Synthesis of novel benzimidazole and benzothiazole derivatives

Article abstract of DOI:10.3987/COM-13-12873

1-(Benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2) were used as potential scaffolds for biologically interesting azoloazine derivatives via their reaction with the diazonium salts

Full text of DOI:10.3987/COM-13-12873

HETEROCYCLES, Vol. 89, No. 1, 2014
113
HETEROCYCLES, Vol. 89, No. 1, 2014, pp. 113 - 125. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 28th October, 2013, Accepted, 25th November, 2013, Published online, 10th December, 2013
DOI: 10.3987/COM-13-12873
SYNTHESIS OF NOVEL BENZIMIDAZOLE AND BENZOTHIAZOLE
DERIVATIVES
Ahmed F. Darweesh,a Ahmed E. M. Mekky,a,b Amani A. Salman,a and Ahmad
M. Faraga,*
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613,
b
Egypt; On leave to Chemistry Department, Faculty of Science, King Abdulaziz
University, North Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia
*Corresponding author: E-mail: afarag49@yahoo.com
Abstract
–
1-(Benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and
1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2) were used
as potential scaffolds for biologically interesting azoloazine derivatives via their
reaction with the diazonium salts of 5-aminopyrazole, 5-amino[1,2,4]triazole and
2-aminobenzimidazole. Coupling of the β-ketosulfones 1 or 2 with diazotized
aromatic amines afforded the corresponding arylhydrazone derivatives which have
been utilized as versatile building blocks for the synthesis of biologically
interesting pyridazine ring systems.
INTRODUCTION
Benzothiazole and benzimidazole ring systems are very important classes of compounds due to their wide
spectrum of biological activities. Many of their derivatives are used as antiviral,1-4 antifungal,5-8
antitumor9-12 and antihelminthic agents in veterinary medicinel.13-15 Some of benzimidazole derivatives
are now included in many of commercialized drugs.16-18 On the other hand, β-ketosulfone moiety is
readily available from a variety of precursor functionalities and displays a broad range of synthetic
versatility.19,20 These are also important group of intermediates in Michael and Knoevengel reactions.21
Compounds containing β-ketosulfones moiety have attracted considerable attention of synthetic chemists
in the past decade.22 As part of our ongoing research program directed towards the synthesis of a variety
of heterocycles for biological evaluation,23,34 we report here on the synthesis of several heterocyclic ring
systems incorporation benzothiazole and benzimidazole moieties starting from the versatile hitherto
unreported 1-(benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-benzimidazol-2-yl)-2-
(phenylsulfonyl)-1-ethanone (2).

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RESULTS AND DISCUSSION
Treatment of each of the 1-(benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-
benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2) with the diazonium salts of 3-(4-chlorophenyl)-5-
amino-1H-pyrazole (3) and 4-cyano-5-amino-1H-pyrazole (4) afforded the corresponding non-isolable
azo intermediates 5 and 6, respectively. The latter intermediates underwent in situ intramolecular
cyclization, yielding the corresponding pyrazolo[5,1-c][l,2,4]triazine derivatives 7a,b and 8a,b,
respectively (Scheme 1). The structures of the isolated products 7a,b and 8a,b were established on the
basis of their elemental analyses and spectral data. For example, the IR spectrum of the compounds 7b
and 8b revealed, in each case, no bands corresponding to the endocyclic NH group and showed
absorption band due to nitrile group near 2233 cm-1. Their mass spectra showed, in each case, a peak
1
corresponding to the molecular ion. Their H NMR spectra revealed, in each case, a singlet signal near
8.64 ppm due pyrazole CH proton and a multiplet signal corresponding to aromatic protons in the range
7.20-8.14 ppm.
R'
N
O
N
R'
O
N2+ Cl
NH
O
O
S
O
S
H
°
0-5 C
N
Ph
+
NH
R
R
Ph
Py
O
N
N
X
N
X
1; X= S
2; X= NMe
3; R= C6H4Cl-p, R'= H
4; R= H, R'= CN
5; X= S
6; X= NMe
-H2O
O
O
7; X= S
N
N
S
8; X= NMe
R
N
R'
Ph
N
a
b
C6H4Cl-p
H
H
CN
R'
N
X
R
Sheme 1
In a similar manner, the β-ketosulfones 1 and 2 reacted with the diazonium salts of 5-amino-l,2,4-triazole
(9) and afforded products identified as 4-(benzothiazol-2-yl)-3-(phenylsulfonyl)-[1,2,4]triazolo[5,1-c]-
[1,2,4]triazine (12) and 4-(1-methylbenzimidazol-2-yl)-3-(phenysulfonyl)-[1,2,4]triazolo[5,1-c][1,2,4]-
triazine (13), respectively (Scheme 2).
The structures of the reaction products 12 and 13 were established on the basis of their elemental analyses
and spectral data (see Experimental part).

