Nano-TiCl2/cellulose: an eco-friendly bio-based catalyst for one-pot synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives

Article abstract of DOI:10.1007/s11164-016-2725-2

Abstract: Cellulose is among the most abundant natural carbon-based biopolymers containing free OH groups with nucleophilic character for bonding to Lewis acids such as TiCl₄. Nano-TiCl₂/cellulose as a bio-based and eco-friendly Lewi

Full text of DOI:10.1007/s11164-016-2725-2

Res Chem Intermed
DOI 10.1007/s11164-016-2725-2
Nano-TiCl /cellulose: an eco-friendly bio-based catalyst
2
for one-pot synthesis of 4H-pyrimido[2,1-
b]benzothiazole derivatives
1
1
Sara Azad
•
Bi Bi Fatameh Mirjalili
Received: 28 June 2016 / Accepted: 31 August 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Cellulose is among the most abundant natural carbon-based biopolymers con-
taining free OH groups with nucleophiliccharacterforbondingtoLewisacidssuch as TiCl4.
Nano-TiCl /cellulose as a bio-based and eco-friendly Lewis acid catalyst was prepared via
2
reaction of nano-cellulose and TiCl in dichloromethane as solvent under room temperature
4
conditions. This catalyst has been characterized by Fourier transform infrared spectroscopy,
field emission scanning electron microscopy, powder X-ray diffraction, energy dispersive
X-ray spectroscopy, X-ray fluorescence techniques, and transmission electron microscopy.
Nano-TiCl /cellulose has been shown to effectively promote multi-component synthesis of
2
4H-pyrimido[2,1-b]benzothiazole derivatives by reaction of aldehydes, b-ketoester, and
2
-amino benzothiazole under thermal conditions in polyethylene glycol 400 as solvent.
Simple methodology,an eco-friendly catalyst, a clean procedure, easy work-up, and
excellent yields are some of the important advantages of this protocol.
Graphical Abstract
&
Bi Bi Fatameh Mirjalili
fmirjalili@yazd.ac.ir
1
Department of Chemistry, College of Science, Yazd University, Yazd 89195-741,
Islamic Republic of Iran
123

S. Azad, B. B. F. Mirjalili
Keywords 4H-pyrimido[2,1-b]benzothiazole Á Nano-TiCl /cellulose Á Solid acid Á
2
Supported Lewis acid Á Nano-cellulose Á Bio-based catalyst
Introduction
Benzothiazoles and their condensed system make a broader class of nitrogen and
sulfur-containing compounds with a wide range of biological activities [1–11]. Among
condensed benzothiazoles, pyrimido[2,1-b]benzothiazoles have attracted considerable
interest because of their potent and significant pharmacological activities. A survey of
the literature revealed that pyrimido[2,1-b]benzothiazoles display various biological
activities like anti-tumor [12, 13], anti-allergic [14], anti-inflammatory [15], anticon-
vulsant [16], antiproliferative [17], and antimicrobial activities [18–20].
In view of the importance of pyrimido[2,1-b]benzothiazoles, the development of
effective strategies for the synthesis of these fused heterocyclic compounds will be
interesting in both organic synthesis and medicinal chemistry. A common synthetic
approach to pyrimido[2,1-b]benzothiazole derivatives involves three-component
condensation of 2-amino benzothiazole, aldehydes, and b-ketoesters [21–24].
0
0
Previously, this protocol has been catalyzed by acetic acid [13], 1,1,3,3-N,N,N ,N -
tetramethylguanidinium trifluoroacetate (TMGT) [22], tetrabutylammonium hydro-
gen sulfate (TBAHS) [23], N-sulfonic acid modified poly(styrene-maleic anhydride)
(
SMI-SO H) [26], Chitosan [24] and aluminum chloride [27]. Some of these
3
catalysts suffer from drawbacks such as long reaction times [21, 25], high working
temperature [23] and low yield [22, 25]. Therefore, development of new solid acids
with numerous advantages such as cost-effectiveness, environmentally benign, easy
workup and good stability for the synthesis of pyrimido[2,1-b]benzothiazole
derivatives is of prime importance. Hence, we aim to develop inexpensive and
available solid acid bio-based catalysts for this transformation.
Considering the new trends of science and technology towards using natural
materials such as cellulose, the research efforts on green and eco-friendly methods
have become popular and desirable. Cellulose is one of the most abundant natural
carbon-based biopolymers containing free OH groups with nucleophilic character. It
has been used for synthesis of some compounds used in enantioselective chromatog-
raphy [28], protein immobilization [29], antibodies [30] and retarded drug release
[
31]. Cellulose is a potentially biodegradable material that can also be used as an
efficient support for bonding several functional groups to produce clean and
impressive biopolymer-based catalysts [32]. Cotton is a natural, cheap, and readily
available source of cellulose. In this study, we have investigated the preparation of
nano-cellulose by sulfuric acid hydrolysis (65 wt% H SO ,10 mL/g cellulose, 45 °C)
2
4
of pure cellulose isolated from cotton and synthesis of nano-TiCl /cellulose by
2
bonding TiCl to OH groups of D-glucose units in nano-cellulose. We intend to report
4
herein nano-TiCl /cellulose as a new, biodegradable, inexpensive and eco-friendly
2
bio-based catalyst for one-pot synthesis of pyrimido[2,1-b]benzothiazoles via three-
component reaction of aldehydes, ethyl acetoacetate and 2-amino benzothiazole under
thermal conditions.
1
23

