Urea nitrate–catalyzed C-N and C-S bond formation: A mechanochemical approach for 5-chloro-2-arylbenzo[d]thiazole derivatives

Article abstract of DOI:10.1002/jhet.4224

A series of substituted 5-chloro-2-arylbenzo[d]thiazoles were synthesized using 4-chloro-2-aminothiophenol and aromatic aldehydes in the presence of urea nitrate as a catalyst using the mechanochemical grindstone technique. This protocol was effectively carried out under metal-free conditions at room temperature, and the desired products were obtained in high to excellent yields in short reaction time (30–60 s). The structure of all the synthesized derivatives was confirmed by spectral characterization. The designed protocol has several benefits like eco-friendly, solvent-free, high yields, easy workup, and recyclability of catalyst. The catalyst was reusable at least four times without significant loss of activity. The good functional group tolerance with a series of derivatives has been demonstrated.

Full text of DOI:10.1002/jhet.4224

Received: 29 July 2020
DOI: 10.1002/jhet.4224
Revised: 27 October 2020
Accepted: 4 January 2021
A R T I C L E
Urea nitrate–catalyzed C-N and C-S bond formation: A
mechanochemical approach for 5-chloro-2-arylbenzo[d]
thiazole derivatives
Ayushi Sethiya
| Nusrat Sahiba
| Jay Soni
| Shikha Agarwal
Synthetic Organic Chemistry Laboratory,
Department of Chemistry, Mohanlal
Sukhadia University, Udaipur, Rajasthan,
India
Abstract
A series of substituted 5-chloro-2-arylbenzo[d]thiazoles were synthesized using
4-chloro-2-aminothiophenol and aromatic aldehydes in the presence of urea
nitrate as a catalyst using the mechanochemical grindstone technique. This
protocol was effectively carried out under metal-free conditions at room tem-
perature, and the desired products were obtained in high to excellent yields in
short reaction time (30–60 s). The structure of all the synthesized derivatives
was confirmed by spectral characterization. The designed protocol has several
benefits like eco-friendly, solvent-free, high yields, easy workup, and recycla-
bility of catalyst. The catalyst was reusable at least four times without signifi-
cant loss of activity. The good functional group tolerance with a series of
derivatives has been demonstrated.
Correspondence
Shikha Agarwal, Synthetic Organic
Chemistry Laboratory, Department of
Chemistry, Mohanlal Sukhadia
University, Durga Nursery Road, Udaipur,
Rajasthan 313001, India.
Email: shikhaagarwal@mlsu.ac.in
Funding information
Council of Scientific and Industrial
Research-India, Grant/Award Number:
09/172(0088)2018-EMR-I; University
Grants Commission, Grant/Award
Number: 201819-MANF-2018-19-RAJ-
91971
1 | INTRODUCTION
biologically active scaffolds based on 2-aryl benzothiazole
are illustrated in Figure 1.
Heterocyclic compounds are pervasive to various sectors
of life. They are the most felicitous structural units in
pharmaceutical chemistry as the presence of heteroatoms
augments their properties [1,2]. Among the heterocyclic
compounds, N- and S-bearing scaffolds are of much inter-
est for the researchers [3,4]. One of the prominent hetero-
cyclic moieties, benzothiazole (BT) possesses a thiazole
ring, fused with a benzene ring, and serves as a funda-
mental building block in several organic syntheses and
acts as a chief model for the development of numerous
therapeutic and potent agents [5–7]. It possesses a pleth-
ora of biological and industrial applications, namely anti-
microbial [8], anticonvulsant [9], anti-HIV [10],
antidiabetic [11], antiparkinson [12], antiproliferative
[13], falciparum inhibitors [14], anti-leishmanial [15],
Mycobacterium tuberculosis shikimate kinase inhibitor
[16], polymer chemistry [17], clothing textiles [18], pesti-
cides [19], corrosion inhibitors [20], and so on. Some
Due to their pleiotropic nature and immense impor-
tance in biological and other related fields, they have
drawn the attention of researchers and chemists all
across the world. Several synthetic pathways have been
designed from time to time for the synthesis of
2-arylbenzothiazole derivatives to enhance their yield
and to make the protocol eco-friendly. Still, there is a
huge upsurge to design a facile and green procedure for
the fabrication of 2-arylbenzothiazole derivatives. Here
in, we have employed a green and efficient protocol by
grinding of 5-chloro-2-aminothiophenol with different
aromatic aldehydes under solvent-free conditions in the
presence of urea nitrate as a catalyst.
