Sodium alginate: Biopolymeric catalyst for the synthesis of 2-amino-4-arylthiazole derivatives in aqueous medium

Article abstract of DOI:10.1016/j.molstruc.2021.129900

Regarded as a naturally occurring macromolecule and without any post-modification, sodium alginate which possesses a granular form was found to be an efficient and recoverable bifunctional heterogeneous organocatalyst for the synthesis of 2-amino-4-arylthiazole derivatives was carried out by the reaction of substituted phenyl acetylene and thiourea in an eco-friendly condition in the presence of TBBDA (tetrabromobenzene-1,3-disulfonamide (tetrabromobenzene-1,3-disulfonamide). Mild reaction conditions, simple reaction procedure, easy purification, high yields of products, eco-friendly catalyst usage and convenient reusability are the highlighted points of this protocol.

Full text of DOI:10.1016/j.molstruc.2021.129900

Journal of Molecular Structure 1231 (2021) 129900
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Sodium alginate: Biopolymeric catalyst for the synthesis of
2-amino-4-arylthiazole derivatives in aqueous medium
∗
Samareh Gorji, Ramin Ghorbani-Vaghei , Sedigheh Alavinia
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 6517838683, Hamadan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Regarded as a naturally occurring macromolecule and without any post-modification, sodium alginate
which possesses a granular form was found to be an efficient and recoverable bifunctional heteroge-
neous organocatalyst for the synthesis of 2-amino-4-arylthiazole derivatives was carried out by the reac-
tion of substituted phenyl acetylene and thiourea in an eco-friendly condition in the presence of TBBDA
Received 18 September 2020
Revised 3 December 2020
Accepted 29 December 2020
Available online 13 January 2021
(
tetrabromobenzene-1,3-disulfonamide (tetrabromobenzene-1,3-disulfonamide). Mild reaction conditions,
Keywords:
simple reaction procedure, easy purification, high yields of products, eco-friendly catalyst usage and con-
venient reusability are the highlighted points of this protocol.
2-amino-4-arylthiazol
Thiourea
©
2021 Elsevier B.V. All rights reserved.
Phenyl acetylene
Alginate/TBBDA
1. Introduction
in the cell walls of brown algae, sodium alginate, which is the
sodium salt of alginic acid, can be regarded as a natural anionic
macromolecule.
Currently, noticing the environmental pollution and its ef-
fects on human life compels the researchers to develop pro-
cedures using eco-friendly materials and chemical methods. In
this sense, chemical processes applying more eco-friendly cata-
lysts, chemicals, solvents and atom-efficient processes would re-
ceive more and more attention [1,2]. Accordingly, heterogeneous
catalysis – due to the products’ higher purity the separation sim-
plicity and recycling of the catalysts – has been regarded as a
useful tool [3]. In this respect, a wide variety of heterogeneous
catalysts has been developed by the immobilization of transi-
tion metals on the inorganic materials’ surface, and synthetic or-
ganic polymers as support material [4-7]. Moreover, as alterna-
tive to synthetic organic polymers in heterogeneous catalytic sys-
tems, important attention has been paid to bioploymeric macro-
molecules. The biopolymers’ popularity, i.e. starch, cellulose, chi-
tosan, collagen, wool and alginates [8-10] would arise from their
environmental sustainability. Nonetheless, macromolecules’ use in
pure form, as heterogeneous catalysts, has become basically sig-
nificant due to the elimination of metals’toxicity, biodegradabil-
ity and eco-friendly properties, cost-effectiveness and availability
Alginic acid is a polysaccharide distributed widely as a linear
polysaccharide in the cell walls of the brown algae and as capsu-
lar polysaccharides in soil bacteria, In addition, it can be extracted
from the main source in brown seaweeds of the class Phaeo-
phyceae, such as Ascophyllum nodosum, Laminariaspp, etc. [13,14].
α-(1→4)-l-guluronic acid (G) and β-(1→4)-d-mannuronic acid
(M) were the monomers of alginate. Moreover, alginates can be re-
garded as true block copolymers, composed of homopolymeric re-
gions of M and G blocks, interspersed with alternating MG blocks
(Fig. 1).
Detailed investigations have shown that alginates have no reg-
ular repeating unit. The different proportions (M/G) depend on the
source of the derived alginates [15]. Each of these has a different
conformation and, therefore, physical behavior. Alginates have at-
tracted considerable attention in the food, chemical and medicinal
economies, paper, textile, agricultural industries and catalytic ac-
tivity because of the abundant amounts and useful properties [16-
21]. Simultaneously, one can find each monomeric unit of sodium
alginate containing a carboxylate and two hydroxyl groups. Accord-
ingly, the nucleophilic and electrophilic reaction constituents can
be activated by carboxylate groups and hydrogen bonding as a bi-
functional heterogeneous organocatalyst [22,23]. Due to their large
surface area, biodegradable, and good biocompatibility, and algi-
nate would basically receive great attention. Thus, alginate would
greatly be applied; i.e. in drug delivery systems [24], tissue engi-
neering [25], sensors [26] removal of pollution [27] and catalysts.
Nowadays, sodium alginate – as a natural material – would be ap-
[
11,12].
In this sense, it is worth mentioning that; sodium alginate plays
a significant role as a natural and biodegradable polymer. Founded
∗
Corresponding author.
E-mail addresses: rgvaghei@yahoo.com, ghorbani@basu.ac.ir (R. Ghorbani-
Vaghei).
https://doi.org/10.1016/j.molstruc.2021.129900
0
022-2860/© 2021 Elsevier B.V. All rights reserved.

