4.1. Chemistry
Material and equipment
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All chemicals used for the preparation of the target compounds are of analytical grade and can be used without further purification. Solvents were purified and freshly distilled before use according to the standard procedures.
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Reaction progress was monitored by thin layer chromatography (Merck Silica gel 60 F254) on glass plates and visualized with a UV lamp (254 nm).
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Column chromatography was performed using spherical, neutral silica gel of diameter 40–100 µm (Kanto chemical co. Inc., Tokyo, Japan).
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Melting points were recorded at a ATM-02 (AS ONE, Tokyo, Japan).
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IR spectra were recorded at FT/IR-Spectrum Two (PerkinElmer, MA, USA) at the Faculty of Engineering, Yamagata University, Yonezawa, Japan.
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1H-NMR (400 or 500 MHz) and 13C-NMR (100 or 125 MHz) spectra were recorded on either a JNM-ECX400 or JNM-ECX500 (JEOL, Tokyo, Japan) in Faculty of Engineering, Yamagata University, Yonezawa, Japan. Chemical shifts are reported in ppm relative to tetramethylsilane (0 ppm), chloroform (7.26 ppm: 1H, 77.1 ppm: 13C) and dimethyl sulfoxide (2.50 ppm: 1H, 39.6 ppm: 13C). Coupling constant (J) is measured in hertz (Hz). Multiplicity was designated as: s, singlet; d, doublet; t, triplet; q, quartet; p, pentet; dd, doublet of doublet; and m for multiplet.
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Mass spectra (ESI-MS) were carried out using the AccuTOF JMS-T100LC (JEOL, Tokyo, Japan) at the Faculty of Engineering, Yamagata University, Yonezawa, Japan.
4.1.1. General procedure for the synthesis of ethyl 4-(substituted phenyl)-2-hydroxy-4-oxobut-2-enoates (2a-e).
A mixture of diethyl oxalate (2.92 g, 0.02 mol) and substituted acetophenone derivatives (0.01 mol) in ethanol (50 mL) was added to previously prepared sodium ethoxide (sodium, 0.46 g, 0.02 mol, ethanol 100 mL) at 50°C. The reaction mixture was heated under reflux for 2–3 h. After cooling, the solvent was removed, and the residue was taken up in water (200 mL) and acidified with concentrated HCl (1 mL). The aqueous mixture was extracted with ethyl acetate (3x150 mL). The combined extracts were washed with brine (100 mL), dried (MgSO4), and concentrated. The obtained solid was recrystallized from methanol to give compounds 2a-e and the produced compounds used in the next step without further purification [51–53].
4.1.2. General procedure for synthesis of 4-hydrazinylbenzenesulfonamide hydrochloride 4b.
A cold, stirred mixture of sulfanilamide (3.42 g, 0.02 mol), hydrochloric acid (10 mL) and crushed ice (200 g) was diazotized by the dropwise addition of sodium nitrite (1.4 g, 0.02 mol) in water (25 mL) over 30 min. The cold diazonium salt solution thus formed was rapidly added to a well-cooled solution of sodium sulfite (2.52 g) and sodium hydroxide (0.800g) in water (50 mL) with vigorous stirring, and the resulting mixture was left in the ice bath for 15 min, followed by acidification with 10 mL HCl and concentrated. The precipitated 4-hydrazineylbenzenesulfonamide hydrochloride 4b was collected and dried: white crystals; mp :225°C (lit. mp: 225°C); yield 3.9 g (88%) [41].
4.1.3. General procedure for the synthesis of ethyl 1,5 diarypyarzole-3-carboxylate (5a-j).
A mixture of diketoesters 2a-c (0.01mole) and phenylhydrazine 4a (0.01mole) was dissolved in suitable amount of absolute ethanol (40 mL) and refluxed for 5 h to afford compounds 5a-c. A mixture of diketoesters 2d-f and 4-hydrazinylbenzenesulfonamide hydrochloride 4b was refluxed in absolute ethanol for 5 h in the presence of sodium acetate (0.02 mole) to afford compounds 5d-f. The reaction process was monitored by TLC using chloroform: methanol (98: 2) solvent system for compounds 5a-c and chloroform: methanol (95: 5) solvent system for compounds 5d-f. The content of reaction mixture was evaporated under vacuum and the crude product was purified by column chromatography [42].
Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate (5a): Reddish brown solid; yield (75%); mp: 85–87°C (lit. 86°C)[54].
Ethyl 1-phenyl-5-(p-tolyl)-1H-pyrazole-3-carboxylate (5b): Reddish solid; yield (80%), mp: 87–88°C (lit. 84–86°C)[55].
Ethyl 5-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-3-carboxylate(5c): Reddish brown solid; yield (81%); mp: 97–99°C (lit. 97°C)[51].
Ethyl 5-(4-chlorophenyl)-1-phenyl-1H-pyrazole-3-carboxylate (5d): Reddish brown solid; yield (89%); mp: 92–94°C (lit. 95–97°C)[51] .
Ethyl 5-(3,4-dimethoxyphenyl)-1-phenyl-1H-pyrazole-3-carboxylate (5e): Brownish solid, yield (63%); mp: 174–176°C (lit. 177°C)[56].
Ethyl 5-phenyl-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (5f): Reddish powder; yield (66%), mp: 192–194°C (lit. 192)[57].
Ethyl 1-(4-sulfamoylphenyl)-5-(p-tolyl)-1 H -pyrazole-3-carboxylate (5g): Reddish brown; yield (75%), mp: 227–228°C (lit. 227°C)[58].
Ethyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (5h): Reddish brown powder; yield (71%), mp: 207–209°C (lit. 205–207°C)[59].
