Synthesis, anti-HIV, and antifungal activity of new benzensulfonamides bearing the 2,5-disubstituted-1,3,4-oxadiazole moiety

Article abstract of DOI:10.1080/10426500600919074

A series of novel chiral and achiral N-[1-(1,3,4-oxadiazol-2ylthio)alkyl]- 4-methyl/chloro/methoxybenzenesulfonamides 5a-l were prepared by the reaction of 4-(4-methyl, chloro, methoxyphenylsulfonamido)alkyl carboxylic acid hydrazides 4a-l with CS2 and KO

Full text of DOI:10.1080/10426500600919074

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Synthesis, Anti–HIV, and
Antifungal Activity of New
Benzensulfonamides Bearing
the 2,5-Disubstituted-1,3,4-
Oxadiazole Moiety
Muhammad Zareef a , Rashid Iqbal a , Najim A. Al-
Masoudi b , Javid H. Zaidi a , Muhammad Arfan a &
Sohail A. Shahzad c
a Department of Chemistry , Quaid-i-Azam
University , Islamabad, Pakistan
b Universitat Konstanz (Formerly Fachbereich
Chemie) , Postfach, Germany
c International Centre for Chemical Sciences ,
HEJ Research Institute of Chemistry, University of
Karachi , Karachi, Pakistan
Published online: 18 Feb 2007.
To cite this article: Muhammad Zareef , Rashid Iqbal , Najim A. Al-Masoudi , Javid
H. Zaidi , Muhammad Arfan & Sohail A. Shahzad (2007) Synthesis, Anti–HIV, and
Antifungal Activity of New Benzensulfonamides Bearing the 2,5-Disubstituted-1,3,4-
Oxadiazole Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:2,
281-298, DOI: 10.1080/10426500600919074
To link to this article: http://dx.doi.org/10.1080/10426500600919074
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Phosphorus, Sulfur, and Silicon, 182:281–298, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600919074
Synthesis, Anti–HIV, and Antifungal Activity
of New Benzensulfonamides Bearing the
2,5-Disubstituted-1,3,4-Oxadiazole Moiety
Muhammad Zareef
Rashid Iqbal
Department of Chemistry, Quaid-i-Azam University, Islamabad,
Pakistan
Najim A. Al-Masoudi
Universitat Konstanz (Formerly Fachbereich Chemie), Postfach,
Germany
Javid H. Zaidi
Muhammad Arfan
Department of Chemistry, Quaid-i-Azam University, Islamabad,
Pakistan
Sohail A. Shahzad
International Centre for Chemical Sciences, HEJ Research Institute
of Chemistry, University of Karachi, Karachi, Pakistan
A
series of novel chiral and achiral N-[1-(1,3,4-oxadiazol-2ylthio)alkyl]-4-
methyl/chloro/methoxybenzenesulfonamides 5a–l were prepared by the reaction
of 4-(4-methyl, chloro, methoxyphenylsulfonamido)alkyl carboxylic acid hydrazides
4a–l with CS and KOH. Another series of new secondary benzenesulfonamides
2
10a–j and bis-benzenesulfonamides 11a–j have been synthesized by a new ap-
proach using Et N and dimethylaminopyridine. All synthesized compounds were
3
characterized by physical, microanalytical, and spectral data. Some of the synthe-
sized compounds were screened in vitro for their anti–HIV and antifungal activities.
Keywords Antifungal activity; anti–HIV activity; benezenesulfonamides chiral
sulfonamides; 1,3,4-oxadiazole
The 1,3,4-oxadiazole family attracts significant attention due to
their chemotherapeutic importance.1−6 Such compounds showed high
Received February 26, 2006; accepted June 26, 2006.
Address correspondence to Muhammad Zareef, Quaid-i-Azam University, Department
of Chemistry, Islamabad, 45320 Pakistan. E-mail: mkzareef@yahoo.com
281

282
M. Zareef et al.
activity by carrying the potential sulfonamide and free thiol residues.
The sulfonamide moiety is a crucial functionality because of its wide va-
riety of pharmacological, activities, such as antimicrobial, anti–HIV,7
insuline-releasing antidiabetic, carbonic anhydrase inhibitory,8,9 high
ceiling diuretic, and antithyroid and antitumor activities.10−12 In ad-
dition, more recent articles have reported various sets of novel sulfon-
amide drugs, e.g., an inhibitor of membrane-bound human and bovine
®
isozymes IV13 and sildenafil citrate (Viagra ) as a drug for treating
male erectile dysfunction (ED).14 The second-generation antimitotic
sulfonamide, ER-34410, is 2 to 3 times more potent than E7010 in a
panel of various human tumor-cell lines in vitro and can be adminis-
tered intravenously.15
Regarding the free thiol moiety (SH)/free mercaptoaryl group, it
showed facil coordination with transition metal ions, such as Zn (ll),
Cu (ll), and Fe (lll), giving products with highly physiological im-
portance. A large number of metallo-enzymes incorporate Zn (ll) or
Cu (ll) ions coordinated by one or several –SH groups belonging to Cys
residues.1,15,16 Furthermore, the free SH has a strong nucleophilic char-
acter and can easily be derivatized by many electrophiles (E+), such as
haloacetates, maleimides, and activated sulfonyl groups, which show
different physicochemical properties.16 The S-alkylation/arylation, S-
acylation, or S-sulfonylation of the free SH is indeed of exceptional
importance mainly for the design of novel chemotherapeutic agents.1,15
These biological data prompted us to synthesize some novel chiral and
achiral 1,3,4-oxadiazoles-bearing sulfonamides and thiol residues com-
pounds and evaluate their anti–HIV-1 and antifungal activities.
RESULTS AND DISCUSSION
Although a number of methods are available for the synthe-
sis of sulfonamides, they are usually prepared from carboxylic
acids/hydrazides17and sulfonic acids/sulfonylchlorides18 as starting
compounds. We report herein a novel approach using different chiral
and achiral amino acids as a starting material (Scheme 1), together
with a series of new benzenesulfonamides with 2,5-disubstituted-1,3,4-
oxadiazole moiety via a new alternative approach (Scheme 2). The
advantages of these methods include the availability of the starting
materials with high yields of products.
Four amino acids, 1a–d, were converted into their corresponding sul-
fonamides 2a–l by a reaction with 4-methylbenzenesulfonylchloride,
4-chlorobenzenesulfonylchloride, and 4-methoxybenzene-sulfonyl chlo-
ride in an alkaline medium (Scheme 1) using standard methods.19a
Esterfication of 2a–l with ethanol in an acidic medium afforded the

New Benzensulfonamides
283
SCHEME 1 Reagents and conditions (i) aq. 5% NaOH, ether, 23◦C, 6h;
(ii) H2SO4/ethanol, reflux; (iii) NH2-NH2·H2O/ethanol reflux, 9 h; (iv) CS2/KOH,
ethanol, reflux, 17 h.
esters 3a–d following the literature method.19b Treatment of 3a–d,
with 80% hydrazine hydrate, furnished the corresponding hydrazides
4a–l in good yields. The sulfonamides bearing a 2,5-disubstituted-
1,3,4-oxadiazole moiety 5a–l were then prepared by the reaction of hy-
drazides 4a–l with CS2 and KOH employing the literature method.6,20
The structures of the synthesized compounds were determined by the
1H NMR, IR, and mass spectra, as well as the optical rotations (chiral