Nano-TiCl /cellulose: an eco-friendly bio-based catalyst…
2
Materials and methods
General remarks
All compounds were purchased from Merck, Aldrich, and Fluka chemical
companies and used without any additional purification. A refrigerated centrifuge
(
spectra were run on a Bruker, Equinox 55 spectrometer. A Bruker (DRX-400
Appendorf Centrifuge 5417R) was used for preparation of nano-cellulose. FT-IR
1
13
Avanes) NMR was used to record the H-NMR and C-NMR spectra. Melting
points were determined by a Buchi melting point B-540 B. V. CHI apparatus and
were uncorrected. X-ray diffraction (XRD) patterns were obtained by a Philips
˚
Xpert MPD diffractometer equipped with a Cu Ka anode (k = 1.54 A) in the 2h
range from 10° to 80°. Field emission scanning electron microscopy (FESEM) was
obtained on a Mira 3-XMU. Transmission electron microscopy (TEM) was obtained
using a Philips CM120 with a LaB6 cathode and accelerating voltage of 120 kV.
Quantitative elemental information (EDS) of nano-TiCl /cellulose was measured by
2
an EDS instrument and Phenom pro X. XRF analysis was done using a Bruker, S4
Explorer instrument.
Preparation of nano-cellulose from cotton
Cotton fibers were washed with distilled water several times and dried in an air-
circulated oven at 100 ± 2 °C until constant weight. Then, they were chopped to an
approximate length of 5–10 mm. The fibers were then treated with a 17.5 w/v
NaOH solution at 100 °C for 12 h under mechanical stirring. This treatment allowed
purifying cellulose by removing other constituents like lignin, hemicellulose, wax,
organic acids and so on present in the fibers. Subsequently, fibers were filtered and
washed with distilled water until the alkali was completely eliminated. It was then
bleached with 100 mL of 1:1 aqueous dilution of 3.5 % w/v sodium hypochlorite at
8
0 °C for 3 h under mechanical stirring. The resulting alpha cellulose was partially
hydrolyzed using 65 % sulfuric acid aqueous solution with a cotton-to-acid weight
ratio of 1–10 at 45 °C. After 1 h, the obtained suspension was diluted with water
fivefold to stop the hydrolysis reaction. The suspension was centrifuged at
1
2,000 rpm to separate the nano-cellulose from acid solution. The washing with
water and centrifuging was repeated four to five times to remove any remaining free
acid.
Preparation of nano-TiCl /cellulose
2
In a well-ventilated system, TiCl (5 mL) was added dropwise to the mixture of
4
nano-cellulose (5 g) in chloroform (20 mL). The mixture was stirred for 1 h at room
temperature. The resulted suspension was filtered, washed with chloroform and
dried at room temperature.
FT-IR spectrum of nano-TiCl /cellulose (KBr). 3335, 1111, 1056, 1032,
2
-
28 cm .
1
8
123