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
Scheme 1. Comparison of the previous method for the (A) synthesis of thiazole framework (B) with the present work.
are few reports for the synthesis of thiazoles with substituted
phenyl acetylene [49] and it can be introduced as a newer method
than others. Moreover, phenacyl bromide as an intermediate has
been produced in-situ with reaction between phenyl acetylene and
TBBDA. In addition, the synthesis of these compounds under envi-
ronmentally compatible conditions can be extremely important.
In continuous of our study on the preparation of thiazoles using
TBBDA [43,50] and designing reactions according to green chem-
istry [51,52], herein, we report a mild and efficient procedure for
the synthesis of thiazole derivatives in the presence of sodium al-
ginate along with TBBDA in aqueous medium in order to reduce
harmful effects of organic solvents (Scheme 1). Moreover, reaction
time was reduced and different 2-amino-4-arylthiazole derivatives
were synthesized. We believe that alginate can activate substrates
or intermediates with carboxylate and hydroxyl group and act as
a linear polymer support, making the related reaction at its sur-
face easier. Considering these interpretations, this linear support is
more suitable for larger molecules with more space than beta CD
with a cyclic structure. As can participate more effectively in this
chemical reaction, the number of active hydroxyl and carboxylate
groups is more than betacyclodexterine.
Fig. 1. Structure of Alginate.
plied as a solid catalyst in Suzuki cross-coupling [16], Mannich re-
action [12], pyrimidone [28] and pyran synthesis [29].
Another point that should be considered is that solvent is an
inseparable part of chemical reactions and, according to the rules
of green chemistry, water is the best solvent because it is founds
in nature and is environmentally friendly [30,31]. In recent years,
organic reactions in water, due to the insolubility of materials and
organic products in water, have been regarded as a big challenge.
Accordingly, some natural biopolymers such as cellulose, chitosan,
and alginates can be used for organic chemical reactions because
of their green nature, environmental compatibility and absorbing
water [29,32,33].
Moreover sodium alginate’s capability in absorbing 200–300
times of its own weight [24] significantly indicates its catalytic ac-
tivity. In this sense, it is so when the reaction’s byproduct is wa-
ter. These requirements are fully met in the multicomponent reac-
tion (MCR) for the synthesis of 2-amino-4-aryl thiazole derivatives
through condensation of different phenyl acethylene and thiourea.
Thiazole is one of the most important heterocyclic compounds
and its role in many biologically active compounds and drug de-
sign is undeniable. Some examples containing thiazole are anti-
neoplastic agents [34,35], anti-HIV drug [36], antifungal agent [37],
antiparasitic agent [38], anti-inflammatory agents [39,40], antiulcer
agent [41] and insecticide [42]. However, several protocols which
have been reported for synthesis of thiazoles have been done us-
ing acetophenone [43-46] and phenacyl bromide [47,48]; but, there
2
. Experimental
2
.1. Chemicals
All commercial materials were purchased from Merck or Fluka
companies and used without further purification. Sodium alginate
SA, low viscosity) was obtained from sigma-aldrich (China).
(
2.2. Apparatus
Nuclear magnetic resonance (NMR) spectra were recorded in
DMSO–d6 on Bruker Avance spectrometers of 250 MHz, 400 MHz
and 500 MHz for 1H NMR and 62.5, 100 and 125 MHz for 13C
2

