International Journal of Organic Chemistry, 2011, 1, 78-86
doi:10.4236/ijoc.2011.13013 Published Online September 2011 (http://www.SciRP.org/journal/ijoc)
Synthesis and Antimicrobial Activity of a New Class of
Sulfone Linked Bisheterocycles
Venkatapuram Padmavathi*, Thunga Radha Lakshmi,
Bhumireddy Chinnachennaiahgari Venkatesh, Konda Mahesh
Department of Chemistry, Sri Venkateswara University, Tirupati, India
Received June 1, 2011; revised July 20, 2011; accepted August 1, 2011
Abstract
A new and novel class of bis(heterocycles) viz., bis pyrroles, pyrrolyl pyrazoles and pyrrolyl isoxazoles are
prepared from 1-aroyl-2-styrylsulfonylethenes by 1,3-dipolar cycloaddition of tosylmethyl isocyanide, dia-
zomethane, nitrile imines and nitrile oxides. The lead compounds are screened for antimicrobial activity.
Keywords: 1-Aroyl-2-Styrylsulfonylethene, 1,3-Dipolar Cycloaddition, Chloramine-T,
Antimicrobial Activity
1. Introduction
In the last few decades the chemistry of five-membered
heterocycles particularly pyrroles, pyrazolines and iso-
xazolines has received considerable attention owing to
their synthetic and effective biological importance. In-
creasing evidence suggests that pyrazoline derivatives
possess a broad spectrum of biological activities such as
antidepressant, anticonvulsant, psychoanalytic, antihy-
potensive and monamine oxidase inhibitory activities [1,
2]. In fact, Celecoxib, a pyrazole derivative and Valde-
coxib an isoxazole derivative are extensively used as
anti-inflammatory drugs [3]. Besides, pyrrole carboxy-
lates exhibit antibiotic, antiviral and oncolytic properties
[4-8]. Hence, it is thought that a worthwhile programme
would be to prepare molecules having both pyrrole and
pyrazole/isoxazole units. Literature evidenced the syn-
thesis of 3,4-disubstituted pyrroles by cyclocondensation
of Michael acceptors with tosylmethyl isocyanide (Tos-
MIC) [9]. Pyrroles have also been prepared by Paal-
Knorr condensation of alkyl and aryl amines with 1,4-
diketones [10-13]. Similarly, among different methods
for the synthesis of pyrazolines and isoxazolines, 1,3-
dipolar cycloaddition of an ylide onto an alkene in a 3 +
2 manner is a facile one [14,15]. Indeed, diazomethane,
nitrile imines and nitrile oxides have been used exten-
sively as reactive intermediates. The nitrile imines and
nitrile oxides can be generated by dehydrogenation of
araldehyde phenylhydrazones and araldoximes with lead
tetraacetate [16], mercuric acetate [17], 1-chloroben-
zotriazole [18], chloramine-T [19-22] etc. The present
communication deals with the synthesis of sulfone linked
bis heterocycles having a pyrrole in combination with a
pyrazole or an isoxazole unit.
2. Results and Discussion
The synthetic scheme is based on the reactivity of
1-aroyl-2-styrylsulfonylethene (1) towards 1,3-dipolar
reagents viz., TosMIC, diazomethane, nitrile imines, ni-
trile oxides. When compound (1) is treated with TosMIC
in the presence of sodium hydride in a mixture of ether
and DMSO, the reaction took place regioselectively re-
sulting in a mixture of compounds in 3:1 ratio. They are
identified as 4-aroyl-3-(phenylethenesulfonyl)-1H-pyr-
role (2) and 4-aroyl-3-(4’-phenyl-1’H-pyrrol-3’-ylsulfon-
yl)-1H-pyrrole (3) in major and minor amounts, respec-
tively (Scheme 1, Table 1). However, repetition of this
reaction with excess TosMIC resulted in 3 only. The
latter compound is also obtained by treating 2 with one
equivalent of TosMIC. The 1H NMR spectrum of 2a
showed two singlets at δ 7.01 and 8.02 ppm for C2-H,
and C5-H of pyrrole ring protons. Two doublets are ob-
served at 6.79 and 7.48 ppm corresponding to olefin
protons in addition to the signals of the aromatic protons.
The coupling constants value (J = 17.8 Hz) indicates that
they are in trans geometry. Compound 3a exhibited three
singlets at δ 6.89 (C2-H & C2’-H), 6.96 (C5’-H) and 8.04
(C5-H) ppm apart from signals due to aromatic protons
(Table 2).
The olefin moiety in 2 is used to develop different het-

V. PADMAVATHI ET AL. 79
Ar S
OO
Ph
O
N
N
N
H
S
Ar
OO
Ar' Ph
Ph
O
N
O
N
H
S
Ar
OO
Ar'
Ph
O
N
N
N
H
S
Ar
O O
Ar' Ph
Ph
O
N
O
N
H
S
Ar
OO
Ar'
Ph
O
N
H
N
N
H
S
Ar
OOPh
OH
H
H
N
H
N
N
H
S
Ar
OOPh
O
N
H
N
H
S
Ar
O O Ph
O
1'
2'
3' 4'
5'
12
34
5
N
H
S
Ar
OO
Ph
O
12
3
4
5
1'
2'
+
123
56
7
Method 2
Method 3
4
89
A
M
X
Ar Ar'
a) Ph Ph
b) 4-Me. C6H4 4-OMe. C6H4
c) 4-Cl. C6H4 4-Cl.C6H4
Method 1
2 TosMIC / NaH
Et
2
O + DMSO
1'
2'
3'
4' 5'
12
34
5
1'
2'
3'
4' 5'
1'
2'
3' 4'
5'
12
3
4
512
3
4
5
TosMIC / NaH
Et
2
O + DMSO
4 TosMIC / NaH
Et
2
O + DMSO
CH2N2 / Et2O
Et3N
Ar'-CH=NNHPh
Chloramine-T.3H2O
MeOH
Ar' -C H =N OH
Chloramine-T.3H2O
MeOH
Chloranil
Xylene
Chloranil
Xylene
Chloranil
Xylene
Scheme 1. Synthesis of bis heterocycles.