284
M. Zareef et al.
R
R
O
C
H
N
H
N
O
C
O
(i)
NH
R1
NH2
NO2
C
R1
e
R2
6a–
7a–e
R2
(ii)
R, R2 H,
CH
3
1(a)
=
R1
R1
R3 = OCH3
=
R
N
N
R, R2 H,
OCH
3
(b)
=
=
NO2
R1
,
R, R2
O
(c)
(d)
(e)
R2
= Cl
R, R1
R,R2
H
H
R2
R1
=
=
8a–e
= Cl
(iii)
R
N
N
R1
NH2
O
R2
9a–e
O
(iv)
S
R3
Cl
O
CH , OCH
R3=
N
3
3
R
N
N
O
S
N
R
H
N
O
S
N
S
R1
R3
R1
R3
+
O
O
O
O
O
R2
R2
O
j
10a–
11a–j
R3
SCHEME 2 Conditions and reagents (i) p-NO2-PhCOCl, CH3CN, 23◦C, 6 h;
(ii) SOCl2, reflux, 2 h; (iii) Pd/C (10%), ethanol, reflux, 9 h; (iv) Et3N, DMAP,
CHCl3, 70◦C, reflux 11 h.
compounds). Compound 5j was selected for the spectroscopic analysis,
since the analogues 5a–f and 5k–l showed a similar spectral pattern.
The IR spectrum of 5j revealed the presence of characteristic bands for
-NH at 3282 cm−1, 2551 cm−1 for -SH, 1589 cm−1 (C N), and 1375 cm−1
and 1126 cm−1 for the SO2 functional group. The mass spectrum of 5j
1
showed a molecular ion peak at m/z 299 (M+, 45). The H NMR spec-
trum of 5j showed a multiplet signal at δ 4.57–4.65, characteristic for
the chiral CH (Z) center, whereas the other protons were fully analyzed.
To the best of our knowledge, 5g–i are not reported in the literature.
Meanwhile, the new sulfonamides 5a–f, 5j–l, and their corresponding
intermediate compounds were prepared21,22 recently in our laboratory
(Scheme 1).

New Benzensulfonamides
285
Alternatively, hydrazides 6a–e were converted into the N,N-
diacylhydrazines 7a–e by treatment with 4-nitrobenzoylchloride in
dry MeCN. Compounds 7a–e were subjected to dehydrative cycliza-
tion in the presence of thionyl chloride to give 8a–e.23 The reduc-
tion of 8a–e with Pd/C and hydrazine hydrate, following a reported
method,24 afforded the amino compounds 9a–e in good yields. The
treatment of 9a–e with Et3N and dimethylaminopyridine furnished,
after purification, the corresponding sulfonamides 10a–e and 11a–e
(Scheme 2).
1
Structures of the synthesized compounds were characterized by H
NMR, IR, and mass spectra. Compound 10a was selected for the spec-
troscopic interpretation, whereas its analogs revealed similar spectral
patterns. The IR spectrum of 10a revealed the presence of character-
istic bands for NH at 3266 cm−1, 1589 cm−1 for C=N, and 1379 cm−1
and 1149 cm−1 for SO2 functional groups. The mass spectrum of 10a
showed a molecular ion peak at m/z 405 (M+). The 1H NMR spectrum of
10a demonstrated singlets at δ 2.44 and δ 2.84 that were attributed to
CH3-Ar, whereas the doublets at δ 7.26, 7.43, 7.49, 7.81, 8.06, and 8.20
(J ∼ 8.0 Hz) belonged to aromatic protons. The NH signal appeared at δ
10.54, which exchanged with D2O. The IR spectrum of bis-sulfonamide
11a showed no signal for the NH group, whereas it showed a molecular
ion peak at m/z 559 (M+).
ANTI-HIV ACTIVITY
Compounds 4k, 5b, 5c, 5e, 5f, 5g, 9a, 9b, 10a, and 10f were tested
for their anti–HIV-1 and HIV-2 activity in vitro using IIIB and ROD
strains, respectively, in human T-lymphocyte (MT-4) cells. The results
are summarized in Table I in which the data have been included for com-
parison purposes. Compound-induced cytotoxicity was also measured
in MT-4 cells parallel with antiviral activity. None of the oxadiazole
derivatives (sulfonamides bearing a 2,5-disubstituted-1,3,4-oxadiazole
moiety) were found to inhibit HIV-1 and HIV-2 replication in vitro
at EC50 lower than the CC50 in comparison to the antiviral agent
efavirenz (EFV)24 and azidothymidine (AZT).25 On the other hand, 5g
showed IC50 > 18.3 μg/mL and induced cytopathicity in human MT-
4 lymphocyte cells at nontoxic concentrations, with no selectivity (SI
= 3). Meanwhile, it showed an unusual result by the higher value of
anti–HIV-2 activity in comparison to anti–HIV activity with maximum
protection 62.
The cavity on gp41 of HIV plays an important role in the viral
replication process, which could hold a small molecule inhibitor. Non-
reverse transcriptase inhibitors that would fit this cavity have been

286
M. Zareef et al.
TABLE I In vitro anti–HIV-1a and HIV-2b of Some New
Oxadiazole Derivatives
IC50(μg/mL)c
Compound
MT-4
CC50(μg/mL)d
SIe
Max. Prot.
4k
IIIB
ROD
IIIB
ROD
IIIB
ROD
IIIB
ROD
IIIB
ROD
IIIB
ROD
IIIB
ROD
IIIB
>113
>125
>70
= 113
= 125
= 70
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
= 3
<1
<1
<1
<1
<1
<1
<1
<1
1
2
4
5b
5c
>74
= 74
5
>110
>125
>122
>125
>125
>125
>71
= 110
= 125
= 122
= 125
= 125
= 125
= 71
17
32
2
5
1
24
8
62
6
13
1
5
5e
5f
5g
9a
9b
10a
10f
= 18
= 63
>22
= 22
>35
>98
>116
>89
>119
>94
>103
40
63
= 35
= 99
ROD
IIIB
ROD
IIIB
= 116
= 89
1
2
1
3
= 119
= 2.44
= 103
0.003
0.02
ROD
EFV
AZT
a Anti–HIV-1 activity measured with strain IIIB
.
bAnti–HIV-2 activity measured with strain ROD.
cCompound concentrationrequired to reduce the viability of
mock-infected MT-4 cells by 50%.
d Compound concentration required to achieve 50% protection of
MT-4 cells from HIV-1 and 2 induced cytopathogenicity.
e SI: Selectivity index (IC50/CC50).
identified as active precursors26 to inhibit virus replication. Accord-
ingly, our synthetic strategy for the synthesis of new oxadiazole deriva-
tives bearing mercapto ( SH) moieties depends on this hypothesis. In
conclusion, compounds having an oxadiazole backbone carrying thio
congeners offer more opportunity for further antiviral investigation
than amino alkyl groups.
Antifungal Activity
Invasive aspergillosis is one of the most common fungal infections
in immunocompromised patients and carries high mortality rates.27

