Green and highly efficient synthesis of 2-arylbenzothiazoles using glycerol without catalyst at ambient temperature

Article abstract of DOI:10.3390/molecules17056011

A one-pot and clean synthesis of 2-arylbenzothiazoles via the ambient temperature reaction of 2-aminothiophenols and aromatic aldehydes without catalyst in glycerol as a green solvent has been reported. 2012 by the Authors.

Full text of DOI:10.3390/molecules17056011

Molecules 2012, 17, 6011-6019; doi:10.3390/molecules17056011
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Green and Highly Efficient Synthesis of 2-Arylbenzothiazoles
Using Glycerol without Catalyst at Ambient Temperature
Kamal Usef Sadek 1,*, Ramadan Ahmed Mekheimer 1,2, Afaf Mohamed Abdel Hameed 1,
Fatma Elnahas 1 and Mohamed Hilmy Elnagdi 3
1
Chemistry Department, Faculty of Science, El-Minia University, El-Minia 61519, Egypt
2
Chemistry Department, Faculty of Science for Girls, King Abdulaziz University, P.O. Box 50918,
Jeddah 21533, Saudi Arabia
3
Chemistry Department, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
* Author to whom correspondence should be addressed; E-Mail: kusadek@yahoo.com;
Tel.: +20-86-236-4806; Fax: +20-86-236-3011.
Received: 27 March 2012; in revised form: 9 May 2012 / Accepted: 10 May 2012 /
Published: 18 May 2012
Abstract: A one-pot and clean synthesis of 2-arylbenzothiazoles via the ambient
temperature reaction of 2-aminothiophenols and aromatic aldehydes without catalyst in
glycerol as a green solvent has been reported.
Keywords: synthesis; 2-arylbenzothiazoles; glycerol; 2-aminothiophenols
1. Introduction
With technological and scientific advancement comes cost, and with respect to this issue, the most
important cost to be dealt with is the impact of these technologies on our environment [1]. Most
organic reactions occur in a liquid phase. Taking into account the impact of chemical processes on the
environment, the search for green solvents has become a great challenge in organic synthesis, as
solvents are responsible for a large part of the waste and pollution generated by chemical processes, a
key factor in any green chemical process is solvent selection [2].
Glycerol is a non-toxic, biodegradable and recyclable liquid that is highly inert, stable and also
dissolves organic compounds that are poorly miscible in water. It combines the advantages of water
(low toxicity, low price, wide availability) and ionic liquids (highly boiling point, low vapor pressure) [3].
These advantages make it ideal for use as a sustainable solvent in organic synthesis.

Molecules 2012, 17
6012
2-Arylbenzothiazoles can be found in a variety of natural products as well as a number of biologically
active compounds [4]. They are a class of potent and selective antitumor agents which exhibit
nanomolar inhibitory activity against a range of human breast, colon and renal cell lines in vitro [5].
In addition, they possess significant utility as imaging agents for β-amyloid, antitubercullotic,
chemiluminescent agents, calcium channel antagonists, antiparasitics and photosensitizers [6–10].
To date, two common strategies have been developed used for the synthesis of 2-arylbenzothiazoles.
The first approach is through arylation of benzothiazole with aryl bromides catalyzed by Pd(OAc)2,
Cs2CO3 and CuBr with P(t-Bu)3 as a ligand at 150 °C in a sealed tube [11], or Suzuki biaryl coupling
of 2-bromothiazoles with arylboronic acids [12]. The second method is via condensation of
2-aminothiophenols with substituted nitriles, carboxylic acids, aryl chlorides, esters or aldehydes [13].
A number of catalysts such as (PmIm)Br [14], I2 [15], ZrOCl2•8H2O [16], TMSCl [17], PCC [18],
CAN [19], molecular oxygen [20], H2O2 [21], MnO2 [22], Baker,s yeast [23], animal bone meal [24],
electrooxidation [25], Na2S2O5 in refluxing DMF [26] have been used to perform the cyclization step.