Urea nitrate is a user-friendly catalyst and easy to pre-
pare. Previously, it has been used to catalyze a range of
chemical reactions including regioselective nitration [21],
imino Diels–Alder reaction [22], cleavage of oximes
under microwave irradiation [23], aromatization of
J Heterocyclic Chem. 2021;58:873–881.
wileyonlinelibrary.com/journal/jhet
© 2021 Wiley Periodicals LLC.
873

874
SETHIYA ET AL.
FIGURE 1 Biologically active compounds having 2-arylbenzothiazole scaffolds [Colour figure can be viewed at wileyonlinelibrary.com]
1,4-dihydropyridines [24], and so on. It has also been
used to synthesize diversely substituted 2-aryl ben-
zothiazole derivatives by our research group [25], and
inspiring from the results and outcomes of our exhaustive
literature study [26], we have designed an efficient
approach for the synthesis of some new 5-chloro-
2-arylbenzothiazole derivatives which has not been
reported so far. Several researchers and organic chemists
have introduced different pathways for the synthesis
of 5-chloro-2-arylbenzo[d]thiazole derivatives under
diverse reaction conditions using different precursors
illustrated in Scheme 1. Park et al. synthesized
hydroperoxide (TBHP) as an oxidant [31]. Similarly, Shah
and group synthesized them in the presence of catalytic
amount of Na2S2O5 using DMF as a solvent and refluxing
for 2 h [32]. All of these synthetic protocols have their
own merits but include harsh reaction conditions, long
reaction time (2–15 h), tedious workup, poor yield, exper-
imental setup, hazardous solvents, high catalyst loading,
and costly substrates for the synthesis of catalyst, while
our synthetic protocol comprises of several benefits,
namely cost-effectiveness, eco-friendly, rapid process,
solvent-free, avoid tedious work up, and no need of tough
experimental setup and gave high yield of products
Scheme 1e.
substituted
2-arylbenzothiazole
analogues
using
substituted 2-iodoanilines, aldehydes, and NaSHÁnH2O
catalyzed by 2 mol% of CuCl in the presence of MgSO4
and DMSO as a solvent Scheme 1a [27]. Furthermore,
the desired product was synthesized by Guntreddi and
coworkers [28] using o-chloro nitroarenes and aryl acetic
acid by the sulfur-mediated decarboxylative redox cycli-
zation Scheme 1b. Another alternative strategy for
2-arylbenzothiazole scaffolds was designed by Srivastav
et al. using diversely substituted 2-aminothiophenol with
β-oxodithioesters Scheme 1c [29]. Yu and coworkers have
synthesized 5-chloro-2-arylbenzothiazole derivatives
A comparative study of present protocol with the pre-
viously reported literature for the synthesis of 5-chloro-
2-aryl benzothiazole derivatives using 4-chloro-
2-aminothiophenol with aromatic aldehydes has been
illustrated in (Table 1).
2 | RESULTS AND DISCUSSION
2.1 | Chemistry
from
4-chloro-2-aminothiophenol
with
nitriles
In progression to our research efforts toward the develop-
ment of synthetic methodologies for the biologically active
2-arylbenzothiazole and 1,2-disubstituted benzimidazole
derivatives [25,34] herein, we have reported a simple and
facile synthesis for 5-chloro-2-arylbenzothiazole deriva-
tives from 4-chloro-2-aminothiophenol with substituted
Scheme 1d [30]. In addition to all these methods,
Senapak et al. devised similar derivatives from
2-aminothiophenol with aromatic aldehydes using Brön-
sted acid-surfactant-combined ionic liquid (BASILs)
[bsdodecim][OTf] as a catalyst in water and tert-butyl

SETHIYA ET AL.
875
SCHEME 1 Synthesis of substituted 5-chloro-2-phenylbenzo[d]thiazole (present and previous approaches) [Colour figure can be viewed
at wileyonlinelibrary.com]
TABLE 1 A comparative study of the present work with different catalysts for the synthesis of 5-chloro-2-aryl benzothiazole derivatives
using 4-chloro-2-aminothiophenol and aromatic aldehydes
Entry
Catalyst
Reaction conditions
Yields (%)
Reference
1
[bsdodecim][OTf] (1 mL)
Tert-butyl hydroperoxide (TBHP),
73–81%
Senapak et al. [31]
stirring at room temperature for 1.5 h
2
3
8
Na2S2O5
DMF, reflux, 2 h
41–93%
76–88%
87–94%
Shah et al. [32]
Fan et al. [33]
Present work
RuCl3 (0.05 equivalent)
Urea nitrate (15 mol%)
[bmim]PF6, air, 80ꢀC, 0.5 h
Solvent-free, grinding, rt
aromatic aldehydes under green reaction conditions using
urea nitrate as a catalyst by simple grinding method
(Scheme 1e). Urea nitrate is a low-cost, easy to prepare,
and neutralized by water, but it should be tackled with
care as being unstable in the presence of moisture and lib-
erates nitric acid [35–36]. It reduces the reaction time by
providing solid H+ ion. The reaction protocol was initiated
using 5 mol% of urea nitrate catalyst via mechano-
chemical grinding in a mortar and pestle in solvent-free
product was obtained in high yields in just few mins. Fur-
thermore, the catalyst loading was studied by successively
increasing the catalyst amount to 15 mol%. The results
obtained were encouraging, and excellent yields were
obtained in short reaction time (Table 2). Further increase
in the concentration of catalyst resulted in no change in
the yield of reaction.
