Skip to content
BY 4.0 license Open Access Published online by De Gruyter (O) August 4, 2022

Crystal structure of (E)-7-bromo-2-(4-methoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one, C18H15BrO2

Yu-Long Zhang, Shu-Lian Liu, Gui-Ge Hou ORCID logo, Xiao-Fan Zhang ORCID logo, Lei Wang ORCID logo and Wen-Yu Xin

Abstract

C18H15BrO2, monoclinic, P21/n (no. 14), a = 9.1704(9) Å, b = 16.5309(13) Å, c = 10.3528(12) Å, β = 112.368(12)°, V = 1451.3(3) Å3, Z = 4, R gt (F) = 0.0405, wR ref (F2) = 0.0677, T = 149.99(10) K.

CCDC no.: 2161857

The molecular structure is shown in the figure. Displacement ellipsoids are drawn at the 40% probability level. 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: 0.14 × 0.12 × 0.10 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 2.834 mm−1
Diffractometer, scan mode: SuperNova
θmax, completeness: 25.5°, >99%
N(hkl)measured, N(hkl)unique, Rint: 6642, 2694, 0.046
Criterion for Iobs, N(hkl)gt: Iobs > 2 σ(Iobs), 1924
N(param)refined: 191
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
Br1 1.14469 (3) 0.10658 (2) 1.01994 (4) 0.02932 (13)
C1 0.8313 (3) 0.09750 (18) 0.8161 (4) 0.0187 (8)
H1 0.807693 0.073498 0.887069 0.022
C2 0.9838 (3) 0.12313 (19) 0.8398 (4) 0.0200 (8)
C3 1.0195 (3) 0.15912 (19) 0.7355 (4) 0.0208 (8)
H3 1.122135 0.175817 0.753186 0.025
C4 0.9027 (3) 0.17049 (18) 0.6043 (4) 0.0219 (9)
H4 0.927398 0.195144 0.534404 0.026
C5 0.6201 (3) 0.1537 (2) 0.4332 (4) 0.0215 (8)
H5A 0.611318 0.103741 0.381547 0.026
H5B 0.647639 0.196599 0.382756 0.026
C6 0.4605 (3) 0.17306 (19) 0.4431 (4) 0.0201 (8)
H6A 0.465240 0.226296 0.483907 0.024
H6B 0.378756 0.173909 0.350024 0.024
C7 0.4194 (3) 0.11158 (18) 0.5304 (4) 0.0175 (8)
C8 0.5500 (3) 0.07868 (19) 0.6569 (4) 0.0190 (8)
C9 0.7139 (3) 0.10863 (18) 0.6828 (4) 0.0175 (8)
C10 0.7478 (3) 0.14516 (18) 0.5760 (4) 0.0185 (8)
C11 0.2729 (3) 0.08307 (19) 0.5047 (4) 0.0197 (8)
H11 0.266369 0.042066 0.563761 0.024
C12 0.1223 (3) 0.10820 (18) 0.3957 (4) 0.0168 (8)
C13 0.0890 (3) 0.18799 (18) 0.3462 (4) 0.0189 (8)
H13 0.166563 0.227525 0.379100 0.023
C14 −0.0590 (3) 0.20823 (19) 0.2486 (4) 0.0200 (8)
H14 −0.080132 0.261313 0.217325 0.024
C15 −0.1757 (3) 0.1495 (2) 0.1974 (4) 0.0197 (8)
C16 −0.1452 (3) 0.07011 (19) 0.2444 (4) 0.0194 (8)
H16 −0.221899 0.030364 0.208992 0.023
C17 0.0011 (3) 0.05112 (19) 0.3448 (4) 0.0201 (8)
H17 0.019526 −0.001388 0.379460 0.024
C18 −0.4403 (3) 0.1179 (2) 0.0440 (4) 0.0307 (10)
H18A −0.406666 0.076397 −0.003329 0.046
H18B −0.532917 0.143859 −0.020774 0.046
H18C −0.464033 0.094194 0.118449 0.046
O1 0.5271 (2) 0.03091 (14) 0.7381 (3) 0.0270 (6)
O2 −0.3167 (2) 0.17663 (13) 0.1006 (3) 0.0279 (6)

Source of material

7-Bromo-3,4-dihydronaphthalene-1(2H)-one (BDHA) was prepared according to the procedures delineated in existing literatures [4, 5]. In the next step, BDHA (0.50 g, 2.20 mmol) and 4-methoxybenzaldehyde (0.30 g, 2.20 mmol) were dissolved in 5 mL of methanol. 25% NaOH solution (2 mL) was added to the above solution and the mixture was stirred for 3.5 h at room temperature (monitored by TLC). The solution was poured to 20 mL water and extracted three times with 10 mL ethyl acetate. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude product was purified to obtain the title compound by silica gel column chromatography (Eluent: Petroleum ether/Ethyl acetate/Methanol = 10:10:1, v/v/v). The product was dissolved in methanol and light yellow crystals suitable for single crystal X-ray diffraction were obtained by slow evaporation.