Recently, some green approaches for the preparation of 2-arylbenzothiazoles based on the direct
condensation of 2-aminothiophenols with aromatic aldehydes have been reported. They involve
the use of PTSA either in water at 70 °C or PEG, 200/400 under microwave heating [27,28],
Cu(OAc)2/MCM41 supported catalyst under ultrasound irradiation [29], NIBTS at ambient temperature
under solvent free conditions [30], Dowex 50W reusable catalyst in water at 70 °C [31], TCCA in
MeTHF at ambient temperature [32], heating in water at 110 °C [33], 2,4,6-trichloro-1,3,5-triazine
under mild conditions [34], H2SO4/SiO2 as a reusable catalyst at room temperature [35] or sulfamic
acid as a reusable catalyst in water at room temperature [36]. Although, these methods each have
specific merits, they suffering from some drawbacks such as high temperature conditions, long
reaction times and sometimes low yields. In addition, the catalysts employed in most of these
cyclization steps are not always inexpensive or eco-friendly, and consequently, serious environmental
pollution often results when the catalysts contaminate the environment. Since glycerol is able to
dissolve organic compounds that are poorly miscible in water, its use as a green solvent without
catalyst would overcome such drawbacks. Also, conducting the reaction at ambient temperature will
increase the energy efficiency of the reaction. Very recently, a one-step synthesis of 2-arylbenzothiazoles
from the reaction of gem-dibromomethylarenes with 2-aminothiophenol employing t-BuOK and a
catalytic amount of iodine in pyridine at reflux temperature has been reported [37]. In 2012, Cheng and
co-workers have described another approach to 2-arylbenzothiazoles via Jacobson’s cyclization of
thiobenzanilides catalyzed by aerobic visible light, but this route requires a multistep reaction
sequence [38]. In this regard, employing a benign solvent under catalyst free conditions for the
synthesis of the target molecules will be of great interest in the area of green chemistry.
In continuation of our work aiming at development of efficient, simple and green technologies for
the synthesis of heterocycles [39–41], we reported herein a one-pot synthesis of 2-arylbenzothiazoles
from the ambient temperature reaction of 2-aminothiophenols 1 with aromatic aldehydes 2 in glycerol
under catalyst free conditions.

Molecules 2012, 17
6013
2. Results and Discussion
With the initial aim of optimising the experimental conditions, we explored the reaction of
2-aminothiophenol (1a) and benzaldehyde (2a) using glycerol as a solvent to afford the desired
2-phenyl-1,3-benzothiazole (4a) (Scheme 1). Thus, when a mixture of 1a (0.1 mol) and 2a (0.1 mol) in
glycerol (10 mL) was stirred at room temperature, it was observed that reactants were recovered almost
unchanged after a long period of time. The reaction promoted by just heating the reaction mixture until
the reactants were dissolved and then left at room temperature for 30 min afforded 4a in excellent
yield. The structure of compound 4a could be established on the basis of analytical and spectral data
and comparison with authentic specimen prepared via an alternative route [18]. Similarly, compounds
1a–c reacted with 2b–k, under the same reaction conditions, to afford 4b–k in excellent yields.
Scheme 1. One-pot synthesis of 2-arylbenzothiazoles 4a–k.
R
R
R
O
SH
SH
S
gl ycero l
RT
gly cerol
Ar
Ar
H
N
N
NH2
2a -k
Ar
4a-k (80-9 3%)
3
1
a, R= H
b, R= Cl
c, R= OCH3
2,4
Ar
R
H
H
C6H5
a
b
4-CH O-C6H
3
4
c
3-NO2-C6H
H
H
H
4
4-Cl-C6H4
d
e
f
3,4- (CH3O)2-C6H3
4-NO2-C6H4
H
H
H
H
g
3,4,5-(CH O)3-C6H2
3
2-OH-C6H4
2-thienyl
h
i
j
Cl
4-CH O-C6H4
3
k
4-NO -C6H4
OCH3
2
In order to study the effect of solvent on the rate of the reaction we carried out the same reaction in
different solvents, such as H2O, acetone and CHCl3, under the same reaction conditions, and the
reactants were recovered almost unchanged. Next, we studied the effect of aromatic aldehyde
substituents on the reaction rate and the overall yield. With both electron withdrawing and electron
donating groups, the reaction proceeds smoothly, with a slight increase in the yield when the aryl
substituent bore an electron withdrawing group. We also studied the generality and applicability of
such protocol via examining the reaction of substituted 2-aminothiophenols bearing both electron
donating and electron withdrawing groups. In both cases, the reaction proceeds smoothly with good
yields. Although until now the reasons behind the promoting effect of glycerol are still unclear, a
mechanism to account for the formation of 4a–k is postulated in Scheme 2.

