Synthesis and biological activity of a new class of sulfone-linked pyrrolylpyrazoles and pyrrolylisoxazoles from methyl-3-aryl-2-(E- arylethenesulfonyl)acrylate

Article abstract of DOI:10.1248/cpb.57.1200

A new class of sulfone-linked bis heterocycles, methyl-3-(4′-aryl- 1′H-pyrazol-3′-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (8), methyl-3-(1′-phenyl-3′,5′-diaryl-1′H-pyrazol-4′- ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (9) and methyl-3-(3′,5′- diaryl

Full text of DOI:10.1248/cpb.57.1200

1200
Chem. Pharm. Bull. 57(11) 1200—1205 (2009)
Vol. 57, No. 11
Synthesis and Biological Activity of a New Class of Sulfone-Linked
Pyrrolylpyrazoles and Pyrrolylisoxazoles from Methyl-3-aryl-2-(E-
arylethenesulfonyl)acrylate
Venkatapuram PADMAVATHI,* Thunga RADHA LAKSHMI, Konda MAHESH, and Adivireddy PADMAJA
Department of Chemistry, Sri Venkateswara University; Tirupati–517 502, India.
Received April 9, 2009; accepted August 18, 2009; published online August 31, 2009
A new class of sulfone-linked bis heterocycles, methyl-3-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-aryl-3H-pyr-
role-3-carboxylate (8), methyl-3-(1ꢀ-phenyl-3ꢀ,5ꢀ-diaryl-1ꢀH-pyrazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxy-
late (9) and methyl-3-(3ꢀ,5ꢀ-diarylisoxazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (10) were prepared by
the regioselective reaction of methyl-3-aryl-2-(E-arylethenesulfonyl)acrylate (2) with tosylmethyl isocyanide fol-
lowed by fuctionalization of olefin moiety with 1,3-dipolar reagents. The lead compounds were tested for their
antimicrobial activity.
Key words pyrroly-pyrazole; isoxazole; 1,3-dipolar cycloaddition; antimicrobial activity
In recent years there has been an intense effort to develop zomethane, nitrile imines and nitrile oxides (Chart 1). The
biologically potent heterocycles. In fact, molecules contain- compound 2 is prepared by the Knoevenagel condensation of
ing five-membered heterocycles have elicited considerable E-styrylsulfonylacetic acid methyl ester (1) with araldehydes
1
interest with an astonishingly wide range of applications in in the presence of piperidine in ethanol. The H-NMR spec-
synthetic organic chemistry. Amongst them pyrrole, pyrazole trum of 2a displayed two doublets at 7.68, 6.58 for HA and
and isoxazole derivatives are important intermediates in or- HB and a singlet at 7.98 ppm for HC. Apart from these an-
ganic synthesis and useful building blocks for biologically other singlet is observed at 3.81 ppm for methoxy protons of
active compounds. Pyrroles are abundant as constituents of carbomethoxy group. The compound 2 is treated with
natural products and have broad synthetic utility in both ma- TosMIC in the presence of sodium hydride in a mixture of
terials science and medicine.1—3) Pyrrole containing pharma- ether and DMSO. The solid obtained indicated two spots in
ceuticals include the cholesterol lowering drug lipitor.4) In TLC which are identified as methyl-3-(4ꢀ-aryl-1ꢀH-pyrrol-3ꢀ-
addition, pyrazolines and isoxazolines have gained impor- ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (3) and methyl-
tance due to their various chemotherapeutic properties. In 4-aryl-3-(arylethenesulfonyl)-3H-pyrrole-3-carboxylate (4)
deed, Celecoxib a pyrazole derivative and Valdecoxib an in minor and major amounts, respectively (Chart 1). How-
isoxazole derivative are now widely used in the market as ever, repetition of this reaction with excess TosMIC resulted
anti-inflammatory drugs.5) Apart from varied biological in 3 only. The compound 3a showed four singlets at 7.19,
properties the lability of 2-isoxazoline ring led to a variety of 7.09, 6.78 and 7.01 ppm due to C2-H, C5-H, C2ꢀ-H and C5ꢀ-H
1,3-bifunctionalized compounds such as a,b-aminoalcohols, of pyrrole ring protons and another singlet at 3.69 ppm due to
b-hydroxyketones, 1,3-diketones, b-hydroxy nitriles, acids methoxy protons of carbomethoxy group as well as signals
and esters which are used widely in the synthesis of a variety due to aromatic protons. The compound 4a exhibited two
of natural products.6—9) In the literature, multistep synthetic doublets at 7.72, 6.59 ppm due to HA and HB and three sin-
routes to 3,4-disubstituted pyrroles have been reported either glets at 7.14, 7.01 and 3.64 ppm due to C2-H, C5-H and
by coupling of imines and nitroalkanes or by using Friedal- methoxy protons of carbomethoxy group.
Craft’s acylation in the presence of an electron-withdrawing
The olefin moiety in 4 is used to develop pyrazoline and
group on the pyrrole nitrogen or on 3,4-silylated precur- isoxazoline rings by 1,3-dipolar cycloaddition of diazo-
sors.10—12) 3,4-Disubstituted pyrroles have also been synthe- methane, nitrile imines and nitrile oxides. Treatment of 4
sized from Michael acceptors and tosylmethyl isocyanide with diazomethane at ꢁ20 to ꢁ15 °C for 48 h in the presence
(TosMIC).13—16) Amongst different methods for the prepara- of triethylamine produced methyl-3-(4ꢀ,5ꢀ-dihydro-4ꢀ-aryl-
tion of pyrazolines, isoxazolines, the 1,3-dipolar cycloaddi- 1ꢀH-pyrazol-3-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate
1
tion is the most important and versatile one. The dipolar (5). The H-NMR spectrum of 5a showed an AMX splitting
reagents can be generated by the dehydrogenation of aralde- pattern for pyrazoline ring protons exhibiting three double
hyde hydrazones and araldoximes with lead tetracetate,17) doublets at 4.57 (HA), 4.24 (HM) and 3.88 ppm (HX) in addi-
mercury acetate,18) 1-chlorobenzotriazole,19) chloramine-T tion to signals due to pyrrole ring, carbomethoxy and aro-
(CAT)20—25) etc. In fact, we have reported novel oxo-linked matic protons. The coupling constant values JAMꢂ12.0 Hz,
bis heterocycles by 1,3-dipolar cycloaddition of dipolar
JMXꢂ8.0 Hz and JAXꢂ4.0 Hz indicates that HA, HM are cis,
reagents viz., TosMIC, diazomethane, nitrile imines and ni- HA, HX are trans and HM, HX are geminal.20,21) The cyclocon-
trile oxides to symmetrical and unsymmetrical bischal- densation of 4 with araldehyde phenylhydrazones in the pres-
cones.26,27) In our endeavour to prepare sulfone-linked bis ence of chloramine-T in methanol resulted in methyl-3-
heterocycles the present work has been taken up.
