An efficient green synthesis of new benzothiazoles containing sulfonamide or cyclic imide moieties

Article abstract of DOI:10.1002/jhet.3753

An efficient and convenient protocol for the one-pot synthesis of new benzothiazoles bearing sulfonamide or cyclic imide moieties using Cesium salt of Wells-Dawson heteropolyacid (Cs₅HP₂W₁₈O₆₂) as solid catalyst and water as solvent under ultrasound irradiation was reported. The reaction speed was remarkably catalyzed with the aid of ultrasound irradiation. Moreover, this approach prepares multiple other benefits such as operational ease, higher yields, and energy performance.

Full text of DOI:10.1002/jhet.3753

Received: 8 January 2019
DOI: 10.1002/jhet.3753
Revised: 8 September 2019
Accepted: 10 September 2019
A R T I C L E
An efficient green synthesis of new benzothiazoles
containing sulfonamide or cyclic imide moieties
Chafika Bougheloum1
Abdelrani Messalhi1
| Sabrina Alioua1 | Robila Belghiche2 | Nesma Benali1
|
1Advanced Materials Laboratory, Badji
Mokhtar Annaba-University, Annaba,
Algeria
2Chemistry Inorganic Materials
Laboratory, Badji Mokhtar
Abstract
An efficient and convenient protocol for the one-pot synthesis of new ben-
zothiazoles bearing sulfonamide or cyclic imide moieties using Cesium salt of
Wells-Dawson heteropolyacid (Cs5HP2W18O62) as solid catalyst and water as
solvent under ultrasound irradiation was reported. The reaction speed was
remarkably catalyzed with the aid of ultrasound irradiation. Moreover, this
approach prepares multiple other benefits such as operational ease, higher
yields, and energy performance.
Annaba-University, Annaba, Algeria
Correspondence
Chafika Bougheloum, Advanced Materials
Laboratory, Badji Mokhtar Annaba-
University. B. P 12, Annaba 23000,
Algeria.
Email: c_bougheloum@yahoo.fr
described by Ibrahim et al as highly potent inhibitors of
1 | INTRODUCTION
carbonic anhydrase isoforms I, II, IX, and XII[21]
(Figure 1).
Several methods have been reported for the synthesis
Benzothiazole derivatives containing scaffolds have been
rated as one of the new emerging areas in heterocyclic
chemistry because of their various biological and phar-
macological properties. These compounds have enor-
mous applications in organic and medicinal chemistry.
They possess a wide range of bioactivities including
antimicrobial,[1] anticancer,[2] anti-inflammatory,[3] anti-
convulsant,[4] antidiabetic,[5] anti-Alzheimer,[6] antipsy-
chotic,[7] protein tyrosine inhibitor,[8] and diuretic[9]
activities.
Several drugs are developed from benzothiazole deriv-
atives. For example, riluzole (1) is a glutamate receptor
antagonist, used to treat amyotrophic lateral sclerosis and
anxiety disorders,[10] Zopolrestat (2) demonstrates anti-
diabetic effects,[11] and Frentizole (3), the urea derivative
of benzothiazole is used as antiviral agent.[12]
The introduction of the sulfonamide group with some
rings such as oxazolidinone,[13] phthalimide,[14] and
quinolone,[15] could be very interesting due to its high
biological activities.[16–19]
Also, this combination is found with benzothiazole
scaffold such as: Ethoxzolomide (4), the sulfonamide drug
serving as diuretic and molecules (5) as antitubercular.[20]
Moreover, new benzothiazole-6-sulfonamides (6) were
of benzothiazole compounds from different starting
materials, still remains a great demand for the introduc-
tion of efficient, simple and more practical methods.
Recently, the application of ultrasound as a powerful
technique in synthetic organic chemistry has become
extremely efficient and attractive. Prominent features of
the ultrasound approach are enhanced organic reaction
rates, formation of purer products in high yields and
under mildes reaction conditions. Further, it is consid-
ered a processing aid in terms of energy conservation and
waste minimization compared to traditional methods.
Prompted by the aforementioned biological and phar-
maceutical activities of benzothiazole derivatives, and as
a part of an ongoing program aiming at the synthesis of
new heterocyclic compounds.[22–24] We describe herein
an efficient procedure for the synthesis of a novel series
of new benzothiazole derivatives, using ultrasound irradi-
ation in the presence of Cesium salt of Wells-Dawson
heteropolyacid (Cs5HP2W18O62) as catalyst.
This latter catalyst has been reported in our recent
work[24] for the synthesis of substituted N-acylsulfonamides
and cyclic imides containing sulfonyl group. It not only
J Heterocyclic Chem. 2019;1–12.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

2
BOUGHELOUM ET AL.
FIGURE 1 Some molecules with both sulfonamide and benzothiazole moieties
afforded the products in good to excellent yields, but also
1.2 | Preparation of benzothiazole
addresses challenges associated with catalysts such as ease
of handling, recovery, safety and pollution.
derivatives containing sulfonamide moiety
(2a-2u)
One millimole of sulfonamide were added to a mixture of
cyclic anhydride (2 mmol) and Cs5HP2W18O62 (10 mmol
%) in 2 mL of water. Then reaction mixture was subjected
to ultrasonication by an ultrasonic bath with a frequency
of 35 kHz for appropriate time (3-6 min) at 25ꢀC. Then,
1 mmol of 2-amino benzothiazole derivative were added
with additional irradiation (<10 min). Reaction was mon-
itored by TLC. After completion of the reaction, the cata-
lyst was removed by filtration. The filtrate was washed by
water (10 mL) and extracted with EtOAc (3 × 15 mL).
The combined organic layers were dried over anhydrous
Na2SO4 then the solvent was evaporated in vacuum and
the crude compound was purified by flash chromatogra-
phy (Merck silica gel 60 H, CH2Cl2/MeOH, 9:1) to afford
the corresponding products.
1.1 | Experimental section
All the chemicals were commercially available and
used as received. Cesium salt of Wells-Dawson hetero-
polyacid (Cs5HP2W18O62) was prepared according to
the literature,[25] and characterized in our previous
work[24] by spectroscopic methods (IR, 31PNMR). All
the reactions were monitored by thin-layer chromatog-
raphy (TLC) carried out on 0.25 mm E. Merck silica
gel plates (60F-254) using UV light (254 nm) as the
visualizing agent and ninhydrine solution and heat as
developing agents. Melting points were determined in
open capillary tubes on Buchi B-540. Proton nuclear
magnetic resonance was determined with a 400-MHz
Brucker spectrometer using CDCl3 or MeOD as solvent
and TMS as an internal standard. Chemical shifts are
reported in d units (ppm). All coupling constants J are
reported in Hertz. Multiplicity is indicated as s (sin-
glet), d (doublet), t (triplet), q (quadruplet), m (multi-
plet), and combination of these signals. The mass
spectra were recorded on a DSQ Thermoelectron appa-
ratus (70 eV) by chemical ionization (gaseous ammo-
nia) by direct introduction. Elemental analysis was
performed with a Perkin-Elmer 2400 C, H, N analyzer
and determined values were within the acceptable
limits of the calculated values. Sonication was per-
formed in a Fischerbrand FB11020 ultrasonic bath
with a frequency of 35 kHz.
N1-(Benzo[d]thiazol-2-yl)-N4-tosylsuccinamide
(2a).
Yield: 77%, mp 171ꢀC, Rf = 0.46 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.38 (s, 3H, CH3-Ph), 2.62(s,
4H, (CH2)-COamide), 7.23 (d, J = 8.1 Hz, 2H, Ar-H), 7.40
(d, J = 8.2 Hz, 2H, Ar-H), 7.60 (d, J = 8.2 Hz, 1H, Ar-H),
7.65 (d, J = 8.2 Hz, 1H, Ar-H), 7.70 (d, J = 8.2 Hz, 1H,
Ar-H), 7.85(d, J = 8.2 Hz, 2H, Ar-H), 8.08(s, 1H, NH),
9.10 (s, 1H, NH). 13C NMR (CDCl3, δ ppm): 21.6, 30.9,
118.9, 120.6, 124.6, 125.1, 127.1, 130.0, 131.2, 136.9, 143.9,
153.1, 172.6, 173.9, 174.5. MS (ESI+ 70 eV m/z):
404.07([M + 1]+, 70%). Elemental anal. (%), calculated: C,
53.58; H, 4.25; N, 10.41; found: C, 53.62; H, 4.28; N, 1037.
N1-(Benzo[d]thiazol-2-yl)-N4-tosylfumaramide
(2b).
Yield: 64%, mp 166ꢀC, Rf = 0.47 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.51 (s, 3H, CH3), 6.48 (s, 2H,
CH = CH), 7.65(d, J = 8.1 Hz, 2H, Ar-H), 7.75(d,