erocyclic rings such as pyrazoles and isoxazoles. Treat-
ment of 2 with diazomethane at –20˚C to –15˚C for 48 h
gave a solid which is identified as 4-aroyl-3-(4’-phe-
nyl-4’,5’- dihydro-1’ H-pyrazol-3’-ylsulfonyl)-1H-pyrrole
(4) by spectral analysis. The 1H NMR spectrum of 4a
showed an AMX splitting pattern for the pyrazoline ring
protons exhibiting three double doublets at δ 4.54 (HA),
3.99 (HM) and 3.64 (HX) ppm, apart from the signals of
aromatic and pyrrole ring protons. The observed cou-
pling constant values JAM = 11.6, JAX = 5.1 and JMX =
10.3 Hz indicates that HA and HM are cis, HA and HX are
trans and HM and HX are geminal (Table 2). Similarly,
1,3-dipolar cycloaddition reaction of nitrile imines and
nitrile oxides generated from araldehyde phenylhydra-
zones and araldoximes to 2 resulted in 4-aroyl-3-(1’,5’-
diphenyl-3’-aryl-4’,5’-dihydro-1’H-pyrazol-4’-ylsulfonyl)-
1H-pyrrole (5) and 4-aroyl-3-(3’-aryl-5’-phenyl-4’,5’-
dihydroisoxazol-4’-ylsulfonyl)-1H-pyrrole (6), respec-
tively (Scheme 1, Table 1). The 1H-NMR spectra of 5a
and 6a displayed two doublets at δ 5.19, 5.22 and 5.58,
5.66 ppm, which are assigned to C4’-H and C5’-H, the
two methine protons of the pyrazoline and isoxazo- line
rings. The J values (J = 6.3 & 6.4 Hz) shows that they
are in trans geometry.
The olefin moiety in 2 is used to develop different
heterocyclic rings such as pyrazoles and isoxazoles.
Treatment of 2 with diazomethane at –20˚C to –15˚C for
48 h gave a solid which is identified as 4-aroyl-3-
(4’-phenyl-4’,5’-dihydro-1’H-pyrazol-3’-ylsulfonyl)-1H-
pyrrole (4) by spectral analysis. The 1H NMR spectrum
of 4a showed an AMX splitting pattern for the pyra-
zoline ring protons exhibiting three double doublets at δ
4.54 (HA), 3.99 (HM) and 3.64 (HX) ppm, apart from the
signals of aromatic and pyrrole ring protons. The ob-
erved coupling constant vales JAM = 11.6, JAX = 5.1 s
u

V. PADMAVATHI ET AL.
80
Table 1. Physical characterization data of compounds 2-9.
Found % (Calcd)
Compd m.p. (C) Yield (%) Mol. Formula (Mol. wt.)
C H N
2a 178 - 80 56 C19H15NO3S (337.39) 67.71 (67.64) 5.01 (4.48) 4.22 (4.15)
2b 169 - 71 54 C20H17NO3S (351.42) 68.50 (68.36) 4.82 (4.88) 4.04 (3.99)
2c 211 - 13 60 C19H14ClNO3S (371.84) 61.32 (61.37) 3.83 (3.79) 3.81 (3.77)
3a 185 - 87 16, 70a, 72b C
21H16N2O3S (376.43) 67.12 (67.00) 4.27 (4.28) 7.52 (7.44)
3b 192 - 94 10, 64a, 71b C
22H18N2O3S (390.45) 67.75 (67.67) 4.69 (4.65) 7.14 (7.17)
3c 220 - 22 12, 68a, 76b C
21H15ClN2O3S (410.87) 61.46 (61.39) 3.70 (3.68) 6.85 (6.82)
4a 196 - 98 67 C20H17N3O3S (379.43) 63.26 (63.31) 4.57 (4.52) 11.11 (11.07)
4b 207 - 09 70 C21H19N3O3S (393.46) 64.18 (64.10) 4.84 (4.87) 10.72 (10.68)
4c 235 - 37 73 C20H16ClN3O3S (413.88) 58.00 (58.04) 3.94 (3.90) 10.22 (10.15)
5a 225 - 27 72 C32H25N3O3S (531.62) 72.37 (72.30) 4.80 (4.74) 7.96 (7.90)
5b 212 - 14 69 C34H29N3O4S (575.68) 70.88 (70.94) 5.05 (5.08) 7.36 (7.30)
5c 243 - 45 75 C32H23Cl2N3O3S (600.51) 64.06 (64.00) 3.82 (3.86) 7.05 (7.00)
6a 202 - 04 76 C26H20N2O4S (456.51) 68.50 (68.41) 4.44 (4.42) 6.10 (6.14)
6b 215 - 17 74 C28H24N2O5S (500.57) 67.14 (67.18) 4.82 (4.83) 5.63 (5.60)
6c 231 - 33 78 C26H18Cl2N2O4S (525.40) 59.51 (59.44) 3.50 (3.45) 5.38 (5.33)
7a 204 - 06 65 C20H15N3O3S (377.42) 63.73 (63.65) 4.04 (4.01) 11.26 (11.13)
7b 214 - 16 62 C21H17N3O3S (391.44) 64.49 (64.43) 4.40 (4.38) 10.80 (10.73)
7c 247 - 49 67 C20H14ClN3O3S (411.86) 58.38 (58.32) 3.48 (3.43) 10.30 (10.20)
8a 237 - 39 64 C32H23N3O3S (529.61) 72.70 (72.57) 4.37 (4.38) 8.00 (7.93)
8b 242 - 44 70 C34H27N3O4S (573.66) 71.29 (71.19) 4.79 (4.74) 7.28 (7.32)
8c 269 - 71 68 C32H21Cl2N3O3S (598.50) 64.31 (64.22) 3.51 (3.54) 7.08 (7.02)
9a 211 - 13 66 C26H18N2O4S (454.50) 68.78 (68.71) 4.03 (3.99) 6.13 (6.16)
9b 227 - 29 63 C28H22N2O5S (498.55) 67.48 (67.46) 4.48 (4.45) 5.57 (5.62)
9c 246 - 48 72 C26H16Cl2N2O4S (523.39) 59.75 (59.66) 3.08 (3.06) 5.41 (5.35)
aYield in Method-2; bYield in Method-3

V. PADMAVATHI ET AL. 81
Table 2. IR, 1H and 13C NMR spectral characterization data of compounds 2-9.
