A facile access to some new pyrazole, 1,3,4-thiadiazole, and thiophene derivatives via β-ketosulfones

Article abstract of DOI:10.1080/10426500902796980

3-Bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) reacts with sodium benzenesulfinate to give the corresponding ketosulfone 2. Treatment of 2 with hydrazonoyl chlorides 3a,b gives the 3,3'-bipyrazoles 5a,b. Ketosulfone 2 reacts also with arylidenemalononitriles to give the pyrazolylpyridones 10a,b. The reaction of compound 2 with phenylisothiocyanate and potassium hydroxide and treating intermediate with hydrazonoyl halides and with -haloketones gives the 1,3,4-thiadiazoles 18a-c and thiophenes 21a-f, respectively.

Full text of DOI:10.1080/10426500902796980

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Phosphorus, Sulfur, and Silicon and the
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A Facile Access to Some New Pyrazole,
1,3,4-Thiadiazole, and Thiophene
Derivatives via β-Ketosulfones
Kamal M. Dawood a , Nabila A. Kheder a , Eman A. Ragab a & Sanaa
N. Mohamed a
a Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
Published online: 03 Feb 2010.
To cite this article: Kamal M. Dawood , Nabila A. Kheder , Eman A. Ragab & Sanaa N. Mohamed
(2010): A Facile Access to Some New Pyrazole, 1,3,4-Thiadiazole, and Thiophene Derivatives via β-
Ketosulfones, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:2, 330-339
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Phosphorus, Sulfur, and Silicon, 185:330–339, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902796980
A FACILE ACCESS TO SOME NEW PYRAZOLE,
1,3,4-THIADIAZOLE, AND THIOPHENE DERIVATIVES
VIA β-KETOSULFONES
Kamal M. Dawood, Nabila A. Kheder, Eman A. Ragab,
and Sanaa N. Mohamed
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
3-Bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) reacts with sodium benzenesul-
finate to give the corresponding ketosulfone 2. Treatment of 2 with hydrazonoyl chlorides
3a,b gives the 3,3ꢀ-bipyrazoles 5a,b. Ketosulfone 2 reacts also with arylidenemalononitriles
to give the pyrazolylpyridones 10a,b. The reaction of compound 2 with phenylisothiocyanate
and potassium hydroxide and treating intermediate with hydrazonoyl halides and with α-
haloketones gives the 1,3,4-thiadiazoles 18a–c and thiophenes 21a–f, respectively.
Keywords Hydrazonoyl halides; ketosulfones; pyrazoles; pyridines; 1,3,4-thiadiazoles; thio-
phenes
INTRODUCTION
Among sulfur-containing compounds, β-ketosulfones are valuable precursors in or-
ganic synthesis.1–5 Diverse biological activities are associated with ketosulfones. For exam-
ple, they have been used as antiviral,6 antitubercular,7 anti–human renin,8 and antimicrobial9
agents. Pyrazole derivatives are also attracting important applications in the field of medic-
inal chemistry.10,11 Furthermore, 1,3,4-thiadiazoles were recently reported by us and others
as highly anti-inflammatory,12,13 and anticonvulsant12,14 agents. In continuation of our work
on 1,3,4-thiadiazole derivatives,15–22 herein we aimed to synthesize some new pyrazole,
1,3,4-thiadiazole, thiophene, and pyridone derivatives through a reactive ketosulfone as key
intermediate.
RESULTS AND DISCUSSION
When 3-bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) reacted with
sodium benzenesulfinate in refluxing ethanol. It afforded the novel 1,5-diphenyl-3-
(2-(phenylsulfonyl)acetyl)-1H-pyrazole-4-carbonitrile (2), as shown in Scheme 1. The
structure of compound 2 was established on the basis of its elemental analysis and spectral
data. For example, its IR spectrum showed the presence of a strong absorption peak at
Received 23 November 2008; accepted 4 February 2009.
Address correspondence to Prof. Dr. K. M. Dawood, Department of Chemistry, Faculty of Science, Cairo
University, Giza 12613, Egypt. E-mail: dr dawood@yahoo.com
330

NEW PYRAZOLE DERIVATIVES VIA β-KETOSULFONES
331
1666 cm−1 due to a carbonyl group, and its 1H NMR spectrum revealed a singlet signal at
δ 5.25 characteristic for the active methylene protons.
