An efficient and green synthesis of 2-arylbenzothiazoles in an ionic liquid, [pmIm]Br under microwave irradiation

Article abstract of DOI:10.1246/cl.2004.274

An efficient and green procedure for the synthesis of 2-arylbenzothiazoles has been developed by a simple condensation of 2-aminothiophenol and aromatic aldehyde in an inexpensive ionic liquid, 1-pentyl-3-methylimidazolium bromide ([pmIm]-Br) by microwave irradiation under solvent and catalyst-free condition. The ionic liquid is recycled for subsequent reactions.

Full text of DOI:10.1246/cl.2004.274

274
Chemistry Letters Vol.33, No.3 (2004)
An Efficient and Green Synthesis of 2-Arylbenzothiazoles in an Ionic Liquid,
[pmIm]Br under Microwave Irradiation
Brindaban C. Ranu,Ã Ranjan Jana, and Suvendu S. Dey
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta - 700 032, India
(Received December 2, 2003; CL-031215)
An efficient and green procedure for the synthesis of 2-aryl-
A wide variety of aromatic aldehydes underwent condensa-
tions with 2-aminothiophenol by this procedure to produce the
corresponding benzothiazoles in very high yields. The results
benzothiazoles has been developed by a simple condensation of
2-aminothiophenol and aromatic aldehyde in an inexpensive
ionic liquid, 1-pentyl-3-methylimidazolium bromide ([pmIm]-
Br) by microwave irradiation under solvent and catalyst-free
condition. The ionic liquid is recycled for subsequent reactions.
Table 1. Synthesis of 2-arylbenzothiazoles catalyzed by
[pmIm]Br
NH2
SH
N
S
[pmIm]Br
RCHO
R
The realization of simple and green synthetic procedures
constitutes an important goal in organic synthesis. To combat
the harmful effect of organic solvents frequently used in large
quantities for organic transformations ionic liquids have been re-
cently introduced as alternative green reaction media.1,2 As a
part of our drive3 toward that direction we have recently initiated
a program4 to explore the use of benign and inexpensive ionic
liquid as catalyst as well as reaction medium for the synthesis
of useful molecules.
The 2-arylbenzothiazole nucleus constitutes the core unit of
many therapeutic agents including antitumour drugs.5 Thus, syn-
thesis of this heterocyclic system is of much interest and a num-
ber of procedures have been developed.6 However, many of
these procedures are associated with one or more disadvantages
such as involving toxic (nickel complex)6d and expensive (palla-
dium derivative)6g catalysts, hazardous and carcinogenic organic
solvents like nitrobenzene,6c acetonitrile,6f dioxane6g for reac-
tions, multistep process and non-recovery of the catalyst. Hence,
a simple, green, and efficient procedure avoiding these draw-
backs will be of much use.
We report here a very simple synthesis of 2-arylbenzothia-
zoles by the condensation of 2-aminothiophenol and aromatic al-
dehydes in ionic liquid, 1-pentyl-3-methylimidazolium bro-
mide7 ([pmIm]Br) under microwave irradiation without
requiring any other solvent and catalyst (Scheme 1).
In a typical general experimental procedure, a mixture of 2-
aminothiophenol (3 mmol) and an aromatic aldehyde (3 mmol)
in [pmIm]Br (300 mg) was irradiated under microwave in a do-
mestic microwave oven (10% power, 120 W) for 3–5 mins. The
reaction mixture after being cooled was extracted with ether.
The ether extract was evaporated to leave the crude solid. The
pure product was obtained by recrystallization of the crude solid
from ethanol-water. All the products are properly characterized
by their mp and spectroscopic data. The residual ionic liquid was
once again washed with ether, dried under vacuum (1 mm of Hg)
at 80 ꢀC for 1 h and reused for subsequent reactions without any
appreciable loss of efficiency8
Microwave Heating Conventional Heating
Time/min Yield/%a Time/h Yield/%a
Entry
R
3
5
99