BOUGHELOUM ET AL.
3
J = 8.2 Hz, 2H, Ar-H), 8.09(d, J = 8.6 Hz, 2H, Ar-H),
8.30(d, J = 8.7 Hz, 2H, Ar-H), 9.00(s, 1H, NH). 13C NMR
(CDCl3, δ ppm): 23.3, 118.8, 120.6, 124.6, 125.2, 127.3,
129.5, 131.2, 135.8, 136.5, 141.3, 153.2, 166.4, 175.1. Ele-
mental anal. (%), calculated: C, 53.85; H, 3.77; N, 10.47;
found: C, 53.81; H, 3.79; N, 10.51.
N1-(6-Methylbenzo[d]thiazol-2-yl)-N4-tosylfumaramide
(2 g). Yield: 63%, mp 169ꢀC, Rf = 0.49 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 2.38 (s, 6H, CH3), 6.50 (s,
2H, CH=CH), 7.40(d, J = 7.5 Hz, 2H, Ar-H), 7.60(s, 1H,
Ar-H), 7.65(d, J = 8.2 Hz, 1H, Ar-H), 7.75(d, J = 8.4 Hz,
2H, Ar-H), 8.10(d, J = 8.5, 2H, Ar-H), 9.00(s, 1H, NH). 13
C
N1-(Benzo[d]thiazol-2-yl)-2,3-dichloro-N4-
NMR (CDCl3, δ ppm): 23.3, 118.5, 120.7, 124.9, 125.4,
127.9, 129.3, 131.2, 134.8, 135.8, 137.2, 150.3, 166.9, 167.4,
175.2. Elemental anal. (%), calculated: C, 54.92; H,
4.12; N, 10.11; found: C, 54.95; H, 4.10; N, 10.14.
tosylmaleamide (2c). Yield: 60%, mp 166ꢀC, Rf = 0.47
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.51 (s,
3H, CH3), 6.90(d, J = 6.7 Hz, 1H, Ar-H), 7.15(t,
J = 7.6 Hz, 1H, Ar-H), 7.32(d, J = 7.8 Hz, 2H, Ar-H),
7.55(d, J = 8.2 Hz, 2H, Ar-H), 7.69(d, J = 8.4 Hz, 2H, Ar-
H), 8.25(s, 1H, NH), 9.00(s, 1H, NH). 13C NMR (CDCl3, δ
ppm): 23.3, 118.8, 120.6, 124.6, 125.2, 127.3, 129.5, 131.2,
135.8, 136.5, 141.3, 153.2, 166.4, 174.8. Elemental anal.
(%), calculated: C, 52.72; H, 3.58; N, 9.34; found: C,
52.75; H, 3.60; N, 9.30.
N1-(6-Methyl
benzo[d]thiazol-2-yl)-2,3-dichloro-N4-
tosylmaleamide (2 h). Yield: 59%, mp 168ꢀC, Rf = 0.48
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.37 (s,
6H, CH3), 7.34(d, J = 7.8 Hz, 2H, Ar-H), 7.62(d,
J = 8.1 Hz, 2H, Ar-H), 7.76(d, J = 8.3 Hz, 2H, Ar-H),
8.01(s, 1H, NH), 9.00(s, 1H, NH). 13C NMR (CDCl3, δ
ppm): 21.4, 22.9, 118.5, 120.6, 124.6, 127.2, 128.5, 131.2,
135.8, 136.5, 137.3, 141.3, 151.2, 166.4, 168.3, 174.8. Ele-
mental anal. (%), calculated: C, 47.11; H, 3.12; N, 8.68;
found: C, 47.16; H, 3.09; N, 8.70.
N1-(Benzo[d]thiazol-2-yl)-N5-tosylglutaramide
(2d).
Yield: 67%, mp 173ꢀC, Rf = 0.49(CH2Cl2/MeOH, 9/1). 1H
NMR (CDCl3, δ ppm): 1.25 (m, 2H, CH2-CH2-CH2, 2.45(t,
J = 7.5, 4H, CH2-CO), 2.46 (s, 3H, CH3), 7.28 (d,
J = 8.1 Hz, 2H, Ar-H), 7.57 (d, J = 8.2 Hz, 2H, Ar-H),
7.67 (d, J = 8.2 Hz, 2H, Ar-H), 7.95(s, 1H, NH), 9.02(s,
1H, NH). 13C NMR (CDCl3, δ ppm): 20.9, 21.6, 32.5, 34.9,
118.8, 120.6, 124.6, 125.2, 127.1, 129.2, 131.8, 137.3, 142.9,
153.7, 172.7, 173.7, 174.7. Elemental anal. (%),
calculated: C, 54.66; H, 4.59; N, 10.06; found: C, 54.64; H,
4.62; N, 10.03.
N1-(6-Methyl benzo[d]thiazol-2-yl)- N5-tosylglutaramide
(2i). Yield: 68%, mp 174ꢀC, Rf = 0.50 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 1.25 (m, 2H, CH2-CH2-CH2,
2.45(t, J = 6.5 Hz, 4H, CH2-CO), 2.46 (s, 6H, CH3), 7.30(d,
J = 7.5 Hz, 1H, Ar-H), 7.35 (d, J = 8.1 Hz, 2H, Ar-H), 7.71
(d, J = 8.2 Hz, 2H, Ar-H), 7.75 (s, 1H, Ar-H), 7.85 (d,
J = 8.4 Hz, 1H, Ar-H), 8.02(s, 1H, NH), 9.04(s, 1H, NH).
13C NMR (CDCl3, δ ppm): 20.9, 21.6, 21.9, 32.5, 34.9, 118.8,
121.6, 128.1, 128.7, 129.2, 131.8, 135.3, 138.9, 152.4, 173.8,
174.6, 174.9. Elemental anal. (%), calculated: C, 55.67; H,
4.91; N, 9.74; found: C, 55.64; H, 4.92; N, 9.80.
N1-(Benzo[d]thiazol-2-yl)-N- tosylphthalamide (2e).
Yield: 49%, mp 176ꢀC, Rf = 0.49 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.45 (s, 3H, CH3-Ph), 7.38 (d,
J = 8.1 Hz, 2H, Ar-H), 7.84 (d, J = 8.2 Hz, 2H, Ar-H),
7.94 (d, J = 8.2 Hz, 2H, Ar-H), 8.05 (m, 4H, Ar-H), 8.09
(d, 1H, Ar-H), 8.09(s, 1H, NH), 9.08(s, 1H, NH). 13C NMR
(CDCl3, δ ppm): 21.6, 118.7, 120.5, 123.8, 124.6, 125.3,
127.7, 128.3, 130.0, 131.4, 131.9, 132.1, 134.5, 137.2, 137.9,
153.1, 172.9, 173.7, 174.8. Elemental anal. (%),
calculated: C, 58.52; H, 3.79; N, 9.31; found: C, 58.55; H,
3.82; N, 9.28.
N1-(6-Methyl benzo[d]thiazol-2-yl)-N2- tosylphthalamide
(2j). Yield: 48%, mp 178ꢀC, Rf = 0.47 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.45 (s, 6H, CH3-Ph), 7.38 (d,
J = 8.1 Hz, 1H, Ar-H), 7.44 (d, J = 8.1 Hz, 2H, CHarom),
7.72 (d, J = 8.2 Hz, 2H, Ar-H), 7.75 (s, 1H, Ar-H), 7.94(m,
4H, Ar-H), 8.02 (d, J = 8.5 Hz, 1H, Ar-H), 8.07(s, 1H, NH),
9.05(s, 1H, NH). 13C NMR (CDCl3, δ ppm): 21.6, 22.2,
118.7, 120.5, 123.8, 124.6, 125.3, 127.7, 128.3, 130.0, 131.4,
131.9, 132.1, 134.6, 137.2, 137.9, 153.1, 172.9, 173.7, 174.2,
174.8. Elemental anal. (%), calculated: C, 59.34; H, 4.11; N,
9.03; found: C, 59.36; H, 4.14; N, 9.01.
N1-(6-Methylbenzo[d]thiazol-2-yl)-N4-tosylsuccinamide
(2f). Yield: 76%, mp 172ꢀC, Rf = 0.48 (CH2Cl2/MeOH,
9/1). 1H NMR (CDCl3, δ ppm): 2.38 (s, 6H, CH3-Ph),
2.64(s, 4H, (CH2)-COamide), 7.30 (d, J = 8.1 Hz, 2H, Ar-H),
7.60 (s, 1H, Ar-H), 7.63 (d, J = 8.2 Hz, 1H, Ar-H), 7.78 (d,
J = 8.2 Hz, 2H, Ar-H), 8.08 (s, 1H, Ar-H), 8.08 (s, 1H,
NH), 9.10 (s, 1H, NH). 13C NMR (CDCl3, δ ppm): 21.6,
21.9, 30.9, 118.9, 121.6, 127.1, 128.2, 128.7, 130.0, 131.2,
131.8, 134.1, 136.9, 143.9, 153.1, 153.6, 172.6, 173.9, 174.5,
174.8. MS (ESI+ 70 eV m/z): 418.20([M + 1]+, 100%). Ele-
mental anal. (%), calculated: C, 54.66; H, 4.59; N, 10.06;
found: C, 54.62; H, 4.56; N, 10.13.
N1-(6-Nitrobenzo[d]thiazol- 2-yl)-N4-tosylsuccinamide
(2 k). Yield: 43%, mp 175ꢀC, Rf = 0.43 (CH2Cl2/MeOH,
9/1). 1H NMR (CDCl3, δ ppm): 2.33 (s, 3H, CH3-Ph),
2.67(s, 4H, (CH2)-COamide), 7.32 (d, J = 8.1 Hz, 2H, Ar-
H), 7.40 (s, 1H, Ar-H), 7.76 (d, J = 8.2 Hz, 2H, Ar-H),
8.08(s, 1H, NH), 8.20 (d, J = 8.2 Hz, 1H, Ar-H), 8.78 (s,
1H, Ar-H), 9.00 (s, 1H, NH). 13C NMR (CDCl3, δ ppm):
21.6, 21.9, 30.9, 117.8, 119.2, 121.9, 128.2, 131.2, 137.3,
137.7, 144.9, 159.5, 173.9, 174.5, 174.8. MS (ESI+
70 eV m/z): 448.07([M]+, 100%). Elemental anal. (%),