S. Azad, B. B. F. Mirjalili
General procedure for synthesis of 4H-pyrimido[2,1-b]benzothiazole
derivatives
A mixture of 2-aminobenzothiazole I (1 mmol), aldehyde II (1 mmol), ethyl
acetoacetate III (1 mmol), and PEG-400 (0.5 mL) was heated at 70 °C in the
presence of nano-TiCl /cellulose (0.03 g). After completion of the reaction
2
(
monitored by TLC), hot ethanol (10 mL) was added to the mixture and filtered
off for separation of catalyst. By adding water to filtrate, the product appeared as a
pure solid in high yields.
Spectroscopic data of Ethyl-2-methyl-4-(4-nitrophenyl)-4H-pyrimido[2,1-b] [1,3]
1
benzothiazole-3-carboxylate (Table 4, IV ). Yellow solid. H NMR (Acetone-d ,
b
6
4
00 MHz): d 8.18 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz,
H), 7.41 (d, J = 8 Hz, 1H), 7.32 (t, J = 8 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 6.69
1
(
s, 1H), 4.09–4.16 (m, 2H), 2.37 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H). IR (KBr): 3074,
-
1
2
981, 1700, 1670, 1585, 1501, 1347, 1272, 1242, 1202, 745 cm . mp: 171–173 °C.
Spectroscopic data of Ethyl-2-methyl-4-(2-ethoxyphenyl)-4H-pyrimido[2,1-b]
1
1,3] benzothiazole-3-carboxylate (Table 4, IV ). Yellow solid. H NMR (Ace-
[
h
tone-d , 400 MHz): d 7.63 (d, J = 8 Hz, 1H), 7.53 (dd, J = 7.6, 1.6 Hz, 1H), 7.47
6
(
d, J = 8 Hz, 1H), 7.29 (m, 1H), 7.15–7.18 (m, 2H), 6.88–6.92 (m, 2H), 6.75 (s,
1
1
1
H), 4.10–4.14 (m, 2H), 4.03 (q, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.50–1.54 (m, 3H),
.16–1.20 (m, 3H). IR (KBr): 2980, 1692, 1600, 1511, 1493, 1242, 1201, 1075,
-
1
040, 752 cm . mp: 171–175 °C.
Spectroscopic data of Ethyl-2-methyl-4-(2,4-dimethoxyphenyl)-4H-pyrimido[2,1-
1
b] [1,3] benzothiazole-3-carboxylate (Table 4, IV ). Yellow solid. H NMR (Ace-
l
tone-d , 400 MHz): d 7.62 (d, J = 7.6 Hz, 1H), 7.45 (d, J = 8 Hz, 1H), 7.37 (d,
6
J = 8.4 Hz, 1H), 7.30 (td, J = 8, 1.2 Hz, 1H), 7.15 (td, J = 7.6, 1.2 Hz, 1H), 6.68
(
s, 1H), 6.44–6.48 (m, 2H), 4.05 (q, J = 6.8 Hz, 2H), 3.93 (s, 3H), 3.71 (s, 3H), 2.36
s, 3H), 1.19 (t, J = 6.8 Hz, 3H). IR (KBr): 1694, 1583, 1497, 1271, 1239, 1203,
(
-
1
1
075, 836, 739 cm . mp: 164–166 °C.
Results and discussion
Catalyst characterization
The particle sizes of nano-cellulose and nano-TiCl /cellulose were investigated by
2
field emission scanning electron microscopy (FESEM) and transmission electron
microscopy (TEM) in which the achieved dimensions of catalyst were below 50 nm
(
Fig. 1).
Comparison of nano-TiCl /cellulose with nano-cellulose was achieved by FT-IR
2
(
at 3337 cm
ATR) spectra (Fig. 2). The FT-IR spectrum of nano-cellulose shows a broad band
-
1,
which corresponds to the stretching vibrations of OH groups. The
-
1
absorption bands around 1055 and 1108 cm display the stretching vibrations of
the C–O bonds. For nano-TiCl /cellulose, cellulose absorptions appear in addition to
2
-
1
the stretching vibrations of C–O–Ti at 828 cm ; indicating that titanium chloride is
supported on nano-cellulose.
1
23

