Chitosan-SO3H: A green approach to 2-aryl/heteroaryl benzothiazoles under solvent-free conditions at room temperature

Article abstract of DOI:10.14233/ajchem.2018.21209

An efficient green protocol have been developed for the synthesis of 2-aryl/heteroaryl benzothiazole derivatives by intramolecular cyclocondensation of 2-mercaptoaniline with various substituted aryl/heteroaryl aldehydes using chitosan-SO3H as an efficien

Full text of DOI:10.14233/ajchem.2018.21209

Asian Journal of Chemistry; Vol. 30, No. 7 (2018), 1512-1516
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21209
Chitosan-SO3H: A Green Approach to 2-Aryl/Heteroaryl
Benzothiazoles under Solvent-Free Conditions at Room Temperature
1
3
SURENDRA BOSE BATHULA1,2,*, MUKKANTI KHAGGA and HARIHARAKRISHNAN VENKATASUBRAMANIAN
1Chemistry Division, Institute of Science and Technology, JNT University, Kukatpally, Hyderabad-500 072, India
2Alekhya Drugs Pvt. Ltd, Plot No: 145-150, IDA-Kondapalli, Ibrahimpatnam, Vijayawada-521 228, India
3RA Chem Pharma Ltd., Plot No. 26 & 27, Technocrats Industrial Estate, Balanagar, Hyderabad-500 037, India
*Corresponding author: E-mail: surendrabose.bathulajntuh@gmail.com
Received: 1 December 2017;
Accepted: 9 February 2018;
Published online: 31 May 2018;
AJC-18922
An efficient green protocol have been developed for the synthesis of 2-aryl/heteroaryl benzothiazole derivatives by intramolecular
cyclocondensation of 2-mercaptoaniline with various substituted aryl/heteroaryl aldehydes using chitosan-SO3H as an efficient biocompatible
and reusable heterogenous solid acid catalyst in presence of air under solvent free conditions at room temperature. 1H NMR and 13C NMR
spectra recorded are in agreement with the reported data.
Keywords: Green synthesis, Chitosan-SO3H, Benzothiazoles, Intramolecular cyclocondensation, Solvent-free condition.
acids, acid chlorides or esters via Hofmann synthesis [4],
oxidative intramolecular cyclization of thiobenzanilides via
Jacobson cyclization [5] and palladium-catalyzed coupling of
2-bromobenzothiazole with arylboronic acids via Suzuki biaryl
coupling [6].
However, many of the reported methods are quite effective
and useful, but suffer by using acidic reagents or hazardous
organic solvents that are not environmentally compatible.
Moreover, harsh reaction conditions, multistep process, longer
reaction times, higher temperatures, use of expensive reagents,
metal oxidants and produce a large amounts of waste with
observed side product formation are the other drawbacks of
these methodologies. Consequently, there is a need to over-
come the above limitations by developing an efficient, simple
and green methodology for the synthesis of 2-substituted
benzothiazoles in terms of selectivity, reusability and biocom-
patibility.
INTRODUCTION
Benzothiazole ring is a fused bicyclic ring often constr-
ucted from acyclic reactants [1]. This core nucleus bearing N
and S atoms at symmetrical position have been studied exten-
sively owing to their interesting pharmacological activities.
Especially, among those 2-arylbenzothiazoles (Fig. 1) are of
great interest as these structural frameworks have proved to be
as an important class of biological active motifs and hence
play a pivotal role in the field of medicinal and industrial chemistry.
They are the basic constituents of several antitumor, anticon-
vulsant, antiviral and anticancer drugs [2].
NH2
S
N
S
N
S
CH3
NH2
N
HO
Anticancer agent
Topoisomerase II inhibitors
Replication & Mitosis
Inhibitors
Recently, the direction of science and technology has been
shifting more towards eco-friendly, natural product resources
and reusable catalysts. Thus natural biopolymers have emerged
as potential candidates for preparing solid acid support cata-
lysts enabling high selectivity of the reactions under solvent-
free conditions [7]. Researchers have demonstrated that solvent-
free organic syntheses are generally faster, selective, higher
yielding with cleaner products, environmentally benign and
involve simple operational procedure as compared to the
classical reactions [8]. To the best of our knowledge, as far as
O
N
CN
CH3
NH2
S
N
S
N
O
N
S
N
N
N
Antibacterial agent
Antimicrobial agent
Antitumor reagent
Fig: 1. Biological activity profile of certain 2-substituted benzothiazole
scaffolds [Ref. 3]
Traditionally, the common synthetic strategies to construct
these bioactive compounds relies on majorly condensation of
2-mercaptoaniline with aldehydes, β-diketones, carboxylic

Vol. 30, No. 7 (2018)
Chitosan-SO3H: A Green Approach to 2-Aryl/Heteroaryl Benzothiazoles under Solvent-Free Conditions 1513
concerned to the literature revealed there are no reports found
using this present methodology. We wish to report herein a
simple procedure for the synthesis of 2-substituted benzo-
thiazoles using chitosan-SO3H as a reusable solid acid catalyst
under solvent-free conditions at room temperature with high
selectivity.