Ethyl 5-(4-chlorophenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (5i): Reddish brown powder; yield (80%), mp: 107–109°C (lit. 108°C)[59].
Ethyl 5-(3,4-dimethoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylate (5j): Reddish brown powder; yield (64%); mp: 214–215°C[60].
4.1.4. General procedure for the synthesis of 1,5-diarypyrazole carboxylic acids 6a-j.
A mixture of methanolic solution of compounds 5a-j (4 mmol), potassium hydroxide (KOH, 20%, 10 mL) was stirred at 60°C for 4 h. After cooling, the mixture solution was poured into water and acidified with hydrochloric acid solution (1 M) to pH = 3. The aqueous mixture was extracted with ethyl acetate (3x50 mL) and the aqueous layer was discarded. The combined organic extracts were dried with anhydrous MgSO4. The organic solvent was evaporated under vacuum to obtain solid products 6a-j [61].
1,5-Diphenyl-1 H -pyrazole-3-carboxylic acid (6a): Brown powder; yield (84%); mp: 180–182°C (lit. 182–183)[52].
1-Phenyl-5-(p-tolyl)-1 H -pyrazole-3-carboxylic acid (6b): Reddish powder; yield (87%); mp: 171–172°C[62].
5-(4-Methoxyphenyl)-1-phenyl-1 H -pyrazole-3-carboxylic acid (6c): Reddish brown powder; yield (79%); mp: 192–195°C (lit. 196–197°C)[60].
5-(4-Chlorophenyl)-1-phenyl-1 H -pyrazole-3-carboxylic acid (6d): Yellowish brown powder; yield (78%); mp: > 300°C[58].
5-(3,4-Dimethoxyphenyl)-1-phenyl- 1H -pyrazole-3-carboxylic acid (6e): Brown powder; yield (84%); mp: 213–214°C; 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 7.94 7.52 (m, 5H, Ar-H), 7.39 (s, 1H, pyrazole-H), 6.94–6.68 (m, 3H, Ar-H), 3.79 (s, 3H, OCH3), 3.77 (s, 3H, OCH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 163.36, 160.36, 145.81, 144.09, 142.55, 130.71, 128.76, 127.45, 126.47, 125.40, 122.05, 120.40, 115.26, 110.45, 56.23, 56.12; ESI-MS m/z [M + H]+ for C18H17N2O4 calculated: 325.1183, found: 325.256.
5-Phenyl-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylica acid(6f): Yellowish brown powder; yield (78%), mp: 184–186°C (lit. 188°C)[61].
1-(4-Sulfamoylphenyl)-5-( p -tolyl)-1 H -pyrazole-3-carboxylic acid (6g): Reddish brown powder; yield (88%); mp: 194–195°C[52].
5-(4-Methoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylic acid (6h): Brownish powder; yield (73%), mp: 197–198°C[63].
5-(4-Chlorophenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylic acid (6i): Yellowish brown powder; yield (84%); mp: 212–214°C[64].
5-(3,4-Dimethoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylic acid (6j): Reddish brown powder; yield (77%); mp: 206–208°C; 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 10.76 (s, 1H, OH), 7.99 (s, 1H, Ar-H), 7.91(d, J = 8.00 Hz, 2H, Ar-H), 7.79 (d, J = 8.00 Hz, 2H, Ar-H), 7.65–7.60 (m, 4H, 2Ar-H, SO2NH2), 7.43 (s, 1H, pyrazole-H), 3.89 (s, 6H, 2 OCH3);13C-NMR (100MHz, DMSO-d6) δ (ppm): 163.36, 159.98, 147.36, 145.23, 141.21, 131.47, 130.17, 128.82, 126.87, 125.54, 122.87, 119.99, 115.14, 107.53, 56.38, 56.21; ESI-MS m/z [M + H]+ for C18H18N3O6S calculated: 404.0911, found: 404.0271.
4.1.5. General procedure for synthesis of 4-acetyl-2-methoxyphenyl 5-(4-subistituted-phenyl) 1-(4-substituted-phenyl)-1H-pyrazole-3-carboxylate 7a-j.
A mixture of pyrazole carboxylic acid derivatives 6a-j (0.001 mol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) (0.384 g, 0.002 mol), 1-hydroxybenzotriazole (HOBt) (0.306 g, 0.002 mol), were stirred in dry DMF (5 mL) for 30 min, then N,N-diisopropylethylamine (DIPEA) (0.258 g, 0.002 mol) and 4-hydroxy-3-methoxyacetophenone (0.002 mol) were added to the mixture and stirred for 12 h. 20 mL Distilled water was added followed by acidification with dil. HCl. Extraction twice with ethyl acetate and purification were performed by using column chromatography with chloroform as eluent for compounds 7a-e and chloroform: methanol 98:2 for compounds 7f-j.
4-Acetyl-2-methoxyphenyl 1,5-diphenyl-1 H -pyrazole-3-carboxylate (7a): Yellowish brown solid; yield (75%); mp: 98–100°C; IR (ATR) cm− 1; 1748 (COO-Ph), 1725 (Co-CH3), 1574 (C = C); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.65 (d, J = 8.50 Hz, 1H, Ar-H), 7.46 (d, J = 8.00 Hz, 2H, Ar-H), 7.43–7.39 (m, 3H, Ar-H), 7.38 (s, 1H, Ar-H), 7.34–7.32 (m, 3H, Ar-H), 7.30 (s, 1H, pyrazole-H), 7.28–7.27 (m, 2H, Ar-H), 6.84 (d, J = 8.50 Hz, 1H, Ar-H), 3.75 (s, 3H, OCH3), 2.57 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.35, 160.07, 151.86, 147.61, 146.33, 145.04, 143.48, 142.86, 141.18, 139.68, 136.44, 129.91, 129.45, 129.11, 126.55, 123.97, 122.69, 114.98, 111.62, 56.74, 27.17; ESI-MS m/z [M + Na]+ for C25H20N2NaO4 calculated: 435.13208, found: 435.13095.
