, as reported elsewhere [45]. The solution was
stirred at room temperature, then montmorillonite K-10 (25 mg) was added. Air was
bubbled continuously through the reaction system, at a speed of 60 bubbles per
minute on average, by means of a small air pump. After completion of the reaction
(monitored by TLC) the catalyst was recovered by filtration and washed with EtOH.
The filtrate was concentrated and purified by short column chromatography on silica
gel, with petroleum ether or a mixture of petroleum ether and ethyl acetate as
eluent, to give the pure product. The products (3a–r) are all known compounds and
1
were identified by H NMR spectroscopy, by comparison of their melting points
with those reported in the literature, and by comparison of their TLC Rf values with
those of standards.
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A simple and eco-friendly process catalyzed by montmorillonite K-10
Acknowledgments The project was supported by the Students’ Innovative Entrepreneurship Training
Project of Hebei University (2013077) and the Natural Science Foundation of Hebei Province
(B2011201072).
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