Short communication
Room-Temperature Synthesis of 2-Arylbenzothiazoles using Sulfuric Acid Immobilized on Silica as a Reusable Catalyst under Heterogeneous Condition
Behrooz Maleki,* Hafezeh Salehabadi and Mona Khodaverdian Moghaddam
Department of Chemistry, Sabzevar Tarbiat Moallem University, Postal Code 397, Sabzevar, Khorasan, Iran * Corresponding author: E-mail: malekibehrooz@gmail.com
Received: 11-07-2009
Abstract
Application of sulfuric acid immobilized on silica gel as an efficient and benign catalyst has been explored in the synthesis of 2-arylbenzothiazoles via condensation reaction of aldehydes with 2-aminothiophenol. The reactions proceed under heterogeneous and mild conditions in ethanol at room temperature to provide 2-arylbenzothiazoles in high yields.
Keywords: 2-Arylbenzothiazole, aldehyde, silica-supported sulfuric acid, heterogeneous catalyst
1. Introduction
Compounds containing benzothiazole nucleus belong to an important class of heterocycles which are known to possess important biological and pharmaceutical activities such as antitumors1 and anticancers.2 In addition, some of these compounds exhibit nonlinear optical,3 and luminescent4/fluorescent5 properties, and have therefore found applications in designing sensor molecules of specific interest. Consequently, preparation of benzothiazole derivatives with interesting biological activities has attracted particular attention, and a variety of methods for the synthesis of 2-arylbenzothia-zoles have been developed.611 The most common method for their synthesis involves direct condensation of aldehydes with 2-aminothiophenol in the presence of various catalysts such as MnO2/SiO2,12 p-TsOH or graphite supported on solid minerals under microwave irra-diation,13 I2/DMF,14 1-phenyl-3-methylimidazolium bromide [pmIm]Br by microwave irradiation,15 activated carbon (Shirasagi KL or Darco® KB) under oxygen atmosphere,16 O2 or H2O2 in the presence of Sc(OTf)3,17 cerium (IV) ammonium nitrate (CAN),18 dowex 50W,19 electrooxidation,20 and direct condensation of 2-aminot-hiophenol with aromatic aldehydes under microwave ir-radiation.21
2. Experimental
IR spectra were recorded on a Shimadzu 435-U-04 spectrophotometer (KBr pellets). 1H NMR spectra were obtained using Jeol FT NMR 90 MHz spectrometer in CDCl3 as solvent and TMS as an internal reference. Melting points were determined in open capillary tubes in a Stuart BI Branstead Electrothermal apparatus and are un-corrected.
2. 1. General Procedure for Synthesis of 2-Arylbenzothiazoles Catalyzed by H2SO4/SiO2
To a mixture of aldehyde 1a-m (1 mmol) and 2-ami-nothiophenol (1.2 mmol) dissolved in ethanol (5 ml) was added H2SO4.SiO2 (5 mg). The resulting mixture was stirred at room temperature for 15-40 min. After completion of the reaction as monitored by TLC, the solvent was removed under reduced pressure. The residue was dissolved in diethyl ether (5 ml) and heated to 40 °C for 3-5 minutes. The mixture was then cooled to room temperature and filtered to remove the catalyst. The filtrate was evaporated under reduced pressure to isolate a solid residue which was recrystallized from ethanol (2 x 5 ml) to afford pure products (2a-m).
2. 1. 1. Spectral Data of the Selected Compounds
2-Phenyl-benzothiazole (2a)
NMR (90 MHz, CDCl3): 5 (ppm) 7.41-8.08 (m, 9H, Ar-H). 13C NMR (22.5 MHz, CDCl3): 5 (ppm) 77.10 (CDCl3), 121.53, 123.23, 125.09, 126.22, 127.52, 128.91, 130.83, 133.64, 135.08, 154.19, 167.93. IR (KBr): v (cm-1) 3064, 1588, 1555, 1509, 1478, 1433, 1244, 962, 766.