Molecules 2012, 17
6014
Scheme 2. A proposed mechanism for the formation of 2-arylbenzothiazoles 4a–k.
O
H
O
H
OH
R
SH
R
SH
O 


N
NH2

Ar
Ar
H
1a-c
2a-k
H
O
OH
H
O
R
R
S
S
O /air
- H2O
Ar
Ar
H
N
N
H
4a -k
3
The highly solving action of glycerol on the reactants makes them readily available to interact and the
carbonyl carbon of the aldehyde will be activated because of the intermolecular hydrogen bonding with
the hydroxyl groups of glycerol. In addition, the formed intermediates could be stabilized by several
types of complexations and hydrogen bonding with the hydroxyl groups of glycerol. This was followed
by cyclization to form the corresponding thiazoline intermediate 3 which, on dehydrogenation, via aerial
oxidation, is converted to the thiazole 4 which will enjoy the aromaticity (i.e., stabilization) of the
benzothiazole ring system. Conducting the reaction of 1a with 2a in the absence of air resulted in a
sluggish reaction inconvenient for complete product formation even after a longer reaction time. It is
worth mentioning that strong oxidants or more interestingly catalytic aerobic oxidation involving oxygen
as a terminal oxidant have received considerable attention in the synthesis of benzothiazoles [21]. The
advantage of our protocol is the use of only atmospheric air as the oxidant at ambient temperature.
However, we cannot totally rule out that the presence of trace amount of acidic and basic derivatives in
glycerol can act as possible catalysts.
3. Experimental
3.1. General
Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected.
2-Aminothiophenol (1a–c) and aldehydes 2a–k were commercially available. Infrared spectra were
1
measured with a Schimadzu Model 470 spectrophotometer. The H- and 13C-NMR spectra were
1
13
recorded on a Bruker AM 400 spectrometer (at 400 MHz for H-NMR and 100 MHz for C-NMR)
with DMSO-d6 as solvent and TMS as internal reference, chemical shifts are expressed as δ ppm. Mass
spectra were measured on a GCMS-QP1000EX mass spectrometer. Analytical data were determined

Molecules 2012, 17
6015
on the Microanalytical Data Unit at Kuwait University. Analytical TLC was performed with a silica
gel plates using silica gel 60 PF254 (Merck).
3.2. Synthesis of 2-Arylbenzothiazoles 4a–k
A mixture of thiophenols 1a–c (1.25 g, 10 mmol) and the appropriate aldehyde 2 (10 mmol) in
glycerol (10 mL) was heated until a clear solution was obtained and then left at room temperature for
0.5–5 h (TLC control). The reaction mixture was quenched with water and the resulting solid product
was collected by filtration, dried and recrystallised from EtOH to afford compounds 4a–k.
2-Phenyl-1,3-benzothiazole (4a). Yield: 92%; reaction time 0.5 h; mp 112–113 °C (Lit. [18] 115–116);
IR (KBr):  = 3,060, 3,020, 1,609, 1,590 cm−1; 1H-NMR: δ = 8.17 (d, 1H), 8.12–8.07 (m, 3H), 7.59–7.50
13
(m, 4H), 7.45 (t, 1H) ppm; C-NMR: δ = 167.30, 153.56, 134.45, 132.85, 131.44, 129.42, 127.20,
126.68, 125.57, 122.90, 122.38 ppm; MS m/z (rel. int. %) 211 (M+, 100); Anal. Calcd. for C13H9NS
(211.28): C, 73.90; H, 4.29; N, 6.63; S, 15.18. Found: C, 73.79; H, 4.19; N, 6.81; S, 14.98.
