Amidine Sulfonamides and Benzene Sulfonamides: Synthesis and Their Biological Evaluation

Article abstract of DOI:10.1155/2015/524056

New amidine and benzene sulfonamide derivatives were developed and structures of the new products were confirmed by elemental and spectral analysis (FT-IR, ESI-MS, ¹HNMR, and ¹³CNMR). In vitro, developed compounds were screened for t

Full text of DOI:10.1155/2015/524056

Hindawi Publishing Corporation
Journal of Chemistry
Volume 2015, Article ID 524056, 8 pages
http://dx.doi.org/10.1155/2015/524056
Research Article
Amidine Sulfonamides and Benzene Sulfonamides:
Synthesis and Their Biological Evaluation
Muhammad Abdul Qadir,1 Mahmood Ahmed,1 Hina Aslam,1
Sadia Waseem,1 and Muhammad Imtiaz Shafiq2
1Institute of Chemistry, University of Punjab, Lahore 54590, Pakistan
2Institute of Biochemistry & Biotechnology, University of the Punjab, Lahore 54590, Pakistan
Correspondence should be addressed to Mahmood Ahmed; mahmoodresearchscholar@gmail.com
Received 21 May 2015; Accepted 2 July 2015
Academic Editor: Deniz Ekinci
Copyright © 2015 Muhammad Abdul Qadir et al. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
New amidine and benzene sulfonamide derivatives were developed and structures of the new products were confirmed by elemental
and spectral analysis (FT-IR, ESI-MS, 1HNMR, and 13CNMR). In vitro, developed compounds were screened for their antibacterial
and antifungal activities against medically important bacterial strains, namely, S. aureus, B. subtilis, and E. coli, and fungi, namely,
A. flavus, A. parasiticus, and A. sp. e antibacterial and antifungal activities have been determined by measuring MIC values
(ꢀg/mL) and zone of inhibitions (mm). Among the tested compounds, it was found that compounds 3b, 9a, and 9b have most
potent activity against S. aureus, A. flavus, and A. parasiticus, respectively, and were found to be more active than sulfamethoxazole
and itraconazole with MIC values 40 ꢀg/mL. In contrast, all the compounds were totally inactive against the A. sp. except 10b and
15b to show activity to some extent.
1. Introduction
less soluble in water; therefore, they may readily crystalize in
kidney but with advancement in medical science, and new
Sulfonamides are basis of several drug groups, known as
sulfa drugs. Any compound that has sulfonamide moiety
(SO NH ) in its structure is referred to as sulfonamide. ey
sulfonamides have been synthesized having lower pꢁ value
a
(5-6) to avoid crystallization in kidney [14]. e compounds
having pyridine and amide functional group exhibit various
biological activities like antifungal and antibacterial. So these
biological activities encourage us to synthesize the sulfon-
amides containing such important functional groups [15–18].
e motivation behind this research work was to synthesize
some novel sulfonamides (Schemes 1–4) having antimicrobial
properties. Different amines were chosen and reacted with
sulfonyl chlorides. As a result of substitution, different func-
tional groups were added and resulting compounds exhibited
antibacterial and antifungal activities.
2
2
comprise substantial class of pharmaceutical drugs, contain-
ing various kinds of pharmacological agents having antitu-
mor [1], antibacterial [2], anticarbonic anhydrase [3, 4], diu-
retic [5, 6], hypoglycemic [7], and protease inhibitory activity
[8–10] or antithyroid activity [11] among others. Sulfonamides
are mostly used to treat the bacterial infectious cells because
they do not significantly affect the antigenic properties of the
infective organism or the development of specific antibodies
[12]. Bacteria have liability to acquire resistance against sul-
fonamides by changing their cell wall permeability, enhanc-
ing essential metabolites production, or increasing produc-
tion of enzyme [13]. In this way sulfonamides become inef-
fective to inhibit their production. But their ineffectiveness
in drug therapy can be abstained, due to inductive effect of
SO group. Sulfonamides having first pꢁ value around 10 are
2. Experimental
2.1. Chemistry. Chemicals used in present work were of
analytical grade obtained from E-Merck (Germany), Sigma
Aldrich (USA), and BDH (UK) without further purification
2
a

2
Journal of Chemistry
O
S
R
NH
R
S
R2
Cl
NH
O
O
S
HN
R1
O
5
N
O
S
R2
R1
O
O
O
O
S
O
2
3a, 3b
6a
R
NH
+
Cl
R1
R
NH
NH2
1
O
O
S
N
S
R1
R1
O
O
4a, 4b
Scheme 1: Amidine sulfonamides.
O
S
R2
Cl
R
S
R
O
O
HN
R1
O
11
N
O
S
S
R2
R1
O
O
O
R
O
12a
9a, 9b
+
NH2
R1
Cl
S
7
R
O
8
O
O
N
S
S
R1
R1
O O
10a, 10b
Scheme 2: Benzene sulfonamides (series 1).
