Organic & Biomolecular Chemistry
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mixture was refluxed under stirring for 8 h, stored at 4–5 °C for (300 MHz, DMSO) δ: 2.50 (s, 3H), 3.58–3.61 (m, 3H), 3.93 (d,
24 h, and the precipitate formed was filtered off, then washed J = 2.04 Hz, 3H), 5.68 (d, J = 6.93 Hz, 1H), 7.01 (d, J = 2.19 Hz,
with cool ethanol. The synthesized compound was purified by 1H), 7.31 (t, J = 2.01 Hz, 2H), 7.65 (d, J = 2.19 Hz, 1H), 7.83 (t,
crystallization from ethanol in a refrigerator and allowed to J = 7.13 Hz, 2H), 9.79 (s, 1H), MS (ESI): 701 (C25H18Br2F3N4O6,
air-dry to obtain the 4,5-dihydropyrazole derivatives.
[M + H]+). Anal C25H17Br2F3N4O6. Calcd for: C, 42.76; H, 2.44;
N, 7.98. Found: C, 42.58; H, 2.29; N, 7.91%.
4.5. General method of synthesis of compounds (4a–4t)
4.5.6. (E)1-(5-(3,5-Dichloro-2-(2,6-dinitro-4-(trifluoromethyl)-
To a solution of pyrazoline derivatives (1 mmol) in dichloro- phenoxy)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-
methane (5 mL) acetic acid (5 mL) was added, together with 1-yl)ethanone (4f). White solid, mp: 198–200 °C. 1H NMR
EDC (1.2–1.5 mmol) and HOBt (1.2–1.5 mmol). The mixture (300 MHz, DMSO) δ: 2.19 (s, 3H), 3.45 (d, J = 2.04 Hz, 4H), 4.33
was refluxed under stirring for 8 h. After completion of the (s, 2H), 7.61 (d, J = 2.19 Hz, 1H), 7.78 (t, J = 2.01 Hz, 2H),
reaction, the contents were cooled, and then evaporated to 8.16–8.26 (m, 2H), 10.92 (s, 2H), 11.52 (d, J = 12.78 Hz, 1H),
dryness in vacuo. Aqueous hydrochloric acid (0.1 M, 30 mL) was MS (ESI): 701 (C25H18Cl2F3N4O6, [M
+
H]+). Anal
added and the mixture extracted with ethyl acetate (3 × 5 mL). C25H17Cl2F3N4O6. Calcd for: C, 48.96; H, 2.79; N, 9.13. Found:
The combined ethyl acetate layers were back-extracted with satu- C, 48.88; H, 2.72; N, 9.11%.
rated sodium bicarbonate (3 × 5 mL) and brine (3 × 5 mL), dried
over MgSO4, filtered, and evaporated in vacuo. The residue was phenoxy)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-
crystallized from ethanol to obtain the target compounds.
1-yl)ethanone (4g). White solid, mp: 245–247 °C. 1H NMR
4.5.7. (E)1-(5-(5-Bromo-2-(2,6-dinitro-4-(trifluoromethyl)-
4.5.1. (E)1-(5-(3,5-Dibromo-2-(2,6-dinitro-4-(trifluoromethyl)- (300 MHz, DMSO) δ: 2.28 (s, 3H), 3.75 (d, J = 12.06 Hz, 4H),
phenoxy)phenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone 3.97–4.06 (m, 2H), 5.51–5.56 (m, 1H), 6.77 (d, J = 8.61 Hz, 1H),
1
(4a). White solid, mp: 203–205 °C. H NMR (300 MHz, DMSO) 6.88 (s, 1H), 6.97 (d, J = 8.79 Hz, 2H), 7.18–7.22 (m, 1H), 7.67
δ: 1.98 (s, 3H), 2.33 (d, J = 6.42 Hz, 3H), 3.76–3.83 (m, 1H), (d,
J = 8.79 Hz, 2H), 9.96 (s, 1H), MS (ESI): 701
3.99–4.06 (m, 2H), 5.64–5.69 (m, 1H), 7.00 (d, J = 2.19 Hz, 1H), (C25H19BrF3N4O7, [M + H]+). Anal C25H18BrF3N4O7. Calcd for:
7.30 (t, J = 8.78 Hz, 2H), 7.65 (t, J = 6.30 Hz, 1H), 7.80–7.85 (m, C, 48.17; H, 2.91; N, 8.99. Found: C, 48.28; H, 2.92; N, 9.11%.
2H), 9.85 (s, 1H), MS (ESI): 685 (C25H18Br2F3N4O6, [M + H]+).
4.5.8. (E)1-(5-(5-Chloro-2-(2,6-dinitro-4-(trifluoromethyl)-
Anal C25H17Br2F3N4O6. Calcd for: C, 43.76; H, 2.50; N, 8.16. phenoxy)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-
Found: C, 43.68; H, 2.45; N, 8.21%.
