Synthesis and antimicrobial activity of pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles

Article abstract of DOI:10.1248/cpb.59.1509

A new class of pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, and 1,2,4- triazoles were prepared and tested for antimicrobial activity. Amongst the tested compounds, 5c displayed high antimicrobial activity.

Full text of DOI:10.1248/cpb.59.1509

December 2011
Regular Article
Chem. Pharm. Bull. 59(12) 1509—1517 (2011)
1509
Synthesis and Antimicrobial Activity of Pyrrolyl/Pyrazolyl
Arylaminosulfonylmethyl 1,3,4-Oxadiazoles, 1,3,4-Thiadiazoles and
1,2,4-Triazoles
Adivireddy PADMAJA,* Akkarapalli MURALIKRISHNA, Chittoor RAJASEKHAR, and
Venkatapuram PADMAVATHI
Department of Chemistry, Sri Venkateswara University; Tirupati–517 502, India.
Received August 10, 2011; accepted September 20, 2011; published online October 3, 2011
A new class of pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, and 1,2,4-
triazoles were prepared and tested for antimicrobial activity. Amongst the tested compounds, 5c displayed high
antimicrobial activity.
Key words pyrrolyl/pyrazolyl-1,3,4-oxadiazole; 1,3,4-thiadiazole; 1,2,4-triazole; 1,3-dipolar cycloaddition; antimicrobial activity
A wide variety of heterocyclic systems have been explored methyl)-5-[Z-(styrylsulfonylmethyl)]-1,3,4-oxadiazole (3)
for developing pharmaceutically important molecules. (Chart 1 and Mechanism). Interconversion of oxadiazole
Amongst them, five membered aromatic heterocycles viz., to thiadiazole was effected by treating 3 with thiourea in
pyrroles, pyrazoles, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and tetrahydrofuran (THF) to get 2-(arylaminosulfonylmethyl)-5-
1,2,4-triazoles are important class of heterocyclic com- [Z-(styrylsulfonylmethyl)]-1,3,4-thiadiazole (4). On the other
pounds. The wide spread use of them as scaffold in medici- hand, the reaction of 3 with hydrazine hydrate in the presence
nal chemistry establishes these moieties as a member of the of KOH in n-butanol produced 4-amino-3-(arylaminosul-
privileged structures class. As constituents of cytotoxic drugs fonylmethyl)-5-[Z-(styrylsulfonylmethyl)]-1,2,4-triazole (5)
1
such as netrospin and distamycin, 4-aminopyrrole-2-carboxy- (Chart 1). The H-NMR spectra of 3a and 4a displayed two
lates have been used as the main compounds in the construc- singlets at d 4.86, 5.09 and 5.11, 5.35 due to methylene pro-
tion of a diverse series of DNA-binding ligands exhibiting tons attached to C-5 and C-2 while 5a at 5.05 and 5.28 ppm
antibiotic, antiviral, and oncolytic properties.1,2) The related due to methylene protons attached to C-5 and C-3. The
3-aminopyrroles also exhibit anticonvulsant activity by downfield signal was assigned to the one adjacent to sulfon-
blocking sodium channels.3) Pyrazole nucleus has pro- amide moiety. Apart from this, one doublet was observed at
nounced pharmacological applications as antianxiety,4) anti- 6.59, 6.77 and 6.72 ppm due to olefin proton HB. The olefin
diabetic,5) antimicrobial,6,7) herbicidal,8) anti-inflammatory9) proton, HA adjacent to aryl group displayed a signal at down-
and antibacterial.10,11) Further, 1,3,4-oxadiazoles are very field region, merged with aromatic protons. The coupling
good bioisosteres of amides and esters which can contribute constant value Jꢀ12.0 Hz indicated that they possess cis
substantially in increasing pharmacological activity by par- geometry. The broad signals appeared at 10.31, 10.39 and
ticipating in hydrogen bonding interactions with the recep- 10.15 ppm in 3a, 4a and 5a was assigned to NH which disap-
tors.12) Besides, it has been well documented that pyrazoles13) peared on deuteration. Moreover, compound 5a exhibited a
and oxadiazoles14,15) have cytotoxic activity. The therapeutic broad signal at 5.64 ppm due to NH2 which disappeared on
effects of compounds containing 1,3,4-thiadiazole rings have deuteration.
been studied for a number of pathological conditions includ-
1,3-Dipolar cycloaddition of dipolar reagents to dipo-
ing inflammation,16,17) pain18,19) and hypertension.20) Substi- larophiles is one of the facile techniques for the preparation
tuted-1,2,4-triazoles have received the most attention during of five membered heterocycles. The olefin moiety present in
last two decades as potential antimicrobial, antitubercular, 3, 4 and 5 was used to develop five membered heterocycles-
anti-human immunodeficiency virus (HIV), anti-inflamma- pyrroles and pyrazoles. The reaction of 3, 4 and 5 with tosyl-
tory, central nervous system (CNS) stimulants, sedative and methyl isocyanide in the presence of sodium hydride in a sol-
antianxiety agents.21—24) In previous communications, we vent mixture of DMSO and ether yielded 2-(arylaminosul-
have reported clubbed pyrazoles with other heterocycles and fonylmethyl)-5-(4ꢀ-aryl-1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-
studied their antimicrobial and antioxidant activities.25) The 1,3,4-oxadiazole (6), 2-(arylaminosulfonylmethyl)-5-(4ꢀ-
present study illustrates the details of further structural modi- aryl-1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (7)
fications carried out on clubbed pyrroles and pyrazoles with and 4-amino-3-(arylaminosulfonylmethyl)-5-(4ꢀ-aryl-1ꢀH-
1,3,4-oxadiazoles/1,3,4-thiadiazoles/1,2,4-triazoles and anti- pyrrol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (8) (Chart 2). The
oxidant activities. The synthetic route and sequence of reac- 1H-NMR spectra of 6a, 7a and 8a displayed two singlets at d
tions are depicted in Charts 1 and 2.
5.06, 5.03, 5.09 and 5.30, 5.19, 5.29 ppm due to two methyl-
Chemistry The synthetic scheme involves the prepara- ene protons attached to C-5 and C-2 of oxadiazole/thiadia-
tion of bis heterocycles, pyrrolyl/pyrazolyl-oxadiazoles, thia- zole and C-5 and C-3 of triazole units. In addition to these,
diazoles and triazoles from synthetically vulnerable interme- one singlet was observed at 6.64, 6.68 and 6.71 due to Cꢀ-H
5
diates arylaminosulfonylacetic acid hydrazide (1) and Z- of pyrrole ring whereas the other proton, Cꢀ-H appeared at
2
styrylsulfonylacetic acid (2). The cyclocondensation of 1 and downfield region and merged with aromatic protons. The
2 in the presence of POCl3 led to 2-(arylaminosulfonyl- compounds 6a, 7a and 8a also showed two broad singlets at
© 2011 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: adivireddyp@yahoo.co.in

1510
Vol. 59, No. 12
8.75, 8.35, 8.41 and at 10.47, 10.10, 10.32 ppm due to NH of gioselectively. This may be due to the more electron with-
pyrrole ring and NH–SO2 and also 8a exhibited a broad sin- drawing capacity of SO2.26) The pyrazoline ring protons dis-
1
glet at 5.58 due to NH2 which were disappeared on deutera- played an AMX splitting pattern in the H-NMR spectra of
tion. The 1,3-dipolar cycloadditon of diazomethane to 3, 4 9a, 10a and 11a. Thus three double doublets observed at d
and 5 in the presence of Et3N in ether at ꢁ20 to ꢁ15 °C for 3.58, 4.21, 4.57 in 9a, at 3.54, 4.26, 4.61 in 10a and at 3.64,
48 h gave 2-(arylaminosulfonylmethyl)-5-(4ꢀ-aryl-4ꢀ,5ꢀ-dihy- 4.09, 4.53 ppm in 11a were assigned to HX, HM and HA,
dro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (9), respectively. The coupling constant values JAMꢀ12.4,
2-(arylaminosulfonylmethyl)-5-(4ꢀ-aryl-4ꢀ,5ꢀ-dihydro-1ꢀH- JMXꢀ10.6 and JAXꢀ6.5 Hz indicated that HA, HM are cis, HA,
pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (10) and 4- HX are trans while HM, HX are geminal. Aromatization of the
amino-3-(arylaminosulfonylmethyl)-5-(4ꢀ-aryl-4ꢀ,5ꢀ-dihy- compounds 9, 10 and 11 with chloranil in xylene resulted in
dro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (11) re- 2-(arylaminosulfonylmethyl)-5-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-yl-
Chart 1
Mechanism: Formation of Oxadiazole from Acid Hydrazide and Carboxylic Acid
Chart 2

December 2011
1511
Table 1. The in Vitro Antibacterial Activity of Compounds 3—14
Diameter of zone of inhibition (mm)
Gram-positive bacteria
Compound
Gram-negative bacteria
P. aeruginosa K. pneumoniae
50 mg/well 100 mg/well 50 mg/well 100 mg/well
11 13
S. aureus
B. subtilis
50 mg/well
100 mg/well
50 mg/well
100 mg/well
3a
8
—
15
20
13
28
24
18
32
—
—
13
17
11
25
20
15
29
9
—
11
15
9
24
20
14
25
8
10
—
16
22
15
31
27
21
35
—
—
14
19
13
28
23
17
31
12
—
14
18
10
26
21
16
27
9
10
—
13
18
16
29
23
20
35
—
—
11
15
12
26
19
18
28
11
—
10
14
10
23
19
17
24
9
13
—
15
19
18
32
25
22
38
—
—
13
18
14
28
22
20
31
12
—
12
15
12
25
21
19
26
12
—
14
19
16
30
24
21
36
38
—
9
—
12
16
13
24
21
15
30
—
—
10
14
11
21
20
14
25
—
—
—
13
8
20
18
13
20
—
—
11
15
12
22
20
15
29
27
—
15
—
20
25
20
34
30
25
40
—
—
16
21
16
31
28
21
35
9
—
11
19
16
29
27
21
31
—
—
17
24
19
31
29
23
39
42
—
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
9a
9b
9c
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
—
14
19
15
26
23
17
32
—
—
12
16
13
23
21
16
27
10
—
11
15
11
22
20
15
23
—
—
13
18
15
25
22
16
31
30
—
—
18
22
18
32
28
22
38
—
—
14
20
15
29
26
19
32
—
—
—
17
14
27
25
20
28
—
—
16
22
17
30
28
20
36
40
—
—
14
19
13
26
22
16
31
33
—
—
16
21
14
29
25
19
33
35
—
—
12
17
14
27
21
19
33
34
—
14a
14b
14c
Chloramphenicol
Control (DMSO)
(—) No activity.