R
concentration of all the compounds was 10–20 mg in 0.8–
1.0 mL of solvent. Purification and progress of the synthesized
compounds were confirmed on precoated TLC silica plate
(Merck-Germany).
H3C
H3C
N
O
S
R1
O
O
R
15a
R
+
R1
NH
Cl
S
2.2. Antimicrobial Assay. Escherichia coli ATCC 25922,
Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC
6633, Aspergillus flavus ATCC 9643, Aspergillus parasiticus
ATCC 15517, and Acremonium sp. ATCC 200667 were col-
lected from Mycology Department, University of Punjab,
Lahore, Pakistan, and were maintained in tryptic soy agar
(TSA) and potato dextrose agar (PDA) medium, respectively,
slants at 5∘C until use. A series of four 2-fold dilutions (320,
160, 80, and 40 ꢀg/mL) were made from stock solution of
640 ꢀg/mL in dimethyl sulphoxide (DMSO). All the dilutions
were made sterile in an autoclave at 121∘C for 30 min with
15 psi pressure afer filtration through 0.22 ꢀm membrane
filter. e minimal inhibitory concentration (MIC) was
reported as absence of no observable growth by the lowest
concentration of tested compounds afer twofold serial dilu-
tion. Five individually numbered test tubes with screw caps
were sterilized. Tube 1 was filled with 2 mL of tryptic soy broth
culture media including the stock solution of synthesized
compounds. 1.0 mL of this solution was introduced into 2
tubes and diluted with 1.0 mL culture media and we repeated
the procedure up to tube 5. e tubes were incubated at
25∘C for 72 hrs. Ciprofloxacin and sulfamethoxazole (sulfa
drug) were used as reference (positive control to check
H3C
13
O
14
N
O
S
R1
O
15b
Scheme 3: Benzene sulfonamides (series 2).
to synthesize desired compounds, and high purity water
(0.01 ꢀS/cm) was prepared in our own laboratory using Milli-
Q purification system (USA). Alpha IR spectrometer (FTIR-
ATR) and NMR spectrometer, Bruker, were used to record the
IR and 1HNMR (500 MHz) and 13CNMR (125 MHz) spectra,
respectively. PG-T80+ UV-Vis spectrophotometer (UK) and
Flash HT Plus elemental analyzer (ermo Scientific, UK)
were used for ꢂmax, and concentration of hydrogen (H),
carbon (C), nitrogen (N), and sulfur (S) of synthesized
compounds, respectively, while the melting point was mea-
sured by Gallenkamp apparatus. JMS-HX-110 spectrometer
with electron spray ionization (ESI) interface was used for
mass spectra. e HNMR and 13CNMR spectra of all the
1
synthesized compounds were measured using MeOD and

Journal of Chemistry
3
R
R2
R1
OH
N
3a, 4a
O
CH3
OH
OH
3b, 4b
N
O
O
CH3
H3C
6a
N
CH3
H3C
N
9a, 10a
9b, 10b
N
N
H3C
12a
15a
15b
H3C
O
H3C
OH
O
H3C
H3C
OH
Scheme 4
8
the sensitivity of tested bacterial strains). 1–3 × 10 cfu/mL
of each of Gram negative E. coli and Gram positive S. aureus
and B. subtilis was obtained afer adjusting the optical density
of inoculum at 0.2–0.3 and 0.3–0.4 (620 nm), respectively,
while fungal suspension (A. flavus, A. parasiticus, and A. sp.)
with cell density of 105 cfu/mL was studied in present work
and the itraconazole was used as reference antifungal agent.
All the compounds and reference solutions were applied
(50 ꢀL) onto a 6 mm sterile filter paper disc separately and
the inoculated plates incubated at 37∘C for 24 hrs. e zones
of inhibition (mm) were measured and we evaluated the anti-
bacterial activities.
of reaction was examined by the change in pH value due to
formation of HCl by the consumption of sulphonyl chlorides
during the reaction. On completion of the reaction pH was
adjusted at 2-3 using HCl solution (2 M). e precipitates
formed were filtered through Whatman filter paper number
42, washed several times with distilled water, and recrystal-
lized using methanol and dried using rotary evaporator.