As per the previously reported literature [25,37], urea
nitrate gave good results under solvent-free conditions.
Keeping this in mind and also from environmental point
of view, we did not examine the reaction under different
solvents. With the optimized conditions in hand, a
conditions
with
4-chloro-2-aminothiophenol
and
benzaldehdye. The progression of reaction was envisioned
by the change in color and monitored by TLC. The desired

876
SETHIYA ET AL.
TABLE 2 Effect of catalyst loading on the model reaction
S. No.
Catalyst loading
No catalyst
5 mol%
Time
10 min
5 min
2 min
1 min
30 s
Yield (%)
1
2
3
4
5
6
50
80
88
89
92
92
10 mol%
12 mol%
15 mol%
20 mol%
30 s
TABLE 3 Synthesis of 2-aryl benzothiazole derivatives in the presence of urea nitrate as the catalyst
M.P. (ꢀC)
Entry
Aldehyde
Symbol for product
Yield (%)
Observed
132–134ꢀC
124–126ꢀC
90–93ꢀC
120–121ꢀC
118–119ꢀC
147–148ꢀC
111–112ꢀC
155–156ꢀC
168–170ꢀC
140ꢀC
Literature
1
C6H5
3a
3b
3c
3d
3e
3f
92
92
95
87
88
90
93
94
89
91
89
87
135ꢀC [32]
128ꢀC [32]
–
121ꢀC [32]
120ꢀC [32]
148ꢀC [32]
113–114ꢀC [38]
158ꢀC [32]
–
2
4-OCH2CH3 C6H4
4-CH2CH3 C6H4 (novel)
Furfural
3
4
5
Thiophene
6
4-OMe C6H4
4-F C6H4
7
3g
3h
3i
8
4-Cl C6H4
9
4-CN C6H4
3-Cl C6H4
10
11
12
3j
142–144ꢀC [39]
2,5-(OMe)2C6H3 (novel)
2-Br
3k
3l
102–103ꢀC
115ꢀC
–
112–114ꢀC [29]
variety of aldehydes having electron withdrawing and
donating substituents and heteroaromatic aldehydes were
examined, and all gave high yields irrespective of the
nature of substituents (Table 3). These results proved that
urea nitrate is efficient toward liquid as well as solid alde-
hydes. The compounds (3a–l) were synthesized and char-
acterized by spectral characterization techniques.
activated aldehyde reacted with the amino group of
thiophenol and formed Schiff base under aerobic condi-
tions which resulted in the formation of desired 2-aryl
benzothiazole derivatives (Scheme 2).
2.2 | Recovery and reuse of catalyst
The present work has several benefits like cost-effi-
cient, solvent-free, avoid tedious work up, no need of
experimental set up, reusability and recyclability of cata-
lyst. The probable mechanism for the reaction suggested
that Schiff base was formed as an intermediate that on
intramolecular cyclization gave the desired product. The
formation of Schiff base was achieved by the activation of
carbonyl group of aldehyde due to urea nitrate. This
The catalyst urea nitrate is soluble in water and could be
easily recovered from the reaction mixture. After comple-
tion of the reaction, the ice-cold water was poured to the
crude reaction mixture and stirred for some time. A solid
mass was seen and filtered. The water was evaporated
under reduced pressure to recover urea from the filtrate
that can be reused further to make urea nitrate. This

SETHIYA ET AL.
877
SCHEME 2 Proposed mechanism
for the formation of substituted
2-arylbenzothiazole using urea nitrate as
a catalyst [Colour figure can be viewed
at wileyonlinelibrary.com]
TABLE 4 Recyclability of urea
nitrate catalyst for the synthesis of
substituted 2-arylbenzothiazole
Catalyst cycle
Fresh
I
II
III
IV
V
VI
75%
Isolated yield
95%
93%
90%
87%
82%
80%
100
90
80
70
60
50
40
30
20
10
0
purification. 4-Chloro-2-aminothiophenol was purchased
from Sigma-Aldrich. An agate mortar and pestle was used
for the synthesis and cleaned with ethanol and acetone.