2-(4-Methoxyphenyl)-1,3-benzothiazole (4b). Yield 90%; reaction time 4h; mp 126–128 °C (Lit. [25]
1
119–120 °C); IR (KBr):  = 3,100, 3,060, 1,605, 1,585 cm−1; H-NMR: δ = 8.12 (d, 1H), 8.1–8.0 (m,
3H), 7.53 (t, 1H), 7.45 (t, 1H), 7.13 (d, 2H), 3.85 (s, 3H) ppm; 13C-NMR: δ = 167.05, 153.67, 134.23,
128.88, 126.52, 125.52, 125.11, 122.47, 122.20, 114.75, 55.5 ppm; MS m/z (rel. int. %) 241 (M+, 100);
Anal. Calcd. for C14H11NOS (241.31): C, 69.68; H, 4.59; N, 5.80; S, 13.29. Found: C, 69.55; H, 4.52;
N, 5.94; S, 13.18.
2-(3-Nitrophenyl)-1,3-benzothiazole (4c). Yield 92%; reaction time 2 h; mp 184–186 °C (Lit. [18]
181–183 °C); IR (KBr):  = 3,080, 3,035, 1,612, 1,580 cm−1; 1H-NMR: δ = 8.84 (s, 1H), 8.44 (d, 1H),
13
8.41 (d, 1H), 8.24 (d, 1H), 8.16 (d, 1H), 7.88 (t, 1H), 7.60 (t, 1H), 7.54 (t, 1H) ppm; C-NMR:
δ = 161.9, 157.5, 149.4, 142.8, 133.3, 130.7, 130.2, 126.5, 126.3, 122.5, 120.3, 119.5, 111.8 ppm; MS
m/z (rel. int. %) 256.0 (M+, 100); Anal. Calcd. for C13H8N2O2S (256.28): C, 60.93; H, 3.15; N, 10.93;
S, 12.51. Found: C, 60.86; H, 3.27; N, 11.02; S, 12.64.
2-(4-Chlorophenyl)-1,3-benzothiazole (4d). Yield 93%; reaction time 3 h; mp 116–118 °C (Lit. [25]
115–117 °C); IR (KBr):  = 3,088, 3,030, 1,615, 1,590 cm−1; 1H-NMR: δ = 8.18 (d, 1H), 8.09 (d, 1H),
7.68 (d, 2H), 7.57 (d, 2H), 7.48 (m, 2H) ppm; Anal. Calcd. for C13H8ClNS (245.73): C, 63.54; H, 3.28;
Cl, 14.43; N, 5.70; S, 13.05. Found: C, 63.47; H, 3.39; Cl, 14.58; N, 5.76; S, 12.87.
2-(3,4-Dimethoxyphenyl)-1,3-benzothiazole (4e). Yield 83%; reaction time 4 h; mp 130–132 °C (Lit. [19]
130–132 °C); IR (KBr):  = 3,078, 3,052, 2,962, 2,835, 1,600 cm−1; 1H-NMR: δ = 8.10 (d, 1H), 8.09–8.02
(m, 1H), 7.66–7.60 (m, 2H), 7.53 (t, 1H), 7.41 (t, 1H), 7.12 (d, 1H), 3.88 (s, 3H), 3.85 (s, 3H) ppm;
MS m/z (rel. int. %) 271 (M+, 100); Anal. Calcd. for C15H13NO2S (271.33): C, 66.40; H, 4.83; N, 5.16;
S, 11.82. Found: C, 66.36; H, 4.73; N, 5.25; S, 11.69.
2-(4-Nitrophenyl)-1,3-benzothiazole (4f). Yield 94%; reaction time 2 h; mp 224–225 °C (Lit. [25]
224–226 °C); IR (KBr):  = 3,082, 3,035, 1,615, 1,580 cm−1; 1H-NMR: δ = 8.32 (d, 2H), 8.21 (d, 1H),
8.10 (d, 2H), 8.01 (d, 1H), 7.53–7.44 (m, 2H) ppm; MS m/z (rel. int. %) 256.0 (M+, 100); Anal. Calcd.