Reaction of the ketosulfone 2 with hydrazonoyl chlorides 3a,b in ethanolic sodium
ethoxide solution at room temperature afforded, in each case, a single product (as examined
by TLC). The structures of the isolated products were established as 5ꢁ-acetyl-1-aryl-2ꢁ,5-
diphenyl-4ꢁ-(phenylsulfonyl)-1H,2ꢁH-3,3ꢁ-bipyrazole-4-carbonitriles 5a,b (Scheme 1) on
1
the basis of their elemental and spectral analyses. The H NMR spectrum of compound
5a revealed a singlet signal at δ 2.59 due to COCH3 protons, in addition to an aromatic
multiplet in the region δ 7.17–8.23.
Cl
O
CN
CN
Ph
Ph
PhSO2Na
3
N-NH-Ar
O
O
O
S
N
N
Ph
N
NaOEt / EtOH
Ph
N
Ph
Br
2
1
O
Ph
N
CN
O
Ph
CN
O
Ph
O
-H2O
Ph
O
N
S
Ph
Ph
N
S
O
N
O
Ar
N
N
H
O
N
Ar
N
4
5
a
Ar
C6H5
4-ClC6H4
5
b
Scheme 1
The reactivity of the ketosulfone 2 towards arylidenemalononitiriles 6a,b was also
investigated. Thus, treatment of compound 2 with benzylidenemalononitrile 6a in pyri-
dine under reflux conditions gave only one product as examined by TLC. Two possible
structures 10 and 11 can be drawn for the reaction product as shown in Scheme 2. How-
ever, the elemental analyses and spectroscopic data of the reaction product established its
structure as 3-(1,6-dihydro-6-oxo-4-phenyl-3-(phenylsulfonyl)pyridin-2-yl)-1,5-diphenyl-
1H-pyrazole-4-carbonitrile (10a) and ruled out the expected arylidene exchange adduct
11a. The IR spectrum of the reaction product showed three absorption peaks at 3322,
2228, and 1640 cm−1 corresponding to NH, C N, and C O functions, respectively. In
addition, its mass spectrum revealed among other fragments, a fragment at m/z 554 due
to the molecular ion (M+) of compound 10a. Similar treatment of the ketosulfone 2 with
p-chlorobenzylidene malononitrile 6b under the same reaction conditions, furnished the
corresponding 6-pyridone derivative 10b as shown in Scheme 2. Formation of the pyridone
derivatives 10a,b is suggested to take place via the formation of the intermediate iminopy-
rane adduct 9 followed by a Dimroth-type rearrangement, then loss of hydrogen cyanide
molecule to give the corresponding pyridone derivatives 10a,b as illustrated in Scheme 2.
Coupling of the ketosulfone 2 with p-chlorobenzenediazonium chloride (12a) was
also conducted to afford the corresponding hydrazone derivative 13a (Scheme 2). The
IR spectrum of compound 13a showed two absorption bands at 3210 and 1629 cm−1

332
K. M. DAWOOD ET AL.
CN
Ph
O
O
Ph
N
S
Ph
N
O
11
CN
Ar
- CH2(CN)2
CN
Ph
CN
Ph
Ar
O
S
CN
O
O
6a, b
EtOH/ Pip.
O
S
Ph
N
N
Ph
N
Ph
Ph
N
O
2
O
NC
Ar
ArN2+Cl-
7
CN
12
Ph
Ph
CN
O
N
Ph
O
CN
N
Ph
N
S
O
S
Ph
Ph
N
O
HO
13
N
O
N
Ar
H
N
Ar
13
a
Ar
4-ClC6H4
CN
8
HN
N
b
Ph
Ph
Ph
Ph
Ph
N
N
CN
O
S
N
10
a
Ar
C6H5
4-ClC6H4
CN
O
S
N
- HCN
Dimroth Rearrang.
Ph
Ph
O
b
HN
O
O
HN
Ar
O
Ar
CN
10
9
Scheme 2
due to hydrazone-NH and carbonyl functions, respectively. The ketosulfone 2 coupled
similarly with diazotized 5-amino-3-phenyl-1H-pyrazole (12b) to afford the corresponding
hydrazone derivative 13b as shown in Scheme 2.