Melting points were recorded in open capillary tubes and
were uncorrected. The FT-IR spectrum was analyzed using
KBr pellets on a Bruker FT-IR spectrometer. The 1H NMR
(500 MHz) and 13C NMR (125 MHz) spectra were exam-
ined on a Bruker Avance II 500 spectrometer. Tetra-
methylsilane (TMS) is used as an internal standard and
DMSO-d6 and CDCl3 as a solvent. The purity of synthe-
sized compounds was confirmed by thin layer chromatog-
raphy (TLC) using silica gel G as an adsorbent and eluting
with hexane: ethyl acetate. The catalyst urea nitrate was
synthesized from the previously reported literature [37].
Fresh
I Run II Run III Run IV Run V Run VI Run
Efficiency (%)
FIGURE 2 Graphical representation of urea nitrate reusability
[Colour figure can be viewed at wileyonlinelibrary.com]
3.2 | General procedure for synthesis of
2-arylbenzothiazoles (3a–l)
recovered urea was further converted to urea nitrate for
its reuse as a catalyst. The catalytic efficiency has been
appended below in Table 4 and Figure 2.
4-Chloro-2-aminothiophenol (1 mmol), aromatic alde-
hyde, and urea nitrate (15 mol%) were grounded together
in a mortar and pestle under solvent-free conditions at
room temperature. In all the cases, initially reactant
became a pasty mass on grinding and then converted to
fine powder. A drastic change in color and physical state
appeared in just few seconds (30–60 s; Figure 3). The
completion of reaction was monitored by TLC. The cata-
lyst was separated from the reaction mixture by pouring
3 | EXPERIMENTAL DESIGN
3.1 | General
All the chemicals were purchased from Sigma-Aldrich,
Alfa-Aesar, and Hi-Media and used without further

878
SETHIYA ET AL.
FIGURE 3 Reaction between 4-chloro-2-aminothiophenol and 2-thiophene carbaldehdye in the presence of catalytic amount of urea
nitrate. A, reactants with catalyst before reaction; B, during grinding, the reaction mixture became pasty mass; C, after the reaction, the
pasty mass turned into powder [Colour figure can be viewed at wileyonlinelibrary.com]
ice-cold water to it and stirred for 30 min. The solid resi-
due left after filtration was recrystallized with ethanol.
2.61–2.69 (q, J = 7.3 Hz, 2H, CH2CH3), 7.25–7.34 (m, 3H,
Ar-H), 7.77(d, J = 8.35 Hz, 1H, Ar-H), 7.97–8.03(m, 3H,
Ar-H), 13C NMR (125 MHz, DMSO d6) δ 15.5, 28.8, 125.4,
127.2, 127.6, 128.2, 128.6, 130.7, 132.2, 133.2, 137.9, 143.5,
155.0, 170.1; MS (EI): m/z 273.04 [M+].
3.3 | Spectral characterization
3.3.1 | 5-Chloro-2-phenylbenzo[d]
thiazole (3a)
3.3.4 | 5-Chloro-2-(furan-2-yl)benzo[d]
thiazole (3d)
White solid; yield 92%; m.p. 132–134ꢀC; IR(KBr): 2925, 1620,
1485, 1421, 1050, 755 cm−1; 1H NMR (500 MHz, DMSOd6) δ
7.19 (d, J = 3 Hz, 2H), 7.33–7.37(m, 2H), 7.52 (s, 1H), 7.64 (s,
1H), 8.20–8.26 (m, 2H); 13C NMR (125 MHz, CDCl3): δ
122.4, 122.6, 122.8, 124.3, 126.1, 129.62, 129.64, 130.22,
130.29, 131.9, 133.8, 154.8, 168.9; MS (EI): m/z 245.01 [M+].
Light yellow solid; yield 87%; m.p. 120–121ꢀC; IR(KBr):
2895, 1742, 1554, 1421, 1232, 1150, 980, 780 cm−1; H
1
NMR: (500 MHz, DMSO d6) δ 7.16 (dd, J = 8.5 Hz, 1 Hz,
1H,), 7.26 (dd, J = 6.5 Hz, J = 2 Hz, 1H), 7.30–7.36 (m,
1H), 7.58 (dd, 1H, J = 7 Hz, 1 Hz), 7.59–7.60 (m, 1H),
7.89 (dd, J = 8 Hz, 1.5 Hz, 1H); 13C NMR (125 MHz,
DMSO d6) δ 117.1, 122.7, 124.8, 125.3, 125.6, 127.0, 128.1,
129.0, 141.4, 149.2, 154.5; MS (EI): m/z 235.69 [M+].