New Benzensulfonamides
287
TABLE II Antifungal Activity of Some New Oxadiazole Derivatives
and Inhibition Zones (%)
Compound No.
Standard
Name of Fungi
5b
5c
5e
5f 5g 5k
5l
8a
Drug
Trichphyton longifusus
Candida albicans
Aspergillus flavus
Microsporum canis
Fusarium solani
90
0
100
0
0
50
50
0
0
0
0
0
0
50
0
30
0
0
0
0
0
50
0
0
0
0
0
0
0
50
0
0
0
0
0
0
50
0
0
0
0
0
0
0
50
0
Miconazole
Miconazole
Amphotericin
Miconazole
Miconazole
Miconazole
Candida glabrata
0
0
Conc. of sample 200 μg/mL of DMSO at 27◦C, incubation period 7 days.
Sulfonamides, especially sulfamethoxazole-trimethoprim, are antimi-
crobial agents frequently employed in AIDS patients to prevent bac-
terial and fungal infections.28 Therefore, 16 selected representatives
of newly synthesized sulfonamides and 1,3,4-oxadiazoles 5b, 5c, 5e–
f, 5g, 5k–l, 8a, 8c, 8e, 10a–b, 10e, 11a–b, and 11e were screened
in vitro for their antifungal activity against six species using the
agar plate technique.29 Linear growth of the fungus was obtained
by measuring the diameter of the fungal colony after 7 days. The
amount of growth inhibition in each case was calculated as per-
centage inhibition. The screening results are given in Tables II and
III. It is worthwhile to note that compounds 5b, 8e, and 10e ex-
hibited significant antifungal activities, which might be attributed
to the presence of a free SH at position 5 of the oxadiazole ring,
as well as the NO2 and Cl substituents of the 1,3,4-oxadiazole
ring.
TABLE III Antifungal Activity of Some Synthesized Compounds and
Inhibition Zones (%)
Compound No.
Standard
Name of Fungi
8c
8e 10a 10b 10e 11a 11b 11e
Drug
Trichphyton longifusus 35
0
60
100
90
0
50
0
0
0
0
0
50
0
60
40
0
90
60
50
40
0
0
0
0
0
50
0
0
40
0
0
0
0
0
0
Miconazole
Miconazole
Amphotericin
Miconazole
Candida albicans
Aspergillus flavus
Microsporum canis
Fusarium solani
Candida glabrata
0
0
40
40
0
40 Miconazole
Miconazole
0
0
0
0
0
Conc. of sample 200 μg/mL of DMSO at 27◦C, incubation period 7 days.

288
M. Zareef et al.
EXPERIMENTAL
General Procedure
Melting points were determined on a Gallenkamp melting-point appa-
ratus and were uncorrected. Optical rotation data were recorded on a
Perkin-Elmer 241 polarimeter. IR spectra were recorded in KBr disc
on an FTIR model FTS 3000 MX spectrometer. Elemental analysis was
performed on a Carlo Erba 1106 elemental analyzer. 1H NMR (400 and
500 MHz) spectra were recorded on a Bruker NMR spectrophotometer,
using tetramethylsilane (TMS) as internal standard with δ values and
coupling constants in Hz. Mass spectra were recorded on a MAT 312
and MAT 311A mass spectrometer. TLC was performed on precoated
silica gel 60 F254 aluminum sheets (Merck, Darmstadt, Germany).
Preparation of the Sulfonamides 2a–l and the Corresponding
Esters 3a–l
Compounds 2a–l were prepared from the corresponding amino acids
1a–d using 3 different sulfonyl chlorides, whereas the corresponding
esters 3a–l were prepared following the established procedure men-
tioned in the literature.19a,b Compound 2c [m.p. 149◦C (72%), lit.19c
149◦C]. Compounds 2–8 were recrystallized from aq. Ethanol; mean-
while, compounds 10a–j and 11a–j were purified by TLC using ethyl
acetate/pet. ether.
General Procedure for Preparation of Compounds 4a–l
A mixture of 3a (10 mmol) and hydrazine monohydrate (80%) in ab-
solute EtOH (50 mL) was heated under reflux for 9 h. The solution
was concentrated, and the precipitate was filtered, washed with water,
and recrystallized from 60% aqueous ethanol. Hydrazides 4b–l were
prepared in a similar fashion.
4a. Yield: 76%, m.p. 92–94◦C. νmax (cm−1) 3316, 3286 (NH), 1651
1
(C O), 1365 (SO2), 1147 (SO2). H NMR (acetone-d6) δ 1.65–1.72 (m,
2H, CH2), 2.5 (t, 2H, J= 7.4 Hz, CH2), 2.7 (t, 2H, J= 6.6 Hz, CH2), 2.4
(s, 3H, CH3), 7.35 (d, 2H, J= 8.0 Hz, ArH), 7.7 (d, 2H, J= 8.0 Hz, ArH),
9.3 (br s., 2H, NH2), 10.5 (br s., 1H, NH). EI-MS: m/z 271 (M+).
4b. Yield: 75%, m.p. 91–93◦C. νmax (cm−1) 3377, 3285 (NH), 1671
(C O), 1376, 1155 (SO2). 1H NMR (acetone-d6) δ 1.66–1.75 (m, 2H, CH2),
2.55 (t, 2H, J= 7.4 Hz, CH2), 7.45 (d, 2H, J= 8.0 Hz, ArH), 7.89 (d, 2H,
J= 8.0 Hz, ArH), 9.61 (br s., 2H, NH), 11.29 (br s., 1H, NH). EI-MS: m/z
291 (M+).