Molecules 2012, 17
6016
for C13H8N2O2S (256.28): C, 60.93; H, 3.15; N, 10.93; S, 12.51. Found: C, 60.88; H, 3.25; N, 11.05;
S, 12.64.
2-(3,4,5-Timethoxyphenyl)-1,3-benzothiazole (4g). Yield 82%; reaction time 5 h; mp 130–131 °C; IR
1
(KBr):  = 3,082, 3,055, 2,965, 2,833, 1,600 cm−1; H-NMR: δ = 8.09–8.02 (m, 1H), 7.66–7.60 (m,
2H), 7.53 (t, 1H), 7.41 (s, 1H), 7.22 (s, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 3.84 (s, 3H) ppm; Anal. Calcd.
for C16H15NO3S (301.36): C, 63.77; H, 5.02; N, 4.65; S, 10.64. Found: C, 63.66; H, 5.03; N, 4.56;
S, 10.72.
2-(2-Hydroxyphenyl)-1,3-benzothiazole (4h). Yield 80%; reaction time 5 h; mp 123–124 °C; IR (KBr):
 = 3,450, 3,080, 3,042, 1,625 cm−1; 1H-NMR: δ = 8.21 (d, 1H), 8.16–8.01 (m, 3H), 7.62 (t, 1H), 7.53
(t, 1H), 7.07 (d, 2H) ppm; Anal. Calcd. for C13H9NOS (227.28): C, 68.70; H, 3.99; N, 6.16; S, 14.11.
Found: C, 68.73; H, 4.01; N, 6.21; S, 14.24.
2-Thienyl-1,3-benzothiazole (4i). Yield 81%; reaction time 5 h; mp 97–99 °C (Lit. [19] 97–99 °C); IR
1
(KBr):  = 3,083, 3,040, 1,630 cm−1; H-NMR: δ = 8.22 (d, 1H), 8.14 (d, 1H), 7.72 (d, 1H), 7.69 (d,
1H), 7.63–7.54 (m, 2H), 7.31 (t, 1H) ppm; MS m/z (rel. int. %) 217.0 (M+, 100); Anal. Calcd. for
C11H7NS2 (217.31): C, 60.80; H, 3.25; N, 6.45; S, 29.51. Found: C, 60.71; H, 3.19; N, 6.62; S, 29.33.
6-Chloro-2-(4-methoxyphenyl)benzothiazole (4j). Yield 88%; reaction time 4 h; mp 137–138 °C (Lit. [28]
136–138 °C); IR (KBr):  = 3,090, 3,060, 1,610, 1,590 cm−1; 1H-NMR: δ = 8.19 (s, 1H), 8.02 (d, 2H),
7.89 (d, 1H), 7.68 (d, 1H), 7.08 (d, 2H), 3.83 (s, 3H) ppm; Anal. Calcd. for C14H10ClNOS (275.75):
C, 60.98; H, 3.66; N, 5.08. Found: C, 60.88; H, 3.96; N, 5.22.
6-Methoxy-2-(4-nitrophenyl)benzothiazole (4k). Yield 80%; reaction time 5 h; mp 156–157 °C (lit. [28]
156–158 °C); IR (KBr):  = 3,080, 3,035, 1,620, 1,580 cm−1; 1H-NMR: δ = 8.23 (d, 2H), 8.08 (d, 2H),
13
7.73 (s, 1H), 7.58 (d, 1H), 7.19 (d, 1H), 3.83 (s, 3H) ppm; C-NMR: δ = 170.0, 156.7, 149.6, 147.9,
146.7, 136.8, 128.4, 124.6, 122.8, 114.7, 104.9, 55.8 ppm; MS m/z (rel. int. %) 286 (M+, 100); Anal.
Calcd. for C14H10N2O3S (286.31): C, 58.73; H, 3.52; N, 9.78 . Found: C, 58.66; H, 3.55; N, 9.66.
4. Conclusions
Glycerol has been employed for the first time as a benign solvent for the one-pot synthesis of
2-arylbenzothiazoles under catalyst free conditions and at ambient temperature. The procedure proved
to be simple both in conducting the reaction and isolation of the products. The yields obtained are
excellent and the products were recovered in pure form from the reaction mixture. To the best of our
knowledge, it is one of the few reported one-pot syntheses of 2-arylbenzothiazoles, from the reaction
of 2-aminothiophenol with aromatic aldehydes, at ambient temperature without catalyst.