2.4. N-{Imino[(phenylsulfonyl)amino]methyl}-N-methylglycine
(3a, C H N O S). Yield: 397.9 mg (64.7%); m.p.: 172–
10 13
3
4
174∘C; TLC: ꢃꢀ = 0.72 (H O-BuOH-Acetic acid 1 : 4 : 1);
2
IR (FTIR): ꢄ
=
3215 (O-Hcarboxylic, stretching), 3084 (C-
Haromatic, stretching), 1768 (C=Ocarboxylic, stretching), 1707
(C=Nimine, stretching), 1438 (O-Hcarboxylic, bending), 1033
(S=Ostretching), 1165 (-N- S=Ostretching), 1458 (C=C-
Caromatic, stretching), 706 (Ø-Sstretching); UV-Vis (methanol, ꢅ =
2.3. General Procedure for Synthesis of Sulfonamides. A simple
method in aqueous media under dynamic pH control is
adopted for synthesis of sulfonamides. Filtration afer acidi-
fication is involved for isolation of products [19–21]. All the
amines were weighed accurately and dissolved completely
by addition of distilled water by constant stirring using
magnetic stirrer. e pH of the reaction contents was strictly
monitored and maintained at 8–10 at regular intervals during
the experimental reaction using Na CO solution (1 M). en
benzene sulfonyl chloride or p-toluene sulphonyl chloride
was accurately weighed and added carefully into the above
solution. e reaction was carried in round bottom flask
equipped with magnetic stirrer. During stirring sulphonyl
chloride initially floats on the surface and the completion
2
⋅
10−35 mol dm−3):
ꢂ
max(ꢆ)
=
208 (25050) nm
(mol−1 dm cm−1); 1HNMR (500 MHz, MeOD) ꢇ = 9.91 (br,
s, 1H, NH), 7.98 (d, ꢈ = 7.48 Hz, 1H, CH), 7.68 (t, ꢈ = 7.59 Hz,
1H, CH), 7.56 (d, ꢈ = 7.63 Hz, 1H, CH), 4.71 (d, ꢈ = 13.16 Hz,
2H, CH ), 3.15 (s, 3H, CH ); 13CNMR (125 MHz, MeOD)
2
3
ꢇ = 168 (C-16), 155 (C-11), 141 (C-1), 135 (C-4), 129 (C-3),
51 (C-15), 35 (C-14); ESI-MS: m/z = 273.38 [M + 2]+, 271.31
[M]+.
2
3
2.5. N-(Imino{[(4 methylphenyl)sulfonyl]amino}methyl)-N-
methylglycine (3b, C H N O S). Yield: 779.9 mg (82.7%);
11 15
3
4

4
Journal of Chemistry
m.p.: 185–187∘C; TLC: ꢃꢀ = 0.64 (H O-BuOH-Acetic acid
7.91 (s, H, CH), 7.87 (d, ꢈ = 8.11 Hz, 1H, CH), 7.73 (s, H, CH),
2
1 : 4 : 1); IR (FTIR): ꢄ = 3224 (O-Hcarboxylic, stretching), 2992
(C-Haromatic, stretching), 1767 (C=Ocarboxylic, stretching), 1699
(C=Nimine, stretching), 1438 (O-Hcarboxylic, bending), 1028
(S=Ostretching), 1199 (-N- S=Ostretching), 1498 (C=C-
Caromatic, stretching), 701 (Ø-Sstretching); UV-Vis (methanol,
7.73 (d, ꢈ = 8.01 Hz, 1H, CH), 4.73 (s, 2H, CH ), 3.15 (s, 3H,
2
CH ), 2.44 (s, 3H, CH ); (125 MHz, MeOD) ꢇ = 168 (C-26),
3
3
156 (C-14), 143 (C-1), 141 (C-17), 132 (C-20), 131 (C-2), 129
(C-3), 53 (C-25), 39 (C-24), 23 (C-7); ESI-MS: m/z = 427.53
[M + 2]+, 425.48 [M]+.
ꢅ
=
2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 222 (22500) nm
1
(mol−1 dm3 cm−1); HNMR (500 MHz, MeOD) ꢇ = 9.96
(br, s, 1H, NH), 7.71 (s, 1H, CH), 7.38 (d, ꢈ = 8.11 Hz, 1H,
CH), 4.68 (s, 2H, CH ), 3.15 (s, 3H, CH ), 2.26 (s, 3H, CH );
2.9. N-(Pyridin-2-yl)benzene Sulfonamide (9a, C H N O S).
11 10
2
2
Yield: 869.6 mg (83.1%); m.p.: 145–147∘C; TLC: ꢃꢀ = 0.61
(H O-BuOH-Acetic acid 1 : 4 : 1); IR (FTIR): ꢄ = 3367 (N-
2
2
3
3
Hamine, stretching), 1666 (N-Hamine, bending), 1024 (S=Ostretching),
1177 (-N- S=Ostretching), 1445 (C=C-Caromatic, stretching), 687 (Ø-
13CNMR (125 MHz, MeOD) ꢇ = 168 (C-17), 156 (C-12), 143
(C-1), 138 (C-4), 129 (C-2), 52 (C-16), 35 (C-15), 22 (C-7);
ESI-MS: m/z = 287.39 [M + 2]+, 285.34 [M]+.