(4ꢀ,5ꢀ-dihydro-1ꢀ-phenyl-3ꢀ,5ꢀ-diaryl-pyrazol-4ꢀ-ylsulfonyl)-
Chemistry The present communication deals with the 4-aryl-3H-pyrrole-3-carboxylate (6) (Chart 1). Similar reac-
reactivity of methyl-3-aryl-2-(E-arylethenesulfonyl)acrylate tion of 4 with araldoximes produced methyl-3-(4ꢀ,5ꢀ-dihy-
(2) towards TosMIC and 1,3-dipolar reagents viz., dia- dro-3ꢀ,5ꢀ-diarylisoxazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-
© 2009 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: vkpuram2001@yahoo.com

November 2009
1201
Chart 1
carboxylate (7). The 1H-NMR spectra of 6a and 7a displayed disc) as standard drug. Fungi cultures were grown on potato
two doublets at 5.21, 5.16 (C4ꢀ-H) and at 5.58, 5.75 ppm dextrose agar medium (PDA) at 25 °C for 3 d. The spore sus-
(C5ꢀ-H) in addition to signals due to other protons. The dehy- pension was adjusted to 106 pores/ml at an mg/ml concentra-
drogenation of pyrazoline and isoxazoline rings in 5, 6 and 7 tion by the Vincent and Vincent method.28)
is effected with chloranil in xylene. Thus the compounds
The results of the compounds of preliminary antibacterial
methyl-3-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-aryl-3H-pyr- testing are shown in Table 1. The results revealed that the
role-3-carboxylate (8), methyl-3-(1ꢀ-phenyl-3ꢀ,5ꢀ-diaryl-1ꢀH- compounds 3a—c and 4a—c exhibited least activity against
pyrazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (9) and the Gram-positive bacteria and almost no activity against the
methyl-3-(3ꢀ,5ꢀ-diarylisoxazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyr- Gram-negative bacteria. However, the other compounds
role-3-carboxylate (10) are prepared (Chart 1). The absence of showed higher inhibitory activity against the Gram-positive
signals due to pyrazoline and isoxazoline ring protons indi- bacteria than that of the Gram-negative bacteria. The com-
cated the formation of 8, 9 and 10. The structures of these pounds 8b and 10b displayed excellent activity against the
compounds are further established by 13C-NMR spectra.
Gram-positive bacteria (inhibitory zone ꢃ34 mm) and good
Antimicrobial Testing The compounds 3, 4, 8—10 activity against Gram-negative bacteria (inhibitory zone
were tested for antimicrobial activity at two different concen- ꢃ24 mm). Thus the compounds having pyrrole 8a—c and
trations 100 and 200 mg/ml. The antibacterial activity was isoxazole 10a—c units exhibited good activity when com-
screened against Staphylococcus aureus, Bacillus subtilis pared with the compounds having pyrrole unit 3a—c and
(Gram-positive bacteria) and Escherichia coli, Klebsiella 4a—c. However, the compounds with tetrasubstituted pyra-
pneumoniae (Gram-negative bacteria) on nutrient agar plates zole ring 9a—c exhibited least activity against both bacteria.
at 37 °C for 24 h using chloramphenicol (25 mg per disc) as All the test compounds showed moderate to high inhibitory
reference drug. The compounds were also evaluated for their effect towards tested fungi. The presence of chloro sub-
antifungal activity against Fusarium solani, Curvularia lu- stituent enhances the antimicrobial activity (Table 2).
nata and Aspergillus niger using ketoconazole (25 mg per
The MIC values were determined as the lowest concentra-

1202
Vol. 57, No. 11
Table 2. Antifungal Activity of 3, 4, 8—10
Table 1. Antibacterial Activity of 3, 4, 8—10
Zone of inhibition (mm)
Zone of inhibition (mm)
Gram (ꢄ)ve Gram (ꢁ)ve
Concentration
Compound
Concentration
(mg)
Compound
F. solani
C. lunata
A. niger
(mg/ml)
S. aureus B. subtilis E. coli K. pneumoniae
3a
3b
3c
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
14
17
16
19
13
15
12
16
15
17
11
14
27
32
36
39
33
35
15
20
17
22
19
20
23
27
26
30
24
27
38
42
12
14
13
16
13
16
13
16
14
16
10
12
27
33
39
41
33
37
14
19
18
23
15
22
22
26
26
29
27
30
41
44
15
18
12
16
14
16
14
17
12
15
13
17
30
34
31
34
32
36
18
22
15
18
16
20
21
25
27
31
24
29
36
39
3a
3b
3c
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
14
17
14
18
13
15
—
10
09
12
—
09
21
25
32
38
30
34
16
18
19
22
16
19
21
24
32
36
27
30
35
39
12
14
15
17
11
14
—
—
—
11
—
—
19
23
32
36
28
32
17
19
20
23
17
18
20
23
29
34
29
32
38
41
—
10
10
12
—
—
—
—
—
—
—
—
14
18
25
27
21
25
11
14
13
15
12
14
16
18
23
25
19
22
40
44
—
10
—
11
—
—
—
—
—
—
—
—
13
17
22
26
20
23
10
13
14
16
10
13
17
19
21
24
18
21
42
45
4a
4a
4b
4c
4b
4c
8a
8a
8b
8c
8b
8c
9a
9a
9b
9c
9b
9c
10a
10b
10c
10a
10b
10c
Ketoconazole 100
200
Chloramphenicol 100
200
Table 3. Minimal Inhibitory Concentrations (MIC, mg/ml) of Compounds 8b and 10b
Minimal inhibitory concentration (MIC, mg/ml)
Compound
S. aureus
B. subtilis
E. coli
K. pneumoniae
F. solani
C. lunata
A. niger
8b
10b
25
50
6.25
—
50
100
6.25
—
50
100
6.25
—
50
100
12.5
—
50
100
—
25
100
—
25
100
—
Chloramphenicol
Ketoconazole
12.5
6.25
6.25
tion that completely inhibited visible growth of the microor- role-3-carboxylate (10) were prepared by the regioselective
ganisms (Table 3). The structure–antimicrobial activity rela- reaction of methyl-3-aryl-2-(E-arylethenesulfonyl)acrylate
tionship of the tested compounds revealed that disubstituted (2) with TosMIC followed by functionalization of olefin moi-
pyrazole and trisubstituted isoxazole in combination with ety towards 1,3-dipolar cycloaddition reaction with dia-
pyrrole displayed greater activity. The compounds having zomethane, nitrile imines and nitrile oxides. The antimicro-
tetrasubstituted pyrazole with pyrrole exhibited least activity. bial testing showed that the compounds 8b and 10b exhibited
The maximum activity was observed with the compounds 8b greater antimicrobial activity.
and 10b.