References and Notes
1. Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice; Oxford University Press:
New York, NY, USA, 1998.

Molecules 2012, 17
6017
2. Candeias, N.R.; Branco, L.C.; Gois, P.M.P.; Afonso, C.A.M.; Trindade, A.F. More Sustainable
approaches for the synthesis of N-based heterocycles. Chem. Rev. 2009, 109, 2703–2802.
3. Gu, Y.; Jerome, F. Glycerol as a sustainable solvent for green chemistry. Green Chem. 2010, 12,
1127–1138.
4. Tasler, S.; Muller, O.; Wieber, T.; Herz, T.; Peyoraro, W.S.; Lang, M.; Krauss, R.; Totzke, F.;
Zirrgiebel, U.; Ehlert, J.E.; et al. Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead
optimization. Bioorg. Med. Chem. 2009, 19, 6728–6737.
5. Kashiyama, E.; Hutchinson, I.; Chua, M.S.; Stinson, S.F.; Phillipes, L.R.; Kaur, G.; Sausville, E.A.;
Bradshaw, T.D.; Westwell, A.D.; Stevens, M.F. Antitumor benzothiazoles 8. Synthesis, metabolic
and biological properties of the C- and N-oxidation products of antitumor 2-(4-aminophenyl)
benzothiazole. J. Med. Chem. 1999, 42, 4172–4184.
6. Mathis, C.A.; Bacski, B.J.; Kajdasz, S.T.; McLellan, M.E.; Frosch, M.P.; Hyman, B.T.; Holt, D.P.;
Wany, Y.; Huany, G.-F.; Debnath, M.L.; et al. A Lipophilic thioflavin-T. derivatives for positron
emission tomography (PET) imagin of amyloid brain. Bioorg. Med. Chem. Lett. 2002, 12, 295–298.
7. Yamamoto, K.; Fujitta, M.; Tabashi, K.; Kawashima, Y.; Kato, E.; Oya, M.; Iso, T.; Iwao, J.
Novel calcium antagonists. Synthesis and structure-activity relationship studies of benzothiazoline
derivatives. J. Med. Chem. 1988, 31, 919–930.
8. Yoshida, H.; Nakao, R.; Nohta, H.; Yamaguchi, M. Chemiluminescent properties of some
luminol-related compounds-part 3. Dyes Pigm. 2000, 47, 239–245.
9. Lee, B.C.; Jung, J.H.; Jeong, J.M.; Kim, S.E. Aromatic radioflurination and biological evaluation
of 2-aryl-6-[18F]fluorobenzthiazoles as a potential positron emission tomography imaging probe
for β-amyloid plakues. Bioorg. Med. Chem. 2011, 19, 2980–2990.
10. Xie, Y.; Deng, S.; Chen, Z.; Yan, S.; landry, D.W. Identification of small-molecule inhibitors of
the AB-ABAD interaction. Bioorg. Med. Chem. Lett. 2006, 16, 4657–4660.
11. Alagille, D.; Baldwin, R.M.; Tamagnan, G.D. One-pot synthesis of 2-arylbenzothiazole (BTA)
and benzoxazole precoursers for in vivo imaging of β-amyloid plaques. Tetrahedron Lett. 2005,
46, 1349–1351.
12. Majo, V.J.; Prabhakaran, J.; Mann, J.J.; Kumar, J.S.D. An efficient palladium catalyzed synthesis
of 2-arylbenzothiazoles. Tetrahedron Lett. 2003, 44, 8535–8537.
13. Sharghi, H.; Asemani, O. Methansulfonic acid/SiO2 as an efficient combination for the synthesis
of 2-substituted aromatic and aliphatic benzothiazoles from carboxylic acids. Synth. Commun.
2009, 39, 860–867.
14. Ranu, B.C.; Jana, R.; Dey, S. An efficient and green synthesis of 2-arylbenzothiazoles in an ionic
liquid [PmIm]Br under microwave irradiation. Chem. Lett. 2004, 33, 274–275.