4
BOUGHELOUM ET AL.
calculated: C, 48.21; H, 3.60; N, 12.49; found: C, 48.26; H,
3.63; N, 12.43.
Yield: 88%, mp 148ꢀC, Rf = 0.51 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.80(s, 4H, CH2-COamide),
3.30(t, J = 6.8 Hz, 4H, CH2-N), 3.75(t, J = 6.8 Hz, 4H,
CH2-N), 7.05(m, 3H, Ar-H), 7.30(t, 2 J = 7.5 Hz, H, Ar-
H), 7.75(d, J = 7.7 Hz, 2H, Ar-H), 8.25 (d, J = 8.1, 1H, Ar-
H), 8.04(d, J = 8.4, 1H, Ar-H). 13C NMR (CDCl3, δ ppm):
29.6, 31.1, 46.5, 49.1, 117.1, 118.7, 121.1, 121.9, 124.9,
125.7, 129.5, 130.8, 150.6, 153.4, 173.5, 174.4, 175.1. MS
(ESI+ 70 eV m/z): 474.10 ([M + H]+, 100%). Elemental
anal. (%), calculated: C, 53.26; H, 4.90; N, 14.79; found: C,
53.30; H, 4.92; N, 14.77.
N1-(Benzo[d]thiazol-2-yl)-N4-(N-butylsulfamoyl)succinamide
(2 l). Yield: 89%, mp 137ꢀC, Rf = 0.48 (CH2Cl2/MeOH,
9/1). 1HNMR (CDCl3,δppm): 0.75 (t, 3H, J = 5.8 Hz, CH3),
1.22 (m, 2H, CH2), 1.33 (m, 2H, CH2), 2.65(s, 4H, CH2-
COamide), 2.85 (m, 2H, CH2-N), 7.36(d, J = 7.8 Hz, 2H, Ar-
H), 7.70(d, J = 8.5 Hz, 1H, Ar-H), 7.80(d, J = 8.5 Hz, 1H,
Ar-H). 13C NMR (CDCl3, δ ppm): 13.5, 19.8, 29.6, 29.7,
30.9, 43.5, 118.6, 121.8, 124.9, 125.7, 130.8, 153.4, 173.5,
174.4, 175.1. Ms (ESI+ 70 eVm/s): 385.13([M + 1]+, 100%).
Elemental anal. (%), calculated: C, 46.86; H, 5.24; N, 14.57;
found: 46.89; H, 5.28; N, 14.59.
N1-(Benzo[d]thiazol-2-yl)-N4-(N- phenylsulfamoyl)
fumaramide (2q). Yield: 89%, mp 141ꢀC, Rf = 0.51
1
N1-(Benzo[d]thiazol-2-yl)-N4-(N-tert-butylsulfamoyl)
succinamide (2 m). Yield: 92%, mp 139ꢀC, Rf = 0.50
(CH2Cl2/MeOH, 9/1), H NMR (CDCl3, δ ppm): 6.70(s,
2H, CH=CH), 7.25(m, 5H, Ar-H), 7.45(d, J = 7.5 Hz,
2H, Ar-H), 7.64(d, J = 7.8 Hz, 2H, Ar-H), 8.04(s, 1H,
N-H), 9.00(s, 1H, N-H). 13C NMR (CDCl3, δ ppm):
118.6, 119.5, 121.2, 121.8, 124.3, 124.9, 125.7, 126.1,
135.8, 138.7, 153.4, 168.2, 169.6, 175.8. MS (ESI+
70 eV m/z): 402 ([M]+, 100%). Elemental anal. (%),
calculated: C, 50.74; H, 3.51; N, 13.92; found: C,
50.75; H, 3.54; N, 13.90.
1
(CH2Cl2/MeOH, 9/1). HNMR (CDCl3,δppm): 1.28(s, 9H,
3(CH3), 2.46(s, 4H, CH2-COamide), 7.65(d, J = 7.5 Hz, 2H,
Ar-H), 7.75(d, J = 7.7 Hz, 1H, Ar-H), 8.02(d, J = 8.2 Hz,
1H, Ar-H), 9.02(s, 1H, NH), 9.08(s, 1H, NH). 13CNMR
(CDl3, δppm): 29.4, 29.7, 44.6, 118.6, 121.8, 124.9, 125.7,
130.8, 153.4, 173.5, 174.4, 175.1. Ms (ESI+ 70 eVm/s):
155.03(67%), 255.02(14%), 407.13 ([M + Na]+, 100%). Ele-
mental anal. (%), calculated: C, 46.86; H, 5.24; N, 14.57;
found: C, 46.90; H, 5.22; N, 14.60.
N1-(Benzo[d]thiazol-2-yl)-2,3-dichloro-N4-((4-methoxy
phenyl)sulfonyl)maleamide (2r). Yield: 82%, mp 169ꢀC,
Rf = 0.45 (CH2Cl2/MeOH, 9/1). 1H NMR (DMSO, δ
ppm): 3.72 (s, 3H, CH3), 6.92(d, J = 7.6 Hz, 2H, Ar-H),
7.20(d, J = 7.9 Hz, 2H, Ar-H), 7.60–7.73(2d, J = 7.9, 4H,
Ar-H), 7.74(s, 1H, N-H), 8.80(s, 1H, NH). 13C NMR
(CDCl3, δ ppm): 55.7, 112.8, 115.2, 117.7, 121.6, 124.6,
130.8, 133.8, 135.9, 140.8, 150.1, 157.9. MS (ESI+ 70 eV m/
z): 485.10 ([M]+, 100%). Elemental anal. (%),
calculated: C, 44.45; H, 2.69; N, 8.64; found: C, 44.47; H,
2.67; N, 8.67.
N1-(Benzo[d]thiazol-2-yl)-N4-(N-
phenylsulfamoyl)
succinamide (2n). Yield: 84%, mp 148ꢀC, Rf = 0.48
1
(CH2Cl2/MeOH, 9/1), H NMR (CDCl3, δ ppm): 2.67(s,
4H, CH2-COamide), 4.05(s, 1H, NH), 6.79(m, 5H, Ar-H),
7.74(d, J = 7.5 Hz, 2H, Ar-H), 7.92(d, J = 7.8 Hz, 1H, Ar-
H), 8.04(d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ
ppm): 29.8, 29.9, 118.6, 121.2, 121.8, 124.3, 124.9, 125.7,
126.1, 130.8, 140.4, 153.4, 173.6, 174.6, 175.8. MS (ESI+
70 eV m/z): 406 ([M]+, 100%). Elemental anal. (%), cal-
culated: C, 50.48; H, 3.99; N, 13.85; found: C, 50.45; H,
3.98; N, 13.89.
N1-(Benzo[d]thiazol-2-yl)-2,3-dichloro-N4-((4-chlorophenyl)
sulfonyl)maleamide (2 s). Yield: 80%, mp 169ꢀC,
Rf = 0.47 (CH2Cl2/MeOH, 9/1). 1H NMR (DMSO, δ
ppm): 7.32(d, J = 7.8 Hz, 2H, Ar-H), 7.43(d, J = 8.1 Hz,
2H, Ar-H), 7.64 (d, J = 8.3 Hz, 2H, Ar-H), 7.66 (d,
J = 8.4 Hz, 2H, Ar-H), 8.20(s, 1H, NH), 9.10(s, 1H, NH).
13C NMR (CDCl3, δ ppm): 118.8, 121.6, 124.6, 125.2,
128.8, 129.2, 131.2, 137.8, 138.5, 153.2, 163.4, 168.7,
174.8. MS (ESI+ 70 eV m/z): 489.08 ([M]+, 100%). Ele-
mental anal. (%), calculated: C, 41.60; H, 2.05; N, 8.56;
found: C, 41.63; H, 2.06; N, 8.54.
N1-(Benzo[d]thiazol-2-yl)-N4-((3,4-dihydroisoquinolin-
2(1H)yl)sulfonyl)succinamide (2o). Yield: 90%, mp 143ꢀC,
Rf = 0.39 (CH2Cl2/MeOH, 9/1). 1H NMR (CDCl3, δ
ppm): 2.69(s, 4H, CH2-CO amide), 2.88(t, 2H, J = 5.8 Hz,
CH2-Ar), 3.60(t, 2H, J = 5.7 Hz, CH2N), 4.51(s, 2H, Ar-
CH2N), 7.05(m, 1H, Ar-H), 7.09(m, 1H, Ar-H), 7.17(m,
2H, Ar-H), 7.56(d, J = 7.8 Hz, 2H, Ar-H), 7.92(d,
J = 8.3 Hz, 1H, Ar-H), 8.07(s, 1H, NHamide), 8.04(d,
J = 8.5 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ ppm): 22.4,
20.0, 32.3, 52.1, 53.2, 119.8, 122.6, 124.3, 125.7, 126.2,
127.1, 128.4, 129.6, 132.4, 135.4, 152.5, 168.4, 171.2, 172.5.
MS (ESI+ 70 eV m/z): 445.07([M + 1]+, 68%). Elemental
anal. (%), calculated: C, 54.04; H, 4.53; N, 12.60; found: C,
54.06; H, 4.50; N, 12.64.
N1-(6-Methoxybenzo[d]thiazol-2-yl)-2,3-dichloro-N4-
tosylmaleamide (2 t). Yield: 83%, mp 166ꢀC,
Rf = 0.48(CH2Cl2/MeOH, 9/1). 1H NMR (CDCl3, δ ppm):
2.41 (s, 3H, CH3), 3.76 (s, 3H, CH3), 7.35(d, J = 6.7 Hz,
1H, Ar-H), 7.63(d, J = 7.8, 2H, Ar-H), 7.75–7.80(2d, 4H,
Ar-H), 7.78(d, J = 8.2 Hz, 1H, NH), 8.15(s, 1H, NH). 13C
NMR (CDCl3, δ ppm): 21.3, 56.8, 104.9, 114.8, 118.8,
128.6, 129.6, 131.2, 136.8, 137.3, 145.3, 156.8, 163.4, 168.4,
N1-(Benzo[d]thiazol-2-yl)-N4-((4-phenylpiperazin-1-yl)
sulfonyl)succinamide (2p).

