Synthesis of a new class of sulfone linked bisheterocycles

Article abstract of DOI:10.1002/jhet.1534

A new class of sulfone linked bisheterocycles - pyrrolyl pyrazoles, bispyrazoles, and pyrazolyl isoxazoles - were prepared from 1-aroyl-2- styrylsulfonylethenes, and the products were characterized by spectral parameters and elemental analyses.

Full text of DOI:10.1002/jhet.1534

Month 2013
Synthesis of a New Class of Sulfone Linked Bisheterocycles
Venkatapuram Padmavathi, Nemallapudi Revathi, Chittoor Rajasekhar, and Chokkappagari Premakumari
Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India
*
E-mail: vkpuram2001@yahoo.com
Received February 27, 2010
DOI 10.1002/jhet.1534
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
O
O
S
S
Ph
Ph
O
Ph
NH
Ar'
X
NH
Ar
S
Ar
O
O
N
Ar
N
N
H
N
1
6
7 / 8
7 X = N-Ph; 8 X = O
Ar = Ph, 4-MePh, 4-ClPh
Ar' = Ph, 4-OMePh, 4-ClPh
A new class of sulfone linked bisheterocycles—pyrrolyl pyrazoles, bispyrazoles, and pyrazolyl
isoxazoles—were prepared from 1-aroyl-2-styrylsulfonylethenes, and the products were characterized by
spectral parameters and elemental analyses.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
chloride under Friedel–Craft’s conditions followed by
condensation with sodium styryl sulfinate [19]. The reaction
of 1 with hydrazine hydrate in ethanol resulted in 4,5-
dihydro-3-aryl-5-(styrylsulfonyl)-1H-pyrazole (2) (Scheme 1).
The 1H-NMR spectrum of 2a displayed an AMX splitting pat-
tern for pyrazoline ring protons exhibiting three double doub-
lets at d 5.92 (HA), 3.34 (HM), and 3.08 ppm (HX). The
coupling constant values JAM = 12.6 Hz, JMX = 10.6 Hz, and
JAX = 5.5 Hz show that HA and HM are cis; HA and HX are
trans; and HM and HX are geminal. In addition, a doublet ob-
served at d 6.65 ppm was assigned to HC, whereas the signal
due to HD merged with aromatic protons [18]. The coupling
constant value J= 14.2 Hz indicated their trans geometry.
The olefin moiety in 2 was used to develop different
heterocyclic rings such as pyrroles, pyrazoles, and isoxazoles
by using 1,3-dipolar cycloaddition reagents, viz. TosMIC
[20], nitrile imines, and nitrile oxides [21]. The compound
2 was treated with TosMIC in the presence of sodium hy-
dride in a mixture of ether and DMSO. The solid obtained
was identified as 3-aryl-5-(4′-phenyl-1′H-pyrrol-3′-ylsulfo-
Among different heterocycles, the chemistry and
pharmacological relevance of five membered heterocycles
has received much attention [1]. In fact, pyrazole and
isoxazole derivatives have gained importance because of
their various chemotherapeutic properties, viz. bacteriostatic,
antibiotic, analgesic, anti-inflammatory, antifungal, and
antiviral [2–7]. Celecoxib, a pyrazole derivative, and
Valdecoxib, an isoxazole derivative are now widely used
as anti-inflammatory drugs [8]. Among the different methods
for the synthesis of pyrazolines and isoxazolines, the 1,3-
dipolar cycloaddition of an ylide onto an alkene in a 3 + 2
manner is a facile one [9]. In addition, pyrroles are important
class of heterocyclic compounds and are structural units found
in several natural products [10], organic material [11], and
bioactive molecules [12]. Pyrroles also play a crucial role in
nonlinear optical materials and in supramolecular chemistry
[13]. Classical methods for their preparation include the Knorr
[14], Hantzsch [15], and Paal–Knorr condensation reactions
[16] or by transition metal catalyzed reactions [17]. In fact,
the development of practical methods for the preparation
of differently substituted bisheterocycles has become an
important and critical goal in organic synthesis. In continua-
tion of our efforts to develop bisheterocyclic systems from
the multifunctional synthetic intermediate 1-aroyl-2-
styrylsulfonylethene [18], the present work has been taken up.
