Vol. 25, No. 7 (2013)
Synthesis and Biological Screening of N-Substituted (5-Chloro-2-methoxyphenyl)benzene Sulfonamide 3737
where, Control = Total enzyme activity without inhibitor. Test
= Activity in the presence of test compound. IC50 values were
calculated using EZ-Fit Enzyme Kinetics software (Perrella
Scientific Inc. Amherst, USA).
N-Isopropyl-N-(5-chloro-2-methoxyphenyl)benzene
sulfonamide (5c): Brown needle like crystals, Yield: 59 %,
m.p. 90-92 ºC. IR (KBr, νmax, cm-1): 3019 (aromatic C-H), 1446,
1342 (SO2), 1229 (-OCH3), 1149 (aliphatic C-N str.); 1H NMR
(500 MHz, CD3OD): δ 7.64 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and
H-6'), 7.61 (br.t, J = 7.5 Hz, 1H, H-4'), 7.52 (br.t, J = 7.5 Hz,
2H, H-3' and H-5'), 7.32 (dd, J = 8.5, 2.5 Hz, 1H, H-4), 7.19
(d, J = 2.5 Hz, 1H, H-6), 6.80 (d, J = 8.5 Hz, 1H, H-3), 4.50
(m, 1H, H-1"), 3.34 (s, 3H, -OCH3), 1.01 (d, J = 6.6 Hz, 6H,
CH3-2" and CH3-3"); EIMS: m/z 339 [M+], 324 [M-CH3]+,
308 [M-OCH3]+, 275 [M-SO2]+, 198 [M-PhSO2]+, 198
[PhSO2]+.
DPPH assay: The stable 1,1-diphenyl-2-picrylhydrazyl
radical (DPPH) was used for the determination of antioxidant
activity. Different concentrations of compounds in respective
solvents were added at an equal volume (10 µL) to 90 µL of
100 µM methanolic DPPH in a total volume of 100 µL in
96-well plates. The contents were mixed and incubated at 37 ºC
for 0.5 h. The absorbance was measured at 517 nm using
Synergy HT BioTek® USA microplate reader. Quercetin and
L-ascorbic acid were used as standard antioxidants. The
experiments were carried out in triplicates. IC50 values were
calculated using EZ-Fit5 Perrella Scientific Inc.Amherst USA
software. The decrease in absorbance indicates increased
radical scavenging activity which was determined by the
following formula16.
N-(2-Bromoethyl)-N-(5-chloro-2-methoxyphenyl)benzene
sulfonamide (5d): Dark brown solid, Yield: 64 %, IR (KBr,
νmax, cm-1): 3022 (aromatic C-H), 1449, 1337 (SO2), 1232
1
(-OCH3), 1145 (aliphatic C-N str.); H NMR (500 MHz,
CD3OD): δ 7.96 (br.s, H-2' and H-6'), 7.62 (m, 1H, H-4'), 7.51
(br.t, J = 7.5 Hz, 2H, H-3' and H-5'), 7.37 (d, J = 2.5 Hz, 1H,
H-6), 7.32 (dd, J = 8.5, 2.5 Hz, 1H, H-4), 6.88 (d, J = 8.5 Hz,
1H, H-3), 3.90 (br.s, 2H, CH2-1"), 3.43 (t, J = 6.5, 2H, CH2-
2"), 3.27(s, 3H, -OCH3); EIMS: m/z 404 [M+], 389 [M-CH3]+,
373 [M-OCH3]+, 340 [M-SO2]+, 263 [M-PhSO2]+, 141
[PhSO2]+.
Control − Test
Antiradical activity (Inhibition %) =
×100
Control
Statistical analysis: All the measurements were done in
triplicate and statistical analysis was performed by Microsoft
Excel 2003. Results are presented as mean sem.
N-Allyl-N-(5-chloro-2-methoxyphenyl)benzene sulfon
amide (5e): Dark brown gammy solid,Yield: 82 %, IR (KBr,
νmax, cm-1): 3019 (aromatic C-H), 1443, 1336 (SO2), 1227
Spectral characterization of the synthesized compounds
N-(5-Chloro-2-methoxyphenyl)benzene sulfonamide
(3): Colourless needle like crystals, Yield: 91 %, m.p. 140-
142 ºC. IR (KBr, νmax, cm-1): 3120 (N-H str.), 3020 (C-H
aromatic str.), 1447, 1338 (SO2), 1225 (-OCH3); 1H NMR (500
MHz, CD3OD): δ 7.71 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and
H-6'), 7.55 (br.t, J = 7.5 Hz, 1H, H-4'), 7.45 (br.t, J = 7.5 Hz,
2H, H-3' and H-5'), 7.41 (d, J = 2.5 Hz, 1H, H-6), 7.05 (dd,
J = 8.5, 2.5 Hz, 1H, H-4), 6.79 (d, J = 8.5 Hz, 1H, H-3), 3.51
(s, 3H, -OCH3); EIMS: m/z 297 [M+], 288 [M-CH3]+, 266
[M-OCH3]+, 233 [M-SO2]+, 156 [M-PhSO2]+, 141 [M-
C6H3(Cl)(OCH3NH)]·+.