15. Li, Y.; Wang, Y.L.; Wang, J.Y. A simple iodine promoted synthesis of 2-substituted benzothiazoles
by condensation of aldehydes with 2-aminothiophenol. Chem. Lett. 2006, 35, 460–461.
16. Moghadhan, F.M.; Ismaili, H.; Bardajee, C.R. Zirconium (IV) oxide chloride and anhydrous
copper (II) sulfate mediated synthesis of 2-substituted benzothiazoles. Heteroatom Chem. 2006,
17, 136–141.
17. Robukhin, S.V.; Plaskon, A.S.; Volochnyuk, D.M.; Tolmachev, A.A. Synthesis of fused
imidazoles and benzothiazoles from (hetero) aromatic ortho-diamines or ortho-aminothiophenols
and aldehydes promoted by chlorotrimethylsilane. Synthesis 2006, 2006, 3715–3726.

Molecules 2012, 17
6018
18. Praveen, C.; Hemanthkumar, K.; Muralidharan, D.; Perumal, P.T. Oxidative cyclization of
thiophenolic and phenolic Schiff’s bases promoted by PCC. A new oxidant for 2-substituted
benzothiazoles and benzoxazoles. Tetrahedron 2008, 64, 2369–2374.
19. Al-Qalaf, F.; Mekheimer, R.A.; Sadek, K.U. Cerium (IV) ammonium nitrate (CAN) catalyzed
one-pot synthesis of 2-arylbenzothiazoles. Molecules 2008, 13, 2908–2914.
20. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Synthesis of 2-arylbenzothiazoles and imidazoles
using scandium triflate as a catalyst for both a ring closing and an oxidation step. Heterocycles
2004, 63, 2769–2783.
21. Bahrami, K.; Khodaei, M.M.; Naali, F. Mild and highly efficient method for the synthesis of
imidazoles and 2-arylbenzothiazoles. J. Org. Chem. 2008, 73, 6835–6837.
22. Wilfred, C.D.; Taylor, R.J.K. Preparation of 2-substituted benzimidazoles and related heterocycles
directly from activated alcohols using top methodology. Synlett 2004, 2004, 1628–1630.
23. Prutap, U.R.; Mali, J.R.; Jawale, D.V.; Mane, R.A. Baker,s yeast catalyzed synthesis of
benzothiazoles in an organic medium. Tetrahedron Lett. 2009, 50, 1352–1354.
24. Riadi, Y.; Mamouni, R.; Azzelaou, R.; El Haddad, M.; Routier, S.; Guillaumet, G.; Lazar, S.
An efficient and reusable heterogenious catalyst animal bone meal for the synthesis of
benzimidazoles, benzoxazoles and benzothiazoles. Tetrahedron Lett. 2011, 52, 3492–3495.
25. Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata, M.; Tomozawa, K.; Chiba, T.
Electrooxidative cyclization of benzylideneaminothiophenols to the corresponding 2-arylbenzo-
thiazoles. Heterocycles 2008, 75, 35–42.
26. Khan, K.M.; Rahim, F.; Halim, S.A.; Taha, M.; Khan, M.; Perveen, S.; Haq, Z.; Mesaik, M.A.;
Choudhary, M.I. Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton
and study of their binding affinity by molecular docking. Bioorg. Med. Chem. 2011, 19, 4286–4294.
27. Azizi, N.; Amiri, A.K.; Baghi, R.; Bolourtchian, M.; Hashemi, M.M. PTSA catalyzed simple and
green synthesis of benzothiazole derivatives in water. Monatsh. Chem. 2009, 140, 1471–1473.
28. Deligeorgiev, T.G.; Kaloyanova, S.; Vasilev, A.; Vaquero, J.J. Novel green procedure for the
synthesis of 2-arylbenzothiazoles under microwave irradiation in PEG 200 or PEG 400.
Phosphorus Sulfur Silicon Relat. Elem. 2010, 185, 2292–2302.