Treatment of the ketosulfone 2 with phenylisothiocyanate and potassium hydroxide
in dimethylformamide at room temperature afforded the potassium salt intermediate 14, and
its reaction with hydrazonoyl halides 15a–c, as a route to 1,3,4-thiadiazole systems, was also
examined. Thus, when the potassium salt 14 was treated with N-phenylbenzohydrazonyl
chloride (15a), it afforded a single product (based on TLC analysis) that was identi-
fied as 3-(2-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)-2-(phenylsulfonyl)acetyl)-1,5-
diphenyl-1H-pyrazole-4-carbonitrile (18a) (Scheme 3). Elemental analysis and spectral
data were in complete accordance with the assigned structure 18a. Similar treatment of
the intermediate 14 with an equimolar amount of hydrazonoyl chlorides 15b,c afforded, in
each case, only one isolable product. Elemental analyses and spectral data of the reaction
products were compatible with the 1,3,4-thiadiazole structures 18b,c. The IR spectrum of
18b revealed the presence of three absorption bands at 1756, 1672, and 2232 cm−1 due
1
to two carbonyl and one nitrile functions, respectively. The H NMR spectrum of 18b
exhibited a triplet and quartet signals at δ 1.25 and 4.35, respectively, due to ethyl-ester
group in addition to aromatic multiplets. A proposed mechanism for the formation of the
1,3,4-thiadiazole structure 18 is depicted in Scheme 3.

NEW PYRAZOLE DERIVATIVES VIA β-KETOSULFONES
333
Cl
CN
Ph
CN
Ph
R
O
O
PhNCS
N-NH-Ar
O
Ph
O
S
N
15a-c
S
Ph
N
N
Ph
N
DMF/KOH
Ph
O
S K+
PhHN
O
2
14
CN
Ph
CN
Ph
O
O
O
O
Ph
Ph
N
S
N
Ph
S
N
Ph
-PhNH2
N
O
O
H
S
PhHN
Ar
S
PhHN
R
N
N
R
N
N
CN
Ar
Ph
17
H
16
O
S
O
Ph
N
R
Ar
Ph
CO2Et Ph
CO2Et 4-ClC6H4
15-18
Ph
N
O
Ph
a
b
c
Ar
N
S
N
R
18a-c
Scheme 3
Next, the reactivity of the potassium salt 14 towards various α-haloketones was
also investigated. Thus, treatment of 14 with α-chloroacetone gave one product that was
identified as 3-(2-acetyl-5-(phenylamino)-4-(phenylsulfonyl)thiophen-3-yl)-1,5-diphenyl-
pyrazole-4-carbonitrile (21a) as shown in Scheme 4. The other possible structures 22a and
23a were ruled out based on the elemental analyses and spectroscopic data of the obtained
product. The IR spectrum of the reaction product showed three absorption bands at 3309,
2234, and 1700 cm−1 characteristic for NH, C N, and C O functions, respectively. The
1H NMR spectrum of compound 21a revealed a broad signal at δ 9.69 due to NH proton,
in addition to a multiplet at δ 7.24–7.75 due to the aromatic protons.
Similarly, treatment of the salt 14 with ethyl chloroacetate and p-bromophenacyl
bromide afforded the corresponding thiophene derivatives 21b,c as outlined in Scheme 4.
The thiophene structures 21b,c were confirmed from their elemental analyses and spectral
data. For example, the IR spectra of the reaction products showed, in each case, characteristic
carbonyl and NH absorptions in the regions 1623–1672 and 3275–3299 cm−1, respectively.
In addition, some 3-bromoacetylheterocycles, namely 3-bromoacetyl-1,5-diphenyl-
1H-pyrazole-4-carbonitrile (1), 2-bromoacetylbenzothiazole (19e), and 3-bromoacetyl
coumarin-2-one (19f) reacted in a similar fashion with the potassium salt 14, under the
same reaction conditions mentioned above, to afford the corresponding thiophene deriva-
tives 21d–f (Scheme 4). The assignment of structures 21 was supported by the appearance
of NH peak around 3300 cm−1 (in IR spectra) and near δ 9.7 (in their 1H NMR spectra).
