Iodine-catalyzed, one-pot, solid-phase synthesis of benzothiazole derivatives

Article abstract of DOI:10.1080/00397910701575657

Molecular iodine was utilized in a one-pot, solid-phase, solvent-free reaction between 2-aminothiophenol and benzoic acid derivatives to obtain highly economical and excellent yield of benzothiazole derivatives in comparison to polyphosphoric acid- and [pmIm]-Br-catalyzed microwave synthesis reactions. The results of the studies revealed that the new method reduces cost by approximately 17-fold in comparison to polyphosphoric acid and has a significant cost reduction in comparison to [pmIm]-Br. Moreover, it becomes even more economical because no additional chemicals and solvents are necessary for the reaction. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701575657

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Iodine‐Catalyzed, One‐Pot, Solid‐Phase
Synthesis of Benzothiazole Derivatives
a
a
a
Sayan Dutta Gupta , Hemendra Pratap Singh & N. S. H. N. Moorthy
a
School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki
Vishwavidyalaya , Bhopal, Madhya Pradesh, India
Published online: 14 Dec 2007.
To cite this article: Sayan Dutta Gupta , Hemendra Pratap Singh & N. S. H. N. Moorthy (2007)
Iodine‐Catalyzed, One‐Pot, Solid‐Phase Synthesis of Benzothiazole Derivatives, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:24, 4327-4329, DOI:
10.1080/00397910701575657
To link to this article: http://dx.doi.org/10.1080/00397910701575657
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Synthetic Communications , 37: 4327–4329, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701575657
Iodine-Catalyzed, One-Pot, Solid-Phase
Synthesis of Benzothiazole Derivatives
Sayan Dutta Gupta, Hemendra Pratap Singh, and
N. S. H. N. Moorthy
School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki
Vishwavidyalaya, Bhopal, Madhya Pradesh, India
Abstract: Molecular iodine was utilized in a one-pot, solid-phase, solvent-free reaction
between 2-aminothiophenol and benzoic acid derivatives to obtain highly economical and
excellent yield of benzothiazole derivatives in comparison to polyphosphoric acid- and
[
pmIm]-Br-catalyzed microwave synthesis reactions. The results of the studies revealed
that the new method reduces cost by approximately 17-fold in comparison to polypho-
sphoric acid and has a significant cost reduction in comparison to [pmIm]-Br.
Moreover, it becomes even more economical because no additional chemicals and
solvents are necessary for the reaction.
Keywords: 2-aminothiophenol, benzothiazole, molecular iodine, one-pot, solid-phase
INTRODUCTION
Simple and effective methods to synthesize benzothiazole derivatives include
cyclization (Jacobson cyclization) of substituted nitrothiobenzanilidine (in the
presence of aqueous sodium hydroxide and potassium ferricyanide), followed
by reduction (in presence of stannous chloride–water and ethanol); reaction
of 2-aminothiophenol with substituted benzoic acid (in the presence of poly-
[
1]
phosporic acid at 2208C); and reaction of 2-aminothiophenol with substituted
benzoic acid and benzaldehyde (using polyphosphoric acid and microwave
[2]
irradiation in our laboratory) and 1-pentyl-3-methyl imidizolium bromide
Received May 8, 2007
Address correspondence to N. S. H. N. Moorthy, School of Pharmaceutical
Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi
Nagar, Bhopal, Madhya Pradesh 462 036, India. E-mail: nshnm@yahoo.co.in
4
327

4
328
S. D. Gupta, H. P. Singh, and N. S. H. N. Moorthy
Scheme 1. Synthesis of benzothiazole derivatives.
[3]
[pmIm]-Br). In the present investigation, we selected iodine for the synthesis
(
of benzothiazole derivatives (Scheme 1). The advantages of using iodine are
that it is inexpensive, requires a very small amount, can be carried out under
[4–6]
solvent-free condition, takes less reaction time, and is nonselective.
RESULTS AND DISCUSSION
The synthesis of benzothiazole derivatives was carried out by the reaction of
-aminothiophenol with the corresponding acid using molecular iodine under
solvent-free conditions (Table 1).
2
EXPERIMENTAL
Synthesis of Benzothiazole Derivatives
Molecular iodine (0.20 g, 0.008 mM of 10 M%) and the required amount of
benzoic acid or its derivatives (0.0084 mM) were transferred to a mortar.
To it, 0.85 ml (0.008 mM) of 2-aminothiophenol was added dropwise with
trituration. Trituration was continued until the reaction was completed as
Table 1. Detail of the benzothiazole derivatives synthesized by iodine catalyst
S.
no
Recrystallizing
solvent
R
Reactant 1
Reactant 2
Product
1
2
3
4
5
6
OH
2-Amino
thiophenol
2-Amino
thiophenol
2-Amino
thiophenol
2-Amino
thiophenol
2-Amino
thiophenol
2-Amino
thiophenol
p-Hydroxy
benzoic acid
p-Amino
2-(4-Hydroxyphenyl) 60% methanol
benzothiazole
NH
2
2-(4-Aminophenyl)
benzothiazole
70% methanol
benzoic acid
p-Methoxy
benzoic acid
Benzoic acid
OCH
H
3
2-(4-Methoxyphenyl) Chloroform
benzothiazole
2-Phenyl
benzothiazole
70% ethanol
70% ethanol
60% ethanol
Cl
p-Chloro
2-(4-Chlorophenyl)
benzothiazole
benzoic acid
p-Nitro
benzoic acid
NO
2
2-(4-Nitrophenyl)
benzothiazole

Benzothiazole Derivatives
4329
evident from thin-layer chromatography (TLC). The crude product was then
recrystallized using a suitable solvent. The reaction was complete within
1
0 min.
ACKNOWLEDGMENT
The authors are thankful to the Vice Chancellor, Rajiv Gandhi Proudyogiki
Vishwavidyalaya, Bhopal, for providing the laboratory facility and to All
India Council for Technical Education (AICTE), New Delhi, India for
providing a scholarship during this project.
REFERENCES
1
2
3
. Shi, D. F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.; Lelieveld, P.; Fichtner, I.;
Stevens, M. F. G. Antitumor benzothiazoles—synthesis of 2-(4-aminophenyl)ben-
zothiazoles and evaluation of their activities against breast cancer cell lines in
vitro and in vivo. J. Med. Chem. 1996, 39, 3375–3384.
. Dubey, R.; Moorthy, N. S. H. N. Microwave assisted synthesis, its validation and
biological evaluations of potent anti-tumor benzothiazole derivatives and their
dimmers. M. Pharm Thesis, School of Pharmaceutical Sciences, RGPV: Bhopal,
India, 2005; pp. 38–45.
. Ranu, B. C.; Jana, R.; Dey, S. S. An efficient and green synthesis of 2-aryl benzo-
thiazoles in an ionic liquid, ([pmIm]-Br), under microwave irradiation. Chem. Lett.
2004, 33, 274–275.
4
5
6
. Chen, W. R.; Lu, J. Molecular iodine catalyzed one-pot synthesis of 1,5-Benzo-
diazepine derivatives under solvent free condition. Synlett 2005, 8, 1337–1339.
. Vaino, A. R.; Szarek, W. A. Iodine in methanol: a simple selective method for the
cleavage of p-methoxy benzyl ethers. Synlett 1995, 1157–1158.
. Lipshutz, B. H.; Keith, J. Selective deprotection of alkyl vs. aryl silyl ethers. Tetra-
hedron Lett. 1998, 39, 2494–2498.