S
stretching); UV-Vis (methanol, ꢅ = 2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ)
= 230 (43800) nm (mol−1 dm3 cm−1); HNMR (500 MHz,
MeOD) ꢇ = 11.49 (br, s, 1H, NH), 7.91 (d, ꢈ = 5.21 Hz, 1H, CH),
7.81 (d, ꢈ = 7.61 Hz, 1H, CH), 7.65 (t, ꢈ = 8.31 Hz, 1H, CH),
7.61 (t, ꢈ = 7.51 Hz, 1H, CH), 7.55 (t, ꢈ = 7.61 Hz, 1H, CH),
7.25 (t, ꢈ = 7.21 Hz, 1H, CH), 7.15 (d, ꢈ = 8.39 Hz, 1H, CH);
13CNMR (125 MHz, MeOD) ꢇ = 148 (C-2), 145 (C-6), 140 (C-
11), 137 (C-4), 132 (C-14), 129 (C-13), 127 (C-12), 115 (C-5), 112
(C-3); ESI-MS: m/z = 236.31 [M + 2]+, 234.28 [M]+.
1
2.6. N-[[Bis(phenylsulfonyl)amino](imino)methyl]-N-methyl-
glycine (4a, C H N O S ). Yield: 931.8 mg (81.3%); m.p.:
16 17
3
6
2
210–212∘C; TLC: ꢃꢀ
=
0.67 (H O-BuOH-Acetic acid
2
1 : 4 : 1); IR (FTIR): ꢄ = 3062 (O-Hcarboxylic, stretching), 1767
(C=Ocarboxylic, stretching), 1621 (C=Nimine, stretching), 1445 (O-
Hcarboxylic, bending), 1037 (S=Ostretching), 1163 (-N- S=Ostretching),
1445 (C=C-Caromatic, stretching), 689 (Ø-Sstretching); UV-Vis
(methanol, ꢅ =−21 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 210 (17250) nm
(mol−1 dm3 cm ); 1HNMR (500 MHz, MeOD) ꢇ = 10.86 (br,
s, 1H, NH), 8.21 (t, ꢈ = 7.61 Hz, 1H, CH), 8.08 (d, ꢈ = 7.61 Hz,
1H, CH), 7.93 (s, 1H, CH), 4.75 (s, 2H, CH ), 3.16 (s, 3H, CH );
2.10. 4-Methyl-N-(pyridin-2-yl)benzene Sulfonamide (9b,
C H N O S). Yield: 935.6 mg (82.1%); m.p.: 178–180∘C;
12 12
2
2
TLC: ꢃꢀ = 0.72 (H O-BuOH-Acetic acid 1 : 4 : 1); IR (FTIR):
2
ꢄ = 3328 (N-Hamine, stretching), 1665 (N-Hamine, bending), 1019
(S=Ostretching), 1161 (-N- S=Ostretching), 1455 (C=C-
Caromatic, stretching), 680 (Ø-Sstretching); UV-Vis (methanol,
2
3
13CNMR (125 MHz, MeOD) ꢇ = 168 (C-25), 156 (C-13), 141
(C-1), 132 (C-4), 131 (C-5), 53 (C-24), 37 (C-23); ESI-MS: m/z
= 413.59 [M + 2]+, 411.48 [M]+.
ꢅ
=
23 ⋅ 1−01−5 mol dm−3): ꢂmax(ꢆ) = 224 (15380) nm
(mol−1 dm cm ); 1HNMR (500 MHz, MeOD) ꢇ = 11.43 (br,
2.7. N-[{Bis[(4-methylphenyl)sulfonyl]amino}(imino)methyl]-
N-methylglycine (4b, C H N O S ). Yield: 872.1 mg
s, 1H, NH), 7.97 (d, ꢈ = 8.11 Hz, 1H, CH), 7.61 (d, ꢈ = 8.31 Hz,
1H, CH), 7.25 (t, ꢈ = 7.21 Hz, 1H, CH), 7.20 (s, 1H, CH), 7.11
(t, ꢈ = 8.41 Hz, 1H, CH), 7.15 (d, ꢈ = 8.39 Hz, 1H, CH), 2.48
(s, 3H, CH ); 13CNMR (125 MHz, MeOD) ꢇ = 148 (C-2), 145
18 21
3
6
2
(82.2%); m.p.: 195–197∘C; TLC: ꢃꢀ = 0.63 (H O-BuOH-Ace-
2
tic acid 1 : 4 : 1); IR (FTIR): ꢄ = 3265 (O-Hcarboxylic, stretching),
3
1707 (C=Ocarboxylic, stretching), 1600 (N-Hamine, bending), 1660
(C=Nimine, stretching), 1399 (O-Hcarboxylic, bending), 1043
(S=Ostretching), 1182 (-N- S=Ostretching), 1445 (C=C-
Caromatic, stretching), 685 (Ø-Sstretching); UV-Vis (methanol,
(C-6), 143 (C-14), 137 (C-4), 129 (C-13), 115 (C-5), 111 (C-3),
21 (C-17); ESI-MS: m/z = 250.35 [M + 2]+, 248.30 [M]+.