Compd IR (KBr) cm-1 1H NMR (, ppm) (J in Hz) 13C NMR (  , ppm)
2a
3326 (NH), 1660
(C=O), 1641
(C=C), 1334, 1131
(SO2)
6.79 (d, 1H, C1’-H, J = 17.8 Hz), 7.01 (s, 1H, C2-H),
7.48 (d, 1H, C2’-H, J = 17.8 Hz), 7.14 - 7.85 (m, 10H,
Ar-H), 8.02 (s, 1H, C5-H), 10.79 (bs, 1H, NH)
108.6 (C-3), 117.3 (C-4), 120.0 (C-1’), 121.4 (C-2),
136.9 (C-5), 137.7 (C-2’), 189.4 (C=O), 128.4, 129.6,
130.9, 131.5, 132.9, 133.7, 134.4 (aromatic carbons)
2b
3330 (NH), 1667
(C=O), 1634
(C=C), 1328, 1139
(SO2)
2.28 (s, 3H, Ar-CH3), 6.73 (d, 1H, C1’-H, J = 17.5 Hz),
7.05 (s, 1H, C2-H), 7.42 (d, 1H, C2’-H, J = 17.5 Hz),
7.17 - 7.82 (m, 9H, Ar-H), 8.05 (s, 1H, C5-H), 10.72
(bs, 1H, NH)
21.7 (Ar-CH3), 109.1 (C-3), 117.9 (C-4), 120.8
(C-1’), 121.6 (C-2), 136.4 (C-5), 137.1 (C-2’), 188.7
(C=O), 129.5, 130.6, 131.9, 132.5, 133.4, 134.0,
134.8 (aromatic carbons)
2c
3335 (NH), 1664
(C=O), 1635
(C=C), 1337, 1130
(SO2)
6.77 (d, 1H, C1’-H, J = 17.7 Hz), 7.07 (s, 1H, C2-H),
7.46 (d, 1H, C2’-H, J = 17.7 Hz), 7.21 - 7.89 (m, 9H,
Ar-H), 8.01 (s, 1H, C5-H), 10.81 (bs, 1H, NH)
108.8 (C-3), 118.3 (C-4), 121.2 (C-1’), 121.3 (C-2),
136.2 (C-5), 137.4 (C-2’), 189.6 (C=O), 128.2, 129.6,
130.3, 131.7, 133.8, 134.9, 135.6 (aromatic carbons)
3a 3329 (NH), 1662 (C=O), 1331, 1129
(SO2)
6.89 (s, 2H, C2-H and C2’-H), 6.96 (s, 1H, C5’-H), 7.25
- 7.78 (m, 10H, Ar-H), 8.04 (s, 1H, C5-H), 10.42 (bs,
2H, NH)
105.3 (C-4’), 109.6 (C-3 and C-3’), 115.3 (C-4),
118.5 (C-2 and C-2’), 119.7 (C-5’), 138.2 (C-5),
188.4 (C=O), 128.2, 129.5, 130.6, 131.3, 132.9,
133.7, 134.6, 135.2 (aromatic carbons)
3b 3324 (NH), 1668
(C=O), 1335, 1139
(SO2)
2.25 (s, 3H, Ar-CH3), 6.85 (s, 2H, C2-H and C2’-H),
6.99 (s, 1H, C5’-H), 7.19-7.74 (m, 9H, Ar-H), 8.02 (s,
1H, C5-H), 10.32 (bs, 2H, NH)
22.4 (Ar-CH3), 105.7 (C-4’), 109.2 (C-3 and 3’),
116.0 (C-4), 118.9 (C-2 and 2’), 119.4 (C-5’), 137.9
(C-5), 187.0 (C=O), 129.8, 131.2, 131.7, 132.3,
132.9, 133.4, 133.9 (aromatic carbons)
3c 3330 (NH), 1666
(C=O), 1329, 1126
(SO2)
7.13 (s, 2H, C2-H and C2’-H), 7.35 (s, 1H, C5’-H), 7.26
- 7.99 (m, 9H, Ar-H), 8.12 (s, 1H, C5-H), 10.55 (bs,
2H, NH)
104.8 (C-4’), 108.3 (C-3 and C-3’), 115.3 (C-4),
118.5 (C-2 and C-2’), 121.8 (C-5’), 138.3 (C-5),
187.5 (C=O), 128.3, 129.1, 129.8, 130.6, 132.4,
133.0, 137.4, 138.3 (aromatic carbons)
4a
3323 (NH), 1664
(C=O), 1570
(C=N), 1325, 1138
(SO2)
3.64 (dd, 1H, HX), 3.99 (dd, 1H, HM, JMX = 10.3 Hz),
4.54 (dd, 1H, HA, JAM = 11.6 Hz, JAX = 5.1 Hz), 6.18
(s, 1H, C2-H), 7.22 - 7.40 (m, 10H, Ar-H), 7.80 (s, 1H,