1
nyl)-4,5-dihydro-1H-pyrazole (3). The H-NMR spectrum
of 3b showed two singlets at d 6.87 and 7.11 ppm due to
C2′–H and C5′–H of pyrrole ring, apart from signals due to
pyrazoline and aromatic protons. Similarly, 1,3-dipolar cy-
cloaddition reaction of 2 with nitrile imines and nitrile oxides
generated from araldehyde phenylhydrazones and araldox-
imes in the presence of chloramine-T in methanol resulted
in 3-aryl-5-(4′,5′-dihydro-1′,5′-diphenyl-3′-aryl-1′H-pyrazol-
4′-ylsulfonyl)-4,5-dihydro-1H-pyrazole (4) and 3-aryl-5-
(4′,5′-dihydro-3′-aryl-5′-phenylisoxazol-4′-ylsulfonyl)-4,
5-dihydro-1H-pyrazole (5), respectively (Scheme 1). The
1H-NMR spectra of 4a and 5a displayed two doublets at
RESULTS AND DISCUSSION
The synthetic intermediate 1-aroyl-2-styrylsulfonylethene
(1) was prepared by passing vinyl chloride gas into aroyl
© 2013 HeteroCorporation

V. Padmavathi, N. Revathi, C. Rajasekhar, and C. Premakumari
Vol 000
Scheme 1. i) N2H4. H2O, EtOH; ii) TosMIC, NaH, Et2O + DMSO; iii) Ar’-CH=NNHPh, Chloramine-T.3H2O, MeOH; iv) Ar’-CH = NOH, Chloramine-
T.3H2O, MeOH; v) Chloranil, Xylene. a) Ar = Ph; b) Ar = 4-MePh; c) Ar = 4-ClPh, a) Ar’ = Ph; b) Ar’ = 4-OMePh; c) Ar’ = 4-ClPh.
HM
HX
HA
O
Ar
HC
O
Ph
i
4
3
S
Ar
N 2
Ph
5
O
O
1
S
N
O
H
1
2
HD
iii
O
iv
O
ii
O
O
O
O
HA
HM
S
Ph
S
S
Ph
Ph
4
5
4
3
5'
4
3
5
4' 5'
3'
2'
N
5
4'
3'
3' 4'
HX
3
1NH
Ar'
5
1'O
1NH
1'N
2'
1NH
Ar'
5'
2
N
2
N
1'
2
N
2'
N
Ph
Ar
Ar
Ar
N
H
3
4
v
v
v
O
O
O
O
O
O
S
S
S
Ph
Ph
Ph
NH
NH
Ar'
NH
Ar'
O
N
Ph
Ar
Ar
Ar
N
N
N
N
N
N
H
6
7
8
Table 1
Physical and analytical data of compounds 3–8.
Analysis %
Calcd/found
H
Compound
Mp (ꢀC)
147–149
153–155
172–174
197–199
185–187
204–206
165–167
171–173
194–196
166–168
175–177
Ar
C6H5
Ar′
–
Yield %
75
Mol. formula
C19H17N3O2S
C20H19N3O2S
C19H16ClN3O2S
C30H26N4O2S
C32H30N4O3S
C
N
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
64.93
64.79
65.73
65.62
59.14
59.21
71.12
71.22
69.79
69.87
62.63
62.49
66.85
66.65
65.66
65.63
57.63
57.71
65.31
65.20
66.09
66.00
4.87
4.92
5.23
5.17
4.18
4.11
5.17
5.12
5.49
5.53
4.20
4.27
4.90
4.98
5.29
5.36
3.82
3.75
4.32
4.39
4.71
4.65
11.95
12.03
11.49
11.55
10.88
10.93
11.05
11.14
10.17
10.25
9.73
9.62
9.73
9.64
8.83
8.89
8.39
8.45
4-MeC6H4
4-ClC6H4
C6H5
–
69
–
76
C6H5
68
4-MeC6H4
4-ClC6H4
C6H5
4-OMeC6H4
4-ClC6H4
C6H5
72
75
C30H24Cl2N4O2S
C24H21N3O3S
C26H25N3O4S
C24H19Cl2N3O3S
C19H15N3O2S
C20H17N3O2S
66
4-MeC6H4
4-ClC6H4
C6H5
4-OMeC6H4
4-ClC6H4
–
65
69
70
12.02
12.09
11.56
11.50
4-MeC6H4
–
71
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Some Novel Heterocycles
Table 1
(Continued)
Analysis %
Calcd/found
H
Compound
Mp (ꢀC)
Ar
Ar′
Yield %
75
Mol. formula
C
N
6c
183–185
4-ClC6H4
–
C19H14ClN3O2S
59.45
59.37
71.69
71.55
70.30
70.19
63.09
62.91
67.43
67.52
66.22
66.31
58.07
58.18
3.67
3.60
4.41
4.48
4.79
4.83
3.54
3.48
4.00
3.93
4.48
4.42
3.04
3.10
10.94
10.88
11.14
11.03
10.24
10.32
9.80
9.75
9.82
9.94
8.91
7a
7b
7c
8a
8b
8c
212–214
232–234
225–227
198–200
217–219
225–227
C6H5
C6H5
69
74
72
71
74
76
C30H22N4O2S
C32H26N4O3S
C32H20Cl2N4O2S
C24H17N3O3S
C26H21N3O4S
C24H15Cl2N3O3S
4-MeC6H4
4-ClC6H4
C6H5
4-OMeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
4-OMeC6H4
4-ClC6H4
8.99
8.46
8.55
75.5MHz (Table 3). All chemical shifts were reported in d (ppm)
using TMS as an internal standard. The microanalyses were
performed on Perkin-Elmer 240C elemental analyzer (Waltham,
MA). The starting compounds 1-aroyl-2-styrylsulfonylethene
(1) and 4,5-dihydro-3-aryl-5-(styrylsulfonyl)-1H-pyrazole (2) were
prepared as per the literature procedure [18].