HETEROCYCLES, Vol. 89, No. 1, 2014
115
O
N2 NO3
O O
S
O O
S
N
N
N
0-5 °C
Py
N
N
Ph
+
Ph
NH
H
NH
N
X
O
N
N
X
1; X= S
2; X= NMe
9
10; X= S
11; X= NMe
N
N
N
N
N
-H2O
X
O
S
O
N Ph
12; X= S
13; X= NMe
Scheme 2
Also, the β-ketosulfones 1 and 2 reacted with the diazonium salt of 2-amino-1H-benzimidazole (14) to
afford the corresponding 4-(benzothiazol-2-yl)-3-(phenylsulfonyl)-1,2,4-triazino[4,3-a]benzimidazole
(17) and 4-(1-methylbenzimidazol-2-yl)-3-(phenylsulfonyl)-1,2,4-triazino[4,3-a]benzimidazole (18),
respectively (Scheme 3). The mass spectra of the reaction products showed, in each case, a peak
corresponding to the molecular ion. The 1H NMR spectrum of compound 18, taken as an example of the
prepared compounds revealed a singlet signal at δ 4.02 due to N-CH3 protons and a multiplet signals at δ
7.38-8.16 due to aromatic protons.
O O
S
N
O
O O
S
N
N
N
N
Ph
+
Ph
0-5 °C
Py
N2 HSO4
H
NH
O
X
N
H
N
1; X= S
2; X= NMe
X
14
N
N
15; X= S
16; X= NMe
N
N
O
-H2O
S
X
O
Ph
N
17; X= S
18; X= NMe
Scheme 3
Similar to their behavior towards diazotized heterocyclic amines 3, 9, 14, the β-ketosulfones 1 and 2
coupled with diazotized aromatic amines derivatives 19a-c, to give the corresponding arylhydrazone

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HETEROCYCLES, Vol. 89, No. 1, 2014
derivatives 22a-c and 23a-c, respectively (Scheme 4). The structures of the compounds 22a-c and 23a-c
were established on the basis of their elemental analyses and spectral data (see Experimental part).
O
N
O
N
X
N
X
O
S
Ph
O
S
Ph
O
O
O
O
O
N
+
S
N
N
N
NH
N
Ph
0 °C
X
EtOH
R
1; X= S
2; X= NMe
19a-c
R
R
22a-c; X= S
23a-c; X= NMe
20a-c; X= S
21a-c; X= NMe
19, 22, 23
R
a
b
c
H
Cl
Me
Scheme 4
The obtained arylhydrazones 22a-c and 23a-c have been utilized as building blocks for the synthesis of
biologically interesting pyridazine ring system. Thus, the arylhydrazones 22a-c and 23a-c undergo
cyclocondensation with 2-cynomethylbenzothiazole (24) under both heating in ethanol and under
microwave irradiation conditions, to afford the corresponding pyridazine derivatives 27a-c and 28a-c,
respectively in almost quantitative yield (Scheme 5). The IR spectra of the obtained compounds revealed,
in each case, absorption band near 3332 cm-1 due to NH function whereas their 1H NMR spectra revealed,
in each case, a singlet signal near 11.88 ppm due NH protons. Other signals appeared at their respective
chemical shifts.
O
N
X
O
S
O
S
N
NH
Ph
CN
S
N
reflux/4 h
N
+
C N
HN
N
N
X
microwave/15 min
R
24
Ph S
O
R
O
22a-c; X= S
23a-c; X= NMe
25a-c; X= S
26a-c; X= NMe
S
N
N
NH
27; X= S
28; X= NMe
R
X
N
N
Ph
S
R
a
b
c
H
Cl
Me
O
O
Scheme 5

HETEROCYCLES, Vol. 89, No. 1, 2014
117
Similarly, condensation of the arylhydrazones 22a-c and 23a-c with malononitril afforded the
corresponding 1-aryl-4-(benzothiazol-2-yl)-5-(cyano)-1,6-dihydro-6-imino-3-(phenylsulfonyl)pyridazine
(31a-c) and 1-aryl-4-(1-methylbenzimidazol-2-yl)-5-(cyano)-1,6-dihydro-6-imino-3-(phenylsulfonyl)-
pyridazine (32a-c), respectively (Scheme 6). The structures of the products 31a-c and 32a-c were
established on the basis of their elementals analysis and spectral data (see Experimental part).
O
N
X
O
S
O
NC
N
NH
Ph
CN
CN
N
X
reflux/4 h
C
N
+
HN
N
R
microwave/15 min
Ph
S
O
O
R
29a-c; X= S
30a-c; X= NMe
22a-c; X= S
23a-c; X= NMe
NC
N
N
NH
31; X= S
32; X= NMe
X
R
N
Ph
S
O O
a
b
c
H
Cl
Me
R
Scheme 6
EXPERIMENTAL
Melting points were determined in open glass capillaries with a Gallenkamp apparatus. The IR spectra
were recorded using KBr disks on a Pye Unicam SP 3-300 or a Shimadzu FTIR 8101 PC IR
spectrophotometer. The NMR spectra were recorded with a Varian Mercury VXR-300 NMR
spectrometer at 300 and 75 MHz (1H and 13C NMR spectra, respectively) using CDCl3 and DMSO-d6 as
solvents. Chemical shifts were related to that of the solvent. Mass spectra (EI) were obtained at 70 eV
with a Shimadzu GCMQP 1000 EX spectrometer. TLC analyses were performed using precoated silica
gel 60778 plates (Fluka), and the spots were visualized with UV light at 254 nm. Fluka silica gel 60741
(70–230 mesh) was used for flash column chromatography. Microwave experiments were carried out
using a CEM Discover LabMate microwave apparatus (300 W with ChemDriver Software). 2-Bromo-1-
(1-methyl-1H-benzimidazol-2-yl)ethanone35 3-(4-chlorophenyl)-(1H)-pyrazole-5-diazonium chloride
(3),36 4-cyano-1H-pyrazole-3-diazonium chloride (4),37 1H-1,2,4-triazole-5-diazonium salt (9),37 1H-
benzimidazol-2-diazonium salt (14),37 benzothiazole-2-acetonitrile (24),38 2-bromo-1-benzothiazol-2-yl-
ethanone,39 were prepared following literature procedures.