4-Acetyl-2-methoxyphenyl-1-phenyl 5- p -tolyl-1 H -pyrazole-3-carboxylate (7b): Yellowish solid; yield (81%); mp: 110–112°C; IR (ATR) cm− 1; 1743 (COO-Ph), 1710 (CO-CH3), 1575 (C = C); 1H-NMR (500 MHz, CDCl3) δ (ppm): 7.65 (s, 1H, Ar-H), 7.53–7.50 (m, 6H, Ar-H), 7.36–7.35 (m, 2H, Ar-H), 7.15 (s, 1H, pyrazole-H), 6.92–6.94 (m, 3H, Ar-H), 3.88 (s, 3H, OCH3), 2.62 (s, 3H, CH3), 2.33 (s, 3H, CH3); 13C-NMR (100MHz, CDCl3 ) δ (ppm): 197.40, 159.67, 150.10, 146.64, 143.95, 142.51, 139.46, 138.90, 136.03, 130.16, 129.85, 128.80, 125.35, 124.00, 122.97, 121.94, 111.97, 109.93, 56.48, 26.65, 21.49; ESI-MS m/z [M + Na]+ for C26H22N2NaO4 calculated: 449.1477, found: 449.14830.
4-Acetyl-2-methoxyphenyl − 5-(4-methoxyphenyl) 1-phenyl-1 H -pyrazole-
3-carboxylate (7c): Yellowish brown solid; yield (85%); mp: 69–71°C; IR (ATR) cm− 1; 1743 (COO-Ph), 1725 (CO-CH3), 1577 (C = C); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.64 (d, J = 7.00 Hz, 1H, Ar-H), 7.46 (d, J = 8.50 Hz, 2H, Ar-H), 7.42 (s, 1H, Ar-H), 7.38 (d, J = 7.00 Hz, 1H, Ar-H), 7.34 (d, J = 7.50 Hz, 2H, Ar-H), 7.22 (s, 1H, pyrazole-H), 7.17 (d, J = 8.50 Hz, 2H, Ar-H), 6.88–6.85 (m, 3H, Ar-H), 3.84 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 2.58 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.73, 159.99, 151.77, 148.69, 145.56, 143.22, 142.20, 139.78, 136.74, 130.95, 130.16, 129.55, 125.76, 124.02, 122.28, 116.09, 115.07, 111.96, 110.36, 57.17, 55.74, 26.65; ESI-MS m/z [M + Na]+ for C26H22N2NaO5 calculated: 465.1426, found: 465.14282.
4-Acetyl-2-methoxyphenyl-5-(4-chlorophenyl) 1-phenyl-1 H -pyrazole- ---3-carboxylate (7d): Yellowish brown solid; yield (73%); mp: 85–87°C; IR (ATR) cm− 1; 1739 (COO-Ph), 1728 (CO-CH3), 1575 (C = C); 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.60 (s, 1H, Ar-H), 7.56 (d, J = 6.00 Hz, 1H, Ar-H), 7.50–7.46 (m, 4H, Ar-H), 7.32–7.35 (m, 2H, Ar-H), 7.17–7.15 (m, 2H, Ar-H), 7.14 (s, 1H, pyrazole-H), 6.90 (d, J = 6.50 Hz, 2H, Ar-H), 3.88 (s, 3H, OCH3), 2.51 (s, 3H, CH3); 13C-NMR (100MHz, CDCl3) δ (ppm): 197.11, 160.00, 150.43, 147.01, 146.31, 143.53, 143.23, 138.32, 135.31, 133.65, 129.23, 128.88, 127.17, 126.08, 125.74, 123.01, 113.97, 111.69, 109.80, 56.14, 27.26; ESI-MS m/z [M + H]+ for C25H20ClN2O4 calculated: 447.1106, found: 447.10859.
4-Acetyl-2-methoxyphenyl-5-(3,4-dimethoxyphenyl) 1-phenyl-1 H -pyrazole-3-carboxylate (7e): Reddish yellow solid; yield (71%); mp: 74–76°C; IR (ATR) cm− 1; 1740 (COO-Ph), 1715 (CO-CH3), 1589 (C = C); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.65 (s, 1H, Ar-H), 7.63 (s, 1H, Ar-H), 7.56 (d, J = 8.50 Hz, 1H, Ar-H), 7.46 (d, J = 8.50 Hz, 2H, Ar-H), 7.38–7.41 (m, 3H, Ar-H), 7.30 (s, 1H, pyrazole-H), 6.97 (d, J = 8.50 Hz, 1H, Ar-H), 6.85–6.83 (m, 2H, Ar-H), 3.84 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 3.71 (s, 3H, OCH3), 2.59 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.38, 160.00, 153.54, 151.71, 149.03, 147.99, 147.03, 142.92, 140.14, 136.74, 130.54, 130.34, 129.55, 127.07, 123.73, 122.65, 121.95, 115.07, 112.67, 112.01, 110.57, 57.15, 56.48, 55.44, 26.95; ESI-MS m/z [M + H]+ for C27H25N2O6 calculated: 473.1707, found: 473.17144.