Nano-TiCl /cellulose: an eco-friendly bio-based catalyst…
2
2
Fig. 1 a FESEM image of nano-cellulose, b FESEM of nano-TiCl /cellulose and c TEM of nano-
2
TiCl /cellulose
2
Fig. 2 FT-IR spectra of (a) nano-cellulose, (b) nano-TiCl /cellulose
Existence of Ti and Cl in catalyst was confirmed by EDS analysis data (Fig. 3).
The percentages of Ti and Cl in TiCl are 25.24 and 74.76, respectively. Thus, the
4
amounts of Ti and Cl in EDS data (Ti: 20.3 %, Cl: 14.9 %) revealed the absence of
any unreacted TiCl in catalyst. Hence, XRF analysis of nano-TiCl /cellulose was
performed to determine its elemental component (Table 1; Fig. 4).
4
2
To obtain the Ti:Cl ratio in nano-TiCl /cellulose using XRF analysis, Killo
2
Counts Per Seconds (KCPS) of elements in catalyst were compared with KCPS of
the same elements in pure samples, NaCl and TiO . By this comparison, the
2
obtained amount of Ti and Cl was 12.02 g (0.25 mol) and 14.3 g (0.4 mol),
respectively. Thus, the ratio of Ti:Cl in catalyst is approximately 1:2.
The X-ray diffraction (XRD) pattern of nano-TiCl /cellulose is depicted in
2
Fig. 5. The values of 2h and FWHM are shown in Table 2. According to the XRD
pattern, the three signals in 2 O– equal to 15.13, 16.74, and 22.93 with FWHM equal
to 0.472, 0.944, and 0.472, respectively, show the existence of cellulose. Other
signals in 2 O– equal to 20.55, 28.56, 34.63, and 41.84 prove the bonding of Ti to the
cellulose backbone.
123

S. Azad, B. B. F. Mirjalili
Fig. 3 EDS (EDX) spectra of nano-TiCl
2
/cellulose
Table 1 Results of XRF
Elemental TiCl /nano-
component cellulose
2
NaCl
TiO
2
2
analysis of nano-TiCl /cellulose
and pure samples NaCl and TiO
2
KCPS wt%
KCPS wt% KCPS wt%
Cl
123.5
464.3
6.8
22.2
516.5 62.4
2318.4
TiO
2
99.1
CO
CaO
SiO
Al
SO
2
1.6
37.6
7.1
67.1
1.9
2
1.43
2
O
3
2.3
0.558
0.504
3
5.3
MgO
Total
1.9
0.374
100.86
According to the above-mentioned data, we have proposed a structure for nano-
TiCl /cellulose (Fig. 6). This catalyst does not need special precautions for
2
preparation, handling or storage, and it can be stored at an ambient temperature for
months without losing its catalytic activity.
Catalyst testing for synthesis of 4H-pyrimido[2,1-b]benzothiazole
derivatives
The catalytic activity of nano-TiCl /cellulose was investigated for the synthesis of
2
4
2
H-pyrimido[2,1-b]benzothiazole derivatives via three-component reactions of
-aminobenzothiazole, aldehydes and ethyl acetoacetate. In order to optimize the
reaction conditions, including solvent, temperature and catalyst loading, the model
reaction of 2-aminobenzothiazole, 4-nitrobenzaldehyde and ethyl acetoacetate was
initially carried out under different conditions in the presence of nano-TiCl /cel-
2
lulose (Table 3). Different solvents including THF, H O, CH CN, C H OH, MeOH,
2
3
2 5
PEG-200, and PEG-400 were screened (Table 3, Entries 3–10); condensation of
1
23

Nano-TiCl /cellulose: an eco-friendly bio-based catalyst…
2
2
Fig. 4 XRF analysis of nano-TiCl /cellulose
Fig. 5 XRD pattern of nano-
TiCl /cellulose
2
Table 2 Nano-TiCl
2
/cellulose reflexes in XRD diffractogram
No
1
2
3
4
5
6
7
Pos. [°2h]
FWHM [°2h]
15.130
0.472
16.748
0.944
20.553
0.472
22.935
0.472
28.563
0.708
34.634
0.295
41.846
1.728
2
Fig. 6 Proposed structure of nano-TiCl /cellulose
123