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HETEROCYCLES, Vol. 89, No. 1, 2014
1-(Benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1). A mixture of 2-bromo-1-benzothiazol-2-yl-
ethanone (2.56 g, 10 mmol) and sodium benzenesulfinate (1.64 g 10 mmol), in absolute EtOH (20 mL)
was refluxed for 3 h, and then left to cool to rt. The precipitated solid was filtrated off, washed with water
and dried. Recrystallization from EtOH afforded the title compound. Yield (79%); mp 142 °C; IR (KBr)
vmax/cm-1: 1690 (C=O), 1325, 1160 (SO2); 1H NMR (DMSO-d6) δ 5.41 (s, 2H, CH2), 7.35−8.03 (m, 9H,
13
ArH); C NMR (DMSO-d6) δ 60.45, 121.66, 123.43, 124.60, 128.34, 129.34, 133.56, 136.01, 138.69,
145.47, 155.12, 182.34; MS (m/z, %): 317 (M+, 23.7). Anal. Calcd for C15H11NO3S2 (317.38): C, 56.76;
H, 3,49; N, 4.41; S, 20.21%. Found: C, 56.55; H, 3.44; N, 4.49; S, 20.23 %
1-(1-Methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2). To
a
solution of
triethylbenzylammonium chloride (TEBAC) (0.2 g) in MeCN (25 mL) was added sodium
benzenesulfinate (1.80 g, 12 mmol) and the suspension was stirred at rt for 15 min. To this mixture was
added a solution of 2-bromo-1-(1-methyl-1H-benzimidazol-2yl)ethanone (2.58 g 10 mmol) in MeCN (20
mL). The progress of the reaction was monitored by TLC till the disappearance of the reactants. After the
reaction was complete (about 1h), the mixture was filtered off, and the solid material (NaBr) was washed
with MeCN. The washings along with mother liquor were mixed and evaporated under reduced pressure.
The residue was taken up in CH2Cl2 (50 mL) and washed with water (2 × 10 mL). The organic layer was
separated and dried over anhydrous MgSO4 then evaporated under reduced pressure. The residue was
crystallized from hexane-benzene (9:1) to afford 2. Yield (90%), mp 159−161 °C; IR (KBr) νmax/cm-1:
1
1690 (C=O), 1325 and 1160 (SO2); H NMR (DMSO-d6) δ 4.03 (s, 3H, NCH3), 5.41 (s, 2H, CH2),
13
7.38−7.95 (m, 9H, ArH); C NMR (DMSO-d6) δ 31.97, 60.45, 111.01, 120.43, 123.31, 128.32, 129.34,
133.56, 134.01, 138.29, 138.41, 140.12, 179.34; MS (m/z, %): 314 (M+, 29.2). Anal. Calcd for
C16H14N2O3S (314.36): C, 61.13; H, 4.49; N, 8.91; S, 10.20%. Found: C, 61.16; H, 4.46; N, 8.93; S,
10.18%.
Reaction of the β-ketosulfones 1 and 2 with diazotized heterocyclic amines.
General procedure:
To a stirred cold solution (ice bath at 0−5 °C) of the appropriate β-ketosulphone 1 or 2 (2 mmol), in
pyridine (30 mL) was added the appropriate heterocyclic diazonium salt of the heterocyclic amines 3, 4, 9
and 14 (2 mmol) portionwise over a period of 30 min. The reaction mixture was stirred for further 3 h at
0−5 °C. The precipitate solid was collected by filtration, washed with water and dried. Recrystallization
from DMF/H2O afforded the corresponding fused ring systems 7a,b, 8a,b, 12, 13, 17 and 18,
respectively.
4-(Benzothiazol-2-yl)-7-(4-chlorophenyl)-3-(phenylsulfonyl)pyrazolo[5,1-c][1,2,4]triazine (7a): Yield
1
(78%), mp 170−172 °C; IR (KBr) νmax/cm-1: 1597 (C=N); H NMR (DMSO-d6) δ 6.99 (s, 1H,