4-Acetyl-2-methoxyphenyl-5-phenyl 1-(4-sulfamoylphenyl)-1 H -pyrazole-3
-carboxylate (7f): Yellowish solid; yield (65%); mp: 69–72°C; IR (ATR) cm− 1; 1735 (COO-Ph), 1724 (CO-CH3), 1589 (C = C aromatic), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.91 (s, 1H, Ar-H), 7.87 (d, J = 8.50 Hz, 2H, Ar-H), 7.80 (d, J = 8.00 Hz, 1H, Ar-H), 7.68–7.64 (m, 3H, Ar-H), 7.55 (d, J = 8.50 Hz, 2H), 7.53 (s, 2H, SO2NH2), 7.41–7.39 (m, 2H, Ar-H), 7.35 (s, 1H, pyrazole-H), 7.31 (d, J = 8.00 Hz, 1H, Ar-H), 3.85 (s, 3H, OCH3), 2.57 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.75, 167.77, 159.18, 151.90, 144.65, 144.14, 142.86, 141.18, 135.65, 132.33,129.48, 129.40, 127.04, 125.27, 124.50, 123.58, 122.00, 112.02, 111.12, 56.74, 28.85; ESI-MS m/z [M + Na]+ for C25H21N3 Na O6S calculated: 514.1049, found: 514.10449.
4-Acetyl-2-methoxyphenyl-1-(4-sulfamoylphenyl) 5- p -tolyl-1 H -pyrazole-3-carboxylate (7g): Yellowish solid; yield (78%), mp: 83–85°C; IR (ATR) cm− 1; 1746 (COO-Ph), 1718 (CO-CH3), 1595 (C = C), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.95 (d, J = 8.50 Hz, 1H, Ar-H), 7.86 (d, J = 8.50 Hz, 2H, Ar-H), 7.69–7.63 (m, 2H, Ar-H), 7.55 (d, J = 8.50 Hz, 2H, Ar-H), 7.52 (s, 2H, SO2NH2), 7.39 (d, J = 8.50 Hz, 2H, Ar-H), 7.29 (s, 1H, pyrazole-H), 7.19 (d, J = 8.50 Hz, 2H, Ar-H), 3.84 (s, 3H, OCH3), 2.60 (s, 3H, CH3), 2.28 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.74, 163.64, 151.71, 146.50, 144.25, 143.93, 142.21, 139.63, 130.19, 129.12, 128.82, 128.45, 127.77, 126.14, 125.04, 123.75, 122.31, 112.64, 110.31, 56.44, 27.25, 21.47; ESI-MS m/z [M + Na]+ for C26H23N3NaO6S calculated: 528.1205, found: 528.12058.
4-Acetyl-2-methoxyphenyl 5-(4-methoxyphenyl) 1-(4-sulfamoylphenyl)-1 H -
pyrazole-3-carboxylate (7h):Yellowish solid; yield (55%), mp: 80–83°C; IR (ATR) cm− 1; 1750 (COO-Ph), 1720 (CO-CH3), 1585 (C = C), 1164 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 7.86 (d, J = 9.00 Hz, 2H, Ar-H), 7.66 (s, 1H, Ar-H), 7.64 (d, J = 7.50 Hz, 2H, Ar-H), 7.55 (d, J = 9.00 Hz, 2H, Ar-H), 7.51 (s, 2H, SO2NH2), 7.39 (d, J = 8.00 Hz, 1H, Ar-H), 7.13 (s, 1H, pyrazole-H), 7.26–7.23 (m, 3H, Ar-H), 3.84 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 2.60 (s, 3H, CH3); 13C NMR (100MHz, DMSO-d6) δ (ppm): 197.35, 160.08, 151.86, 148.90, 144.65, 143.35, 141.58, 136.44, 130.40, 129.61, 127.43, 126.55, 123.98, 123.58, 121.01, 115.47, 113.69, 111.12, 57.53, 55.85, 26.68; ESI-MS m/z [M + Na]+ for C26H23N3 Na O7S calculated: 544.1154, found: 544.11530.
4-Acetyl-2-methoxyphenyl-5-(4-chlorophenyl) 1-(4-sulfamoylphenyl)-1 H -
pyrazole-3-carboxylate (7i): Yellowish brown solid; yield (76%); mp: 71–74°C; IR (ATR) cm− 1; 1744 (COO-Ph), 1726 (CO-CH3), 1591 (C = C), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm):, 7.89 (d, J = 8.00 Hz, 2H, Ar-H), 7.86 (s, 1H, Ar-H), 7.80 (d, J = 9.00 Hz, 1H, Ar-H), 7.65 (d, J = 9.00 Hz, 1H, Ar-H), 7.57 (d, J = 10.00 Hz, 2H, Ar-H), 7.52 (s, 2H, SO2NH2), 7.47 (d, J = 8.00 Hz, 2H, Ar-H), 7.38 (s, 1H, pyrazole-H), 7.33 (d, J = 10.00 Hz, 2H, Ar-H), 3.84 (s, 3H, OCH3), 2.69 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.80, 162.85, 159.53, 144.43, 143.25, 143.15, 141.69, 136.56, 132.33, 129.46, 127.90, 127.43, 126.56, 126.09, 123.83, 122.31, 120.09, 112.31, 111.90, 57.14, 27.14; ESI-MS m/z [M-H]− for C25H20ClN3NaO6S calculated: 524.0689, found: 524.06882.
4-Acetyl-2-methoxyphenyl-5-(3,4-dimethoxyphenyl) 1-(4-sulfamoylphenyl)
-1 H -pyrazole-3-carboxylate (7j): Yellowish brown solid; yield (52%); mp: 75–78°C; IR (ATR) cm− 1; 1749(COO-Ph), 1727 (CO-CH3), 1579 (C = C), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 8.05 (d, J = 8.50 Hz, 2H, Ar-H), 7.96 (d, J = 7.50 Hz, 1H, Ar-H), 7.80 (s, 1H, Ar-H), 7.74 (d, J = 8.50 Hz, 2H, Ar-H), 7.69 (s, 2H, SO2NH2), 7.56 (d, J = 7.50 Hz, 1H, Ar-H), 7.50 (s, 1H, Ar-H), 7.10 (d, J = 7.50 Hz, 1H, Ar-H), 7.05 (s, 1H, pyrazole-H), 6.95 (d, J = 7.50 Hz, 1H, Ar-H), 3.99 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 2.75 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.75, 163.93, 151.47, 149.29, 148.89, 145.80, 144.68, 143.33, 142.86, 142.08, 136.04, 129.13, 127.41, 126.55, 125.27, 123.58, 122.29, 121.00, 112.90, 111.12, 109.84, 57.13, 56.74, 54.96, 27.17; ESI-MS m/z [M + Na]+ for C27H25N3NaO8S calculated: 574.1260, found: 574.12616.
