A.H. Abdelazeem, A.G.S. El-Din, H.H. Arab et al.
Journal of Molecular Structure 1240 (2021) 130565
carried out as followed in the literature when necessary. Following
up the reactions and ensuring the purity of the compounds have
been checked using thin-layer chromatography (TLC). TLC analy-
sis was proceeded using Macherey-Nagel Alugram Sil G/UV254 sil-
ica gel plats in which their eluting system is Hexane-Ethyl acetate
(6:4). Determination of the melting points are carried out using IA
9100MK-Digital melting point apparatus where the obtained values
are uncorrected. Elemental analyses for C, H, and N were achieved
using Perkin- Elmer 2400 analyzer (Perkin-Elmer, Norwalk, CT) at
the mycology and biotechnology regional center at Al Azhar Uni-
versity, Egypt. Infrared spectra (IR) were recorded using a Bruker
FT-IR spectrophotometer Vector 22 in wavenumber (cm−1) from
KBr discs at the micro-analytical center, Faculty of Science, Cairo
University. Chemical shifts of 1H NMR and 13C NMR spectra were
recorded and J values were given in Hz using Bruker APX400 spec-
trometer at 400 MHz and 101 MHz, respectively in the DMSO–
d6 at the Faculty of Pharmacy, Beni-Suef University. Mass spec-
tra were verified using Finnegan MAT, SSQ 7000, Mass spectrome-
ter, at 70 eV (EI) at the micro-analytical center, Faculty of Science,
Cairo University.
and 1H of -NCH(H)CH2-), 3.31 (m, 1H, -NCH(H)CH2-), 3.02–3.08
(m, 1H, -NCH(H)CH2), 2.69–2.75 (m, 1H, -CHCOO-), 1.89–1.99
(m, 2H, -CHCH(H)-), 1.55–1.61 (m, 2H, -CHCH(H)-), 1.19–1.21 (m,
3H, –CH2CH3). 13C NMR (101 MHz, DMSO–d6): δ 174.22, 160.35,
157.34, 154.60, 145.03, 140.21, 131.11, 129.44, 129.29, 127.35, 127.50,
126.63, 60.53, 46.20, 29.08, 28.10, 14.53. MS (EI): m/z 483 (M+).
Anal. Calcd. For C23H25N5O5S: C, 57.13; H, 5.21; N, 14.48. Found: C,
57.50; H, 5.38; N, 14.72.
5-phenyl-1-(4-sulfamoylphenyl)-N-(4-(trifluoromethyl)phenyl)−1H-
1,2,4-triazole-3-carboxamide (5d): Brown solid (63%); m.p. 277–
279 °C. IR (cm−1): 3325 (NH), 3112 (CH aromatic), 1701 (CONH),
1530 (C = N), 1331, 1166 (SO2NH2). 1H NMR (400 MHz, DMSO–
d6): δ 10.97 (s, 1H, NH exchangeable with D2O), 8.13–8.15 (d,
J = 8 Hz, 2H, Ar-H), 7.98–8.00 (d, J = 8 Hz, 3H, Ar-H), 7.67 (m,
4H, Ar-H)), 7.54–7.60 (m, 4H, Ar-H), 7.49–7.51 (d, J = 8 Hz, 2H,
SO2NH2 exchangeable with D2O). 13C NMR (101 MHz, DMSO–d6):
δ 158.01, 156.81, 155.70, 145.32, 142.33, 140.12, 131.29, 129.58,
129.29, 127.52, 127.15, 126.84, 126.42, 126.13, 123.43, 121.09. MS
(EI): m/z 487 (M+). Anal. Calcd. For C22H16 F3N5O3S: C, 54.21; H,
3.31; N, 14.37. Found: C, 54.43; H, 3.59; N, 14.50.
