Agar: A novel, efficient, and biodegradable catalyst for the one-pot three-component and green synthesis of 2,3-dihydroquinazolin-4(1H)-one, 4H-pyrimidobenzothiazole and 2-aminobenzothiazolomethylnaphthol derivatives

Article abstract of DOI:10.1007/s11164-014-1818-z

3-(2′-Benzothiazolyl)-2,3-dihydroquinazolin-4(1H)- one, 1-((benzo[d]thiazol-2-ylamino) (aryl)-methyl)naphthalen-2-ol and 4H-pyrimido[2,1-b][1,3]benzothiazoles derivatives were prepared via one-pot three-component reaction of arylaldehydes, 2-aminobenzothiazole and isatoic anhydride or β-naphthol or ethyl/methyl acetoacetate in the presence of agar as a highly efficient homogenous catalyst. The use of a non-toxic and biodegradable catalyst, as well as high yields, short reaction time, simple work-up and green conditions are the most important advantages of this method. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-014-1818-z

Res Chem Intermed
DOI 10.1007/s11164-014-1818-z
Agar: a novel, efficient, and biodegradable catalyst
for the one-pot three-component and green synthesis
of 2,3-dihydroquinazolin-4(1H)-one, 4H-
pyrimidobenzothiazole and 2-
aminobenzothiazolomethylnaphthol derivatives
•
Ashraf Moradi Reza Heydari
Malek Taher Maghsoodlou
•
Received: 25 June 2014 / Accepted: 17 September 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract 3-(20-Benzothiazolyl)-2,3-dihydroquinazolin-4(1H)- one, 1-((benzo[d]thia-
zol-2-ylamino) (aryl)-methyl)naphthalen-2-ol and 4H-pyrimido[2,1-b][1,3]benzothiaz-
oles derivatives were prepared via one-pot three-component reaction of arylaldehydes,
2-aminobenzothiazole and isatoic anhydride or b-naphthol or ethyl/methyl acetoacetate
in the presence of agar as a highly efficient homogenous catalyst. The use of a non-toxic
and biodegradable catalyst, as well as high yields, short reaction time, simple work-up
and green conditions are the most important advantages of this method.
Keywords 3-(20-Benzothiazolyl)-2,3-dihydroquinazolin-4(1H)-ones ꢀ
1-((Benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ol ꢀ 4H-pyrimido
[2,1-b][1,3]benzothiazole ꢀ Agar ꢀ Green chemistry
Introduction
The development of environmentally benign, efficient, and economical methods for
the synthesis of biologically interesting compounds remains a significant challenge
in synthetic chemistry [1, 2]. One-pot multi-component reaction strategies (MCRs)
are believed to exhibit negative activation volumes owing to the condensation of
several molecules into a single reactive intermediate and product because of their
convergence, productivity, facile performance and high yields [3].
Dihydroquinazolin-4(1H)-ones constitute an important class of heterocyclic
compounds that exhibit a wide spectrum of biological and physiological activities
and pharmacological properties [4, 5], such as anticancer, antidiuretic, anticonvul-
sant, antibacterial, antifungal activity [6], and mono-amine oxidase inhibition, and
A. Moradi ꢀ R. Heydari (&) ꢀ M. T. Maghsoodlou
Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan,
P.O. Box 98135-674, Zahedan, Iran
e-mail: heydari@chem.usb.ac.ir
123