2.11. N-(Phenylsulfonyl)-N-(pyridin-2-yl)benzene Sulfonamide
2 3 ⋅ 1−01−5 mol dm−3): ꢂmax(ꢆ) = 222 (19000) nm
(10a, C H N O S ). Yield: 909.8 mg (71.7%); m.p.:
ꢅ
=
17 14
2
4
2
166–168∘C; TLC: ꢃꢀ
=
0.62 (H O-BuOH-Acetic acid
(mol−1 dm cm ); 1HNMR (500 MHz, MeOD) ꢇ = 10.76 (br,
s, 1H, NH), 7.81 (d, ꢈ = 8.11 Hz, 1H, CH), 7.78 (d, ꢈ = 8.14 Hz,
1H, CH), 4.73 (s, 2H, CH ), 3.15 (s, 3H, CH ), 2.46 (s, 3H,
2
1 : 4 : 1); IR (FTIR): ꢄ = 3348 (N-Hamine, stretching), 1619 (N-
Hamine, bending), 1030 (S=Ostretching), 1186 (-N- S=Ostretching),
1445 (C=C-Caromatic, stretching), 688 (Ø-Sstretching); UV-
2
3
CH ); 13CNMR (500 MHz, MeOD) ꢇ = 168 (C-27), 156
3
Vis (methanol, ꢅ
=
2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 215
(C-14), 143 (C-1), 139 (C-4), 132 (C-6), 53 (C-26), 37 (C-24),
21 (C-25); ESI-MS: m/z = 441.53 [M + 2]+, 439.58 [M]+.
(12830) nm (mol−1 dm3 cm−1); HNMR (500 MHz, MeOD)
ꢇ = 8.13 (m, 1H, CH), 8.11 (m, 1H, CH), 7.95 (m, 1H, CH), 7.88
(m, 1H, CH), 7.81 (m, 1H, CH), 7.65 (qd, ꢈ = 8.39 Hz, 1.21 Hz,
1H, CH), 7.48 (qd, ꢈ = 7.29 Hz, 5.21 Hz, 1H, CH); 13CNMR
(125 MHz, MeOD) ꢇ = 148 (C-6), 142 (C-13), 138 (C-2), 131
(C-16), 130 (C-14), 117 (C-5), 113 (C-3); ESI-MS: m/z = 376.45
[M + 2]+, 374.44 [M]+.
1
2.8. N-{Imino[[(4-methylphenyl)sulfonyl](phenylsulfonyl) ami-
no]methyl}-N-methylglycine (6a, C H N O S ). Yield:
17 19
3
6
2
626.4 mg (70.6%); m.p.: 182–184∘C; TLC: ꢃꢀ
=
0.61
(H O-BuOH-Acetic acid 1 : 4 : 1); IR (FTIR): ꢄ = 3277
2
(O-Hcarboxylic, stretching), 1707 (C=Ocarboxylic, stretching), 1599
(N-Hamine, bending), 1659 (C=Nimine, stretching), 1399 (O-
Hcarboxylic, bending), 1040 (S=Ostretching), 1185 (-N- S=Ostretching),
1444 (C=C-Caromatic, stretching), 684 (Ø-Sstretching); UV-Vis
2.12. 4-Methyl-N-(phenylsulfonyl)-N-(pyridin-2-yl)benzene
Sulfonamide (10b, C H N O S ). Yield: 1140.5 mg (84.3%);
19 18
2
4
2
m.p.: 164–166∘C; TLC: ꢃꢀ = 0.68 (H O-BuOH-Acetic acid
(methanol, ꢅ = 2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 218 (26150) nm
(mol−1 dm3 cm−1); 1HNMR (500 MHz, MeOD) ꢇ = 10.79 (br,
s, 1H, NH), 8.21 (d, ꢈ = 7.61 Hz, 1H, CH), 8.10 (s, H, CH),
2
1 : 4 : 1); IR (FTIR): ꢄ = 3348 (N-Hamine, stretching), 1621 (N-
Hamine, bending), 1027 (S=Ostretching), 1162 (-N- S=Ostretching),

Journal of Chemistry
5
1445 (C=C-Caromatic, stretching), 681 (Ø-Sstretching); UV-Vis
3. Results and Discussion
(methanol, ꢅ
=
2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 222
A total of twelve novel sulfonamides were synthesized in
aqueous basic media by simple reaction of creatine (amidine
derivatives), amino pyridine (benzene sulfonamide series 1),
and methyl alanine (benzene sulfonamide series 2) with ben-
zene sulfonyl chloride and para toluene sulphonyl chloride,
respectively, with continuous stirring and details of reaction
conditions are explained in Experimental section and syn-
thetic pathways of sulfonamides are explained in Schemes 1,
2, 3, and 4. Compounds 3a, 3b, 9a, 9b, 15a, and 15b were
synthesized in equimolar concentration of creatine, amino
pyridine, and methyl alanine with benzene sulphonyl chlo-
ride and para toluene sulphonyl chloride, respectively, while
4a, 4b, 9a, and 9b were obtained by bimolar concentration
of respective sulphonyl chlorides, respectively. Compounds
6a and 12a were synthesized by the reaction of 3b and 9b
with benzene sulphonyl chloride and para toluene sulphonyl
chloride in equimolar concentration, respectively. All the
compounds except compound 15a (57.5%) were obtained in
good yield. Elemental analysis was performed for the confor-
mation of all the compounds and measurement of absorption
maximum (ꢂmax) provided the justification. e analytical
data of synthesized sulfonamides are presented in Table 1.