EXPERIMENTAL
Melting points were measured on a Gallenkamp apparatus. IR spectra were recorded
on a Shimadzu FT-IR 8101 PC infrared spectrophotometer. 1H NMR spectra were

334
K. M. DAWOOD ET AL.
CN
Ph
CN
Ph
O
O
O
R
Ph
O
S
PhNCS
DMF
N
S
N
Ph
Ph
N
N
Ph
O
S K+
2
O
PhHN
14
O
19-23
a
X
R
CH3
19
OC2H5
b
c
4-BrC6H4
CN
CN
Ph
Ph
O
O
N
d
Ph
N
R
Ph
N
S
Ph
N
O
N
S
O
NHPh
e
f
S
20
O
O
-H2O
-PhNH2
-H2O
CN
Ph
CN
Ph
CN
Ph
O
O
O
O
S
Ph
O
N
Ph
Ph
Ph
S
S
N
N
N
Ph
Ph
N
O
N
O
O
R
O
R
S
Ph
N
S
S
NHPh
O
21
R
23
22
Scheme 4
determined in CDCl3 or DMSO-d6 at 300 MHz on a Varian Mercury VX-300 NMR
spectrometer using TMS as an internal standard. Mass spectra were measured on
a GCMS-QP1000 EX spectrometer at 70 eV. Elemental analyses were carried out
at the Microanalytical Center of Cairo University. Arylidenemalonotiriles 6a,b,23,24
hydrazonoyl halides 3a,25 3b,26 15a,27 15b,c,28,29 5-pyrazolediazonium salt 12b,30 4-
bromophenacylbromide (19c),31 3-bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile
(1),19 2-bromoacetylbenzothiazole (19e),32 and 3-bromoacetylcoumarin-2-one (19f)33
were prepared according to the procedures in the literature.
1,5-Diphenyl-3-(2-(phenylsulfonyl)acetyl)-1H-pyrazole-4-carbonitrile (2)
To a solution of 3-bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) (3.66 g,
l0 mmol) in absolute ethanol (50 mL), sodium benzenesulfinate (1.64 g, 10 mmol) was
added. The mixture was then refluxed for 4 h, then left to cool to room temperature. The
solid that formed was filtered off, washed with ethanol, and dried. Recrystallization from
ethanol gave the corresponding ketosulfone derivative 2. Yield (85%), mp 165–167◦C. IR
(cm−1) 2230 (C N), 1666 (C O), 1596 (C N). 1H NMR (DMSO-d6) δ 5.25 (s, 2H, CH2),

NEW PYRAZOLE DERIVATIVES VIA β-KETOSULFONES
335
7.33–7.47 (m, 4H, ArH), 7.49–7.65 (m, 7H, ArH), 7.68–7.95 (m, 4H, ArH); MS m/z (%)
427 (M+, 3.8), 362 (5.5), 286 (11.5), 273 (17.1), 227 (92.3), 135 (64.0), 77 (100). Calcd.
for C24H17N3O3S (427.42): C, 67.44; H, 4.01; N, 9.83. Found: C, 67.64; H, 3.89; N, 9.92.
Reaction of the Ketosulfone 2 with Hydrazonoyl Halides 3a,b
1,5-Diphenyl-3-(2-(phenylsulfonyl)acetyl)-1H-pyrazole-4-carbonitrile (2) (0.854 g,
2 mmol) was added to an ethanolic sodium ethoxide solution [prepared from sodium
metal (0.046 g, 2 mmol) and absolute ethanol (25 mL)]. After stirring for 10 min, the
appropriate hydrazonoyl chloride 3a,b (2 mmol) was added, and stirring was continued for
an additional 30 min. The reaction mixture was then left to stir at room temperature for 12
h. The solid product that formed was collected by filtration, washed with water, and dried.
Recrystallization from ethanol gave the corresponding pyrazole derivatives 5a,b.
5ꢀ -Acetyl-1,2ꢀ,5-triphenyl-4ꢀ -(phenylsulfonyl)-1H,2ꢀH-3,3ꢀ -bipyrazole-4-
carbonitrile (5a). Yield (78%), mp > 300◦C. IR (cm−1) 2230 (C N), 1695 (C O),
1
1592 (C N). H NMR (DMSO-d6) δ 2.59 (s, 3H, CH3), 7.17–7.44 (m, 11H, ArH),
7.46–7.78 (m, 6H, ArH), 7.81–8.23 (m, 3H, ArH); MS m/z (%) 569 (M+, 9.8), 554 (100),
325 (25), 244 (11.8), 143 (35.7), 78 (22.2), 65 (40.2). Calcd. for C33H23N5O3S (569.65):
C, 69.55; H, 4.07; N, 12.29. Found: C, 69.79; H, 4.20; N, 12.04.
