Abstract
C9H12N2O2, triclinic, P1̅ (no. 2), a = 6.6954(7) Å, b = 7.6325(8) Å, c = 9.8928(11) Å, α = 95.908(9)°, β = 92.810(9)°, γ = 108.360(8)°. V = 475.49(9) Å3, Z = 2, Rgt(F) = 0.0606, wRref(F2) = 0.1549, T = 296(2) K.
The figure shows the asymmetric unit of the title structure. Tables 1–3 contain details of the methods used and a list of the atoms including atomic coordinates and displacement parameters.
Data collection and handling.
| Crystal: | Colourless, plate, size 0.040×0.317×0.540 mm |
| Wavelength: | Mo Kα radiation (0.71073 Å) |
| μ: | 0.91 cm−1 |
| Diffractometer, scan mode: | STOE IPDS 2, ω scans |
| 2θmax: | 57.92° |
| N(hkl)measured, N(hkl)unique: | 9019, 2509 |
| N(param)refined: | 122 |
| Programs: | X-Area [9], SHELX [10] |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).
| Atom | Site | x | y | z | Uiso |
|---|---|---|---|---|---|
| H(1) | 2i | 0.2341 | 0.3611 | −0.0394 | 0.118 |
| H(1A) | 2i | −0.2924 | 0.2720 | −0.0314 | 0.124 |
| H(1B) | 2i | −0.3091 | 0.1033 | 0.0503 | 0.124 |
| H(1C) | 2i | −0.2598 | 0.0912 | −0.1030 | 0.124 |
| H(3) | 2i | −0.0147 | 0.1783 | 0.2125 | 0.072 |
| H(6) | 2i | 0.7137 | 0.3781 | 0.3140 | 0.073 |
| H(8A) | 2i | 0.7951 | 0.3856 | 0.66740 | 0.124 |
| H(8B) | 2i | 0.9125 | 0.3245 | 0.5472 | 0.124 |
| H(8C) | 2i | 0.7607 | 0.1740 | 0.6244 | 0.124 |
| H(9A) | 2i | 0.3381 | 0.2624 | 0.7143 | 0.124 |
| H(9B) | 2i | 0.3913 | 0.0773 | 0.6824 | 0.124 |
| H(9C) | 2i | 0.1696 | 0.0870 | 0.6323 | 0.124 |
Fractional coordinates and atomic displacement parameters (Å2).
| Atom | Site | x | y | z | U11 | U22 | U33 | U12 | U13 | U23 |
|---|---|---|---|---|---|---|---|---|---|---|
| O(1) | 2i | 0.1092(2) | 0.3321(2) | −0.0671(1) | 0.0770(9) | 0.107(1) | 0.0560(8) | 0.0321(9) | 0.0070(7) | 0.0188(8) |
| O(2) | 2i | 0.4218(2) | 0.3925(2) | 0.1072(1) | 0.0608(8) | 0.104(1) | 0.0670(8) | 0.0196(7) | 0.0154(6) | 0.0352(8) |
| N(1) | 2i | 0.2620(2) | 0.2152(2) | 0.4169(2) | 0.0632(9) | 0.062(1) | 0.0519(8) | 0.0202(7) | 0.0068(7) | 0.0125(7) |
| N(2) | 2i | 0.3994(3) | 0.2154(2) | 0.5212(2) | 0.075(1) | 0.0603(9) | 0.0505(8) | 0.0259(8) | 0.0061(7) | 0.0105(7) |
| C(1) | 2i | −0.2376(3) | 0.1722(4) | −0.0188(2) | 0.067(1) | 0.101(2) | 0.078(1) | 0.027(1) | −0.008(1) | 0.001(1) |
| C(2) | 2i | −0.0075(3) | 0.2498(3) | 0.0239(2) | 0.067(1) | 0.065(1) | 0.059(1) | 0.0266(9) | 0.0081(9) | 0.0044(9) |
| C(3) | 2i | 0.0754(3) | 0.2360(3) | 0.1501(2) | 0.057(1) | 0.067(1) | 0.058(1) | 0.0182(8) | 0.0123(8) | 0.0139(8) |
| C(4) | 2i | 0.2944(3) | 0.3072(2) | 0.1873(2) | 0.061(1) | 0.057(1) | 0.0525(9) | 0.0234(8) | 0.0118(8) | 0.0117(8) |
| C(5) | 2i | 0.3857(3) | 0.2848(2) | 0.3202(2) | 0.0573(9) | 0.051(1) | 0.0533(9) | 0.0199(7) | 0.0103(7) | 0.0093(7) |
| C(6) | 2i | 0.5988(3) | 0.3282(3) | 0.3632(2) | 0.059(1) | 0.065(1) | 0.062(1) | 0.0230(9) | 0.0089(8) | 0.0101(9) |
| C(7) | 2i | 0.6036(3) | 0.2820(3) | 0.4932(2) | 0.065(1) | 0.058(1) | 0.063(1) | 0.0272(9) | −0.0002(8) | 0.0027(8) |
| C(8) | 2i | 0.7841(4) | 0.2925(4) | 0.5918(2) | 0.084(1) | 0.093(2) | 0.076(1) | 0.038(1) | −0.012(1) | 0.005(1) |
| C(9) | 2i | 0.3176(4) | 0.1554(4) | 0.6484(2) | 0.103(2) | 0.095(2) | 0.056(1) | 0.035(1) | 0.012(1) | 0.022(1) |
Source of material
A solution of ethyl 1,5-dimethyl-1H-pyrazole-3-carboxylate (12 mmol) in THF (25 mL) was added to a suspension of sodium (22 mmol) in THF (50 mL), and then acetone (1.2 g; 20.6 mmol) was added at 273 K. The resulting mixture was stirred at 273 K for 48 h and the formed residue was filtered, washed with THF, and neutralized with acetic acid to pH 5 after being dissolved in water. The organic layer was extracted with CH2Cl2, dried and concentrated in vacuum. The resulting mixture was chromatographed on silica using CH2Cl2 as eluant to give the target product. Crystals suitable for X-ray diffraction analysis were obtained by slow evaporated of methanol from the mixture; yield: 37%; M.p. 356–357 K.