4.1.6. General procedure for synthesis of (E)-4-(1-(hydroxyimino)ethyl)-2-methoxyphenyl 5-(4-substituted phenyl)-1-(4-substituted phenyl)-1H-pyrazole-3-carboxylate 8a-j.
A mixture of the appropriate ketone derivatives 7a-j (0.001 mol) and hydroxylamine hydrochloride (0.138 g, 0.002 mol) in 30 mL of absolute ethanol was heated under reflux for 8–12 h and then left to cool to room temperature. The separated solid was filtered off, washed with 10% ammonia solution, then with distilled water, dried, and crystallized from absolute ethanol, affording the target products 8a-j.
( E )-4-(1-(Hydroxyimino)ethyl)2-methoxyphenyl 1,5-diphenyl-1 H -pyrazole-3-carboxylate (8a): Yellowish brown solid; yield (67%); mp: 167–170°C; IR (ATR) cm− 1; 3191 (OH), 1756 (C = O), 1594 (C = C aromatic); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.30 (s, 1H, OH), 7.47 (s, 1H, Ar-H), 7.41–7.37 (m, 4H, Ar-H), 7.33–7.30 (m, 3H, Ar-H), 7.28–7.23 (m, 3H, Ar-H), 7.20 (s, 1H, pyrazole-H), 7.00 (d, J = 8.00 Hz, 1H, Ar-H), 6.78 (d, J = 8.00 Hz, 1H, Ar-H), 3.73 (s, 3H, OCH3), 2.06 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 160.07, 152.75, 148.50, 148.01, 144.05, 142.67, 139.72, 136.71, 132.58, 130.41, 129.62, 128.72, 127.84, 126.55,, 123.37, 119.35, 118.92, 116.26, 109.46, 56.24, 12.14; ESI-MS m/z [M + Na]+ for C25H21N3NaO4 calculated: 450.1430, found: 450.14238.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 1-phenyl-5- p -tolyl-
1 H -pyrazole-3-carboxylate (8b): Yellowish green powder; yield (75%); mp: 123–125°C; IR (ATR) cm− 1; 3138 (OH), 1736 (C = O), 1593 (C = C aromatic); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.36 (s, 1H, OH), 7.40–7.35 (m, 3H, Ar-H), 7.29 (s, 1H, Ar-H), 7.15–7.05 (m, 5H, 4 Ar-H, pyrazole-H), 6.96 (d, J = 7.50 Hz, 2H, Ar-H), 6.75 (d, J = 7.50 Hz, 2H, Ar-H), 3.74 (s, 3H, OCH3), 2.21 (s, 3H, Ph-CH3), 2.02 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 160.73, 153.20, 152.18, 151.13, 147.97, 147.97, 142.01, 139.43, 136.85, 129.81, 129.06, 128.64, 126.07, 124.01, 119.19, 116.09, 115.42, 111.97, 108.89, 56.78, 21.85, 11.83; ESI-MS m/z [M + H]+ for C26H24N3O4 calculated: 442.1761, found: 442.17438.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(4-methoxyphenyl) 1
-phenyl-1 H -pyrazole-3-carboxylate (8c): Yellowish brown powder; yield (75%); mp: 132–135°C; IR (ATR) cm− 1; 3400 (OH), 1739(C = O), 1590 (C = C aromatic); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.43 (s, 1H, OH), 7.47 (d, J = 8.50 Hz, 1H, Ar-H), 7.34 (d, J = 10.00 Hz, 2H, Ar-H), 7.25 (s, 1H, Ar-H), 7.18 (d, J = 10.00 Hz, 2H, Ar-H), 7.11–7.08 (m, 2H, Ar-H), 7.04 (s, 1H, pyrazole-H), 7.95 (d, J = 8.50 Hz, 1H, Ar-H), 6.80–6.77 (m, 3H, Ar-H), 3.68 (s, 3H, OCH3), 3.62 (s, 3H, OCH3), 2.02 (s, 3H, CH3); 13C NMR (100MHz, DMSO-d6) δ (ppm): 162.15, 159.58, 150.58, 147.22, 145.43, 143.76, 142.47, 140.80, 136.88, 130.90, 129.61, 127.83, 126.55, 123.18, 121.16, 120.61, 115.87, 114.57, 109.43, 56.74, 54.96, 14.71; ESI-MS m/z [M + H]+ for C26H24N3O5 calculated: 458.17160, found: 458.17154.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(4-chlorophenyl)-
1-phenyl-1 H -pyrazole-3-carboxylate (8d): Yellowish brown powder; yield (65%); mp: 106–109°C; IR (ATR) cm− 1; 3228 (OH), 1744 (C = O), 1593 (C = C aromatic); 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 10.90 (s, 1H, OH), 7.60 (d, J = 8.40 Hz, 1H, Ar-H), 7.42 (d, J = 10.00 Hz, 2H, Ar-H), 7.39 (d, J = 10 Hz, 2H, Ar-H), 7.36 (s, 1H, Ar-H), 7.26–7.21 (m, 3H, 2Ar-H, pyrazole-H), 7.00 (d, J = 8.00 Hz, 2H, Ar-H), 6.75 (d, J = 8.00 Hz, 2H, Ar-H), 3.74 (s, 3H, OCH3), 2.07 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 160.00, 153.68, 151.87, 147.38, 143.64, 142.89, 139.83, 139.48, 136.84, 134.19, 132.02, 131.01, 129.71, 128.38, 126.38, 123.19, 119.48, 115.55, 109.63, 55.38, 12.45; ESI-MS m/z [M + H]+ for C25H21ClN3O4 calculated: 462.11889, found: 462.11846.