5ꢀ-Acetyl-1,5-diphenyl-2ꢀ-(4-chlorophenyl)-4ꢀ-(phenylsulfonyl)-1H,2ꢀH-3,
3ꢀ-bipyrazole-4-carbonitrile (5b). Yield (76%), mp > 300◦C. IR (cm−1) 2235 (C N),
1700 (C O), 1592 (C N). 1H NMR (DMSO-d6) δ 2.64 (s, 3H, CH3), 7.25–7.29 (m, 7H,
ArH), 7.31–7.60 (m, 10H, ArH), 8.32 (d, 2H, J = 8.1 Hz, ArH); MS m/z (%) 604 (M+,
15.8), 589 (29.9), 510 (16.1), 405 (100), 364 (25.3), 261 (12.6), 171 (31.0), 116 (17.2).
Calcd. for C33H22N5O3SCl (604.09): C, 65.61; H, 3.67; N, 11.59. Found: C, 65.76; H,
3.85; N, 11.38.
3-(4-Aryl-1,6-dihydro-6-oxo-3-(phenylsulfonyl)pyridin-2-yl)-
1,5-diphenyl-1H-pyrazole-4-carbonitrile Derivatives (10a,b)
A
mixture of the 1,5-diphenyl-3-(2-(phenylsulfonyl)acetyl)-1H-pyrazole-4-
carbonitrile (2) (0.427 g, 1 mmol) and the appropriate arylidenemalononitrile 6a,b (1
mmol) in ethanol (20 mL) was refluxed for 5 h then cooled. The reaction mixture was
poured onto ice-cold water and neutralized with 10% hydrochloric acid until its pH was 7.
The solid product was collected, washed with water, dried, and finally recrystallized from
EtOH:DMF (3:1) to afford the corresponding pyridine derivatives 10a,b in 76% and 70%
yields, respectively.
3-(1,6-Dihydro-6-oxo-4-phenyl-3-(phenylsulfonyl)pyridin-2-yl)-1,5-
diphenyl-1H-pyrazole-4-carbonitrile (10a). Yield (76%), mp. 270–271◦C. IR
1
(cm−1) 3322 (NH), 2228 (C N), 1640 (C O). H NMR (DMSO-d6) δ 7.39–7.49 (m,
13H, ArH), 7.50–7.57 (m, 4H, ArH), 7.59–7.71 (m, 3H, ArH), 7.8 (s, 1H, CH); MS m/z
(%) 554 (M+, 12.4), 550 (38.2), 466 (90.2), 452 (54.9), 194 (13.7), 113 (22.5), 77 (100).
Calcd. for C33H22N4O3S (554.63): C, 71.46; H, 4.00; N, 10.10. Found: C, 71.32; H, 3.91;
N, 10.22.
3-(4-(4-Chlorophenyl)-1,6-dihydro-6-oxo-3-(phenylsulfonyl)pyridin-
2-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (10b). Yield (70%), mp > 300◦C. IR
(cm−1) 3325 (NH), 2333 (C N), 1624 (C O). 1H NMR (DMSO-d6) δ 7.26 (s, 1H, CH),
7.42–7.51 (m, 11H, ArH), 7.65–7.75 (m, 6H, ArH), 7.95 (d, 2H, J = 7.8 Hz, ArH); MS

336
K. M. DAWOOD ET AL.
m/z (%) 591 (M++2, 74.7), 590 (M++1, 64.7), 589 (M+, 55.2), 511 (44.6), 169 (88.1), 91
(100). Calcd. for C33H21N4O3SCl (589.08): C, 67.29; H, 3.59; N, 9.51. Found: C, 67.17;
H, 3.33; N, 9.41.