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

1-Tetralones, a wide collection of aromatic bicyclic compounds containing a moiety of 3,4-dihydronaphthalen-1(2H)-one (DHN), are gaining more attention due to their chemical characteristics and potential application in pharmaceutical industry. Recent researches demonstrated that 1-tetralones had a broad spectrum of biological activity, and acted as anticancer drugs [6], antifungal agents [7], and protein inhibitors [8]. In order to obtain new drugs, it is necessary to modify the structure of existing biologically active matrices. A set of aryliden-1-tetralone derivatives have been designed and investigated [9], [10], [11], [12]. 6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one was found to possess antineoplastic and antiviral properties [13]. As adenosine receptor antagonists, (E)-7-hydroxy-2-(4-hydroxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one was proved to be an optimal drug candidate to treat neurodegenerative disorders [14]. As a part of our aim to design new anti-neuroinflammatory agents, aromatic-1-tetralones with chloro, fluoro, bromo, methyl and methoxy groups were synthesized by the Claisen–Schmidt condensation reaction, the crystals of (E)-7-bromo-2-(4-methoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one were obtained and its structure is reported here.

X-ray crystallographic analysis reveals that the title compound crystallizies in the monoclinic space group P 21/n with one molecule in the asymmetric unit (cf. the figure). The torsion angle of C8–C7–C11–C12 is 175.2(3)°, meaning that the title compound adopts the E stereochemistry. The length of C7=C8 olifinic bond is 1.351(4) Å, which is similar to those reported in tetralone-containing compounds [15], [16], [17], [18]. Because of the sp3 hybridization of C5 and C6 atoms, the cyclohexanone ring of 3,4-dihydronaphthalen-1(2H)-one displays a chair conformation. Simultaneously, the two benzene rings are turned to each other with a dihedral angle of 51.7(3)°. Though no classic hydrogen bonds were found in the crystal structure, adjacent molecules are connected to form one dimensional structure via the C18–H18A–O1 weak hydrogen bond, wich is further linked to form one layer in the ac plane by the C4–H···4pi interaction (pi represents the center of the methoxylbenzene ring, C4···pi = 3.548(4) Å). Because of the existence of dihydronaphthalenone and methoxy groups, the title compound may establish effectively hydrophobic interactions with some proteins. Additionally, the bromine atom will be able to enhance cell permeability and metabolic stability of the title compound. It is of great importance in the design and optimization of halogenated drugs.


Corresponding author: Wen-Yu Xin, School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, P. R. China, E-mail:

Funding source: Shandong Provincial Natural Science Foundation

Award Identifier / Grant number: ZR2019MB032

Funding source: College Youth Innovation Science and Technology Support Programme of Shandong Province

Award Identifier / Grant number: 2020KJK003

Funding source: Key R&D Programme of Shandong Province

Award Identifier / Grant number: 2019JZZY011104

Funding source: Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Shandong Provincial Natural Science Foundation (No. ZR2019MB032), College Youth Innovation Science and Technology Support Programme of Shandong Province (No. 2020KJK003), Key R&D Programme of Shandong Province (No. 2019JZZY011104), Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Rigaku, O. D. CrysAlisPRO; Rigaku Oxford Diffraction Ltd: Yarnton, Oxfordshire, England, 2017.Search in Google Scholar

2. Sheldrick, G. M. A short history of SHELX. Acta Cryst. 2008, A64, 112–122; https://doi.org/10.1107/s0108767307043930.Search in Google Scholar PubMed

3. Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Cryst. 2015, C71, 3–8; https://doi.org/10.1107/s2053229614024218.Search in Google Scholar

4. Ameer, F., Giles, R. G. F., Green, I. R., Pearce, R. Synthesis of methoxy-2-hydroxy-1,4-naphthoquinones and reaction of one isomer with aldehydes under basic conditions. Synth. Commun. 2004, 34, 1247–1258; https://doi.org/10.1081/scc-120030312.Search in Google Scholar

5. Zhang, Z., Sangaiah, R., Gold, A., Ball, L. M. Synthesis of uniformly 13C-labeled polycyclic aromatic hydrocarbons. Org. Biomol. Chem. 2011, 9, 5431–5435; https://doi.org/10.1039/c0ob01107j.Search in Google Scholar PubMed

6. Wang, Y., Hedblom, A., Koerner, S. K., Li, M., Jernigan, F. E., Wegiel, B., Sun, L. Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation. Bioorg. Med. Chem. Lett. 2016, 26, 5703–5706; https://doi.org/10.1016/j.bmcl.2016.10.063.Search in Google Scholar PubMed PubMed Central

