Home Crystal structure of (E)-7-methoxy-2-((6-methoxypyridin-2-yl)methylene)-tetralone, C18H17NO3
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Crystal structure of (E)-7-methoxy-2-((6-methoxypyridin-2-yl)methylene)-tetralone, C18H17NO3

  • Lei Wang ORCID logo , Qing-Guo Meng and Gui-Ge Hou ORCID logo EMAIL logo
Published/Copyright: July 12, 2021

Abstract

C18H17NO3, triclinic, P 1 (no. 2), a = 4.0929(4) Å, b = 12.9527(11) Å, c = 14.4228(12) Å, α = 70.171(8)°, β = 87.229(8)°, γ = 87.567(8)°, V = 718.16(12) Å3, Z = 2, R gt (F) = 0.0549, wR ref (F2) = 0.1526, T = 99.9(3) K.

CCDC no.: 2090577

The molecular structure is shown in Figure. 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: 0.15 × 0.12 × 0.11 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.09 mm−1
Diffractometer, scan mode: SuperNova,
θmax, completeness: 25.5°, >99%
N(hkl)measured, N(hkl)unique, Rint: 4714, 2660, 0.042
Criterion for Iobs, N(hkl)gt: Iobs > 2σ(Iobs), 2124
N(param)refined: 201
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 0.8932 (5) 0.65626 (14) 0.16741 (13) 0.0215 (4)
C2 0.7312 (5) 0.72771 (14) 0.21974 (13) 0.0203 (4)
C3 0.7835 (5) 0.69310 (13) 0.32835 (13) 0.0224 (4)
H3A 0.639175 0.736137 0.357335 0.027*
H3B 1.007410 0.706690 0.339160 0.027*
C4 0.7151 (5) 0.57074 (14) 0.37833 (13) 0.0226 (4)
H4A 0.771521 0.548179 0.447041 0.027*
H4B 0.483280 0.559332 0.376104 0.027*
C5 0.9975 (5) 0.39189 (15) 0.38072 (14) 0.0248 (5)
H5 0.935214 0.361534 0.447066 0.030*
C6 1.1765 (5) 0.32829 (15) 0.33572 (14) 0.0273 (5)
H6 1.232012 0.255789 0.371612 0.033*
C7 1.2744 (5) 0.37250 (15) 0.23654 (14) 0.0249 (5)
C8 1.1857 (5) 0.47998 (14) 0.18311 (14) 0.0226 (4)
H8 1.248110 0.509892 0.116740 0.027*
C9 1.0022 (5) 0.54312 (14) 0.22931 (13) 0.0204 (4)
C10 0.9074 (5) 0.50092 (14) 0.32894 (13) 0.0210 (4)
C11 0.5586 (5) 0.81598 (14) 0.16365 (13) 0.0225 (4)
H11 0.551297 0.821417 0.097805 0.027*
C12 0.3809 (5) 0.90467 (14) 0.18738 (13) 0.0223 (4)
C13 0.2055 (5) 0.98777 (14) 0.29846 (14) 0.0244 (5)
C14 0.0570 (5) 1.07664 (15) 0.22600 (15) 0.0288 (5)
H14 −0.049705 1.133695 0.241718 0.035*
C15 0.0759 (5) 1.07572 (15) 0.13119 (14) 0.0295 (5)
H15 −0.017966 1.132873 0.080569 0.035*
C16 0.2371 (5) 0.98832 (15) 0.11154 (14) 0.0249 (5)
H16 0.248408 0.986000 0.047716 0.030*
C17 0.3289(6) 0.89823 (15) 0.46620 (14) 0.0325 (5)
H17A 0.238639 0.831305 0.465483 0.049*
H17B 0.286711 0.905347 0.529839 0.049*
H17C 0.560790 0.896779 0.452808 0.049*
C18 1.5485 (6) 0.34415 (17) 0.09731 (15) 0.0344 (5)
H18A 1.355831 0.363651 0.059011 0.052*
H18B 1.673117 0.288442 0.080016 0.052*
H18C 1.679046 0.407776 0.084055 0.052*
N1 0.3651 (4) 0.90504 (11) 0.28168 (11) 0.0225 (4)
O1 1.4560 (4) 0.30353 (10) 0.19940 (10) 0.0328 (4)
O2 0.9342 (4) 0.68720 (10) 0.07762 (9) 0.0310 (4)
O3 0.1806 (4) 0.98961 (10) 0.39229 (10) 0.0302 (4)

Source of material

The title compound {systematic name: (E)-7-methoxy-2-((6-methoxypyridin-2-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one} was prepared according to a literature protocol [4]. 7-Methoxy-1-tetralone (0.53 g, 3.0 mmol) and 6-methoxy-2-pyridinecarbaldehyde (0.41 g, 3.0 mmol) were dissolved in methanol (10 mL). Aqueous NaOH (0.60 g, 15.0 mmol) solution (3 mL) was added to the above solution. The reaction mixture was stirred until completion of the reaction (monitored by TLC). Then, it was cooled in an ice bath for 20 min. The solids were filtered off and the residues were purified on a silica gel by column chromatography using petroleum ether/ethyl acetate (2:1, v/v) as the eluent to produce light yellow powders. Crystals suitable for X-ray diffraction were obtained by slow evaporation from methanol at room temperature.

Experimental details

The H atoms were placed in idealized positions and treated as riding on their parent atoms, with d (C–H) = 0.93 Å (aromatic) and 0.97 Å (methylene), Uiso(H) = 1.2Ueq(C), and d(C–H) = 0.96 Å (methyl), Uiso(H) = 1.5Ueq(C). Displacement ellipsoids are drawn at the 35% probability level.