3.3.2 | 5-Chloro-2-(4-ethoxyphenyl)benzo
[d]thiazole (3b)
Yellow solid; yield 92%; m.p. 124–126ꢀC; IR(KBr): 3030,
3.3.5 | 5-Chloro-2-(thiophen-2-yl)
benzothiazole (3e)
1
2925, 2890, 1637, 1485, 1398, 1261, 1050, 790 cm−1; H
NMR (500 MHz, CDCl3) δ 1.41 (t, 3H, OCH2CH3), 4.20
(q, J = 6.8 Hz, 2H, OCH2CH3), 6.50 (d, J = 7.65 Hz, 1H,
Ar-H), 7.06 (dd, J = 50 Hz, 8 Hz, 1H, Ar-H), 7.25–7.36
(m, 1H, Ar-H), 7.45(d, J = 7.9 Hz, 1H, Ar-H), 7.78 (d,
J = 8.3 Hz, 1H, Ar-H), 7.98(d, J = 7.95 Hz, 2H, Ar-H),
13C NMR (125 MHz,CDCl3) δ 14.8, 63.7, 114.7, 114.9,
122.6, 125.1, 125.8, 128.5, 128.7, 129.2, 129.7, 155, 158.3,
161.6, 169.8; MS (EI): m/z 289.03 [M+].
Golden yellow solid; yield 88%; m.p. 118–119ꢀC; IR(KBr):
1
2945, 1625, 1456, 1374, 1219, 1046, 775 cm−1; H NMR
(500 MHz, CDCl3) δ 7.12 (dd, J = 5 Hz, 3.75 Hz), 7.31
(dd, J = 8.5 Hz, 2 Hz, 1H), 7.51 (dd, J = 5 Hz, 1.1 Hz,
1H), 7.64 (dd, J = 3.75 Hz, 1.1 Hz, 1H); 7.72 (d,
J = 8.5 Hz, 1H), 7.98 (d, J = 1.95 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ 124.8, 125.3, 127.0, 128.1, 129, 129.8,
132.4, 132.9, 154.5, 163.1; MS (EI): m/z 251.75 [M+].
3.3.3 | 5-Chloro-2-(4-ethylphenyl)benzo
[d]thiazole (3c)
3.3.6 | 5-Chloro-2-(4-methoxyphenyl)
benzo[d]thiazole (3f)
Light mehandi green; yield 95%; m.p. 90–93ꢀC; IR(KBr):
1
2957, 1648, 1449, 1321, 1250, 980, 790 cm−1; H NMR
White solid; 90% yield; m.p. 147–148ꢀC; IR(KBr): 2921,
1
(500 MHz, CDCl3) δ 1.26 (t, J = 7.5 Hz, 3H, CH2CH3),
2850, 1662, 1558, 1445, 1211, 1090, 759 cm−1; H NMR

SETHIYA ET AL.
879
(500 MHz, CDCl3)] δ 3.8 (s, 3H, CH3-H), 7.26 (dd,
J = 8.79 Hz, 1.33 Hz, 2H, Ar-H), 7.46 (dd, J = 8.5 Hz,
1.8 Hz, 1H, Ar-H), 7.54 (dd, J = 7.5 Hz, 1 Hz, 1H, Ar-H),
7.8 (dd, J = 8.7 Hz, 1.5 Hz, 2H, Ar-H), 7.9 (dd, J = 1.83,
0.5 Hz, 1H, Ar-H); 13C NMR (125 MHz,CDCl3) δ 55.8,
114.2, 114.5, 121.2, 122.9, 124.5, 127.3, 128.8, 129.2, 130.5,
134, 150.7, 160.4, 167.1; MS (EI): m/z 275.02 [M+].
1H NMR (500 MHz, DMSOd6)] δ 7.40–7.44 (m, 2H, Ar-
H), 7.50 (dd, J = 8.55 Hz, 2.1 Hz, 2H, Ar-H), 8.12 (d,
J = 1.95 Hz, 1H, Ar-H), 8.13–8.16 (m, 2H, Ar-H), 8.18 (d,
J = 0.25 Hz, 1H, Ar-H), 13C NMR (125 MHz, DMSO d6) δ
116.3, 116.5, 122.1, 123.7, 125.5, 129.0, 129.6, 131.3, 133.2,
154.2, 168.3; MS (EI): m/z 278.97 [M+].
