Zr (HSO4)4: An efficient catalyst for the Synthesis of 3-(2'-benzothiazolyl)-2, 3-dihydroquinazolin-4 (1H)-ones

Article abstract of DOI:10.1155/2012/515029

A simple and efficient synthesis of 3- (2'-benzothiazolyl)-2, 3-dihydroquinazolin-4 (1H)-ones has been accomplished by the one-pot condensation of isatoic anhydride, aldehydeand 2-aminobenzothiazole under solvent-free conditionsin the presence of Zr (HSO₄)₄.

Full text of DOI:10.1155/2012/515029

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 739-743
Zr(HSO4)4: An Efficient Catalyst for the
Synthesis of 3-(2'- Benzothiazolyl)-2,
3-dihydroquinazolin- 4(1H)-ones
LIQIANG WU
School of Pharmacy, Xinxiang Medical University,
Xinxiang, Henan 453003, P. R. China
wliq870@163.com
Received 29 August 2011; Accepted 27 October 2011
Abstract: A simple and efficient synthesis of 3-(2'-benzothiazolyl)-2,3-dihydro
quinazolin-4(1H)- ones has been accomplished by the one-pot condensation of
isatoic anhydride, aldehyde and 2-aminobenzothiazole under solvent-free
conditions in the presence of Zr(HSO4)4.
Keywords: Aldehydes, 2,3-Dihydroquinazolin-4(1H)-ones, Zr(HSO4)4, Heterocycles, Solvent-free.
Introduction
2,3-Dihydroquinazolinones are an important class of bioactive compounds that are
prescribed as plant growth regulators and as anticancer drugs1. In addition, these compounds
are also key intermediates for the synthesis of quinazolin-4(3H)-ones. Benzothiazoles are
used for the development of pharmaceutical agents of various applications. Compounds with
the motif show a wide range of pharmacological activities, such as anti-tumour2,
anticonvulsant3, antibacterial4 calcium-inhibiting5 and topoisomerase II inhibitory6. The
formation of 3-(2'-benzothiazolyl)-2,3- dihydroquinazolin-4(1H)-ones is generally
accomplished by condensation reaction of isatoic anhydride, aldehyde and
8
2-aminobenzothiazole in the presence of [bmim]Br7, Al5(P3O10)3 or under thermal solvent-
free conditions9. However, most of these procedures have signicant drawbacks such as long
reaction times, low yields, expensive reagents etc. Thus, there is still need of a simple and
general for the one-pot synthesis of 3-(2'-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)-ones.
In recent years, metal hydrogen sulfates have been used as an efficient reagent in organic
chemistry10. A broad range of reactions including deprotection, oxidation, C-C, C-N and C-O
bond formation and cleavage took place in the presence of these reagents under mild and
heterogeneous conditions. In addition, stability, cheapness, ability to produce highly efficient
products in a short time and in many cases reusability is among other important advantages
of these reagents. Herein, we report a rapid and convenient procedure for the preparation of
3-(2'-benzothiazolyl)-2,3- dihydroquinazolin-4(1H)-ones using a catalytic amount of
Zr(HSO4)4 under solvent-free conditions (Scheme 1).

740 LIQIANG WU
O
O
N
S
N
S
Zr(HSO4)4
N
O
+
H2N
RCHO
+
neat, 110°C
N
H
R
N
H
O
4
3
2
1
Scheme 1
Experimental
IR spectra were determined on FTS-40 infrared spectrometer; 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; Commercially available reagents were used throughout
without further purification unless otherwise stated.
General Procedure for the Preparation of 4
A mixture of the isatoic anhydride (1mmol), aldehyde (1 mmol) 2-aminobenzothiazole (1
mmol), and Zr(HSO4)4 (0.02 mmol) was stirred at 110 ºC for the appropriate time according
to Table 2. Completion of the reaction was indicated by TLC. The reaction was cooled to
room temperature, water was added and the mixture stirred for 5 min. The solid obtained
was removed by filtration and recrystallized from acetonitril. All products were
1
characterized by comparison of their physical data and H and 13C NMR data with those of
authentic samples.
Spectral data of new product
3-(2′-Benzothiazolyl)-2,3-dihydro-2-(3-chlorophenyl)-quinazolin-4(1H)-one (4g).
1
IR (KBr) ν: 3372, 1652, 1599, 1498, 1420, 1362, 1209; H NMR (DMSO-d6, 400 MHz) δ:
8.10 (d, 1H, J = 4.4 Hz. NH), 7.99 (d, 1H, J = 7.6 Hz. CH), 7.93 (d, 1H, J = 7.6 Hz. CH), 7.72-
7.66 (m, 3H, CH), 7.48-7.10 (m, 6H, CH), 6.92-6.88 (m, 2H); Anal. calcd for C21H14ClN3OS: C
64.36, H 3.60, N 10.72, S 8.18%; found: C 64.50, H 3.42, N 10.60, S 8.02%
Results and Discussion
In an initial endeavor, isatoic anhydride, benzaldehyde and 2-aminobenzothiazole were
stirred at 120 °C under solvent-free conditions. After 5 h, only 15% of the expected
product 3-(2′-benzothiazolyl)-2,3-dihydro-2- (phenyl)-quinazolin-4(1H)-one was obtained.
To improve the yield and optimize the reaction conditions, the same reaction was carried
out in the presence of a variety of catalysts under similar conditions, it was found that
when the reaction occurred using catalysts such as I2, ZnCl2, H2SO4, HCl and NaHSO3 it
resulted in poor yields. However, catalysts such as p-TsOH, NaHSO4, Fe(HSO4)3 could
push the reaction forward with moderate yields. A significant improvement was observed
and the yield of 3-(2′-benzothiazolyl)-2,3-dihydro-2- (phenyl)-quinazolin-4(1H)-one was
increased to 90% in the presence of 2 mol % Zr(HSO4)4 (Table 1). Then we tried to
optimize the amount of catalyst and the reaction temperature for this reaction. As could be
seen on Table 1, the reaction using 2 mol % Zr(HSO4)4 at 110 °C proceeded in highest
yield.
Table 1. Synthesis of 3-(2′-benzothiazolyl)-2,3-dihydro-2-(phenyl)-quinazolin-4(1H)-one
under various conditionsa.