Comment

1-Tetralones, also known as 3,4-dihydronaphthalen-1(2H)-ones, have attracted the attention of chemists and pharmacists because of their potential applications for novel modulators of allergic and inflammatory phenomena and inhibitors of retinoic acid (RA)-metabollizing enzymes [5, 6]. In order to obtain novel pharmaceutical agents, 3,4-dihydronaphthalen-1(2H)-one and its derivatives were designed and synthesized to innovative 1-tetralone derivatives with judicious functional groups and different substituents. (E)-2-(3,4-dimethoxybenzylidene)-7-methoxy-tetralone exhibits obvious inhibition activity against Bcl-2 (B cell lymphoma 2) protein [7]. 2-(2-Bromo-3,4,5-trimethoxybenzylidene)-6-methoxy-tetralone possesses potent inhibitory activity against monoamine oxidase and acetylcholinesterase, which can be a promising agent for the treatment of Alzheimer’s disease [8]. Some 2-arylidene-1-tetralones with methoxy groups showed the antioxidant activity against radical scavenging [9]. These results demonstrate that active 1-tetralone derivatives all contain the fraction of α,β-unsaturated keto and methoxy group. The pharmacophore of α,β-unsaturated keto can establish the primary binding interaction with bio-thiols from susceptible neoplasms with lower toxicity [10]. The methoxy group can improve molecular lipophilicity and increase the ability of the membrane permeability. Based on these consideration, 2-arylidene-1-tetralones with methoxy groups were designed and synthesized in our laboratory, which show evident anti-neuroinflammatory property with relatively low toxicity [11]. Additionally, 1-tetralone derivatives that contain pyridinyl groups demonstrated antiproliferative activity against a variety of cancer cell lines [12]. As a part of the search for new anti-inflammatory and antitumor agents, a new 1-tetralone derivative with methoxy group and pyridine ring was synthesized by the aldol condensation reaction.

There is one independent molecule in the asymmetric unit (cf. the Figure). The bond length of C2–C11 is 1.349(2) Å, which represents a typical C=C double bond, and the ethylene moiety in the enone linkage adopts an E configuration [13]. Other bond lengths and bond angles are all in the normal ranges [1417]. In the title molecule, the cyclohexanone ring displays an envelope conformation with the flap atom C4 deviating by 0.493(3) Å from the least-squares plane of the ring. The dihedral angle between the benzene and pyridine rings is 24.28(7)°. In the crystal, molecules are connected through weak C–H–O hydrogen bonds. It is noteworthy that the peripheric heteroatoms with free electron pairs (such as O and N) can be considered as the potential hydrogen bonding acceptors and such weak interactions will play a crucial role in the biological activity [18].


Corresponding author: Gui-Ge Hou, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China, E-mail:

Funding source: Project of Shandong Province Higher Educational Science and Technology Program 10.13039/501100015642

Award Identifier / Grant number: J18KA092

Acknowledgements

This work was supported by Project of the Shandong Province Higher Educational Science and Technology Program (J18KA092).

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

  2. Research funding: Project of the Shandong Province Higher Educational Science and Technology Program (J18KA092).

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

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Received: 2021-05-25
Accepted: 2021-06-17
Published Online: 2021-07-12
Published in Print: 2021-09-27

© 2021 Lei Wang et al., published by De Gruyter, Berlin/Boston

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

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  59. The crystal structure of 4-bromobenzyl chloride, C7H6BrCl
  60. The crystal structure of di-tert-butyl dicarbonate, C10H18O5
  61. The crystal structure of (2-(4-chlorophenyl)-5-methyl-1,3-dioxan-5-yl)methanol, C12H15ClO3
  62. The crystal structure of the co-crystal: 2-hydroxybenzoic acid – N′-(butan-2-ylidene)pyridine-4-carbohydrazide, C10H13N3O·C7H6O3
  63. Crystal structure and anti-inflammatory activity of (E)-7-fluoro-2-((5-methoxypyridin-3-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one, C17H14FNO2
  64. Crystal structure of (E)-7-fluoro-2-((6-methoxypyridin-3-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one, C17H14FNO2
  65. Crystal structure of 1,1′-(butane-1,4-diyl)bis(3-propyl-1H-imidazol-3-ium) bis(hexafluoridophosphate), C32H56F24N8P4
  66. The crystal structure of dichlorido-bis(3-methyl-3-imidazolium-1-ylpropionato-κ2)-cadmium(II), C14H20CdCl2N4O4
  67. Crystal structure of 1-(2-cyanobenzyl)-3-cyano-4-phenyl-4-(2-cyanobenzyl)-1,4-dihydropyridine monohydrate, C56H42N8O
  68. The crystal structure of 3-(carboxymethyl)-1-ethenyl-1H-imidazol-3-ium chloride, C7H9N2O2Cl
  69. The crystal structure of adamantylmethoxydiphenylsilane, C23H28OSi
  70. Redetermination of the crystal structure of (2E,4Z,13E,15Z)-3,5,14,16-tetramethyl-2,6,13,17-tetraazatricyclo[16.4.0.07,12]docosa-1(22),2,4,7,9,11,13,15,18,20-decaene, C22H24N4
  71. Crystal structure of (E)-7-hydroxy-2-((6-methoxypyridin-2-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one, C17H15NO3
  72. Crystal structure of catena-poly[diaqua-bis(μ2-1,3-di(1H-imidazol-1-yl)propane-κ2 N:N′)cobalt(II)] dinitrate, C18H28N10O8Co
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