A. Moradi et al.
Fig. 1 The structure of an
agarose polymer
OH
O
OH
O
OH
O
O
H
O
OH
OH
n
are also used as 5-hydroxytryptamine (5-HT) receptor ligands [7]. Recently,
Lindsley and coworkers observed the metabotropic glutamate receptor (mGluR)
properties of this class of compounds [8]. Thus, developing versatile approaches to
the synthesis of 2,3-dihydroquinazolin-4(1H)-ones, 4H-pyrimido [2,1-b][1,3]ben-
zothiazoles and 1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ols still
remains a highly desired goal in organic synthesis, because of their potential
biological and pharmaceutical activities. There are many reports on the synthesis of
dihydroquinazolin-4(1H)-ones, 4H-pyrimido [2,1-b][1,3]benzothiazole and
1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ol derivatives by three-
component reaction of aldehydes, 2-aminobenzothiazole and isatoic anhydride or b-
naphthol or ethyl/methyl acetoacetate in the presence of heterogeneous catalysts, for
example Fe3O4 nanoparticles [9], copolymer-p-TSA [10], p-TSA–NaHSO3 [11],
silica sulfuric acid [12], gallium(III) triflate [13], Amberlyst-15 [14], KAl(SOO(a-
lum) [12], montmorillonite K-10 [15], zinc(II) perfluorooctanoate [16], the ionic
liquids 1-butyl-3-methylimidazolium bromide[bmim]Br or [bmim]PF6 [17, 18],
[Al(H2PO4)3] [22], tetramethylguanidinium trifluoroacetate (TMGT) [19], silica
sulfuric acid (SSA) [20], and sulfamic acid (SA) [21].
In recent years, the emphasis of science and technology has shifted more toward
environmentally benign and sustainable resources and progress: in this regard, use
of natural catalysts has received considerable attention in organic chemistry. In
particular, natural biopolymers are important candidates to explore for catalysts, and
their properties provide the possibility to perform reactions for acid-sensitive
substrates, under milder reaction conditions and better selectivity [23–25, 33].
Agar is derived from the polysaccharide agarose, which forms the supporting
structure in the cell walls of certain species of algae. These algae are known as
agarophytes and belong to the Rhodophyta (red algae) phylum [27, 28]. Generally,
agar is actually a mixture of components: the linear polysaccharide agarose, agarose
polymer, sugars such as galactose, gluconic acid and xylose, and amino acids such
as garyn, glutamic acid, threonine, and a heterogeneous mixture of smaller
molecules called agaropectin [29]. In chemical terms, agar is a polymer made up of
subunits of the sugar galactose (Fig. 1). This small natural product contains many
hydroxyl groups and can therefore can act as a mild catalytic system [30].
During the course of our studies in developing efficient synthetic methodologies
for the synthesis of substituted benzothiazole heterocyclic compounds, and our
interest in multi-component reactions [31–33], we report a practical method in
which commercially available agar acts as a bio-resource catalyst in synthesizing
benzothiazoquinazoline, 1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-
2-ol and 4H-pyrimido [2,1-b][1,3]benzothiazole derivatives employing the one-
pot three-component condensation reactions strategy of aldehyde 1 with
123

A novel, efficient, and biodegradable catalyst
Scheme 1 Synthesis of 3-(20-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)-one, 1-((benzo[d]thiazol-2-
ylamino)(aryl)-methyl)naphthalen-2-ol and 4H-pyrimido [2,1-b][1,3]benzothiazole derivatives in the
presence of agar as the catalyst
2-aminobenzothiazole 2 and isatoic anhydride 3 or b-naphthol 4 or ethyl/methyl
acetoacetate/acetacetate 5aand 5b under classical heating conditions (Scheme 1).
Experimental
Materials and equipment’s
All reagents were purchased from Merck, Fluka and Aldrich and used without
further purification. The NMR spectra were recorded on a Bruker Avance DPX
300 MHz spectrometer using CDCl3 or DMSO, as solvent. Chemical shifts have
been expressed in (ppm) downfield from TMS. IR spectra were recorded on a
JASCO FT-IR 460 plus spectrophotometer. Melting points were determined in open
capillaries with a BUCHI 510 melting point apparatus. All the reactions are
monitored by thin layer chromatography (TLC), which was performed on silica-gel
Poly Gram SIL G/UV 254 plates.
General procedure for the synthesis of 3-(20-benzothiazolyl)-2,3-
dihydroquinazolin-4(1H)-one derivatives
A mixture of an aldehyde (1.0 mmol), 2-aminobenzothiazole (1.0 mmol), isatoic
anhydride (1.0 mmol) and agar (0.15 g) in water–ethanol (3:1) was stirred under
reflux condition. The progress of the reaction was monitored by TLC. After
123