General procedure for the synthesis of compounds (5a-e):
11-(5-phenyl-1-(4-sulfamoylphenyl)−1H-1,2,4-triazole-3-
Compound 4 (3.44 g, 10 mmol) was dissolved in acetic acid
(50 mL), followed by addition of the appropriate amine (10 mmol)
and heated under reflux for 3 h in presence of anhydrous sodium
acetate. The reaction mixture was poured onto ice water (50 mL)
after cooling to room temperature affording precipitate which was
filtered off. Recrystallized of the precipitate was carried out us-
ing ethanol after washing with water giving the pure desired com-
pound 5.
carboxamido)undecanoic acid (5e): White solid (63%); m.p. 244–
246 °C. IR (cm−1): 3400–2500 (COOH), 3036 (CH aromatic), 2922
(CH aliphatic), 1723 (COOH), 1560 (C = N), 1322, 1164 (SO2NH2).
1H NMR (400 MHz, DMSO–d6): δ 12.02 (s, 1H, COOH), 8.69 (s, 1H,
NH exchangeable with D2O), 7.94–7.96 (d, J = 8 Hz, 2H, Ar-H),
7.66–7.68 (d, J = 8 Hz, 2H, Ar-H), 7.51–7.65 (m, 7H, 5H of Ar-H and
2H of SO2NH2 exchangeable with D2O), 3.29 (m, 2H, -NHCH2-),
2.19 (m, 2H, -CH2COOH-), 1.50 (m, 4H, 2H of -CH2CH2CH2COOH
and 2H of –NHCH2CH2CH2-), 1.26 (m, 12H, -CH2CH2CH2-). 13C
NMR (101 MHz, DMSO–d6): δ 174.99, 158.85, 157.32, 155.19, 145.11,
140.23, 131.12, 129.47, 127.24, 127.45, 127.38, 126.66, 34.13, 29.53,
29.43, 29.36, 29.22, 29.02, 26.88, 24.97. MS (EI): m/z 527 (M+).
Anal. Calcd. For C26H33N5O5S: C, 59.18; H, 6.30; N, 13.27. Found:
C, 59.46; H, 6.57; N, 13.56.
4-(5-phenyl-1-(4-sulfamoylphenyl)−1H-1,2,4-triazole-3-
carboxamido)butanoic acid (5a): Off-white solid (51%); m.p.
232–236 °C. IR (cm−1): 3500–2800 (COOH), 3333 (NH), 2934 (CH
aliphatic), 1710 (COOH), 1684 (CONH-), 1501 (C = N), 1325 and
1162 (SO2NH2).1H NMR (400 MHz, DMSO–d6): δ 10.92 (s, 1H,
COOH exchangeable with D2O), 8.79 (s, 1H, NH exchangeable with
D2O), 7.94–7.96 (d, J = 8 Hz, 2H, Ar-H), 7.66–7.68 (d, J = 8 Hz,
2H, Ar-H), 7.57 (m, 2H, Ar-H), 7.51–7.53 (m, 3H, Ar-H), 7.47–7.49
(d, J = 8 Hz, 2H, SO2NH2 exchangeable with D2O), 2.27–2.31 (t,
J = 8 Hz, 2H, -NHCH2-), 1.91(m, 1H, -CH(H)COOH-), 1.78–1.81 (t,
J = 8 Hz, 2H,-CH2CH2CH2-), 1.24 (m, 1H,-CH(H)COOH-). 13C NMR
(101 MHz, DMSO–d6): δ 174.71, 159.07, 157.20, 155.25, 145.10,
140.23, 131.14, 129.47, 129.25, 127.58, 126.69, 120.83, 31.58, 24.97,
21.51. MS (EI): m/z 429 (M+). Anal. Calcd. For C19 H19 N5O5S: C,
53.14; H, 4.46; N, 16.31. Found: C, 53.50; H, 4.69; N, 16.52.
N-(adamantan-1-yl)−5-phenyl-1-(4-sulfamoylphenyl)−1H-1,2,4-
triazole-3-carboxamide (5b):
5-phenyl-1-(4-sulfamoylphenyl)−1H-1,2,4-triazole-3-carbonyl
azide (8): A cold solution of hydrazide intermediate 7 (0.358 g,
1.0 mmol) was prepared by dissolving in mixture of acetic acid
(6 mL): 1 N HCl (3 ml): water (25 mL), followed by addition of a
solution of NaNO2 (0.87 g, 1.0 mmol) in 3 mL cold water. During
stirring, a yellow syrup was formed, extracted with ethyl acetated,
washed with cold 3% NaHCO3, H2O. The extract was dried over
Na2SO4 followed by the next procedure without purification.