S. Azad, B. B. F. Mirjalili
Table 3 The reaction of 2-aminobenzothiazole, 4-nitrobenzaldehyde, and ethyl acetoacetate in the
presence of nano-TiCl /cellulose under various conditions
2
a
Entry
Solvent
Catalyst (g)
Condition
Time (h)
Yield (%)
b
1
2
3
4
5
6
7
8
9
–
Catalyst (0.05)
R. T
70 °C
Reflux
Reflux
Reflux
Reflux
R. T
Reflux
70
6
6
7
7
6
6
7
5
4
1
1
2
4
1
1
3
4
7
7
1
1
1
1
1
30
70
41
53
59
60
37
50
75
92
80
65
40
85
96
78
70
–
b
–
Catalyst (0.05)
b
THF
Catalyst (0.05)
b
H
2
O
Catalyst (0.05)
b
CH CN
3
Catalyst (0.05)
b
C
2
2
H
5
5
OH
OH
Catalyst (0.05)
b
C
H
Catalyst (0.05)
b
MeOH
Catalyst (0.05)
b
PEG-200
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-200
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
Catalyst (0.05)
b
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
Catalyst (0.05)
70
b
Catalyst (0.05)
100
50
b
Catalyst (0.05)
b
Catalyst (0.05)
R. T
70
b
Catalyst (0.04)
b
Catalyst (0.03)
70
b
Catalyst (0.02)
70
b
Catalyst (0.03)
70
–
–
R.T
70
30
92
88
85
82
80
b
Catalyst (0.03), second run
b
Catalyst (0.03), third run
70
70
b
Catalyst (0.03), forth run
b
Catalyst (0.03), fifth run
70
70
b
Catalyst (0.03), sixth run
70
The amount ratios of 2-aminobenzothiazole (mmol), 4-nitrobenzaldehyde (mmol) and ethyl acetoacetate
(mmol) are equal to 1:1:1
a
Isolated yield
b
2
nano-TiCl /cellulose
2
-aminobenzothiazole, 4-nitrobenzaldehyde and ethyl acetoacetate was easier and
gave the highest yield in the presence of PEG-400 as solvent (Table 3, Entry 10).
The effect of reaction temperature was also examined (Table 3, Entry 10–13), and
the reaction was found to proceed smoothly at 70 °C (Table 3, Entry 10). To
1
23

Nano-TiCl /cellulose: an eco-friendly bio-based catalyst…
2
Table 4 Comparative study of the present method and some other reported methods for synthesis of4H-
pyrimido[2,1-b]benzothiazole derivatives
a
Entry Solvent
Catalyst
Temperature Time (h) Yield (%)
(°C)
1
2
3
4
5
a
MeOH
Acetic acid (20 mol%)
b
65
18
2
62 [13]
Ethylene glycol
–
TBAHS (30 mol%)
c
TMGT (0.080 g)
120
100
70
72 [11]
5
53 [10]
Acetic acid (2 %) Chitosan (0.080 g)
1.6
1
93 [12]
PEG-400
Nano-TiCl
2
/cellulose (0.03 g)
70
97 This work
Isolated yield
b
Tetrabutylammonium hydrogen sulfate
0 0
,1,3,3-N,N,N ,N -tetramethylguanidinium trifluoroacetat
c
1
optimize the catalyst amount, the model reaction was performed in the presence of
various amounts of the catalyst and according to the obtained results (Table 3,
Entries 14–16) 0.03 g of the catalyst was chosen as the best catalyst amount
(Table 3, Entry 15). In conclusion, the best reaction condition for this transforma-
tion is the use of 0.03 g of the catalyst in the presence of PEG-400 as solvent at
7
0 °C (Table 3, Entry 15).
Moreover, reusability of the catalyst was investigated. After the reaction was
completed, followed by the filtration, the filtered catalyst was washed with acetone
and dried for 3 h at 70 °C, and then saved for the next reaction. The reusability of
the catalyst was tested at least five times, and the desired product was isolated in
each run (Table 3, Entries 20–24). It was found that the reactivity of the catalyst
decreases slightly for the next run.
Comparison of the results of the nano-TiCl /cellulose-catalyzed reaction of
2
4
-nitrobenzaldehyde (1 mmol), 2-aminobenzothiazole (1 mmol) and ethylacetoac-
etate (1 mmol) with previously reported methods shows the merit of the present
protocol (Table 4).
Based on the optimized reaction conditions, a range of 4H-pyrimido[2,1-
b]benzothiazole derivatives were synthesized by the reaction of 2-aminobenzoth-
iazole (I, 1 mmol), aldehydes (II, 1 mmol) and ethyl acetoacetate (III, 1 mmol)
(
Table 5). Electronic effects and the nature of substituents on the aldehyde showed a
significant effect in terms of the yield and reaction time under the optimized
reaction conditions. The electron-withdrawing groups increased reactivity and
afforded higher yields compared to the electron-donating groups.
The suggested mechanism for the synthesis of 4H-pyrimido[2,1-b]benzothiazole
IV) is displayed in Scheme 1 in which supported titanium chloride could act as a
(
Lewis acid to activate the carbonyl groups. It seems benzaldehyde (II) as an
electrophile and b-ketosters (III) as active methylene compounds take part through
an in situ Knoevenagel reaction and an alkene is primarily formed.
Afterwards, during the Michael addition reaction, 2-aminbenzothiazole, as a
Michael donor, attacks alkene during nucleophilic reaction, so an iminium ion is
123