97
6
90
83
1
2
C6H5
6.5
4
95
7
86
3
4
5
6
7
(p-Cl)C6H4
3
98
90
92
93
7
88
82
92
89
4
6.5
5.5
6
(p-NO2)C6H4
(o-OH)C6H4
(m-OH)C6H4
3.5
3
3.5
95
6.5
92
8
(p-OH)C6H4
3.5
3
94
95
98
5.5
5.5
5
88
91
94
9
(o-OMe)C6H4
(m-OMe)C6H4
(p-OMe)C6H4
10
11
3
12
13
14
4
95
5.5
87
OMe
OH
5
98
5
94
OCH2Ph
3.5
93
6
87
O
O
15
16
2.5
3
94
92
6
91
87
O
S
5.5
NH2
N
[pmIm]Br
2.5
87
5
82
17
RCHO
R
N
MW 3-5 min
SH
S
aThe yields refer to those of pure isolated products charac-
1
Scheme 1.
terized by spectroscopic ( IR, H, 13C NMR ) data.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.3 (2004)
275
are presented in Table 1. The heterocyclic aldehydes such as fur-
fural, 2-thiophene- and 2-pyridinecarboxaldehydes (Entries 15–
17) also furnish the corresponding benzothiazoles without any
difficulty. A variety of substituents like Cl, NO2, OH, OMe,
OCH2Ph, methylenedioxy on the aromatic ring are compatible
with this reaction condition.
References and Notes
1
a) J. S. Wikes, Green Chem., 4, 73 (2002). b) R. Sheldon,
Chem. Commun., 2001, 2399. c) P. Wasserscheid and W.
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2
a) H. M. Zerth, N. M. Leonard, and R. S. Mohan, Org. Lett.,
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These reactions under microwave are in general, very fast
(3–5 min) and clean. For comparison, when all these reactions
are carried out by conventional heating (80 ꢀC) much longer pe-
riods (5–7 h) are required (Table 1). The activation by micro-
wave irradiation was also reported earlier by Soufiaoui and his
coworkers6c,6e in a similar condensation over PhNO2/SiO2 and
MnO2/SiO2 surface. The catalytic activity of ionic liquid,
[pmIm]Br has been established by the fact that when the reaction
is run without ionic liquid no benzothioazole is obtained and the
reaction is arrested with the formation of imine. Although mech-
anism of action of this ionic liquid is yet to be established by fur-
ther experiments, it may be assumed that the bromide ion of
[pmIm]Br is hydrogen-bonding to –SH increasing the nucleophi-
licity of sulfur atom. This makes the thiolate anion a stronger nu-
cleophile towards efficient condensation with aldehydes fol-
lowed by cyclization.
In conclusion, the present procedure catalyzed by a simple
and inexpensive ionic liquid, [pmIm]Br provides an efficient
methodology for the synthesis of 2-arylbenzothiazoles by the
microwave-assisted condensation of 2-aminothiophenol and ar-
omatic aldehydes. The significant advantages of this procedure
are: a) very fast reaction (3–5 min); b) mild reaction condition
compatible with a variety of sensitive groups; c) high yields
(above 90%); d) cost efficiency providing recyclability of the
catalyst and e) green aspects avoiding hazardous solvent, toxic
catalyst and waste. Moreover, this leaves much promise for fur-
ther applications of ionic liquids as catalysts.
3
4
a) B. C. Ranu and A. Hajra, Tetrahedron, 57, 4767 (2001). b)
B. C. Ranu, A. Hajra, and S. S. Dey, Org. Process Res. Dev.,
6, 817 (2002). c) B. C. Ranu and A. Hajra, Green Chem., 4,
551 (2002). d) B. C. Ranu, S. S. Dey, and A. Hajra, Green
Chem., 5, 44 (2003).
a) B. C. Ranu, A. Das, and S. Samanta, J. Chem. Soc., Perkin
Trans. 1, 2002, 1520. b) B. C. Ranu, S. S. Dey, and A. Hajra,
Tetrahedron, 59, 2417 (2003). c) B. C. Ranu and S. S. Dey,
Tetrahedron Lett., 44, 2865 (2003).
5
6
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In the recycling experiment of ionic liquid carried out for
the reaction in Entry 1 (Table 1) yields of products are as
follows: 1st Run À95%; 2nd Run À92%; 3rd Run À82%.
7
8
This work has enjoyed financial support from CSIR, New
Delhi [Grant No. 01(1739)/02]. R. J. and S. S. D. are also
thankful to CSIR for their fellowships.
Published on the web (Advance View) February 2, 2004; DOI 10.1246/cl.2004.274