Chitosan is a linear polyamine derivative briefed as [poly-
(β-1/4)-2-amino-2-deoxy-D-glucopyranose] obtained by
partial and controlled deacetylation of chitin [9]. Chitosan can
easily be subjected to a variety of chemical modifications. One
such chemical modification is sulfonation at the reactive amine
function to produce chitosan-SO3H (CS-SO3H) and has been
used as a solid acid catalyst in many organic reactions [10].
Prompted by these reports, we herein report CS-SO3H as an
efficient, reusable heterogeneous solid acid catalyst for the
synthesis of 2-aryl/heteroaryl benzothaizole derivatives under
solvent free conditions at room temperature.
135.0, 131.1, 129.7, 127.5, 126.2, 125.0, 123.1, 121.5, 21.4;
MS (m/z) [M+H]+: 226.
2-(4-Methoxyphenyl)benzothiazole (3c): White solid;
m.p.: 120-122 °C (Lit. [13] 120-122 °C); IR (KBr, νmax, cm-1):
3021, 3048, 2837, 1609, 1590, 1483, 830; 1H NMR (400 MHz,
CDCl3, ppm) δ 8.04 (d, J = 8.4 Hz, 3H), 7.88 (d, J = 8.0 Hz,
1H), 7.47 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.00 (d,
13
J = 8.4 Hz, 2H), 3.88(s, 3H); C NMR (100 MHz, CDCl3,
ppm) δ 167.8, 162.0, 154.3, 134.9, 129.1, 126.5, 126.1, 124.7,
122.8, 121.4, 114.4, 55.4; MS (m/z) [M+H]+: 242.
2-(2-Hydroxyphenyl)benzothiazole (3d): Yellow solid;
m.p.: 127-128 °C (Lit. [14] 126-128 °C); IR (KBr, νmax, cm-1):
3285, 3090, 2900, 1619, 1590, 1490, 1423, 874, 751; 1H NMR
(400 MHz, CDCl3, ppm) δ 6.95-699 (t, 1H, J = 8.0 Hz, Ar-H)
7.12 (d, 1H, J = 8.0 Hz, Ar-H), 7.38-7.44 (m,2H, Ar-H) 7.50-
7.54 (t, 1H, J = 8.4 Hz, Ar-H) 7.71 (d, 1H, J = 8.0 Hz, Ar-H)
7.92 (d, 1H, J = 8.4Hz, Ar-H) 8.01 (d, 1H, J = 8.0 Hz, Ar-H)
12.54 (s, 1H, OH); 13C NMR (100 MHz, CDCl3, ppm) δ 116.8,
117.9, 119.5, 121.5, 122.2, 125.6, 126.7, 128.4, 132.6, 132.8,
151.8, 157.9, 169.4; MS (m/z) [M+H]+: 228.
EXPERIMENTAL
1H NMR and 13C NMR spectra were recorded on Bruker-
AV (400 and 100 MHz, respectively) spectrometer by using
CDCl3 solvent and tetramethylsilane (TMS) as an internal
standard. The FT-IR spectra were obtained with KBr pellets
in the range 4000-400 cm-1 with a Perkin Elmer 550 spectro-
meter. Melting points were uncorrected and determined in open
capillary tubes using sulphuric acid bath and Mass spectra on
an Agilent LC-MS instrument giving only M+ values in Q+1
mode. All starting materials, chitosan were purchased from
TCI and Alfa-aesar.
General procedure for the preparation of 2-aryl/hete-
roaryl benzothiazoles catalyzed by chitosan-SO3H: In a
round bottom equipped flask 2-mercaptoaniline (1) (1 mmol),
substituted aryl/heteroaryl aldehydes 2(a-o) (1 mmol) and CS-
SO3H (2 mol %) is stirred at room temperature for 30 min in
presence of oxygen balloon. The reaction was monitored by
using TLC. Upon completion of the reaction, the reaction mass
was quenched to absolute ethanol. The precipitated CS-SO3H
was filtered and reused for subsequent reactions. The filterate
was concentrated and obtained the curde product. Further the
crude product was recrystallized from ethanol and obtained
pure products 3(a-o).
