Tribromomelamine: A novel and efficient catalyst for the synthesis 2-arylthiazolines under solvent-free conditions

Article abstract of DOI:10.1155/2012/972109

A novel procedure for the synthesis of 2-arylthiazolines through one-pot condensation of of nitriles with 2-aminoethanethiol in the presence of tribromomelamine as catalyst under solvent-free conditions is described.

Full text of DOI:10.1155/2012/972109

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 1035-1041
Tribromomelamine: A Novel and Efficient Catalyst
for the Synthesis 2-Arylthiazolines under Solvent-free
Conditions
LIQIANG WU
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China
Email: wliq870@163.com
Received 20 July 2011; Accepted 5 September 2011
Abstract: A novel procedure for the synthesis of 2-arylthiazolines through
one-pot condensation of of nitriles with 2-aminoethanethiol in the presence of
tribromomelamine as catalyst under solvent-free conditions is described.
Keywords: 2-Arylthiazolines, 2-Aminoethanethiol, Nitriles, Tribromomelamine, Synthesis
Introduction
1
Natural compounds possessing thiazoline moiety have been attracted by their antibiotic ,
2
3
4
5
antitumor , antimalarial , antiproliferative , anti-HIV activities . A plethora of biological
6
activities have also been associated with a large number of synthetic thiazoline analogs .
7
In the last decade organocatalysis has became a field of great interest . Organocatalysts
are usually robust, inexpensive, readily available, non-toxic and inert towards moisture and
oxygen. Because of the absence of transition metals, organocatalytic methods seem to be
especially attractive for the preparation of compounds that do not tolerate metal
contamination such as pharmaceutical products.
In this article, we wish to report a metal-free synthesis of 2-arylthiazolines using a new,
efficient and easily prepared reagent, tribromomelamine (TBM) (Scheme 1).

1
036 Liqiang Wu
N
TBM (0.5%)
ArCN + HS
NH2
Ar
1
00°C, neat
S
1
2
3
Scheme 1
2
TBM is readily prepared by the dropwise addition of Br to 5 M NaOH mixture of
8
melamine at at room temperature . It is interesting to note that the producing of TBM is easy
and clean without a difficult work-up procedure. This yellow
nonhygroscopic solid is very stable under reaction conditions.(Scheme 2).
homogeneous,
BrHN
N
NHBr
H N
N
NH2
2
NaOH (aq.)
+
Br2
N
N
N
N
NHBr
TBM
NH2
Scheme 2
Experimental
NMR spectra were recorded on Bruker AV-400 spectrometer at room temperature using
TMS as an internal standard, coupling constants (J) were measured in Hz; Elemental
analysis were performed by a Vario-III elemental analyzer; Melting points were determined
on a XT-4 binocular microscope and were uncorrected; TBM was prepared by available
8
method ; Commercially available reagents were used throughout without further purification
unless otherwise stated.
General Procedure for synthesis of 3
A mixture of the nitrile (1mmol), 2-aminoethanethiol (1 mmol), and TBM (0.005 mmol)
was stirred at 100 ºC for the appropriate time according to Table 3.Completion of the
reaction was indicated by TLC. The reaction was cooled to room temperature, and the crude
product purified by silica gel column chromatography using n-hex-ane/EtOAc (v:v = 2:1) as
eluent to afford the pure product.