3.3.11 | 5-Chloro-
2-(2,5-dimethoxyphenyl)benzo[d]
thiazole (3k)
3.3.7 | 5-Chloro-2-(4-fluorophenyl)benzo
[d]thiazole (3g)
White solid; 93% yield; m.p. 111–112ꢀC; IR(KBr): 2975,
White solid; 89% yield; m.p. 102–103ꢀC; IR (KBr): 3050,
1
1664, 1451, 1402, 1210, 1096, 780 cm−1
;
1H NMR
2950, 1455, 1232, 1205, 1148, 1022, 850, 758 cm−1; H
(500 MHz, CDCl3)] δ 7.24–7.31 (m, 3H, Ar-H), 7.55 (d,
J = 1 Hz, 1H, Ar-H), 7.65 (d, J = 7.5 Hz, 1H, Ar-H), 7.73
(d, J = 7.5 Hz, 1H, Ar-H), 8.02 (d, J = 1 Hz, 1H, Ar-H),
13C NMR (125 MHz, CDCl3) δ 115.08, 115.1, 119.4, 122.4,
122.6, 122.7, 127.8, 129.1, 130.9, 136.3, 153.6, 160.1, 168.9;
MS (EI): m/z 263.71 [M+].
NMR (500 MHz, CDCl3)] δ 3.90 (s, 3H, OCH3), 4.01 (s,
3H, OCH3), 6.99 (d, J = 9 Hz, 1H, Ar-H), 7.03 (dd,
J = 9 Hz, 3 Hz, 1H, Ar-H), 7.32 (dd, J = 8.5 Hz, 2 Hz, 1H,
Ar-H), 7.80 (d, J = 8.5 Hz, 1H, Ar-H), 8.05 (m, 2H, Ar-H)
13C NMR (125 MHz, CDCl3) δ 56.0, 56.4, 112.6, 113.4,
119.2, 121.9, 122.4, 122.5, 125.1, 131.8, 134.5. 151.9, 152.9,
153.9, 164.7; MS (EI): m/z 305.78 [M+].
3.3.8 | 5-Chloro-2-(4-chlorophenyl)benzo
[d]thiazole (3h)
3.3.12 | 5-Chloro-2-(2-bromophenyl)
benzo[d]thiazole (3l)
White solid; 93% yield; m.p. 155–156ꢀC; IR (KBr): 2949,
1
1596, 1450, 1332, 1218, 1154, 1042 743 cm−1; H NMR
Light yellow; solid; 87% yield; m.p. 140ꢀC; IR (KBr):
(500 MHz, CDCl3)] δ 7.33 (dd, J = 8.5 Hz, 2 Hz, 1H, Ar-
H), 7.43–7.45 (m, 2H, Ar-H), 7.76 (d, J = 8.5 Hz, 1H, Ar-
H), 7.95–7.98 (m, 2H, Ar-H), 8.01 (d, J = 1.9 Hz, 1H, Ar-
H), 13C NMR (125 MHz, CDCl3) δ 122.3, 123.1, 125.8,
128.7, 129.3, 131.7, 132.5, 133.2, 137.4, 154.9, 168.4; MS
(EI): m/z 278.97 [M+].
2872, 1530, 1475, 1272, 1168, 1032, 950, 745, 650 cm−1
;
1H NMR (500 MHz, DMSO d6)] δ 7.51–7.58 (m, 4H, Ar-
H), 7.78 (dd, J = 7.7 Hz, 1.4 Hz, 1H, Ar-H), 8.16 (dd,
J = 7.6 Hz,1.95 Hz, 1H, Ar-H), 8.30–8.82 (s, 1H, Ar-H),
13C NMR (125 MHz, DMSO d6) δ 120.7, 121.2, 122.9,
124.9, 127.6, 127.7, 130.6, 130.7, 131.7, 132.0, 134.1, 154.5,
167.8; MS (EI): m/z 324.62 [M+].
3.3.9 | 5-Chloro-2-(4-cyanophenyl)benzo
[d]thiazole (3i)
4 | CONCLUSION
White solid; 89% yield; m.p. 168–170ꢀC; IR (KBr): 2972,
The search of privileged structures in drug discovery is a
hastily emerging area in synthetic chemistry. For this,
designing of an eco-benign protocol is inevitable. In lieu
of this, a facile, green, cost-effective pathway for biologi-
cally active scaffold has been designed using 4-chloro-
2-aminothiophenol with aromatic aldehydes catalyzed by
urea nitrate. 5-Chloro-2-aryl benzo[d]thiazole derivatives
were synthesized through eco-friendly pathway in signifi-
cant yields in a very short period of reaction time. The
present work is highly beneficial as it involved a low-cost
robust catalyst, solvent-free, easy work up, no waste gen-
eration, metal-free, and no need of column chromatogra-
phy. Moreover, the developed synthetic pathway will be
helpful to fabricate diversely substituted benzothiazole
derivatives as it has good compatibility with all types of
1
2250, 1630, 1455, 1232, 1178, 1042, 980, 743 cm−1; H
NMR (500 MHz, CDCl3)] δ 7.41 (dd, J = 8.55 Hz, 2.0 Hz,
1H, Ar-H), 7.78–7.80 (m, 2H, Ar-H), 7.84 (d, J = 8.5 Hz,
1H, Ar-H), 8.08 (d, J = 1.95 Hz, 1H, Ar-H), 8.17–8.19 (m,
2H, Ar-H), 13C NMR (125 MHz, CDCl3) δ 114.5, 118.1,
122.5, 123.5, 126.6, 128.0, 132.8, 132.9, 133.5, 137.0, 154.8,
167.1; MS (EI): m/z 270.73 [M+].