HETEROCYCLES, Vol. 89, No. 1, 2014
119
pyrazole-8-CH), 7.42-8.13 (m, 13H, ArH’s); MS (m/z, %): 503 (M+, 100%). Anal. Calcd for
C24H14N5ClO2S2 (503.98): C, 57.20; H, 2.80; N, 13.90; S, 12.72%. Found: C, 57.24; H, 2.83; N, 13.94; S,
12.68%.
4-(Benzothiazol-2-yl)-3-(phenylsulfonyl)pyrazolo[5,1-c]-[1,2,4]triazine-8-carbonitrile (7b): Yield
1
(79%), mp 152−154 °C; IR (KBr) νmax/cm-1: 2233 (C≡N); H NMR (DMSO- d6) δ 7.42−8.14 (m, 9H,
ArH’s), 8.64 (s, 1H, pyrazole-7-CH); MS (m/z, %): 418 (M+,100%); Anal. Calcd for C19H10N6O2S2
(418.45): C, 54.54; H, 2.41; N, 20.08; S, 15.33%. Found: C, 54.49; H, 2.40; N, 20.05; S, 15.35 %.
7-(4-Chlorophenyl)-4-(1-methyl-1H-benzimidazol-2-yl)-3-(phenylsulfonyl)pyrazolo[5,1-c][1,2,4]tri-
1
azine (8a): Yield (72%), mp 188−189 °C.IR (KBr) νmax/cm-1: 1597 (C=N); H NMR (DMSO-d6) δ 4.02
(s, 3H, NCH3), 6.89 (s, 1H, pyrazole-8-CH), 7.20−7.89 (m, 13H, ArH’s); MS (m/z, %): 500 (M+, 100%);
Anal. Calcd for C25H17N6ClO2S (500.96): C, 59.94; H, 3.42; N, 16.78; S, 6.40%. Found: C, 59.96; H,
3.39; N, 16.80; S, 6.41%.
4-(1-Methyl-1H-benzimidazol-2-yl)-3-(phenylsulfonyl)pyrazolo[5,1-c][1,2,4]triazine-8-carbonitrile
(8b): Yield (77%), mp 168−170 °C; IR (KBr) νmax/cm-1: 2233 (C≡N); 1H NMR (DMSO-d6) δ 4.02 (s, 3H,
NCH3), 7.20−8.04 (m, 9H, ArH’s), 8.64 (s, 1H, pyrazole-7-CH). MS (m/z, %): 415 (M+, 100%); Anal.
Calcd for C20H13N7O2S (415.43): C, 57.82; H, 3.15; N, 23.60; S, 7.72%. Found: C, 57.85; H, 3.18; N,
23.62; S, 7.75%.
4-(Benzothiazol-2-yl)-3-(phenylsulfonyl)-[1,2,4]triazolo[5,1-c][1,2,4]triazine (12): Yield (72%), mp
205−206 °C; IR (KBr) νmax /cm–1: 1607 (C=N); 1H NMR (DMSO-d6) δ 7.43−8.14 (m, 9H, ArH’s), 8.57
13
(s, 1H, triazole-7-CH). C NMR (DMSO-d6) δ 120.23, 121.53, 124.30, 125.32, 128.10, 129.57, 133.43,
133.02, 136.22, 152.54, 156.04, 156.05,156.63; MS (m/z, %): 394 (M+, 100%); Anal. Calcd for
C17H10N6O2S2 (394.43): C, 51.77; H, 2.56; N, 21.31; S, 16.26%. Found: C, 51.73; H, 2.59; N, 21.34; S,
16.23%.
4-(1-Methylbenzimidazol-2-yl)-3-(phenysulfonyl)-[1,2,4]-triazolo[5,1-c][1,2,4]-triazine (13): Yield
1
(72%), mp 160−162 °C; IR (KBr) νmax/cm-1: 1607 (C=N); H NMR (DMSO-d6) δ 4.02 (s, 3H, NCH3),
13
7.20−8.04 (m, 9H, ArH’s), 8.47 (s, 1H, triazole-7-CH); C NMR (DMSO-d6) δ 31.97 (NCH3), 111.67,
121.43, 123.60, 128.10, 129.22, 133.36, 134.01, 136.02, 140.54 (aromatic carbons), 141.11 (C-2
benzimidazole ring), 148.45, 148.57 (-N-CH, triazole ring); MS (m/z, %): 391 (M+, 100%); Anal. Calcd
for C18H13N7O2S (391.41): C, 55.23; H, 3.35; N, 25.05; S, 8.19%. Found: C, 55.19; H, 3.29; N, 25.09; S,
8.21%.
4-(Benzothiazol-2-yl)-3-(phenylsulfonyl)-[1,2,4]triazino[4,3-a]benzimidazole (17): Yield (70%), mp
1
166−167 °C; IR (KBr) νmax/cm-1: 1607 (C=N). H NMR (DMSO-d6) δ 7.41−8.16 (m, 13H, ArH’s); MS
(m/z, %): 443(M+, 100%); Anal. Calcd for C22H13N5O2S2 (443.50); C, 59.58; H, 2.95; N, 15.79; S,
14.46%. Found: C, 59.53; H, 2.98; N, 15.76; S, 14.42%.