7. Gupta, D., Jain, D. K. Chalcone derivatives as potential antifungal agents: synthesis, and antifungal activity. J. Adv. Pharm. Technol. Res. 2015, 6, 114–117; https://doi.org/10.4103/2231-4040.161507.Search in Google Scholar PubMed PubMed Central

8. Wang, F., Zhang, R., Cui, Y., Sheng, L., Sun, Y., Tian, W., Liu, X., Liang, S. Design, synthesis and biological evaluation of 3,4-dihydronaphthalen-1(2H)-one derivatives as Bcl-2 inhibitors. Res. Chem. Intermed. 2017, 43, 5933–5942; https://doi.org/10.1007/s11164-017-2972-x.Search in Google Scholar

9. Ranjbar, S., Akbari, A., Edraki, N., Khoshneviszadeh, M., Hemmatian, H., Firuzi, O., Khoshneviszadeh, M. 6-Methoxy-3,4-dihydronaphthalenone chalcone-like derivatives as potent tyrosinase inhibitors and radical scavengers. Lett. Drug Des. Discov. 2018, 15, 1170–1179; https://doi.org/10.2174/1570180815666180219155027.Search in Google Scholar

10. Leng, J., Qin, H. L., Zhu, K., Jantan, I., Hussain, M. A., Sher, M., Amjad, M. W., Naeem-ul-Hassan, M., Ahmad, W., Bukhari, S. N. A. Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer’s disease. Chem. Biol. Drug Des. 2016, 88, 889–898; https://doi.org/10.1111/cbdd.12822.Search in Google Scholar PubMed

11. Sun, Y., Gao, Z., Wang, C., Hou, G. Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives. Acta Crystallogr. 2019, C75, 1157–1165; https://doi.org/10.1107/s2053229619010118.Search in Google Scholar

12. Gauni, B., Mehariya, K., Shah, A., Duggirala, S. M. Tetralone scaffolds and their potential therapeutic applications. Lett. Drug Des. Discov. 2021, 18, 222–238; https://doi.org/10.2174/1570180817999201013165656.Search in Google Scholar

13. Manvar, D., Fernandes, T. d. A., Domingos, J. L. O., Baljinnyam, E., Basu, A., Junior, E. F. T., Costa, P. R. R., Kaushik-Basu, N. Synthesis and biological evaluation of α-aryl-α-tetralone derivatives as hepatitis C virus inhibitors. Eur. J. Med. Chem. 2015, 93, 51–54; https://doi.org/10.1016/j.ejmech.2015.01.057.Search in Google Scholar PubMed

14. Legoabe, L. J., Van der Walt, M. M., Terre’Blanche, G. Evaluation of 2-benzylidene-1-tetralone derivatives as antagonists of A1 and A2A adenosine receptors. Chem. Biol. Drug Des. 2018, 91, 234–244; https://doi.org/10.1111/cbdd.13074.Search in Google Scholar PubMed

15. El-Sayed, N. N. E., Almaneai, N. M., Ghabbour, H. A., Alafeefy, A. M. Crystal structure of (E)-2-(4-hydroxy-3-methoxybenzylidene)-6-methoxy-3,4-dihydronaphthalen-1(2h)-one, C19H18O4. Z. Kristallogr. N. Cryst. Struct. 2017, 232, 203–205; https://doi.org/10.1515/ncrs-2016-0195.Search in Google Scholar

16. Luan, M. Z., Wang, H. Y., Zhang, M., Song, J., Xu, Y. R., Zhao, F. L., Meng, Q. G. Crystal structure of (E)-2-(4-fluoro-2-(trifluoromethyl) benzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2h)-one, C19H14F4O2. Z. Kristallogr. N. Cryst. Struct. 2021, 236, 245–247.10.1515/ncrs-2020-0484Search in Google Scholar

17. Wang, L., Meng, Q. G., Hou, G. G. Crystal structure of (E)-7-methoxy-2-((6-methoxypyridin-2-yl)methylene)-tetralone, C18H17NO3. Z. Kristallogr. N. Cryst. Struct. 2021, 236, 1023–1025; https://doi.org/10.1515/ncrs-2021-0207.Search in Google Scholar

18. Zhang, X. F., Wang, H. Y., Zhao, S. N., Zhang, S. N., Zhao, F. L., Meng, Q. G. Crystal structure of (E)-2-(4-fluoro-3-(trifluoromethyl) benzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C19H14F4O2. Z. Kristallogr. N. Cryst. Struct. 2021, 236, 47–49; https://doi.org/10.1515/ncrs-2020-0448.Search in Google Scholar

Received: 2022-06-18
Accepted: 2022-07-15
Published Online: 2022-08-04

© 2022 the author(s), published by De Gruyter, Berlin/Boston

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

Scroll Up Arrow