C5-H), 8.94 (bs, 1H, NH), 10.41 (bs, 1H, NH)
48.7 (C-5’), 57.5 (C-4’), 109.8 (C-3), 116.4 (C-4),
121.8 (C-2), 138.3 (C-5), 151.8 (C-3’), 188.7 (C=O),
127.1, 128.5, 128.8, 129.4, 130.7, 132.9, 134.1, 137.3
(aromatic carbons)
4b
3342 (NH), 1662
(C=O), 1576
(C=N), 1317, 1140
(SO2)
2.28 (s, 3H, Ar-CH3), 3.85 (dd, 1H, HX), 4.22 (dd, 1H,
HM, JMX = 8.2 Hz), 4.54 (dd, 1H, HA, JAM = 12.0 Hz,
JAX = 4.3 Hz), 6.94 (s, 1H, C2-H), 7.22 - 7.64 (m, 9H,
Ar-H), 7.95 (s, 1H, C5-H), 8.89 (bs, 1H, NH), 10.36
(bs, 1H, NH)
22.4 (Ar-CH3), 48.1 (C-5’), 58.5 (C-4’), 108.9 (C-3),
116.6 (C-4), 121.9 (C-2), 136.3 (C-5), 152.8 (C-3’),
188.6 (C=O), 128.3, 129.2, 130.4, 131.6, 132.7,
133.8, 134.2, 135.3 (aromatic carbons)
4c
3320 (NH), 1669
(C=O), 1569
(C=N), 1321, 1131
(SO2)
3.83 (dd, 1H, HX), 4.27 (dd, 1H, HM, JMX = 8.0 Hz),
4.56 (dd, 1H, HA, JAM = 12.1 Hz, JAX = 4.5 Hz), 6.97
(s, 1H, C2-H), 7.29 - 7.74 (m, 9H, Ar-H), 7.93 (s, 1H,
C5-H), 8.94 (bs, 1H, NH), 10.39 (bs, 1H, NH)
48.7 (C-5’), 59.2 (C-4’), 108.1 (C-3), 116.9 (C-4),
122.6 (C-2), 136.9 (C-5), 153.2 (C-3’), 187.1 (C=O),
128.6, 129.4, 130.8, 131.7, 132.6, 133.2, 135.6, 138.1
(aromatic carbons)
5a
3332 (NH), 1682
(C=O), 1572
(C=N), 1328, 1123
(SO2)
5.19 (d, 1H, C4’-H, J = 6.3 Hz), 5.58 (d, 1H, C5’-H, J =
6.3 Hz), 6.99 (s, 1H, C2-H), 7.21 - 7.74 (m, 20H, Ar &
Ar’-H), 8.01 (s, 1H, C5-H), 10.71 (bs, 1H, NH)
61.9 (C-4’), 82.8 (C-5’), 108.9 (C-3), 117.4 (C-4),
121.9 (C-2), 136.2 (C-5), 155.2 (C-3’), 188.4 (C=O),
127.3, 128.1, 128.6, 129.2, 130.2, 131.2, 132.7,
133.4, 134.6, 136.3 (aromatic carbons)
5b
3336 (NH), 1678
(C=O), 1564
(C=N), 1335, 1133
(SO2)
2.25 (s, 3H, Ar-CH3), 3.72 (s, 3H, OCH3), 5.23 (d, 1H,
C4’-H, J = 6.5 Hz), 5.54 (d, 1H, C5’-H, J = 6.5 Hz),
6.94 (s, 1H, C2-H), 7.29 - 7.71 (m, 18H, Ar & Ar’-H),
7.98 (s, 1H, C5-H), 10.67 (bs, 1H, NH)
22.6 (Ar-CH3), 55.6 (-OCH3), 62.5 (C-4’), 84.8
(C-5’), 108.2 (C-3), 117.9 (C-4), 121.2 (C-2), 135.2
(C-5), 154.9 (C-3’), 187.7 (C=O), 126.2, 127.6,
128.7, 129.4, 130.9, 131.2, 132.7, 133.2, 134.8, 135.6
(aromatic carbons)
5c
3347 (NH), 1684
(C=O), 1573
(C=N), 1331, 1135
(SO2)
5.27 (d, 1H, C4’-H, J = 6.8 Hz), 5.64 (d, 1H, C5’-H, J =
6.8 Hz), 6.98 (s, 1H, C2-H), 7.25 - 7.88 (m, 18H, Ar &
Ar’-H), 8.03 (s, 1H, C5-H), 10.64 (bs, 1H, NH)
63.1 (C-4’), 83.2 (C-5’), 108.5 (C-3), 117.5 (C-4),
121.8 (C-2), 135.6 (C-5), 155.5 (C-3’), 188.6 (C=O),
127.2, 128.6, 129.2, 129.9, 130.5, 131.8, 132.3,
133.1, 135.2, 137.1 (aromatic carbons)