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4-(1-Methylbenzimidazol-2-yl)-3(phenylsulfonyl)-1,2,4-triazino[4,3-a]benzimidazole (18): Yield
1
(70%), mp 175−176 °C; IR (KBr) νmax/cm-1: 1607 (C=N); H NMR (DMSO-d6) δ 4.02 (s, 3H, NCH3),
7.38−7.94 (m, 13H, ArH’s); MS (m/z, %): 440 (M+, 100%); Anal. Calcd for C23H16N6O2S (440.48): C,
62.72; H, 3.66; N, 19.08; S, 7.28%. Found: C, 62.68; H, 3.64; N, 19.12; S, 7.33%.
Reaction of the β-ketosulfones 1 and 2 with arene diazonium chlorides (19a-c). To a stirred solution
of the appropriate ketosulfone 1 or 2 (20 mmol), in EtOH (50 mL) was added sodium acetate trihydrate (8
g). After stirring for 10 min, the mixture was cooled to 0 °C then treated with the appropriate arene
diazonium salt 19 [prepared by diazotizing the corresponding aromatic amine (20 mmol) in hydrochloric
acid (6M, 6 mL) with sodium nitrite solution [(1.4 g, 20 mmol), in H2O (15 mL)]. The addition of the
diazonium salt was carried out with rapid stirring over a period of 30 min. The reaction mixture was
stirred for further 2 h at 0 °C, and then left for 6 h at 4 °C in a refrigerator. The resulting solid was
collected by filtration, washed thoroughly with water then dried. The crude product was recrystallized
from EtOH to afford the corresponding hydrazone derivatives 22a-c and 23a-c, respectively.
1-(Benzothiazol-2-yl)-2-(2-phenylhydrazono)-2-(phenylsulfonyl)ethanone (22a): Yield (80%), mp
180−182 °C; IR (KBr) νmax/cm-1: 3215 (NH), 1630 (CO), 1597 (C=N); 1H NMR (DMSO-d6) δ 7.07−8.33
(m, 14H, ArH’s), 11.11 (s, 1H, D2O-exchangable, NH); 13C NMR (DMSO-d6) δ 113.05, 120.94, 122.74,
124.35, 125.29, 128.40, 129.20, 129.28, 133.52, 138.27, 139.40, 142.16, 160.25, 162.67, 182.35, 154.21;
MS (m/z, %): 421 (M+, 100%); Anal. Calcd for C21H15N3O3S2 (421.49): C, 59.84; H, 3.59; N, 9.97; S,
15.21%. Found: C, 59.79; H, 3.62; N, 10.00; S, 15.23%
1-(Benzothiazol-2-yl)-2-(2-(4-chlorophenyl)-hydrazono)-2-(phenylsulfonyl)ethanone (22b): Yield
(68%), mp 210−212 °C; IR (KBr) νmax/cm-1: 3243 (NH), 1634 (CO), 1611 (C=N); 1H NMR (DMSO-d6) δ
7.09−8.14 (m, 13H, ArH’s), 11.08 (s, 1H, D2O-exchangable, NH); 13C NMR (DMSO-d6) δ 116.39,
119.31, 122.82, 123.41, 125.13, 125.44, 127.93, 128.1, 128.87, 129.36, 133.79, 136.59, 139.74, 140.67,
141.24, 152.46, 181.8; MS (m/z, %): 455 (M+, 100%); Anal. Calcd for C21H14ClN3O3S2 (455.94): C,
55.32; H, 3.09; N, 9.22; S, 14.07%. Found: C, 55.30; H, 3.11; N, 9.26; S, 14.05 %.
1-(Benzothiazol-2-yl)-2-(phenylsulfonyl)-2-(2-p-tolylhydrazono)ethanone (22c): Yield (74%), mp
188−190 °C; IR (KBr) νmax/cm-1: 3227 (NH), 1637 (CO), 1601 (C=N); 1H NMR (DMSO-d6) δ 2.32 (s, 3H,
13
CH3), 6.48−8.14 (m, 13H, ArH’s), 11.10 (s, 1H, D2O-exchangable, NH); C NMR (DMSO-d6) δ 20.52,
117.58, 123.34, 125.26, 127.41, 127.84, 128.22 128.66, 129.39, 129.96, 133.62, 134.61, 135.9, 136.45,
139.91, 141.15, 152.85, 182.43; MS (m/z, %): 435 (M+, 100%); Anal. Calcd for C22H17N3O3S2 (435.52):
C, 60.67; H, 3.93; N, 9.65; S, 14.72%. Found: C, 60.71; H, 3.91; N, 9.68; S, 14.74%.
1-(1-Methyl-1H-benzimidazol-2-yl)-2-(2-phenylhydrazono)-2-(phenylsulfonyl)ethanone (23a): Yield
(74%), mp 204−206 °C; IR (KBr) νmax/cm-1: 3240 (NH), 1648 (CO), 1611 (C=N); 1H NMR (DMSO-d6) δ