New Benzensulfonamides
289
4c. Yield: 62%, m.p. 110–112◦C. νmax (cm−1) 3332, 3260 (NH), 1656
(C O), 1372, 1161 (SO2). 1H NMR (acetone-d6) δ 1.69–1.78 (m, 2H, CH2),
2.84 (t, 2H, J= 7.8 Hz, CH2), 2.78 (t, 2H, J= 6.9 Hz, CH2), 7.25 (d, 2H,
J= 8.1 Hz, ArH), 7.59 (d, 2H, J= 8.2 Hz, ArH), 9.57 (br s., 2H, NH2),
10.75 (br s., 1H, NH). EI-MS: m/z 287 (M+).
4d. Yield: 83%, m.p. 156–158◦C. νmax (cm−1) 3342, 3285 (NH), 1653
1
(C O), 1365 (SO2), 1149 (SO2). H NMR (acetone-d6) δ 0.93 (dd, 3H,
J= 7.4 Hz, J= 7.4 Hz, CH3), 1.83–1.89 (m, 2H, CH2), 2.38 (s, 3H, CH3),
4.40 (dd, 1H, J= 7.5 Hz, J= 7.6 Hz, CH), 7.32 (d, 2H, J= 8.1 Hz, ArH),
7.76 (d, 2H, J= 8.0 Hz, ArH), 9.50, 10.70 (2xbr s., 2H, 2xNH). EI-MS:
m/z 271 (M+).
4e. Yield: 85%, m.p. 161–163◦C. νmax (cm−1) 3319, 3292 (NH), 1653
1
(C O), 1365, 1149 (SO2). H NMR (acetone-d6) δ 0.98 (dd, 3H, J= 7.2
Hz, CH3), 1.82–1.92 (m, 2H, CH2), 4.38 (t, 1H, J= 7.5 Hz, CH), 7.65
(d, 2H, J= 8.0 Hz, ArH), 8.01 (d, 2H, J= 8.0 Hz, ArH), 9.72 (br s., 2H,
NH2), 11.25 (br s., 1H, NH). EI-MS m/z: 291 (M+).
4f. Yield: 65%, m.p. 165–167◦C. νmax (cm−1) 3297, 3242 (NH), 1671
(C O), 1375, 1166 (SO2). 1H NMR (acetone-d6) δ 0.89 (t, 3H, J= 7.4 Hz,
CH3), 1.84–1.89 (m, 2H, CH2), 3.91 (s, 3H, OCH3), 4.37 (t, 3H, J= 7.4
Hz, CH3), 7.12 (d, 2H, J= 8.2 Hz, ArH), 7.72 (d, 2H, J= 8.2 Hz, ArH),
9.75 (br s., 2H, NH2), 10.75 (br s., 1H, NH). EI-MS: m/z 287 (M+).
4g. Yield: 61%, m.p. 114–116◦C. νmax (cm−1) 3365, 3282 (NH), 1675
(C O), 1367, 1155 (SO2).1H NMR (acetone-d6) δ 2.03(s, 3H, CH3S), 2.12–
2.24 (m, 2H, CH2), 2.52–2.59 (m, 2H, CH2), 2.38 (s, 3H, CH3), 4.68 (dd,
1H, J= 8.0 Hz, J= 8.0 Hz, CH), 7.35 (d, 2H, J= 8.0 Hz, ArH), 7.68 (d,
2H, J= 8.0 Hz, ArH), 9.30 (br s., 2H, NH2), 10.51 (br s., 1H, NH). EI-MS:
m/z 317 (M+).
4h. Yield: 55%, m.p. 121–123◦C. νmax (cm−1) 3342, 3271 (NH), 1672
1
(C O), 1375, 1167 (SO2). H NMR (acetone-d6) δ 2.11 (s, 3H, CH3S),
2.15–2.27 (m, 2H, CH2), 2.56–2.63 (m, 2H, CH2), 4.65 (dd, 1H, J= 8.2
Hz, J= 8.2 Hz, CH), 7.57 (d, 2H, J= 8.2 Hz, ArH), 7.91 (d, 2H, J= 8.2
Hz, ArH), 9.57(br s., 2H, NH2), 11.27 (br s., 1H, NH). EI-MS: m/z 337
(M+).
4j. Yield: 81%, m.p. 151–153◦C. νmax (cm−1) 3366, 3251 (NH), 1675
(C O), 1378, 1165 (SO2). EI-MS: m/z 257 (M+).
4k. Yield: 89%, m.p. 155–157◦C. νmax (cm−1) 3375, 3281 (NH), 1671
1
(C O), 1369, 1165 (SO2). H NMR (acetone-d6) δ 1.25 (d, 3H, J =7.0
∗
Hz, CH3), 4.73–4.81 (m, 1H, CH), 7.55 (d, 2H, J= 8.0 Hz, ArH), 7.80
(d, 2H, J= 8.0 Hz, ArH), 9.12 (br s., 2H, NH2), 9.47, 10.38 (2xbr s., 2H,
2xNH). EI-MS: m/z 277 (M+).
4l. Yield: 64%, m.p. 160–162◦C. νmax (cm−1) 3388, 3282 (NH), 1672
(C O), 1375, 1166 (SO2). 1H NMR (acetone-d6) δ 1.35 (d, 3H, J= 7.4 Hz,
CH3), 3.91 (s, 3H, OCH3), 4.55–4.63 (m, 1H, CH), 7.12 (d, 2H, J= 8.0 Hz,

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ArH), 7.66 (d, 2H, J= 8.0 Hz, ArH), 9.45 (br s., 2H, NH2), 10.92 (br s.,
1H, NH). EI-MS: m/z 273 (M+).
General Procedure for Preparation of Compounds 5a–l
To a solution of 4a (5.5 mmol) in absolute EtOH (80 mL) was added
CS2 (6.6 mmol), followed by an addition of aq. solution of KOH (10 mL,
5.5 mmol). The reaction mixture was stirred for 15 min and then re-
fluxed for 17 h. The solution was concentrated, diluted with water, and
acidified with 4N HCl to pH 2–3. The solid obtained was filtered, washed
with water, and recrystallized from 60% aqueous EtOH. Compounds
5b–l were synthesized in a similar manner.
5a. Yield: 85%, m.p. 145–147◦C. νmax (cm−1) 3206 (NH), 2564 (SH),
1589 (C N), 1379 (SO2 asym), 1179 (SO2 sym). 1H NMR (acetone-d6) δ
1.89–1.96 (m, 2H, CH2), 2.4 (s, 3H, CH3), 2.8 (t, 2H, J= 7.4 Hz, CH2),
3.04 (t, 2H, J= 6.6 Hz, CH2), 7.38 (d, 2H, J= 8.10 Hz, ArH), 7.72 (d,
2H, J= 8.2 Hz, ArH), 12.8 (bs, 1H, NH). Anal. calcd. for C12H15O3N3S2
(313.39): C, 45.99; H, 4.82; N, 13.41. Found: C, 45.71; H, 4.49; N, 13.22.
EI-MS: m/z 313(M+).
5b. Yield: 85%, m.p. 171–172◦C. νmax (cm−1) 3287 (NH), 2545 (C N),
1375, 1165 (SO2). 1H NMR (acetone-d6) δ 1.92–1.98 (m, 2H, CH2), 2.80
(t, 2H, J= 7.5 Hz, CH2), 3.09 (t, 2H, J= 6.7 Hz, CH2), 7.63 (d, 2H,
J= 8.1 Hz, ArH), 7.87 (d, 2H, J= 8.2 Hz, ArH), 12.80 (br s.,1H, NH).
Anal. calcd. for C11H12O3N3S2Cl (333.79): C, 39.58; H, 3.62; N, 12.59.
Found: C, 39.68; H, 3.74; N, 12.77. EI-MS: m/z 335 (M+).
5c. Yield: 87%, m.p. 159–161◦C. νmax (cm−1) 3216 (NH), 2548 (SH),
1
1589 (C N), 1369, 1179 (SO2). H NMR (acetone-d6) δ 1.89–1.96 (m,
2H, CH2), 2.79 (t, 2H, J= 6.5 Hz, CH2), 3.00 (q, 2H, J= 6.7 Hz, CH2),
3.88 (s, 3H, OCH3), 7.07 (d, 2H, J= 8.1 Hz, ArH), 7.76 (d, 2H, J= 8.2
Hz, ArH) 12.92(br s., 1H, NH). Anal. calcd. for C12H15O4N3S2 (329.39):
C, 43.76; H, 4.60; N, 12.76. Found: C, 43.44; H, 4.56; N, 12.87. EI-MS:
m/z 330 (M+).
5d. Yield: 87%, m.p. 205–205◦C, [α]D = +44◦ (c = 1.05, acetone). νmax
(cm−1) 3266 (NH), 2565 (SH), 1582 (C N), 1356, 1145 (SO2). 1H NMR
(acetone-d6) δ 0.92 (t, 3H, J= 7.4 Hz, CH3), 1.82–1.90 (m, 2H, CH2),
2.38 (s, 3H, CH3), 4.38 (dd, 1H, J= 7.5 Hz, J= 7.6 Hz, CH), 7.32 (d, 2H,
J= 8.1 Hz, ArH), 7.66 (d, 2H, J= 8.2 Hz, ArH,), 12.7 (br s., 1H, NH).
Anal. calcd. for C12H15O3N3O3S2 (313.39): C, 45.99; H, 4.82; N, 13.41.
Found: C, 45.81; H, 4.56; N, 13.26. EI-MS: m/z 313 (M+).
5e. Yield: 81%, m.p. 191–192◦C, [α]D = +24◦ (c = 0.60, acetone). νmax
(cm−1) 3233 (NH), 2545 (SH), 1589 (C N), 1365, 1149 (SO2). 1H NMR
(acetone-d6) δ 0.94 (t, 3H, J= 7.4 Hz, CH3), 1.84–1.90 (m, 2H, CH2), 4.39
(dd, 1H, J= 7.8 Hz, J= 7.5 Hz, CH), 7.61 (d, 2H, J= 8.0 Hz, ArH), 7.85