A. Moradi et al.
completion of the reaction, the reaction mixture was cooled to room temperature,
and diluted with water. The mixture was filtered and then washed with distilled
water for separation of the product. The crude product was recrystallized from
ethanol to afford the pure 3-(20-benzothiazolyl)-2, 3-dihydroquinazolin-4(1H)-one
derivatives. The desired pure products were characterized by comparison of their
1
physicaldata (melting points, IR and H NMR) with those of known compounds in
the literature [18, 26, 34, 35].
General procedure for the synthesis of 1-((benzo[d]thiazol-2-ylamino)(aryl)-
methyl)naphthalen-2-ol derivatives
A mixture of an aldehyde (1.0 mmol), 2-aminobenzothiazole (1.0 mmol), b-
naphthol (1.0 mmol) and agar (0.1 g) was added to 4 mL of ethanol. Then, the
reaction mixture was stirred under reflux condition for an appropriate time. The
progress of the reaction was monitored by TLC. After completion of the reaction,
the reaction mixture was cooled to room temperature, and diluted with water. The
mixture was filtered and then washed with distilled water for separation of the
product. The crude product was recrystallized from ethanol to afford the pure
1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ol derivatives. The
desired pure products were characterized by comparison of their physical data
1
(melting points, IR and H NMR) with those of known compounds in the literature
[37–39].
General procedure for the synthesis of 4H-pyrimido [2,1-b][1,3]benzothiazoles
A mixture of an aldehyde (1.0 mmol), 2-aminobenzothiazole (1.0 mmol), ethyl/
methyl acetoacetate (1.0 mmol) and agar (0.1 g) in water–ethanol (1:1), was
stirred at reflux condition. The progress of the reaction was monitored by TLC.
After completion of the reaction, the reaction mixture was cooled to room
temperature, and diluted with water. The mixture was filtered, washed with
distilled water for separation of the product. The crude product was recrystallized
from ethanol to afford the pure 4H-pyrimido [2,1-b][1,3]benzothiazole derivatives.
The desired pure products were characterized by comparison of their physical data
1
(melting points, IR and H NMR) with those of known compounds in the literature
[40–44].
Some spectral data for selected products are represented below
3-(20-Benzothiazolyl)-2,3-dihydro-2(4-nitrophenyl)-quinazolin-4(1H)-one (6c)
m.p = 242–244 °C; IR (KBr, cm-1): 3,375, 1,647, 1,613, 1,521; 1HNMR
(300 MHz, DMSO-d6): d (ppm) = 6.81 (1H, t, 1CH), 7.00 (1H, d, 1CH), 7.34
(1H, t, 1CH), 7.41 (1H, t, 1CH), 7.44 (1H, t, 1CH), 7.57 (2H, d, 2CH), 7.67 (1H, s,
1CH), 7.77 (1H, d, 1CH), H7.81 (1H, d, 1CH), 8.05 (1H, d, 1CH), 8.15 (2H, d,
2CH), 8.46 (1H, s, 1NH).
123