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
Table 1
Optimization the reaction condition.
Entry
Conditions
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
TBBDA (0.25 mmol), water, 70 °C, Alginate (0)
TBBDA (0.2 mmol), H2O, 70 °C, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O, 70 °C, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O/EtOH, 70 °C, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O/MeCN, 70 °C, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O, RT, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O, Reflux, Alginate (0.05 g)
TBBDA (0.25 mmol), H2O, 70 °C, Alginate (0.025 g)
TBBDA (0.25 mmol), H2O, 70 °C, Alginate (0.1 g)
TBBDA (0.25 mmol), H2O, 70 °C, Chitosan (0.1 g)
TBBDA (0.25 mmol), H2O, 70 °C, Starch (0.1 g)
NBS (0.25 mmol), H2O, 70 °C, Alginate (0.1 g)
HBr, H2O, 70 °C, Alginate (0.1 g)
8
N.R
75
4
2
87
2
72
2
63
4
44
2
87
2
80
2
88
1
1
1
1
0
1
2
3
5
40
24
24
24
Trace
50
N.R
aReaction conditions: phenyl acetylene, TBBDA and thiourea in H2O (10 mL).
bIsolated yield.
NMR using TMS as an internal standard; chemical shifts were ex-
pressed in parts per million (ppm). Infrared (IR) spectroscopy was
conducted on a Perkin Elmer GX FT-IR spectrometer. Mass spec-
tra were recorded on a Shimadzu QP 1100 BX Mass Spectrometer.
Melting points were determined on a Stuarf Scientific SMP3 ap-
paratus. Energy dispersive X-ray (EDX) and Scanning electron mi-
croscopy (SEM) analysis of the prepared catalyst was fulfilled on a
FESEM-SIGM (Germany) instrument.
2
.3. General procedure for the synthesis of 2-amino-4-arylthiazoles
In a round bottom flask (25 mL), a mixture of phenyl acetylene
(
1 mmol), TBBDA (0.25 mmol), thiourea (2 mmol) and sodium algi-
nate (10 mol%) in H O (10 mL) was stirred at 70 °C. The progress of
2
Fig. 2. IR spectrum of mixture in the middle of the reaction.
the reaction was monitored by TLC (eluent: n-hexane–EtOAc, 6:1).
Solvent was evaporated and, then, the crude product was dissolved
in boiling water, extracted with ether (3 × 30 ml), and, finally ad-
justed to pH=10 with the amount of ammonia to gain the pure
product. The products were characterized using physical and spec-
troscopic (IR, NMR, MS) data.
4
-phenylthiazol-2-amine (3a)
Yellow solid, Yield: 87%, mp: 149–150 °C, [lit. mp: 148–150 °C]
−
1
[
56], IR (KBr): 3436, 3251, 1599 cm
.
1
H NMR (250 MHz, DMSO–d ): δ (ppm): 6.9 (s, 1H, thiazole
6
H
H), 7.0 (s, 2H, NH ), 7.24 (t, 1H, J = 7.25 Hz, ArH), 7.36 (t, 2H,
2
13
J = 7 Hz, ArH), 7.7 (d, 2H, J = 11.6 Hz, ArH). C NMR (63 MHz,
DMSO–d ): 101.9, 125.9, 127.6, 128.9, 135.3, 150.3, 168.7 ppm. MS
6
Fig. 3. IR spectrum for investigation of the recyclability of alginate as a catalyst.
(
m/z): 176.
4
-p-Tolylthiazol-2-amine (3b)
4-(2-Aminothiazol-4-yl) phenol (3c)
Yellow solid, Yield: 85%, mp: 133–135 °C, [lit. mp: 130–132 °C]
−
1
[
56], IR (KBr): 3454, 3299, 1637cm
.
Yellow solid, Yield: 74%, mp: 174–176 °C, [lit. mp: 175–177 °C]
1
−1
H NMR (250 MHz, DMSO–d ): δ (ppm): 2.2 (s, 3H, CH ), 6.9
[56], IR (KBr): 3434, 3316, 1639 cm
.
6
H
3
(
s, 1H, thiazole H), 6.99 (s, 2H, NH ), 7.15 (d, 2H, ArH, J = 8.25 Hz),
1H NMR (400 MHz, DMSO–d ): δ
(ppm) 6.71 (d, 2H,
2
6
H
13
7
.67 (d, 2H, ArH, J = 8.25 Hz), C NMR (63 MHz, DMSO–d ): δ
c
J = 8.8 Hz, ArH), 6.83 (s, 1H, thiazole H), 7.37 (d, 2H, J = 8.8 Hz,
6
2
1.2, 101.0, 125.9, 129.4, 132.5, 136.88, 150.1, 168.6 ppm, MS (m/z):
ArH), 8.62 (s, 1H, OH); 13C NMR (100 MHz, DMSO–d ): δc 99.8,
6
190
115.7, 119.7, 127.4, 139.3, 158.5, 170.1 ppm, MS (m/z): 192.
3