sulfonylmethyl)-1,3,4-oxadiazole (12), 2-(arylaminosulfonyl- at 28 °C for 48 h. The perceived data on the antimicrobial ac-
methyl)-5-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4- tivity of the tested compounds and control drugs are shown
thiadiazole (13) and 4-amino-3-(arylaminosulfonylmethyl)- in Tables 1—3.
5-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole
Investigation of antibacterial screening data shown in
(14) (Chart 2). The absence of AMX splitting pattern due to Table 1 indicated that Gram-negative bacteria were more sus-
pyrazoline ring protons in 12, 13 and 14 indicated that aro- ceptible towards the tested compounds than Gram-positive
matization took place. The structures of these compounds ones. When compared to the standard drug Chloramphenicol
were further confirmed by IR and 13C-NMR spectra.
it was seen that 5c and 14c were effective particularly against
Antimicrobial Testing The compounds 3—14 were Pseudomonas aeruginosa at 50 and 100 mg. However,
screened for antimicrobial activity at two different concentra- amongst bis heterocyclic compounds, 8 and 14 displayed
tions 50 and 100 mg. The antibacterial activity was carried good antibacterial activity against both Gram-positive and
out against Staphylococcus aureus, Bacillus subtilis (Gram- Gram-negaive bacteria. On the other hand, compounds 7 and
positive bacteria) and Pseudomonas aeruginosa, Klebsiella 13 exhibited moderate activity against both bacteria. The
pneumoniae (Gram-negative bacteria) on nutrient agar plates compounds 3, 6, 9 and 12 showed least activity. The presence
at 37 °C for 24 h using Chloramphenicol as reference drug. of chloro substituent on the aromatic ring enhances the activ-
The compounds were also evaluated for antifungal activity ity (Fig. 1).
against Penicillium chrysogenum, Curvularia lunata and As-
All the tested compounds inhibited the spore germination
pergillus niger using Ketoconazole as standard drug. Fungi against tested fungi. In general, most of the compounds
cultures were grown on potato dextrose agar medium (PDA) showed slightly higher antifungal activity towards Penicil-

1512
Vol. 59, No. 12
Fig. 1. Antibacterial Activity of 3c—14c
Fig. 2. Antifungal Activity of 3c—14c
lium chrysogenum than Curvularia lunata and Aspergillus dal and fungicidal effects greater than 2ꢂMIC. It was ob-
niger. The compounds 5c and 14c displayed excellent activ- served that mono heterocyclic compounds exhibited excel-
ity particularly against Penicillium chrysogenum almost lent activity than bis heterocyclic systems. This may be due
equivalent to the standard drug Ketoconazole (Table 2, Fig. to the presence of styrylsulfonyl moiety in mono heterocyclic
2). Compounds 4, 7, 8, 10, 11 and 13 also showed moderate compounds. Amongst different heterocyclic systems, com-
inhibition against the tested fungi. However, the compounds pounds having thiadiazole and triazole units displayed
3, 6, 9 and 12 exhibited least activity.
greater activity than those having oxadiazole units. The
The minimum inhibitory concentration (MIC), minimum pyrrolyl/pyrazolyl-thiadiazoles and triazoles (7, 8, 13, 14)
bactericidal concentration (MBC) and minimum fungicidal showed greater activity than pyrrolyl/pyrazolyl-oxadiazoles
concentration (MFC) values of the tested compounds are (6, 12). There is no marked difference in activity with com-
listed in Table 3. The compound 5c exhibited low MIC val- pounds having pyrrolyl and pyrazolyl units. It was also ob-
ues when compared with 4c, 8c and 14c. Besides, the MBC served that amongst pyrazolinyl and pyrazolyl bis heterocy-
value is 2ꢂMIC in case of Bacillus subtilis and P. aerugi- cles, the pyrazolyl compounds 12—14 exhibited greater an-
nosa and MFC value is 2ꢂMIC in case of P. chrysogenum. timicrobial activity than pyrazolinyl compounds 9—11. From
On the other hand, the other compounds displayed bacterici- these results it could be conclude that the chloro substituted

December 2011
1513
Table 2. The in Vitro Antifungal Activity of Compounds 3—14
Diameter of zone of inhibition (mm)
Compound
P. chrysogenum
C. lunata
A. niger
50 mg/well
100 mg/well
50 mg/well
100 mg/well
50 mg/well
100 mg/well
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
9a
9b
9c
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
10
—
18
23
17
31
27
21
35
—
—
14
19
14
27
23
20
33
9
—
10
18
12
25
22
18
30
9
12
—
21
24
19
33
28
24
38
—
—
17
22
16
29
25
22
35
10
—
13
20
14
27
24
20
32
11
—
18
23
18
31
26
23
37
38
—
13
—
21
25
20
32
28
24
36
—
—
16
23
17
29
26
21
35
—
—
10
22
15
26
25
20
32
11
—
19
24
18
30
27
22
35
38
—
14
—
23
28
22
34
30
26
40
—
—
18
25
19
31
28
23
37
10
—
12
24
18
29
27
22
33
13
—
21
26
21
32
29
24
39
41
—
9
—
17
21
16
29
26
20
32
—
—
14
18
14
26
22
17
31
—
—
9
17
13
24
21
17
29
8
—
15
20
15
27
24
18
30
33
—
11
—
19
23
18
30
28
22
34
—
—
16
20
15
29
24
19
33
11
—
11
20
15
26
24
20
31
10
—
18
22
17
30
26
19
33
36
—
—
16
21
16
29
25
21
34
36
—
13c
14a
14b
14c
Ketoconazole
Control (DMSO)
(—) No activity.
Table 3. MIC, MBC and MFC of Compounds 4c, 5c, 8c and 14c
Minimum inhibitory concentration
Compound
MIC (MBC/MFC) mg
S. aureus
B. subtilis
P. aeruginosa
K. pneumoniae P. chrysogenum
C. lunata
A. niger
4c
5c
8c
100 (ꢃ200)
25 (100)
50 (ꢃ200)
25 (100)
6.25
100 (ꢃ200)
25 (50)
100 (ꢃ200)
50 (200)
6.25
50 (200)
12.5 (25)
50 (200)
25 (100)
12.5
200
50 (200)
100 (ꢃ200)
100 (ꢃ200)
12.5
50 (ꢃ200)
25 (50)
100 (200)
50 (200)
—
100 (ꢃ200)
25 (100)
50 (ꢃ200)
50 (200)
—
200
50 (200)
200
50 (ꢃ200)
—
6.25
14c
Chloramphenicol
Ketoconazole
—
—
—
—
12.5
6.25
(—) No activity.
triazole derivatives shows higher activity when compared Conclusion
with other analogues. The presence of aminosulfonylmethyl A new class of bis heterocycles-pyrrolyl/pyrazolyl aryl-
group at 2nd position of thiadiazole and at 3rd position of tri- aminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles
azole units enhances the activity.
and 1,2,4-triazoles were prepared and tested for antimicrobial
activity. The presence of arylaminosulfonylmethyl group en-

1514
Vol. 59, No. 12
49.64; H, 3.93; N, 9.65. Found: C, 49.70; H, 3.97; N, 9.70.
hances the antimicrobial activity. Amongst the tested com-
2-(p-Methylphenylaminosulfonylmethyl)-5-[Z-(p-methylstyrylsulfonyl-
methyl)]-1,3,4-thiadiazole (4b): White solid, yield 68%, mp 166—168 °C;
1H-NMR (CDCl3) d: 2.23 and 2.29 (s, 6H, Ar–CH3), 5.07 (s, 2H, SO2–CH2),
5.27 (s, 2H, CH2–SO2–NH), 6.68 (d, 1H, HB, Jꢄ11.2 Hz), 7.11—7.62 (m,
9H, HA, Ar–H), 10.34 (br s, 1H, NH). 13C-NMR (CDCl3) d: 21.5 and 21.9
(Ar–CH3), 42.8 (SO2–CH2), 50.7 (CH2–SO2–NH), 120.9 (C–HB), 139.8
(C–HA), 158.2 (C-5), 159.6 (C-2), 124.8, 125.6, 126.7, 127.4, 128.5, 129.2,
130.7, 132.6 (aromatic carbons). IR (KBr) cmꢁ1: 3236 (NH), 1619 (CꢄC),
1559 (CꢄN), 1324, 1139 (SO2). Anal. Calcd for C20H21N3O4S3: C, 51.82; H,
4.57; N, 9.06. Found: C, 51.89; H, 4.56; N, 9.02.
