Open Access Pre-published online by De Gruyter (O) July 21, 2021

Crystal structure of (E)-7-fluoro-2-(4-methoxy-2-(trifluoromethyl)benzylidene)-3,4-dihydronaphthalen-1(2H)-one, C19H14F4O2

Qing-Guo Meng, Sheng-Nan Zhao ORCID logo, Zhong-Hao Sun, Guang-Zhi Shan and Qing-Guo Meng

Abstract

C19H14F4O2, monoclinic, P21/c (no. 14), a = 11.8614(10) Å, b = 7.9148(6) Å, c = 16.7999(16) Å, β = 99.150(9)°, V = 1557.1(2) Å3, Z = 4, Rgt(F) = 0.0446, wRref(F2) = 0.1150, T = 100 K.

CCDC no.: 2079820

Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.13 × 0.12 × 0.11 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.13 mm-1
Diffractometer, scan mode: SuperNova
θmax, completeness: 25.5°, >99%
N(hkl)measured, N(hkl)unique, Rint: 6570, 2891, 0.033
Criterion for Iobs, N(hkl)gt: Iobs > 2σ(Iobs), 2362
N(param)refined: 227
Programs: CRYSALISPRO [1], SHELX [2, 3]
Table 2:

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).

Atom x y z Uiso*/Ueq
C1 0.28309 (15) 0.5351 (2) 0.78121 (11) 0.0242 (4)
C2 0.27811 (15) 0.5544 (2) 0.86916 (11) 0.0236 (4)
C3 0.36931 (15) 0.6621 (2) 0.91647 (11) 0.0284 (4)
H3A 0.367680 0.648498 0.973661 0.034*
H3B 0.354869 0.779988 0.902764 0.034*
C4 0.48686 (16) 0.6116 (3) 0.89791 (11) 0.0327 (5)
H4A 0.543716 0.689546 0.924611 0.039*
H4B 0.505830 0.499491 0.919318 0.039*
C5 0.59270 (16) 0.6416 (2) 0.77932 (12) 0.0323 (5)
H5 0.658930 0.662887 0.815598 0.039*
C6 0.59774 (17) 0.6400 (2) 0.69787 (12) 0.0322 (5)
H6 0.666504 0.657909 0.679216 0.039*
C7 0.49842 (17) 0.6113 (2) 0.64475 (11) 0.0287 (4)
C8 0.39622 (16) 0.5805 (2) 0.67011 (11) 0.0269 (4)
H8 0.330568 0.560696 0.633021 0.032*
C9 0.39252 (15) 0.5795 (2) 0.75310 (11) 0.0236 (4)
C10 0.49092 (15) 0.6120 (2) 0.80877 (11) 0.0262 (4)
C11 0.19726 (15) 0.4668 (2) 0.89900 (11) 0.0255 (4)
H11 0.151055 0.397381 0.862845 0.031*
C12 0.17339 (14) 0.4679 (2) 0.98250 (11) 0.0237 (4)
C13 0.14704 (14) 0.3193 (2) 1.02263 (11) 0.0222 (4)
C14 0.12003 (14) 0.3241 (2) 1.09972 (11) 0.0236 (4)
H14 0.103418 0.224366 1.124732 0.028*
C15 0.11756 (14) 0.4778 (2) 1.14019 (11) 0.0239 (4)
C16 0.14380 (15) 0.6255 (2) 1.10272 (11) 0.0256 (4)
H16 0.143609 0.728480 1.129337 0.031*
C17 0.17037 (15) 0.6187 (2) 1.02523 (11) 0.0268 (4)
H17 0.186882 0.719063 1.000702 0.032*
C18 0.0905 (2) 0.6203 (2) 1.26099 (12) 0.0370 (5)
H18A 0.166907 0.663892 1.271356 0.056*
H18B 0.064546 0.597491 1.311225 0.056*
H18C 0.041027 0.701959 1.231018 0.056*
C19 0.15198 (15) 0.1506 (2) 0.98292 (11) 0.0268 (4)
F1 0.50222 (10) 0.61374 (15) 0.56421 (7) 0.0421 (3)
F2 0.25497 (9) 0.11891 (13) 0.96276 (8) 0.0411 (3)
F3 0.07742 (10) 0.13620 (13) 0.91407 (7) 0.0377 (3)
F4 0.12968 (10) 0.02243 (12) 1.02984 (7) 0.0356 (3)
O1 0.20172 (11) 0.48343 (16) 0.73312 (8) 0.0323 (3)
O2 0.08882 (11) 0.46776 (15) 1.21546 (8) 0.0307 (3)

Source of material

5 mL of sodium hydroxide aqueous solution (25%) was added dropwise to the mixture of 7-fluoro-3,4-dihydronaphthalen-1(2H)-one (700 mg, 4.26 mmol) and 4-methoxy-2-(trifluoromethyl)benzaldehyde (870 mg, 4.26 mmol) in 10 mL methanol and stirred at room temperature for 4 h. The in process-control was monitored by silica gel thin layer chromatography (TLC, 254 nm). When the reaction was finished, the precipitate was suction filtered out, and a 50% methanol aqueous solution was added dropwise to wash, and the filter cake was vacuum dried at 65 °C to obtain a light yellow solid. Suitable crystals of the title compound were obtained by recrystallization in dichloromethane and methanol (1:1, v/v) system and dried under vacuum at 65 °C for 5 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) = 1.5 Ueq(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). Displacement ellipsoids are drawn at the 40% probability level.

Comment

Studies have shown that the development of an anti-inflammatory and low toxic NF-/KB inhibitor is of great significance for the treatment of inflammatory neurodegenerative CNS diseases [4], [5], [6].

Existing studies have used 3,4-dihydronaphthalen-1(2H)-one (DHN) derivatives with anti-tumor and anti-inflammatory activities as novel allergic and inflammatory responses modifiers [7] and as potential retinoic acid (RA)-metabolizing enzymes inhibitors to treat skin diseases and cancer. However, there are few studies on DHN derivatives as anti-neuroinflammatory drugs. Therefore, it is of great significance to study the synthesis and crystal structure of novel benzylidene-substituted DHN derivatives with anti-neuroinflammatory activity. Our group also synthesized some of these compounds in the early stage, and studied their anti-neuroinflammatory activity. The results showed that the fluorine-substituted compounds had better activity [8], [9], [10]. In this study, a new benzylidene-substituted DHN derivative was designed and synthesized through Claisen–Schmidt condensation reactions (see the Figure).

Single-crystal structure analysis revealed that the title compound crystallized in the monoclinic space group P21/c. The ORTEP diagram is presented in the Figure. Bond lengths and angles are all in the expected ranges [1113]. There is only one molecule in the asymmetric unit. The molecule adopts the E stereochemistry [14]. The 3,4-dihydronaphthalen-1(2H)-one, the 7-fluorophenyl and 4-methoxy-2-(trifluoromethyl) phenyl groups are not coplanar. This twisted configuration may increase likelihood of interactions with bioactive molecules, for the purposes of creating more potent biological activity [15].

Funding source: Science and Technology Innovation Development Plan of Yantai

Award Identifier / Grant number: 2020XDRH105

Funding source: National Natural Science Foundation of China10.13039/501100001809

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: This work was supported by 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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Received: 2021-05-25
Accepted: 2021-06-28
Published Online: 2021-07-21

© 2021 Qing-Guo Meng et al., published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.