New Benzensulfonamides
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(d, 2H, J= 8.0 Hz, ArH) 12.89 (br s., 1H, NH). Anal. calcd. for C11H12O3
ClN3S2 (333.79): C, 39.58; H, 3.62; N, 12.59. Found: C, 39.59; H, 3.65;
N, 12.20. EI-MS: m/z 332/334 (M+).
5f. Yield: 91%, m.p. 211–213◦C, [α]D = +43◦ (c = 1.04, acetone). νmax
(cm−1) 3266 (NH), 2565 (SH), 1582 (C N), 1356, 1145(-SO2). 1H NMR
(acetone-d6) δ 0.92 (t, 3H, J= 7.5 Hz, CH3), 1.82–1.89 (m, 2H, CH2),
3.86 (s, 3H, OCH3), 4.36 (dd, 1H, J= 7.6 Hz, J= 7.7 Hz, CH), 7.01 (d,
2H, J= 8.0 Hz, ArH), 7.71 (d, 2H, J= 8.2 Hz, ArH). Anal. calcd. for
C12H15O4N3S2 (329.39): C, 43.76; H, 4.60; N, 12.76; Found: C, 43.56; H,
4.37; N, 12.78. EI-MS: m/z 330 (M+).
5g. Yield: 61%, m.p. 163–165◦C, [α]D = +42◦ (c = 1.02, acetone). νmax
(cm−1) 3275 (NH), 2550 (SH), 1589 (C N), 1351, 1161 (SO2). 1H NMR
(acetone-d6) δ 2.01 (s, 3H, CH3S), 2.08–2.15 (m, 2H, CH2), 2.39 (s, 3H,
CH3-Ar), 2.50–2.59 (m, 2H, CH2), 4.69 (dd, 1H, J= 8.1 Hz, J= 8.0 Hz,
CH), 7.35 (d, 2H, J= 8.0 Hz, ArH), 7.67 (d, 2H, J= 8.1 Hz, ArH), 12.88
(br s., 1H, NH). Anal. calcd. for C13H17O3N3S3 (359.35): C, 43.42; H,
4.77; N, 11.69. Found: C, 43.16; H, 4.85; N, 11.53. EI-MS: m/z 359 (M+).
5h. Yield: 67%, m.p. 171–172◦C, [α]D = +45◦ (c = 1.07, acetone). νmax
(cm−1) 3235 (NH), 1586 (C N), 2553 (SH), 1379, 1167 (SO2). 1H NMR
(acetone-d6) δ 2.01 (s, 3H, CH3S), 2.09–2.15 (m, 2H, CH2), 2.48–2.57 (m,
2H, CH2), 4.73 (dd, 1H, J= 8.0 Hz, J= 8.0 Hz, CH), 7.57 (d, 2H, J= 8.1
Hz. ArH), 7.83 (d, 2H, J= 8.1 Hz, ArH), 12.86 (br s., 1H, NH). Anal.
calcd. for C12H14O3Cl N3S3 (379.89): C, 37.94; H, 3.72; N, 11.06. Found:
C, 37.65; H, 3.72; N, 11.14. EI-MS: m/z 378/380 (M+).
5i. Yield: 65%, m.p. 158–160◦C, [α]D = +29◦ (c = 0.65, acetone). νmax
1
(cm−1) 3271 (NH), 1585 (C N), 1357, 1166 (SO2). H NMR (acetone-
d6) δ 2.02 (s, 3H, CH3S), 2.07–2.14 (m, 2H, CH2), 2.50–2.58 (m, 2H,
CH2), 3.88 (s, 3H, OCH3), 4.37 (dd, 1H, J= 8.0 Hz, J= 8.0 Hz, CH),
7.01 (d, 2H, J= 8.1 Hz, ArH), 7.69 (d, 2H, J= 8.2 Hz, ArH), 12.89 (br
s., 1H, NH). Anal. calcd. for C13H17O4N3S3 (375.34): C, 41.57; H, 4.57;
N, 11.21. Found: C, 41.75; H, 4.66; N, 11.36. EI-MS: m/z 375 (M+).
5j. Yield: 83%, m.p. 205–207◦C, [α]D = +23◦ (c = 0.55, acetone). νmax
(cm−1) 3282 (NH), 2551 (SH), 1589 (C N), 1375, 1126 (SO2). 1H NMR
(acetone-d6) δ 1.46 (d, 3H, CH3), 2.40 (s, 3H, CH3), 4.57–4.65 (m, 1H,
CH), 7.34 (d, 2H, J= 8.2 Hz, ArH), 7.68 (d, 2H, J= 8.2 Hz, ArH),
12.85 (br s., 1H, NH). Anal. calcd. for C11H13O3N3S2(299.36): C, 44.13;
H, 4.38; N, 14.04; Found: C, 44.07; H, 4.43; N, 14.31. EI-MS: m/z
299 (M+).
5k. Yield: 90%, m.p. 172–174◦C, [α]D = +42◦ (c = 1.0, acetone). νmax
(cm−1) 3285 (NH), 2550 (SH), 1611 (C N), 1356 (SO2 asym), 1149 (SO2
1
sym). H NMR (acetone-d6) δ 1.51 (d, 3H, J= 7.0 Hz, CH3), 4.73–4.65
(m, 1H, CH), 7.58 (d, 2H, J= 8.0 Hz, CH2), ArH, 7.83 (d, 2H, J= 8 Hz,
ArH), 12.86 (br s., 1H, NH). Anal. calcd. for C10H10O3ClN3S2 (319.78):