2-(p-Chlorophenylaminosulfonylmethyl)-5-[Z-(p-chlorostyrylsulfonyl-
methyl)]-1,3,4-thiadiazole (4c): White solid, yield 72%, mp 182—184 °C;
1H-NMR (CDCl3) d: 5.18 (s, 2H, SO2–CH2), 5.41 (s, 2H, CH2–SO2–NH),
6.81 (d, 1H, HB, Jꢄ11.8 Hz), 7.18—7.73 (m, 9H, HA, Ar–H), 10.42 (br s,
1H, NH). 13C-NMR (CDCl3) d: 44.2 (SO2–CH2), 51.5 (CH2–SO2-NH),
121.9 (C–HB), 141.5 (C–HA), 158.6 (C-5), 159.5 (C-2), 126.4, 127.1, 128.0,
128.7, 129.2, 130.6, 132.0, 134.7 (aromatic carbons). IR (KBr) cmꢁ1: 3250
(NH), 1623 (CꢄC), 1573 (CꢄN), 1326, 1151 (SO2). Anal. Calcd for
C18H15Cl2N3O4S3: C, 42.86; H, 3.00; N, 8.33. Found: C, 42.91; H, 3.01; N,
8.40.
pounds, 5c is the most potent antimicrobial agent.
Experimental
Melting points were determined in open capillaries on a Mel-Temp appa-
ratus and are uncorrected. The purity of the compounds was checked by
TLC (silica gel H, BDH, hexane/ethyl acetate, 3 : 1). The IR spectra were
run on a Thermo Nicolet IR 200 FT-IR spectrometer as KBr pellets and the
1
wave numbers were given in cmꢁ1. The H-NMR spectra were recorded in
CDCl3/DMSO-d6 on a Jeol JNM l-400 MHz. The 13C-NMR spectra were
recorded in CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
100 MHz. All chemical shifts are reported in d (ppm) using TMS as an in-
ternal standard. The microanalyses were performed on a Perkin-Elmer 240C
elemental analyzer. The Z-styrylsulfonylacetic acid (2) was prepared as per
the literature procedure.27,28)
General Procedure of Synthesis of Arylaminosulfonylacetic Acid Hy-
drazide (1a—c) The compound methyl arylaminosulfonylacetate (10
mmol), hydrazine hydrate (11 mmol), methanol (6 ml) and three drops of
pyridine were refluxed for 6—8 h. The reaction mixture was cooled and the
solid separated was collected by filtration, dried and recrystallized from
methanol.
General Procedure of Synthesis of 2-(Arylaminosulfonylmethyl)-5-[Z-
General Procedure of Synthesis of 4-Amino-3-(arylaminosulfonyl-
methyl)-5-[Z-(styrylsulfonylmethyl)]-1,2,4-triazole (5a—c) To a solu-
tion of compound 3 (5 mmol) in n-butanol (25 ml), hydrazine hydrate
(15 mmol) was added and refluxed for 6—8 h. Then, KOH (10 mmol) was
added to the reaction media and the precipitate formed was filtered. The
solid obtained was acidified with conc. HCl to pHꢄ3 and washed with
water. It was dried and recrystallized from ethanol.
4-Amino-3-(phenylaminosulfonylmethyl)-5-[Z-(styrylsulfonylmethyl)]-
1,2,4-triazole (5a): White solid, yield 66%, mp 158—160 °C; 1H-NMR
(DMSO-d6) d: 5.05 (s, 2H, SO2–CH2), 5.28 (s, 2H, CH2–SO2–NH), 5.64 (br
s, 2H, NH2), 6.72 (d, 1H, HB, Jꢄ11.7 Hz), 7.10—7.74 (m, 11H, HA, Ar–H),
10.15 (br s, 1H, NH). 13C-NMR (DMSO-d6) d: 45.0 (SO2–CH2), 50.6
(CH2–SO2–NH), 122.0 (C–HB), 142.8 (C–HA), 157.6 (C-5), 159.1 (C-3),
124.9, 125.8, 126.7, 127.4, 128.4, 129.5, 130.2, 133.1 (aromatic carbons).
IR (KBr) cmꢁ1: 3478, 3361 (NH2), 3254 (NH), 1626 (CꢄC), 1561 (CꢄN),
1319, 1136 (SO2). Anal. Calcd for C18H19N5O4S2: C, 49.87; H, 4.42; N,
16.16. Found: C, 49.90; H, 4.45; N, 16.25.
(styrylsulfonylmethyl)]-1,3,4-oxadiazole (3a—c)
A mixture of aryl-
aminosulfonylacetic acid hydrazide (1) (10 mmol), Z-styrylsulfonylacetic
acid (2) (10 mmol) and POCl3 (7 ml) was heated under reflux for 5—7 h.
The excess POCl3 was removed under reduced pressure and the residue was
poured onto crushed ice. The resulting precipitate was filtered, washed with
saturated sodium bicarbonate solution and then with water. It was dried and
recrystallized from ethanol.
2-(Phenylaminosulfonylmethyl)-5-[Z-(styrylsulfonylmethyl)]-1,3,4-oxadi-
1
azole (3a): White solid, yield 67%, mp 122—124 °C; H-NMR (CDCl3) d:
4.86 (s, 2H, SO2–CH2), 5.11 (s, 2H, CH2–SO2–NH), 6.59 (d, 1H, HB,
Jꢄ11.7 Hz), 7.11—7.69 (m, 11H, HA, Ar–H), 10.31 (br s, 1H, NH). 13C-
NMR (CDCl3) d: 44.3 (SO2–CH2), 49.7 (CH2–SO2–NH), 121.6 (C–HB),
140.2 (C–HA), 157.3 (C-5), 158.2 (C-2), 124.7, 125.6, 126.4, 128.3, 128.9,
129.4, 130.2, 131.1 (aromatic carbons). IR (KBr) cmꢁ1: 3227 (NH), 1630
(CꢄC), 1572 (CꢄN), 1305,1160 (SO2). Anal. Calcd for C18H17N3O5S2: C,
51.54; H, 4.08; N, 10.02. Found: C, 51.60; H, 4.10; N, 10.12.
2-(p-Methylphenylaminosulfonylmethyl)-5-[Z-(p-methylstyrylsulfonyl-
methyl)]-1,3,4-oxadiazole (3b): White solid, yield 65%, mp 101—103 °C;
1H-NMR (CDCl3) d: 2.21 and 2.27 (s, 6H, Ar–CH3), 4.69 (s, 2H, SO2–CH2),
5.06 (s, 2H, CH2–SO2–NH), 6.42 (d, 1H, HB, Jꢄ11.5 Hz), 7.03—7.59 (m,
9H, HA, Ar-H), 10.02 (br s, 1H, NH). 13C-NMR (CDCl3) d: 21.2 and 21.9
(Ar-CH3), 42.8 (SO2–CH2), 48.4 (CH2–SO2–NH), 120.8 (C–HB), 137.1
(C–HA), 154.5 (C-5), 155.1 (C-2), 122.5, 123.7, 124.4, 124.9, 126.3, 127.9,
128.5, 129.6 (aromatic carbons). IR (KBr) cmꢁ1: 3210 (NH), 1622 (CꢄC),
1565 (CꢄN), 1312, 1155 (SO2). Anal. Calcd for C20H21N3O5S2: C, 53.68; H,
4.73; N, 9.39. Found: C, 53.63; H, 4.72; N, 9.47.
2-(p-Chlorophenylaminosulfonylmethyl)-5-[Z-(p-chlorostyrylsulfonyl-
methyl)]-1,3,4-oxadiazole (3c): White crystals, yield 69%, mp 140—142 °C;
1H-NMR (CDCl3) d: 5.02 (s, 2H, SO2–CH2), 5.25 (s, 2H, CH2–SO2–NH),
6.87 (d, 1H, HB, Jꢄ12.0 Hz), 7.17—7.71 (m, 9H, HA, Ar–H), 10.45 (br s,
1H, NH). 13C-NMR (CDCl3) d: 47.6 (SO2–CH2), 50.9 (CH2–SO2–NH),
122.5 (C–HB), 143.1 (C–HA), 158.1 (C-5), 159.7 (C-2), 127.7, 128.6, 129.0,
129.7, 130.5, 130.6, 132.6, 136.6 (aromatic carbons). IR (KBr) cmꢁ1: 3235
(NH), 1625 (CꢄC), 1580 (CꢄN), 1318, 1169 (SO2). Anal. Calcd for
C18H15Cl2N3O5S2: C, 44.27; H, 3.10; N, 8.60. Found: C, 44.22; H, 3.07; N,
8.56.