Experimental
Melting points were determined in open capillaries on a Mel-Temp appa-
Conclusion
ratus and are uncorrected. The purity of the compounds was checked by
TLC (silica gel H, BDH, ethyl acetate/hexane, 3 : 1). The IR spectra were
recorded on a Thermo Nicolet IR 200 FT-IR spectrometer as KBr pellets and
A new class of sulfone-linked bis heterocycles, methyl-
3-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-
carboxylate (8), methyl-3-(1ꢀ-phenyl-3ꢀ,5ꢀ-diaryl-1ꢀH-pyra-
zol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (9) and
methyl-3-(3ꢀ,5ꢀ-diarylisoxazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyr-
1
the wave numbers were given in cm-1. The H-NMR spectra were recorded
in CDCl3/DMSO-d6 on a Jeol JNM l-300 MHz. The 13C-NMR spectra were
recorded in CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
75.5 MHz. All chemical shifts were reported in d (ppm) using TMS as an

November 2009
1203
internal standard. The microanalyses were performed on Perkin-Elmer 240C
elemental analyzer. The starting compound E-styrylsulfonylacetic acid
methyl ester (1) was prepared as per the literature procedure.29)
General Procedure of Synthesis of Methyl-3-aryl-2-(E-arylethenesul-
fonyl)acrylate (2a—c) To an equimolar (0.01 mol) mixture of E-styrylsul-
fonylacetic acid methyl ester 1, araldehyde and absolute ethanol (10 ml),
piperidine (0.3 ml) was added and refluxed for 6—8 h. The solid separated
on cooling was collected and recrystallized from 2-propanol.
Methyl-3-phenyl-2-(E-phenylethenesulfonyl)acrylate (2a): White solid,
yield 66%, mp 97—99 °C; IR (KBr) cmꢁ1: 1733 (CꢂO), 1634 (CꢂC), 1332,
1131 (SO2); 1H-NMR (CDCl3) d: 3.81 (s, 3H, OCH3), 6.58 (d, 1H, HB,
Jꢂ14.2 Hz), 7.68 (d, 1H, HA, Jꢂ14.2 Hz), 7.98 (s, 1H, HC), 7.11—7.59 (m,
10H, Ar, Arꢀ-H ); 13C-NMR (CDCl3) d: 54.8 (OCH3), 125.4 (ꢂCHSO2),
129.7 (SO2-Cꢂ(CO2Me), 142.1 (ꢂCH-Arꢀ), 145.4 (ꢂCH-Ar), 172.4 (Cꢂ
O), 128.6, 129.2, 129.4, 130.6, 131.8, 132.4, 131.9, 133.1 (aromatic car-
bons).
Methyl-3-(4ꢀ-(p-methylphenyl)-1ꢀH-pyrrol-3ꢀ-ylsulfonyl)-4-(p-
chlorophenyl)-3H-pyrrole-3-carboxylate (3c): Yellow solid, yield 74%, mp
149—151 °C; IR (KBr) cmꢁ1: 3342 (NH), 1744 (CꢂO), 1562 (CꢂN), 1128,
1333 (SO2); 1H-NMR (DMSO-d6) d: 2.21 (s, 3H, Ar-CH3), 3.67 (s, 3H,
OCH3), 6.76 (s, 1H, C2ꢀ-H), 6.89, 7.05 (s, 2H, C5ꢀ-H, C5-H), 7.17 (s, 1H, C2-
H) 7.21-7.68 (m, 8H, Ar, Arꢀ-H), 8.81 (br s, 1H, NH); 13C-NMR (DMSO-d6)
d: 22.4 (Ar-CH3), 53.1 (OCH3), 76.9 (C-3), 115.5, 117.1 (C-4ꢀ, C-4), 120.7
(C-3ꢀ), 124.3, 126.9 (C-5ꢀ, C-5), 124.3, (C-2ꢀ) 156.2 (C-2), 162.8 (CꢂO),
128.4, 129.6, 130.2, 131.9, 132.6, 133.2, 133.9, 136.6 (aromatic carbons):
Anal. Calcd for C23H19ClN2O4S: C, 60.72; H, 4.21; N, 6.16; Found: C,
60.63; H, 4.16; N, 6.20.
General Procedure of Synthesis of Methyl-4-aryl-3-(arylethenesul-
fonyl)-3H-pyrrole-3-carboxylate (4a—c) (Method 3) The compound 4
was also obtained by adding an equimolar (0.005 mol) mixture of 3-aryl-2-
(E-arylethenesulfonyl)acrylate 2 and TosMIC in Et2O–DMSO (2 : 1) drop-
wise under stirring to a suspension of NaH (25 mg) in Et2O (6 ml) at room
temperature. Stirring was continued for 4—5 h. Then, the contents were di-
luted with water and extracted with Et2O. The ethereal layer was dried over
anhydrous Na2SO4. The solvent was removed under vacuum. The resultant
solid was purified by column chromatography (ethyl acetate/hexane, 1 : 4).
Methyl-4-phenyl-3-(phenylethenesulfonyl)-3H-pyrrole-3-carboxylate
(4a): Yellow solid, yield 72%, mp 133—135 °C; IR (KBr) cmꢁ1: 1731 (Cꢂ
Methyl-3-(p-chorophenyl)-2-(E-phenylethenesulfonyl)acrylate
(2b):
White solid, yield 74%, mp 129—131 °C; IR (KBr) cmꢁ1: 1735 (CꢂO),
1
1632 (CꢂC), 1333, 1129 (SO2); H-NMR (CDCl3) d: 3.79 (s, 3H, OCH3),
6.56 (d, 1H, HB, Jꢂ14.1 Hz), 7.61 (d, 1H, HA, Jꢂ14.1 Hz), 7.95 (s, 1H, HC),
7.36—7.64 (m, 9H, Ar, Arꢀ-H); 13C-NMR (CDCl3) d: 52.8 (OCH3), 124.7
(ꢂCHSO2), 129.3 (SO2-Cꢂ(CO2Me), 142.8 (ꢂCH-Arꢀ), 145.2 (ꢂCH-Ar),
174.3 (CꢂO), 128.8, 129.4, 129.9, 131.4, 131.8, 132.0, 132.4, 132.8 (aro-
matic carbons).
1
O), 1635 (CꢂC), 1569 (CꢂN), 1337, 1121 (SO2); H-NMR (DMSO-d6) d:
3.64 (s, 3H, OCH3), 6.59 (d, 1H, HB, Jꢂ14.1 Hz), 7.01 (s, 1H, C5-H), 7.14
(s, 1H, C2-H), 7.72 (d, 1H, HA, Jꢂ14.1 Hz), 7.19—7.66 (m, 10H, Ar, Arꢀ-
H); 13C-NMR (DMSO-d6) d: 52.7 (OCH3), 76.4 (C-3), 117.9 (C-4), 124.8
(C-5), 125.4 (ꢂCHSO2), 145.4 (ꢂCH-Ar), 156.6 (C-2), 163.2 (CꢂO),
127.6, 129.1, 130.7, 131.4, 132.3, 133.0, 133.6, 134.2 (aromatic carbons):
Anal. Calcd for C20H17NO4S: C, 65.38; H, 4.66; N, 3.81; Found: C, 65.26;
H, 4.69; N, 3.85.
Methyl-3-(p-chorophenyl)-2-(E-(p-methylphenyl)ethenesulfonyl)acrylate
(2c): White crystals, yield 69%, mp 112—114 °C; IR (KBr) cmꢁ1: 1744
1
(CꢂO), 1636 (CꢂC), 1326, 1130 (SO2); H-NMR (CDCl3) d: 2.29 (s, Ar-
CH3), 3.82 (s, 3H, OCH3), 6.68 (d, 1H, HB, Jꢂ14.4 Hz), 7.67 (d, 1H, HA, Jꢂ
14.4 Hz), 7.89 (s, 1H, HC), 7.26—7.55 (m, 8H, Ar, Arꢀ-H); 13C-NMR
(CDCl3) d: 21.6 (Ar-CH3), 53.9 (OCH3), 125.9 (ꢂCHSO2), 127.9 (SO2-Cꢂ
(CO2Me), 143.9 (ꢂCH-Arꢀ), 146.4 (ꢂCH-Ar), 173.8 (CꢂO), 128.2, 128.8,
129.6, 130.4, 130.8, 131.6, 132.0, 135.4 (aromatic carbons).