A novel, efficient, and biodegradable catalyst
123

A. Moradi et al.
123

A novel, efficient, and biodegradable catalyst
3-(20-Benzothiazolyl)-2,3-dihydro-2(4-cholorophenyl)-quinazolin-4(1H)-one (6e)
m.p = 192–193 °C; IR (KBr, cm-1): 3,334, 1,635, 1,609, 1,506, 1,405, 1,251;
1HNMR (300 MHz, DMSO-d): d (ppm) = 6.81 (1H, t, 1CH), 6.96 (1H, d, 1CH),
7.30 (2H, d, 2CH), 7.36 (1H, t, 1CH), 7.38 (2H, d, 2CH), 7.42 (1H, t, 1CH), 7.46
(1H, t, 1CH),7.54 (1H, d, 1CH(sp3)), 7.78 (1H, d, 1CH), 7.79 (1H, d, 1CH),8.06
(1H, d, 1CH), 8.34 (1H, NH).
3-(20-Benzothiazolyl)-2,3-dihydro-2(4-methylphenyl)-quinazolin-4(1H)-one (6i)
m.p = 198–199 °C; IR (KBr, cm-1): 3,342, 1,630, 1,612, 1,503, 1,432, 1,251;
1HNMR (300 MHz, DMSO-d6): d (ppm) = 2.17 (3H, s, CH3), 6.78 (1H, t, CH),
6.93 (1H, d, CH), 7.08 (2H, d, 2CH), 7.17 (2H, d, 2CH), 7.35 (1H, t, CH),7.38(1H, t,
CH), 7.45 (1H, t, CH), 7.51(1H, d, CH(sp3)), 7.77 (1H, t, CH), 7.79 (1H, d, CH),
8.04 (1H, d, CH), 8.30 (1H, d, NH).
3-(20-Benzothiazolyl)-2,3-dihydro-2(4-methoxyphenyl)-quinazolin-4(1H)-one (6k)
m.p = 183–185 °C; IR (KBr, cm-1): 3,347, 1,635, 1,608, 1,508, 1,433, 1,304,
1,230; 1HNMR (300 MHz, DMSO-d6): d (ppm) = 3.63 (3H, s, OCH3), 6.78 (1H, t,
CH), 6.83 (2H, d, 2CH), 6.94 (1H, d, CH),7.21 (2H, d, 2CH), 7.34 (1H, t, CH), 7.39
(1H, t, CH), 7.44(1H, t, CH), 7.52 (1H, br s, CH(sp3)), 7.78(1H, d, CH), 7.81 (1H, d,
CH), 8.04 (1H, d, CH), 8.32 (1H, br s, NH).
1-((Benzo[d]thiazol-2-ylamino)(4-chloro-phenyl)methyl)naphthalen-2-ol (7e)
m.p = 209–210 °C; IR (KBr, cm-1): 3,383, 1,604, 1,568, 1,503, 1,450 cm-1
;
1HNMR (300 MHz, DMSO-d6): d (ppm) = 6.99–7.82 (m, 15H, 14Harom and CH-
NH), 8.82 (s, 1H, NH), 10.19 (s, 1H, OH).
1-((Benzo[d]thiazol-2-ylamino)(4-methoxy-phenyl)methyl)naphthalen-2-ol (7k)
m.p = 175–176 °C; IR (KBr, cm-1): 3,366, 1,589, 1,546, 1,509, 1,451 cm-1
;
1HNMR (300 MHz, DMSO-d6): d (ppm) = 3.68 (s, 3H, OCH3), 6.82–7.81 (m, 15H,
14Harom and CH–NH), 8.78 (s, 1H, NH), 10.14 (s, 1H, OH).
2-Methyl-4-(2-chlorophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylic
acid methyl ester (8c)
m.p = 128–129 °C. IR (KBr, cm-1): 2,935, 1,680, 1,596, 1,516, 1,383, 1,182, 974,
827, 690 cm-1; 1HNMR (300 MHz, CDCl3): d (ppm) = 1.24 (t, 3H, CH3), 2.44 (s,
3H, CH3), 4.15 (q, 2H, OCH2), 6.74 (s, 1H, CH), 7.08–7.16 (m, 2H, Ar–H),
7.19–7.28 (m, 2H, Ar–H), 7.39 (d, 1H, Ar–H), 7.46 (d, 2H, Ar–H), 7.62 (d, 1H, Ar–
H).
123