4-Amino-3-(p-methylphenylaminosulfonylmethyl)-5-[Z-(p-methylstyryl-
sulfonylmethyl)]-1,2,4-triazole (5b): White solid, yield 68%, mp 179—
181 °C; 1H-NMR (DMSO-d6) d: 2.21 and 2.25 (s, 6H, Ar–CH3), 4.94 (s, 2H,
SO2–CH2), 5.21 (s, 2H, CH2–SO2–NH), 5.62 (br s, 2H, NH2), 6.69 (d, 1H,
HB, Jꢄ11.1 Hz), 7.06—7.69 (m, 9H, HA, Ar–H), 10.11 (br s, 1H, NH). 13C-
NMR (DMSO-d6) d: 21.3 and 21.5 (Ar–CH3), 44.5 (SO2–CH2), 50.2
(CH2–SO2–NH), 121.6 (C–HB), 140.4 (C–HA), 158.2 (C-5), 159.5 (C-3),
125.9, 126.8, 127.2, 128.0, 128.9, 129.5, 130.2, 131.6 (aromatic carbons).
IR (KBr) cmꢁ1: 3471, 3365 (NH2), 3259 (NH), 1621 (CꢄC), 1557 (CꢄN),
1314, 1132 (SO2). Anal. Calcd for C20H23N5O4S2: C, 52.04; H, 5.02; N,
15.17. Found: C, 52.10; H, 5.00; N, 15.26.
4-Amino-3-(p-chlorophenylaminosulfonylmethyl)-5-[Z-(p-chlorostyryl-
sulfonylmethyl)]-1,2,4-triazole (5c): White solid, yield 71%, mp 193—
195 °C; 1H-NMR (DMSO-d6) d: 5.08 (s, 2H, SO2–CH2), 5.32 (s, 2H,
CH2–SO2–NH), 5.71 (br s, 2H, NH2), 6.78 (d, 1H, HB, Jꢄ11.9 Hz), 7.15—
7.77 (m, 9H, HA, Ar–H), 10.26 (br s, 1H, NH). 13C-NMR (DMSO-d6) d:
45.7 (SO2–CH2), 50.9 (CH2–SO2–NH), 122.3 (C–HB), 140.9 (C–HA), 158.7
(C-5), 159.8 (C-3), 126.4, 127.0, 127.9, 128.8, 129.5, 130.1, 131.6, 132.4
(aromatic carbons). IR (KBr) cmꢁ1: 3480, 3382 (NH2), 3266 (NH), 1624
(CꢄC), 1566 (CꢄN), 1322, 1143 (SO2). Anal. Calcd for C18H17Cl2N5O4S2:
C, 43.03; H, 3.41; N, 13.94. Found: C, 43.07; H, 3.42; N, 14.00.
General Procedure of Synthesis of 2-(Arylaminosulfonylmethyl)-5-(4ꢀ-
aryl-1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (6a—c)/2-(Ary-
laminosulfonylmethyl)-5-(4ꢀ-aryl-1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,3,4-
thiadiazole (7a—c)/4-Amino-3-(arylamino-sulfonylmethyl)-5-(4ꢀ-aryl-
1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (8a—c) A mixture of
compound 3/4/5 (1 mmol) and TosMIC (2 mmol) in Et2O–DMSO (2 : 1) was
added dropwise under stirring to a suspension of NaH (0.05 g) in Et2O
(20 ml) at room temperature and stirring was continued for 5—7 h. Then,
water was added and the reaction mass was extracted with Et2O. The ethe-
real layer was dried over anhydrous Na2SO4 and filtered. Evaporation of the
solvent in vacuo gave a crude product which was purified by column chro-
matography using silica gel (hexane–ethyl acetate; 4 : 1).
General Procedure of Synthesis of 2-(Arylaminosulfonylmethyl)-5-[Z-
(styrylsulfonylmethyl)]-1,3,4-thiadiazole (4a—c) In a sealed test tube,
the compound 3 (5 mmol), thiourea (20 mmol) and tetrahydrofuran (5 ml)
were taken and heated at 120—130 °C in an oil bath for 22—25 h. After the
reaction was completed, it was extracted with dichloromethane. The organic
layer was washed with water, brine solution and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure and the resultant
solid was recrystallized from methanol.
2-(Phenylaminosulfonylmethyl)-5-[Z-(styrylsulfonylmethyl)]-1,3,4-thiadi-
1
azole (4a): White solid, yield 70%, mp 153—155 °C; H-NMR (CDCl3) d:
5.09 (s, 2H, SO2–CH2), 5.35 (s, 2H, CH2–SO2–NH), 6.77 (d, 1H, HB,
Jꢄ11.4 Hz), 7.14—7.68 (m, 11H, HA, Ar–H), 10.39 (br s, 1H, NH). 13C-
NMR (CDCl3) d: 43.5 (SO2–CH2), 51.8 (CH2–SO2–NH), 121.4 (C–HB),
140.4 (C–HA), 157.7 (C-5), 158.8 (C-2), 125.3, 126.1, 126.8, 127.6, 128.8,
129.4, 130.1, 131.2 (aromatic carbons). IR (KBr) cmꢁ1: 3242 (NH), 1628
(CꢄC), 1562 (CꢄN), 1310, 1142 (SO2). Anal. Calcd for C18H17N3O4S3: C,
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrrol-3ꢀ-ylsulfonyl-
methyl)-1,3,4-oxadiazole (6a): Yellow solid, yield 68%, mp 129—131 °C;
1H-NMR (CDCl3) d: 5.06 (s, 2H, SO2–CH2), 5.30 (s, 2H, CH2–SO2–NH),

December 2011
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Ar–CH3), 5.04 (s, 2H, SO2–CH2), 5.23 (s, 2H, CH2–SO2–NH), 5.54 (br s,
2H, NH2), 6.58 (s, 1H, C5ꢀ–H), 7.11—7.72 (m, 9H, C2ꢀ–H, Ar–H), 8.36 (br s,
1H, NH), 10.22 (br s, 1H, NH–SO2). 13C-NMR (DMSO-d6) d: 21.6 and 21.9
(Ar–CH3), 46.8 (SO2–CH2), 51.4 (CH2–SO2–NH), 102.0 (C-4ꢀ), 116.1 (C-
3ꢀ), 117.8 (C-5ꢀ), 121.5 (C-2ꢀ), 157.9 (C-5), 158.8 (C-3), 126.1, 127.5,
6.64 (s, 1H, C5ꢀ-H), 7.21—7.84 (m, 11H, C2ꢀ-H, Ar–H), 8.75 (br s, 1H, NH),
10.47 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 46.6 (SO2–CH2), 52.0
(CH2–SO2–NH), 104.3 (C-4ꢀ), 110.5 (C-3ꢀ), 117.8 (C-5ꢀ), 121.8 (C-2ꢀ),
155.6 (C-5), 156.3 (C-2), 124.8, 126.2, 127.6, 128.5, 129.1, 130.4, 132.6,
138.2 (aromatic carbons). IR (KBr) cmꢁ1: 3254 (NH), 1629 (CꢄC), 1584
(CꢄN), 1331, 1132 (SO2). Anal. Calcd for C20H18N4O5S2: C, 52.39; H, 3.96;
N, 12.22. Found: C, 52.43; H, 3.95; N, 12.29.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-1ꢀH-
pyrrol-3ꢀ-ylsulfonyl-methyl)-1,3,4-oxadiazole (6b): Yellow solid, yield 66%,
mp 140—142 °C; 1H-NMR (CDCl3) d: 2.22 and 2.28 (s, 6H, Ar–CH3), 4.99
(s, 2H, SO2–CH2), 5.24 (s, 2H, CH2–SO2–NH), 6.56 (s, 1H, C5ꢀ-H), 7.18—
7.88 (m, 9H, C2ꢀ–H, Ar–H), 8.69 (br s, 1H, NH), 10.40 (br s, 1H, NH–SO2).
13C-NMR (CDCl3) d: 21.3 and 21.8 (Ar–CH3), 46.1 (SO2–CH2), 51.4
(CH2–SO2–NH), 103.8 (C-4ꢀ), 109.7 (C-3ꢀ), 116.9 (C-5ꢀ), 121.0 (C-2ꢀ),
155.0 (C-5), 155.9 (C-2), 125.7, 126.5, 127.2, 128.6, 129.3, 130.1, 131.0,
138.8 (aromatic carbons). IR (KBr) cmꢁ1: 3251 (NH), 1625 (CꢄC), 1581
(CꢄN), 1324, 1129 (SO2). Anal. Calcd for C22H22N4O5S2: C, 54.31; H, 4.56;
N, 11.51. Found: C, 54.28; H, 4.57; N, 11.56.
128.4, 129.9, 130.2, 131.4, 132.6, 136.5 (aromatic carbons). IR (KBr) cmꢁ1
:
3428, 3309 (NH2), 3259 (NH), 1626 (CꢄC), 1589 (CꢄN), 1321, 1131
(SO2). Anal. Calcd for C22H24N6O4S2: C, 52.78; H, 4.83; N, 16.79. Found: C,
52.83; H, 4.87; N, 16.87.