1-yl)ethanone (4h). White solid, mp: 255–257 °C. 1H NMR
4.5.2. (E)1-(5-(3,5-Dichloro-2-(2,6-dinitro-4-(trifluoromethyl)- (300 MHz, DMSO) δ: 2.34 (d, J = 18.84 Hz, 3H), 3.76 (t, J =
phenoxy)phenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone 10.98 Hz, 4H), 3.99 (s, 2H), 5.56 (d, J = 7.68 Hz, 1H), 6.82 (t, J =
(4b). White solid, mp: 245–247 °C. 1H NMR (300 MHz, DMSO) 11.34 Hz, 2H), 6.99 (d, J = 8.79 Hz, 2H), 7.10 (d, J = 8.79 Hz,
δ: 2.00 (s, 3H), 2.50 (t, J = 1.83 Hz, 3H), 3.40 (s, 1H), 4.42 (J = 1H), 7.70 (d, J = 8.61 Hz, 2H), 9.99 (s, 1H), MS (ESI): 579
4.56 Hz, 2H), 5.66 (m, 1H), 7.57–7.64 (m, 3H), 7.74–7.78 (m, (C25H19ClF3N4O7, [M + H]+). Anal C25H18ClF3N4O7. Calcd for:
1H), 8.28 (m, 1H), 11.98 (m, 1H), 12.40 (s, 1H), MS (ESI): 597 C, 51.87; H, 3.13; N, 9.68. Found: C, 51.78; H, 3.02; N, 9.71%.
(C25H18Cl2F3N4O6, [M + H]+). Anal C25H17Cl2F3N4O6. Calcd for:
C, 50.27; H, 2.87; N, 9.38. Found: C, 49.98; H, 2.85; N, 9.31%.
4.5.9. (E)1-(5-(3,5-Dibromo-2-(2,6-dinitro-4-(trifluoromethyl)-
phenoxy)phenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-
4.5.3. (E)1-(5-(5-Bromo-2-(2,6-dinitro-4-(trifluoromethyl)- ethanone (4i). White solid, mp: 199–201 °C. 1H NMR
phenoxy)phenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (300 MHz, DMSO) δ: 2.41 (d, J = 18.84 Hz, 3H), 3.77 (s, 2H),
1
(4c). White solid, mp: 245–247 °C. H NMR (300 MHz, DMSO) 3.83 (d, J = 7.68 Hz, 1H), 5.65–5.70 (m, 1H), 7.01 (s, 1H), 7.30
δ: 1.98 (s, 3H), 2.32 (d, J = 7.14 Hz, 3H), 3.72–3.82 (m, 1H), (t, J = 8.87 Hz, 2H), 7.64 (d, J = 2.19 Hz, 1H), 7.83 (t, J = 8.61
3.99–4.06 (m, 2H), 5.54–5.59 (m, 1H), 6.79 (d, J = 8.61 Hz, 1H), Hz, 2H), 9.79 (s, 1H), MS (ESI): 689 (C25H15Br2F4N4O6,
6.91 (d, J = 2.01 Hz, 1H), 7.21–7.26 (m, 3H), 7.65 (d, J = [M + H]+). Anal C25H14Br2F4N4O6. Calcd for: C, 41.76; H, 2.04;
7.86 Hz, 2H), 9.99 (s, 1H), MS (ESI): 607 (C25H19BrF3N4O6, N, 8.12. Found: C, 41.78; H, 2.02; N, 8.11%.
[M + H]+). Anal C25H18BrF3N4O6. Calcd for: C, 49.44; H, 2.99;
N, 9.23. Found: C, 49.38; H, 2.95; N, 9.21%.
4.5.10. (E)1-(5-(3,5-Dichloro-2-(2,6-dinitro-4-(trifluoromethyl)-
phenoxy)phenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-
4.5.4. (E)1-(5-(5-Chloro-2-(2,6-dinitro-4-(trifluoromethyl)- ethanone (4j). White solid, mp: 213–215 °C. 1H NMR
phenoxy)phenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (300 MHz, DMSO) δ: 2.43 (d, J = 2.19 Hz, 3H), 3.79 (d, J = 2.19
(4d). White solid, mp: 260–262 °C. 1H NMR (300 MHz, DMSO) Hz, 2H), 3.85 (d, J = 8.87 Hz, 1H), 5.70 (s, 1H), 7.04 (s, 1H),
δ: 1.99 (s, 3H), 2.35 (d, J = 2.04 Hz, 3H), 3.72–3.82 (m, 1H), 7.32 (d, J = 8.87 Hz, 2H), 7.67 (t, J = 2.19 Hz, 1H), 7.85 (d, J =
3.99–4.06 (m, 2H), 5.54–5.59 (m, 1H), 6.87 (d, J = 3.69 Hz, 1H), 8.87 Hz, 2H), 9.92 (s, 1H), MS (ESI): 601 (C25H15Cl2F4N4O6,
6.96 (d, J = 2.01 Hz, 1H), 7.24 (s, 3H), 7.69 (d, J = 2.07 Hz, 2H), [M + H]+). Anal C25H14Cl2F4N4O6. Calcd for: C, 47.94; H, 2.35;
9.93 (s, 1H), MS (ESI): 563 (C25H19ClF3N4O6, [M + H]+). Anal N, 9.32. Found: C, 47.78; H, 2.32; N, 9.21%.
C25H18ClF3N4O6. Calcd for: C, 53.34; H, 3.22; N, 9.95. Found:
C, 53.38; H, 3.19; N, 9.91%.
4.5.11. (E)1-(5-(5-Bromo-2-(2,6-dinitro-4-(trifluoromethyl)-
phenoxy)phenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-
4.5.5. (E)1-(5-(3,5-Dibromo-2-(2,6-dinitro-4-(trifluoromethyl)- ethanone (4k). White solid, mp: 215–217 °C. 1H NMR
phenoxy)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol- (300 MHz, DMSO) δ: 2.30 (s, 3H), 3.89 (d, J = 8.4 Hz, 2H), 3.95
1-yl)ethanone (4e). White solid, mp: 245–247 °C. 1H NMR (s, 1H), 5.75 (s, 1H), 6.79 (t, J = 7.13 Hz, 1H), 7.06 (d, J =
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Org. Biomol. Chem., 2014, 12, 998–1008 | 1005