A. Moradi et al.
123

A novel, efficient, and biodegradable catalyst
Table 4 Preparation of 3-(20-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)- one, 1-((benzo[d]thiazol-2-
ylamino)(aryl)-methyl)naphthalen-2-ol and 4H-pyrimido [2,1-b][1,3]benzothiazole derivatives in the pre-
sence of agar as biodegradable catalyst in green solvent under reflux condition
a
Entry
1
Aldehyde
Subestrate
Product
Time(min) Yield(%)
m.p(°C)/Lit. m.p [Ref]
233-235/(234-236)
[18]
O
CHO
6a
6b
6c
6d
6e
6f
25
20
20
20
25
25
20
45
35
40
45
94
95
96
91
94
91
93
90
89
90
88
O
N
O
S
N
H
N
H
O
O
O
O
O
O
O
O
O
O
O
N
H
O
CHO
NO2
2
3
252-253/(251-253)
[18]
O
N
O
O
O
O
O
O
O
O
O
O
S
N
H
N
H
NO2
N
H
CHO
O
241-244/(242-244)
[34]
O
N
H
O2N
S
N
N
H
N
H
NO2
Cl
O
CHO
4
160-163/(162-163)
[34]
O
N
S
N
H
N
H
N
H
Cl
O
CHO
5
193-195/(192-193)
[18]
O
N
H
S
S
S
S
S
S
N
N
N
Cl
Br
N
H
N
H
Cl
Br
CHO
O
6
231-233/(231-234)
[18]
O
N
H
N
H
N
H
O
Cl
7
6g
6h
6i
232-235/(229-239)
[26]
O
N
H
CHO
Cl
N
H
N
H
Cl
Cl
O
CHO
Me
8
200-203/(200-202)
[18]
O
N
H
N
N
H
N
H
Me
CHO
O
9
197-198/(198-199)
[18]
O
N
H
Me
N
N
N
H
N
H
Me
O
CHO
OMe
10
11
6j
225-228/(227-228)
[36]
O
N
H
N
H
N
H
MeO
CHO
O
6k
184-187/(183-185)
[18]
O
N
MeO
S
N
H
N
H
N
H
OMe
123

A. Moradi et al.
Table 4 continued
a
Entry
12
Aldehyde
Subestrate
Product
Time(min) Yield(%)
m.p(°C)/Lit. m.p [Ref]
OH
CHO
OH
7a
7b
7c
7d
40
30
35
45
93
95
95
90
204-206/(202-203)
N
[37]
S
N
OH
CHO
NO2
OH
13
14
15
197-200/(198-199)
[38]
N
S
S
N
NO2
CHO
H
O
OH
187-191/(190-191)
[37]
N
N
O2N
NO2
Cl
OH
OH
CHO
OH
191-192/(192-194)
[39]
N
S
N
Cl
CHO
OH
16
17
7e
7f
40
50
94
91
209-213/(209-210)
[37]
N
S
S
S
N
Cl
F
Cl
F
OH
CHO
OH
186-188/(188-189)
[37]
N
N
OH
OH
CHO
Cl
OH
18
19
7g
7h
50
30
88
95
207-208/(206-207)
[37]
N
N
Cl
Cl
OH
Cl
CHO
216-218/(214-215)
[36]
N
S
N
NC
CN
CHO
O
H
OH
20
7i
65
91
182-184/(182-183)
[38]
N
S
N
Me
Me
OH
OH
OH
CHO
OMe
OH
21
22
23
7j
7k
7l
75
60
80
88
91
87
166-169/(165-167)
[39]
N
S
N
MeO
OH
CHO
172-174/(175-176)
[39]
N
S
MeO
MeO
N
OMe
OMe
CHO
OMe
OH
160-162/(161-163)
[39]
N
S
N
MeO
123