2-(4-Bromophenyl)benzothiazole (3e): White solid; m.p.:
129-131 °C (Lit. [15] 130-132 °C); IR (KBr, νmax, cm-1): 1503,
1
1392, 1311, 1224, 968, 820, 754, 722, 477; H NMR (400
MHz, CDCl3, ppm) δ = 8.06 (d, J = 8.2 Hz, 1H), 7.95 (d, J =
8.6 Hz, 2H), 7.89 (d, J = 7.8 Hz, 1H), 7.64- 7.60 (m, 2H), 7.50
(t, J = 7.4 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ = 166.7, 154.1, 135.0, 132.5, 132.2, 128.9,
126.5, 125.4, 125.4, 123.3, 121.6; MS (m/z) [M+H]+: 289.
2-(4-Chlorophenyl)benzothiazole (3f): White solid; m.p.:
114-116 °C (Lit. [16] 116-118 °C); IR (KBr, νmax, cm-1): 3055,
2358, 1560, 1455, 1430, 1317, 1275, 1060, 965, 750, 725; 1H
NMR (400 MHz, CDCl3, ppm) δ 7.37-7.39 (m, 2H, Ar-H)
7.51-7.53 (d, 2H, J = 7.6 Hz, Ar-H) 7.58-7.61 (m, 1H, Ar-H)
7.77-7.79 (m, 1H, Ar-H) 8.19-8.22 (d, 2H, J = 7.6 Hz, Ar-H);
13C NMR (100 MHz, CDCl3, ppm) δ 121.8, 123.1, 125.2,
126.8, 129.1, 129.8, 132.7, 135.2, 137.1,154.4, 166.2; MS
(m/z) [M+H]+: 247.
2-(4-Fluorophenyl)benzothiazole (3g): White solid;
m.p.: 97-98 °C (Lit. [15] 98-100 °C); IR (KBr, νmax, cm-1):
1
1710, 1520, 1362, 1226, 1092,967, 837, 756, 728, 499; H
NMR (400 MHz, CDCl3, ppm) δ = 8.09-8.04 (m, 3H), 7.88
(d, J = 7.9 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 7.6
Hz, 1H), 7.20-7.14 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm)
δ = 166.2 (d, J = 101.9 Hz), 163.2, 154.1, 135.0, 130.0 (d, J =
3.1 Hz), 129.5 (d, J = 8.6 Hz), 126.4, 125.2, 123.2, 121.6,
116.1 (d, J = 22.0 Hz); MS (m/z) [M+H]+: 230.
Physical and spectral data
2-Phenylbenzothiazole (3a): White solid, m.p.: 111-112
°C (Lit. [11] 110-111 °C); IR (KBr, νmax, cm-1): 3066, 3017,
2835, 1608, 1587, 1476,1430, 830, 763; 1H NMR (400 MHz,
CDCl3, ppm) δ 7.37 (t, J = 8.0 Hz, 1H), 7.39-7.51 (m, 4H),
2-(4-Trifluoromethylphenyl)benzothiazole (3h): White
13
7.89 (d, J = 8.0 Hz, 1H), 8.06-8.10 (m, 3H); C NMR (100
solid; m.p.: 160-162 °C (Lit. [17] 160-162 °C); IR (KBr, νmax
,
cm-1): 1483, 1434, 1323, 1110, 970,839, 760, 620, 439; H
NMR (400 MHz, CDCl3, ppm) δ 8.21 (d, J = 8.3 Hz, 2H),
8.11 (d, J = 8.1 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.75 (d, J =
8.3 Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H);
13C NMR (100 MHz, CDCl3, ppm) δ 166.0, 154.0, 136.8,
135.2, 132.3 (q, J = 32.6 Hz), 127.8, 126.7, 126.0 (q, J = 3.7
Hz), 123.7 (q, J = 270.8 Hz), 123.6, 121.7; MS (m/z) [M+H]+:
280.
1
MHz, CDCl3, ppm) δ 121.59, 123.24, 125.16, 126.29, 127.56,
128.99, 130.93,133.64, 135.07, 154.16, 168.03; MS (m/z)
[M+H]+: 212.