Zr(HSO4)4: An Efficient Catalyst for the Synthesis 741
Entry
1
Catalyst
Temperature /oC
120
120
120
120
120
120
120
120
120
120
120
120
25
Time /h Yield /%b
-
5
15
43
50
49
42
35
81
80
82
57
69
88
0
2
I2, 2 mol%
3
3
ZnCl2, 2 mol%
3
4
H2SO4, 2 mol%
4
5
HCl, 2 mol%
4
6
NaHSO3, 2 mol%
p-TsOH, 2 mol%
NaHSO4, 2 mol%
Fe(HSO4)3, 2 mol%
Zr(HSO4)4, 0.5 mol%
Zr(HSO4)4, 1 mol%
Zr(HSO4)4, 1.5 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 2 mol%
Zr(HSO4)4, 3 mol%
Zr(HSO4)4, 3 mol%
Zr(HSO4)4, 4 mol%
Zr(HSO4)4, 5 mol%
4
7
1
8
1
9
0.5
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1
0.5
5
50
5
0
90
100
110
120
130
100
110
2
69
87
93
92
90
80
89
91
93
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
110
110
aReaction conditions: isatoic anhydride (1 mmol); benzaldehyde (1 mmol); 2-aminobenzothiazole
(1 mmol); neat. b Isolated yield.
Encouraged by this result, in order to build the generality of the reaction, our attention
moved to the reactions of other aldehydes, and the results are summarized in Table 2. As
expected, this reaction proceeded smoothly and the desired products were obtained in good
to excellent yields. A series of aldehydes with either electron- donating or electron-
withdrawing groups attaching to aromatic ring were investigated. The substitution groups on
the aromatic ring had no obvious effect on the yield. When aromatic aldehydes were
replaced by with aliphatic aldehyde, the corresponding products were obtained with high
yields as well (Table 2, entries 10 and 11).
Table 2. Preparation of 3-(2'-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)-onesa.
Entry
R
C6H5
Time/ h
0.5
0.5
0.5
0.5
1
Productsb
Yield/ %b
m.p. (lit.)/ oC
232-234 (233-236)7
192-193 (198-200) 8
197-199 (198-199)7
182-184 (179-183)8
242-245 (245-246)7
250-255 251-253)7
160-162
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
90
88
92
91
87
88
86
88
89
4-Cl-C6H4
4-Me-C6H4
4-MeO-C6H4
4-NO2-C6H4
3-NO2-C6H4
3-Cl-C6H4
2-Me-C6H4
2-MeO-C6H4
1
0.5
0.5
0.5
1
1
199-201 (198-201)8
222-225 (225-230)8
10
11
CH3
C6H13
4j
4k
81
80
219-221 (215-222)7
149-152 (148-151) 7
aReaction conditions: isatoic anhydride (1 mmol); aldehyde (1 mmol); 2-amino benzothiazole
(1 mmol); Zr(HSO4)4 (0.02 mmol); 110 oC; neat. bIsolated yield.
To show merit of the present work in comparison with reported results in the literature,
we compared results of Zr(HSO4)4 with [bmim]Br, Al5(P3O10)3 as catalysts in the reaction of

742 LIQIANG WU
isatoic anhydride, benzaldehyde and 2-aminobenzothiazole. As shown in Table 3, Zr(HSO4)4
can act as high efficiency catalyst with fast time and high yields of the obtained products.
Table 3. Zr(HSO4)4-catalyzed synthesis of 3-(2′-benzothiazolyl)-2,3-dihydro-2-(phenyl)-
quinazolin-4(1H)-one in comparison with other literatures.
Entry
Catalyst and conditions
[bmim]Br (136 mol%); neat; 130 oC
Al5(P3O10)3 (16 mol%); neat; 100 oC
neat; 130 oC
Time/ min Yield/ %
Ref.
7
8
9
1
2
3
4
30
20
93
85
66
93
132
30
Zr(HSO4)4 (2 mol%); neat; 110 oC
The work
Conclusion
fi
3-(2'-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)- ones
-aminobenzothiazole
Zr(HSO4)4
Acknowledgment
We are pleased to acknowledge the financial support from Xinxiang Medical University.
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