Abstract
C17H14FNO2, monoclinic, P21/c (no. 14), a = 14.0279(13) Å, b = 7.0527(5) Å, c = 14.4150(16) Å, β = 113.165(12)°, V = 1311.2(2) Å3, Z = 4, Rgt(F) = 0.0524, wRref(F2) = 0.1358, T = 100 K.
The molecular structure is shown in the Figure. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.
Data collection and handling.
| Crystal: | Colourless block |
| Size: | 0.15 × 0.13 × 0.11 mm |
| Wavelength: | Mo Kα radiation (0.71073 Å) |
| μ: | 0.10 mm−1 |
| Diffractometer, scan mode: | SuperNova |
| θmax, completeness: | 25.5°, 99% |
| N(hkl)measured, N(hkl)unique, Rint: | 4957, 2438, 0.031 |
| Criterion for Iobs, N(hkl)gt: | Iobs > 2 σ(Iobs), 1910 |
| N(param)refined: | 191 |
| Programs: | CrysAlisPRO [1], SHELX [2], [,3] |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).
| x | y | z | Uiso*/Ueq | |
|---|---|---|---|---|
| C1 | 0.47372 (16) | 0.5363 (3) | 0.60726 (15) | 0.0216 (5) |
| C2 | 0.52721 (16) | 0.7232 (3) | 0.64029 (15) | 0.0206 (5) |
| C3 | 0.46085 (16) | 0.8992 (3) | 0.62279 (16) | 0.0229 (5) |
| H3A | 0.447439 | 0.948526 | 0.555991 | 0.027* |
| H3B | 0.498772 | 0.995243 | 0.671525 | 0.027* |
| C4 | 0.35743 (16) | 0.8621 (3) | 0.63186 (17) | 0.0244 (5) |
| H4A | 0.369926 | 0.842488 | 0.702299 | 0.029* |
| H4B | 0.313485 | 0.972875 | 0.608510 | 0.029* |
| C5 | 0.19429 (16) | 0.6850 (3) | 0.52630 (16) | 0.0252 (5) |
| H5 | 0.155941 | 0.791073 | 0.528701 | 0.030* |
| C6 | 0.14291 (17) | 0.5233 (3) | 0.47724 (17) | 0.0277 (5) |
| H6 | 0.070919 | 0.520037 | 0.446411 | 0.033* |
| C7 | 0.20129 (17) | 0.3674 (3) | 0.47532 (16) | 0.0250 (5) |
| C8 | 0.30745 (16) | 0.3677 (3) | 0.51677 (16) | 0.0228 (5) |
| H8 | 0.344735 | 0.260862 | 0.513213 | 0.027* |
| C9 | 0.35843 (16) | 0.5333 (3) | 0.56472 (15) | 0.0201 (5) |
| C10 | 0.30175 (16) | 0.6922 (3) | 0.57194 (15) | 0.0213 (5) |
| C11 | 0.63138 (16) | 0.7192 (3) | 0.68050 (15) | 0.0220 (5) |
| H11 | 0.659874 | 0.598055 | 0.691636 | 0.026* |
| C12 | 0.70752 (16) | 0.8725 (3) | 0.70972 (16) | 0.0216 (5) |
| C13 | 0.81155 (16) | 0.8328 (3) | 0.77370 (16) | 0.0225 (5) |
| C14 | 0.86833 (17) | 1.1292 (3) | 0.75901 (17) | 0.0270 (5) |
| H14 | 0.922433 | 1.215867 | 0.774860 | 0.032* |
| C15 | 0.77038 (17) | 1.1868 (3) | 0.69688 (16) | 0.0254 (5) |
| H15 | 0.758412 | 1.310006 | 0.672016 | 0.031* |
| C16 | 0.69004 (17) | 1.0579 (3) | 0.67206 (16) | 0.0243 (5) |
| H16 | 0.623403 | 1.094834 | 0.629762 | 0.029* |
| C17 | 0.93629 (16) | 0.6116 (4) | 0.87542 (18) | 0.0304 (6) |
| H17A | 0.980048 | 0.637150 | 0.839771 | 0.046* |
| H17B | 0.942323 | 0.480371 | 0.894641 | 0.046* |
| H17C | 0.957201 | 0.689483 | 0.934725 | 0.046* |
| F1 | 0.15087 (10) | 0.2050 (2) | 0.42968 (10) | 0.0362 (4) |
| N1 | 0.88976 (14) | 0.9528 (3) | 0.79815 (13) | 0.0254 (5) |
| O1 | 0.52231 (11) | 0.3891 (2) | 0.61177 (12) | 0.0296 (4) |
| O2 | 0.83063 (11) | 0.6529 (2) | 0.81134 (11) | 0.0279 (4) |
Source of material
7-Fluoro-3,4-dihydro-1(2H)-naphthalenone (0.7 g, 4.26 mmol) and 2-fluoro-3-formylpyridine (0.53 g, 4.26 mmol) were dissolved in 10 mL methanol. A sodium hydroxide aqueous solution (25%) was added to the mixture and stirred for 3 h at room temperature. The response endpoint was detected by thin layer chromatography (TLC, 254 nm). When 7-fluoro-3,4-dihydro-1(2H)-naphthalenone disappeared, the precipitate was filtered from the reaction mixture and dissolved with dichloromethane. The organic phase was washed respectively with deionized water and brine, dried over anhydrous sodium sulfate and condensed under vacuum. The crude product was purified by silica-gel column chromatography (petroleum ether: ethyl acetate = 10:1, v/v). Single crystal was obtained under ambient conditions via solvent evaporation in the mixed solvents of dichloromethane and methanol (1:1, v/v) and drying under vacuo at 333 K for 3 h.