V. PADMAVATHI ET AL.
82
6a
3340 (NH), 1662
(C=O), 1577
(C=N), 1336, 1131
(SO2)
5.22 (d, 1H, C4’-H, J = 6.4 Hz), 5.66 (d, 1H, C5’-H, J =
6.4 Hz), 6.93 (s, 1H, C2-H), 7.19 - 7.71 (m, 15H, Ar &
Ar’-H), 8.01 (s, 1H, C5-H), 10.61 (bs, 1H, NH)
62.4 (C-4’), 83.6 (C-5’), 108.7 (C-3), 116.9 (C-4),
122.5 (C-2), 136.8 (C-5), 155.0 (C-3’), 189.5 (C=O),
128.3, 129.1, 129.9, 130.2, 130.6, 131.2, 132.7,
133.4, 134.6, 136.3 (aromatic carbons)
6b
3337 (NH), 1669
(C=O), 1581
(C=N), 1329, 1130
(SO2)
2.23 (s, 3H, Ar-CH3), 3.69 (s, 3H, OCH3), 5.24 (d, 1H,
C4’-H, J = 6.5 Hz), 5.71 (d, 1H, C5’-H, J = 6.5 Hz),
6.98 (s, 1H, C2-H), 7.21 - 7.68 (m, 13H, Ar & Ar’-H),
7.99 (s, 1H, C5-H), 10.52 (bs, 1H, NH)
21.7 (Ar-CH3), 56.1 (-OCH3), 63.1 (C-4’), 84.6
(C-5’), 108.3 (C-3), 117.6 (C-4), 122.1 (C-2), 135.3
(C-5), 155.6 (C-3’), 188.3 (C=O), 127.2, 128.3,
129.6, 130.9, 131.4, 133.4, 133.9, 134.0, 134.5 (aro-
matic carbons)
6c
3332 (NH), 1667
(C=O), 1570
(C=N), 1339, 1142,
(SO2)
5.27 (d, 1H, C4’-H, J = 6.4 Hz), 5.76 (d, 1H, C5’-H, J =
6.4 Hz), 7.02 (s, 1H, C2-H), 7.25 - 7.78 (m, 13H, Ar &
Ar’-H), 8.06 (s, 1H, C5-H), 10.47 (bs, 1H, NH)
62.7 (C-4’), 84.0 (C-5’), 108.9 (C-3), 116.5 (C-4),
122.9 (C-2), 134.9 (C-5), 154.2 (C-3’), 189.1 (C=O),
128.7, 129.2, 130.9, 131.4, 132.7, 133.2, 134.8,
135.3, 137.2 (aromatic carbons)
7a
3339 (NH), 1656
(C=O), 1632
(C=C), 1564
(C=N), 1337, 1121
(SO2)
6.38 (bs, 1H, NH), 6.98 (s, 1H, C2-H), 7.26 - 7.62 (m,
11H, C5’-H & Ar-H), 7.96 (s, 1H, C5-H), 8.84 (bs, 1H,
NH)
110.1 (C-3), 115.9 (C-4), 122.1 (C-2), 135.2 (C-5),
137.3 (C-5’), 139.8 (C-4’), 153.4 (C-3’), 188.3
(C=O), 128.1, 129.7, 130.7, 131.1, 132.4, 133.9,
134.2, 135.2 (aromatic carbons)
7b
3328 (NH), 1668
(C=O), 1644
(C=C), 1574
(C=N), 1326, 1138
(SO2)
2.31 (s, 3H, Ar-CH3), 6.44 (bs, 1H, NH), 7.01 (s, 1H,
C2-H), 7.28 - 7.71 (m, 10H, C5’-H & Ar-H), 7.99 (s,
1H, C5-H), 8.72 (bs, 1H, NH)
22.7 (Ar-CH3), 109.5 (C-3), 115.1 (C-4), 122.9 (C-2),
134.8 (C-5), 136.6 (C-5’), 138.3 (C-4’), 154.7 (C-3’),
189.4 (C=O), 128.6, 129.3, 130.1, 131.8, 132.7,
133.2, 134.0, 134.9 (aromatic carbons)
7c
3336 (NH), 1666
(C=O), 1640
(C=C), 1567
(C=N), 1330, 1122
(SO2)
6.39 (bs, 1H, NH), 6.97 (s, 1H, C2-H), 7.21 - 7.78 (m,
10H, C5’-H & Ar-H), 8.03 (s, 1H, C5-H), 8.79 (bs, 1H,
NH)
110.4 (C-3), 114.7 (C-4), 122.2 (C-2), 135.0 (C-5),
135.1 (C-5’), 138.2 (C-4’), 155.2 (C-3’), 188.9
(C=O), 127.4, 128.7, 130.6, 131.2, 132.3, 133.5,
134.6, 135.0, 135.6 (aromatic carbons)
8a
3331 (NH), 1658
(C=O), 1637
(C=C), 1578
(C=N), 1335, 1126
(SO2)
7.04 (s, 1H, C2-H), 7.19 - 7.65 (m, 20H, Ar & Ar’-H),
7.97 (s, 1H, C5-H), 10.46 (bs, 1H, NH)
109.9 (C-3), 116.4 (C-4), 121.9 (C-2), 136.9 (C-5),
146.5 (C-3’), 147.8 (C-4’), 153.2 (C-5’), 187.8
(C=O), 127.0, 127.9, 128.7, 129.2, 129.9, 130.9,
131.8, 132.4, 133.9, 134.2, 135.3 (aromatic carbons)
8b
3338 (NH), 1669
(C=O), 1641
(C=C), 1569
(C=N), 1339, 1130
(SO2)
2.29 (s, 3H, Ar-CH3), 3.71 (s, 3H, OCH3), 6.98 (s, 1H,
C2-H), 7.22 - 7.71 (m, 18H, Ar & Ar’-H), 7.99 (s, 1H,
C5-H), 10.38 (bs, 1H, NH)
22.4 (Ar-CH3), 56.6 (-OCH3), 109.2 (C-3), 116.9
(C-4), 122.6 (C-2), 136.2 (C-5), 146.9 (C-3’), 148.2
(C-4’), 152.9 (C-5’), 188.5 (C=O), 128.2, 129.1,
129.7, 130.2, 131.5, 132.9, 133.5, 134.0, 134.7
(aromatic carbons)
8c
3335 (NH), 1671
(C=O), 1645
(C=C), 1565
(C=N), 1333, 1128
(SO2)