Methyl-4-(p-chlorophenyl)-3-(phenylethenesulfonyl)-3H-pyrrole-3-car-
boxylate (4b): Yellow solid, yield 76%, mp 146—148 °C; IR (KBr) cmꢁ1: 1748
1
General Procedure of Synthesis of Methyl-3-(4ꢀ-aryl-1ꢀH-pyrrol-
3ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (3) and Methyl-4-aryl-3-
(arylethenesulfonyl)-3H-pyrrole-3-carboxylate (4) (Method 1) A mixture
of TosMIC (0.01 mol) and methyl 3-aryl-2-(E-arylethenesulfonyl)acrylate 2
(0.005 mol) in Et2O–DMSO (2 : 1) was added dropwise under stirring to a
suspension of NaH (50 mg) in Et2O (10 ml) at room temperature and stirring
was continued for 5—6 h. Then, water was added and extracted with Et2O.
The ethereal fraction was dried over anhydrous Na2SO4. The solvent was re-
moved in vacuo. The resulting mixture was separated by column chromatog-
raphy (hexane–ethyl acetate; 4 : 1) and identified as methyl 3-(4ꢀ-aryl-1ꢀH-
pyrrol-3ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate 3 (minor) and methyl-
4-aryl-3-(arylethenesulfonyl)-3H-pyrrole-3-carboxylate 4 (major).
(CꢂO), 1641 (CꢂC), 1572 (CꢂN), 1326, 1138 (SO2); H-NMR (DMSO-d6)
d: 3.62 (s, 3H, OCH3), 6.62 (d, 1H, HB, Jꢂ14.0 Hz), 7.08 (s, 1H, C5-H), 7.18
(s, 1H, C2-H), 7.76 (d, 1H, HA, Jꢂ14.0 Hz), 7.24—7.71 (m, 9H, Ar, Arꢀ-H);
13C-NMR (DMSO-d6) d: 53.5 (–OCH3), 77.9 (C-3), 117.0 (C-4), 125.9 (C-
5), 124.1 (ꢂCHSO2), 145.9 (ꢂCH-Ar), 157.0 (C-2), 162.5 (CꢂO), 128.6,
129.2, 129.9, 130.6, 131.9, 132.6, 133.4, 135.7 (aromatic carbons): Anal.
Calcd for C20H16ClNO4S: C, 59.78; H, 4.01; N, 3.49; Found: C, 59.84; H,
4.05; N, 3.46.
Methyl-4-(p-chlorophenyl)-3-(p-methylphenylethenesulfonyl)-3H-pyr-
role-3-carboxylate (4c): Yellow solid, yield 75%, mp 157—159 °C; IR (KBr)
cmꢁ1: 1731 (CꢂO), 1634 (CꢂC), 1565 (CꢂN), 1330, 1122 (SO2); 1H-NMR
(DMSO-d6) d: 2.22 (s, 3H, Ar-CH3), 3.69 (s, 3H, OCH3), 6.59 (d, 1H, HB,
Jꢂ14.1 Hz), 6.99 (s, 1H, C5-H), 7.11 (s, 1H, C2-H), 7.71 (d, 1H, HA, J
ꢂ14.1 Hz), 7.22—7.69 (m, 8H, Ar, Arꢀ-H); 13C-NMR (DMSO-d6) d: 22.6 (Ar-
CH3), 54.1 (OCH3), 76.3 (C-3), 116.8 (C-4), 124.6 (C-5), 124.9 (ꢂCHSO2),
146.8 (ꢂCH-Ar), 156.4 (C-2), 163.9 (CꢂO), 128.0, 129.4, 129.3, 130.9,
131.6, 132.3, 134.5, 135.9 (aromatic carbons): Anal. Calcd for
C21H18ClNO4S: C, 60.65; H, 4.36; N, 3.37; Found: C, 60.73; H, 4.41; N,
3.41.
General Procedure of Synthesis of Methyl-3-(4ꢀ-aryl-1ꢀH-pyrrol-3ꢀ-yl-
sulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (3a—c) (Method 2) The com-
pound 3 was also prepared by adding a mixture of TosMIC (0.02 mol) and
methyl 3-aryl-2-(E-arylethenesulfonyl)acrylate
2 (0.005 mol) in Et2O–
DMSO (2 : 1) was added dropwise under stirring to a suspension of NaH
(50 mg) in Et2O (10 ml) at room temperature and stirring was continued for
5—6 h. Then, water was added and extracted with Et2O. The ethereal frac-
tion was dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure. The resulting solid was purified by column chromatogra-
phy (hexane–ethyl acetate; 4 : 1.5).
General Procedure of Synthesis of Methyl-3-(4ꢀ,5ꢀ-dihydro-4ꢀ-aryl-
1H-pyrazol-3ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (5a—c) To
a cooled solution of 4 (0.005 mol) in dichloromethane (20 ml), an ethereal
solution of diazomethane (40 ml, 0.4 M) and triethylamine (0.12 g) were
added. The reaction mixture was kept at ꢁ20 to ꢁ15 °C for 40—48 h. The
solvent was removed under reduced pressure and the resultant solid was re-
crystsllized from 2-propanol.
Methyl-3-(4ꢀ-phenyl-1ꢀH-pyrrol-3ꢀ-ylsulfonyl)-4-phenyl-3H-pyrrole-3-
carboxylate (3a): Pale yellow solid, yield 70%, mp 156—158 °C; IR (KBr)
1
cmꢁ1: 3320 (NH), 1736 (CꢂO), 1582 (CꢂN), 1330, 1126 (SO2); H-NMR
(DMSO-d6) d: 3.69 (s, 3H, OCH3), 6.78 (s, 1H, C2ꢀ-H,) 7.01, 7.09 (s, 2H, C5ꢀ-
H, C5-H), 7.19 (s, 1H, C2-H), 7.21—7.62 (m, 10H, Ar, Arꢀ-H), 8.71 (br s, 1H,
NH); 13C-NMR (DMSO-d6) d: 53.2 (OCH3), 76.8 (C-3), 117.5, 118.3 (C-4ꢀ,
C-4), 121.6 (C-3ꢀ), 123.5, 125.2 (C-5ꢀ, C-5), 127.0, (C-2ꢀ) 157.8 (C-2),
164.2 (CꢂO), 128.6, 129.3, 130.2, 131.6, 132.3, 133.5, 134.6, 135.9 (aro-
matic carbons): Anal. Calcd for C22H18N2O4S: C, 65.01; H, 4.46; N, 6.89;
Found: C, 65.12; H, 4.47; N, 6.93.