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
Table 2
Synthesis of 2-amino-4-arylthiazole 3(a-j) using alginate/ TBBDAa
Entry
1
Phenylacetylene
Time (h), Yield (%)b
(2 h, 87 %)
2
3
4
(2 h, 85 %)
(2 h, 74 %)
(2 h, 80 %)
5
(4 h, 80 %)
6
(2 h, 92 %)
7
(2 h, 94 %)
(
continued on next page)
4

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
Table 2 (continued)
Entry
8
Phenylacetylene
Time (h), Yield (%)b
(2 h, 90 %)
9
(3 h, 80 %)
1
0
(4 h, 74 %)
aReaction condition: phenylacetylene (1 mmol), thiourea (2 mmol), TBBDA (0.25 mmol) and sodium alginate (0.05 g) at 70 °C in H2O (10 mL).
bIsolated yield.
Fig. 4. SEM of sodium alginate.
4
-(4-Methoxyphenyl) thiazol-2-amine (3d)
4-(4-Chlorophenyl) thiazol-2-amine (3f)
Yellow solid, Yield: 80%, mp: 200–202 °C, [lit. mp: 200–203 °C]
White solid, Yield: 92%, mp: 205–207 °C, [lit. mp: 203–205 °C]
−1
−1
[
56], IR (KBr): 3439, 3284, 1634 cm
.
[56], IR (KBr): 3439, 3284, 1634 cm
.
1
1
H NMR (250 MHz, DMSO–d ): δ (ppm): 3.76 (s, 3H, OCH ),
H NMR (400 MHz, DMSO–d ): δ (ppm): 6.91 (1H, s, thia-
6 H
6
H
3
6
.81 (s, 1H, thiazole H), 6.91 (d, 2H, ArH, J = 7.5 Hz), 6.95 (s, 2H,
zole H), 6.95 (2H, s, NH ), 7.26 (d, 2H, J = 8.4 Hz, ArH), 7.6 (d,
2
13
13
NH ), 7.71 (d, 2H, ArH, J = 7.5 Hz), C NMR (63 MHz, DMSO–d ):
2H, J = 8.4 Hz, ArH), C NMR (100 MHz, DMSO–d ): 102.2, 127.1,
2
6
6
5
2
5.5, 99.7, 114.2, 127.2, 129.3, 150.1, 158.9, 168.5 ppm, MS (m/z):
128.4, 131.4, 133.7, 148.5, 168.3 ppm, MS(m/z): 210.
06.
4
-(4-Nitrophenyl) thiazol-2-amine (3g)
4
-(4-aminophenyl)thiazol-2-amine (3e)
White solid, Yield: 94%, mp: 284–286 °C, [lit. mp: 283–285 °C]
56], IR (KBr): 3398, 3302, 1641 cm 1
−
.
[
1
Yellow solid, Yield: 80%, mp: 173–174 °C [lit. ref: 174–175 °C]
H NMR (400 MHz, DMSO–d ): δ (ppm): 7.11 (2H, s, NH ),
6 H 2
[
57].
7.26 (1H, s, thiazole H), 7.9 (d, 2H, J = 8.8 Hz, ArH) 8.08 (d, 2H,
5