S. Azad, B. B. F. Mirjalili
Table 5 Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (IVa-m) in the presence of nano-
TiCl /cellulose at 70 °C
2
a
Entry
R (IIa–j
)
Product (Va–j
)
Time (h)
Yield (%)
M.P. [Ref]
1
2
3
4
5
6
7
8
9
H (II
4-NO
4-Cl-(II
4-Br (II
4-OH-(II
2-NO
2-Cl-(II
2-EtO-(II
3-NO -(II
3-OH-(IIj)
2,4-(Cl) -(II
2,4-(MeO) -(II
3,4-(OH) -(II
a
)
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
a
b
c
d
e
f
1.5
1
80
96
97
95
79
85
97
75
90
80
91
74
68
178–180 [14]
171–173 [15]
87–89 [14]
110–114 [10]
210–212 [15]
122–125
2
-(II
b
)
c
)
1
d
)
1
e
)
2
2
-(II
f
)
1.5
1
g
)
g
h
i
124–126 [11]
171–175
h
)
2
2
i
)
1.5
2
222–224 [14]
260–263
10
11
12
13
j
2
k
)
k
l
1
133–135 [11]
164–166
2
l
)
2.5
2.5
2
m
)
m
225–227
2
I (mmol): II (mmol): III (mmol): nano-TiCl /cellulose (g) is equal to 1:1:1:0.03
a
Isolated yield
formed. Subsequently, with a proton transformation and an intramolecular
cyclization, products IVa-m are produced. The structure of the products IV
a-m
1
was deduced from its mp, IR and H NMR spectra. In the FTIR spectra, the ester
-
1
C=O stretching frequency appeared around 1650 cm due to conjugation. H NMR
1
spectra of products IVa-m exhibited a singlet at about d = 5.54–6.33 ppm for H-4.
Hot filtration test
A hot filtration test was conducted to confirm that the nano-catalyst was indeed
heterogeneous. In this test, a mixture of 2-aminobenzothiazole I (1 mmol), aldehyde
II (1 mmol), ethyl acetoacetate III (1 mmol), and PEG-400 (0.5 mL) was heated at
7
TiCl /cellulose was then filtered off from the hot reaction mixture, and the reaction
0 °C in the presence of nano-TiCl /cellulose (0.03 g) for 30 min. The nano-
2
2
in the filtrate was still monitored. No increase in conversion was observed in the
filtrate.
1
23

Nano-TiCl /cellulose: an eco-friendly bio-based catalyst…
2
Scheme 1 Proposed mechanism for the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives IVa-m
Leaching test
AAS (Atomic Absorption Spectroscopy) technique was employed to be sure that no
leaching of Ti took place after the catalytic reaction. After the completion of
reaction, chloroform was added to the mixture and filtered off for separation of
catalyst. The filtrate (reaction mixture) was analyzed using AAS with a hollow
cathode lamp at a wavelength of 346 nm using a C2H2/N2O flame, which indicates
that no Ti species was detected in the filtrate solution.
Conclusion
In conclusion, nano-TiCl /cellulose can be described as a green, cheap, natural,
2
biodegradable, and readily available biopolymer solid acid catalyst. The catalytic
activity of the prepared catalyst was investigated in the synthesis of 4H-
pyrimido[2,1-b]benzothiazole derivatives through one-pot three-component reac-
tion of aldehydes, ethyl acetoacetate, and 2-aminobenzothiazole in the presence of
PEG-400 as solvent at 70 °C. Environmentally benign conditions, clean synthesis,
easy work-up, and high yields are among the advantages of this novel methodology.
Acknowledgments The Research Council of Yazd University is gratefully acknowledged for the
financial support for this work.
123

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