Methyl-3-(4ꢀ-phenyl-1ꢀH-pyrrol-3ꢀ-ylsulfonyl)-4-(p-chlorophenyl)-3H-
pyrrole-3-carboxylate (3b): Yellow solid, yield 67%, mp 174—176 °C; IR
(KBr) cmꢁ1: 3323 (NH), 1738 (CꢂO), 1568 (CꢂN), 1339, 1126 (SO2); 1H-
NMR (DMSO-d6) d: 3.74 (s, 3H, OCH3), 6.85 (s, 1H, C2ꢀ-H), 6.92, 7.06 (s,
2H, C5ꢀ-H, C5-H), 7.22 (s, 1H, C2ꢀ-H), 7.26—7.63 (m, 9H, Ar, Arꢀ-H), 8.88
(br s, 1H, NH); 13C-NMR (DMSO-d6) d: 53.8 (OCH3), 77.6 (C-3), 116.2,
118.9 (C-4ꢀ, C-4), 120.8 (C-3ꢀ), 123.9, 126.4 (C-5ꢀ, C-5), 127.6, (C-2ꢀ) 157.4
(C-2), 165.7 (CꢂO), 128.0, 129.7, 130.3, 131.0, 131.9, 132.7, 133.7, 135.3
(aromatic carbons): Anal. Calcd for C22H17ClN2O4S: C, 59.93; H, 3.89; N,
6.35; Found: C, 59.97; H, 3.86; N, 6.39.
Methyl-3-(4ꢀ,5ꢀ-dihydro-4ꢀ-phenyl-1H-pyrazol-3ꢀ-ylsulfonyl)-4-phenyl-
3H-pyrrole-3-carboxylate (5a): Yellow solid, yield 82%, mp 169—171 °C;
IR (KBr) cmꢁ1: 3347 (NH), 1742 (CꢂO), 1569 (CꢂN), 1336, 1131 (SO2); 1H-
NMR (CDCl3) d: 3.75 (s, 3H, OCH3), 3.88 (dd, 1H, HX, JAXꢂ4.0 Hz,
JMXꢂ8.0 Hz), 4.24 (dd, 1H, HM, JAMꢂ12.0 Hz), 4.57 (dd, 1H, HA), 7.04 (s,
1H, C5-H), 7.17 (s, 1H, C2-H), 7.25—7.61 (m, 10H, Ar, Arꢀ-H), 10.51 (br s,
1H, NH); 13C-NMR (CDCl3) d: 49.9 (C-5ꢀ), 53.1 (OCH3), 59.6 (C-4ꢀ), 77.4
(C-3), 117.4 (C-4), 125.3 (C-5), 150.5 (C-3ꢀ), 156.4 (C-2), 162.7 (CꢂO),
127.4, 128.1, 128.8, 129.3, 130.4, 131.3, 133.6, 134.2 (aromatic carbons):
Anal. Calcd for C21H19N3O4S: C, 61.60; H, 4.68; N, 10.26; Found: C, 61.69;
H, 4.72; N, 10.33.
Methyl-3-(4ꢀ,5ꢀ-dihydro-4ꢀ-phenyl-1H-pyrazol-3ꢀ-ylsulfonyl)-4-(p-
chlorophenyl)-3H-pyrrole-3-carboxylate (5b): Yellow solid, yield 77%, mp
155—157 °C; IR (KBr) cmꢁ1: 3333 (NH), 1740 (CꢂO), 1583 (CꢂN), 1329,
1
1130 (SO2); H-NMR (CDCl3) d: 3.68 (s, 3H, OCH3), 3.81 (dd, 1H, HX,
JAXꢂ3.9 Hz, JMXꢂ7.8 Hz), 4.21 (dd, 1H, HM, JAMꢂ11.7 Hz), 4.51 (dd, 1H,

1204
Vol. 57, No. 11
(m, 15H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 54.3 (–OCH3), 63.7 (C-
4ꢀ), 76.6 (C-3), 84.3 (C-5ꢀ), 115.1 (C-4), 125.4 (C-5), 156.4 (C-3ꢀ), 156.7
(C-2), 163.9 (CꢂO), 128.1, 129.7, 130.9, 132.3, 132.9, 133.2, 134.6, 135.1
(aromatic carbons): Anal. Calcd for C27H22N2O5S: C, 66.65; H, 4.56; N,
5.76; Found: C, 66.72; H, 4.55; N, 5.82.
Methyl-3-(4ꢀ,5ꢀ-dihydro-3ꢀ-(p-chlorophenyl)-5ꢀ-phenylisoxazol-4ꢀ-ylsul-
fonyl)-4-(p-chlorophenyl)-3H-pyrrole-3-carboxylate (7b): White solid, yield
63%, mp 169—171 °C; IR (KBr) cmꢁ1: 1743 (CꢂO), 1571 (CꢂN), 1317,
1140 (SO2); 1H-NMR (DMSO-d6) d: 3.75 (s, 3H, OCH3), 5.22 (d, 1H,
C4ꢀ-H, Jꢂ5.8 Hz), 5.79 (d, 1H, C5ꢀ-H, Jꢂ5.8 Hz), 7.02 (s, 1H, C5-H), 7.18
(s, 1H, C2-H), 7.22—7.89 (m, 13H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO
-d6) d: 53.2 (–OCH3), 62.8 (C-4ꢀ), 75.8 (C-3), 83.8 (C-5ꢀ), 116.3 (C-4),
125.1 (C-5), 156.2 (C-3ꢀ), 157.8 (C-2), 162.7 (CꢂO), 128.1, 129.6, 131.9,
132.5, 134.2, 135.1, 136.8, 137.1 (aromatic carbons): Anal. Calcd for
C27H20Cl2N2O5S: C, 58.39; H, 3.63; N, 5.04; Found: C, 58.30; H, 3.67; N,
5.00.
HA), 6.98 (s, 1H, C5-H), 7.13 (s, 1H, C2-H), 7.22—7.73 (m, 9H, Ar, Arꢀ-H),
10.46 (br s, 1H, NH); 13C-NMR (CDCl3) d: 50.5 (C-5ꢀ), 53.9 (OCH3), 60.7
(C-4ꢀ), 76.3 (C-3), 116.8 (C-4), 124.7 (C-5), 151.7 (C-3ꢀ), 156.9 (C-2),
163.5 (CꢂO), 127.9, 128.0, 128.6, 129.2, 131.7, 132.8, 137.9, 138.2 (aro-
matic carbons): Anal. Calcd for C21H18ClN3O4S: C, 56.82; H, 4.09; N, 9.47;
Found: C, 56.85; H, 4.07; N, 9.53.