General procedure for synthesis of compounds (10a-f):
The acyl azide 8 (0.369 g, 1.0 mmol) was heated for 1 hour
in dry toluene affording the isocyanate 9. The reaction mixture
was allowed to be cooled, where the isocyanate intermediate 9
was dissolved in anhydrous pyridine then the appropriate amine
(0.01 mmol) was added. The mixture was undergone to reflux for
24 h followed by pouring onto ice/H2O containing drops of concen-
trated HCl. Extraction of the compound was carried out using ethyl
acetate followed by drying over anhydrous MgSO4. The purification
was performed using column chromatography which elutes the fi-
nal compounds 10a-f using petroleum ether:ethyl acetate gradient.
4-(3-(3-cyclohexylureido)−5-phenyl-1H-1,2,4-triazol-1-
Off-white solid (53%); m.p. 263–267 °C. IR (cm−1): 3320 (NH),
3238 (CH aromatic), 2921 (CH aliphatic), 1663 (CONH), 1501
(C = N), 1327, 1159 (SO2NH2). 1H NMR (400 MHz, DMSO–d6): δ
8.33 (s, 1H, NH exchangeable with D2O), 7.94–7.96 (d, J = 8 Hz,
2H, Ar-H), 7.67–7.52 (m, 3H, Ar-H), 7.44–7.49 (m, 6H, 4H of Ar-
H and 2H of SO2NH2 exchangeable with D2O), 2.10–1.99 (m, 6H,
-NHCCH2-), 1.75–1.91 (m, 3H, -CH(CH2)2-), 1.60–1.67 (m, 6H, -
CHCH2CH-). 13C NMR (101 MHz, DMSO–d6): δ 164.93, 158.05,
154.28, 152.37, 144.69, 140.59, 133.96, 130.81, 129.27, 127.48,
126.36, 52.10, 36.36, 29.29, 24.21. MS (EI): m/z 477 (M+). Anal.
Calcd. For C25H27N5O3S: C, 62.87; H, 5.70; N, 14.66. Found: C,
62.71; H, 5.86; N, 14.85.
yl)benzenesulfonamide (10a): White solid (54%); m.p. 250–252 °C.
IR (cm−1): 3361 (NH), 3159 (CH aromatic), 2928 (CH aliphatic),
1669 (NHCONH), 1563 (C = N), 1322, 1160 (SO2NH2).1H NMR
(400 MHz, DMSO–d6): δ 7.82–7.84 (d, J = 8 Hz, 2H, Ar-H), 7.72 (m,
2H, Ar-H), 7.47 (m, 3H, Ar-H), 7.38–7.40 (m, 4H, 2H of Ar-H and 2H
of SO2NH2 exchangeable with D2O), 5.74 (s, 1H, NH exchangeable
with D2O), 4.14 (s, 1H, NH exchangeable with D2O), 2.98 (m, 1H,
-NHCHCH2-), 1.55–1.59 (m, 4H, -NHCHCH2CH2-), 1.29 (m, 2H,
-(CH2)2CH2(CH2)2-), 1.12–1.14 (m, 2H, -CHCH2CH(H)CH2-), 0.87–
0.88 (m, 2H,-CHCH2CH(H)CH2-).13C NMR (101 MHz, DMSO–d6):
Ethyl
1-(5-phenyl-1-(4-sulfamoylphenyl)−1H-1,2,4-triazole-3-
carbonyl)piperidine-4-carboxylate (5c): White solid (57%); m.p.
144–146 °C. IR (cm−1): 3442 (NH), 3076 (CH aromatic), 2972 (CH
aliphatic), 1729 (C = O), 1494 (C = N), 1350, 1166 (SO2NH2). 1H
NMR (400 MHz, DMSO–d6): δ 7.95–7.97 (d, J = 8 Hz, 2H, Ar-H),
7.67–7.69 (d, J = 8 Hz, 2H, Ar-H), 7.57 (m, 2H, Ar-H), 7.49–7.51
(m, 5H, 3H of Ar-H and 2H of SO2NH2 exchangeable with D2O),
4.38–4.41 (m, 1H, -NCH(H)CH2-), 4.09–4.15 (m, 3H, 2H of –CH2CH3
4