HETEROCYCLES, Vol. 89, No. 1, 2014
121
13
4.02 (s, 3H, NCH3), 6.79−7.86 (m, 14H, ArH’s), 11.02 (s, 1H, D2O-exchangable, NH). C NMR
(DMSO-d6) δ 31.95, 111.67, 114.62, 121.40, 121.43, 123.60, 128.10, 129.11, 129.22, 133.36, 134.01,
137.05, 139.45, 141.11, 142.36, 145.21, 182.34; MS (m/z, %): 418 (M+, 100%); Anal. Calcd for
C22H18N4O3S (418.47): C, 63.14; H, 4.34; N, 13.39; S, 7.66%. Found: C, 63.12; H, 4.31; N, 13.36; S,
7.70%
2-(2-(4-Chlorophenyl)hydrazono)-1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)ethanone
(23b): Yield (75%), mp 210−212 °C; IR (KBr) νmax/cm-1: 3251 (NH), 1648 (CO), 1612 (C=N); 1H NMR
(DMSO-d6) δ 4.02 (s, 3H, NCH3), 7.08−7.83 (m, 13H, ArH’s), 11.10 (s, 1H, D2O-exchangable, NH); 13C
NMR (DMSO-d6) δ 32.13, 111.88, 116.02, 121.61, 124.25, 126.92, 127.05, 128.01, 128.12, 129.25, 129.4,
133.65, 136.97, 137.67, 140.92, 141.46, 145.18, 180.44; MS (m/z, %): 452 (M+, 100%); Anal. Calcd for
C22H17ClN4O3S (452.91): C, 58.34; H, 3.78; N, 12.37; S, 7.08%. Found: C, 58.32; H, 3.81; N, 12.39; S,
7.05%
1-(1-Methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-2-(2-p-tolylhydrazono)ethanone (23c): Yield
(76%), mp 180−182 °C; IR (KBr) νmax/cm-1: 3247 (NH), 1638 (CO), 1611 (C=N); 1H NMR (DMSO-d6) δ
2.32 (s, 3H, CH3), 4.02 (s, 3H, NCH3), 6.49−7.83 (m, 13H, ArH’s), 11.12 (s, 1H, D2O-exchangable, NH);
MS (m/z, %): 432 (M+, 100%); Anal. Calcd for C23H20N4O3S (432.49): C, 63.87; H, 4.66; N, 12.95; S,
7.41%. Found: C, 63.83; H, 4.69; N, 12.97; S, 7.45%.
Reactions of the hydrazones 22a-c and 23a-c with (benzothiazol-2-yl)acetonitrile (24) and
malononitrile.
(A)-Thermal method
General procedure:
To a solution of the appropriate hydrazone 22 or 23 (10 mmol) and (benzothiazol-2-yl)acetonitrile (24) or
malononitrile (10 mmol), in EtOH (50 mL), was added few drops of piperdine. The reaction mixture was
refluxed for 3-4 h, then poured into ice cold water, and neutralized with dil. HCl. The resulting solid
product was collected by filtration washed with EtOH, dried and finally recrystalized from DMF, to
afford the corresponding pyridazine derivatives 27a-c, 28a-c, 31a-c, and 32a-c, respectively.
(B)-Microwave method (MW)
General procedure:
A mixture of the appropriate hydrazone 22a or 23a (1mmol) and (benzothiazol-2-yl)acetonitrile (24) or
malononitrile (1 mmol) and a catalytic amount of triethylamine was added in a process vial. The vial was
capped properly and irradiated under the appropriate condition (17.2 bars, 150 °C) for 15 min. The
reaction mixture was left to cool then poured into ice cold water, and neutralized with dil. HCl. The
resulting solid product was collected by filtration washed with ethanol, dried and recrystallized from