2-(4-Methoxyphenyl)-benzothiazole (2c)
1H NMR (90 MHz, CDCl3): 5 (ppm) 3.82 (s, 3H, OMe), 7.00-7.95 (m, 8H, Ar-H). 13C NMR (22.5 MHz, CDCl3): 5 (ppm) 77.10 (CDCl3), 55.45 (OCH3), 114.43, 121.53, 122.90, 124.81, 126.21, 129.16, 134.91, 154.38, 162,02, 167.85. IR (KBr): v (cm-1) 3023, 2996, 2900, 2836, 1605, 1521, 1485, 1260, 832.
2-(4-Methylphenyl)-benzothiazole (2e)
1H NMR (90 MHz, CDCl3): 5 (ppm) 2.38 (s, 3H, CH3), 7.30-8.01 (m, 8H, Ar-H). IR (KBr): v (cm-1) 3024, 2905, 1609, 1521, 1484, 1456, 1434, 1384, 1312, 760.
2-(4-Cyanophenyl)-benzothiazole (2l)
1H NMR (90 MHz, CDCl3): 5 (ppm) 7.37-7.96 (m, 8H, Ar-H). 13C NMR (22.5 M3 Hz, CDCl3): 5 (ppm) 113.93, 118.08, 121.66, 123.68, 125.96, 126.69, 127.68, 132.50, 137.20, 153.88, 165.09. IR (KBr): v (cm-1) 3061, 2226, 1606, 1514, 1479, 1432, 1405, 764 cm-1.
2-(3-Nitrophenyl)-benzothiazoles (2m)
1H NMR (90 MHz, CDCl3): 5 (ppm) 7.44-8.30 (m, 7H, Ar-H). 8.85 (s, 1H, Ar-H). IR (KBr): v (cm-1) 3058, 1611, 1576, 1529, 1459, 1433, 1347, 761.
2. 2. Preparation and Reusability of the H2SO4.SiO2 Catalyst
To a slurry of silica gel (10 g, 200-400 mesh) in dry diethyl ether (50 ml) was added concentrated H2SO4 (3 ml) with shaking for 5 min. The solvent was evaporated under reduced pressure to obtain dry H2SO4.SiO2 catalyst which was then heated at 120 C for 3 hours.
In the next step, we investigated the reusability and recycling effect of H2SO4.SiO2 catalyst in these reactions At the end of each reaction, the catalyst was filtered, washed with diethyl ether, dried at 120 C for 3 hours, and reused in a subsequent reaction cycle. The recycled catalyst was employed consecutively for three reactions and no significant loss in its efficiency was observed.
3. Results and Discussion
In recent years, many heterogeneous organic reactions have been performed using various reagents supported on solid materials.22-29 Such procedures have many advantages over unsupported reagents such as cleaner
reactions, easier work up, reduced reaction times, high yields, and are environmentally benign.
H2SO4.SiO2 catalyst is an inexpensive, heterogeneous and stable catalyst possessing very high reactivity in comparison with unsupported H2SO4. This catalyst has been used in many different reactions including fisher type glycol silylation30 and acetylation of sugar derivatives.31
In continuation of our research on synthetic applications of heterogeneous catalysts32-34 and on synthesis of 2-arylbenzothiazoles,35 we report here a very simple synthesis of 2-arylbenzothiazoles by condensation of 2-aminot-hiophenol with aromatic aldehydes under heterogeneous and mild reaction conditions, catalyzed by H2SO4.SiO2 catalyst at room temperature (Scheme 1).
Scheme 1
To achieve the best results in terms of yield and reaction time, we examined the efficiency of different reaction media and catalyst amounts in condensation reaction of benzaldehyde 1a (1 mmol) with 2-aminothiophe-nol (1.2 mmol) as a model reaction. As shown in Table 1, a significant enhancement of the reaction rate and improvement of the yield of the reaction were observed when 5 mg of H2SO4.SiO2 in ethanol was used (entry 1). In the absence of H2SO4.SiO2 catalystno formation of the expected product was detected even after 2 hours (entries 5 and 6). In order to evaluate the effect of the catalyst concentration, the reaction was also conducted in the presence of various amounts of the catalyst (3 and 8 mg) at room temperature (entries 7 and 8).
Table 1. Screening of the reaction conditions for the synthesis of 2-phenylbenzothiazoles (2a).