A novel, efficient, and biodegradable catalyst
Table 4 continued
a
Entry
24
Aldehyde
Subestrate
Product
Time(min) Yield(%)
m.p(°C)/Lit. m.p [Ref]
O
O
CHO
8a
8b
45
92
170-174/173-175
O
[40]
OEt
EtO
H
N
S
3C
N
NO2
CHO
O
O
25
70
91
154-157/156-158
[40]
OEt
O2N
O
3C
O
EtO
H
N
N
S
O
O
CHO
Cl
O
O
26
27
8c
65
60
93
92
128-129/125-127
[43]
Cl
S
OEt
OEt
EtO
H
N
N
3C
Cl
CHO
8d
140/142-143
[42]
Cl
O
EtO
H
N
S
S
S
3C
N
Br
CHO
CHO
O
O
O
O
115-116/112-114
[40]
28
29
8e
8f
65
80
94
94
t
OE
OE
Br
O
EtO
H
N
3C
N
Me
150-152/153-154
[42]
t
Me
O
3C
O
EtO
H
N
N
O
O
CHO
Me
O
O
30
31
8g
8h
100
115
87
83
138-141/140-141
[40]
Me
S
t
t
OE
EtO
H
N
N
3C
OMe
CHO
192-194/(194-196)
[41]
OE
MeO
HO
O
EtO
H
N
S
S
3C
N
OH
CHO
O
O
32
8i
110
89
213-214/209-210
[44]
OEt
O
3C
O
EtO
H
N
N
O
O
CHO
O
O
33
34
8j
40
50
90
93
142-145/144-145
[40]
OMe
OMe
MeO
H
N
N
S
3C
Cl
CHO
8k
142-143/139-140
[42]
O
MeO
H
N
N
Cl
S
3C
123

A. Moradi et al.
Table 4 continued
a
Entry
35
Aldehyde
Subestrate
Product
Time(min) Yield(%)
m.p(°C)/Lit. m.p [Ref]
Cl
O
O
CHO
8l
8m
8n
8o
50
135
60
96
89
95
90
176-178/179-180
OMe
[42]
Cl
O
MeO
H
N
N
N
S
S
S
3C
N
F
O
O
O
CHO
CHO
CHO
O
O
O
36
37
38
158-162/160-161
[42]
OMe
F
O
MeO
H
3C
N
Br
167/166-167
[42]
e
OM
Br
O
MeO
H
3C
N
Me
70
153-156/154-155
[42]
OMe
Me
O
MeO
H
N
S
3C
N
N
O
O
CHO
OMe
CHO
O
O
39
40
8p
8q
120
110
87
84
142/145-146 [42]
OMe
O
OMe
OMe
MeO
3C
N
S
H
OMe
148-151/150-153
[40]
MeO
O
C
MeO
H3
N
N
S
a
Yields refer to isolated pure product
Results and discussion
In preliminary experiments, the model reaction of aldehyde, 2-aminobenzothi-
azole, isatoic anhydride (molar ratio: 1:1:1) in EtOH was studied to establish the
optimal conditions in the presence of different amounts of the catalyst at
different temperature under thermal conditions. The results are summarized in
Table 1. In the absence of a catalyst, only a trace amount of the desired product
6a was obtained, even after long reaction time and refluxing (Table 1, entries 1,
2). The reaction was also examined in solvents such as EtOH, MeOH and H2O-
EtOH under similar conditions. The best result was obtained with H2O-EtOH
(3:1) (Table 1, entry 12). To determine the appropriate amount of catalyst, the
model reaction was investigated with different quantities of agar, such as 0.05,
0.1, 0.15, 0.2 g. The results indicate that 0.15 g of agar is enough to carry out
the reaction efficiently (Table 1, entry 14). Increasing the amount of agar neither
improved the yield nor reaction time. As shown from Table 1, the best results
used 0.15 g of the catalyst in H2O-EtOH (3:1) under reflux condition (Table 1,
entry 14).
123