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(3,4-dimethoxy phenyl)-1-phenyl-1 H -pyrazole-3-carboxylate (8e): Yellowish white powder; yield (77%); mp: 115–118°C; IR (ATR) cm− 1; 3300 (OH), 1740 (C = O), 1593 (C = C aromatic); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.43 (s, 1H, OH), 7.56 (s, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 7.40 (d, J = 6.50 Hz, 1H, Ar-H), 7.25–7.19 (m, 4H, Ar-H), 7.01–6.98 (m, 2H, Ar-H), 7.16 (s, 1H, pyrazole-H), 6.79 (d, J = 8.50, 2H, Ar-H), 3.73 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 2.06 (s, 3H, CH3); 13C NMR (100MHz, DMSO-d6) δ (ppm): 161.75, 159.58, 153.64, 150.58, 150.19, 149.29, 148.01, 145.05, 144.15, 142.86, 139.50, 130.41, 127.84, 125.76, 121.67, 121.62, 121.41, 119.71, 115.86, 112.90, 109.84, 56.74, 55.85, 54.56, 11.65; ESI-MS m/z [M + H]+ for C27H24N2NaO6 calculated: 488.1816, found: 488.18086.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-phenyl-1-(4-sulfamoyl phenyl)-1 H -pyrazole-3-carboxylate (8f): Yellowish powder; yield (53%); mp:122–124°C; IR (ATR) cm− 1; 3681 (OH), 1744 (C = O), 1590 (C = C aromatic), 1165 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.17 (s, 1H, OH), 7.86 (d, J = 6.50 Hz, 2H, Ar-H), 7.55 (d, J = 6.5 Hz, 2H, Ar-H), 7.51 (s, 2H, SO2NH2),7.40–7.35 (m, 4H, Ar-H), 7.32–7.30 (m, 3H, Ar-H), 7.24 (s, 1H, Ar-H) 7.19 (s, 1H, pyrazole-H), 3.79 (s, 3H, OCH3), 2.06 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 165.53, 159.99, 153.18, 151.12, 145.63, 143.53, 142.52, 141.49, 139.80, 136.74, 130.18, 129.18, 127.77, 126.80, 123.77, 123.30, 118.83, 111.65, 109.60, 55.71, 12.56; ESI-MS m/z [M + Na]+for C25H22N4 Na O6S calculated: 529.1158, found: 529.1158.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 1-(4-sulfamoylphenyl)
-5- p -tolyl-1 H -pyrazole-3-carboxylate (8g): Yellowish white powder; yield (69%); mp: 195–197°C; IR (ATR) cm− 1; 3255(OH), 1740 (C = O), 1594 (C = C aromatic), 1164 (SO2NH2), 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.34 (s, 1H, OH), 7.95 (d, J = 7.50, 1H, Ar-H), 7.86 (d, J = 7.5 Hz, 2H, Ar-H), 7.68 (d, J = 7.50 Hz, 1H, Ar-H), 7.54 (d, J = 8.50 Hz, 2H, Ar-H), 7.52 (s, 2H, SO2NH2), 7.40 (s, 1H, Ar-H), 7.27 (s, 1H, pyrazole-H), 7.24–7.19 (m, 4H, Ar-H), 3.78 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.16 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 160.42, 153.19, 151.27, 145.80, 144.61, 142.05, 139.88, 139.41, 136.67, 130.21, 129.17, 127.98, 127.33, 126.51, 126.10, 123.30, 118.84, 111.67, 110.12, 56.45, 21.50, 12.56; ESI-MS m/z [M + Na]+ for C26H24N4NaO6S calculated: 543.1314, found: 543.13044.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (8h):Yellowish white powder; yield (49%), mp: 125–127°C; IR (ATR) cm− 1; 3400 (OH), 1742 (C = O), 1596 (C = C aromatic), 1165 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.27 (s, 1H, OH), 7.87(d, J = 8.50 Hz, 2H, Ar-H), 7.55 (d, J = 9.50 Hz, 2H, Ar-H), 7.51 (s, 2H, SO2NH2), 7.40 (s, 1H, Ar-H), 7.24–7.20 (m, 4H, Ar-H), 7.19 (s, 1H, pyrazole-H), 6.95 (d, J = 9.50 Hz, 2H, Ar-H), 3.79 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 2.16 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 161.75, 159.18, 153.97, 151.07, 145.93, 144.64, 143.75, 142.47, 139.90, 136.44, 130.41, 129.62, 127.78, 123.18, 122.03, 121.41, 118.82, 115.47, 111.11, 56.74, 55.85, 12.14; ESI-MS m/z [M + Na]+ for C26H24N4NaO7S calculated: 559.1263, found: 559.12740.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(4-chlorophenyl)-1-
(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (8i): Yellowish brown powder; yield (67%); mp:110–112°C; IR (ATR) cm− 1; 3371 (OH), 1743 (C = O), 1595 (C = C aromatic), 1161 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.44 (s, 1H, OH), 7.85 (d, J = 10.00 Hz, 2H, Ar-H), 7.76 (d, J = 6.50 Hz, 1H, Ar-H), 7.61 (s, 1H, Ar-H), 7.49 (s, 2H, SO2NH2), 7.40–7.33 (m, 4H, 3Ar-H, pyrazole-H), 7.26 (d, J = 10.00 Hz, 2H, Ar-H), 7.19 (d, J = 10.00 Hz, 2H, Ar-H), 3.71 (s, 3H, OCH3), 1.90 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 159.57, 150.82, 144.50, 144.38, 143.30, 141.53, 136.59, 134.61, 132.25,, 129.43, 128.25, 127.46, 126.50, 124.90, 123.26, 120.17, 119.66, 118.84, 109.89, 56.38, 11.76; ESI-MS m/z [M + 1]+ for C25H22ClN4O6S calculated: 541.0943, found: 541.09486.