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DMF, to afford the pyridazine derivative 27a, 28a, 31a and 32a, respectively. The isolated products were
found to be identical in all respects [mp, mixture mp and spectra] with those obtained by method (A)
above.
4,5-(Bisbenzothiazol-2-yl)-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(phenyl)pyridazine (27a): Yield
1
(MW) 79%; yield (thermally) 70%, mp 258−260 °C; IR (KBr) νmax/cm-1: 3332 (NH), 1620 (C=N); H
NMR (DMSO-d6) δ 6.74−8.14 (m, 18H, ArH’s), 11.88 (s, 1H, D2O-exchangable, NH); MS (m/z, %): 577
(M+, 100%); Anal. Calcd for C30H19N5O2S3 (577.70): C, 62.37; H, 3.32; N, 12.12; S, 16.65%. Found: C,
62.35; H, 3.34; N, 12.08; S, 16.68%
4,5-(Bisbenzothiazol-2-yl)-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(4-chlorophenyl)pyridazine
1
(27b): Yield (65%), mp > 300 °C; IR (KBr) νmax/cm-1: 3339 (NH), 1610 (C=N); H NMR (DMSO-d6) δ
6.60−8.14 (m, 17H, ArH’s), 11.82 (br. s, 1H, D2O-exchangable, NH); MS (m/z, %): 611 (M+, 100%);
Anal. Calcd for C30H18ClN5O2S3 (612.14): C, 58.86; H, 2.96; N, 11.44; S, 15.71%. Found: C, 58.83; H,
2.97; N, 11.41; S, 15.75%.
4,5-(Bisbenozthiazol-2-yl)-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(4-methylphenyl)pyridazine
(27c): Yield (72%), mp > 300 °C; IR (KBr) νmax /cm-1: 3328 (NH), 1598 (C=N); 1H NMR (DMSO-d6) δ
2.32 (s, 3H, CH3), 6.42−8.14 (m, 17H, ArH’s), 11.80 (s, br, 1H, D2O-exchangable, NH); MS (m/z, %):
591 (M+, 100%); Anal. Calcd for C31H21N5O2S3 (591.73): C, 62.92; H, 3.58; N, 11.84; S, 16.26%. Found:
C, 62.89; H, 3.61; N, 11.85; S, 16.24%.
5-(Benzothiazol-2-yl)-1,6-dihydro-6-imino-3-(1-methylbenzimidazol-2-yl)-3-(phenylsulphonyl)-1-
(phenyl)pyridazine (28a): Yield (MW) 82%; yield (thermally) 75%, mp 258−260 °C; IR (KBr)
1
νmax/cm-1: 3330 (NH), 1645 (CO); H NMR (DMSO-d6) δ 4.02 (s, 3H, NCH3), 6.67- 8.14 (m, 18H,
ArH’s), 11.85 (br. s, 1H, D2O-exchangable, NH); 13C NMR (DMSO-d6) δ 32.03, 111.43, 113.32, 120.23,
123.25, 123.48, 124.66, 124.9, 125.51, 126.16, 126.4, 127.5, 127.64, 128.48, 128.6, 129.1, 129.32, 129.56,
131.62, 133.83, 134.19, 135.72, 137.88, 140.45, 142.77, 151.46, 157.42; MS (m/z, %): 574 (M+, 100%);
Anal. Calcd for C31H22N6O2S2 (574.68): C, 64.79; H, 3.86; N, 14.62; S, 11.16%. Found: C, 64.75; H,
3.89; N, 14.65; S, 11.14%.
5-(Benzothiazol-2-yl)-1,6-dihydro-6-imino-3-(1-methylbenzimidazol-2-yl)-3-(phenylsulphonyl)-1-(4-
chlorophenyl) pyridazine (28b): Yield (68%), mp > 300 °C; IR (KBr) νmax/cm-1: 3341 (NH), 1649 (CO);
1H NMR (DMSO-d6) δ 4.02 (s, 3H, NCH3), 6.62−8.14 (m, 17H, ArH’s), 11.79 (s, br, 1H,
D2O-exchangable, NH); MS (m/z, %): 608 (M+, 100%); Anal. Calcd for C31H21ClN6O2S2 (609.12): C,
61.13; H, 3.47; N, 13.80; S, 10.53%. Found: C, 61.10; H, 3.49; N, 13.83; S, 10.51%.
5-(Benzothiazol-2-yl)-1,6-dihydro-6-imino-3-(1-methylbenzimidazol-2-yl)-3-(phenylsulphonyl)-1-(4-
methylphenyl) pyridazine (28c): Yield (72%), mp > 300 °C; IR (KBr) νmax/cm-1: 3325 (NH), 1651
1
(CO); H NMR (DMSO-d6) δ 2.32 (s, 3H, CH3), 4.02 (s, 3H, NCH3), 6.43−8.14 (m, 17H, ArH’s), 11.75