Tribromomelamine: A Novel and Efficient Catalyst 1037
Spectral data of new 2-arylbenzothiazole
1
2
-(3-Florophenyl)thiazoline (3h). IR (KBr) ν: 1600 (CN); H NMR (CDCl , 400 MHz)
3
δ: 7.68 (s, 1H, Ar), 7.53 (d, 1H, J = 7.6 Hz, Ar), 7.38 (d, 1H, J = 7.6 Hz. Ar), 7.22 (t, 1H, J =
.6 Hz, Ar), 4.20 (t, J = 8.0 Hz, 2H, CH N), 3.32 (t, J = 8.0 Hz, 2H, CH S)); Anal. calcd for
7
2
2
C H FNS C 59.65, H 4.45, N 7.73, S 17.69%; found: C 60.01, H 4.39, N 7.70, S 17.55%.
9
8
:
Results and Discussion
In order to optimize the reaction conditions, first, the effect of temperature on the rate of the
reaction was studied for the preparation of 2-phenylthiazoline in presence of 0.5 mol%
TBM under solvent-free conditions (Table 1). At 100 °C, the reaction proceeded smoothly
and gave short reaction time and high yield. Therefore, we kept the reaction temperature at
1
00 °C.
a
Table 1. Temperature optimization for the synthesis of synthesis of 2-phenylthiazoline .
o
b
Entry
Temperature / C
Time /min.
Yield/ %
1
2
3
4
5
6
7
8
9
25
50
120
0
90
60
30
30
10
3
0
60
18
30
52
78
98
98
96
97
70
80
90
100
110
120
130
3
2
1
0
2
a
Reaction conditions: benzonitrile (1 mmol); 2-aminoethanethiol (1 mmol); TBM (0.005
mmol); neat.
b
Isolated yield.
Next, the study set out to determine optimal amount of TBM, the reaction was carried
out by varying amount of the catalyst (Table 2). Maximum yield was obtained with 0.5

1
038 Liqiang Wu
mol% of the catalyst. Further increase in amount of alum in the mentioned reaction did not
has any significant effect on the product yield.
a
Table 2. The amounts of catalyst optimization for the synthesis of 2-phenylthiazoline .
b
Entry
TBM/ mol%
Time/ min
Yield/ %
1
2
3
4
5
6
7
8
9
0
60
10
4
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
72
81
89
95
98
98
97
96
98
98
4
3
3
3
3
2
1
0
1
2
1
2
a
Reaction conditions: benzonitrile (1 mmol); 2-aminoethanethiol (1 mmol); 100 °C; neat.
Isolated yield.
b
In order to extend the above reaction to a library system, various kinds of arylnitriles
Table 3) were subjected to react with 2-aminoethanethiol to give the corresponding
(
2
-arylthiazolines, and representative examples are shown in Table 3. All of arylnitriles gave
expected products at high yields, either bearing electron-withdrawing groups (such as
halide, nitro) or electron-donating groups (such as alkyl group) under the same reaction
condition. To further demonstrate the scope and limitation of the substrates, aliphatic nitriles,
such as pentanenitrile, heptanenitrile,
, were used as reactants to react with
2
-aminoethanethiol. However, the desired products were not found and obtained
1
successfully. All of the structures were characterized by IR, H NMR and elemental
analysis.

Tribromomelamine: A Novel and Efficient Catalyst 1039
a
Table 3. Preparation of 2-arylthiazolines .
b
b
o
Entry
Ar
Time/ min
Products
3a
Yield/ %
98
m.p. (lit.)/ C
6
i
1
2
3
4
5
6
7
8
9
C H
6
3
2
6
6
2
3
5
5
4
7
5
3
6
127-129 (126-128)
5
6n
4-Cl-C H
3b
3c
96
51-53 (53-55)
6
4
6
n
4-Me-C H
82
40-41 (39-41)
55-56 (53-55)
6
4
6
i
4-MeO-C H
3d
3e
81
6
4
6n
4-NO -C H
4
88
147-149 (148-150)
2
6
6
n
4-F-C H
3f
92
oil (oil)
6
4
6i
3-NO -C H
4
3g
87
133-134 (135-137)
2
6
3-F-C H
3h
3i
93
oil
6
4
6
n
2-Cl-C H
99
Oil (oil)
90-92 (91-93)
110-112 (111-113)
6
4
6
n
1
0
1
2-Pyridyl
3-Pyridyl
4-Pyridyl
2-Thienyl
3j
98
6i
1
3k
3l
94
6
n
1
1
2
3
99
72-73 (74-76)
39-40 (40-42)
6
i
3m
90
a
Reaction conditions: nitrile (1 mmol); 2-aminoethanethiol (1 mmol); TBM (0.005 mmol);
1
00 °C; neat.
b
Isolated yield.
HN
N
NH
BrHN
N
N
NHBr
N
N
N
NH
NHBr
Br
SH
NH-Br
HN
H N
2
Ar
SH
Ar-C N Br
Ar-C N
H
N
N
+
Ar
NH Br
+ NH + Br
3
Ar
2
S
S
Scheme 3