Experimental details
The H atoms were placed in idealized positions and treated as riding on their parent atoms, with d(C—H) = 0.96 Å (methyl), Uiso(H) = 1.5Ueq(C), and d(C—H) = 0.97 Å (methylene), Uiso(H) = 1.2Ueq(C), and d(C—H) = 0.93 Å (aromatic), Uiso(H) = 1.2Ueq(C).
Comment
Microglia become activated under brain injury and immunological stimuli and undergo several alterations from a resting state to an active state. This activation and consequent neuroinflammation are substantially involved in the pathological development of inflammatory neurodegenerative diseases in the central nervous system (CNS) [4], [, 5]. It has been reported that pro-inflammatory cytokines [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β] secreted from M1 microglia increase blood-brain barrier (BBB) permeability by activating the nuclear factor kappa B (NF-κB) signaling pathway during inflammatory neurodegenerative diseases in CNS [6], [7], [8]. Concomitantly, the disruption of the blood-brain barrier can result in severe inflammatory response that aggravates the brain injury [9]. In addition, activated microglia can produce reactive oxygen species (ROS), which may indirectly induce neuroinflammation by activating NF-κB [10], [, 11]. Therefore, NF-κB inhibitor with anti-neuroinflammatory activity may represent a therapeutic option for the treatment of inflammatory neurodegenerative diseases [12], [13], [14].
3,4-Dihydronaphthalen-1(2H)-one (DHN) derivatives with antitumor and anti-inflammatory activities have been investigated as novel modulators of allergic and inflammatory responses [15], [, 16]. Our interests lie in developing these derivatives as anti-neuroinflammatory drugs. In this study, we designed and synthesized a new DHN derivative through Claisen–Schmidt condensation reaction.
Single crystals of the title compound were prepared under ambient conditions, with crystallization obtained via solvent evaporation in the mixed solvents of methanol and dichloromethane. Single-crystal structure analysis revealed that the title compound, here termed XF-1-4-2, crystallized in the monoclinic space group P21/c. The ORTEP diagram is presented in the Figure. There is only a drug molecule in the asymmetric unit. With respect to the C(12) = C(11) olefinic bonds, 2-methoxyphenyl and carbonyl groups adopt the E stereochemistry [17]. Because of the distorting effect of 3,4-dihydrobenzo[b]oxepin-5(2H)-one, the 7-fluorophenyl and 2-methoxyphenyl groups are not coplanar with each other, with a dihedral angle of approximately 37.8(3)°. This twisted configuration may increase the likelihood of interactions with bioactive molecules or the purposes of creating more potent biological activity [18], [, 19]. All geometric parameters are in the expected ranges [20]. Displacement ellipsoids are drawn at the 50% probability level.
Funding source: Science and Technology Innovation Development Plan of Yantai
Award Identifier / Grant number: 2020XDRH105
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 81473104
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Science and Technology Innovation Development Plan of Yantai (No. 2020XDRH105) and the National Natural Science Foundation of China (No. 81473104).
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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© 2020 Xiao-Fan Zhang and Qing-Guo Meng, published by De Gruyter, Berlin/Boston
This work is licensed under the Creative Commons Attribution 4.0 International License.