e synthesized compounds were characterized by FT-IR,
and the characteristics band at 1621–1707 cm−1 for imine
stretching of amidine sulfonamides, 3280–3367 cm−1 of N-H
amide stretching for benzene sulfonamides (series 1), 3250–
3268 cm−1 for O-H stretching (benzene sulfonamide series 2),
and 1082–1199 cm−1 for (-N-S=O) and 1019–1054 cm−1 (S=O)
for all compounds reveals the formation of sulfonamides. [M
+ 2]+ peaks obtained by ESI-MS represented the isolation of
sulfonyl group in all synthesized compounds. e structures
of all the compounds were also confirmed by 1HNMR
1
(13855) nm (mol−1 dm3 cm−1); HNMR (500 MHz, MeOD)
ꢇ = 8.19 (s, H, CH), 8.02 (d, ꢈ = 8.09 Hz, 1H, CH), 7.87 (t,
ꢈ = 8.41 Hz, 1H, CH), 7.68 (d, ꢈ = 8.11 Hz, 1H, CH), 7.61 (d,
ꢈ = 8.37 Hz, 1H, CH), 7.55 (d, ꢈ = 7.27 Hz, 1H, CH), 2.46 (s,
3H, CH ); 13CNMR (125 MHz, MeOD) ꢇ = 148 (C-6), 138 (C-
3
2), 132 (C-15), 117 (C-5), 113 (C-3), 22 (C-27); ESI-MS: m/z =
404.55 [M + 2]+, 402.51 [M]+.
2.13. 4-Methyl-N-(phenylsulfonyl)-N-(pyridin-2-yl)benzene
Sulfonamide (12a, C H N O S ). Yield: 529.5 mg (65.1%);
18 16
2
4
2
m.p.: 188–190∘C; TLC: ꢃꢀ = 0.76 (H O-BuOH-Acetic acid
2
1 : 4 : 1); IR (FTIR): ꢄ = 3280 (N-Hamine, stretching), 1620 (N-
Hamine, bending), 1021 (S=Ostretching), 1158 (-N- S=Ostretching),
1445 (C=C-Caromatic, stretching), 682 (Ø-Sstretching); UV-Vis
(methanol, ꢅ = 2 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 220 (42550) nm
(mol−1 dm3 cm−1); HNMR (500 MHz, MeOD) ꢇ = 8.15 (d,
1
ꢈ = 7.69 Hz, 1H, CH), 8.07 (d, ꢈ = 8.11 Hz, 1H, CH), 7.98 (d,
ꢈ = 7.61 Hz, 1H, CH), 7.91 (t, ꢈ = 8.37 Hz, 1H, CH), 7.65 (d,
ꢈ = 8.17 Hz, 1H, CH), 7.51 (d, ꢈ = 7.17 Hz, 1H, CH), 7.45 (d,
ꢈ = 7.17 Hz, 1H, CH), 2.44 (s, 3H, CH ); 13CNMR (125 MHz,
3
MeOD) ꢇ = 147 (C-6), 138 (C-2), 132 (C-15), 117 (C-5), 112
(C-3), 21 (C-27); ESI-MS: m/z = 390.53 [M + 2]+, 388.49
[M]+.
2.14. N-Methyl-N-(phenylsulfonyl)alanine (15a, C H NO S).
10 13
4
Yield: 786.1 mg (51.7%); m.p.: 132–134∘C; TLC: ꢃꢀ = 0.72
(H O-BuOH-Acetic acid 1 : 4 : 1); IR (FTIR): ꢄ = 3215 (O-
2
Hcarboxylic, stretching), 1743 (C=Ocarboxylic, stretching), 1444 (O-
Hcarboxylic, bending), 1041 (S=Ostretching), 1183 (-N- S=Ostretching),
1444 (C=C-Caromatic, stretching), 688 (Ø-Sstretching); UV-Vis
and 13CNMR by dissolving in MeOD. HNMR spectra of
1
(methanol, ꢅ =−21 ⋅ 10−5 mol dm−3): ꢂmax(ꢆ) = 215 (13070) nm
(mol−1 dm3 cm ); HNMR (500 MHz, MeOD) ꢇ = 7.73 (d,
1
compounds 3a and 3b showed a broad signal at ꢇ 9.91,
9.96 while signal at ꢇ 10.76–10.86 for 4a, 4b, and 9a and
11.43, 11.49 ppm for 9a and 9b corresponds to NH group
of sulfonamide. A broad singlet at ꢇ 3.75 ppm due to -OH
group was also obtained for compounds 15a and 15b. e
characteristics C-SO-NH signals at ꢇ 155-156 ppm and ꢇ 138–
140 ppm for amidine and benzene sulfonamides, respectively,
were showed by 13CNMR which identified the structures
correctly.