29. Sadjadi, S.; Sepehrian, H. Cu(OAc)2/MCM-41: An efficient and solid acid catalyst for synthesis
of 2-arylbenzothiazoles under ultrasound irradiation. Ultrason. Sonochem. 2011, 18, 480–483.
30. Veisi, H.; Ghorbani-Vaghei, R.; Fraji, A.; Ozturk, T. Application of N,N′-diiodo-N,N′-1,2-
ethandiylbis(p-toluene sulfonamide) as a new reagent for synthesis of 2-arylbenzimidazoles and
2-arylbenzothiazoles under solvent-free conditions. Chin. J. Chem. 2010, 28, 2249–2254.
31. Mukhopadhyay, C.; Datta, A. Water-promoted dowex 50W catalyzed highly efficient green
protocol for 2-arylbenzothiazole formation. J. Heterocycl. Chem. 2009, 46, 91–95.
32. Xiao, H.-L.; Chen, J.-X.; Liu, M.-C.; Zhu, D.-J.; Ding, J.-C; Wu, H.-Y. Trichloroisocyanuric acid
(TCCA) as a mild and efficient catalyst for the synthesis of 2-arylbenzothiazoles. Chem. Lett.
2009, 38, 170–171.
33. Chakraborti, A.K.; Rudrawar, S.; Jadhav, K.B.; Kaur, G.; Chankeshwara, S.V. “On water”
organic synthesis: A highly efficient and clean synthesis of 2-aryl/heteroaryl/styryl benzothiazoles
and 2-alkyl/aryl alkyl benzothiazolines. Green Chem. 2007, 9, 1335–1340.

Molecules 2012, 17
6019
34. Maleki, B.; Azarifar, D.; Hojati, S.F.; Gholizadeh, M.; Veisi, H.; Salehabadi, H.;
Khodaverdian Moghadam, M. Efficient 2,4,6-trichloro-1,3,5-triazine-catalyzed synthesis of 2-
arylbenzothiazoles and bisbenzothiazoles by condensation of 2-aminithiophenol with aldehydes
under mild conditions. J. Heterocycl. Chem. 2011, 48, 449–453.
35. Maleki, B.; Salehabadi, H.; Khodaverdian Moghaddam, M. Room-temperature synthesis of
2-arylbenzothiazoles using sulfuric acid immobilized on silica as a reusable catalyst under
heterogeneous conditions. Acta Chim. Solv. 2010, 57, 741–745.
36. Rostami, A.; Yari, A. Sulfamic acid as a recyclable and green catalyst for rapid and highly
efficient synthesis of 2-arylbenzothiazols in water at room temperature. J. Iran. Chem. Soc. 2012,
doi:10.1007/s13738-011-0059-y.
37. Siddappa, C.; Kambappa, V.; Umashankara, M.; Rangappa, K.S. One-pot approach for the
synthesis of 2-arylbenzothiazoles via a two-component coupling of gem-dibromomethylarenes
and o-aminothiophenols. Tetrahedron Lett. 2011, 52, 5474–5477.
38. Cheng, Y.; Yang, J.; Qu, Y.; Li, P. Aerobic visible-light photoredox radical C-H functionalization:
Catalytic synthesis of 2-substituted benzothiazoles. Org. Lett. 2012, 14, 98–101.
39. Mekheimer, R.A.; Abdel-Hameed, A.; Sadek, K.U. Solar thermochemical reactions: Four component
synthesis of polyhydroquinoline derivatives induced by solar thermal energy. Green Chem. 2008,
10, 592–593.
40. Sadek, K.U.; Mekheimer, R.A.; Mohamed, T.M.; Moustafa, M.S.; Elnagdi, M.H. Regioselectivity
in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide
dimethylacetal under controlled microwave heating. Beilstein J. Org. Chem. 2012, 8, 18–24.
41. Mekheimer, R.; Hilmy, N.M.; Abdel Hameed, A.; Dacrory, S.; Sadek, K.U. Simple, three
component, highly efficient green synthesis of thiazolo[3,2-a]pyridine derivatives under neat
conditions. Synth. Commun. 2011, 41, 2511–2516.
Sample Availability: Samples of the compounds 4a–k are available from the authors.
© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).