1,5-Diphenyl-3-(2-arylhydrazono-2-phenylsulfonyl)acetyl-
1H-pyrazol-4-carbonitriles 13a,b
To a cold solution of the ketosulfone 2 (0.854 g, 2 mmol) in ethanol (50 mL),
sodium acetate trihydrate (3 g) was added, then the appropriate diazonium salt 12a,b (2
mmol) (prepared by diazotization of the appropriate amine with nitrous acid) were added
portionwise with stirring at 0–5◦C over a period of 30 min. After complete addition, the
reaction mixture was stirred for additional 4 h, then kept in an ice chest overnight. The
reaction mixture was then diluted with water, dried, and finally recrystallized from acetic
acid to afford the corresponding hydrazones 13a,b in 69% and 64% yields, respectively.
1,5-Diphenyl-3-(2-(4-chlorophenyl)hydrazono)-2-(phenylsulfonyl)acetyl)-
1H-pyrazole-4-carbonitrile (13a). Yield (64%), mp 208◦C. IR (cm−1) 3210 (NH),
1
2230 (C N), 1629 (C O). H NMR (DMSO-d6) δ 7.24–7.35 (m, 6H, ArH), 7.37–7.46
(m, 8H, ArH), 7.57–7.69 (m, 3H, ArH), 8.22 (d, 2H, J = 8.1Hz, ArH), 12.58 (br.s, 1H,
NH); MS m/z (%) 566 (M+, 7.2), 561 (21.7), 533 (61.3), 442 (29.2), 381 (100), 272 (58.5),
180 (68.9), 104 (52.8). Calcd. for C30H20N5O3SCl (566.98): C, 63.55; H, 3.56; N, 12.35.
Found: C, 63.27; H, 3.48; N, 12.33.
1,5-Diphenyl-3-(2-(3-phenyl-1H-pyrazol-5-yl)hydrazono)-2-(phenylsulfon
yl)-acetyl)-1H-pyrazol-4-carbonitrile (13b). Yield (69%), mp 181–183◦C. IR (cm−1
)
1
3345, 3276 (2NH), 2230 (C N), 1695 (C O). H NMR (DMSO-d6) δ 7.41–7.72 (m,
10H, ArH), 7.74–7.90 (m, 10H, ArH), 8.16 (s, 1H, CH), 8.62 (br.s, 1H, NH), 9.15 (br.s,
1H, D2O-exchangable, NH). Calcd. for C33H23N7O3S (597.66): C, 66.32; H, 3.88; N,
16.41. Found: C, 66.27; H, 3.82; N, 16.50.
Synthesis of 1,3,4-Thiadiazole Derivatives 18a–c
To a stirred solution of potassium hydroxide (60 mg, 1 mmol) in dimethylformamide
(15 mL), 1,5-diphenyl-3-(2-(phenylsulfonyl)acetyl)-1H-pyrazole-4-carbonitrile (2) (0.427
g, 1 mmol) was added. After stirring for 30 min, phenylisothiocyanate (0.135 g, 1 mmol)
was added to the resulting mixture. The stirring was continued for a further 6 h, then
the appropriate hydrazonoyl halide 15a–c (1 mmol) and the reaction mixture was further
stirred overnight then diluted with water (5 mL). The solid product was filtered off, washed
with water, dried, and finally recrystallized from DMF/EtOH to afford the corresponding
1,3,4-thiadiazole derivatives 18a–c.
3-(2-(3,5-Diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)-2-(phenylsulfonyl)acet
yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (18a). Yield (63%), mp 290◦C. IR
1
(cm−1) 2233 (C N), 1675 (C O), 1594 (C N); H NMR (DMSO-d6) δ 6.87–7.99 (m,
ArH). Calcd. for C38H25N5O3S2 (663.77): C, 68.76; H, 3.80; N, 10.55; S, 9.66. Found: C,
66.87; H, 3.85; N, 10.65; S, 9.34.