BOUGHELOUM ET AL.
5
174.8. MS (ESI+ 70 eV m/z): 499.05 ([M]+, 100%). Ele-
mental anal. (%), calculated: C, 45.61; H, 3.02; N, 8.40;
found: C, 45.64; H, 3.06; N, 8.42.
1-(Benzo[d]thiazol-2-yl) piperidine-2,6-dione (4d).
Yield: 86%, mp 121ꢀC, Rf = 0.64 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 2.12(m, 2H, CH2-CH2), 2.24(t,
J = 6.5, 4H, CH2-CO), 7.50 (d, J = 8.2 Hz, 2H, Ar-H), 8.10
(d, J = 8.4 Hz, 1H, Ar-H), 8.22 (d, J = 8.2 Hz, 1H, Ar-H).
13C NMR (CDCl3, δ ppm): 18.1, 32.3, 118.2, 122.3, 125.9,
126.2, 135.1, 138.9, 158.2, 170.0. MS (ESI+ 70 eV m/z):
247.10 ([M + 1]+, 90%), 264.14 ([M + NH4]+, 25%). Ele-
mental anal. (%), calculated: C, 58.52; H, 4.09; N, 11.37;
found: C, 58.55; H, 4.07; N, 11.36.
2-(Benzo[d]thiazol-2-yl) isoindoline-1,3-dione (4e).
Yield: 75%, mp 133ꢀC, Rf = 0.66 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 7.45 (d, J = 8.2 Hz, 2H, Ar-H),
7.80 (m, 4H, Ar-H), 7.86 (d, J = 8.1 Hz, 1H, Ar-H), 8.15
(d, J = 8.3 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ ppm):
118.5, 121.5, 123.8, 124.6, 125.3, 132.4, 133.1, 136.1, 139.8,
161.2, 169.2. MS (ESI+ 70 eV m/z): 281.08 ([M + 1]+,
35%), 298.10 ([M + NH4]+, 100%). Elemental anal. (%),
calculated: C, 64.27; H, 2.88; N, 9.99; found: C, 64.29; H,
2.85; N, 9.98.
N1-(6-Methylbenzo[d]thiazol-2-yl)-2,3-dimethyl-N4-tosyl
maleamide (2u). Yield: 86%, mp 160ꢀC, Rf = 0.53 (CH2Cl2/
1
MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.35 (s, 6H, CH3),
2.62 (s, 6H, CH3), 7.35(d, J = 6.7, 2H, Ar-H), 7.60(d,
J = 7.9 Hz, 1H, Ar-H), 7.65(d, J = 6.9 Hz, 2H, Ar-H),
7.78(d, J = 8.2 Hz, 2H, Ar-H), 8.12(s, 1H, NH), 8.98(s, 1H,
NH). 13C NMR (CDCl3, δ ppm): 7.8, 8.1, 19.2, 19.6, 116.8,
119.5, 125.6, 128.6, 129.5, 131.8, 133.4, 138.4, 138.9, 150.1,
164.8, 169.2, 175.2. MS (ESI+ 70 eV m/z): 443.10 ([M]+,
100%). Elemental anal. (%), calculated: C, 56.87; H, 4.77; N,
9.47; found: C, 56.90; H, 4.78; N, 9.44.
1-Tosylpyrrolidine-2,5-dione (3a). Yield: 30%, mp
1
126ꢀC, Rf = 0.88 (CH2Cl2/MeOH, 9/1). H NMR (CDCl3,
δ ppm): 2.45 (s, 3H, CH3-Ph), 2.65(s, 4H, (CH2)-COamide),
7.40 (d, J = 8.1 Hz, 2H, Ar-H), 7.75 (d, J = 8.2 Hz, 2H,
Ar-H). 13C NMR (CDCl3, δ ppm): 21.5, 26.9, 128.5, 129.3,
137.6, 137.9, 175.8. MS (ESI+ 70 eV m/z): 254.09
([M + 1]+, 40%), 271.02 ([M + NH4]+, 100%). Elemental
anal. (%), calculated: C, 52.16; H, 4.38; N, 5.53; found: C,
52.19; H, 4.29; N, 5.59.
1-(6-Methylbenzo[d]thiazol-2-yl) pyrrolidine-2,5-dione
(4f). Yield: 90%, mp 118ꢀC, Rf = 0.69 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 2.35(s, 3H, CH3), 2.86(s,
4H, (CH2)-CO), 7.60 (s, 1H, Ar-H), 7.73 (d, J = 8.2 Hz,
1H, Ar-H), 8.02 (s, 1H, Ar-H). 13C NMR (CDCl3, δ ppm):
20.2, 30.8, 117.4, 121.1, 126.7, 130.7, 135.3, 150.4, 161.1,
174.2. MS (ESI+ 70 eV m/z): 247.10 ([M + 1]+, 100%).
Elemental anal. (%), calculated: C, 58.52; H, 4.09; N,
11.37; found: C, 58.56; H, 4.07; N, 11.40.
1-(Benzo[d]thiazol-2-yl) pyrrolidine-2,5-dione (4a).
Yield: 94%, mp 121ꢀC, Rf = 0.86 (CH2Cl2/MeOH, 9/1). 1H
NMR (CDCl3, δ ppm): 2.82(s, 4H, (CH2)-CO), 7.50 (d,
J = 8.2 Hz, 2H, Ar-H), 8.10 (d, J = 8.1 Hz, 1H, Ar-H), 8.22
(d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ ppm): 30.8,
124.1, 125.6, 128.1, 129.7, 136.8, 139.7, 161.8, 176.2. MS
(ESI+ 70 eV m/z): 233.13 ([M + 1]+, 35%), 250.10
([M + NH4]+, 100%). Elemental anal. (%), calculated: C,
56.88; H, 3.47; N, 12.06; found: C, 56.82; H, 3.53; N, 12.12.
1-(6-Methylbenzo[d]thiazol-2-yl)-1H-pyrrole-2,5-dione
(4 g). Yield: 89%, mp 115ꢀC, Rf = 0.57 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 2.39(s, 3H, CH3), 6.85 (s,
2H, CH=CH), 7.40 (d, J = 8.2 Hz, 1H, Ar-H), 7.75 (s, 1H,
Ar-H), 7.81 (d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ
ppm): 21.5, 118.1, 122.3; 125.2, 126.5, 132.1, 135.1, 151.7,
159.8, 161.3. MS (ESI+ 70 eV m/z): 245.07 ([M + 1]+,
85%), 262.14 ([M + NH4]+, 100%). Elemental anal. (%),
calculated: C, 59.00; H, 3.30; N, 11.47; found: C, 59.03; H,
3.32; N, 11.45.
1-(Benzo[d]thiazol-2-yl)-1H-pyrrole-2,5-dione
(4b).
Yield: 92%, mp 115ꢀC, Rf = 0.69 (CH2Cl2/MeOH, 9/1).
1H NMR (CDCl3, δ ppm): 6.85 (s, 2H, CH=CH), 7.65 (t,
J = 6.8 Hz, 1H, Ar-H), 7.75 (t, J = 6.9 Hz, 1H, Ar-H), 8.15
(d, J = 8.2 Hz, 1H, Ar-H), 8.30 (d, J = 8.2 Hz, 1H, Ar-H).
13C NMR (CDCl3, δ ppm): 118.4, 121.6, 124.3, 125.7,
135.4, 136.3, 139.9, 160.9, 167.2. MS (ESI+ 70 eV m/z):
231.13 ([M + 1]+, 28%), 248.10 ([M + NH4]+, 100%). Ele-
mental anal. (%), calculated: C, 57.38; H, 2.63; N, 12.17;
found: C, 57.40; H, 2.62; N, 12.12.
1-(6-Methylbenzo[d]thiazol-2-yl)
-3,4-dichloro-1H-
pyrrole −2,5-dione (4h). Yield: 80%, mp 125ꢀC, Rf = 0.64
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.39(s,
3H, CH3), 7.32 (d, J = 8.1 Hz, 1H, Ar-H), 7.70 (s, 1H, Ar-
H), 7.85 (d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ
ppm): 20.3, 118.5, 121.5, 125.6, 130.8, 134.8, 137.7, 150.7,
161.2, 162.2. MS (ESI+ 70 eV m/z): 314.13 ([M + 1]+,
100%). Elemental anal. (%), calculated: C, 46.02; H,
1.93; N, 8.95; found: C, 46.00; H, 1.96; N, 8.92.
1-(Benzo[d]thiazol-2-yl) -3,4-dichloro-1H- pyrrole
−2,5-dione (4c). Yield: 89%, mp 123ꢀC, Rf = 0.66
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 7.55 (d,
J = 7.6 Hz, 2H, Ar-H), 7.90 (d, J = 8.2 Hz, 1H, Ar-H),
8.10 (d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ ppm):
118.5, 121.5, 125.6, 127.8, 136.8, 137.5, 139.7, 161.2, 162.2.
MS (ESI+ 70 eV m/z): 299.1 ([M]+, 100%), 322.2
(M + Na)+, 67%). Elemental anal. (%), calculated: C,
44.17; H, 1.35; N, 9.36; found: C, 44.21; H, 1.32; N, 9.40.
1-(6-Methylbenzo[d]thiazol-2-yl) piperidine-2,6-dione
(4i). Yield: 78%, mp 124ꢀC, Rf = 0.60 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 2.12(m, 2H, CH2-CH2),
2.24(t, 4H, CH2-CO), 2.33(s, 3H, CH3), 7.60 (s, 1H, Ar-H),