7.01 (s, 1H, C2-H), 7.27 - 7.83 (m, 18H, Ar & Ar’-H),
8.01 (s, 1H, C5-H), 10.42 (bs, 1H, NH)
109.5 (C-3), 116.1 (C-4), 121.8 (C-2), 136.4 (C-5),
146.1 (C-3’), 148.9 (C-4’), 152.2 (C-5’), 189.4
(C=O), 128.7, 129.4, 129.9, 130.5, 131.9, 132.2,
133.3, 134.6, 135.9 (aromatic carbons)
9a
3328 (NH), 1682
(C=O), 1656
(C=C), 1571
(C=N), 1327, 1138
(SO2)
6.96 (s, 1H, C2-H), 7.09 - 7.68 (m, 15H, Ar & Ar’-H),
8.01 (s, 1H, C5-H), 10.48 (bs, 1H, NH)
108.4 (C-3), 116.1 (C-4), 119.3 (C-2), 138.4 (C-5),
147.1 (C-4’), 148.3 (C-3’), 151.8 (C-5’), 187.7
(C=O), 130.0, 130.3, 130.4, 130.6, 130.8, 131.0,
132.7, 134.1 (aromatic carbons)
9b
3339 (NH), 1678
(C=O), 1651
(C=C), 1579
(C=N), 1321, 1135
(SO2)
2.26 (s, 3H, Ar-CH3), 3.67 (s, 3H, -OCH3), 6.92 (s,
1H, C2-H), 7.14 - 7.76 (m, 13H, Ar & Ar’-H), 8.03 (s,
1H, C5-H), 10.31 (bs, 1H, NH)
22.7 (Ar-CH3), 57.8 (-OCH3), 109.1 (C-3), 117.2
(C-4), 122.9 (C-2), 135.7 (C-5), 146.9 (C-4’), 148.8
(C-3’), 152.9 (C-5’), 189.9 (C=O), 127.6, 128.2,
128.7, 130.7, 131.3, 131.9, 132.8, 133.1, 134.8
(aromatic carbons)
9c
3332 (NH), 1684
(C=O), 1648
(C=C), 1583
(C=N), 1339, 1145
(SO2)
7.03 (s, 1H, C2-H), 7.21 - 7.82 (m, 13H, Ar & Ar’-H),
7.99 (s, 1H, C5-H), 10.43 (bs, 1H, NH)
109.6 (C-3), 117.9 (C-4), 122.4 (C-2), 135.9 (C-5),
146.2 (C-4’), 148.3 (C-3’), 153.4 (C-5’), 189.7
(C=O), 128.6, 129.5, 130.4, 131.2, 132.6, 133.1,
133.9, 134.7, 135.9 (aromatic carbons)

V. PADMAVATHI ET AL.
83
and JMX = 10.3 Hz indicates that HA and HM are cis, HA
and HX are trans and HM and HX are geminal (Table 2).
Similarly, 1,3-dipolar cycloaddition reaction of nitrile
imines and nitrile oxides generated from araldehyde
phenylhydrazones and araldoximes to 2 resulted in 4-
aroyl-3-(1’,5’-diphenyl-3’-aryl-4’,5’-dihydro-1’H-pyrazo
l-4’-ylsulfonyl)-1H-pyrrole (5) and 4-aroyl-3-(3’-aryl-
5’-phenyl-4’,5’-dihydroisoxazol-4’-ylsulfonyl)-1H-pyrro
le (6), respectively (Scheme 1, Table 1). The 1H-NMR
spectra of 5a and 6a displayed two doublets at δ 5.19,
5.22 and 5.58, 5.66 ppm, which are assigned to C4’-H
and C5’-H, the two methine protons of the pyrazoline and
isoxazoline rings. The J values (J = 6.3 & 6.4 Hz) shows
that they are in trans geometry.
The compounds 4, 5 and 6 upon oxidation with
chloranil in xylene gave the corresponding pyrazoles and
isoxazoles, 4-aroyl-3-(4’-phenyl-1’H-pyrazol-3’-ylsul-
fonyl)-1H-pyrrole (7), 4-aroyl-3-(1’,5’-diphenyl-3’-aryl-
1’H-pyrazol-4’-ylsulfonyl)-1H-pyrrole (8) and 4-aroyl-
3-(3’-aryl-5’-phenylisoxazol-4’-ylsulfonyl)-1H-pyrrole
(9) (Scheme 1, Table 1). The disappearance of signals
due to pyrazoline/isoxazoline ring protons in the 1H
NMR spectra of 7-9 confirms their formation. The struc-
tures of 2-9 are further established by elemental analyses,
IR and 13C NMR spectroscopy (Tables 1 and 2).
3. Antimicrobial Testing
The compounds 2, 3, 7-9 were tested for antimicrobial
activity at two different concentrations 100 and 200
μg/mL. The antibacterial activity was screened against
Staphylococcus aureus, Bacillus subtilis (Gram-positive
bacteria) and Escherichia coli, Klebsiella pneumoniae
(Gram-negative bacteria) on nutrient agar plates at 37˚C
for 24 hr using chloramphenicol as reference drug. The
compounds were also evaluated for their antifungal ac-
tivity against Fusarium solani, Curvularia lunata and
Aspergillus niger using ketoconazole as standard drug.