Ethyl 5-(2-(4-Cyano-1,5-diphenyl-1H-pyrazol-3yl)-2-oxo-1-(phenylsulfonyl)
ethylidene)-4-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-carboxylate (18b). Yield
1
(62%), mp 245–247◦C. IR (cm−1) 2232 (C N) 1756, 1672 (2 C O), 1590 (C N); H
NMR (DMSO-d6) δ 1.25 (t, 3H, J = 7.2 Hz, CH3CH2), 4.35 (q, 2H, J = 7.2 Hz, CH3CH2),
6.81–7.02 (m, 4H, ArH), 7.19–7.32 (m, 6H, ArH), 7.34–7.53 (m, 7H, ArH), 7.54–7.71 (m,
3H, ArH); MS m/z (%) 659 (M+, 7.3), 644 (9.1), 518 (12.1), 464 (9.1), 364 (8.1), 272

NEW PYRAZOLE DERIVATIVES VIA β-KETOSULFONES
337
(54.4), 228 (2.0), 181 (8.1), 141 (10.1), 77 (100). Calcd. for C35H25N5O5S2 (659.75): C,
63.72; H, 3.82; N, 10.62; S, 9.72. Found: C, 63.44; H, 4.67; N, 10.82; S, 9.65.
Ethyl 5-(2-(4-Cyano-1,5-diphenyl-1H-pyrazol-3yl)-2-oxo-1-(phenylsulfonyl)
ethylidene)-4-(4-chlorophenyl)-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate
(18c). Yield (68%), mp 260◦C. IR (cm−1) 2233 (C N), 1757, 1674 (2C O), 1592
(C N); 1H NMR (DMSO-d6) δ 1.26 (t, 3H, J = 7.2 Hz, CH3CH2), 4.38 (q, 2H, J = 7.2
Hz, CH3CH2), 6.98–7.24 (m, 6H, ArH), 7.29–7.42 (m, 10H, ArH), 7.44–7.63 (m, 3H,
ArH); MS m/z (%) 694 (M+, 18.7), 687 (18), 497 (9.0), 463 (14.4), 411 (4.5), 272 (29.7),
180 (15.3), 154 (18.0), 118 (42.3), 77 (100). Calcd. for C35H24N5O5S2Cl (694.19): C,
60.56; H, 3.48; N, 10.09; S, 9.24. Found: C, 60.87; H, 3.35; N, 9.99; S, 9.15.
Synthesis of Thiophene Derivatives 21a–f
A similar procedure to the one that was used for the synthesis of 1,3,4-thiadiazole
is applied here using the appropriate α-haloketone [chloroacetone (19a), ethyl chloroac-
etate (19b), p-bromophenacyl bromide (19c), bromoacetylpyrazole (1), 2-(bromoacetyl)
benzothiazole (19e), and bromoacetylcoumarine (19f)] (2 mmol each) instead of the hy-
drazonoyl halides 15a–c. The formed solid product was filtered off, washed with ethanol,
dried, and finally recrystallized from DMF/EtOH to afford the corresponding thiophene
derivatives 21a–f, respectively.
3-(2-Acetyl-5-(phenylamino)-4-(phenylsulfonyl)thiophen-3-yl)-1,5-diphen
yl-1H-pyrazole-4-carbonitrile (21a). Yield (65%), mp 281–283◦C. IR (cm−1) 3309
1
(NH), 2234 (C N), 1640 (C O); H NMR (DMSO-d6) δ 2.07 (s, 3H, CH3), 7.24–7.28
(m, 4H, ArH), 7.32–7.49 (m, 10H, ArH), 7.73–7.76 (m, 6H, ArH), 9.69 (s, 1H, NH,
D2O-exchangeable); MS m/z (%) 600 (M+, 100), 522 (34.3), 422 (27.4), 272 (15.8), 180
(19.5), 77 (87.5). Calcd. for C34H24N4O3S2 (600.72): C, 67.98; H, 4.03; N, 9.33; S, 10.68.
Found: C, 67.72; H, 4.11; N, 9.01; S, 10.59.
Ethyl
3-(4-Cyano-1,5-diphenyl-1H-pyrazol-3-yl)-5-(phenylamino)-4-
(phenylsulfonyl)-thiophene-2-carboxylate (21b). Yield (63%), mp 211–213◦C. IR
(cm−1) 3299 (NH), 2234 (C N), 1623 (C O); H NMR (DMSO-d6) δ 1.15 (t, 3H, J =
1
7.2 Hz, CH3CH2), 4.14 (q, 2H, J = 7.2 Hz, CH3CH2), 7.26–7.37 (m, 8H, ArH), 7.38–7.5
(m, 7H, ArH), 7.74–7.77 (m, 5H, ArH), 9.6 (s, 1H, NH); MS m/z (%) 631 (M++1, 65.2),
630 (M+, 77.9), 520 (19.3), 494 (28.3), 371 (24.5), 272 (39.0), 180 (14.7), 77 (100). Calcd.
for C35H26N4O4S2 (630.75): C, 66.65; H, 4.15; N, 8.88; S, 10.17. Found: C, 66.86; H,
4.27; N, 8.71; S, 10.30.