( E )-4-(1-(Hydroxyimino)ethyl)-2-methoxyphenyl 5-(3,4-dimethoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxylate (8j): Yellowish powder; yield (48%); mp: 129–131°C; IR (ATR) cm− 1; 3300 (OH), 1731(C = O), 1595 (C = C aromatic); 1164 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.26 (s, 1H, OH), 7.87 (d, J = 9.00 Hz, 2H, Ar-H), 7.85 (d, J = 9.00 Hz, 2H, Ar-H), 7.52 (s, 2H, SO2NH2), 7.41 (s, 1H, Ar-H), 7.32 (s, 1H, Ar-H), 7.25–7.24 (m, 1H, Ar-H), 6.93 (d, J = 8.50 Hz, 1H, Ar-H), 6.88 (s, 1H, pyrazole-H), 6.81–6.75 (m, 2H, Ar-H), 3.79 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 3.60 (s, 3H, OCH3), 2.17 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 167.78, 159.18, 152.75, 149.29, 148.50, 145.44, 144.65, 143.36, 141.58, 140.30, 136.44, 132.58, 129.12, 127.83, 126.15, 122.30, 121.40, 119.33, 112.91, 110.73, 109.84, 56.28, 56.06, 55.89, 11.75; ESI-MS m/z [M + Na]+ for C27H26N4NaO8S calculated: 589.1369, found: 589.13803.
4.1.7. General procedure for synthesis of N-(4-acetylphenyl)-5-(4-subistitutedphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxamide 9a-c.
To the suspension of 1,5-diarylpyrazole carboxylic acid derivatives 6f, 6h and 6j (0.001 mol) in 20 mL of benzene, thionyl chloride (2 mL) was added and heated under reflux for 4 h. Evaporation of the solvent was carried out under vacuum to give a residue of the corresponding acyl chloride that was utilized in the following steps without purification. A mixture of acyl chloride in dry DMF, few drops of triethylamine and 4-aminoacetophenone (0.270 g, 0.002 mol) were heated under reflux for 8h. Then, 20 mL of cold distilled water was added, followed by acidification with dil. HCl and extraction twice with ethyl acetate. Purification was performed by column chromatography using chloroform: methanol 98:2 as eluent to afford compounds 9a-c [64].
N -(4-Acetylphenyl)-5-phenyl-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxamide (9a): Yellowish brown solid; yield (88%); mp: 81–83°C; IR (ATR) cm− 1; 1725 (CO-CH3), 1675 (CONH), 1591 (C = C aromatic), 1161 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.53 (s, 1H, NH), 7.96 (d, J = 9.00 Hz, 2H, Ar-H), 7.86 (d, J = 9.00 Hz, 2H, Ar-H), 7.68–7.62 (m, 3H, Ar-H), 7.57 (d, J = 9.00 Hz, 2H, Ar-H), 7.49 (s, 2H, SO2NH2), 7.40 (d, J = 9.00 Hz, 2H, Ar-H), 7.30–7.32 (m, 2H, Ar-H), 7.20 (s, 1H, pyrazole-H), 2.52 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.09, 167.91, 154.18, 145.63, 144.56, 143.96, 142.53, 133.27, 132.23, 131.21, 129.83, 127.84, 125.96, 125.26, 120.60, 119.04, 109.61, 26.95; ESI-MS m/z [M + Na]+ for C24H20N4 NaO4S calculated: 483.1103, found: 483.11090.
N -(4-Acetylphenyl)-5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -
pyrazole-3-carboxamide (9b):Yellowish brown solid; yield (66%); mp: 74–76°C; IR (ATR) cm− 1; 1715 (CO-CH3),1681 (CONH), 1594 (C = C aromatic), 1160 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 11.18 (s, 1H, NH), 7.87 (d, J = 7.60 Hz, 2H, Ar-H), 7.84 (d, J = 7.6.0 Hz, 2H, Ar-H), 7.80 (d, J = 9.00 Hz, 2H, Ar-H), 7.62 (d, J = 9.00 Hz, 2H, Ar-H), 7.54 (s, 2H, SO2NH2), 7.33 (s, 1H, pyrazole-H), 6.98 (d, J = 7.60 Hz, 2H, Ar-H), 6.96 (d, J = 7.60 Hz, 2H, Ar-H), 3.82 (s, 3H, OCH3), 2.47 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 195.96, 167.20, 154.55, 146.06, 144.59, 142.88, 133.27, 132.59, 131.09, 130.12, 129.18, 126.18, 125.30, 123.46, 120.64, 118.98, 113.06, 55.42, 26.61; ESI-MS m/z [M-H]− for C25H21N4O5S calculated: 489.1238, found: 489.12547.