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
1
3
J = 8.8 Hz, ArH). C NMR (100 MHz, DMSO–d ): 106.5, 123.9,
6
1
26.2, 140.7, 145.9, 147.6, 168.5 ppm, MS (m/z): 221.
4
-(4-Bromophenyl) thiazol-2-amine (3h)
Yellow solid, Yield: 90%, mp: 228–230 °C, [lit. mp: 227–230 °C]
−
1
[
56], IR (KBr): 3388, 3283, 1634 cm
.
1
H NMR (250 MHz, DMSO–d ): δ (ppm): 7.09 (s, 1H, thia-
6
H
zole H), 7.12 (s, 2H, NH ), 7.54 (d, 2H, J = 8 Hz), 7.73 (d, 2H,
2
13
J = 8 Hz), C NMR (62.5 MHz, DMSO–d ): δc: 102.8, 120.5, 128.0,
6
1
31.8, 134.5, 149.0, 168.8 ppm, MS (m/z): 255.
4
-(3-Nitrophenyl) thiazol-2-amine (3i)
Fig. 5. EDS spectrum of sodium alginate.
Yellow solid, Yield: 80%, mp: 285–286 °C, [lit. mp: 282–283 °C]
−
1
[
58], IR (KBr): 3431, 3296, 1634 cm
.
1
H NMR (500 MHz, DMSO–d ): δ (ppm): 7.21 (s, 2H, NH ),
6
H
2
7
.32(s, 1H, thiazole H), 7.64 (t, 1H, J = 8.15 Hz), 8.09 (d, 1H,
13
J = 8.15 Hz), 8.22 (d, 1H, J = 8.15 Hz), 8.60 (s, 1H, ArH), C NMR
125 MHz, DMSO–d ): δc 104.2, 119.8, 121.6, 130.0, 131.4, 136.3,
(
6
147.3, 148.2, 168.5 ppm, MS (m/z): 221.
4
-(Pyridin-3-yl) thiazol-2-amine (3j)
Brown solid, Yield: 74%, mp: 198–200 °C, [lit. mp: 200 °C] [59],
−
1
1
IR (KBr): 3320, 3149, 1676 cm
. H NMR (250 MHz, DMSO–d ):
6
δH (ppm) 6.98 (s, 1H, thiazole H), 7.21 (s, 2H, NH ), 7.55 (t, 1H,
2
J = 6.25 Hz), 8.26 (d, 1H, J = 7.25 Hz), 8.78 (d, 1H, J = 5 Hz), 9.11
(
s, 1H, ArH), 13C NMR (62.5 MHz, DMSO–d ): δc: 111.4, 122.1, 130.5,
6
132.2, 138.3, 147.8, 149.4, 168.5 ppm.
Fig. 6. Recycling of catalyst for synthesis of 4-phenylthiazol-2-amine.
3. Results and discussion
4
2
-(4-nitrophenyl)thiazol-2-amine 3g and 4-(4-bromophenyl)thiazol
-amine 3h.
Initial studies were carried out using phenyl acetylene, thiourea
in the absence of sodium alginate and it found trace amount of
product (Table 1, entry 1). Afterwards, the reaction was checked
in the presence of alginate/TBBDA (Table 1, entries 2, 3) and, then,
the amount of TBBDA was investigated. The data of Table 1 show
that the best amount is 0.25 mmol (Table 1, entry 3). Because of
hydrophilic structure of alginate, we tried some organic solvents
with water (Table 1, entries 1–5); but, according to table 1, using
Since alginate is known as linear polymer, it can be used as a
support for the interaction of reactants. The interaction between
alginate and phenyl acetylene was investigated and it was shown
revealed that, in the absence of alginate, the reaction would take
longer than when alginate reacted in the reaction media. This in-
dicates that phenyl acetylene or TBBDA is activated by alginate.
The role of alginate was illustrated by IR spectrum of mixture
of the model reaction for 60 min (the reaction was completed
in 120 min) (Fig. 2). It showed that the peak of C = S bond in
H O as solvent resulted in increased yields. Subsequently, the ef-
2
fect of temperature has been checked on the reaction (Table 1, en-
tries 6, 7). The best result was observed at 70 °C (Table 1, entry 3).
Sodium alginate plays a basic role in this reaction and it is consid-
ered as an advantage to accelerate this reaction. Based on results of
entries 8 and 9, optimum amount of sodium alginate was chosen
−1 −1
1036 cm has been moved to 1094 cm indicating that thiourea
is activated by alginate. The recyclability of alginate as a cata-
lyst was investigated by reaction of phenyl acethylene (1 mmol),
TBBDA (0.25 mmol), and thiourea (2 mmol) in H O as a model. Af-
2
0
.05 g or 10 mol% (Table 1, entry 3). Due to the structural similar-
ter 5 times, the structure of catalyst didn’t make much difference
ity of starch and chitosan with alginate, the progress of the reac-
tion in the presence of starch and chitosan was examined; but, the
corresponding product was obtained with low efficiency (Table 1,
entries 10, 11). Finally, we examined the model reaction using NBS
and HBr along with sodium alginate. As can be seen in Table 1, the
TBBDA/alginate exhibited superior behavior in the synthesis of the
product as compared to NBS or HBr (entries 12–13 vs 3).
(
Fig. 3).
Chemical characterization of sodium alginate has been provided
with SEM and EDX analysis. SEM was applied to obtain information
on the surface morphology. In the SEM images, sodium alginate
shows microspherical shape (Fig. 4).
The EDX peaks in Fig. 5 shows the peak of C, O and Na in the
sodium alginate structure. The amount of percentage of weight and
atomic is given in the Table 3.
In this sence, a wide range of substituted phenyl acetylene with
both electron-withdrawing and electron-donating groups was used
to synthesize 2-amino-4-arylthiazole derivatives by green condi-
tions (Table 2). It was also observed that the substituted phenyl
acetylene containing electron-donating groups (Table 2- entries 2–
Table 3
Atomic composition of sodium alginate
determined by EDX.
5
& 10), leads to decrease the yield of the corresponding products.
The substituted phenyl acetylene containing electron-withdrawing
groups (Table 2, entries 6–9) has better results. The excellent yields
of 2-amino-4-arylthiazoles were obtained with para-substituted
phenyl acetylene containing electron-withdrawing groups within
the lowest reaction time, i.e. 4-(4-chlorophenyl)thiazol 2-amine 3f,
Element
Weight (%)
Atomic (%)
C
44.95
53.78
1.27
52.27
46.96
0.77
O
Na
6