2-(4-Methylphenyl)benzothiazole (3b): White solid;
m.p.: 82-84 °C (Lit. [12] 83-85 °C); IR (KBr, νmax, cm-1): 3024,
2905, 1610, 1519, 1480, 1435, 1383, 1312, 821, 759; 1H NMR
(400 MHz, CDCl3, ppm) δ 8.06 (d, J = 8.0 Hz, 1H), 7.98 (d, J
= 8.0 Hz, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.6 Hz,
1H), 7.37 (t, J = 7.4 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 2.42 (s,
3H); 13C NMR (100 MHz, CDCl3, ppm) δ 168.2, 154.2, 141.3,
2-(3-Nitrophenyl)benzothiazole (3i): White solid; m.p.:
181-183 °C (Lit. [18] 181-182 °C); IR (KBr, νmax, cm-1): 3039,

1514 Bathula et al.
Asian J. Chem.
2936, 1522, 1460, 1345, 1103, 1041, 851, 750; 1H NMR (400
MHz, CDCl3, ppm) δ 8.94 (s, 1H), 8.43 (d, J = 7.6 Hz, 1H),
8.34 (d, J = 7.6 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.96 (d, J =
8.0 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H),
7.46 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ
164.9, 153.9, 148.7, 135.3, 135.2, 133.0, 130.1, 126.8, 126.0,
125.1, 123.7, 122.3, 121.8; MS (m/z) [M+H]+: 257.
RESULTS AND DISCUSSION
In continuation of our research on synthetic applications
of green catalysts [24] for pharmacologically active heterocyclic
compounds herein we wish to report a simple synthesis of
2-aryl/heteroaryl benzothiazoles by condensation of 2-mercapto-
aniline with various substituted aryl/heteroaryl aldehydes under
solvent-free conditions catalyzed by CS-SO3H at room tempe-
rature as depicted in Scheme-I.
2-(3-Bromo-4-methylphenyl)benzothiazole (3j): White
solid, m.p.: 115 -117 °C. (Lit. [19] 115-117 °C); IR (KBr,
ν
max, cm-1): 1472,1433, 1375, 1310, 1284, 973, 824, 756, 724,
433; 1H NMR (400 MHz, CDCl3, ppm) δ 8.29 (d, J = 1.4 Hz,
1H), 8.07 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 7.9 Hz, 2H), 7.50 (t,
J = 7.7 Hz, 1H), 7.39 (t, J = 7.3 Hz, 1H), 7.34 (d, J = 7.9 Hz,
1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 166.3,
154.0, 141.0, 135.0, 132.9, 131.2, 131.0, 126.4, 126.3, 125.5,
125.3, 123.2, 121.6; MS (m/z) [M+H]+: 303.
NH2
SH
N
S
Chitosan-SO3H
RCHO
R
solvent free
air, 30min
R = Aryl,
3(a-o)
Heteroaryl
2(a-o)
1
Scheme-I: Synthesis of 2-aryl/heteroaryl benzothiaozles
2-(Naphthalen-2-yl)benzothiazole (3k): White solid;
m.p.: 125-127 °C (Lit. [20] 126-128 °C); IR (KBr, νmax, cm-1):
1496, 1453, 1361, 1311, 981, 934, 852, 829, 747, 728, 476;
1H NMR (400 MHz, CDCl3, ppm) δ 8.56 (d, J = 1.2 Hz, 1H),
8.20 (dd, J = 8.7 Hz, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.98-7.86
(m, 4H), 7.56-7.49 (m, 3H), 7.40 (t, J = 7.6 Hz, 1H; 13C NMR
(100 MHz, CDCl3, ppm) δ 168.1, 154.2, 135.1, 134.6, 133.2,
131.0; MS (m/z) [M+H]+: 262.
Initially, we selected our catalyst of choice chitosan-SO3H
(CS-SO3H) and is prepared by following the reported proce-
dure [10a]. To demonstrate the green protocol, we selected
2-mercaptoaniline (1) and simple benzaldehyde (2a) as the
model reaction in presence of CS-SO3H (50 mol %) as a catalyst
in ethanol at room temperature in presence of air balloon and
achieved the cyclized compound 3(a) in 60 % yield (Table-1,
entry-1). The analytical data of the obtained compound was
in agreement with the reported data [11].