1
040 Liqiang Wu
Conclusion
In conclusion, an efficient protocol for the one-pot preparation of 2-arylthiazolines from
the condensation reaction of nitriles with 2-aminoethanethiol in the presence of TBM was
described. The reactions were carried out under thermal solvent-free conditions with short
reaction time and produced the corresponding products in good to excellent yields.
Acknowledgments
We are pleased to acknowledge the financial support from Xinxiang Medical University.
References
1
2
. Aaron, M. S.; Richard, A. L.; David, C. R. J. Nat. Prod. 2007, 70, 1793.
. (a) Yu, L.; Li, Z.; Peng, C.; Li, Z.; Guo, Y. Helv. Chim. Acta. 2009, 92, 607; (b) Matsuo, Y.;
Kanoh, K.; Imagawa, H.; Adachi, K.; Nishizawa, M.; Shizuri, Y. J. Antib. 2007, 60, 256;
(
c) Gerwick, W. H.; Proteau, P. J.; Nagle, D. G.; Hamel, E.; Blokhin, A.; Slate, D. J. Org.
Chem. 1994, 59, 1243.
3
. Linington, R. G.; Gonzalez, J.; Urena, L.; Romero, L. I.; Ortega-Barria, E.; Gerwick, W. H.
J. Nat. Prod. 2007, 70, 397.
4
5
6
. Teruya, T.; Sasaki, H.; Fukazawa, H.; Suenaga, K. Org. Lett. 2009, 11, 5062.
. Perez. L. J.; Faulkner, D. J. J. Nat. Prod. 2003, 66, 247.
. (a) Fu, B.; Qi, Q.-Q.; Lu, X.-H.; Cheng, X.-M.; Xiao, Y.-M.; Li, N. Chin. J. Org.Chem.
2
008, 28, 1358; (b) Davyt, D.; Serra, G.; Mar. Drugs 2010, 8, 2755; (c) Sondhi, S. M.;
Dwivedi, A. D.; Singh, J.; Gupta, P. P. Indian J. Chem., Sect B 2010, 49B, 1076; (d)
Padmavathi, V.; Mahesh, K.; Reddy, G. Dinneswara; Padmaja, A. Eur. J. Med. Chem.
2
2
010, 45, 3178; (e) Saeed, A.; Shaheen, U.; Hameed, A.; Kazmi, F. J. Fluorine Chem.
010, 131, 333; (f) Sondhi, S. M.; Rani, R.; Gupta, P. P.; Agrawal, S. K.; Saxena, A. K.
Mol. Divers. 2009, 13, 357; (g) Seijas, J. A.; Vazquez-Tato, M. P.; Crecente-Campo, J.
Tetrahedron 2008, 64, 9280; (h) Singh, R. K.; Lange, T. S.; Kim, K. K.; Singh, A. P.;
Hopson, R.; Vorsa, N.; Brard, L. Lett. Org. Chem. 2008, 5, 103; (i)
Mohammadpoor-Baltork, I.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.; Hojati, S.
F. Catal. Commun. 2008, 9, 1153; (j) Mohammadpoor-Baltork, I.; Moghadam, M.;
Tangestaninejad, S.; Mirkhani, V.; Hojati, S. F. Polyhedron 2008, 27, 750; (k) Fukuhara,
T.; Hasegawa, C.; Hara, S. Synthesis 2007, 1528; (l) Sanemitsu, Y.; Kawamura, S.; Satoh,
J.; Katayama, T.; Hashimoto, S. J. Pestic. Sci. 2006, 31, 305; (m) Bonde, C. G.; Gaikwad,
N. J. Bioorg. Medi. Chem. 2004, 12, 2151; (n) Shaabani, A.; Seyyedhamzeh, M.; Maleki,
A.; Rezazadeh, F. Appl. Catal. A 2009, 358, 146.

Tribromomelamine: A Novel and Efficient Catalyst 1041
7
8
. (a) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. Engl. 2004, 43, 5138; (b) Duthaler, R.
O. Angew. Chem. Int. Ed. Engl. 2003, 42, 975.
. Ghorbani-Choghamarani, A.; Zolfigol, M. A.; Hajjami, M.; Jafari, S. J. Chin. Chem. Soc.
2
008, 55, 1208.

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