Entry	Catalyst	Solvent	Time	Yield
			(min)	(%)a
1	H2SO4.SiO2 (5 mg)	EtOH	25	80
2	H2SO4.SiO2 (5 mg)	MeOH	35	60
3	H2SO4.SiO2 (5 mg)	ch3cn	40	40
4	H2SO4.SiO2 (5 mg)	CHCl3	45	20
5	SiO2 (5 mg)	EtOH	120	-
6	-	EtOH	120	-
7	H2SO4.SiO2 (3 mg)	EtOH	35	60
8	H2SO4.SiO2 (8 mg)	EtOH	25	74
a Isolated yields.
The optimized reaction conditions were conveniently extended to a variety of aromatic aldehydes 1b-m, and the results obtained are summarized in Table 2.
Table 2. Synthesis of 2-arylbenzothiazoles via condensation of 2-aminothiophenol with various aldehydes using H2SO4.SiO2 as a catalyst (5 mg) in EtOH at room temperature.
Entry Aldehyde
(1)
2-Arylbenzo-thiazole (2)
Time (min)
Yielda Observed
(%) mp (°C)
Literature
b
25
80 111-112 112-113
30
70 226-227 225-227
ct>o-<
20
94 120-122 120-121
40
70 126-128 125-126
35
78 83-85
84-86
f Q-
40
64 54-56
53-54
20
84 130-131 130-131
25
80 84-86
84-86

20
88 160-162 160-161
20
60
115-117 115-117
30
80 102-104 101-103

15
94 161-162 162-164
CN
35
92 180-183 181-182
a Isolated yields. b The yields refer to the isolated products characterized by spectroscopic (IR, 'H and 13C NMR) analysis and by comparison with the literature data.11-20,36
a
b
c
d
e
g
h
k
m
In order to examine the efficiency of the recycled catalyst in these reactions, the reaction of benzaldehyde 1a (1 mmol) with 2-aminothiophenol (1.2 mmol) was performed in the presence of fresh H2SO4.SiO2 catalyst (5 mg) at room temperature (Table 3). The recovered catalyst in this reaction work up was reused in subsequent reactions and found to be almost as reactive as the fresh catalyst with no significant loss of efficiency.
In these reactions, H2SO4.SiO2 catalyst can possibly act as a convenient proton source. The proposed mecha-
nism for this reaction is presented in Scheme 2 and involves (i) initial nucleophilic attack of NH2 group on aldehyde C=O group, activated by H2SO4.SiO2 catalyst, (ii) formation of an alkylidene intermediate [A], followed by cyclization to yield the adduct [B], and (iii) subsequent oxidation of [B] with H2SO4.SiO2/O2 (from air), followed by dehydration to furnish the products (2a-m). It is important to note that, when these reactions were conducted under nitrogen atmosphere using similar reaction conditions, they stopped at the benzothiazoline [B] stage with no furt-
Table 3. The efficiency of recycled H2SO4.SiO2 catalyst. CHO
fY" + rS |*YVT\
^^ ElOH,25mm,r.t.	\=/
1a	2a
Run	Time (min)	Yield (%)a
1	25	80
2	35	74
3	50	60
a Isolated yields.
her progress towards the expected benzothiazoles (2a-m). This implies that, the oxygen does not play any important role in the formation of benzothiazoline. However, the presence of air in the second, oxidation step of the reaction is essential to result in the formation of benzothiazoles.
4. Conclusion
We have demonstrated that H2SO4.SiO2 catalyst is as a cheap, reusable and eco-friendly catalyst for the synthesis of 2-arylbenzothiazoles.
5. Acknowledgements
Authors wish to dedicate the present work to Professor D. Azarifar, of Bu-Ali Sina University, Hamedan, Iran, for his remarkable lifetime contributions to research in chemistry and his constant inspirations given to his students.
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Povzetek
V prispevku je predstavljena uporaba žveplove (VI) kisline, imobilizirane na silikagelu kot učinkovitega in neškodljivega katalizatorja pri sintezi 2-arilbenzotiazolov v kondenzacijski reakciji aldehidov z 2-aminofenolom. Reakcije potekajo z visokimi izkoristki, pod milimi heterogenimi pogoji, pri sobni temperaturi in v etanolu kot topilu.