ꢈ = 7.69 Hz, 1H, CH), 7.53 (d, ꢈ = 7.51 Hz, 1H, CH), 7.36 (t,
ꢈ = 7.61 Hz, 1H, CH), 4.51 (q, ꢈ = 7.17 Hz, 1H, CH), 3.75 (br,
s, 1H, OH), 2.71 (s, 3H, CH ), 1.11 (d, ꢈ = 7.17 Hz, 3H, CH );
3
3
13CNMR (125 MHz, MeOD) ꢇ = 178 (C-14), 138 (C-1), 131 (C-
4), 62 (C-12), 29 (C-11), 15 (C-13); ESI-MS: m/z = 245.38 [M +
2]+, 243.35 [M]+.
2.15. N-Methyl-N-[(4-methylphenyl)sulfonyl]alanine (15b,
Synthesized compounds were also screened for their
antibacterial against Gram negative bacteria E. coli and Gram
positive S. aureus and B. subtilis by following the guidelines
of CLSI [22, 23] using ciprofloxacin and sulfamethoxazole
as reference antibacterial agents. Antifungal activity was also
evaluated for synthesized compounds against three strains,
namely, A. flavus, A. parasiticus, and A. sp, using itraconazole
as reference antifungal agent. Among the bacterial strains,
compound 3b has excellent antibacterial activities having
MIC 40 ꢀg/mL against S. aureus with zone of inhibition
C H NO S). Yield: 910.9 mg (63.6%); m.p.: 140–142∘C;
11 15
4
TLC: ꢃꢀ = 0.70 (H O-BuOH-Acetic acid 1 : 4 : 1); IR (FTIR):
2
ꢄ = 3268 (O-Hcarboxylic, stretching), 1710 (C=Ocarboxylic, stretching),
1449 (O-Hcarboxylic, bending), 1054 (S=Ostretching), 1146
(-N- S=Ostretching), 1422 (C=C-Caromatic, stretching), 677
(Ø-Sstretching); UV-Vis (methanol, ꢅ = 2 ⋅ 10−5 mol dm−3):
ꢂ
max(ꢆ) = 220 (17250) nm (mol−1 dm3 cm−1); 1HNMR
(500 MHz, MeOD) ꢇ = 7.69 (d, ꢈ = 8.09 Hz, 1H, CH), 7.32
(d, ꢈ = 7.91 Hz, 1H, CH), 4.48 (t, ꢈ = 7.17 Hz, 1H, CH), 3.75
(br, s, 1H, OH), 2.69 (s, 3H, CH ), 2.39 (s, 3H, CH ), 1.08 (d,
comparable with control drug (ciprofloxacin). e pꢁ
3
3
a
ꢈ = 7.17 Hz, 3H, CH ); 13CNMR (125 MHz, MeOD) ꢇ = 178
of compound 3b is 10.8 which has electron withdrawing
inductive effect (mild acidic) for which supports its cell
permeability against the particular bacterial strain to bind
3
(C-14), 138 (C-1), 133 (C-4), 129 (C-5), 61 (C-12), 29 (C-11), 15
(C-13); ESI-MS: m/z = 259.38 [M + 2]+, 257.35 [M]+.

6
Journal of Chemistry
Table 1: Physiochemical and analytical data of sulfonamides.
Elemental analysis (found/cal.) %
Compounds
Molecular weight
C
H
N
S
apꢁ
a
3a
3b
4a
4b
6a
271.29
285.32
411.45
439.51
425.48
234.28
248.30
374.44
402.49
388.46
243.28
257.31
44.33/44.27
46.35/46.30
46.77/46.71
49.17/49.19
47.96/47.99
56.33/56.39
58.03/58.05
54.50/54.53
56.73/56.70
55.63/55.65
49.43/49.37
51.33/51.35
4.85/4.83
5.39/5.31
4.15/4.16
4.89/4.82
4.54/4.50
4.28/4.30
4.81/4.87
3.68/3.77
4.52/4.51
4.11/4.15
5.41/5.39
5.81/5.88
15.42/15.49
14.68/14.73
10.26/10.21
9.58/9.56
7.88/7.98
11.88/11.96
11.22/11.28
7.51/7.48
6.88/6.96
7.16/7.21
5.73/5.76
5.36/5.44
11.83/11.82
11.29/11.24
15.65/15.59
14.57/14.59
15.12/15.07
13.61/13.69
12.85/12.91
17.15/17.13
15.86/15.93
16.46/16.51
13.16/13.18
12.49/12.46
10.8
10.8
4.7
4.7
4.7
8.5
8.5
5.3
5.3
5.3
5.0
4.8
9a
9b
10a
10b
12a
15a
15b
apꢁ values from ACD, Inc.
a
Table 2: Zonea of inhibition and MICb of sulfonamides against pathogenic bacterial strains.