3-Aryl-5-(4′-phenyl-1′H-pyrrol-3′-ylsulfonyl)-4,5-dihydro-1H-
pyrazole (3): general procedure. An equimolar mixture
(1 mmol) of TosMIC and 2 in Et2O/DMSO (10 mL 2:1) was
added dropwise to a stirred suspension of NaH (50 mg) in
dry Et2O (10 mL) at room temperature. The stirring was
d 5.21 and 5.19 ppm and 5.58 and 5.78 ppm, which were
assigned to H-4′ and H-5′, the two methine protons of the
pyrazoline and isoxazoline rings. The coupling constant
value J = 6.2 Hz showed that they are in a trans geometry.
The compounds 3, 4, and 5 upon oxidation with chloranil
in xylene gave the corresponding pyrazoles and isoxazoles,
3-aryl-5-(4′-phenyl-1′H-pyrrol-3′-ylsulfonyl)-1H-pyrazole (6),
3-aryl-5-(1′,5′-diphenyl-3′-aryl-1′H-pyrazol-4′-ylsulfonyl)-
1H-pyrazole (7), and 3-aryl-5-(3′-aryl-5′-phenylisoxazol-
4′-ylsulfonyl)-1H-pyrazole (8). The disappearance of
signals due to pyrazoline/isoxazoline ring protons in the
1H-NMR spectra of 6–8 confirms their formation. The struc-
tures of 2–8 were further confirmed by 13C-NMR spectra.
Table 2
IR data of compounds 2–8.
IR (cmÀ1
)
CONCLUSION
Compound
SO2
C═C
C═N
NH
A new class of sulfone linked bisheterocycles—pyrrolyl
pyrazoles, bispyrazoles, and pyrazolyl isoxazoles—were
prepared from 1-aroyl-2-styrylsulfonylethenes, adopting
the 1,3-dipolar cycloaddition methodology using TosMIC,
nitrile imines, and nitrile oxides.
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
1121
1129
1140
1135
1130
1123
1141
1132
1134
1128
1126
1130
1140
1134
1120
1139
1127
1130
1135
1132
1126
1333
1336
1340
1341
1346
1332
1340
1338
1336
1330
1342
1337
1342
1339
1333
1330
1335
1340
1345
1338
1333
1615
1618
1620
1625
1632
1640
–
–
–
–
–
1575
1571
1585
1576
1580
1570
1585
1582
1576
1575
1580
1577
1574
1570
1572
1583
1578
1571
1582
1585
1576
3335
3339
3345
3290
3295
3291
3335
3329
3330
3334
3340
3335
3330
3295
3330
3340
3336
3331
3298
3336
3340
EXPERIMENTAL
Melting points were determined in open capillaries on a
Mel-Temp apparatus (India) and are uncorrected (Table 1). The
purity of the compounds was checked by TLC (silica gel H,
British Drug Houses Ltd., ethyl acetate/hexane, 3:1). The IR
spectra were recorded on a Thermo Nicolet IR 200 FTIR
spectrometer (Thermo Electron Scientific, Madison, WI) as KBr
pellets, and the wave numbers were given in cmÀ1 (Table 2).
The 1H-NMR spectra were recorded in CDCl3/DMSO-d6 on
a Jeol JNM spectrometer (Oxford Instruments, England) at
l-300MHz (Table 3). The 13C-NMR spectra were recorded in
CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
–
1632
1639
1629
1624
1635
1628
1636
1635
1627
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. Padmavathi, N. Revathi, C. Rajasekhar, and C. Premakumari
Vol 000
Table 3
1H-NMR and 13C-NMR data of compounds 2–8.