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C, 37.56; H, 3.15; N, 13.14. Found: C, 37.74; H, 2.88; N, 13.10. EI-MS:
m/z 318/320 (M+).
5l. Yield 79%, m.p. 177–179◦C, [α]D = +44◦ (c = 1.0, acetone). νmax
(cm−1) 3266 (NH), 2550 (SH), 1586 (C N), 1371, 1162 (SO2). 1H NMR
(acetone-d6) δ 1.53 (d, 3H, J= 7.2 Hz, CH3), 3.89 (s, 3H, OCH3), 4.74–
4.65 (m, 1H, CH), 7.52(d, 2H, J= 8.1 Hz, ArH), 7.76 (d, 2H, J= 8.1 Hz,
ArH), 12.85(br s., 1H, NH). Anal. calcd. for C11H13O4N3S2 (315.36): C,
41.90; H, 4.21; N, 13.32. Found: C, 42.13; H, 4.20; N, 13.22. EI-MS: m/z
315 (M+).
General Procedure for Preparation of N,Nꢀ-Diacylhydrazines
7a–e
To a suspension of 6a–e (5.0 mmol) in dry acetonitrile (50 mL) was
added, in portion, 4-nitrobenzoyl chloride (5.1 mmol), and the reac-
tion mixture was stirred for 5–7 h at 23◦C. The solution was concen-
trated, and the solid product was filtered and recrystallized from aque-
ous EtOH to afford 7a–e. Compound 7a (83%) had m.p. 241–243◦C (lit.2
273–275◦C, 67%).
7b. Yield: 91%, m.p. 231–233◦C. νmax (cm−1) 3181 (NH), 3011 (ArH),
1655 (C O).
7c. Yield: 82%, m.p. 180–182◦C. νmax (cm−1) 3217 (NH), 3037 (ArH),
1649 (C O).
7d. Yield: 79%, m.p. 216–218◦C. νmax (cm−1) 3207 (NH), 3017 (ArH),
1647 (C O).
7e. Yield: 90%, m.p. 277–279◦C. νmax (cm−1) 3241 (NH), 3017 (ArH),
1643 (C O).
General Procedure for Preparation of 2,5-Disubstituted
1,3,4-Oxadiazoles (8a–e)
A mixture of N,Nꢀ-diacylhydrazines 7a–e (2.0 mmol) and thionyl chlo-
ride (10 mL) was heated under reflux for 2 h. After cooling, the resulting
mixture was poured onto crushed ice and stirred vigorously. The solid
product thus obtained was filtered off, washed with water, and recrys-
tallized from aqueous ethanol to afford 8a–e.
8a. Yield: 71%, m.p. 183–185◦C. νmax (cm−1) 1601 (C N), 1275 (Ar-
1
NO2). H NMR (DMSO-d6) δ 2.44 (s, 3H, CH3-Ar), 7.27 (d, 2H, J= 8.0
Hz, ArH), 7.44 (d, 2H, J= 8.0 Hz, ArH), 8.32 (d, 2H, J= 8.2 Hz, ArH),
8.42 (d, 2H, J= 8.2 Hz, ArH). EI-MS: m/z 281 (M+).
8b. Yield: 91%, m.p. 193–195◦C. νmax (cm−1) 1603 (C N), 1271 (Ar-
NO2). 1H NMR (DMSO-d6) δ 3.81 (s, 3H, OCH3), 7.29–7.89 (m, 6H, ArH),
8.21 (d, 2H, J= 7.2 Hz, ArH). EI-MS: m/z 297 (M+).

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8c. Yield: 91%, m.p. 189–191◦C. νmax (cm−1) 1621 (C N), 1277(Ar-
NO2). 1H NMR (DMSO-d6) δ 3.79 (s, 9H, OCH3), 6.95 (s, 2H, ArH), 7.96
(d, 2H, J= 8.0 Hz, ArH), 8.34 (d, 2H, J= 8.0, ArH). EI-MS: m/z 357
(M+).
8d. Yield: 91%, m.p. 176–177◦C. νmax (cm−1) 1621, (C N), 1271 (Ar-
NO2). 1H NMR (DMSO-d6) δ 7.65–7.91 (m, 6H, ArH), 8.32 (d, 2H, J= 8.0
Hz, ArH). EI-MS: m/z 301 (M+).
8e. Yield, 83%, m.p. 210–212◦C. IR (ν, cm−1): 1621 (C N), 1271 (Ar-
1
NO2). H NMR (DMSO-d6) δ 7.66 (d, 2H, J= 7.1 Hz, ArH), 8.13–8.25
(m, 6H, ArH). EI-MS: m/z 301 (M+).
General Procedure for Preparation of Compounds (9a–e)
To a suspension of 8a–e (1.63 mmol) in EtOH (80 mL) containing 10%
Pd/C (0.03 g) was added 10 mL of 80% hydrazine monohydrate dropwise
at 85◦C, followed by heating under reflux for 25 h. After cooling, the
mixture was filtered, and the filtrate was evaporated to dryness. The
crude product was recrystallized from EtOH to give 9a–e.
9a. Yield: 81%, m.p. 191–193◦C, νmax (cm−1) 3454, 3348 (NH), 1606,
1
1581 (C N). H NMR (DMSO-d6) δ 2.38 (s, 3H, CH3-Ar), 6.75 (d, 2H,
J= 8.1 Hz, ArH), 7.26 (d, 2H, J= 8.1 Hz, ArH), 7.8 (d, 2H, J= 8.1 Hz,
ArH), 7.96 (d, 2H, J= 8.2 Hz, ArH). EI-MS: m/z 251 (M+).
9b. Yield: 89%, m.p. 205–207◦C, νmax (cm−1) 3452, 3338 (NH), 1602,
1
1582 (C N). H NMR (DMSO-d6) δ 3.89 (s, 3H, OCH3), 6.72 (d, 2H,
J= 8.0 Hz, ArH), 7.30 (d, 2H, J= 8.0 Hz, ArH), 7.73 (d, 2H, J= 7.7 Hz,
ArH), 7.92 (d, 2H, J= 7.8 Hz, ArH). EI-MS: m/z 267 (M+).
9c. Yield: 93%, m.p. 197–199◦C. νmax (cm−1) 3399, 3348 (NH), 1586,
1
1561 (C N). H NMR (DMSO-d6) δ 3.88 (s, 9H, OCH3), 6.71 (d, 2H,
J= 8.5 Hz, ArH), 7.25 (s, 2H, ArH), 7.86 (d, 2H, J= 8.5 Hz, ArH). EI-
MS: m/z 327 (M+).
9d. Yield: 73%, m.p. 181–183◦C. νmax (cm−1) 3394, 3318 (NH), 1596,
1561 (C N). 1H NMR (DMSO-d6) δ 6.80 (d, 2H, J= 7.4 Hz, ArH), 7.91–
8.14 (m, 6H, ArH). EI-MS: m/z 271(M+).
9e. Yield: 79%, m.p. 210–212◦C. νmax (cm−1) 3424, 3338 (NH), 1606,
1582 (C N). 1H NMR (DMSO-d6) δ 7.20 (d, 2H, J= 8.0 Hz, ArH), 7.76
(d, 2H, J= 8.0 Hz, ArH), 7.85 (d, 2H, J= 8.1 Hz, ArH). EI-MS: m/z 271
(M+).
General Procedure for Preparation of Benzenesulfonamides
Bearing 2,5-Disubstituted 1,3,4-Oxadiazoles (10a–j and 11a–j)
A mixture of 9a–e (0.75 mmol), Et3N (0.22 mmol), and a catalytic
amount of DMAP (25 mg) was stirred in dry CH3Cl (50 mL) for 15 min.