3.3.10 | 5-Chloro-2-(3-chlorophenyl)
benzo[d]thiazole (3j)
Light yellow; solid; 91% yield; m.p. 140ꢀC; IR (KBr):
2972, 2250, 1630, 1455, 1232, 1178, 1042, 980, 743 cm−1
;

880
SETHIYA ET AL.
[11] M. C. V. Zandt, M. L. Jones, D. E. Gunn, L. S. Geraci, J. H.
Jones, D. R. Sawicki, J. Sredy, J. L. Jacot, A. T. DiCioccio, T.
Petrova, A. Mitschler, A. D. Podjarny, J. Med. Chem. 2005, 48,
3141.
[12] J. A. M. Garcia, L. G. Salado, S. S. M. Cristobal, C. Gil, A. P.
Castillo, A. Martínez, D. I. Pérez, ACS Omega 2017, 2(8), 5215.
[13] J. Cui, B. Qi, C. Gan, Z. Liu, H. Huang, Q. Lin, D. Zhao, Y.
Huang, Mar. Drugs. 2015, 13(4), 2488.
aldehydes. In assessment, this one-pot synthesis is found
to be an efficient method to synthesize diversely
substituted 2-aryl benzothiazole derivatives. The simple
experimental setup is supposed to be highly potential for
the synthesis of complex molecules.
ACKNOWLEDGMENTS
The authors are thankful to Department of Chemistry,
MLS University, Udaipur for providing necessary labora-
tory facilities. The authors would also like to acknowl-
edge Sophisticated Analytical Instrumentation Facility,
Chandigarh, India for the spectral analysis. A. Sethiya. is
thankful to UGC-MANF (201819MANF-2018-19-RAJ-
91971) and N. Sahiba. (CSIR [file no. 09/172(0088)
2018-EMR-I]) is thankful to CSIR-India for providing
Junior Research Fellowship to carry out this work.
[14] F. Shah, Y. Wu, J. Gut, Y. Pedduri, J. Legac, P. J. Rosenthal,
M. A. Avery, Med. Chem. Commun. 2011, 2, 1201.
[15] A. A. Dar, M. Shadab, S. Khan, N. Ali, T. A. Khan, J. Org.
Chem. 2016, 81(8), 3149.
[16] R. Mehra, V. S. Rajput, M. Gupta, R. Chib, M. Kumar, P.
Wazir, I. A. Khan, A. Nargotra, J. Chem. Inf. Model. 2016, 56
(5), 930.
[17] Y. T. Huang, W. C. Wang, C. P. Hsu, W. Y. Lu, W. J. Chuang,
M. Y. Chiang, Y. C. Lai, H. Y. Chen, Polym. Chem. 2016, 7,
4367.
[18] G. Luongo, R. Avagyan, R. Hongyu, C. Ostman, Environ. Sci.
Pollut. Res. 2016, 23, 2537.
DATA AVAILABILITY STATEMENT
Data available on request due to privacy/ethical restric-
tions. The data that support the findings of this study are
available on request from the corresponding author. The
data are not publicly available due to privacy or ethical
restrictions.
[19] Y. Zhao, P. Zhang, Y. Zhai, C. Chen, Q. Wang, J. Han, Z.
Zhang, F. Liu, W. Mu, Phytoparasitica. 2016, 44, 115.
[20] M. Bilel, B. Mehdi, S. M. Elhadi, M. Lyamine, B. Ali, M.
Hocine, C. Aissa, B. Sofiane, B. Abdelmalek, Res. Chem. Inter-
med. 2016, 42, 7447.
[21] J. Almog, A. Klein, A. Sokol, Y. Sasson, D. Sonenfeld, T.
Tamiri, Tetrahedron Lett. 2006, 47, 8651.
[22] M. Anniyappan, R. Nagarajan, P. T. Perumal, Synth. Commun.
2002, 32, 99.
[23] P. T. Perumal, M. Anniyappa, D. Muralidharan, J. Chem. Sci.
2004, 116, 261.
[24] M. Anniyappan, D. Muralidharan, P. T. Perumal, Tetrahedron
2002, 58, 5069.