Compound
1H-NMR (d, ppm)
13C-NMR (d, ppm)
Solvent
2a
3.08 (dd, 1H, HX JMX = 10.6, JAX = 5.5 Hz), 3.34 (dd, 1H, 40.2 (C-4), 80.1 (C-5), 132.2 (C-1′), 137.2 (C-2′),
HM), 5.92 (dd, 1H, HA, JAM = 12.6 Hz), 6.65 (d, 1H, Hc, 156.5 (C-3), 128.2, 129.6, 130.8, 131.3, 132.5, 133.1,
JCD = 14.2 Hz), 7.00–7.62 (m, 11H, Ar–H and HD), 10.23 133.6, 134.2 (aromatic carbons)
(bs, 1H, NH)
CDCl3
2b
2c
3a
3b
2.25 (s, 3H, Ar–CH3), 3.03 (dd, 1H, HX, JMX = 10.4,
JAX = 5.3 Hz), 3.38 (dd, 1H, HM), 5.98 (dd, 1H, HA,
JAM = 12.1 Hz), 6.68 (d, 1H, Hc, JCD = 14.1 Hz),
7.02–7.68 (m, 9H, Ar–H and HD), 10.16 (bs, 1H, NH)
3.20 (dd, 1H, HX. JMX = 17.6, JAX = 4.5 Hz), 3.48 (dd,
1H, HM), 5.87 (dd, 1H, HA, JAM = 12.4 Hz), 7.04 (d, 1H, 156.7 (C-3), 127.0, 127.4, 128.3, 129.5, 131.3,
Hc, JCD = 14.4 Hz), 7.09–7.71 (m, 9H, Ar–H and HD),
9.98 (bs, 1H, NH)
3.06 (dd, 1H, HX, JMX = 15.5, JAX = 4.9 Hz), 3.64 (dd,
1H, HM), 5.99 (dd, 1H, HA, JAM = 16.8 Hz), 6.91 (s, 1H,
C2′–H), 7.08, (s, 1H, C5′–H) 7.11–7.62 (m, 10H, Ar–H), 129.4, 130.2, 131.7, 132.5, 133.1, 133.6, 134.2
8.86 (bs, 1H, NH), 10.14 (bs, 1H, NH)
2.32 (s, 3H, Ar–CH3), 3.20 (dd, 1H, HX, JMX = 16.1,
JAX = 3.3 Hz), 3.83 (dd, 1H, HM), 6.03 (dd, 1H, HA,
21.2 (Ar–CH3), 39.4 (C-4), 80.4 (C-5), 132.9 (C-1′),
138.2 (C-2′), 155.9 (C-3), 127.8, 128.9, 130.3, 131.7,
132.9, 133.8, 134.0, 134.9 (aromatic carbons)
CDCl3
38.7 (C-4), 78.9 (C-5), 133.4 (C-1′), 139.7 (C-2′),
CDCl3
134.2, 135.7, 136.2 (aromatic carbons)
41.4 (C-4), 76.2 (C-5), 118.2 (C-4′), 120.7 (C-3′),
124.2 (C-2′), 125.7 (C-5′), 155.1 (C-3), 128.2,
DMSO-d6
DMSO-d6
(aromatic carbons)
21.1 (Ar–CH3), 42.3 (C-4), 77.5 (C-5), 117.9 (C-4′),
121.2 (C-3′), 123.6 (C-2′), 124.9 (C-5′), 156.0 (C-3),
JAM = 17.6 Hz), 6.87 (s, 1H, C2′–H), 7.11 (s, 1H, C5′–H), 125.3, 126.9, 128.8, 129.6, 130.7, 131.0, 137.3,
7.14–7.75 (m, 9H, Ar–H), 8.74 (bs, 1H, NH), 10.17 (bs,
1H, NH)
138.9 (aromatic carbons)
3c
4a
4b
3.14 (dd, 1H, HX, JMX = 16.7, JAX = 4.3 Hz), 3.79 (dd,
1H, HM), 5.82 (dd, 1H, HA, JAM = 17.1 Hz), 6.83 (s, 1H,
C2′–H), 7.12 (s, 1H, C5′–H), 7.25–7.74 (m, 9H, Ar–H),
8.91 (bs, 1H, NH), 10.02 (bs, 1H, NH)
3.08 (dd, 1H, HX, JMX = 15.3, JAX = 4.4 Hz), 3.51 (dd,
1H, HM), 5.21 (d, 1H, C4′–H, J = 6.2 Hz), 5.58 (d, 1H,
C5′–H, J = 6.2 Hz), 5.79 (dd, 1H, HA, JAM = 16.3 Hz),
7.10–7.69 (m, 20H, Ar–H), 10.15 (bs, 1H, NH)
2.26 (s, 3H, Ar–CH3), 3.13 (dd, 1H, HX. JMX = 14.6,
JAX = 4.7 Hz), 3.81 (s, 3H, Ar–OCH3), 3.58 (dd, 1H,
41.9 (C-4), 76.9 (C-5), 116.4 (C-4′), 120.5 (C-3′),
122.9 (C-2′), 123.6 (C-5′), 155.1 (C-3), 128.1,
