Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives
Abstract
:1. Introduction
2. Results and Discussions
3. Materials and Methods
3.1. General Information
3.2. Synthesis
- Method A (Reflux)
- (a)
- A mixture of 2-acetylcyclohexanone (1, 1 mmol), and hydrazines 2 (1.0 mmol) in DMF (10 mL) was heated under reflux for 6–8 h. The precipitated solid product was filtered, washed with ethanol (EtOH), dried and finally recrystallized from DMF.
- (b)
- 2-Acetylcyclohexanone (1, 1 mmol) and hydrazines 2 (1.0 mmol) in AcOH (10 mL) were stirred at 80 °C for the given times. After completion of the reaction, the mixture was cooled to room temperature and the precipitate was filtered and purified by recrystallization from EtOH.
- Method B (MW)
3.3. X-ray Crystallography
3.4. Biological Activity
3.4.1. Measurement of DPPH Radical Scavenging Activity
3.4.2. Measurement of ABTS Radical Scavenging Activity
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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- Sample Availability: Samples of the compounds 3a–f are available from the authors.
Compound | R | Reflux | Microwave (MW) | M.p. °C | ||
---|---|---|---|---|---|---|
DMF | Acid Acetic | 300 W/150 °C | ||||
Time Reaction (h)/Yield (%) | Time Reaction (min)/Yield (%) | |||||
3a | H | 6/55 | 2/28 | 2 | 90 | Oil |
3b | C6H5 | 5/60 | 2.5/46 | 2 | 90 | Oil |
3c | 4-BrC6H4 | 7/47 | 3/41 | 2 | 90 | 150–152 |
3d | 4-CNC6H4 | 6/28 | 2/22 | 2 | 37 | 178–180 |
3e | 4-CO2HC6H4 | 8/33 | 2/25 | 2 | 40 | 133–135 |
3f | 4-FC6H4 | 7/61 | 3.5/43 | 2 | 98 | 118–120 |
Entry | Reaction Temperature °C | Reaction Time (min) | Isolated Yield (%) |
---|---|---|---|
1 | 80 | 5 | - |
2 | 100 | 4 | 32 |
3 | 120 | 4 | 53 |
4 | 150 | 2 | 90 |
5 | 180 | 5 | 90 |
Compound | C15H17N2O2, H2O |
---|---|
Crystal shape, color | Polyhedron, yellow |
Crystal size (mm) | 0.32 × 0.12 × 0.10 |
Crystal system, Space group | Monoclinic, P21/n (N°14) |
a (Å) | 10.704 (2) |
b (Å) | 10.106 (2) |
c (Å) | 13.735 (3) |
β (°) | 95.35 (3) |
V (Å3) | 1479.3 (5) |
Z | 4 |
Wavelength, Mo Kα (Å) | 0.71073 |
T (K) | 297 (2) |
F(000) | 580 |
θ-range (°) | 2.50 < θ < 25.0 |
hkl-range | −12:12, −12:11, −16:16 |
μ (mm−1) | 0.086 |
Reflections collected/Rint/Rσ | 10,360/0.099/0.0909 |
Reflections unique/ parameters | 2588/ 412 |
R1, wR2 [F2 > 2σ (F2)] | 0.0586, 0.0927 |
Goodness-of-Fit on F2 (GooF = S) | 1.106 |
Residual electron density ∆ρmax/∆ρmin (e Å−3) | 0.15/−0.11 |
Compound/(µg/mL) | 100 | 50 | 10 | IC50 |
---|---|---|---|---|
3a | 13.51 ± 1.5 | 8.10 ± 0.6 | 3.78 ± 0.3 | >100 |
3b | 29.19 ± 4.3 | 17.84 ± 3.4 | 11.09 ± 1.7 | >100 |
3c | 31.35 ± 2.6 | 16.49 ± 2.2 | 8.92 ± 1.0 | >100 |
3d | 25.89 ± 5.3 | 13.45 ± 2.8 | 3.05 ± 0.8 | >100 |
3e | 47.72 ± 4.4 | 21.32 ± 2.1 | 7.87 ± 1.2 | >100 |
3f | 85.41 ± 12.6 | 55.14 ± 9.7 | 19.46 ± 6.7 | 42.35 ± 4.3 |
Ascorbic acid | - | - | - | 1 ± 0.3 |
Compound/(µg/mL) | 100 | 75 | 50 | 25 | IC50 |
---|---|---|---|---|---|
3a | 56.47 ± 12.2 | 35 ± 8.7 | 28.62 ± 5.3 | 0 | 87.94 ± 15.8 |
3b | 52.14 ± 10.5 | 37.23 ± 11.6 | 12.04 ± 8.1 | 5.08 ± 0.8 | 92.15 ± 18.3 |
3c | 46.88 ± 9.7 | 27.38 ± 9.9 | 19.67 ± 7.4 | 9.19 ± 1.7 | >100 |
3d | 21.34 ± 10.3 | 17.65 ± 8.7 | 12.10 ± 5.5 | 5.55 ± 2.4 | >100 |
3e | 49.24 ± 15.3 | 31.09 ± 9.0 | 3.87 ± 1.6 | 0 | >100 |
3f | 93.12 ± 17.5 | 88.37 ± 10.3 | 83.79 ± 8.5 | 53.65 ± 3.5 | 17.54 ± 4.8 |
Ascorbic Acid | - | - | - | - | 35 ± 2.7 |
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Polo, E.; Trilleras, J.; Ramos, J.; Galdámez, A.; Quiroga, J.; Gutierrez, M. Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives. Molecules 2016, 21, 903. https://doi.org/10.3390/molecules21070903
Polo E, Trilleras J, Ramos J, Galdámez A, Quiroga J, Gutierrez M. Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives. Molecules. 2016; 21(7):903. https://doi.org/10.3390/molecules21070903
Chicago/Turabian StylePolo, Efrain, Jorge Trilleras, Juan Ramos, Antonio Galdámez, Jairo Quiroga, and Margarita Gutierrez. 2016. "Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives" Molecules 21, no. 7: 903. https://doi.org/10.3390/molecules21070903