Name of bacteria
Gram (+) bacterial strains
Gram (−) bacterial strains
Compounds
S. aureus
B. subtilis
E. coli
(ATCC 25922)
Zone of inhibition
(ATCC 25923)
(ATCC 6633)
Zone of inhibition
MIC
Zone of inhibition
MIC
MIC
3a
3b
4a
4b
6a
9a
9b
10a
10b
12a
—, —, —
32, 29, 26
—, —, —
—, —, —
—, —, —
—, —, —
—, —, —
9, —, —
27, 24, 22
9, —, —
—
40
—
—
—, —, —
—
>160
—
9, —, —
—, —, —
—, —, —
28, 25, 22
>160
8, —, —
—, —, —
—, —, —
—
—
80
—
—
—
—, —, —
9, —, —
—
9, —, —
9, —, —
>160
160
>160
—
>160
80
8, —, —
—, —, —
—, —, —
28, 24, 21
—, —, —
27, 24, 22
36, 33, 31
>160
—, —, —
14, 10, —
—, —, —
—, —, —
—, —, —
28, 25, 20
35, 34, 31
33, 28, 25
—
160
—
—
—
>160
80
80
—
—
80
0.5
40
15a
15b
29, 26, 21
—, —, —
36, 34, 31
—, —, —
—
—
80
0.5
160
Ciprofloxacinc
Sulfamethoxazoled
0.5
—
16, 13, —
aZone of inhibition was measured in mm at concentration of 160, 80, and 40 ꢂg mL
.
−1
bMIC (minimum inhibitory concentrations) were measured in ꢂg mL
.
−1
cControl drug; dsulfa drug.
the proteins. As far as SAR is concerned, amide functional
group further supports its activity. Compounds 4b and 15b
showed better activity against E. coli and compounds 3a,
4a, 4b, and 6a have no activity against the Gram posi-
tive S. aureus and B. subtilis while 10b, 12a, 15a, and 15b
have good activity against these bacterial strains which is
is 5.7. e electrostatic interaction of methyl group with pro-
tein and pyridine further supports their antibacterial activi-
ties [24].
Among the fungal strains, compounds 9a and 9b have
excellent activity against A. parasiticus and A. flavus, respec-
tively, while 10a and 15a showed better activity against A.
higher (MIC 80 ꢀg/mL) than already existing sulfa drug
(sulfamethoxazole; MIC 160 ꢀg/mL). e MIC values and
zone of inhibitions are presented in Table 2. e activities
of above-mentioned compounds are their high permeability
into cell due to their acidic behavior by virtue of their lower
pꢁ values (4.7–5.3), while the pꢁ value of sulfamethoxazole
parasiticus and A. sp. was insensitive to all strains except
compound 15b (MIC 160 ꢀg/mL). e amide bond forma-
tions in the above-mentioned synthesized compounds have
excellent activities against the fungal strains as far as the
SAR is concerned [25–27]. It is concluded that newly synthe-
sized sulfonamides exhibited greater activity than reference
a
a

Journal of Chemistry
Compounds
7
Table 3: Zonea of inhibition and MICb of sulfonamides against pathogenic fungal strains.
Name of fungi
A. parasiticus
A. flavus
A. sp.
(ATCC 15517)
(ATCC 9643)
(ATCC 200667)
Zone of inhibition
MIC
—
—
Zone of inhibition
MIC
—
160
—
—
—
—
40
—
80
160
—
Zone of inhibition
MIC
—
—
—
—
3a
3b
4a
4b
6a
—, —, —
—, —, —
9, —, —
—, —, —
12, —, —
—, —, —
—, —, —
—, —, —
—, —, —
22, 19, 15
—, —, —
24, 20, 18
12, —, —
—, —, —
—, —, —
—, —, —
—, —, —
—, —, —
—, —, —
—, —, —
9, —, —
—, —, —
13, —, —
—, —, —
—, —, —
>160
—, —, —
—, —, —
24, 21, 18
22, 19, 13
21, 18, 12
—, —, —
—, —, —
24, 21, 18
—
—
—
—
9a
40
9b
10a
10b
12a
15a
80
>160
80
—
—
80
—
160
—
—
15b
11, —, —
18, 11, —
>160
—, —, —
—
80
15, 12, —
12, —, —
160
Itraconazolec
160
21, 19, 15
>160
aZone of inhibition was measured in mm at concentration of 160, 80, and 40 ꢂg mL
.
−1
bMIC (minimum inhibitory concentrations) were measured in ꢂg mL
.
−1
cControl drug.
itraconazole. e MIC values and zone of inhibitions are
reported in Table 3.
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Amidine and benzene sulfonamides derivatives were syn-
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Conflict of Interests
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e authors declare that there is no conflict of interests
regarding the publication of this paper.
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