Experimental details
The hydroxyl H atom and H atoms bonded to C atoms were positioned geometrically and were refined using a riding model with Uiso(H) = 1.5Ueq(O) for hydroxyl and Uiso(H) = 1.2Ueq(C) for the others.
Discussion
A new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Their versatile utility in medicinal chemistry is firmly established including anti-HIV [1, 2], antitumor [3–5], anti-influenza [6], antioxidant [7], and anti-inflammatory [8] activities. In this study we coupled ethyl pyrazole carboxylate with acetone to produce the title compound in acceptable yield.
The crystal structure is quite interesting and displays the formation of an intramolecular OH—O hydrogen bond (see the figure). The structure leads to two independent N1, O2 and O1, O2-bidentate units having two different geometries with a very attractive evidence for even semi-combination probably existing between them, leading to a bis-bidentate N1, O2, O1-unit. However, both are held together by means of intra-electrostatic forces and van der Waals interactions. The oxygen atoms O1, O2 are separated by a distance of 2.538 Å. This distance is always found in the case of antibacterial pharmacophore site. Hence, this compound constitutes a promising anti-HIV agent. The whole molecule is almost planar, with an rms deviation of 0.002 Å for all non-hydrogen atoms. In the crystal, π−π stacking interactions [centroid-centroid distance = 3.5901(12) Å] between the pyrazole rings stabilize the molecular packing.
Acknowledgements:
The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding this Prolific Research group (PRG-1437-29).
References
1. Pommier, Y.; Johnson, A. A.; Marchand, C.: Integrase inhibitors to treat HIV/AIDS. Nat. Rev. Drug Discov. 4 (2005) 236–248.10.1038/nrd1660Search in Google Scholar PubMed
2. Egbertson, S. S.; Anthony, N. J.; Summa, V.: From diketo acids to heterocyclic templates: history of HIV integrase medicinal chemistry at Merck West Point and Merck Rome (IRBM) leading to discovery of raltegravir. In: Pharmaceutical & Medicinal Chemistry (Ed. Neamati, N.), pp 197–230, Wiley, 2011.Search in Google Scholar
3. Goldgur, Y.; Craigir, R.; Cohen, G. H.; Fujiwara, T.; Yoshinaga, T.; Fujishita, T.; Sugimoto, H.; Endo, T.; Murai, H.; Davies, D. R.: Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design. Proc. Natl. Acad. Sci. USA, 96 (1999) 13040–13043.10.1073/pnas.96.23.13040Search in Google Scholar PubMed PubMed Central
4. Tan, K. L.; Ali, A.; Du, Y.; Fu, H.; Jin, H. X.; Chin, T. M.; Khan, M.; Go, M. L.: Synthesis and evaluation of bisbenzylidenedioxotetrahydro-thiopranones as activators of endoplasmic reticulum (ER) stress signaling pathways and apoptotic cell death in acute promyelocytic leukemic cells. J. Med. Chem. 57 (2014) 5904–5918.10.1021/jm401352aSearch in Google Scholar PubMed PubMed Central
5. Liang, G.; Shao, L.; Wang, Y.; Zhao, C.; Chu, Y.; Xiao, J.; Zhao, Y.; Li, X.; Yang, S.: Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorg. Med. Chem. 17 (2009) 2623–2631.10.1016/j.bmc.2008.10.044Search in Google Scholar PubMed
6. Ishikawa, Y.; Fujii, S.: Binding mode prediction and inhibitor design of anti-influenza virus diketo acids targeting metalloenzyme RNA polymerase by molecular docking. Bioinformation 6 (2011) 221–225.10.6026/97320630006221Search in Google Scholar PubMed PubMed Central
7. Anand, P.; Thomas, S. G.; Kunnumakkara, A. B.; Sundaram, C.; Harikumar, K. B.; Sung, B.; Tharakan, S. T.; Misra, K.; Priyadarsini, I. K.; Rajasekharan, K. N.; Aggarwal, B. B.: Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem. Pharmacol. 76 (2008) 1590–1611.10.1016/j.bcp.2008.08.008Search in Google Scholar PubMed
8. Liang, G.; Li, X.; Chen, L.; Yang, S.; Wu, X.; Studer, E.; Gurley, E.; Hylemon, P. B.; Ye, F.; Li, Y.; Zhou, H.: Synthesis and anti-inflammatory activities of monocarbonyl analogues of curcumin. Bioorg. Med. Chem. Lett. 18 (2008) 1525–1529.10.1016/j.bmcl.2007.12.068Search in Google Scholar PubMed PubMed Central
9. Stoe & Cie: X-Area & X-RED32 Software; Stoe & Cie GmbH: Darmstadt, Germany, 2002.Search in Google Scholar
10. Sheldrick, G. M.: A short history of SHELX. Acta Crystallogr. A64 (2008) 112–122.10.1107/S0108767307043930Search in Google Scholar PubMed
©2016 Smaail Radi et al., published by De Gruyter.
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