4-Amino-3-(p-chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-
1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (8c): Yellow solid, yield 72%,
1
mp 194—196 °C; H-NMR (DMSO-d6) d: 5.17 (s, 2H, SO2–CH2), 5.36 (s,
2H, CH2–SO2–NH), 5.67 (br s, 2H, NH2), 6.74 (s, 1H, C5ꢀ–H), 7.16—7.81
(m, 9H, C2ꢀ–H, Ar–H), 8.51 (br s, 1H, NH), 10.35 (br s, 1H, NH–SO2). 13C-
NMR (DMSO-d6) d: 47.6 (SO2–CH2), 52.3 (CH2–SO2–NH), 103.3 (C-4ꢀ),
110.8 (C-3ꢀ), 117.0 (C-5ꢀ), 122.4 (C-2ꢀ), 158.0 (C-5), 159.1 (C-3), 126.8,
127.4, 128.6, 129.5, 130.4, 131.2, 132.0, 137.2 (aromatic carbons). IR (KBr)
cmꢁ1: 3445, 3326 (NH2), 3271 (NH), 1629 (CꢄC), 1602 (CꢄN), 1330,
1138 (SO2). Anal. Calcd for C20H18Cl2N6O4S2: C, 44.37; H, 3.35; N, 15.52.
Found: C, 44.34; H, 3.34; N, 15.48.
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-1ꢀH-
pyrrol-3ꢀ-ylsulfonyl-methyl)-1,3,4-oxadiazole (6c): Yellow solid, yield 73%,
1
General Procedure of Synthesis of 2-(Arylaminosulfonylmethyl)-5-(4ꢀ-
aryl-4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole
(9a—c)/2-(Arylaminosulfonyl-methyl)-5-(4ꢀ-aryl-4ꢀ,5ꢀ-dihydro-1ꢀH-
pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (10a—c)/4-Amino-3-(aryl-
aminosulfonylmethyl)-5-(4ꢀ-aryl-4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-3ꢀ-ylsul-
fonyl-methyl)-1,2,4-triazole (11a—c) To a cooled solution of compound
3/4/5 (5 mmol) in dichloromethane (20 ml), an ice-cold ethereal solution of
diazomethane (40 ml, 0.4 m) and triethylamine (0.12 g) were added. The re-
action mixture was kept at ꢁ20 to ꢁ15 °C for 48 h. The solvent was re-
moved under vacuum and the resultant solid was recrystallized from 2-
propanol.
mp 148—150 °C; H-NMR (CDCl3) d: 5.11 (s, 2H, SO2–CH2), 5.38 (s, 2H,
CH2–SO2–NH), 6.70 (s, 1H, C5ꢀ–H), 7.25—7.74 (m, 9H, C2ꢀ–H, Ar–H), 8.71
(br s, 1H, NH), 10.49 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 46.9
(SO2–CH2), 52.1 (CH2–SO2–NH), 104.8 (C-4ꢀ), 110.9 (C-3ꢀ), 118.3 (C-5ꢀ),
122.1 (C-2ꢀ), 154.9 (C-5), 155.6 (C-2), 126.7, 127.4, 128.8, 130.2, 131.5,
132.4, 134.6, 139.5 (aromatic carbons). IR (KBr) cmꢁ1: 3263 (NH), 1630
(CꢄC), 1587 (CꢄN), 1335, 1137 (SO2). Anal. Calcd for C20H16Cl2N4O5S2:
C, 45.55; H, 3.06; N, 10.62. Found: C, 45.60; H, 3.09; N, 10.67.
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrrol-3ꢀ-ylsulfonyl-
methyl)-1,3,4-thiadiazole (7a): Yellow solid, yield 70%, mp 156—158 °C;
1H-NMR (CDCl3) d: 5.03 (s, 2H, SO2–CH2), 5.19 (s, 2H, CH2–SO2–NH),
6.68 (s, 1H, C5ꢀ–H), 7.09—7.70 (m, 11H, C2ꢀ–H, Ar–H), 8.35 (br s, 1H, NH),
10.10 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 46.5 (SO2–CH2), 51.0
(CH2–SO2–NH), 102.9 (C-4ꢀ), 109.6 (C-3ꢀ), 117.5 (C-5ꢀ), 121.7 (C-2ꢀ),
158.2 (C-5), 159.6 (C-2), 125.4, 126.1, 127.4, 128.9, 129.5, 130.0, 131.2,
137.9 (aromatic carbons). IR (KBr) cmꢁ1: 3238 (NH), 1624 (CꢄC), 1592
(CꢄN), 1321, 1140 (SO2). Anal. Calcd for C20H18N4O4S3: C, 50.62; H, 3.82;
N, 11.81. Found: C, 50.60; H, 3.81; N, 11.88.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-1ꢀH-
pyrrol-3ꢀ-ylsulfonyl-methyl)-1,3,4-thiadiazole (7b): Pale yellow solid, yield
66%, mp 160—162 °C; 1H-NMR (CDCl3) d: 2.20 and 2.25 (s, 6H, Ar–CH3),
5.01 (s, 2H, SO2–CH2), 5.14 (s, 2H, CH2–SO2–NH), 6.62 (s, 1H, C5ꢀ–H),
7.04—7.65 (m, 9H, C2ꢀ–H, Ar–H), 8.27 (br s, 1H, NH), 10.03 (br s, 1H,
NH–SO2). 13C-NMR (CDCl3) d: 21.5 and 21.9 (Ar–CH3), 45.9 (SO2–CH2),
50.6 (CH2–SO2–NH), 102.3 (C-4ꢀ), 109.0 (C-3ꢀ), 117.0 (C-5ꢀ), 121.2 (C-2ꢀ),
157.9 (C-5), 159.3 (C-2), 125.8, 126.9, 127.5, 128.7, 129.5, 130.2, 132.0,
137.6 (aromatic carbons). IR (KBr) cmꢁ1: 3235 (NH), 1619 (CꢄC), 1584
(CꢄN), 1319, 1128 (SO2). Anal. Calcd for C22H22N4O4S3: C, 52.57; H, 4.41;
N, 11.15. Found: C, 52.62; H, 4.43; N, 11.10.
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-
3ꢀ-ylsulfonyl-methyl)-1,3,4-oxadiazole (9a): Pale yellow solid, yield 69%,
mp 137—139 °C; 1H-NMR (CDCl3) d: 3.58 (dd, 1H, HX, JAXꢄ6.5 Hz,
JMXꢄ10.6 Hz), 4.21 (dd, 1H, HM, JAMꢄ12.4 Hz), 4.57 (dd, 1H, HA), 4.96 (s,
2H, SO2–CH2), 5.16 (s, 2H, CH2–SO2–NH), 7.17—7.76 (m, 10H, Ar–H),
10.02 (br s, 1H, NH), 10.57 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 47.2
(SO2–CH2), 52.0 (CH2–SO2–NH), 53.7 (C-5ꢀ), 66.4 (C-4ꢀ), 152.8 (C-3ꢀ),
158.1 (C-5), 158.9 (C-2), 127.7, 128.4, 129.7, 130.6, 131.2, 132.0, 132.9,
135.1 (aromatic carbons). IR (KBr) cmꢁ1: 3255 (NH), 1583 (CꢄN), 1335,
1146 (SO2). Anal. Calcd for C19H19N5O5S2: C, 49.45; H, 4.15; N, 15.17.
Found: C, 49.51; H, 4.17; N, 15.24.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-4ꢀ,5ꢀ-di-
hydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (9b): Pale yellow
1
solid, yield 67%, mp 146—148 °C; H-NMR (CDCl3) d: 2.22 and 2.26 (s,
6H, Ar–CH3), 3.54 (dd, 1H, HX, JAXꢄ6.2 Hz, JMXꢄ10.4 Hz), 4.12 (dd, 1H,
HM, JAMꢄ12.2 Hz), 4.50 (dd, 1H, HA), 4.88 (s, 2H, SO2–CH2), 5.14 (s, 2H,
CH2–SO2–NH), 7.14—7.67 (m, 8H, Ar–H), 9.93 (br s, 1H, NH), 10.44 (br s,
1H, NH–SO2). 13C-NMR (CDCl3) d: 21.1 and 21.6 (Ar–CH3), 46.6
(SO2–CH2), 51.5 (CH2–SO2–NH), 52.9 (C-5ꢀ), 65.8 (C-4ꢀ), 151.4 (C-3ꢀ),
158.6 (C-5), 159.7 (C-2), 125.8, 126.6, 127.3, 128.4, 129.5, 130.3, 131.2,
134.8 (aromatic carbons). IR (KBr) cmꢁ1: 3257 (NH), 1587 (CꢄN), 1332,
1139 (SO2). Anal. Calcd for C21H23N5O5S2: C, 51.52; H, 4.74; N, 14.31.
Found: C, 51.56; H, 4.77; N, 14.37.