Methyl-3-(4ꢀ,5ꢀ-dihydro-4ꢀ-(p-methylphenyl)-1H-pyrazol-3ꢀ-ylsulfonyl)-
4-(p-chlorophenyl)-3H-pyrrole-3-carboxylate (5c): Yellow solid, yield 83%,
mp 182—184 °C; IR (KBr) cmꢁ1: 3332 (NH), 1742 (CꢂO), 1575 (CꢂN),
1
1339, 1142 (SO2); H-NMR (CDCl3ꢄDMSO-d6) d: 2.31 (s, 3H, Ar-CH3),
3.79 (s, 3H, OCH3), 3.85 (dd, 1H, HX, JAXꢂ4.3 Hz, JMXꢂ8.4 Hz), 4.23 (dd,
1H, HM, JAMꢂ12.3 Hz), 4.54 (dd, 1H, HA), 6.93 (s, 1H, C5-H), 7.19 (s, 1H,
C2-H), 7.27—7.88 (m, 8H, Ar, Arꢀ-H), 10.11 (br s, 1H, NH); 13C-NMR
(CDCl3ꢄDMSO-d6) d: 22.4 (Ar-CH3), 50.9 (C-5ꢀ), 54.2 (OCH3), 61.2 (C-
4ꢀ), 75.8 (C-3), 117.5 (C-4), 125.3 (C-5), 151.0 (C-3ꢀ), 155.8 (C-2), 162.3
(CꢂO), 128.5, 129.7, 130.8, 131.2, 132.9, 133.4, 135.4, 138.5 (aromatic
carbons): Anal. Calcd for C22H20ClN3O4S: C, 57.70; H, 4.40; N, 9.18;
Found: C, 57.60; H, 4.45; N, 9.24.
Methyl-3-(4ꢀ,5ꢀ-dihydro-3ꢀ-(p-chlorophenyl)-5ꢀ-(p-methylphenyl)isoxa-
zol-4ꢀ-ylsulfonyl)-4-(p-chlorophenyl)-3H-pyrrole-3-carboxylate (7c): White
solid, yield 67%, mp 222—224 °C; IR (KBr) cmꢁ1: 1746 (CꢂO), 1567 (Cꢂ
General Procedure of Synthesis of Methyl-3-(4ꢀ,5ꢀ-dihydro-1ꢀ-phenyl-
3ꢀ,5ꢀ-diaryl-pyrazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate
(6a—c) A mixture of 4 (0.001 mol), araldehyde phenylhydrazone (0.0012
mol) and chloramine-T (0.0012 mol) 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, brine and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure. Recrystallization
of crude product from ethanol resulted in pure compound.
1
N), 1321, 1131 (SO2); H-NMR (DMSO-d6) d: 2.27 (s, 3H, Ar-CH3), 3.69
(s, 3H, OCH3), 5.25 (d, 1H, C4ꢀ-H, Jꢂ5.7 Hz), 5.77 (d, 1H, C5ꢀ-H, Jꢂ
5.7 Hz), 7.06 (s, 1H, C5-H), 7.13 (s, 1H, C2-H), 7.25—7.86 (m, 12H, Ar-H);
13C-NMR (DMSO-d6) d: 22.7 (Ar-CH3), 53.9 (OCH3), 63.4 (C-4ꢀ), 75.0 (C-
3), 82.5 (C-5ꢀ), 115.3 (C-4), 126.2 (C-5), 156.8 (C-3ꢀ), 158.1 (C-2), 163.3
(CꢂO), 128.6, 129.5, 130.9, 131.6, 132.3, 134.4, 136.5, 138.6 (aromatic
carbons): Anal. Calcd for C28H22Cl2N2O5S: C, 59.06; H, 3.89; N, 4.92;
Found: C, 59.01; H, 3.87; N, 4.85.
General Procedure of Synthesis of Methyl-3-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-
ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (8a—c)/Methyl-3-(1ꢀ-phenyl-
3ꢀ,5ꢀ-diaryl-1H-pyrazol-4ꢀ-ylsulfonyl)-4-phenyl-3H-pyrrole-3-carboxylate
(9a—c)/Methyl-3-(3ꢀ,5ꢀ-diarylisoxazol-4ꢀ-ylsulfonyl)-4-phenyl-3H-pyrrole-
3-carboxylate (10a—c) A solution of 5/6/7 (0.001 mol) and chloranil
(0.0014 mol) in xylene (10 ml) was refluxed for 24—32 h. Then, the reaction
mixture was treated with a 5% NaOH solution. The organic layer was sepa-
rated and repeatedly washed with water. It was dried over anhydrous Na2SO4
and the solvent was removed on a rotary evaporator. The resultant solid was
purified by recrystallization from 2-propanol.
Methyl-3-(4ꢀ,5ꢀ-dihydro-1ꢀ,3ꢀ,5ꢀ-triphenyl-pyrazol-4ꢀ-ylsulfonyl)-4-
phenyl-3H-pyrrole-3-carboxylate (6a): White solid, yield 67%, mp 202—
1
204 °C; IR (KBr) cmꢁ1: 1749 (CꢂO), 1580 (CꢂN), 1328, 1123 (SO2); H-
NMR (DMSO-d6) d: 3.68 (s, 3H, OCH3), 5.21 (d, 1H, C4ꢀ-H, Jꢂ6.5 Hz),
5.58 (d, 1H, C5ꢀ-H, Jꢂ6.5 Hz), 7.02 (s, 1H, C5-H), 7.16 (s, 1H, C2-H),
7.19—7.79 (m, 20H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 53.3
(OCH3), 62.4 (C-4ꢀ), 76.4 (C-3), 87.3 (C-5ꢀ), 116.8 (C-4), 126.6 (C-5),
155.8 (C-3ꢀ), 156.3 (C-2), 163.4 (CꢂO), 127.9, 128.3, 128.6, 129.3, 129.9,
130.4, 131.3, 132.9, 133.6, 134.6 (aromatic carbons): Anal. Calcd for
C33H27N3O4S : C, 70.57; H, 4.85; N, 7.48; Found: C, 70.45; H, 4.91; N, 7.42.
Methyl-3-(4ꢀ,5ꢀ-dihydro-1ꢀ,5ꢀ-diphenyl-3ꢀ-(p-chlorophenyl)-pyrazol-4ꢀ-
ylsulfonyl)-4-(p-chlorophenyl)-3H-pyrrole-3-carboxylate (6b): White solid,
yield 65%, mp 214—216 °C; IR (KBr) cmꢁ1: 1739 (CꢂO), 1567 (CꢂN),
1335, 1133 (SO2); 1H-NMR (DMSO-d6) d: 3.64 (s, 3H, OCH3), 5.26 (d, 1H,
C4ꢀ-H, Jꢂ6.9 Hz), 5.62 (d, 1H, C5ꢀ-H, Jꢂ6.9 Hz), 7.05 (s, 1H, C5-H), 7.21 (s,
1H, C2-H), 7.27—7.74 (m, 18H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d:
54.2 (OCH3), 61.3 (C-4ꢀ), 76.9 (C-3), 86.7 (C-5ꢀ), 115.6 (C-4), 125.8 (C-5),
155.2 (C-3ꢀ), 157.4 (C-2), 162.9 (CꢂO), 128.1, 128.3, 129.4, 129.9, 130.9,
131.9, 132.1, 133.9, 134.8, 135.6 (aromatic carbons): Anal. Calcd for
C33H25Cl2N3O4S: C, 62.86; H, 4.00; N, 6.66; Found: C, 62.79; H, 4.05; N,
6.72.