129.2, 130.9, 131.9, 132.8, 133.0, 133.8, 137.2
(aromatic carbons)
40.8 (C-4), 63.7 (C-4′), 77.4 (C-5), 86.9 (C-5′),
154.2 (C-3′), 155.9 (C-3), 127.4, 128.9, 130.1,
131.4, 132.3, 133.6, 134.3, 134.9, 135.2, 137.0
(aromatic carbons)
DMSO-d6
CDCl3
21.6 (Ar–CH3), 56.4 (Ar–OCH3), 41.3 (C-4),
62.4 (C-4′), 78.0 (C-5), 87.2 (C-5′), 153.6 (C-3′),
CDCl3
HM), 5.19 (d, 1H, C4′–H, J = 6.4 Hz), 5.53 (d, 1H, C5′–H, 156.3 (C-3), 128.6, 129.2, 131.9, 132.1, 133.2, 134.0,
J = 6.4 Hz), 5.83 (dd, 1H, HA, JAM = 17.6 Hz), 7.08–7.76
(m, 18H, Ar–H), 10.21 (bs, 1H, NH)
134.7, 135.8, 136.4, 137.2 (aromatic carbons)
4c
5a
5b
3.18 (dd, 1H, HX. JMX = 15.8, JAX = 4.2 Hz), 3.63 (dd,
1H, HM), 5.23 (d, 1H, C4′–H, J = 6.7 Hz), 5.59 (d, 1H,
C5′–H, J = 6.7 Hz), 5.91 (dd, 1H, HA, JAM = 16.9 Hz),
7.14–7.87 (m, 18H, Ar–H), 10.12 (bs, 1H, NH)
3.16 (dd, 1H, HX. JMX = 14.0, JAX = 4.9 Hz), 3.73 (dd,
1H, HM), 5.19 (d, 1H, C4′–H, J = 5.7 Hz), 5.78 (d, 1H,
C5′–H, J = 5.7 Hz), 5.56 (d, 1H, HA, JAM = 16.6 Hz),
7.13–7.75 (m, 15H, Ar–H), 8.98 (bs, 1H, NH)
40.6 (C-4), 63.6 (C-4′), 77.5 (C-5), 86.7 (C-5′),
154.8 (C-3′), 156.9 (C-3), 127.6, 128.7, 130.3,
132.8, 133.8, 134.5, 135.0, 136.9, 137.6, 138.9
(aromatic carbons)
42.3 (C-4), 64.5 (C-4′), 78.7 (C-5), 85.8 (C-5′),
153.8 (C-3), 155.2 (C-3′), 125.5, 126.6, 128.7,
129.5, 130.3, 131.5, 137.3, 139.0 (aromatic carbons)
CDCl3
CDCl3
CDCl3
2.22 (s, 1H, Ar–CH3), 3.77 (s, 3H, Ar–OCH3), 3.12 (dd, 22.8 (Ar–CH3), 57.2 (Ar–OCH3), 42.0 (C-4),
1H, HX. JMX = 14.6, JAX = 4.6 Hz), 3.65 (dd, 1H, HM),
5.21 (d, 1H, C4′–H, J = 5.9 Hz), 5.69 (d, 1H, C5′–H,
J = 5.9 Hz), 5.79 (dd, 1H, HA, JAM = 17.2 Hz), 7.14–7.79
(m, 13H, Ar–H), 9.02 (bs, 1H, NH)
63.8 (C-4′), 77.4 (C-5), 87.2 (C-5′), 154.6 (C-3′),
155.1 (C-3), 128.0, 129.1, 130.7, 131.8, 132.2, 135.0,
135.6, 136.9 (aromatic carbons)
5c
6a
6b
6c
3.10 (dd, 1H, HX. JMX = 14.2, JAX = 4.1 Hz), 3.62 (dd,
1H, HM), 5.24 (d, 1H, C4′–H, J = 5.4 Hz), 5.71 (d, 1H,
C5′–H, J = 5.4 Hz), 5.81 (d, 1H, HA, JAM = 17.5 Hz),
7.12–7.83 (m, 13H, Ar–H), 10.14 (bs, 1H, NH)
6.81 (s, 1H, C2′–H), 6.92 (s, 1H, C5′–H), 7.11–7.64
(m, 11H, Ar–H and C4–H), 8.84 (bs, 1H, NH),
10.04 (bs, 1H, NH)
41.9 (C-4), 62.5 (C-4′), 76.9 (C-5), 86.7 (C-5′),
155.0 (C-3′), 156.6 (C-3), 128.7, 129.4, 129.9,
130.5, 131.2, 132.7, 133.3, 134.6, 137.9 (aromatic
carbons)
117.4 (C-4′), 121.3 (C-3′), 123.2 (C-2′), 124.6 (C-5′), DMSO-d6
138.2 (C-4), 152.2 (C-5), 156.0 (C-3), 127.4, 129.0,
131.9, 132.3, 133.8, 134.0, 133.7 134.1 (aromatic
carbons)
22.4 (Ar–CH3), 116.8 (C-4′), 120.7 (C-3′),