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-1ꢀH-
pyrrol-3ꢀ-ylsulfonyl-methyl)-1,3,4-thiadiazole (7c): Pale yellow solid, yield
1
71%, mp 175—177 °C; H-NMR (CDCl3) d: 5.13 (s, 2H, SO2–CH2), 5.27
(s, 2H, CH2–SO2–NH), 6.77 (s, 1H, C5ꢀ–H), 7.14—7.68 (m, 9H, C2ꢀ–H,
Ar–H), 8.43 (br s, 1H, NH), 10.22 (br s, 1H, NH–SO2). 13C-NMR (CDCl3)
d: 46.8 (SO2–CH2), 51.8 (CH2–SO2–NH), 103.2 (C-4ꢀ), 110.2 (C-3ꢀ), 117.9
(C-5ꢀ), 122.0 (C-2ꢀ), 158.4 (C-5), 159.0 (C-2), 126.6, 128.7, 129.6, 130.4,
131.5, 132.2, 134.1, 138.5 (aromatic carbons). IR (KBr) cmꢁ1: 3241 (NH),
1627 (CꢄC), 1597 (CꢄN), 1322, 1142 (SO2). Anal. Calcd for
C20H16Cl2N4O4S3: C, 44.20; H, 2.97; N, 10.31. Found: C, 44.24; H, 2.98; N,
10.37.
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-4ꢀ,5ꢀ-di-
hydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (9c): Pale yellow
1
solid, yield 73%, mp 152—154 °C; H-NMR (CDCl3) d: 3.63 (dd, 1H, HX,
JAXꢄ6.8 Hz, JMXꢄ10.8 Hz), 4.24 (dd, 1H, HM, JAMꢄ12.8 Hz), 4.59 (dd, 1H,
HA), 5.03 (s, 2H, SO2–CH2), 5.25 (s, 2H, CH2–SO2–NH), 7.21—7.87 (m,
8H, Ar–H), 10.14 (br s, 1H, NH), 10.62 (br s, 1H, NH–SO2). 13C-NMR
(CDCl3) d: 47.9 (SO2–CH2), 52.4 (CH2–SO2–NH), 53.9 (C-5ꢀ), 66.7 (C-4ꢀ),
153.0 (C-3ꢀ), 158.4 (C-5), 159.0 (C-2), 126.7, 127.4, 128.3, 129.0, 130.1,
131.4, 132.7, 136.1 (aromatic carbons). IR (KBr) cmꢁ1: 3269 (NH), 1598
(CꢄN), 1340, 1152, (SO2). Anal. Calcd for C19H17Cl2N5O5S2: C, 43.02; H,
3.23; N, 13.20. Found: C, 43.00; H, 3.22; N, 13.18.
4-Amino-3-(phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrrol-3ꢀ-yl-
sulfonylmethyl)- 1,2,4-triazole (8a): Yellow solid, yield 69%, mp 165—
167 °C; 1H-NMR (DMSO-d6) d: 5.09 (s, 2H, SO2–CH2), 5.29 (s, 2H,
CH2–SO2–NH), 5.58 (br s, 2H, NH2), 6.71 (s, 1H, C5ꢀ–H), 7.12—7.76 (m,
11H, C2ꢀ–H, Ar–H), 8.41 (br s, 1H, NH), 10.32 (br s, 1H, NH–SO2). 13C-
NMR (DMSO-d6) d: 47.0 (SO2–CH2), 51.9 (CH2–SO2–NH), 102.1 (C-4ꢀ),
110.4 (C-3ꢀ), 116.7 (C-5ꢀ), 121.9 (C-2ꢀ), 158.2 (C-5), 159.4 (C-3), 126.4,
127.2, 128.3, 129.1, 130.4, 131.4, 132.0, 137.4 (aromatic carbons). IR (KBr)
cmꢁ1: 3439, 3315 (NH2), 3268 (NH), 1632 (CꢄC), 1599 (CꢄN), 1328,
1137 (SO2). Anal. Calcd for C20H20N6O4S2: C, 50.83; H, 4.27; N, 17.78.
Found: C, 50.88; H, 4.24; N, 17.88.
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-
3ꢀ-ylsulfonyl-methyl)-1,3,4-thiadiazole (10a): Pale yellow solid, yield 68%,
mp 166—168 °C; 1H-NMR (CDCl3) d: 3.54 (dd, 1H, HX, JAXꢄ5.9 Hz,
JMXꢄ9.8 Hz), 4.26 (dd, 1H, HM, JAMꢄ11.8 Hz), 4.61 (dd, 1H, HA), 4.92 (s,
2H, SO2–CH2), 5.19 (s, 2H, CH2–SO2–NH), 7.19—7.69 (m, 10H, Ar–H),
9.86 (br s, 1H, NH), 10.46 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 47.8
(SO2–CH2), 51.1 (CH2–SO2–NH), 52.8 (C-5ꢀ), 66.8 (C-4ꢀ), 151.4 (C-3ꢀ),
157.9 (C-5), 159.0 (C-2), 125.9, 126.5, 127.6, 128.7, 129.4, 130.2, 133.4,
136.6 (aromatic carbons). IR (KBr) cmꢁ1: 3270 (NH), 1601 (CꢄN), 1325,
4-Amino-3-(p-methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-
1ꢀH-pyrrol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (8b): Yellow solid, yield
74%, mp 172—174 °C; 1H-NMR (DMSO-d6) d: 2.19 and 2.24 (s, 6H,

1516
Vol. 59, No. 12
1H-NMR (CDCl3) d: 5.07 (s, 2H, SO2–CH2), 5.31 (s, 2H, CH2–SO2–NH),
6.52 (br s, 1H, NH), 6.84—7.77 (m, 11H, C5ꢀ–H, Ar–H), 10.39 (br s, 1H,
NH–SO2). 13C-NMR (CDCl3) d: 45.2 (SO2–CH2), 52.8 (CH2–SO2–NH),
133.9 (C-4ꢀ), 138.5 (C-5ꢀ), 148.1 (C-3ꢀ), 159.0 (C-5), 159.7 (C-2), 126.9,
127.4, 128.6, 129.7, 131.8, 132.8, 134.2, 138.5 (aromatic carbons). IR (KBr)
cmꢁ1: 3283 (NH), 1642 (CꢄC), 1586 (CꢄN), 1323, 1139 (SO2). Anal.
Calcd for C19H17N5O5S2: C, 49.66; H, 3.73; N, 15.24. Found: C, 49.70; H,
3.71; N, 15.32.
1130 (SO2). Anal. Calcd for C19H19N5O4S3: C, 47.78; H, 4.01; N, 14.66.
Found: C, 47.85; H, 4.14; N, 14.71.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-4ꢀ,5ꢀ-di-
hydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (10b): Pale yel-
1
low solid, yield 65%, mp 174—176 °C; H-NMR (CDCl3) d: 2.21 and 2.27
(s, 6H, Ar–CH3), 3.48 (dd, 1H, HX, JAXꢄ5.7 Hz, JMXꢄ9.6 Hz), 4.15 (dd, 1H,
HM, JAMꢄ11.7 Hz), 4.52 (dd, 1H, HA), 4.81 (s, 2H, SO2–CH2), 5.13 (s, 2H,
CH2–SO2–NH), 7.14—7.67 (m, 8H, Ar–H), 9.78 (br s, 1H, NH), 10.35 (br s,
1H, NH–SO2). 13C-NMR (CDCl3) d: 21.5 and 22.1 (Ar-CH3), 47.0
(SO2–CH2), 50.5 (CH2–SO2–NH), 52.4 (C-5ꢀ), 66.0 (C-4ꢀ), 151.0 (C-3ꢀ),
159.0 (C-5), 159.8 (C-2), 126.3, 127.5, 128.4, 129.5, 130.2, 132.8, 133.5,
135.5 (aromatic carbons). IR (KBr) cmꢁ1: 3268 (NH), 1588 (CꢄN), 1329,
1137 (SO2). Anal. Calcd for C21H23N5O4S3: C, 49.88; H, 4.58; N, 13.85.
Found: C, 49.92; H, 4.56; N, 13.91.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-1ꢀH-pyra-
zol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (12b): Yellow solid, yield 66%,
mp 196—198 °C; 1H-NMR (CDCl3) d: 2.21 and 2.25 (s, 6H, Ar–CH3), 5.03
(s, 2H, SO2–CH2), 5.22 (s, 2H, CH2–SO2–NH), 6.47 (br s, 1H, NH), 6.82—
7.72 (m, 9H, C5ꢀ–H, Ar–H), 10.27 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d:
21.3 and 21.8 (Ar–CH3), 45.0 (SO2–CH2), 52.3 (CH2–SO2–NH), 133.4 (C-
4ꢀ), 138.0 (C-5ꢀ), 147.8 (C-3ꢀ), 158.7 (C-5), 159.6 (C-2), 126.3, 127.5,
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-4ꢀ,5ꢀ-di-
hydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (10c): Pale yellow
128.6, 129.8, 131.4, 133.4, 134.3, 136.0 (aromatic carbons). IR (KBr) cmꢁ1
:
1
solid, yield 72%, mp 182—184 °C; H-NMR (CDCl3) d: 3.61 (dd, 1H, HX,
3274 (NH), 1636 (CꢄC), 1579 (CꢄN), 1318, 1126 (SO2). Anal. Calcd for
C21H21N5O5S2: C, 51.73; H, 4.34; N, 14.36. Found: C, 51.70; H, 4.35; N,
14.44.