6
BOUGHELOUM ET AL.
7.73 (d, J = 8.2 Hz, 1H, Ar-H), 8.02 (s, 1H, Ar-H). 13C
NMR (CDCl3, δ ppm): 18.2, 22.4, 31.9, 118.2, 121.9, 125.9,
130.0, 132.4, 152.1, 162.9, 168.2. MS (ESI+ 70 eV m/z):
261.11 ([M + 1]+, 55%), 278.10 ([M + NH4]+, 100%). Ele-
mental anal. (%), calculated: C, 59.98; H, 4.65; N, 10.76;
found: C, 59.96; H, 4.68; N, 10.79.
1-(6-Methoxybenzo[d]thiazol-2-yl)-1H-pyrrole-2,5-dione
(4o). Yield: 72%, mp 119ꢀC, Rf = 0.60 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 3.84(s, 3H, CH3), 6.85 (s,
2H, CH=CH), 7.40 (d, J = 8.2 Hz, 1H, Ar-H), 7.76 (s, 1H,
Ar-H), 7.82 (d, J = 8.3 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ
ppm): 56.7, 106.6, 117.4, 118.8, 131.5, 143.5, 157.4, 161.1,
174.4. MS (ESI+ 70 eV m/z): 261.07 ([M + 1]+, 80%),
278.14 ([M + NH4]+, 100%). Elemental anal. (%), cal-
culated: C, 55.38; H, 3.10; N, 10.76; found: C, 55.40; H,
3.12; N, 10.73.
2-(6-Methylbenzo[d]thiazol-2-yl) isoindoline-1,3-dione
(4j). Yield: 72%, mp 136ꢀC, Rf = 0.61 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 2.38(s, 3H, CH3), 7.35 (s,
1H, Ar-H), 7.76–7.93 (m, 6H, Ar-H). 13C NMR (CDCl3, δ
ppm): 20.9, 117.5, 121.5, 123.9, 126.5, 130.8, 132.6, 134.3,
150.4, 161.1, 169.2. MS (ESI+ 70 eV m/z): 317.1
[M + Na+, 15%). Elemental anal. (%), calculated: C,
65.29; H, 3.42; N, 9.52; found: C, 65.30; H, 3.46; N, 9.50.
1-(6-Nitrobenzo[d]thiazol-2-yl) pyrrolidine-2,5-dione
(4 k). Yield: 70%, mp 128ꢀC, Rf = 0.48 (CH2Cl2/MeOH,
9/1). 1H NMR (CDCl3, δ ppm): 2.94(s, 4H, CH2-CO), 8.00
(d, J = 8.2 Hz, 1H, Ar-H), 8.25 (d, J = 8.2 Hz, 1H, Ar-H),
8.75 (s, 1H, Ar-H).. 13C NMR (CDCl3, δ ppm): 30.8, 117.8,
119.3, 122.1, 130.7, 144.8, 159.9, 161.8, 176.2. MS (ESI+
70 eV m/z): 277.10 ([M]+, 100%). Elemental anal. (%), cal-
culated: C, 47.65; H, 2.54; N, 15.16; found: C, 47.63; H,
2.56; N, 15.13.
1-(6-Methoxybenzo[d]thiazol-2-yl) -3,4-dichloro-1H-
pyrrole −2,5-dione (4p). Yield: 67%, mp 129ꢀC, Rf = 0.60
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 3.82(s,
3H, CH3), 7.58 (d, J = 8.1 Hz, 1H, Ar-H), 7.80 (s, 1H, Ar-
H), 7.85 (d, J = 8.2 Hz, 1H, Ar-H). 13C NMR (CDCl3, δ
ppm): 57.3, 105.3, 115.5, 119.5, 130.8, 136.8, 143.8, 156.7,
161.2, 163.2. MS (ESI+ 70 eV m/z): 329.13 ([M + 1]+. Ele-
mental anal. (%), calculated: C, 43.79; H, 1.84; N, 8.51;
found: C, 43.77; H, 1.86; N, 8.49.
2-(6-Methoxybenzo[d]thiazol-2-yl)
isoindoline-1,-
3-dione (4q). Yield: 74%, mp 140ꢀC, Rf = 0.59 (CH2Cl2/
1
MeOH, 9/1). H NMR (CDCl3, δ ppm): 3.78(s, 3H, CH3),
7.32 (d, J = 8.1 Hz, 1H, Ar-H), 7.53 (s, 1H, Ar-H), 7.59 (d,
J = 8.2 Hz, 1H, Ar-H), 7.76–7.93 (m, 4H, Ar-H). 13C NMR
(CDCl3, δ ppm): 56.9, 105.5, 117.7, 119.5, 123.9, 131.8,
146.6, 157.4, 161.1, 169.7. MS (ESI+ 70 eV m/z): 311.1
[M + H+, 100%),. Elemental anal. (%), calculated: C,
61.93; H, 3.25; N, 9.03; found: C, 61.90; H, 3.29; N, 9.01.
1-(Benzo[d]thiazol-2-yl) -3,4-dimethyl-1H- pyrrole
−2,5-dione (4r). Yield: 82%, mp 127ꢀC, Rf = 0.68
1-(6-Nitrobenzo[d]thiazol-2-yl)-1H-pyrrole-2,5-dione
(4 l). Yield: 68%, mp 125ꢀC, Rf = 0.46 (CH2Cl2/MeOH,
1
9/1). H NMR (CDCl3, δ ppm): 6.90 (s, 2H, CH=CH),
7.70 (d, J = 8.2 Hz, 1H, Ar-H), 7.85 (d, J = 8.2 Hz, 1H,
Ar-H), 8.05 (s, 1H, Ar-H),. 13C NMR (CDCl3, δ ppm):
118.1, 120.3; 123.2, 132.1, 135.1, 145.7, 159.8, 161.3. MS
(ESI+ 70 eV m/z): 276.08 ([M + 1]+, 85%), 294.14
([M + NH4]+, 100%). Elemental anal. (%), calculated: C,
48.00; H, 1.83; N, 15.27; found: C, 48.03; H,
1.82; N, 15.25.
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.45(s,
6H, CH3), 7.55 (d, J = 7.6 Hz, 2H, Ar-H), 7.90 (d,
J = 8.2 Hz, 1H, Ar-H), 8.10 (d, J = 8.2 Hz, 1H, Ar-H). 13
C
NMR (CDCl3, δ ppm):9.5, 118.5, 121.5, 125.6, 126.2,
136.8, 139.7, 140.1, 161.2, 172.1. MS (ESI+ 70 eV m/z):
258.1 ([M]+, 100%). Elemental anal. (%), calculated: C,
60.45; H, 3.90; N, 10.85; found: C, 60.44; H,
3.92; N, 10.82.
1-(6-Nitrobenzo[d]thiazol-2-yl) -3,4-dichloro-1H- pyr-
role −2,5-dione (4 m). Yield: 67%, mp 125ꢀC, Rf = 0.54
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 8.01 (d,
J = 8.1 Hz, 1H, Ar-H), 8.25 (d, J = 8.2 Hz, 1H, Ar-H),
8.75 (s, 1H, Ar-H). 13C NMR (CDCl3, δ ppm): 118.5,
121.1, 123.6, 131.8, 137.8, 146.7, 161.2, 162.2. MS (ESI+
70 eV m/z): 344.3 ([M + 1]+. Elemental anal. (%), cal-
culated: C, 38.39; H, 0.88; N, 12.21; found: C, 38.37; H,
0.89; N, 12.24.
1-(6-Methylbenzo[d]thiazol-2-yl) -3,4- dimethyl--1H-
pyrrole −2,5-dione (4s). Yield: 80%, mp 120ꢀC, Rf = 0.66
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.22(s,
3H, CH3), 2.38(s, 6H, CH3), 7.75 (d, J = 8.1 Hz, 1H, Ar-
H), 7.79 (s, 1H, Ar-H), 8.01 (d, J = 8.2 Hz, 1H, Ar-H). 13
C
1-(6-Methoxybenzo[d]thiazol-2-yl)
pyrrolidine-2,-
NMR (CDCl3, δ ppm):9.8, 20.3, 118.5, 121.5, 126.3, 130.8,
134.8, 138.5, 150.7, 161.2, 172.2. MS (ESI+ 70 eV m/z):
272.99 ([M + 1]+, 60%), 290.07 ([M + NH4]+, 100%). Ele-
mental anal. (%), calculated: C, 61.75; H, 4.44; N, 10.29;
found: C, 61.77; H, 4.48; N, 10.27.
5-dione (4n). Yield: 74%, mp 117ꢀC, Rf = 0.65 (CH2Cl2/
MeOH, 9/1). 1H NMR (CDCl3, δ ppm): 2.82(s, 4H, (CH2)-
CO), 3.82(s, 3H, CH3), 7.13 (d, J = 8.2 Hz, 1H, Ar-H), 7.51
(d, J = 8.3 Hz, 1H, Ar-H), 7.82 (s, 1H, Ar-H). 13C NMR
(CDCl3, δ ppm): 30.8, 55.2, 117.4, 122.2, 126.2, 130.1,
143.5, 157.4, 162.7, 168.5. MS (ESI+ 70 eV m/z): 263.10
([M + 1]+, 100%). Elemental anal. (%), calculated: C,
54.95; H, 3.84; N, 10.68; found: C, 54.98; H, 3.82; N, 10.67.
1-(6-Nitrobenzo[d]thiazol-2-yl) -3,4-dimethyl-1H- pyr-
role −2,5-dione (4t). Yield: 65%, mp 135ꢀC, Rf = 0.52
1
(CH2Cl2/MeOH, 9/1). H NMR (CDCl3, δ ppm): 2.40(s,
6H, CH3), 8.10 (d, J = 8.1 Hz, 1H, Ar-H), 8.30 (d,