2-(Thiophen-2-yl)benzothiazole (3l): White solid; m.p.:
92-94 °C (Lit. [21] 93-95 °C); IR (KBr, νmax, cm-1): 3096, 3056,
1
1542, 1476, 1312, 1222, 912, 852, 826, 762, 714; H NMR
TABLE-1
(400 MHz, CDCl3, ppm) δ 8.03 (d, J = 8.4 Hz, 1H), 7.85 (d, J
= 8.0 Hz, 1H), 7.66 (d, J = 3.2 Hz, 1H), 7.51-7.45 (m, 2H),
OPTIMIZATION AND VARIATIONS (mol %) OF THE
CATALYST AND SOLVENT EFFECT FOR THE SYNTHESIS
OF 2-ARYL/HETEROARYL BENZOTHIAZOLES (3a)
13
7.37 (t, J = 7.6 Hz, 1H), 7.14 (t, J = 4.2 Hz, 1H); C NMR
(100 MHz, CDCl3, ppm) δ 161.3, 153.7, 137.4, 134.7, 129.2,
128.5, 128.0, 126.4, 125.2, 123.0, 121.4; MS (m/z) [M+H]+:
218.
Mol
(%)
Time
Yield
(%)a
60
65
70
75
80
90
Trace
Entry
Catalyst
Solvent
(min)b
1
2
3
4
5
6
7
CS-SO3H
CS-SO3H
CS-SO3H
CS-SO3H
CS-SO3H
CS-SO3H
No catalyst
50
30
20
10
5
EtOH
CH3CN
PEG-400
THF
Solvent less
Solvent less
Solvent less
60
50
45
40
30
2-(Pyridin-3-yl)benzothiazole (3m): White solid; m.p.:
135-137 °C (Lit. [22] 137-138 °C); IR (KBr, νmax, cm-1): 3050,
3032, 1586, 1574, 1426, 1310, 1234, 964, 814, 766, 702; 1H
NMR (400 MHz, CDCl3, ppm) δ 9.28 (d, J = 1.6 Hz, 1H),
8.70 (dd, J = 0.8, 4.4 Hz, 1H), 8.37-8.34 (m, 1H), 8.09 (d, J =
8.4 Hz, 1H), 7.91 (d, J = 8.0 Hz), 7.53-7.49 (m, 1H), 7.43-
7.39 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 164.5,
153.9, 151.5, 148.5, 134.9, 134.5, 129.6, 126.6, 125.6, 123.7,
123.4, 121.7; MS (m/z) [M+H]+: 213.
2-(Pyridin-4-yl)benzothiazole (3n): White solid; m.p.:
131-133 °C (Lit. [23] 132-134 °C); IR (KBr, νmax, cm-1): 1433,
979, 758, 728, 720; 1H NMR (400 MHz, CDCl3, ppm): δ 8.78
(d, J = 4.8 Hz, 2H), 8.14 (d, J = 8.0 Hz, 1H), 7.96-7.95 (m,
3H), 7.56 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3, ppm): δ 165.1, 154.0, 150.7, 140.5, 135.2,
126.8, 126.2, 123.9, 121.8, 121.2; MS (m/z) [M+H]+: 213.
2-(Furan-2-yl)benzothiazole (3o): Yellow solid; m.p.:
100-102 °C (Lit. [22] 102-104 °C); IR (KBr, νmax, cm-1): 3144,
3122, 3050, 1598, 1578, 1434, 1246, 1114, 898, 748,730; 1H
NMR (400 MHz, CDCl3, ppm) δ 6.57 (dd, J = 1.5, 7.4 Hz,
1H), 7.17 (d, J = 6.9 Hz, 1H), 7.35 (dt, J = 1.0, 8.3 Hz, 1H),
7.47 (dt, J = 1.0, 8.3 Hz, 1H), 7.55-7.59 (m, 1H), 7.86 (d, J =
7.3 Hz, 1H), 8.04 (d, J = 8.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ 111.3, 112.4, 121.4, 123.0, 125.1, 126.4, 134.1,
144.6, 148.6, 153.6, 157.4; MS (m/z) [M+H]+: 202.
2
–
30
600
aIsolated yields; bAll the reactions were performed at room temperature
under oxygen balloon.
We further explored the synthetic protocol and extended
the scope of the reaction by varying the catalyst loadings and
studied the effect of various solvents towards the reaction
profile. Among the attempted conditions CS-SO3H (2 mol %)
under solvent free conditions at room temperature resulted
the cyclized product in 90 % yield with high selectivity (Table-
1, entry-6). The increased mol % of the catalyst towards the
reaction is not satisfactory as depicted in (Table-1, entry: 1-4).