JAXꢄ6.2 Hz, JMXꢄ10.1 Hz), 4.29 (dd, 1H, HM, JAMꢄ12.0 Hz), 4.64 (dd, 1H,
HA), 4.99 (s, 2H, SO2–CH2), 5.21 (s, 2H, CH2–SO2–NH), 7.22—7.72 (m,
8H, Ar–H), 9.91 (br s, 1H, NH), 10.51 (br s, 1H, NH–SO2). 13C-NMR
(CDCl3) d: 48.1 (SO2–CH2), 51.3 (CH2–SO2–NH), 53.5 (C-5ꢀ), 67.2 (C-4ꢀ),
152.3 (C-3ꢀ), 158.6 (C-5), 159.5 (C-2), 127.3, 128.5, 129.6, 130.1, 132.4,
133.8, 134.3, 137.1 (aromatic carbons). IR (KBr) cmꢁ1: 3281 (NH), 1607
(CꢄN), 1338, 1143 (SO2). Anal. Calcd for C19H17Cl2N5O4S3: C, 41.76; H,
3.14; N, 12.82. Found: C, 41.82; H, 3.17; N, 12.87.
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-1ꢀH-pyra-
zol-3ꢀ-ylsulfonyl-methyl)-1,3,4-oxadiazole (12c): Yellow solid, yield 72%,
1
mp 208—210 °C; H-NMR (CDCl3) d: 5.14 (s, 2H, SO2–CH2), 5.37 (s, 2H,
CH2–SO2–NH), 6.54 (br s, 1H, NH), 6.91—7.81 (m, 9H, C5ꢀ–H, Ar–H),
10.44 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 46.3 (SO2–CH2), 53.0
(CH2–SO2–NH), 134.5 (C-4ꢀ), 139.2 (C-5ꢀ), 148.7 (C-3ꢀ), 158.6 (C-5),
159.5 (C-2), 127.1, 127.8, 129.3, 130.4, 131.6, 132.1, 133.5, 137.1 (aromatic
carbons). IR (KBr) cmꢁ1: 3281 (NH), 1644 (CꢄC), 1592 (CꢄN), 1329,
1129 (SO2). Anal. Calcd for C19H15Cl2N5O5S2: C, 43.19; H, 2.86; N, 13.25.
Found: C, 43.23; H, 2.85; N, 13.32.
4-Amino-3-(phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-4ꢀ,5ꢀ-dihydro-
1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (11a): Yellow solid, yield
71%, mp 171—173 °C; 1H-NMR (DMSO-d6) d: 3.64 (dd, 1H, HX,
JAXꢄ6.3 Hz, JMXꢄ10.4 Hz), 4.09 (dd, 1H, HM, JAMꢄ12.1 Hz), 4.53 (dd, 1H,
HA), 5.09 (s, 2H, SO2–CH2), 5.24 (s, 2H, CH2–SO2–NH), 5.69 (br s, 2H,
NH2), 7.17—7.59 (m, 10H, Ar–H), 9.30 (br s, 1H, NH), 10.07 (br s, 1H,
NH–SO2). 13C-NMR (DMSO-d6) d: 45.9 (SO2–CH2), 50.5 (CH2–SO2–NH),
52.3 (C-5ꢀ), 65.9 (C-4ꢀ), 152.7 (C-3ꢀ), 159.2 (C-5), 159.7 (C-3), 127.2,
128.0, 128.9, 130.4, 131.3, 132.1, 134.2, 135.1 (aromatic carbons). IR (KBr)
cmꢁ1: 3482, 3367 (NH2), 3248 (NH), 1612 (CꢄN), 1310, 1138 (SO2). Anal.
Calcd for C19H21N7O4S2: C, 47.99; H, 4.45; N, 20.62. Found: C, 47.97; H,
4.47; N, 20.70.
4-Amino-3-(p-methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-
4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (11b): Pale
yellow solid, yield 69%, mp 186—188 °C; 1H-NMR (DMSO-d6) d: 2.23 and
2.28 (s, 6H, Ar–CH3), 3.52 (dd, 1H, HX, JAXꢄ6.0 Hz, JMXꢄ10.1 Hz), 4.03
(dd, 1H, HM, JAMꢄ11.8 Hz), 4.48 (dd, 1H, HA), 5.03 (s, 2H, SO2–CH2), 5.15
(s, 2H, CH2–SO2–NH), 5.63 (br s, 2H, NH2), 7.14—7.63 (m, 8H, Ar-H),
9.22 (br s, 1H, NH), 10.03 (br s, 1H, NH–SO2). 13C-NMR (DMSO-d6) d:
21.0 and 21.5 (Ar–CH3), 45.1 (SO2–CH2), 50.1 (CH2–SO2–NH), 51.7 (C-
5ꢀ), 65.4 (C-4ꢀ), 152.1 (C-3ꢀ), 158.6 (C-5), 159.4 (C-3), 126.0, 128.7, 129.4,
130.6, 132.1, 132.9, 133.6, 136.9 (aromatic carbons). IR (KBr) cmꢁ1: 3476,
3358 (NH2), 3253 (NH), 1605 (CꢄN), 1313, 1134 (SO2). Anal. Calcd for
C21H25N7O4S2: C, 50.08; H, 5.00; N, 19.47. Found: C, 50.02; H, 5.01; N,
19.57.
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl-
methyl)-1,3,4-thiadiazole (13a): Pale yellow solid, yield 67%, mp 216—
218 °C; 1H-NMR (CDCl3) d: 5.11 (s, 2H, SO2–CH2), 5.27 (s, 2H,
CH2–SO2–NH), 6.50 (br s, 1H, NH), 6.95—7.86 (m, 11H, C5ꢀ–H, Ar–H),
10.40 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 45.7 (SO2–CH2), 51.9
(CH2–SO2–NH), 134.3 (C-4ꢀ), 138.7 (C-5ꢀ), 148.5 (C-3ꢀ), 158.8 (C-5),
159.4 (C-2), 126.8, 127.5, 128.3, 129.5, 131.7, 132.8, 134.4, 138.3 (aromatic
carbons). IR (KBr) cmꢁ1: 3266 (NH), 1639 (CꢄC), 1597 (CꢄN), 1338,
1134 (SO2). Anal. Calcd for C19H17N5O4S3: C, 47.99; H, 3.60; N, 14.73.
Found: C, 48.05; H, 3.64; N, 14.77.
2-(p-Methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-1ꢀH-pyra-
zol-3ꢀ-ylsulfonylmethyl)-1,3,4-thiadiazole (13b): Pale yellow solid, yield
69%, mp 226—228 °C; 1H-NMR (CDCl3) d: 2.20 and 2.24 (s, 6H, Ar–CH3),
5.07 (s, 2H, SO2–CH2), 5.23 (s, 2H, CH2–SO2–NH), 6.46 (br s, 1H, NH),
6.91—7.75 (m, 9H, C5ꢀ–H, Ar–H), 10.31 (br s, 1H, NH–SO2). 13C-NMR
(CDCl3) d: 21.1 and 21.5 (Ar–CH3), 45.5 (SO2–CH2), 51.6 (CH2–SO2–NH),
133.9 (C-4ꢀ), 138.0 (C-5ꢀ), 148.4 (C-3ꢀ), 158.2 (C-5), 159.0 (C-2), 126.0,
127.2, 128.9, 130.5, 131.6, 132.4, 134.6, 136.8 (aromatic carbons). IR (KBr)
cmꢁ1: 3258 (NH), 1637 (CꢄC), 1601 (CꢄN), 1324, 1131 (SO2). Anal.
Calcd for C21H21N5O4S3: C, 50.08; H, 4.20; N, 13.91. Found: C, 50.00; H,
4.23; N, 13.89.
4-Amino-3-(p-chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-
4ꢀ,5ꢀ-dihydro-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (11c): Pale
yellow solid, yield 73%, mp 204—206 °C; 1H-NMR (DMSO-d6) d: 3.68 (dd,
1H, HX, JAXꢄ6.6 Hz, JMXꢄ10.4 Hz), 4.18 (dd, 1H, HM, JAMꢄ12.5 Hz), 4.60
(dd, 1H, HA), 5.15 (s, 2H, SO2–CH2), 5.28 (s, 2H, CH2–SO2–NH), 5.74 (br s,
2H, NH2), 7.20—7.76 (m, 8H, Ar–H), 9.42 (br s, 1H, NH), 10.16 (br s, 1H,
NH–SO2). 13C-NMR (DMSO-d6) d: 46.2 (SO2–CH2), 50.8 (CH2–SO2–NH),
52.8 (C-5ꢀ), 66.6 (C-4ꢀ), 153.0 (C-3ꢀ), 157.8 (C-5), 158.7 (C-3), 127.1,
128.3, 129.5, 130.2, 131.4, 132.0, 132.9, 137.4 (aromatic carbons). IR (KBr)
cmꢁ1: 3490, 3375 (NH2), 3271 (NH), 1609 (CꢄN), 1326, 1145 (SO2). Anal.