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Sulfonyl chloride (1.5 mmol) was then added to the previously men-
tioned solution, and the mixture was refluxed for 5–9 h. The reaction
mixture was washed with dilute HCl, brine solution, and water, and the
organic layer was dried (Na2SO4), filtered, and evaporated to dryness.
The residue was recrystallized from aq. EtOH. The sulfonamides 10a–j
and 11a–j were separated by preparative TLC, using ethyl acetate/pet.
ether as an eluent.
10a. Yield, 61%, m.p. 193–195◦C. νmax (cm−1) 3266 (NH), 1589 (C N),
1379, 1149 (SO2). 1H NMR (acetone-d6) δ 2.44 (s, 3H, CH3-Ar), 2.84 (s,
3H, CH3-Ar), 7.26 (d, 2H, J= 8.1 Hz, ArH), 7.43 (d, 2H, J= 8.1 Hz,
ArH), 7.49 (d, 2H, J= 8.1 Hz, ArH), 7.81 (d, 2H, J= 8.1, Hz, ArH), 8.06
(d, 2H, J= 7.9 Hz, ArH), 8.20 (d, 2H, J= 7.9 Hz, ArH), 10.54 (br s., 1H,
NH). Anal. calcd. for C22H19O3N3S (405.47): C, 65.17; H, 4.72; N, 10.36.
Found: C, 65.24; H, 4.71; N, 10.55. EI-MS: m/z 405 (M+).
10b. Yield: 51%, m.p. 190–191◦C. νmax (cm−1) 3281 (NH), 1595 (C N),
1
1365, 1149 (SO2). 1089 (br s, NH). H NMR (acetone-d6) δ 2.49 (s, 3H,
CH3-Ar), 3.89 (s, 3H, OCH3), 7.1 (d, 2H, J= 7.8 Hz, ArH), 7.45 (d, 2H,
J= 7.9 Hz, ArH), 7.49 (d, 2H, J= 8.0 Hz, ArH), 7.98 (d, 2H, J= 8.1 Hz,
ArH), 8.06 (d, 2H, J= 8.0 Hz, ArH), 8.12 (d, 2H, J= 8.1 Hz, ArH). Anal.
calcd. for C22H19O4N3S (421.47): C, 62.71; H, 4.54; N, 9.97. Found: C,
62.85; H, 4.41; N, 9.66. EI-MS: m/z 421 (M+).
10c. Yield: 54%, m.p. 197–199◦C. νmax (cm−1) 3298 (NH), 1598 (C N),
1
1377, 1164 (SO2). H NMR (acetone-d6) δ 2.45(s, 3H, CH3-Ar), 3.91 (s,
9H, OCH3), 5.74(s, 1H, NH), 7.25 (d, 2H, J= 8.0 Hz, ArH), 7.41 (s,
2H, ArH), 7.50 (d, 2H,J= 8.0 Hz, ArH), 8.16 (d, 2H, J= 8.1 Hz, ArH),
8.22 (d, 2H, J= 8.1 Hz, ArH). 10.84 (br s., 1H, NH). Anal. calcd. for
C24H23O6N3S (481.28): C, 59.85; H, 4.82; N, 8.73. Found: C, 60.13; H,
4.62; N, 8.69. EI-MS: m/z 481 (M+).
10d. Yield: 63%, m.p. 187–188◦C. νmax (cm−1) 3258 (NH), 1581 (C N),
1357, 1149 (SO2). 1H NMR (acetone-d6) δ 2.45 (s, 3H, CH3), 7.48 (d, 2H,
J= 8.1 Hz, ArH), 7.59–8.08 (m, 9H, ArH) 8.14 (s, 1H, ArH). 10.88 (br
s., 1H, NH). Anal. calcd. for C21H16O3ClN3S (425.89): C, 59.22; H, 3.81;
N, 9.87. Found: C, 59.39; H, 3.75; N, 9.66. EI-MS: m/z 424/426 (M+).
10e. Yield: 53%, m.p. 183–185◦C. νmax (cm−1) 3266 (NH), 1587 (C N),
1
1351, 1161 (SO2). H NMR (acetone-d6) δ 2.49 (s, 3H, CH3-Ar), 7.17
(d, 2H, J= 8.1 Hz, ArH), 7.31 (d, 2H, J= 8.1 Hz, ArH), 7.51 (m, 4H,
ArH), 7.78 (d, 2H, J= 8.0 Hz, ArH), 8.10 (d, 2H, J= 8.0 Hz, ArH). 10.91
(br s., 1H, NH). Anal. calcd. for C21H16O3ClN3S (425.89): C, 59.22; H,
3.81; N, 9.91. Found: C, 59.25; H, 3.90; N, 10.11. EI-MS: m/z 424/426
(M+).
10f. Yield: 61%, m.p. 194–195◦C. νmax (cm−1) 3291 (NH), 1582 (C N),
1372, 1166 (SO2). 1H NMR (acetone-d6) δ 2.84 (s, 3H, CH3-Ar), 3.88 (s,
3H, OCH3), 6.92 (d, 2H, J= 7.5 Hz, ArH), 7.41 (d, 2H, J= 8.0 Hz, ArH),

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7.49 (d, 2H, J= 8.0 Hz, ArH), 7.78 (d, 2H, J= 8.1 Hz, ArH), 7.97 (d,
2H, J= 8.1 Hz, ArH), 8.06 (d, 2H, J= 8.0 Hz, ArH). 10.74 (br s., 1H,
NH). Anal. calcd. for C22H19O4N3S (421.47): C, 62.71; H, 4.54; N, 9.97.
Found: C, 62.33; H, 4.71; N, 10.33. EI-MS: m/z 421 (M+).
10g. Yield: 57%, m.p. 177–179◦C. νmax (cm−1) 3289 (NH), 1592 (C N),
1
1379, 1159 (SO2). H NMR (acetone-d6) δ 3.88 (s, 6H, OCH3), 6.91 (d,
4H, J= 7.5 Hz, ArH), 7.49 (d, 2H, J= 7.9 Hz, ArH), 7.91–8.05 (m, 6H,
ArH), 10.89 (br s.,1H, NH). Anal. calcd. for C22H19O5N3S (435.47): C,
60.68; H, 4.41; N, 9.65. Found: C, 60.41; H, 4.63; N, 9.68. EI-MS. m/z
435 (M+).
10h. Yield: 41%, m.p. 187–189◦C. νmax (cm−1) 3295 (NH), 1581 (C N),
1378, 1167 (SO2). 1H NMR (acetone-d6) δ 3.89 (s, 12H, OCH3), 6.91 (d,
2H, J= 7.6 Hz, ArH), 7.12 (d, 2H, J= 7.6 Hz, ArH), 7.26 (s, 1H, ArH),
7.91 (d, 2H, J= 8.1 Hz, ArH), 7.98 (d, 2H, J= 8.1 Hz, ArH). 11.54 (br s.
1H, NH). Anal. calcd. for C24H23O7N3S2(497.52): C, 57.94; H, 4.66; N,
8.45. Found: C, 57.70; H, 4.65; N, 8.18. EI-MS: m/z 497 (M+).
10i. Yield: 45%, m.p. 175–177◦C. νmax (cm−1) 3266 (NH), 1592 (C N),
1
1375, 1166 (SO2). H NMR (acetone-d6) δ 3.86 (s, 3H, OCH3), 7.02 (d,
2H, J= 8.1 Hz, ArH), 7.48 (d, 2H, J= 8.0 Hz, ArH), 7.76 (d, 2H, J= 8.1
Hz, ArH), 7.61–7.90 (m, 5H, ArH), 8.13 (s, 1H, ArH). 11.14 (br s.,1H,
NH). Anal. calcd. for C21H16O4ClN3S (441.89): C, 57.10; H, 3.65; N, 9.51.
Found: C, 57.19; H, 3.68; N, 9.51. EI-MS: m/z 440/442 (M+).
10j. Yield: 48%, m.p. 195–196◦C. νmax (cm−1) 3266 (NH), 1587 ( C N),
1
1351, 1161 (SO2). H NMR (acetone-d6) δ 3.88 (s, 3H, OCH3), 6.92 (d,
2H, J= 7.4 Hz, ArH), 7.15 (d, 2H, J= 7.4 Hz, ArH), 7.49 (d, 2H, J= 8.1
Hz, ArH), 7.76 (d, 2H, J= 8.1 Hz, ArH), 7.84 (d, 2H, J= 7.8 Hz, ArH),
8.14 (d, 2H, J= 7.8 Hz, ArH). 10.67 (br s., 1H, NH). Anal. calcd. for
C31H29O10N3S3 (441.89): C, 57.01; H, 3.65; N, 14.83. Found: C, 57.15;
H, 3.67; N, 14.78. EI-MS: m/z 441 (M+).
11a. Yield: 79%, m.p. 214–216◦C. νmax (cm−1) 1592 (C N), 1369, 1165
1
(SO2). H NMR (acetone-d6) δ 2.49 (s, 6H, CH3-Ar), 2.88 (s, 6H, 2CH3-
Ar-oxa), 7.27 (d, 2H, J= 8.0 Hz, ArH), 7.44 (d, 4H, J= 8.0 Hz, ArH),
7.49 (d, 4H, J= 8.1 Hz, ArH), 7.80 (d, 4H, J= 8.1 Hz, ArH), 8.07 (d,
4H, J= 8.2 Hz, ArH), 8.19 (d, 4H, J= 8.2 Hz, ArH). Anal. calcd. for
C29H25O5N3S2 (559.65). C, 62.24; H, 4.50; N, 7.51. Found: C, 62.20; H,
4.23; N, 7.31. EI-MS: m/z 559 (M+).
11b. Yield: 71%, m.p. 210–212◦C. νmax (cm−1) 1586 (C N), 1378, 1147
1
(SO2). H NMR (acetone-d6) δ 2.48 (s, 6H, 2CH3), 3.88 (s, 3H, OCH3),
6.98 (d, 2H, J= 7.9 Hz, ArH), 7.35 (d, 2H, J= 7.9 Hz, ArH), 7.48 (d,
2H, J= 8.0 Hz, ArH), 7.89 (d, 2H, J= 8.1 Hz, ArH), 7.95 (d, 2H, J= 8.1
Hz, ArH), 8.05 (d, 2H, J= 8.0 Hz, ArH). Anal. calcd. for C29H25O6N3S2
(575.65): C, 60.51; H, 4.38; N, 7.30. Found: C, 60.77; H, 4.19; N, 7.39.
EI-MS m/z 575 (M+).