Fungi cultures were grown on potato dextrose agar me-
dium (PDA) at 25˚C for 3 days. The spore suspension
was adjusted to 106 pores/mL at an mg/mL concentra-
tion by the Vincent and Vincent method [23].
The results of the compounds of preliminary antibac-
terial testing are shown in Table 3. The results revealed
that the compounds 2 and 3 exhibited least activity
against Gram-positive bacteria and almost no activity
against Gram-negative bacteria. However, the other com-
pounds showed higher inhibitory activity against Gram-
positive bacteria than that of Gram-negative bacteria. It
was reported that good DNA binding properties are a
prerequisite for antibacterial activity [8]. This was evi-
denced by the fact that the compounds 7 showed good
activity when compared with compounds 8. This may be
due to the bulkier tetrasubstituted pyrazole destroys
DNA binding and activity. In fact, the compounds hav-
ing trisubstituted pyrazole (7) and disubstituted isoxazole
(9) units exhibited good activity when compared with the
compounds having terasubstituted pyrazole (8) unit. It
was observed that the presence of chloro substituent en-
hances the activity. The compounds 7c and 9c displayed
excellent activity against Gram-positive bacteria (inhibi-
tory zone > 28 mm) and good activity against Gram-
negative bacteria (inhibitory zone > 22 mm). All the test
compounds showed moderate to high inhibitory effect
towards tested fungi (Table 4).
The MIC values were determined as the lowest con-
centration that completely inhibited visible growth of the
microorganisms (Table 5). The structure-antimicrobial
activity relationship of the tested compounds revealed
that disubstituted pyrazole and trisubstituted isoxazole in
Table 3. The in vitro antibacterial activity of compounds 2,
3, 7-9.
Zone of inhibition (mm)
Gram (+)ve Gram (-)ve
Compd Concentration
(g/ml) S.
aureus B. subtilis E. coli K. pneumoniae
2a 100 10 9 - -
200 12 11 - -
2b 100 8 9 - -
200 10 11 - -
2c 100 13 11 18 9
200 15 14 19 11
3a 100 12 13 - -
200 15 15 10 -
3b 100 10 09 - -
200 12 12 - -
3c 100 15 14 11 12
200 18 17 13 14
7a 100 25 22 19 18
200 28 24 22 20
7b 100 19 20 18 16
200 21 23 20 19
7c 100 30 28 22 20
200 32 31 25 23
8a 100 16 15 15 14
200 18 17 17 17
8b 100 15 16 10 12
200 17 18 13 14
8c 100 19 19 15 14
200 21 21 17 17
9a 100 23 21 18 18
200 25 24 20 19
9b 100 22 20 17 15
200 24 23 19 17
9c 100 27 25 21 20
200 29 28 24 23
Chloraphenicol 100 35 38 37 42
200 41 44 42 45

V. PADMAVATHI ET AL.
84
Table 4. The in vitro antifungal activity of compounds 2, 3,
7-9.
Zone of inhibition (mm)
Compd Concentration
(g/ml) F. solani C. lunata A. niger
2a 100 17 13 12
200 21 16 14
2b 100 15 12 10
200 18 14 13
2c 100 17 17 15
200 20 21 19
3a 100 16 13 10
200 18 14 13
3b 100 14 10 9
200 15 12 12
3c 100 18 16 14
200 20 19 17
7a 100 29 26 22
200 32 32 24
7b 100 26 26 23
200 30 31 26
7c 100 33 32 27
200 35 36 29
8a 100 17 17 14
200 20 21 17
8b 100 16 16 15
200 19 20 18
8c 100 17 18 17
200 21 21 20
9a 100 25 26 23
200 27 29 26
9b 100 22 23 19
200 26 25 23
9c 100 28 28 26
200 32 30 29
Ketoconazole 100 38 41 36
200 42 44 39
combination with pyrrole displayed greater activity. The
compounds having tetrasubstituted pyrazole with pyrrole
exhibited least activity. The maximum activity waso-
bserved with the compounds 7c and 9c.
4. Experimental Section
Melting points were determined in open glass capillaries
on a Mel-Temp apparatus and are uncorrected. The pu-
rity of the compounds was checked by TLC (silica gel H,
BDH, ethyl acetate/hexane, 1:3). The IR spectra were
recorded on a Thermo Nicolet IR 200 FT-IR spectrome-
ter as KBr pellets and the wave numbers were given in
cm-1. The 1H and 13C NMR spectra were run in CDCl3/
DMSO-d6 on a Jeol JNM spectrometer operating at 400
and 100 MHz. All chemical shifts were reported in δ
ppm using TMS as an internal standard. The elemental
analyses were determined on a Perkin-Elmer 24˚C ele-
mental analyzer. The starting material 1-aroyl-2-styryl-
sulfonylethene (1) was prepared by the literature proce-
dure [24].
Method 1:
General procedure for the synthesis of 4-aroyl-3-(phen-
ylethenesulfonyl)-1H-pyrrole (2)/4-aroyl-3-(4’-phenyl-
1’H -pyrrol-3’-ylsulfonyl)-1H-pyrrole (3)
A mixture of 1 (0.5 mmol) and TosMIC (1 mmol) in
Et2O-DMSO (2:1) was added dropwise under stirring to
a suspension of NaH (2 mmol) in Et2O (10 mL) at room
temperature and stirring was continued for 5 - 6 hr. Then,
water was added and the reaction mass was extracted
with Et2O. The ethereal fraction was dried over anhy-
drous Na2SO4. The solvent was removed in vacuo. The
resulting mixture was separated by column chromatog-
raphy (hexane-ethyl acetate; 4:1) and identified as
4-aroyl-3-(phenylethenesulfonyl)-1H-pyrrole (2) (major)
and 4-aroyl-3-(4’-phenyl-1’H-pyrrole-3’-ylsulfonyl)-1H-
pyrrole (3) (minor).