1
(-OCH3), 1151 (aliphatic C-N str.); H NMR (500 MHz,
CD3OD): δ 7.64 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and H-6'), 7.62
(br.t, J = 7.5 Hz, 1H, H-4' ), 7.51 (br.t, J = 7.5 Hz, 2H, H-3'
and H-5'), 7.27 (dd, J = 8.5, 2.5 Hz, 1H, H-4),7.17 (d, J = 2.5
Hz, 1H, H-6), 6.85 (d, J = 8.5 Hz, 1H, H-3), 5.74 (m, 1H, H-
2"), 5.06 (dd, J = 17.5, 1.5 Hz, 1H, Hb-3"), 5.00 (dd, J = 10,
1.0 Hz, 1H, Ha-3"), 4.20 (br.s, 2H, H-1"), 3.33 (s, 3H, -OCH3);
EIMS: m/z 337 [M+], 322 [M-CH3]+, 306 [M-OCH3]+, 273
[M-SO2]+, 183 [M-PhSO2]+, 141 [M-C6H3(Cl)(OCH3)
NCH2CH=CH2]·+.
N-Butyl-N-(5-chloro-2-methoxyphenyl)benzene sulfon
amide (5f): Colourless sticky solid,Yield: 72%, IR (KBr, νmax,
cm-1): 3015 (aromatic C-H), 1445, 1337 (SO2), 1225 (-OCH3),
1
1150 (aliphatic C-N str.); H NMR (500 MHz, CD3OD): δ
N-Methyl-(5-chloro-2-methoxyphenyl)benzene sulfon
amide (5a): Yellow coloured crystals, yield: 83 %. m.p. 110-
112 ºC. IR (KBr, νmax, cm-1): 3018 (aromatic C-H), 1445, 1340
(SO2), 1220 (-OCH3)), 1150 (aliphatic C-N str.); 1H NMR (500
MHz, CD3OD): δ 7.65 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and H-
6'), 7.62 (br.t, J = 7.5 Hz, 1H, H-4'), 7.53 (br.t, J = 7.5 Hz, 2H,
H-3' and H-5'), 7.29 (dd, J = 8.5, 2.5 Hz, 1H, H-4),7.23 (d, J =
2.5 Hz, 1H, H-6), 6.89 (d, J = 8.5 Hz, 1H, H-3), 3.34 (s, 3H,
-OCH3), 3.18 (s, 3H, -CH3); EIMS: m/z 311 [M+], 296 [M-
CH3]+, 280 [M-OCH3]+, 247 [M-SO2]+, 170 [M-PhSO2]+, 141
[PhSO2]+.
7.62 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and H-6'), 7.60 (br.t, J = 7.5
Hz, 1H, H-4'), 7.51 (br.t, J = 7.5 Hz, 2H, H-3' and H-5'), 7.30
(dd, J = 8.5, 2.5 Hz, 1H, H-4), 7.18 (d, J = 2.5 Hz, 1H, H-6),
6.88 (d, J = 8.5 Hz, 1H, H-3), 3.57 (br.s, 2H, H-1"), 3.33 (s,
3H,-OCH3), 1.38 (m, 2H, H-3"), 1.27 (m, 2H, H-2"), 0.85 (t,
J = 7.0 Hz, 3H, H-4"); EIMS: m/z 353 [M+], 338 [M-CH3]+,
322 [M-OCH3]+, 289 [M-SO2]+, 212 [M-PhSO2]+, 141
[PhSO2]+.
N-Ethyl-N-(5-chloro-2-methoxyphenyl)benzene sulfon
amide (5b): White amorphous powder,Yield: 79 %, m.p. 79-
81 ºC. IR (KBr, νmax, cm-1): 3022 (aromatic C-H), 1444, 1337
(SO2), 1227 (-OCH3), 1151 (aliphatic C-N str.); 1H NMR (500
MHz, CD3OD): δ 7.64 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and
H-6'), 7.61 (br.t, J = 7.5 Hz, 1H, H-4'), 7.52 (br.t, J = 7.5 Hz,
2H, H-3' and H-5'), 7.32 (dd, J = 8.5, 2.5 Hz, 1H, H-4),7.19
(d, J = 2.5 Hz, 1H, H-6), 6.80 (d, J = 8.5 Hz, 1H, H-3), 3.63
(br.s, 2H, CH2-1"), 3.34 (s, 3H,-OCH3), 1.03 (t, J = 7.5 Hz,
3H, CH3-2"); EIMS: m/z 325 [M+], 310 [M-CH3]+, 294 [M-
OCH3]+, 261 [M-SO2]+, 184 [M-PhSO2]+, 141 [PhSO2]+.
N-Pentyl-N-(5-chloro-2-methoxyphenyl)benzene
sulfonamide (5g): Off white solid,Yield: 67 %, IR (KBr, νmax,
cm-1): 3016 (aromatic C-H), 1442, 1339 (SO2), 1224 (-OCH3),
1
1152 (aliphatic C-N str.); H NMR (500 MHz, CD3OD): δ
7.62 (dd, J = 7.5, 1.5 Hz, 2H, H-2' and H-6'), 7.60 (br.t, J = 7.5
Hz, 1H, H-4' ), 7.51 (br.t, J = 7.5 Hz, 2H, H-3' and H-5' ), 7.32
(dd, J = 8.5, 2.5 Hz, 1H, H-4), 7.18 (d, J = 2.5 Hz, 1H, H-6),
6.90 (d, J = 8.5 Hz, 1H, H-3), 3.58 (br.s, 2H, H-1"), 3.32 (s,
3H, -OCH3), 1.36 (m, 2H, H-2"), 1.33-1.30 (m, 4H, H-3" and
H-4"), 0.86 (t, J = 7.5 Hz, 3H, H-5"); EIMS: m/z 367 [M+],