N -(4-Acetylphenyl)-5-(3,4-dimethoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -
pyrazole-3-carboxamide (9c): Brownish solid; yield (60%); mp: 81–83°C; IR (ATR) cm− 1; 1720 (CO-CH3), 1669 (CONH), 1590 (C = C aromatic), 1160 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.55 (s, 1H, NH), 7.95 (s, 1H, Ar-H), 7.92 (d, J = 9.00 Hz, 2H, Ar-H), 7.84 (d, J = 7.50 Hz, 2H, Ar-H), 7.76 (d, J = 8.50 Hz, 1H, Ar-H), 7.72 (d, J = 9.00 Hz, 2H, Ar-H), 7.62–7.56 (m, 4H, 2 Ar-H, SO2NH2), 7.37 (s, 1H, pyrazole-H), 7.01 (d, J = 8.50 Hz, 1H, Ar-H), 3.82 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 2.53 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 197.06, 164.12, 153.21, 152.80, 150.42, 148.06, 145.60, 143.23, 142.71, 132.93, 130.56, 129.86, 129.15, 126.10, 124.03, 123.54, 119.19,116.49, 110.95, 56.76, 55.71, 26.62; ESI-MS m/z [M-H]− for C26H23N4O6S calculated: 519.1344, found: 519.13451.
4.1.8. General procedure for synthesis of (E)-N-(4-(1-(hydroxyimino)ethyl)
phenyl)-5-(4-subistituted phenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-
carboxamide 10a-c.
A mixture of the appropriate ketone derivatives 9a-c (0.001 mol) and hydroxylamine hydrochloride (0.138 g, 0.002 mol) in 30 mL of absolute ethanol was heated under reflux for 8–12 h and then left to cool to room temperature. The separated solid was filtered off, washed with 10% ammonia solution, then washed with distilled water, dried, and recrystallized from absolute ethanol to afford the target products 10a-c.
( E )- N -(4-(1-(Hydroxyimino)ethyl)phenyl)-5-phenyl-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxamide (10a):Yellowish powder; yield (55%); mp: 168–170°C ; IR (ATR) cm− 1; 3681 (OH), 1680 (CONH), 1598 (C = C aromatic), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.30 (s, 1H, NH), 8.75 (s, 1H, OH), 7.79 (d, J = 8.00 Hz, 2H, Ar-H), 7.63 (d, J = 8.00 Hz, 2H, Ar-H), 7.50–7.56 (m, 3H, Ar-H), 7.47–7.44 (m, 2H, Ar-H), 7.40 (s, 2H, SO2NH2), 7.35 (d, J = 10.00 Hz, 2H, Ar-H), 7.29 (s, 1H, pyrazole-H), 7.21 (d, J = 10.00 Hz, 2H, Ar-H), 2.06 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 160.05, 153.24, 151.71, 148.09, 143.55, 141.92, 133.69, 129.88, 129.39, 129.30, 127.44, 126.52, 126.42, 121.34, 120.78, 120.33, 109.58, 12.14; ESI-MS m/z [M + H]+ for C24H22N5O4S calculated: 476.1387, found: 476.13970.
( E )- N -(4-(1-(Hydroxyimino)ethyl)phenyl)-5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxamide (10b): Yellowish brown powder; yield (51%); mp: 110–112°C; IR (ATR) cm− 1; 3350 (OH), 1677 (CONH), 1596 (C = C aromatic), 1162 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.31 (s, 1H, NH), 10.02 (s, 1H, OH), 7.84 (d, J = 8.00 Hz, 2H, Ar-H), 7.78 (d, J = 8.50 Hz, 2H, Ar-H), 7.52 (d, J = 8.50 Hz, 2H, Ar-H), 7.46 (d, J = 9.00 Hz, 2H, Ar-H), 7.41 (s, 2H, SO2NH2), 7.30 (s, 1H, pyrazole-H), 6.97 (d, J = 8.00 Hz, 2H, Ar-H), 6.91 (d, J = 9.00 Hz, 2H, Ar-H), 3.80 (s, 3H, CH3), 2.07 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 167.18, 155.50, 144.08, 142.51, 133.80, 132.35, 131.38, 130.65, 129.47, 127.11, 126.41, 126.09, 125.97, 123.46, 121.51, 114.33, 111.98, 56.12, 17.34; ESI-MS m/z [M-H]− for C25H22N5O5S calculated: 504.1347, found: 504.13773.
( E )-5-(3,4-Dimethoxyphenyl)- N -(4-(1-(hydroxyimino)ethyl)phenyl)-1-
(4-sulfamoylphenyl)-1 H -pyrazole-3-carboxamide (10c):Brownish powder; yield (44%), mp: 105–107°C; IR (ATR) cm− 1; 3220 (OH), 1680 (CONH), 1591 (C = C aromatic), 1161 (SO2NH2); 1H-NMR (500 MHz, DMSO-d6) δ (ppm): 10.36 (s, 1H, NH), 10.09 (s, 1H, OH), 7.92 (s, 1H, Ar-H), 7.79 (d, J = 7.50 Hz, 1H, Ar-H), 7.63 (d, J = 8.50 Hz, 2H, Ar-H), 7.52 (d, J = 7.50 Hz, 2H, Ar-H), 7.50–7.44 (m, 4H, 2ArH, SO2NH2), 7.36 (d, J = 8.50 Hz, 2H, Ar-H), 7.27 (s, 1H, pyrazole-H), 6.99 (d, J = 7.50 Hz, 1H, Ar-H), 3.77 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 2.08 (s, 3H, CH3); 13C-NMR (100MHz, DMSO-d6) δ (ppm): 167.78, 159.18, 152.75, 149.29, 148.50, 145.44, 144.65, 143.36, 140.30, 136.44, 132.58, 129.12, 127.83, 126.15, 122.30, 121.40, 119.33, 112.91, 109.84, 56.19, 55.96, 12.14; ESI-MS m/z [M-H]− for C26H24N5O6S calculated: 534.14473, found: 534.14307.