3-(2-(4-Bromobenzoyl)-5-(phenylamino)-4-(phenylsulfonyl)thiophen-3-
yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (21c). Yield (72%), mp 253–255◦C.
IR (cm−1) 3275 (NH), 2230 (C N), 1672 (C O); 1H NMR (DMSO-d6) δ 6.97–7.13 (m,
4H, ArH), 7.27–7.41 (m, 8H, ArH), 7.43–7.69 (m, 10H, ArH), 7.72 (d, 2H, J = 8.1 Hz,
ArH), 9.82 (s, 1H, NH, D2O-exchangeable); MS m/z (%) 742 (M+, 66.0), 741 (35.9), 676
(19.4), 645 (24.6), 493 (23.0), 371 (11.7), 183 (52.9), 195 (10.2), 77 (100). Calcd. for
C39H25N4O3S2Br (741.69): C, 63.16; H, 4.40; N, 7.55; S, 8.65. Found: C, 63.24; H, 4.37;
N, 7.32; S, 8.57.
3-(3-(4-Cyano-1,5-diphenyl-1H-pyrazol-3-yl)-5-phenylamino-4-(phenylsul
fonyl)-(thiophene-2-carbonyl))-1,5-diphenyl-1H-pyrazole-4-carbonitrile (21d).
1
Yield (65%), mp > 300◦C. IR (cm−1) 3282 (NH), 2232 (C N), 1631 (C O); H NMR
(DMSO-d6) δ 7.22–7.38 (m, 10H, ArH), 7.39–7.46 (m, 10H, ArH), 7.48–7.50 (m, 8H,
ArH), 7.73–7.76 (d, 2H, J = 7.8 Hz, ArH), 9.78 (s, 1H, NH, D2O-exchangeable). Calcd.

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K. M. DAWOOD ET AL.
for C49H31N7O3S2 (829.945): C, 70.91; H, 3.76; N, 11.81; S, 7.73. Found: C, 70.72; H,
4.03; N, 12.10; S, 7.67.
3-(2-(Benzothiazol-2-yl)carbonyl)-5-(phenylamino)-4-(phenylsulfonyl)
thiophen-3-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (21e). Yield (67%), mp
1
251–253◦C. IR (cm−1) 3252 (NH), 2236 (C N), 1672 (C O); H NMR (DMSO-d6) δ
6.97–7.40 (m, 10H, ArH), 7.41–7.69 (m, 10H, ArH), 7.71–7.72 (m, 4H, ArH), 9.79 (s,
1H, NH, D2O-exchangeable); MS m/z (%) 720 (M++1, 27.4), 719 (M+, 63.3), 579 (13.8),
493 (33.7), 443 (27.7), 312 (15.7), 180 (21.2), 162 (29.2), 134 (19.5), 77 (100). Calcd. for
C40H25N5O3S3 (719.87): C, 66.74; H, 3.05; N, 9.73; S, 13.36. Found: C, 66.83; H, 2.98;
N, 9.59; S, 13.54.
3-(2-(2-Oxo-2H-chromene-3-carbonyl)-5-phenylamino-4-(phenylsulfonyl)-
(thiophen-3-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (21f). Yield (70%),
1
mp > 300◦C. IR (cm−1) 3289 (NH), 2232 (C N), 1729, 1669 (2C O); H NMR
(DMSO-d6) δ 6.72–6.75 (m, 2H, ArH), 6.94–7.20 (m, 7H, ArH), 7.23–7.39 (m, 8H, ArH),
7.42–7.52 (m, 5H, ArH), 7.65–7.69 (m, 2H, ArH), 8.2 (s, 1H, CH), 9.80 (s, 1H, NH,
D2O-exchangeable). Calcd. for C42H26N4O5S2 (730.83): C, 69.03; H, 3.59; N, 7.69 S,
8.78. Found: C, 68.92; H, 3.71; N, 7.62; S, 8.69.
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