122.8 (C-2′), 124.1 (C-5′), 137.7 (C-4), 151.4 (C-5),
155.8 (C-3), 128.1, 129.7, 130.7, 131.1, 132.7, 133.4,
134.2, 135.2 (aromatic carbons)
CDCl3
2.23 (s, 3H, Ar–CH3), 6.76 (s, 1H, C2′–H), 6.88 (s, 1H,
C5′–H), 7.15–7.71 (m, 10H, Ar–H and C4–H), 8.93 (bs,
1H, NH), 10.13 (bs, 1H, NH)
DMSO-d6
6.72 (s, 1H, C2′–H), 6.96 (s, 1H, C5′–H), 7.18–7.82 (m, 10H,
Ar–H and C4–H), 8.89 (bs, 1H, NH), 10.08 (bs, 1H, NH)
115.4 (C-4′), 121.5 (C-3′), 123.3 (C-2′), 124.9 (C-5′), DMSO-d6
138.6 (C-4), 152.8 (C-5), 156.4 (C-3), 128.7, 130.1,
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Some Novel Heterocycles
Table 3
(Continued)
Compound
1H-NMR (d, ppm)
13C-NMR (d, ppm)
Solvent
131.4, 132.5, 133.0, 134.6, 135.0 135.6 (aromatic
carbons)
7a
7.09–7.72 (m, 21H, Ar–H and C4–H), 8.30 (bs, 1H, NH) 145.4 (C-3′), 148.2 (C-4′), 152.8 (C-5′), 138.6 (C-4), CDCl3
153.6 (C-5), 155.2 (C-3), 127.8, 128.4, 129.7, 131.0,
132.9, 133.4, 134.0, 134.9, 135.9, 136.7 (aromatic
carbons)
7b
2.27 (s, 3H, Ar–CH3), 3.78 (s, 3H, Ar–OCH3), 7.16–7.79 21.8 (Ar–CH3), 57.4 (Ar–OCH3), 144.8 (C-3′),
CDCl3
(m, 19H, Ar–H and C4–H), 8.14 (bs, 1H, NH)
149.7 (C-4′), 153.5 (C-5′), 137.9 (C-4), 154.3 (C-5),
156.9 (C-3), 127.3, 127.8, 128.2, 129.4, 131.9, 133.9,
134.2 135.3, 136.2 (aromatic carbons)
7c
8a
8b
7.06–7.85 (m, 19H, Ar–H and C4–H), 8.32 (bs, 1H, NH) 145.4 (C-3′), 147.8 (C-4′), 154.7 (C-5′), 138.2 (C-4), CDCl3
155.7 (C-5), 156.6 (C-3), 127.9, 128.7, 129.1, 130.4,
132.3, 134.7, 135.6 137.4, 137.9 (aromatic carbons)
6.99–7.68 (m, 16H, Ar–H and C4–H), 8.97 (bs, 1H, NH) 144.7 (C-3′), 149.6 (C-4′), 153.4 (C-5′), 137.6 (C-4), CDCl3
154.8 (C-5), 156.8 (C-3), 127.2, 128.9, 131.4, 132.7,
134.3, 135.7, 136.0, 136.5 (aromatic carbons)
2.25 (s, 3H, Ar–CH3), 3.71 (s, 3H, Ar–OCH3), 7.04–7.74 21.9 (Ar–CH3), 58.3 (Ar–OCH3), 143.8 (C-3′),
CDCl3
(m, 14H, Ar–H and C4–H), 8.83 (bs, 1H, NH)
148.3 (C-4′), 154.4 (C-5′), 136.4 (C-4), 155.3 (C-5),
157.5 (C-3), 128.5, 129.2, 131.9, 132.2, 133.7,
134.0, 135.2 136.5 (aromatic carbons)
8c
7.12–7.81 (m, 14H, Ar–H and C4–H), 8.74 (bs, 1H, NH) 145.2 (C-3′), 147.1 (C-4′), 155.2 (C-5′), 137.8 (C-4),
156.5 (C-5), 157.8 (C-3), 128.8, 129.4, 130.4, 131.7,
CDCl3
133.6, 135.8, 136.2, 137.8 (aromatic carbons)
continued for 24 h and diluted with water. It was extracted with
ether, and the organic layer was dried over anhydrous sodium
sulfate. Removal of the solvent under vacuum gave crude
product, which was purified by filtration through a column of
silica gel (BDH, 60–120 mesh) with hexane/EtOAc (3:1) as eluent.