Method 2:
General procedure for the synthesis of 4-aroyl-3-(4’-
phenyl-1’H-pyrrol-3’-ylsulfonyl)-1H-pyrrole (3)
A solution of 1 (1 mmol) and TosMIC (4 mmol) in
Et2O-DMSO (2:1) was added dropwise under stirring to
a suspension of NaH (4 mmol) in Et2O (20 mL) at RT
and stirring was continued for about 3 - 4 hr. Then, water
was added and the reaction mass extracted with Et2O.
The ethereal layer was dried (an. Na2SO4) and the sol-
vent was removed in vacuo. The solid obtained was puri-
fied by column chromatography (ethyl acetate/hexane,
1:4).
Method 3:
The compound 3 was also obtained by adding an
equimolar (5 mmol) mixture of 2 and TosMIC in
Et2O-DMSO (2:1) dropwise under stirring to a suspension
of NaH (1 mmol) in Et2O (6 mL) at RT. Stirring was con-
tinued for 4 - 5 hr. Then, the contents were diluted with wa-
ter and extracted with Et2O. The ethereal layer was dried
over anhydrous Na2SO4. Evaporation of the solvent
Table 5. Minimum inhibitory concentration of compounds 7c and 9c.
Minimum inhibitory concentration (MIC), g/ml
Compd S. aureus B. subtilis E. Coli K. pneumoniae F. solani C. lunata A. niger
7c 50 50 100 50 25 12.5 50
9c 100 100 100 100 100 50 100
Chloramphenicol 6.25 6.25 6.25 12.5 - - -
Ketoconazole - - - - 12.5 6.25 6.25

V. PADMAVATHI ET AL. 85
under vacuum resulted in a solid which was purified by
column chromatography (ethyl acetate/hexane, 1:4).
General procedure for the synthesis of 4-aroyl-3-(4’-
phenyl-4’,5’-dihydro-1’H-pyrazol-3’-ylsulfonyl)-1H-pyr
role (4)
To a cooled solution of 2 (5 mmol) in dichloromethane
(20 mL), an ethereal solution of diazomethane (40 ml,
0.4 M) and triethylamine (0.12 g) were added. The reac-
tion mixture was kept at –20 to –15 ˚C for 40 - 48 hr.
The solvent was removed under reduced pressure and the
resultant solid was recrystallized from 2-pro- panol.
General procedure for the synthesis of 4-aroyl-3-
(1’,5’-diphenyl-3’-aryl-4’,5’-dihydro-1’H-pyrazol-4-yl-
sulfonyl)-1H-pyrrole (5)
A mixture of 2 (1 mmol), araldehyde phenylhydrazone
(2 mmol) and chloramine-T (2 mmol) in methanol (15
mL) was refluxed for 16 - 18 hr on a water bath. The
precipitated inorganic salts were filtered off. The filtrate
was concentrated and the residue was extracted with di-
chloromethane. The organic layer was washed with wa-
ter, saturated brine and dried over anhydrous Na2SO4.
Evaporation of the solvent under reduced pressure af-
forded a crude product which was recrystallized from
ethanol.
General procedure for the synthesis of 4-aroyl-3-
(3’-aryl-5’-phenyl-4’,5’-dihydroisoxazol-4’-ylsulfonyl)-
1H-pyrrole (6)
The compound 2 (1 mmol), araldoxime (2 mmol) and
chloramine-T (2 mmol) in methanol (20 mL) was re-
fluxed for 14-16 hr on a water bath. The precipitated
inorganic salts were filtered off. The filtrate was concen-
trated and the residue was extracted with dichloro-
methane. The organic layer was washed with water, sa-
turated brine and dried over anhydrous Na2SO4. The sol-
vent was removed in vacuo. The solid obtained was puri-
fied by recrystallization from ethanol.
General procedure for the synthesis of 4-aroyl-3-
(4’-phenyl-1’H-pyrazol-3’-ylsulfonyl)-1H-pyrrole (7)/4-
aroyl-3-(1’,5’-diphenyl-3’-aryl-1’H-pyrazol-4’-yl-sulfon
yl)-1H-pyrrole (8)/4-aroyl-3-(3’-aryl-5’-phenylisoxazol-
4’-ylsulfonyl)-1H-pyrrole (9)
A solution of 4-6 (1 mmol) and chloranil (1.4 mmol)
in xylene (10 mL) was refluxed for 25 - 30 hr. 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 Na2SO4 and
the solvent was removed on a rotary evaporator. The
resultant solid was purified by recrystallization from me-
thanol.
5. Conclusions
A new class of bis heterocycles 4-aroyl-3-(4’-phenyl-
1’H-pyrazol-3’-ylsulfonyl)-1H-pyrrole (7), 4-aro-yl-3-
(1’,5’-diphenyl-3’-aryl-1’H-pyrazol-4’-ylsulfonyl)-1H-
pyrrole (8) and 4-aroyl-3-(3’-aryl-5’-phenylisoxazol-
4’-ylsulfonyl)-1H-pyrrole (9) were prepared by the re-
gioselective reaction of tosylmethyl isocyanide and 1,3-
dipolar cycloaddtion reaction of diazomethane, nitrile
imines and nitrile oxides with 1-aroyl-2-styrylsulfonyle-
thene (1). The antimicrobial testing showed that the com-
pounds 7c and 9c exhibited greater antimicrobial acti-
vity.
6. Acknowledgements
The authors are thankful to UGC, New Delhi, India for
financial assistance under major research project.
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