BOUGHELOUM ET AL.
7
J = 8.2 Hz, 1H, Ar-H), 8.60 (s, 1H, Ar-H). 13C NMR
(CDCl3, δ ppm): 9.8, 118.5, 120.5, 121.5, 130.9, 138.8,
143.4, 161.2, 171.2. MS (ESI+ 70 eV m/z): 304.13
([M + 1]+. Elemental anal. (%), calculated: C, 51.48; H,
2.99; N, 13.85; found: C, 51.45; H, 2.97; N, 13.88.
with a slight improvement in the reaction yield (25%)
within 4 hours. To further improve the yield and decrease
the reaction time, the above reaction was carried out
under many conditions.
The corresponding results are listed in Table 1.
The use of ultrasound assisted one-pot, two-step proto-
col was found to be more advantageous in terms of rate-
accelerations, loadings and reaction time (92% in
6 minutes; Table 1, entry 15) in comparison to microwave
irradiation and room temperature methods (76% in
25 minutes and 35% in 240 minutes, respectively; Table 1,
entries 19 and 20). Also, we observed that when the one-
pot, two step reaction was accelerated under ultrasound
irradiation in a shorter reaction time (6 minutes; Table 1,
entry 15) lead to a higher yield (92%) of compound (2a),
compared to a longer reaction times (Table 1, entries
5 and 14).
When the influence of solvents was investigated, we
found that only H2O was critical for the reaction effi-
ciency (Table 1, entry 5). The use of other solvents, such
as acetonitrile, tetrahydrofuran, toluene, and chloroforme
led to a lower yield of product (2a) (Table 1, entries 7-10).
As we all know, water is very green and environmental,
and using water as the solvent for the organic synthesis
could avoid the employment of some toxic solvents, such
as acetonitrile, toluene, etc.
In order to find the minimum amount of H2O required
to get maximum yield in short duration, the reaction was
carried out in different volumes of H2O and it was found
that, the minimum amount of H2O required to get the max-
imum yield of the product is 2 mL. (Table 1, entry 14).
The benzothiazole containing sulfonamide moiety
(2a) (Scheme 1) is obtained in high yields (50%–86%
yield; Table 1, entries 2-5) using a catalytic amount from
5 to 12 mmol% of Cs5HP2W18O62. The results show a sig-
nificant effect of the amount of the catalyst. It is found
that the increase of the catalytic amount of
Cs5HP2W18O62 leads to a considerably increased reaction
rate, from 45 minutes with 5 mmol% to 15 minutes using
10 mmol% of this catalyst (Table 1, entries 2-5). For quan-
tities of catalyst between 5 and 8 mmol%, the reaction
2 | RESULTS AND DISCUSSION
From the point of synthetic simplicity, one-pot reaction
could provide a far more efficient and straightforward
access to the target molecules. In the connection with our
recent work,[24] we envisioned that carboxylic acid (20)
produced in situ from sulfonamide (a) and cyclic anhy-
dride may react with 2-amino benzothiazole to form new
product (b) containing both scaffolds: sulfonamide and
benzothiazole (Scheme 1). Initially, a one-pot, one-step
protocol at room temperature was examined, using the
same already optimized conditions in previous report[24]
(5 mmol% Cs5HP2W18O62 as catalyst and water as sol-
vent) for the preparation of (2a) from sulfonamide (1a),
succinic anhydride and 2-amino benzothiazole as the
model reaction (Scheme 1).
The formation of the desired compound (2a) con-
taining benzothiazole and sulfonamide moieties was
observed with the investigated solid at room temperature,
but the yield was very unsatisfactory (<10%) (Scheme 1).
The low yield is due to the concomitant formation of
by-products, since Cs5HP2W18O62 promotes the conden-
sation of succinic anhydride once with sulfonamide (1a)
to afford cyclic imide (3a), and then with 2-amino ben-
zothiazole to give other cyclic imide (4a).
In order to improve the performance of this one-pot
reaction, it was carried out with another protocol using
two steps.
This protocol involving the reaction of sulfonamide
(1a) with succinic anhydride and Cs5HP2W18O62 in
water, followed by the in situ coupling reaction with
2-amino benzothiazole at room temperature.
It was noted that the one-pot, two-step reaction was
more effective and afforded only the desired product (2a)
SCHEME 1 Model reaction