3-Aryl-5-(4′,5′-dihydro-1′,5′-diphenyl-3′-aryl-1′H-pyrazol-4′-
ylsulfonyl)-4,5-dihydro-1H-pyrazole (4): general procedure. A
was removed on a rotary evaporator. The resultant solid was
purified by recrystallization from methanol.
3-Aryl-5-(1′,5′-diphenyl-3′-aryl-1′H-pyrazol-4′-ylsulfonyl)-
1H-pyrazole (7) and 3-aryl-5-(3′-aryl-5′-phenylisoxazol-4′-
ylsulfonyl)-1H-pyrazole (8): general procedure. A solution of
4/5 (1 mmol) and chloranil (2.2 mmol) in xylene (10 mL) was
refluxed for 24–28 h. Then, it was treated with 5% NaOH
solution. The organic layer was separated, washed with water,
and dried over anhydrous sodium sulfate, and the solvent was
removed under reduced pressure. The solid obtained was
purified by recrystallization from 2-propanol.
mixture of
2
(1 mmol), araldehyde phenylhydrazone
(1.2 mmol), and chloramine-T (1.2 mmol) in methanol (15 mL)
was refluxed for 12–14 h. The precipitated inorganic salts
were filtered off. The filtrate was concentrated, and the residue
was extracted with dichloromethane. The organic layer was
washed with water and brine and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure.
Recrystallization of crude product from ethanol resulted in
pure compound.
Acknowledgments. The authors are thankful to CSIR, New Delhi,
for the financial assistance under a major research project.
3-Aryl-5-(4′,5′-dihydro-3′-aryl-5′-phenylisoxazol-4′-ylsulfonyl)-
4,5-dihydro-1H-pyrazole (5): general procedure. The compound
2 (1 mmol), araldoxime (1.2 mmol), and chloramine-T (2 mmol)
in methanol (20mL) were refluxed for 16–18h on a water bath.
The precipitated inorganic salts were filtered off. The filtrate was
concentrated, and the residue was extracted with dichloromethane.
The organic layer was washed with water and brine and dried
over anhydrous sodium sulfate. The solvent was removed
in vacuo. The solid obtained was purified by recrystallization
from ethanol.
3-Aryl-5-(4′-phenyl-1′H-pyrrol-3′-ylsulfonyl)-1H-pyrazole
(6): general procedure. A solution of 3 (1 mmol) and chloranil
(1.1 mmol) in xylene (10 mL) was refluxed for 20–24 h. Then the
reaction mixture was treated with a 5% NaOH solution. The
organic layer was separated and repeatedly washed with water. It
was then dried over anhydrous sodium sulfate, and the solvent
REFERENCES AND NOTES
[1] Caramella, P.; Grunanger, P. 1,3-Dipolar Cycloaddition
Chemistry A. Padwa Ed.; John Willey & Sons: New York, 1984, 1, 291.
[2] Boarland, M. P. V.; McOmie, J. F. W.; Timms, R. N. J Chem
Soc 1952, 2, 4691.
[3] Buchi, J.; Ammnn, J.; Lieberherr, R.; Eichenberger, E. Helv
Chim Act 1953, 36, 75.
[4] Kornet, M. J.; Thorstenson, J. H.; Lubawy, W. C. J Pharm Sci
1974, 63, 1090.
[5] Richon, A. B.; Maragoudakis, M. E.; Wasvary, J. S. J Med
Chem 1982, 25, 745.
[6] Shisashi, S.; Syoji, O.; Masahiro, T.; Tsutomu, S.; Megumi, I.;
Korekiyo, W.; Itsuo, U. J Med Chem 1998, 41, 1927.
[7] Nagai, A.; Matsushita, Y.; Ono, N.; Takechi, Y. Jpn Kokai
Tokkyo JP 04,173,780 1992; Chem Abstr 1992, 117, 212485.