A novel, efficient, and biodegradable catalyst
This review was conducted for the preparation of 1-((benzo[d]thiazol-2-
ylamino)(aryl)-methyl)naphthalen-2-ol derivatives of 4-Chlorobenzaldehyde
(1.0 mmol), 2-aminobenzothiazole (1.0 mmol) and b-naphthol (1.0 mmol) in the
presence of 0.1 g of agar. It was found that the best results were obtained at reflux
condition with 0.1 g of agar in ethanol (1:1) (Table 2, entry 3). We also tested for
the preparation of 4H-pyrimido [2,1-b][1,3]benzothiazole derivatives by three-
component condensation reaction of benzaldehyde (1.0 mmol), 2-aminobenzothi-
azole (1.0 mmol) and ethyl acetoacetate (1.0 mmol) in the presence of 0.1 g of agar
in ethanol, water–ethanol, and methanol (Table 3). It was found that the best results
were obtained at reflux condition with 0.1 g of agar in water–ethanol (1:1) (Table 3,
entry 6). The results are summarized in Tables 2 and 3.
Using these optimized reaction, the scope and efficiency of the reaction were
explored for the synthesis of a wide variety of substituted 3-(20-benzothiazolyl)-2,3-
dihydroquinazolin-4(1H)- one, 1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naph-
thalen-2-ol and 4H-pyrimido [2,1-b][1,3]benzothiazoles using aldehydes, 2-amino-
benzothiazole, isatoic anhydride or b-naphthol or ethyl/methyl acetoacetate. The
results are summarized in Table 4.
We have not established a mechanism for the formation of 3-(20-benzothiazolyl)-
2,3-dihydroquinazolin-4(1H)- ones ring systems, but a reasonable possibility for this
synthesis in the presence of agar as catalyst is indicated in Scheme 2. We have
Scheme 2 A plausible mechanism for the formation of 3-(20-benzothiazolyl)-2,3-dihydroquinazolin-
4(1H)-one in the presence of agar in water–etahanol under reflux condition
123

A. Moradi et al.
demonstrated that agar forms some kind of micelle-like structures, which can hold
molecules and further catalyze reactions possibly activated by hydrogen bonds [23–
25, 33]. The free OH groups in agarose distributed on the surface of the agarose
activate the carbonyl group. The first step, condensation of 2-aminobenzothiazole 2
and isatoic anhydride 3, produced intermediate 4 with the removal of CO2
molecules. Then, activated aldehyde 1 was reacted with this intermediate 4 through
an imine intermediate 5 synthesis. In the next step, intermediate 6 could be prepared
by intermolecular nucleophilic attack of the amide nitrogen on activated imine
carbon, cyclisation, 1,5-proton transfer and tautomerization, affording the corre-
sponding product (Scheme 2).
Conclusions
In conclusion, we have described a new simple biopolymer catalytic system, and a
simple and efficient method for one-pot three-component synthesis of functional-
ized 3-(20-benzothiazolyl)-2,3-dihydroquinazolin-4(1H)- one, 1-((benzo[d]thiazol-
2-ylamino)(aryl)-methyl)naphthalen-2-ol and 4H-pyrimido [2,1-b][1,3]benzothiaz-
oles using aromatic aldehydes, 2-aminobenzothiazole, isatoic anhydride or ethyl/
methyl acetoacetate or b-naphthol in the presence of agar as a highly effective and
biodegradable green catalyst in ethanol or water–ethanol as a green solvent under
reflux condition.
The present protocol has several significant advantages such as effectiveness,
natural, biodegradable, clean, safe, non-toxic, environmentally friendly, inexpen-
sive, easy-to-handle catalyst, green conditions, high yields, short reaction times,
clean reaction conditions, simple work-up procedure, easy isolation of products, and
mild reaction conditions, which together make a useful and an instrumental
alternative to the existing methodologies. This work was performed for the first
time.
Acknowledgment We are grateful to the University of Sistan and Baluchestan Research Council for the
partial support of this research.
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