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11c. Yield: 69%, m.p. 217–219◦C. νmax (cm−1) 1595 (C N), 1379, 1165
(SO2).1H NMR (acetone-d6) δ 2.49 (s, 3H, CH3-Ar), 3.90 (s, 9H, OCH3),
7.23 (d, 2H, J= 8.4 Hz, ArH), 7.40 (s, 2H, ArH), 7.49 (d, 2H, J= 8.4 Hz,
ArH), 8.14 (d, 2H, J= 8.2 Hz, ArH), 8.21 (d, 2H, J= 8.2 Hz, ArH). Anal.
calcd. for C31H29O8N3S2 (635.71): C, 58.57; H, 4.61; N, 6.61. Found: C,
58.28; H, 4.51; N, 6.40. EI-MS: m/z 635 (M+).
11d. Yield: 62%, m.p. 221–223◦C. νmax (cm−1) 1589 (C N), 1371, 1166
1
(SO2). H NMR (acetone-d6) δ 2.49 (s, 6H, CH3), 7.51 (d, 4H, J= 8.1
Hz, ArH), 7.60–7.98 (m, 11H, ArH), 8.13 (s, 1H, ArH). Anal. calcd. for
C28H22O5ClN3S2 (579.07): C, 58.08; H, 3.83; N, 7.26. Found: C, 58.34;
H, 3.85; N, 7.50. EI-MS: m/z 578/580 (M+).
11e. Yield: 63%, m.p. 214–215◦C. νmax (cm−1) 1585 (C N), 1353, 1159
(SO2). 1H NMR (acetone-d6) δ 2.42 (s, 6H, CH3-Ar), 7.16 (d, 2H, J= 8.0
Hz, ArH), 7.30 (d, 4H, J= 7.9 Hz, ArH), 7.50 (m, 4H, ArH), 7.77 (d,
2H, J= 7.7 Hz, ArH), 8.08 (d, 2H, J= 7.9 Hz, ArH). Anal. calcd. for
C28H22O5ClN3S2 (579.07): C, 58.77; H, 3.83; N, 7.31. Found: C, 58.56;
H, 3.71; N, 7.29. EI-MS: m/z 578/580 (M+).
11f. Yield: 65%, m.p. 219–222◦C. νmax (cm−1) 1583 (C N), 1377, 1165
(SO2). 1H NMR (acetone-d6) δ 2.85 (s, 3H, CH3-Ar), 3.89 (s, 6H, OCH3),
6.93 (d, 4H, J= 8.0 Hz, ArH), 7.15 (d, 2H, J= 8.1 Hz, ArH), 7.46 (d, 2H,
J= 8.0 Hz, ArH), 7.93–7.98 (m, 8H, ArH). Anal. calcd. for C29H25O7N3S2
(559. 59): C, 62.23; H, 4.50; N, 7.51. Found: C, 62.07; H, 4.51; N, 7.81.
EI-MS: m/z 559 (M+).
11g. Yield: 72%, m.p. 207–209◦C. νmax (cm−1) 1579 (C N), 1355, 1161
1
(SO2). H NMR (acetone-d6) δ 3.89 (s, 6H, OCH3), 6.93 (d, 6H, J= 7.2
Hz, ArH), 7.47 (d, 2H, J= 7.5 Hz, ArH), 7.93–7.98 (m, 8H, ArH). Anal.
calcd. for C29H25O8N3S2 (607.65): C, 57.32; H, 4.15; N, 6.92. Found: C,
57.52; H, 4.18; N, 7.23. EI-MS: m/z 607 (M+).
11h. Yield: 69%, m.p. 219–220◦C. νmax (cm−1) 1585 (C N), 1375,
1
1165 (SO2). H NMR (acetone-d6) δ 3.90(s, 15H, OCH3), 6.93 (d, 4H,
J= 7.8 Hz, ArH), 7.13 (d, 2H J= 7.8 Hz, ArH), 7.26 (s, 1H, ArH), 7.78
(d, 2H, J= 8.0 Hz, ArH), 7.79 (d, 4H, J= 8.0 Hz, ArH). Anal. calcd. for
C31H29O10N3S3 (699.77): C, 53.21; H, 4.21; N, 6.01. Found: C, 53.51; H,
4.29; N, 5.94. EI-MS: m/z 699 (M+).
11i. Yield: 64%, m.p. 195–197◦C. νmax (cm−1) 1582 (C N), 1378, 1165
1
(SO2). H NMR (acetone-d6) δ 3.89 (s, 6H, OCH3), 6.92 (d, 4H, J= 8.0
Hz, ArH), 7.12 (d, 2H, J= 8.0 Hz, ArH), 7.75–7.95 (m, 10H, ArH). Anal.
calcd. for C28H22O7ClN3S2 (611.07): C, 55.04; H, 3.63; N, 6.80; S, 10.53
Found: C, 54.86; H, 3.57; N, 7.03. EI-MS: m/z 610/612 (M+).
11j. Yield: 75%, m.p. 230–232◦C. νmax (cm−1) 1569 (C N), 1365, 1148
1
(SO2). H NMR (acetone-d6) δ 3.89 (s, 6H, OCH3), 6.91 (d, 4H, J= 7.0
Hz, ArH), 7.48 (d, 2H, J= 7.1 Hz, ArH), 7.76–7.89 (m, 8H, ArH), 8.12

New Benzensulfonamides
297
(d, 2H, J= 7.5 Hz, ArH). Anal. calcd. for C28H22O7ClN3S2 (611.07): C,
55.01; H, 3.62; N, 6.88. Found: C, 54.90; H, 3.61; N, 7.15. EI-MS: m/z
610/612 (M+).
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