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
Table 4
Comparison of the present methodology with the reported catalysts for the synthesis of 3a. a
.
Entry
Catalyst
Temperature( °C)
Time (h)
Yield (%)
1
2
NBS/β-CD
70
70
4
2
72
87,86,86,83this work
TBBDA/Alginate
a
Reaction condition: phenylacetylene (1 mmol), thiourea (2 mmol) at 70 °C in H2O (10 mL).
Scheme 2. Possible mechanism of synthesis of 2-amino-4-arylthiazoles over TBBDA/alginate.
After completion of the reaction, the catalyst was easily sepa-
The plausible mechanism for this reaction is shown in
Scheme 2. The reaction starts when hydrogen bonding is formed
between the–OH groups which exist on the alginate and the oxy-
gen of sulfonyl group in TBBDA. Evidently the TBBDA would easily
rated from the reaction medium by filtration. Recyclability of cat-
alyst was investigated (Fig. 6). The catalyst was washed with ace-
tone, ethanol and dried in air. The recovered catalyst can be reused
for five rounds without any losing of catalytic properties (87, 87,
+
release Br . During the second step, phenyl acetylene was acti-
8
6, 86, 83).
vated by sodium alginate through hydrogen bonding. Afterwards
the reaction between TBBDA (0.25 mmol) and phenyl acetylene
(1 mmol) produced phenacyl bromide B. In addition under ba-
sic conditions by sodium alginate, thiourea was converted to enol
C. Significantly, the most important issue in the third step would
be the hydrogen bonding between the–OH groups and carbonyl
groups in α–bromo ketones B. Accordingly, intermediate D would
be afforded by the subsequent reaction of the B with thiourea
C, resulting in an intramolecular nucleophilic addition/dehydration
reaction to generate E in the presence of alginate. Finally, inter-
mediate E undergoes neutralization reaction to furnish the de-
As compared to the previous work [49] we did this proto-
col with better yield in shorter time, the use of alginate as
an environmentally friendly material with its unique structure
has highlighted our approach (Table 4, entry 2). This compound
has a higher TOF than β-cyclodextrin and also has a high ther-
mal stability. Furthermore TBBDA has more distinctive features
than NBS such as high resistance, releasing more bromine than
other resource and can happen easily. Morevever TBBDA is in-
soluble in H O as it can be an advantage to purify the product
2
[
53–55].
7

S. Gorji, R. Ghorbani-Vaghei and S. Alavinia
Journal of Molecular Structure 1231 (2021) 129900
sired aminothiazole product. In this mechanism, alginate with hy-
droxyl and carboxylate groups played catalytic role via activating
the thiourea, phenyl acetylene, intermediates and TBBDA with hy-
drogen bonding and the basic catalytic activity.
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Declaration of Competing Interest
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The authors declare that they have no known competing finan-
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