8
BOUGHELOUM ET AL.
TABLE 1 Optimization of the one-pot, two-step reaction conditions
Entrya
1
Catalyst (mmol%)
Without
Solvent (mL)
H2O (2)
Conditions
))))
Time (min)/yield (%)b
45/traces
30/50
2
Cs5HP2W18O62(5)
Cs5HP2W18O62(6)
Cs5HP2W18O62(8)
Cs5HP2W18O62(10)
Cs5HP2W18O62(12)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
Cs5HP2W18O62(10)
H2O (2)
))))
3
H2O (2)
))))
25/61
4
H2O (2)
))))
20/69
5
H2O (2)
))))
15/86
6
H2O (2)
))))
15/86
7
CH3CN (2)
THF (2)
))))
15/48
8
))))
15/54
9
Toluene (2)
CHCl3 (2)
H2O (0.5)
H2O (1)
))))
15/58
10
11
12
13
14
15
16
17
18
19
20
))))
15/40
))))
15/60
))))
15/69
H2O (1.5)
H2O (2)
))))
15/80
))))
10/89
H2O (2)
H2O (2.5)
H2O (3)
))))
))))
06/92
10/85
))))
10/75
H2O (4)
))))
10/64
H2O (2)
RT
240/35
30/76
H2O (2)
MW
Note. The bold values indicate the best result.
aReaction conditions: sulfonamide 1a (1 mmol), succinic anhydride (2 mmol) and 2-aminobenzothiazole (1 mmol) in the presence of the indicated conditions.
bIsolated yield after workup and chromatographic purification of compound 2a.
time is 30 minutes and the yields range from 50% to 69%
yield (Table 1, entries 2-4). Furthermore, without a cata-
lyst, only traces of (2a) are detected (Table 1, entry 1).
The utility of this catalyst to achieve the one-pot, two
step reaction was affirmed not only by these results, but
with another test carried out on step 2 of the reaction.
Herein, the intermediate carboxylic acid (20a) was iso-
lated and reacted with 2-amino benzothiazole in the pres-
ence and without catalyst.
according to the literature,[26,27] coupled to diverse
cyclic anhydrides and some 2-amino benzothiazole
derivatives in the presence of 10 mmol% of
Cs5HP2W18O62 in 2 mL of water as green solvent
under ultrasound irradiation.
The benzothiazole derivatives containing sulfonamide
moiety (2a-2u) were obtained in 48% to 92% yield within
6 to 15 minutes, depending on the structures of the cyclic
anhydride and the amine (Table 2).
It should be noted that the intermediate carboxylic
acid (20a) was already obtained in our recent work[24] in
the presence of 5 mmol% Cs5HP2W18O62 as catalyst and
water as solvent. Also, we found that the second step
does take place only in the presence of this catalyst,
hence its high efficiency.
Thus, reacting all the components in the presence of
10 mmol% of Cs5HP2W18O62 in 2 mL of water under
ultrasound irradiation proved to be the optimum condi-
tions for the one-pot, two-step reaction.
The use of different cyclic anhydrides: Maleic anhy-
dride (MA), 2,3-Dichloro maleic anhydride (DCMA) and
Glutaric anhydride (GA) leads, respectively to the new
benzothiazoles containing sulfonamide moiety (2a-2d)
with 88% to 92% yield when using the 2-amino ben-
zothiazole and sulfonamide (1a). In the case of phthalic
anhydride (PA), the condensation was much slower
because of its steric effects and resulting product (2e) was
obtained with lower yield (58%; Table 2).
Similarly, in the presence of substituted 2-amino ben-
zothiazole such as 2-Amino-6-methylbenzothiazole with
the above series of cyclic anhydrides, the benzothiazoles
containing sulfonamide moiety (2f-2j) were obtained in
59%-88% yield.
To extend the use of Cesium salt of Wells-Dawson
heteropolyacid (Cs5HP2W18O62) and its catalytic reac-
tivity, the reaction conditions were applied on a series
of variously substituted sulfonamides prepared

BOUGHELOUM ET AL.
9
TABLE 2 Cs5HP2W18O62 catalyzed one-pot synthesis of new benzothiazoles containing sulfonamide moiety (2a-2u)
Benzothiazoles containing sulfonamide moiety (2a-2u)a, yield%
(Continues)

10
BOUGHELOUM ET AL.
TABLE 2 (Continued)
aReaction conditions: sulfonamide (1 mmol), cyclic anhydride (2 mmol) in the presence of Cs5HP2W18O62 (10 mmol%) as catalyst and water (2 mL) as solvent,
then 2-aminobenzothiazole derivatives (1 mmol) was added under ultrasound irradiation for both steps.
The employment of 2-amino-6-nitrobenzothiazole
gives moderate yield of product (2k) (48%), due to the
presence of the nitro group (Table 2).
Indeed, reaction of various sulfonamides (derivatives
of primary and secondary, aromatic and aliphatic or
cyclic and acyclic amines) with succinic anhydride and
2-aminobenzothiazole leads to original benzothiazole
derivatives containing sulfonamide moiety (2l-2u) with
excellent yields in the range 83%-92%.
The structures of new benzothizoles containing sul-
fonamide moiety presented in Table 2 were determined
by proton, carbon NMR and mass spectroscopy, as well
as elemental analysis.
Indeed, carrying out the reaction of substituted
2-amino benzothiazole and cyclic anhydrides under the
same conditions (10 mmol% of Cs5HP2W18O62 in 2 mL of
water under ultrasound irradiation) had led to the prepa-
ration of new benzothiazole derivatives containing cyclic
imide fragment (4a-4t) with good to excellent yields
(65%-94%) (Table 3).
The structure of compounds (4a-4t) was established
from the spectral data and the elemental analysis. (see
Supporting Information).
3 | CONCLUSION
As shown in scheme 1, when using only one-pot,
one-step protocol for the synthesis of benzothiazole
containing sulfonamide moiety (2a), we had noticed
the formation of compounds (3a) and (4a). Although
these latter compounds are considered as by-products
but of great importance, since they contain cyclic
The described procedure for the synthesis of new ben-
zothiazoles, which proceeds efficiently under ultrasound
irradiation results in a clean and useful alternative.
The results show that the one-pot reaction using
Cesium
salt
of
Wells-Dawson
heteropolyacid
(Cs5HP2W18O62) as catalyst in water as green solvent,
was effective and afforded the desired benzothiazoles
containing sulfonamide or cyclic imide moieties with
good to excellent yields. The described approach was sim-
ple and environmentally friendly.
imide
moiety
known
by
their
potential
bioactivities.[28–32]
Similar structures to compound (3a) have been
already obtained in our previous works,[22,24] but com-
pound (4a) is never mentioned in the literature.
For this purpose, we have seen that it is interesting to
synthesize such as this type of new molecule (4a), espe-
cially that it contains the benzothiazole fragment (the
title compound).
ORCID
Chafika Bougheloum https://orcid.org/0000-0001-6042-
9579