Methyl-3-(4ꢀ-phenyl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-phenyl-3H-pyrrole-3-
carboxylate (8a): White solid, yield 74%, mp 211—213 °C; IR (KBr) cmꢁ1
:
1
3331 (NH), 1739 (CꢂO), 1574 (CꢂN), 1329, 1125 (SO2); H-NMR (CDCl3)
d: 3.62 (s, 3H, –OCH3), 6.99 (s, 1H, C5-H), 7.19 (s, 1H, C2-H), 7.21—7.65
(m, 11H, C5ꢀ-H, Ar, Arꢀ-H), 8.98 (br s, 1H, NH); 13C-NMR (CDCl3) d: 54.3
(OCH3), 77.4 (C-3), 116.1 (C-4), 125.3 (C-5), 134.3 (C-5ꢀ), 138.6 (C-4ꢀ),
155.4 (C-3ꢀ), 157.6 (C-2), 162.9 (CꢂO), 128.2, 129.2, 130.6, 131.4, 132.0,
133.2, 134.5, 135.7 (aromatic carbons): Anal. Calcd for C21H17N3O4S: C,
61.90; H, 4.21; N, 10.31; Found: C, 61.96; H, 4.26; N, 10.38.
Methyl-3-(4ꢀ-phenyl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-(p-chlorophenyl)-3H-
pyrrole-3-carboxylate (8b): White solid, yield 77%, mp 217—219 °C; IR
(KBr) cmꢁ1: 3334 (NH), 1742 (CꢂO), 1570 (CꢂN), 1334, 1126 (SO2); 1H-
NMR (CDCl3) d: 3.65 (s, 3H, OCH3), 7.01 (s, 1H, C5-H), 7.15 (s. 1H, C2-
H), 7.23—7.85 (m, 10H, C5ꢀ-H, Ar, Arꢀ-H), 8.89 (br s, 1H, NH); 13C-NMR
(CDCl3) d: 53.6 (–OCH3), 76.8 (C-3), 117.5 (C-4), 126.8 (C-5), 133.1 (C-
5ꢀ), 138.7 (C-4ꢀ), 154.7 (C-3ꢀ), 156.6 (C-2), 163.7 (CꢂO), 128.1, 129.0,
129.8, 130.5, 131.1, 133.1, 134.9, 135.7 (aromatic carbons): Anal. Calcd for
C21H16ClN3O4S: C, 57.08; H, 3.65; N, 9.51; Found: C, 57.12; H, 3.62; N,
9.47.
Methyl-3-(4ꢀ-(p-methylphenyl)-1ꢀH-pyrazol-3ꢀ-ylsulfonyl)-4-(p-
chlorophenyl)-3H-pyrrole-3-carboxylate (8c): White solid, yield 78%, mp
236—238 °C; IR (KBr) cmꢁ1: 3339 (NH), 1748 (CꢂO), 1584 (CꢂN), 1331,
1139 (SO2); 1H-NMR (CDCl3) d: 2.27 (s, 3H, Ar-CH3), 3.67 (s, 3H, OCH3),
7.04 (s, 1H, C5-H), 7.11 (s, 1H, C2-H), 7.25—7.84 (m, 9H, C5ꢀ-H, Ar, Arꢀ-
H), 8.80 (br s, 1H, NH); 13C-NMR (CDCl3) d: 22.4 (Ar-CH3), 54.3
(–OCH3), 76.2 (C-3), 118.2 (C-4), 125.6 (C-5), 132.5 (C-5ꢀ), 137.2 (C-4ꢀ),
155.9 (C-3ꢀ), 157.9 (C-2), 163.0 (CꢂO), 129.5, 130.9, 131.6, 132.3, 133.0,
134.9, 135.7, 136.1 (aromatic carbons): Anal. Calcd for C22H18ClN3O4S: C,
57.96; H, 3.98; N, 9.22; Found: C, 58.03; H, 3.94; N, 9.26.
Methyl-3-(4ꢀ,5ꢀ-dihydro-1ꢀ-phenyl-3ꢀ-(p-chlorophenyl)-5ꢀ-(p-
methylphenyl)-pyrazol-4ꢀ-ylsulfonyl)-4-(p-chlorophenyl)-3H-pyrrole-3-car-
boxylate (6c): White solid, yield 62 %, mp 235—237 °C; IR (KBr) cmꢁ1
:
1748 (CꢂO), 1565 (CꢂN), 1336, 1135 (SO2); 1H-NMR (DMSO-d6) d: 2.23
(s, 3H, Ar-CH3), 3.61 (s, 3H, OCH3), 5.29 (d, 1H, C4ꢀ-H, Jꢂ6.7 Hz), 5.68 (d,
1H, C5ꢀ-H, Jꢂ6.7 Hz), 6.96 (s, 1H, C5-H), 7.18 (s, 1H, C2-H), 7.25—7.87
(m, 17H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 21.6 (Ar-CH3), 53.9
(OCH3), 61.6 (C-4ꢀ), 77.3 (C-3), 85.9 (C-5ꢀ), 114.7 (C-4), 126.3 (C-5),
155.9 (C-3ꢀ), 156.1 (C-2), 164.7 (CꢂO), 128.4, 128.8, 129.2, 129.4, 130.3,
131.6, 132.3, 132.1, 133.2, 136.9 (aromatic carbons): Anal. Calcd for
C34H27Cl2N3O4S: C, 63.35; H, 4.22; N, 6.52; Found: C, 63.41; H, 4.19; N,
6.57.
General Procedure of Synthesis of Methyl-3-(4ꢀ,5ꢀ-dihydro-3ꢀ,5ꢀ-di-
arylisoxazol-4ꢀ-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (7a—c)
A
mixture of 4 (0.001 mol), araldoxime (0.0012 mol) and chloramine-T
(0.0012 mol) in methanol (15 ml) was refluxed for 8—10 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, brine and dried over anhydrous Na2SO4. The solvent was re-
moved in vacuo. The solid obtained was purified by recrystallization from
ethanol.
Methyl-3-(4ꢀ,5ꢀ-dihydro-3ꢀ,5ꢀ-diphenylisoxazol-4ꢀ-ylsulfonyl)-4-phenyl-
3H-pyrrole-3-carboxylate (7a): White solid, yield 69%, mp 197—199 °C; IR
(KBr) cmꢁ1: 1742 (CꢂO), 1572 (CꢂN), 1325, 1138 (SO2); 1H-NMR
(DMSO-d6) d: 3.72 (s, 3H, OCH3), 5.16 (d, 1H, C4ꢀ-H, Jꢂ5.6 Hz), 5.75 (d,
1H, C5ꢀ-H, Jꢂ5.6 Hz), 6.99 (s, 1H, C5-H), 7.10 (s, 1H, C2-H), 7.15—7.76
Methyl-3-(1ꢀ,3ꢀ,5ꢀ-triphenyl-1H-pyrazol-4ꢀ-ylsulfonyl)-4-phenyl-3H-pyr-
role-3-carboxylate (9a): Pale yellow solid, yield 78%, mp 221—223 °C; IR
(KBr) cmꢁ1: 1739 (CꢂO), 1582 (CꢂN), 1327, 1135 (SO2); 1H-NMR (DMSO-
d6) d: 3.64 (s, 3H, OCH3), 6.99 (s, 1H, C5-H), 7.17 (s, 1H, C2-H), 7.19—
7.79 (m, 20H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 53.9 (OCH3), 77.4
(C-3), 116.3 (C-4), 124.7 (C-5), 145.4 (C-3ꢀ), 147.4 (C-4ꢀ), 150.6 (C-5ꢀ),
155.8 (C-2), 162.6 (CꢂO), 128.3, 128.7, 129.1, 130.5, 131.4, 132.0, 132.7,
133.0, 134.2 (aromatic carbons): Anal. Calcd for C33H25N3O4S: C, 70.82; H,

November 2009
1205
4.50; N, 7.51; Found: C, 70.86; H, 4.55; N, 7.49.
centration of 800 mg/ml. The two-fold dilution of the solution was prepared
(400, 200, 100, …, 6.25 mg/ml). The microorganism suspensions were incu-
bated at 36 °C for 24 and 48 h for bacteria and fungi, respectively. The mini-
mum inhibitory concentrations of the compounds were recorded as the low-
est concentration of each chemical compounds in the tubes with no turbidity
(i.e. no growth) of inoculated bacteria/fungi.