In the absence of catalyst no formation of the expected product
was detected even after prolonged hours (Table-1, entry-7).
Encouraged by the above appended results, we further
explored the synthetic protocol and the scope of the reaction
by employing substituted aryl/heteroaryl aldehydes func-
tionalized with electron-rich and electron-deficient groups. The
results were depicted in (Table-2, entries 2 to 15).
Clearly, all reactions worked well irrespective of the
substrates present on the aldehydes even with electron-with-

Vol. 30, No. 7 (2018)
Chitosan-SO3H: A Green Approach to 2-Aryl/Heteroaryl Benzothiazoles under Solvent-Free Conditions 1515
O
CS
S O
O
H
O
2a
Ar
O
CS
S O
O
H
H
N
N
Ar
NH2
SH
Ar
-H2O
S
H
SH
O
CS
S O
O
1
A
B
O2
H
N
O
Ar
OH
N
-H2O
H+
CS
S OH
O
Ar
S
S
3a
Regenerated
Catalyst
Scheme-II: Sequential and plausible mechanistic pathway for the preparation of 2-aryl/heteroaryl benzothiazoles by using chitosan-SO3H
TABLE-3
TABLE-2
REUSE OF THE CATALYST FOR THE SYNTHESIS OF
2-ARYL/HETEROARYL BENZOTHIAZOLES
SYNTHESIS OF 2-ARYL/HETEROARYL BENZOTHIAZOLES
USING CS-SO3H AS A CATALYST UNDER SOLVENT
FREE CONDITIONS AT ROOM TEMPERATURE
Run
1
2
3
4
5
Entry
1
2
3
4
5
6
7
8
R-CHO
C6H5
4-CH3C6H4
4- MeOC6H4
2-OHC6H4
4-BrC6H4
Productsa
3(a)
3(b)
3(c)
3(d)
3(e)
Time (min)b
Yields (%)c
Yield (%)a
aIsolated yields.
92
92
91
90
90
30
25
25
40
30
35
30
35
40
30
30
35
30
30
35
90
92
89
85
90
89
88
89
87
92
90
89
92
90
89
can possibly act as a convenient proton source which initiates
the nucleophilic attack of NH2 group on aldehyde carbonyl
group activated by CS-SO3H catalyst followed by the formation
of an azomethine intermediate [A], followed by intramolecular
cyclization to yield the intermediate [B], subsequent oxidation
with O2 from air and expulsion of H2O to furnish the fully
heteroaromatised product (3a) along with the regenerated CS-
SO3H.
4-ClC6H4
4-FC6H4
3(f)
3(g)
3(h)
3(i)
3(j)
3(k)
3(l)
3(m)
3(n)
3(o)
4-CF3C6H4
3-NO2C6H4
3-Br-4-CH3C6H3
2-Naphthyl
2-Thiophenyl
3-Pyridyl
9
10
11
12
13
14
15
Conclusion
4-Pyridyl
2-Furanyl
We have demonstrated that chitosan-SO3H catalyst is
reusable and eco-friendly catalyst for the synthesis of 2-aryl/
heteroaryl benzothiazoles. Nevertheless, without doubt the new
process has significantly improved compared to those in the
known literature in terms of high selectivity, short reactions
times, excellent yields, no thermal heating, no metal oxidant,
large substrate scope and without any waste generation or
byproduct formation. Further no column chromatography is
required. The process designed focuses on being environment
friendly under green chemistry aspects.
aAll Products were characterized by H NMR, 13C NMR and Mass
1
b
spectra. The temperature for all the synthesized products is at room
temperature. cYields refer to isolated pure products.
drawing groups. The process successfully achieved the 2-aryl/
heteroaryl benzothiazole derivatives (3a-o) (Table-2, entries
1-15) in good to excellent yields. After completion of the
reaction the catalyst is easily separated by filteration and reused
after activation at 120 °C for 3 h. The results obviously indicates
no significant loss in its activity with that of fresh catalyst as
depicted in Table-3.
ACKNOWLEDGEMENTS
A plausible mechanistic study is depicted in Scheme-II,
showing the catalytic activation of the CS-SO3H. The catalyst
The authors thank the Management ofAlekhya Drugs Pvt.
Ltd., Vijayawada, India for encouragement and support.

1516 Bathula et al.
Asian J. Chem.
(d) G.W.W. Cave, C.L. Raston and J.L. Scott, Chem. Commun., 21, 2159
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