Calcd for C19H19Cl2N7O4S2: C, 41.92; H, 3.52; N, 18.01. Found: C, 41.97;
H, 3.56; N, 18.10.
General Procedure of Synthesis of 2-(Arylaminosulfonylmethyl)-5-(4ꢀ-
aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-oxadiazole (12a—c)/2-(Aryl-
aminosulfonylmethyl)-5-(4ꢀ-aryl-1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,3,4-
thiadiazole (13a—c)/4-Amino-3-(arylamino-sulfonylmethyl)-5-(4ꢀ-aryl-
1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (14a—c) A solution of
9/10/11 (1 mmol) and chloranil (1.4 mmol) in xylene (10 ml) was refluxed
for 25—30 h. Then, the reaction mixture was treated with 5% NaOH solu-
tion. The organic layer was separated and repeatedly washed with water. It
was dried over anhydrous Na2SO4 and the solvent was removed on a rotary
evaporator. The resultant solid was recrystallized from methanol.
2-(p-Chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-1ꢀH-pyra-
zol-3ꢀ-ylsulfonyl-methyl)-1,3,4-thiadiazole (13c): Yellow solid, yield 71%,
mp 235—237 °C; H-NMR (CDCl3) d: 5.16 (s, 2H, SO2–CH2), 5.34 (s, 2H,
1
CH2–SO2–NH), 6.59 (br s, 1H, NH), 7.04—7.82 (m, 9H, C5ꢀ–H, Ar–H),
10.45 (br s, 1H, NH–SO2). 13C-NMR (CDCl3) d: 46.4 (SO2–CH2), 52.5
(CH2–SO2–NH), 134.8 (C-4ꢀ), 139.4 (C-5ꢀ), 149.2 (C-3ꢀ), 158.9 (C-5),
159.4 (C-2), 127.3, 128.4, 129.7, 131.6, 132.4, 133.7, 134.8, 136.5 (aromatic
carbons). IR (KBr) cmꢁ1: 3273 (NH), 1641 (CꢄC), 1608 (CꢄN), 1342,
1140 (SO2). Anal. Calcd for C19H15Cl2N5O4S3: C, 41.91; H, 2.78; N, 12.86.
Found: C, 41.97; H, 2.81; N, 12.95.
4-Amino-3-(phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrazol-3ꢀ-
ylsulfonylmethyl)-1,2,4-triazole (14a): Yellow solid, yield 73%, mp 220—
222 °C; 1H-NMR (DMSO-d6) d: 5.05 (s, 2H, SO2–CH2), 5.25 (s, 2H,
CH2–SO2–NH), 5.72 (br s, 2H, NH2), 6.51 (br s, 1H, NH), 7.01—7.68 (m,
11H, C5ꢀ–H, Ar–H), 10.27 (br s, 1H, NH–SO2). 13C-NMR (DMSO-d6) d:
47.0 (SO2–CH2), 51.3 (CH2–SO2–NH), 132.9 (C-4ꢀ), 139.0 (C-5ꢀ), 149.1
(C-3ꢀ), 158.5 (C-5), 159.2 (C-3), 126.1, 127.4, 129.2, 130.8, 131.6,
132.4, 133.5, 135.3 (aromatic carbons). IR (KBr) cmꢁ1: 3461, 3328 (NH2),
3268 (NH), 1633 (CꢄC), 1615 (CꢄN), 1321, 1146 (SO2). Anal. Calcd for
C19H19N7O4S2: C, 48.19; H, 4.04; N, 20.71. Found: C, 48.25; H, 4.05; N,
20.80.
4-Amino-3-(p-methylphenylaminosulfonylmethyl)-5-(4ꢀ-p-methylphenyl-
1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (14b): Yellow solid, yield
70%, mp 238—240 °C; 1H-NMR (DMSO-d6) d: 2.21 and 2.27 (s, 6H,
2-(Phenylaminosulfonylmethyl)-5-(4ꢀ-phenyl-1ꢀH-pyrazol-3ꢀ-ylsulfonyl-
methyl)-1,3,4-oxadiazole (12a): Yellow solid, yield 68%, mp 188—190 °C;

December 2011
1517
Ar–CH3), 4.99 (s, 2H, SO2–CH2), 5.16 (s, 2H, CH2–SO2–NH), 5.67 (br s,
2H, NH2), 6.48 (br s, 1H, NH), 6.91—7.70 (m, 9H, C5ꢀ–H, Ar–H), 10.19 (br
s, 1H, NH–SO2). 13C-NMR (DMSO-d6) d: 21.5 and 21.9 (Ar–CH3), 46.7
(SO2–CH2), 50.9 (CH2–SO2–NH), 132.4 (C-4ꢀ), 138.6 (C-5ꢀ), 148.6
(C-3ꢀ), 158.7 (C-5), 159.5 (C-3), 127.2, 128.4, 129.9, 131.7, 132.6, 133.4,
135.4, 137.8 (aromatic carbons). IR (KBr) cmꢁ1: 3453, 3339 (NH2), 3251
(NH), 1629 (CꢄC), 1606 (CꢄN), 1325, 1137 (SO2). Anal. Calcd for
C21H23N7O4S2: C, 50.29; H, 4.62; N, 19.55. Found: C, 50.35; H, 4.65; N,
19.63.
4-Amino-3-(p-chlorophenylaminosulfonylmethyl)-5-(4ꢀ-p-chlorophenyl-
1ꢀH-pyrazol-3ꢀ-ylsulfonylmethyl)-1,2,4-triazole (14c): Yellow solid, yield
76%, mp 246—248 °C; 1H-NMR (DMSO-d6) d: 5.11 (s, 2H, SO2–CH2),
5.31 (s, 2H, CH2–SO2–NH), 5.79 (br s, 2H, NH2), 6.53 (br s, 1H, NH),
7.06—7.89 (m, 9H, C5ꢀ–H, Ar–H), 10.31 (br s, 1H, NH–SO2). 13C-NMR
(DMSO-d6) d: 47.7 (SO2–CH2), 51.9 (CH2–SO2–NH), 133.7 (C-4ꢀ), 139.5
(C-5ꢀ), 149.5 (C-3ꢀ), 159.1 (C-5), 159.7 (C-3), 127.4, 128.7, 129.7, 131.6,
132.5, 133.9, 135.4, 138.2 (aromatic carbons). IR (KBr) cmꢁ1: 3469, 3334
(NH2), 3223 (NH), 1637 (CꢄC), 1611 (CꢄN), 1319, 1142 (SO2). Anal.
Calcd for C19H17Cl2N7O4S2: C, 42.07; H, 3.16; N, 18.08. Found: C, 42.02;
H, 3.15; N, 18.16.
Antimicrobial Testing The compounds 3—14 were dissolved in di-
methyl sulfoxide (DMSO) at different concentrations of 50 and 100 mg. Bac-
terial strains Staphylococcus aureus, Bacillus subtilis, Pseudomonas aerugi-
nosa, Klebsiella pneumoniae and fungi Penicillium chrysogenum, Curvu-
laria lunata and Aspergillus niger were obtained from Department of Micro-
biology, S.V. University, Tirupati, India.
Antibacterial and Antifungal Assays The in vitro antimicrobial studies
were carried out by agar well diffusion method against test organisms.29,30)
Nutrient broth (NB) plates were swabbed with 24 h old broth culture
(100 ml) of test bacteria. Using the sterile cork borer, wells (6 mm) were
made into each petriplate. The compounds were dissolved in DMSO of
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Broth dilution test is used to determine minimum inhibitory concentration
(MIC) of the above mentioned samples.31,32) Freshly prepared nutrient broth
was used as diluents. The 24 h old culture of the test bacteria Staphylococcus
aureus, Bacillus subtilis, Pseudomonas aeruginosa and Klebsiella pneumo-
niae and the test fungi Penicillium chrysogenum, Curvularia lunata and As-
pergillus niger were diluted 100 folds in nutrient broth (100 ml bacterial cul-
tures in 10 ml NB). The stock solution of the synthesized compounds was
prepared in DMSO by dissolving 5 mg of the compound in 1 ml of DMSO.
Increasing concentrations of the test samples (1.25, 2.5, 5, 10, 20, 40 ml of
stock solution contains 6.25, 12.5, 25, 50, 100, 200 mg of the compounds)
were added to the test tubes containing the bacterial and fungal cultures. All
the tubes were incubated at 37 °C for 24 h for bacteria and at 28 °C for 48 h
for fungi. The tubes were examined for visible turbidity and using NB as
control. Control without test samples and with solvent was assayed simulta-
neously. The lowest concentration that inhibited visible growth of the tested
organisms was recorded as MIC.
To determine the MBC33) and MFC34) for each set of test tubes in the MIC
determination, a loopful of broth was collected from those tubes which did
not show any growth and inoculated on sterile nutrient broth (for bacteria)
and PDA (for fungi) by streaking. Plates inoculated with bacteria and fungi
were incubated at 37 °C for 24 h and at 28 °C for 48 h, respectively. After in-
cubation, that concentration was noted as MBC (for bacteria) or MFC (for
fungi) at which no visible growth was observed.
Acknowledgment The authors are thankful to Council of Scientific and
Industrial Research (CSIR), New Delhi for financial assistance under major
research project.
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