BOUGHELOUM ET AL.
11
TABLE 3 Synthesis of benzothiazole derivatives containing cyclic imide
Benzothiazoles containing cyclic imide moiety (4a-4t)a, yield%
aReaction conditions: 2-aminobenzothiazole derivatives (1 mmol), cyclic anhydride (2 mmol) in the presence of Cs5HP2W18O62 (10 mmol%) as catalyst and
water (2 mL) as solvent under ultrasound irradiation.

12
BOUGHELOUM ET AL.
[23] C. Bougheloum, S. Guezane Lakoud, R. Belghiche, A. Messalhi,
Phosphorus Sulfur Silicon Relat. Elem. 2016, 191, 1344.
[24] N. Benali, S. Alioua, C. Bougheloum, R. Belghiche,
A. Messalhi, Synth. Commun. 2018, 48, 3099.
[25] (a) D. Lyon, W. Miller, T. Novet, P. Domaille, E. Evitt,
D. Johnson, R. Finke, J. Am. Chem. Soc. 1991, 113, 7209;
(b) G. Baronetti, L. Briand, U. Sedran, H. Thomas, Appl. Catal. A
Gen. 1998, 173, 265; (c) T. Okuhara, T. Nishimura, H. Watanabe,
M. Misono, J. Mol. Catal. 1992, 74, 247; (d) M. Abbessi. Ph.D.
Thesis, Paris VI University, (France) (1989); (e) G. D. Yadav,
C. K. Mistry, J. Mol. Catal. A Chem. 2001, 172, 135.
REFERENCES
[1] B. Soni, A. Bhandari, M. S. Ranawat, P. Sharma, R. Singh,
S. Sharma, R. P. Prajapat, Pharmacophore 2011, 2, 36.
[2] H. A. Bhuva, S. G. Kini, J. Mol. Graphics Modell. 2010, 29, 32.
[3] R. Paramashivappa, P. P. Kumar, P. V. Rao, A. S. Rao, Bioorg.
Med. Chem. Lett. 2003, 13, 657.
[4] N. Siddiqui, A. Rana, S. A. Khan, M. A. Bhat, S. E. Haque, Bio-
org. Med. Chem. Lett. 2007, 17, 4178.
[5] H. Moreno-Díaz, R. Villalobos-Molina, R. Ortiz-Andrade,
D. Díaz-Coutiño, J. L. Medina-Franco, S. P. Webster,
S. Estrada-Soto, M. Ibarra-Barajas, I. León-Rivera,
G. Navarrete-Vázquez, Bioorg. Med. Chem. Lett. 2008, 18, 2871.
[6] C. Wu, J. Wei, K. Gao, Y. Wang, Bioorg. Med. Chem. 2007, 15,
2789.
[26] (a) M. Abdaoui, G. Dewynter, N. Aouf, G. Favre, A. Morère,
J. L. Montero, Bioorg. Med. Chem. 1996, 4, 1227;
(b) M. Abdaoui, G. Dewynter, J. L. Montero, Tetrahedron Lett.
1996, 37, 5695.
[7] O. Diouf, P. Depreux, D. Lesieur, J. H. Poupaert,
D. H. Caignard, Eur. J. Med. Chem. 1995, 30, 715.
[8] R. B. Sparks, P. Polam, W. Zhu, M. L. Crawley, A. Takvorian,
E. McLaughlin, M. Wei, P. J. Ala, L. Gonneville, N. Taylor,
et al.,Bioorg. Med. Chem. Lett. 2006, 17, 736.
[9] M. S. Yar, Z. H. Ansari, Acta Pol. Pharm. 2009, 66, 387.
[10] C. A. Zarate, J. L. Payne, J. Quiroz, J. Sporn, K. Denicoff,
D. Luckenbaugh, D. Charney, H. K. Manji, Am. J. Psychiatry
2004, 161, 171.
[11] V. F. Carvalho, E. O. Barreto, M. F. Serra, R. S. Cordeiro,
M. A. Martins, Z. B. Fortes, P. M. E Silva, Eur. J. Pharmacol.
2006, 549, 173.
[12] W. Rooth, T. Srikrishnan, J. Chem. Crystallogr. 1999, 29, 1187.
[13] S. J. Kim, M. H. Jung, K. H. Yoo, J. H. Cho, C. H. Oh, Bioorg.
Med. Chem. Lett. 2008, 18, 5815.
[27] G. Wang, C. Li, J. Li, X. Jia, Tetrahedron Lett. 2009, 50, 1438.
[28] M. Laronze, M. Boisbrun, S. Léonce, B. Pfeiffer, P. Renard,
O. Lozach, L. Meijer, A. Lansiaux, C. Bailly, et al., Bioorg. Med.
Chem. 2005, 13, 2263.
[29] A. E. Amr, N. M. Sabry, M. M. Abdulla, Monatsh. Chem. 2007,
138, 699.
[30] F. Zentz, A. Valla, R. Le Guillou, R. Labia, A. G. Mathot,
D. Sirot, Il Farmaco. 2002, 57, 421.
[31] A. A.-M. Abdel-Aziz, K. E. H. El Tahir, Y. A. Asiri, Eur.
J. Med. Chem. 2011, 46, 1648.
[32] A. A.-M. Abdel-Aziz, A. S. El-Azab, S. M. Attia, A. M. Al-
Obaid, M. A. Al-Omar, H. I. El-Subbagh, Eur. J. Med. Chem.
2011, 46, 4324.
[14] A. M. Abdel-Aziz, A. S. El-Azab, M. Ceruso, C. T. Supuran,
Bioorg. Med. Chem. Lett. 2014, 24, 5185.
[15] M. A. Abdelgawad, P. F. Lamie, O. M. Ahmed, Med. Chem.
2016, 6, 604.
[16] D. J. Abraham, Burger's Medicinal Chemistry & Drug Discovery,
John Wiley and Sons, Hoboken 2003.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
[17] A. K. Gadad, C. S. Mahajanshetti, S. Nimbalkar,
A. Raichurkar, Eur. J. Med. Chem. 2000, 35, 853.
How to cite this article: Bougheloum C,
Alioua S, Belghiche R, Benali N, Messalhi A. An
efficient green synthesis of new benzothiazoles
containing sulfonamide or cyclic imide moieties.
J Heterocyclic Chem. 2019;1–12. https://doi.org/10.
1002/jhet.3753
[18] F. Zani, P. Vicini, Arch. Pharm. 1998, 331, 219.
[19] K. C. Majumdar, N. De, S. Mondal, Synthesis 2009, 18, 3127.
[20] N. Nayeem, G. Denny, Der Pharma Chemica. 2012, 4, 1277.
[21] D. A. Ibrahim, D. S. Lasheen, M. Y. Zaky, A. W. Ibrahim,
D. Vullo, M. Ceruso, C. T. Supuran, D. A. Abou El Ella, Bioorg.
Med. Chem. 2015, 23, 4989.
[22] C. Bougheloum, R. Belghiche, A. Messalhi, Phosphorus Sulfur
Silicon Relat. Elem. 2015, 190, 269.