HETEROCYCLES, Vol. 89, No. 1, 2014
123
(s, br, 1H, D2O-exchangable, NH); MS (m/z, %): 588 (M+, 100%); Anal. Calcd for C32H24N6O2S2
(588.70); C, 65.29; H, 4.11; N, 14.28; S, 10.89%. Found: C, 65.25; H, 4.09; N, 14.30; S, 10.85%.
4-(Benzohiazol-2-yl)-5-cyano-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(phenyl)pyridazine (31a):
Yield (thermally) 75%; yield (MW) 88%, mp 240−242 °C; IR (KBr) νmax/cm-1: 3332 (NH), 2233 (C≡N),
1
1597 (C=N); H NMR (DMSO-d6) δ 6.94−8.14 (m, 14H, ArH’s), 11.78 (br. s, 1H, D2O-exchangable,
NH). MS (m/z, %): 469 (M+, 100%); Anal. Calcd for C24H15N5O2S2 (469.54): C, 61.39; H, 3.22; N, 14.92;
S, 13.66%. Found: C, 61.42; H, 3.24; N, 14.88; S, 13.62%.
4-(Benzothiazol-2-yl)-5-cyano-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(4-chlorophenyl)pyridazine
1
(31b): Yield (69%), mp > 300 °C; IR (KBr) νmax/cm-1: 3332 (NH), 2233 (C≡N), 1597 (C=N); H NMR
(DMSO-d6) δ 6.64−8.14 (m, 13H, ArH’s), 11.88 (s, br, 1H, D2O-exchangable, NH); 13C NMR
(DMSO-d6) δ 114.88, 123.01, 124.86, 125.41, 126.16, 126.75, 127.54, 128.03, 129.07, 129.46, 129.69,
130.51, 133.33, 133.69, 135.2, 138.48, 140.05, 141.79, 151.06, 156.04; MS (m/z, %): 503 (M+, 100%);
Anal. Calcd for C24H14ClN5O2S2 (503.98): C, 57.20; H, 2.80; N, 13.90; S, 12.72%. Found: C, 57.23; H,
2.82; N, 13.87; S, 12.74%.
4-(Benzothiazol-2-yl)-5-cyano-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(4-methylphenyl)pyridazine
(31c): Yield (71%), mp 290−292 °C; IR (KBr) νmax/cm-1: 3352 (NH), 2267 (C≡N), 1593 (C=N); 1H NMR
(DMSO-d6) δ 2.32 (s, 3H, CH3), 6.44−8.14 (m, 13H, ArH’s), 11.88 (s, br, 1H, D2O-exchangable, NH);
13C NMR (DMSO-d6) δ 20.88, 113.37, 123.01, 124.86, 125.45, 126.16, 126.66, 127.41, 127.58, 127.99,
129.53, 129.76, 130.87, 131.51, 133.48, 135.11, 136.07, 137.15, 140.22, 150.9, 156.04; MS (m/z, %): 483
(M+, 100%); Anal. Calcd for C25H17N5O2S2 (483.56): C, 62.09; H, 3.54; N, 14.48; S, 13.26%. Found: C,
62.11; H, 3.51; N, 14.52; S, 13.23%.
4-(1-Methylbenzimidazol-2-yl)-5-cyano-1,6-dihydro-6-imino-3-(phenylsulfonyl)-1-(phenyl)-pyrid-
azine (32a: Yield (thermally) 77%; yield (MW) 89%, mp 220−222 °C; IR (KBr) νmax/cm-1: 3332 (NH),
2233 (C≡N), 1597 (C=N); 1H NMR (DMSO-d6) δ 4.02 (s, 3H, NCH3), 6.54−7.92 (m, 14H, ArH’s), 11.79
(br. s, 1H, D2O-exchangable, NH); MS (m/z, %): 466 (M+, 100%); Anal. Calcd for C25H18N6O2S
(466.51): C, 64.36; H, 3.89; N, 18.01; S, 6.87%. Found: C, 64.41; H, 3.86; N, 18.04; S, 6.89%.
4-(1-Methylbenzimidazol-2-yl)-5-cyano-1,6-dihydro-6-imin-3-(phenylsulfonyl)-1-(4-chlorophenyl)-
pyridazine (32b): Yield (74%), mp >300 °C; IR (KBr) νmax/cm-1: 3352 (NH), 2267 (C≡N), 1593 (C=N);
1H NMR (DMSO-d6) δ 4.05 (s, 3H, CH3), 6.59−7.92 (m, 13H, ArH’s), 11.82 (br. s, 1H, D2O-exchangable,
NH); MS (m/z, %): 500 (M+, 100%); Anal. Calcd for C25H17ClN6O2S (500.96): C, 59.94; H, 3.42; N,
16.78; S, 6.40%. Found: C, 59.90; H, 3.46; N, 16.80; S, 6.36%.
4-(1-Methylbenzimidazol-2-yl)-5-cyano-1,6-dihydro-6-imin-3-(phenylsulfonyl)-1-(4-methylphenyl)-
pyridazine (32c): Yield (78%), mp 242−244 °C; IR (KBr) νmax/cm-1: 3352 (NH), 2267 (C≡N), 1593
1
(C=N); H NMR (DMSO-d6) δ 2.32 (s, 3H, CH3), 4.12 (s, 3H, CH3), 6.40−7.92 (m, 13H, ArH’s), 11.81

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(br. s, 1H, D2O-exchangable, NH); MS (m/z, %): 480 (M+, 100%); Anal. Calcd for C26H20N6O2S
(480.54): C, 64.98; H, 4.20; N, 17.49; S, 6.67%. Found: C, 64.95; H, 4.18; N, 17.51; S, 6.70%.
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