[8] Dannahardt, G.; Kiefer, W.; Kramer, G.; Maehrlein, S.;
Nowe, U.; Fiebich, B. Eur J Med Chem 2000, 35, 499.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. Padmavathi, N. Revathi, C. Rajasekhar, and C. Premakumari
Vol 000
[9] (a) Lee, A. G. Synthesis 1982, 508; (b) Bao-Xiang, Z.;
Yang, Y.; Shoji, E. Tetrahedron 1996, 52, 12049.
[10] Lindel,T.; Breckle, G.; Hochgurtel, M.; Volk, C.; Grube, A.;
Kock, M. Tetrahedron Lett 2004, 45, 8149.
[11] (a) Novak, P.; Muller, K.; Santhanam, K. S. V.; Haas, O.
Chem Rev 1997, 97, 207; (b) Higgins, S. J Chem Soc Rev 1997, 26, 247.
[12] Snyder, L. B.; Meng, Z.; Mate, R.; D’Andrea, S. V.; Marinier, A.;
Quesnelle, C. A.; Gill, P.; DenBleyker, K. L.; Fung-Tomc, J. C.; Frosco, M.
B.; Martel, A.; Barrett, J. F.; Bronson, J. J. Bioorg Med Chem Lett 2004,
14, 4735.
[13] Lehn, J. M. Supramolecular Chemistry: Concepts and Perspec-
tives; Wiley VCH: Weinheim, 1995.
[14] (a) Shiner, C. M.; Lash, T. D. Tetrahedron 2005, 61, 11628;
(b) Bellingham, R. K.; Carey, J. S.; Hussain, N.; Morgan, D. O.; Oxley,
P.; Powling, L. C. Org Process Res Dev 2004, 8, 279.
[15] (a) Matiychuk, V. S.; Martyak, R. L.; Obushak, N. D.;
Ostapiuk, Y. V.; Pidlypnyi, N. I. Chem Heterocycl Compd 2004, 40,
1218; (b) Calvo, L.; González-Ortega, A.; Sañudo, M. C. Synthesis
2002, 2450.
[16] (a) Chen, J.; Wu, H.; Zheng, Z.; Jin, C.; Zhang, X.; Su, W.
Tetrahedron Lett 2006, 47, 5383; (b) Minetto, G.; Raveglia, L. F.;
Sega, A.; Taddei, M. Eur J Org Chem 2005, 5277.
[17] (a) Kel’in, A. V.; Sromek, A. W.; Gevorgyan, V. J Am Chem
Soc 2001, 123, 2074; (b) Gabriele, B.; Salerno, G.; Fazio, A. J Org Chem
2003, 68, 7853; (c) Ramanathan, B.; Keith, A. J.; Armstrong, D.; Odom,
A. L. Org Lett 2004, 6, 2957; (d) Shen, H. C.; Li, C. W.; Liu, R. S. Tet-
rahedron Lett 2004, 45, 9245; (e) Kamijo, S.; Kanazawa, C.; Yamamoto,
Y.; J Am Chem Soc 2005, 127, 9260 (f) Gorin, D. J.; Davis, N. R.; Tostz,
F. D. J Am Chem Soc 2005, 127, 11260; (g) Larionov, O. V.; de Meijere,
A. Angew Chem Int Ed 2005, 44, 5664; (h) Alcaide, B.; Almendros, P.;
Redondo, M. C. Chem Commun 2006, 2616.
[18] Padmavathi, V.; Rajagopala Sarma, M.; Venugopal Reddy, K.;
Padmaja, A.; Bhaskar Reddy, D. Heteroatom Chem 2003, 14, 155.
[19] Bhaskar Reddy, D.; Chandrasekhar babu, N.; Venugopal
Reddy, K.; Padmavathi, V. Indian J Chem 2001, 40B, 416.
[20] (a) Van Leusen, A. M.; Siderius, H.; Hoogenboom, B. E.;
Van Leusen, D. Tetrahedron Lett 1972, 5337; (b) Pavri, N. P.;
Trudell, M. L. J Org Chem 1997, 62, 2649; (c) Padmavathi, V.;
Jagan Mohan Reddy, B.; Chandra Obula Reddy, B.; Padmaja, A.
Tetrahedron 2005, 61, 2407.
[21] (a) Hameli, M. H.; Refaat, H. H.; Nehal, M. E. A. H.;
Ahmad, S. S. J Heterocycl Chem 1984, 21, 1013; (b) Padmavathi, V.;
Bhaskar Reddy, A. V.; Sumathi, R. P.; Padmaja, A.; Bhaskar Reddy D.
Indian J Chem 1998, 37B, 1286.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet