Melting points were taken on slides in an electrical apparatus Labindia visual melting range apparatus and are uncorrected. The IR spectra were obtained with a Buck Scientific IR M-500 spectrophotometer. The 1H NMR spectra were recorded on a Bruker (300 MHz) spectrometer using tetramethylsilane as an internal standard. All the compounds gave satisfactory analytical results (within 0.4% of the theoretical values). The starting material 4-formylpyrazoles 2 were prepared by the literature method [32].
2-((3-Aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines (3)
General procedure: To the ethanolic solution of 2-pyridylhydrazine (1, 0.01 mol) was added appropriate 4-formylpyrazole (2, 0.01 mol), and the solution was refluxed for 4-5 min. The solvent was evaporated in vacuo to half its volume and cooled to room temperature. The solid obtained was filtered and washed with ethanol.
2-((1,3-Diphenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3a)
Yield 96%, Mp 210°C, IR (νmax, KBr): 3190 cm-1 (-NH str.); 1H NMR (DMSO-d
6, 300 MHz): δ 6.71-6.74 (m, 1H), 7.18-7.21 (m, 1H, J = 9 Hz), 7.34-7.39 (m, 1H), 7.47-7.63 (m, 6H), 7.74-7.77 (m, 2H), 7.98-8.01 (m, 2H), 8.07-8.09 (d, 1H, J = 6 Hz), 8.17(s, 1H, N=CH), 8.93(s, 1H), 10.66 (bs, 1H, exchangeable with D2O); Anal. Calculated for C21H17N5: C 74.32, H 5.05, N 20.63; Found: C 74.35, H 5.04, N 20.64; ESI-MS m/z: 340.06 [M + 1]+.
2-((1-Phenyl-3-p-tolyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3b)
Yield 94%, Mp 206°C, IR (νmax, KBr): 3194 cm-1 (-NH str.); 1H NMR (DMSO-d
6
, 300 MHz): δ 2.40 (s, 3H), 6.73-6.74 (m, 1H), 7.20-7.23 (d, 1H, J = 9 Hz), 7.32-7.38 (m, 3H), 7.51-7.59 (d, 2H, J = 9 Hz), 7.62-7.65 (m, 3H), 7.98-8.09 (m, 3H), 8.15 (s, 1H), 8.93(s, 1H, N=CH), 10.69 (bs, 1H, exchangeable with D2O); Anal. Calculated for C22H19N5: C 74.77, H 5.42, N 19.82; Found: C 74.79, H 5.45, N 19.79; ESI-MS m/z: 354.12 [M + 1]+
2-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3c)
Yield 89%, Mp 208°C, IR (νmax, KBr): 3189 cm-1 (-NH str.); 1H NMR (DMSO-d
6
, 300 MHz): δ 3.84(s, 3H), 6.70-6.74 (m, 1H), 7.07-7.10 (d, 2H, J = 9 Hz), 7.19-7.22 (m, 1H), 7.45-7.38 (m, 1H), 7.51-7.64 (m, 3H), 7.67-7.70 (d, 2H, J = 9 Hz), 7.97-8.00 (m, 2H), 8.07-8.09 (d, 1H, J = 6 Hz), 8.14 (s, 1H, N=CH), 8.91(s, 1H), 10.67 (bs, 1H, exchangeable with D2O); Anal. Calculated for C22H19N5O: C 71.53, H 5.18, N 18.96; Found: C 71.53, H 5.20, N 18.92; ESI-MS m/z: 370.08 [M + 1]+.
2-((3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3d)
Yield 90%, Mp 224°C, IR (νmax, KBr): 3198 cm-1 (-NH str.); 1H NMR (DMSO-d
6
, 300 MHz): δ 6.71-6.75 (m, 1H), 7.14-7.17 (m, 1H), 7.33-7.39 (m, 3H), 7.52-7.63 (m, 3H), 7.79-7.84 (d, 2H, J = 9 Hz), 7.97-8.00 (d, 2H, J = 9 Hz), 8.08-8.09 (d, 1H, J = 3 Hz), 8.15 (s, 1H, N=CH), 8.93 (s, 1H), 10.66 (bs, 1H, exchangeable with D2O); Anal. Calculated for C21H16FN5: C 70.58, H 4.51, N 19.60; Found: C 70.59, H 4.53, N 19.58; ESI-MS m/z: 358.10 [M + 1]+.
2-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3e)
Yield 90%, Mp 232°C, IR (νmax, KBr): 3200 cm-1 (-NH str.); 1H NMR (DMSO-d
6, 300 MHz): δ 6.70-6.74 (m, 1H), 7.13-7.15 (m, 1H), 7.34-7.39 (m, 1H), 7.52-7.62 (m, 5H), 7.79-7.82 (d, 2H, J = 9 Hz), 7.96-7.99 (d, 2H, J = 9 Hz), 8.07-8.09 (d, 1H, J = 6 Hz), 8.15 (s, 1H, N=CH), 8.91 (s, 1H), 10.64 (bs, 1H, exchangeable with D2O); Anal. Calculated for C21H16ClN5: C 67.47, H 4.31, N 18.73; Found: C 67.41, H 4.30, N 18.75; ESI-MS m/z: 374.10 [M + 1]+, 376.10 [M + 3]+.
2-((3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3f)
Yield 91%, Mp 236°C, IR (νmax, in KBr): 3203 cm-1 (-NH str.); 1H NMR (DMSO-d
6
, 300 MHz): δ 6.69-6.73 (m, 1H), 7.12-7.14 (m, 1H), 7.35-7.38 (m, 1H), 7.50-7.59 (m, 3H), 7.71 (m, 4H), 7.95-7.98 (d, 2H, J = 8.1 Hz), 8.06-8.07 (d, 1H, J = 4.5 Hz), 8.12 (s, 1H, N=CH), 8.93(s, 1H), 10.67 (bs, 1H, exchangeable with D2O); Anal. Calculated for C21H16BrN5: C 60.30, H 3.86, N 16.74; Found: C 60.28, H 3.83, N 16.77; ESI-MS m/z: 385.12 ([M + 1]+, 387.02 [M + 3]+.
2-((3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazine (3g)
Yield 92%, Mp 234°C, IR (νmax, in KBr): 3195 cm-1 (-NH str.) 1335, 1504 (-NO2); 1H NMR (DMSO-d
6
, 300 MHz): δ 6.72-6.76 (m, 1H), 7.12-7.15 (m, 1H), 7.38-7.42 (m, 1H), 7.54-7.63 (m, 3H), 8.00-8.03 (m, 2H, J = 9 Hz), 8.08-8.11 (m, 3H), 8.20 (s, 1H, N=CH), 8.36-8.39 (d, 2H, J = 9 Hz), 9.01 (s, 1H), 10.76 (bs, 1H, exchangeable with D2O); Anal. Calculated for C21H16N6O2: C 65.62, H 4.20, N 21.86; Found: C 65.64, H 4.26, N 21.85; ESI-MS m/z: 267.06 [M + 1]+.
Synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines (4)
General procedure: To a suspension/solution of 3 (0.010 mol) in dichloromethane (25 mL), IBD (0.011 mol) was added in small portions, and the reaction mixture was stirred overnight. Then, the solvent was evaporated on water bath. To the resulting residue was added ethanol (5-10 mL), and the mixture was warmed to obtain a clear solution. On cooling at room temperature, solid separated out was filtered and washed with cold alcohol to give pure fused 1,2,4-triazole derivatives 4a-g.
(1,3-Diphenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4a)
Yield 90%, Mp 162°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 6.89-6.94 (m, 1H), 7.33-7.35 (m, 3H), 7.38-7.45 (m, 2H), 7.54-7.63 (m, 4H), 7.84-7.87 (s, 1H), 7.99-8.05 (m, 2H), 8.15-8.17 (d, 1H, J = 6 Hz), 9.16 (s, 1H); Anal. Calculated for C21H15N5: C 74.76, H 4.48, N 20.76; Found: C 74.77, H 4.45, N 20.73; ESI-MS m/z: 338.09 [M + 1]+.
3-(1-Phenyl-3-p-tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4b)
Yield 88%, Mp 210°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 2.28 (s, 3H) 6.89-6.93 (m, 1H), 7.13-7.16 (m, 2H), 7.38-7.44 (m, 4H), 7.57-7.62 (m, 2H), 7.80-7.84 (m, 1H), 8.01-8.03 (d, 2H, J = 6 Hz), 8.12-8.14 (d, 1H, J = 6 Hz), 9.13 (s, 1H); Anal. Calculated for C22H17N5: C 75.19, H 4.88, N 19.93; Found: C 75.18, H 4.86, N 19.96; ESI-MS m/z: 352.11 [M + 1]+.
3-(3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4c)
Yield 82%, Mp 164°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 3.73 (s, 3H) 6.89-6.94 (m, 3H), 7.36-7.40 (m, 2H), 7.47-7.49 (m, 2H), 7.56-7.61 (m, 2H), 7.80-7.87 (m, 1H), 7.95-8.02 (m, 2H), 8.14-8.16 (m, 1H), 9.12 (s, 1H); Anal. Calculated for C22H17N5O: C 71.92, H 4.66, N 19.06; Found: C 71.91, H 4.64, N 19.07; ESI-MS m/z: 368.06 [M + 1]+.
3-(3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4d)
Yield 85%, Mp 193°C, IR (νmax, KBr): transparent in the region of -NH st.; 1H NMR (DMSO-d
6
, 300 MHz): δ 6.92-6.97 (m, 1H), 7.17-7.23 (m, 2H), 7.39-7.44 (m, 2H), 7.57-7.68 (m, 4H), 7.85-7.88 (m, 1H), 8.02-8.05 (d, 2H, J = 9 Hz), 8.24-8.26 (d, 1H, J = 6 Hz), 9.19 (s, 1H); Anal. Calculated for C21H14FN5: C 70.98, H 3.97, N 19.71; Found: C 70.98, H 3.99, N 19.69; ESI-MS m/z: 356.08 [M + 1]+.
3-(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4e)
Yield 89%, Mp 133°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 6.93-6.98 (m, 1H), 7.41-7.45 (m, 4H), 7.57-7.64 (m, 4H), 7.85-7.88 (m, 1H), 8.02-8.04 (d, 2H, J = 6 Hz), 8.25-8.27 (d, 1H, J = 6 Hz), 9.19 (s, 1H); Anal. Calculated for C21H14ClN5: C 67.83, H 3.80, N 18.84; Found: C 67.81, H 3.84, N 18.80; ESI-MS m/z: 372.01 [M + 1]+, 374.06 [M + 3]+.
3-(3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4f)
Yield 84%, Mp 140°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 6.92-6.96 (m, 1H), 7.38-7.43 (m, 2H), 7.54-7.60 (m, 6H), 7.83-7.86 (m, 1H), 7.99-8.02 (d, 2H, J = 8.1 Hz), 8.23-8.26 (d, 1H, J = 6.9 Hz), 9.17 (s, 1H); Anal. Calculated for C21H14BrN5: C 60.59, H 3.39, N 16.82; Found: C 60.56, H 3.37, N 16.81; ESI-MS m/z: 416.04 [M + 1]+, 418.06 [M + 3]+.
3-(3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine (4g)
Yield 89%, Mp 242°C, IR (νmax, KBr): transparent in the region of -NH str.; 1H NMR (DMSO-d
6
, 300 MHz): δ 6.82-6.86 (m, 1H), 7.34-7.41 (m, 1H), 7.44-7.46 (m, 1H), 7.55-7.60 (m, 3H), 7.83-7.87 (m, 3H), 7.92-7.94 (d, 2H, J = 6 Hz), 8.14-8.17 (d, 2H, J = 9 Hz), 8.71 (s, 1H); Anal. Calculated for C21H14N6O2: C 65.96, H 3.69, N 21.98; Found: C 65.97, H 3.67, N 21.94; ESI-MS m/z: 383.10 [M + 1]+.