Methyl-3-(1ꢀ,5ꢀ-diphenyl-3ꢀ-(p-cholorophenyl)-1H-pyrazol-4ꢀ-ylsul-
fonyl)-4-(p-cholorophenyl)-3H-pyrrole-3-carboxylate (9b): Yellow solid, yield
70%, mp 252—254 °C; IR (KBr) cmꢁ1: 1736 (CꢂO), 1561 (CꢂN), 1321,
1
1137 (SO2); H-NMR (DMSO-d6) d: 3.73 (s, 3H, OCH3), 6.96 (s, 1H, C5-
H), 7.12 (s, 1H, C2-H), 7.21—7.85 (m, 18H, Ar, Arꢀ, Arꢅ-H); 13C-NMR
(DMSO-d6) d: 54.2 (–OCH3), 76.4 (C-3), 118.2 (C-4), 125.3 (C-5), 145.9
(C-3ꢀ), 147.9 (C-4ꢀ), 151.2 (C-5ꢀ), 157.8 (C-2), 163.9 (CꢂO), 128.4, 128.6,
129.5, 129.7, 130.3, 131.8, 132.3, 133.4, 133.9, 135.6, 136.1 (aromatic car-
bons): Anal. Calcd for C33H23Cl2N3O4S: C, 63.06; H, 3.69; N, 6.69; Found:
C, 63.00; H, 3.73; N, 6.73.
Acknowledgements The Department of Science and Technology (DST),
New Delhi, India, is gratefully acknowledged for its financial support.
References
Methyl-3-(1ꢀ-phenyl-5ꢀ-(p-methylphenyl)-3ꢀ-(p-cholorophenyl)-1H-pyra-
zol-4ꢀ-ylsulfonyl)-4-(p-cholorophenyl)-3H-pyrrole-3-carboxylate (9c): Yellow
solid, yield 76%, mp 285—287 °C; IR (KBr) cmꢁ1: 1748 (CꢂO), 1572 (Cꢂ
1) Gribble G. W., “Comprehensive Heterocyclic Chemistry II,” ed. by
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N), 1339, 1145 (SO2); H-NMR (DMSO-d6) d: 2.22 (s, 3H, Ar-CH3), 3.70
(s, 3H, –OCH3), 6.99 (s, 1H, C5-H), 7.19 (s, 1H, C2-H), 7.26—7.89
(m, 17H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 53.7 (OCH3), 76.8
(C-3), 118.7 (C-4), 126.1 (C-5), 146.3 (C-3ꢀ), 148.4 (C-4ꢀ), 150.6 (C-5ꢀ),
155.6 (C-2), 164.1 (CꢂO), 128.2, 128.6, 129.3, 130.4, 130.8, 131.2, 132.6,
133.9, 134.6, 135.5, 136.9, 137.3 (aromatic carbons): Anal. Calcd for
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cmꢁ1: 1741 (CꢂO), 1577 (CꢂN), 1332, 1134 (SO2); H-NMR (DMSO-d6)
d: 3.69 (s, 3H, OCH3), 6.96 (s, 1H, C5-H), 7.11 (s, 1H, C2-H), 7.19—7.74
(m, 15H, Ar, Arꢀ, Arꢅ-H); 13C-NMR (DMSO-d6) d: 54.3 (OCH3), 77.0 (C-
3), 117.9 (C-4), 126.6 (C-5), 146.6 (C-4ꢀ), 147.6 (C-3ꢀ), 153.1 (C-5ꢀ), 157.4
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(C-2), 164.9 (CꢂO), 129.1, 130.5, 131.4, 132.0, 132.7, 133.0, 133.7 134.2 10) Shiraishi H., Nishitani T., Nishihara T., Sakaguchi S., Ishii Y., Tetrahe-
(aromatic carbons): Anal. Calcd for C27H20N2O5S: C, 66.93; H, 4.16; N,
5.78; Found: C, 66.97; H, 4.19; N, 5.83.
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(2000).
1
(SO2); H-NMR (DMSO-d6) d: 3.71 (s, 3H, CO2CH3), 7.04 (s, 1H, C5-H),
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7.17 (s, 1H, C2-H), 7.25—7.82 (m, 13H, Ar, Arꢀ, Arꢅ-H); 13C-NMR
(DMSO-d6) d: 53.9 (–OCH3), 77.5 (C-3), 116.5 (C-4), 125.7 (C-5), 144.7
(C-4ꢀ), 147.3 (C-3ꢀ), 151.2 (C-5ꢀ), 156.7 (C-2), 163.3 (CꢂO), 128.6, 129.7, 15) Padmavathi V., Jagnan Mohan Reddy B., Padmaja A., J. Heterocycl.
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C27H18Cl2N2O5S: C, 58.60; H, 3.28; N, 5.06; Found: C, 58.55; H, 3.24; N, 16) Padmavathi V., Jagnan Mohan Reddy B., Rajagopala Sarma M.,
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Prep. Proc. Intl., 24, 91—94 (1992).
19) Kim J. N., Ryu E. K., Synth. Commun., 20, 1373—1377 (1990).
1
1327, 1137 (SO2); H-NMR (DMSO-d6) d: 2.27 (s, 3H, Ar-CH3), 3.75 (s,
3H, CO2CH3), 7.00 (s, 1H, C5-H), 7.12 (s, 1H, C2-H), 7.19—7.84 (m, 12H, 20) Lokanath Rai K. M., Hassner A., Indian J. Chem., 36B, 242—245
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76.7 (C-3), 115.7 (C-4), 126.1 (C-5), 145.9 (C-4ꢀ), 147.9 (C-3ꢀ), 152.8 (C-
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Antimicrobial Testing The compounds 3, 4, 8—10 were dissolved in
DMSO at different concentrations of 100, 200 and 800 mg/ml.
Antibacterial and Antifungal Assays Preliminary antimicrobial activ-
ity of compounds 3, 4, 8—10 was tested by agar disc-diffusion method. 25) Padmavathi V., Sumathi R. P., Venugopal Reddy K., Somasekhar
Sterile filter paper discs (6 mm diameter) moistened with the test compound
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solution in DMSO of specific concentration 100 mg and 200 mg/disc were
(2000).
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37 °C and the diameter of the growth inhibition zones were measured after
24 h in case of bacteria and after 48 h in case of fungi.
New. J. Chem., 28, 1479—1483 (2004).
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(1944).
29) Bhaskar Reddy D., Muralidhar Reddy M., Subbaraju G. V., Indian J.
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