ORCID
Ayushi Sethiya https://orcid.org/0000-0002-9595-221X
Nusrat Sahiba https://orcid.org/0000-0002-3062-7395
Jay Soni https://orcid.org/0000-0002-2646-2428
Shikha Agarwal https://orcid.org/0000-0003-2946-0409
[25] D. Gandhi, S. Agarwal, Heterocycl. Commun. 2018, 24, 307.
[26] A. Sethiya, N. Sahiba, J. Soni, D. Gandhi, S. Agarwal, Curr.
Org. Chem. 2018, 22, 2681.
[27] N. Park, Y. Heo, M. R. Kumar, Y. Kim, K. H. Song, S. Lee, Eur.
J. Org. Chem. 2012, 10, 1984.
[28] T. Guntreddi, R. Vanjari, K. N. Singh, Org. Lett. 2015, 17, 976.
[29] A. Srivastava, G. Shukla, M. S. Singh, Tetrahedron 2017,
73, 879.
[30] X. Yu, Q. Yin, Z. Zhang, T. Huang, Z. Pu, M. Bao, Tetrahedron
Lett. 2019, 60, 1964.
[31] W. Senapak, R. Saeeng, J. Jaratjaroonphong, U. Sirion, Mol.
Catal. 2018, 458, 97.
[32] S. Shah, K. Arshia, H. Javaid, K. M. Zafar, R. Khan, Z. U.
Khalil, S. Haq, M. I. C. Perveen, Bioorg. Chem. 2018, 78, 269.
[33] X. Fan, Y. Wang, Y. He, X. Zhang, J. Wang, Tetrahedron Lett.
2010, 51, 3493.
[34] N. Sahiba, D. K. Agarwal, A. Manhas, A. Sethiya, J. Soni, P. C.
Jha, S. Agarwal, Polycycl. Aromat. Compd. 2020. https://doi.
org/10.1080/10406638.2020.1768565.
[35] L. Medard, Memorial. Des. Poudres. 1951, 33, 113.
[36] J. C. Oxley, J. L. Smith, S. Naik, J. Moran, J. Energ. Mater.
2008, 27, 17.
REFERENCES
[1] C. Lamberth, J. Dinges, Bioactive Heterocyclic Compound Clas-
ses: Pharmaceuticals, Wiley-VCH Verlag GmbH & Co. KGaA,
2013. https://doi.org/10.1002/9783527664450.ch1.
[2] A. F. Pozharskii, A. T. Soldatenkov, A. R. Katritzky, Heterocy-
cles in Life and Society, John Wiley & Sons, Chichester 1997.
[3] S. Pathania, R. K. Narang, R. K. Rawa, Eur. J. Med. Chem.
2019, 180, 486.
[4] Y. J. Wu, Progress in Heterocyclic Chemistry, (Eds: G. Gribble,
J. Joule 24, Elsevier, 2012.
[5] P. C. Sharma, K. K. Bansal, A. Sharma, D. Sharma, T. Deep,
Eur. J. Med. Chem. 2020, 188, 112016.
[6] M. N. Bhoi, M. A. Borad, H. D. Patel, Synth. Commun. 2014,
44, 2427.
[7] S. Agarwal, D. Gandhi, P. Kalal, Lett. Org. Chem. 2017, 14, 729.
[8] M. Singh, S. K. Singh, M. Gangwar, G. Nath, S. K. Singh, Med.
Chem. Res. 2016, 25, 263.
[9] P. Yogeeswari, D. Sriram, S. Mehta, D. Nigam, M. Kumar, S.
Murugesan, J. P. Stables, IL Farmaco. 2005, 60(1), 1.
[10] S. R. Nagarajan, G. A. De Crescenzo, D. P. Getman, H. F. Lu,
J. A. Sikorski, J. L. Walker, J. J. McDonald, K. A. Houseman,
G. P. Kocan, N. Kishore, P. P. Mehta, C. L. Funkes-Shippy, L.
Blystone, Bioorg. Med. Chem. 2003, 11, 4769.
[37] P. Kumar, R. Bhatia, R. Khanna, A. Dalal, D. Kumar, P.
Surain, R. C. Kamboj, J. Sulfur Chem. 2017, 38(6), 585.

SETHIYA ET AL.
881
[38] D. B. Lima, F. Penteado, M. M. Vieira, D. Alves, G. Perin, C.
~
Santi, E. J. Lenardao, Eur. J. Org. Chem. 2017, 26, 3830.
How to cite this article: Sethiya A, Sahiba N,
Soni J, Agarwal S. Urea nitrate–catalyzed C-N and
C-S bond formation: A mechanochemical approach
for 5-chloro-2-arylbenzo[d]thiazole derivatives.
J Heterocyclic Chem. 2021;58:873–881. https://doi.
org/10.1002/jhet.4224
[39] I. Kazi, G. Sekar, Org. Biomol. Chem. 2019, 17, 9743.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.