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BY 4.0 license Open Access Published by De Gruyter (O) September 2, 2021

Crystal structure of (3E,5E)-3,5-bis(4-fluorobenzylidene)-1-((4-trifluoromethyl)benzenesulfonyl)piperidin-4-one, C26H18F5NO3S

  • Zhong-Fei Gao , Lei Wang ORCID logo , Gui-Ge Hou ORCID logo and Xiao-Fan Zhang ORCID logo EMAIL logo

Abstract

C26H18F5NO3S, triclinic, P 1 (no. 2), a = 7.8831(4) Å, b = 11.9591(7) Å, c = 13.3258(7) Å, α = 69.072(5)°, β = 88.556(4)°, γ = 73.730(5)°, V = 1122.48(11) Å3, Z = 2, R gt (F) = 0.0507, wR ref (F2) = 0.1216, T = 100.0(1) K.

CCDC no.: 2103981

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: Yellow block
Size: 0.14 × 0.12 × 0.10 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.22 mm−1
Diffractometer, scan mode: SuperNova,
θmax, completeness: 29.6°, >99%
N(hkl)measuredN(hkl)uniqueRint: 12,356, 5294, 0.032
Criterion for Iobs, N(hkl)gt: Iobs > 2σ(Iobs), 4144
N(param)refined: 325
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 0.6245 (3) 0.49568 (19) 0.32766 (16) 0.0204 (4)
H1A 0.672869 0.547280 0.266911 0.025*
H1B 0.714554 0.456990 0.387854 0.025*
C2 0.4638 (3) 0.5783 (2) 0.35755 (16) 0.0219 (4)
C3 0.3133 (3) 0.52704 (19) 0.39938 (15) 0.0208 (4)
C4 0.3200 (2) 0.40041 (19) 0.40027 (15) 0.0193 (4)
C5 0.4951 (3) 0.32090 (19) 0.38201 (16) 0.0210 (4)
H5A 0.570449 0.279806 0.448999 0.025*
H5B 0.474953 0.256714 0.359422 0.025*
C6 0.4407 (3) 0.6995 (2) 0.34183 (16) 0.0234 (4)
H6 0.331586 0.740863 0.358513 0.028*
C7 0.5623 (3) 0.7758 (2) 0.30232 (17) 0.0244 (5)
C8 0.4897 (3) 0.9051 (2) 0.24935 (18) 0.0299 (5)
H8 0.367195 0.939410 0.241474 0.036*
C9 0.5950 (3) 0.9826 (2) 0.20869 (18) 0.0324 (5)
H9 0.545673 1.068166 0.172639 0.039*
C10 0.7745 (3) 0.9294 (2) 0.22313 (17) 0.0282 (5)
C11 0.8548 (3) 0.8037 (2) 0.27762 (16) 0.0240 (4)
H11 0.977686 0.771826 0.287092 0.029*
C12 0.7481 (3) 0.7261 (2) 0.31796 (16) 0.0228 (4)
H12 0.799282 0.640971 0.355439 0.027*
C13 0.1691 (3) 0.36798 (19) 0.40819 (15) 0.0201 (4)
H13 0.066478 0.425800 0.414602 0.024*
C14 0.1518 (2) 0.24925 (19) 0.40759 (16) 0.0204 (4)
C15 0.2630 (3) 0.13494 (19) 0.47520 (17) 0.0247 (5)
H15 0.348292 0.133267 0.523102 0.030*
C16 0.2480 (3) 0.0242 (2) 0.47189 (19) 0.0296 (5)
H16 0.321826 −0.052124 0.517421 0.036*
C17 0.1222 (3) 0.0288 (2) 0.40016 (19) 0.0289 (5)
C18 0.0073 (3) 0.1393 (2) 0.33258 (18) 0.0278 (5)
H18 −0.077816 0.139791 0.285263 0.033*
C19 0.0231 (3) 0.2497 (2) 0.33755 (17) 0.0236 (4)
H19 −0.053694 0.325551 0.293321 0.028*
C20 0.3392 (3) 0.53275 (19) 0.12335 (15) 0.0194 (4)
C21 0.3311 (3) 0.6585 (2) 0.08351 (16) 0.0245 (5)
H21 0.433541 0.682656 0.083388 0.029*
C22 0.1691 (3) 0.7477 (2) 0.04396 (17) 0.0265 (5)
H22 0.161566 0.832345 0.017175 0.032*
C23 0.0178 (3) 0.7096 (2) 0.04463 (16) 0.0229 (4)
C24 0.0264 (3) 0.5838 (2) 0.08493 (16) 0.0236 (4)
H24 −0.075989 0.559595 0.085210 0.028*
C25 0.1881 (3) 0.4946 (2) 0.12467 (16) 0.0219 (4)
H25 0.195541 0.409979 0.151978 0.026*
C26 −0.1567 (3) 0.8044 (2) −0.00493 (17) 0.0285 (5)
F1 0.88070 (19) 1.00437 (13) 0.18209 (11) 0.0390 (3)
F2 0.10867 (18) −0.08073 (12) 0.39666 (12) 0.0396 (4)
F3 −0.16273 (17) 0.91979 (13) −0.01286 (12) 0.0398 (3)
F4 −0.19243 (18) 0.81126 (15) −0.10532 (11) 0.0454 (4)
F5 −0.29304 (16) 0.77733 (14) 0.05012 (11) 0.0399 (4)
N1 0.5844 (2) 0.39745 (15) 0.29951 (13) 0.0180 (3)
O1 0.18551 (18) 0.58662 (14) 0.43178 (12) 0.0250 (3)
O2 0.67987 (18) 0.47214 (14) 0.11741 (11) 0.0249 (3)
O3 0.53295 (19) 0.30282 (14) 0.17191 (12) 0.0261 (3)
S1 0.54701 (6) 0.41882 (5) 0.17298 (4) 0.01909 (13)

Source of material

The synthesis of 3,5-bis(4-fluorobenzylidene)piperidin-4-one was carried out by the Claisen–Schmidt condensation reaction [4]. 4-Piperidone hydrochloride (0.68 g, 5 mmol) and 4-fluorobenzaldehyde (1.24 g, 10 mmol) were added into glacial acetic acid (10 mL). Under a dry HCl flow, the mixture was stirred to obtain a clear solution. Then, the reaction continued to be stirred at room temperature for 24 h. The endpoint of which was determined by thin-layer chromatography (TLC). After the reaction was complete, the above mixture was poured to 100 mL water and adjusted to neutral pH by an aqueous Na2CO3 solution. The obtained yellow solids were filtered and washed twice by water. The intermediate 3,5-bis(4-fluorobenzylidene)piperidin-4-one was obtained by the recrystallization of methanol solution. The curcumin analogue and 4-trifluoromethylbenzene-sulfonyl chloride (1.22 g, 5 mmol) were dissolved in dichloromethane (100 mL). The solution was stirred under the catalysis of organic pyridine (two drop) and monitored by TLC. After 24 h, the precipitate was collected and dried under vacuum conditions. The resulting product was recrystallized from dichloromethane/petroleum ether (1:1, v/v). Single crystals of the title compound were prepared by slow evaporation of dichloromethane/methanol solutions at room temperature.

Experimental details

The H atoms were positioned geometrically and treated as riding on their parent atoms, with d (C–H) = 0.97 Å (methylene) and Uiso(H) = 1.2Ueq(C); d(C–H) = 0.93 Å (aromatic) and Uiso(H) = 1.2Ueq(C).

Comment

Curcumin, acknowledged as 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, has attracted extensive attentions because of their potential applications in the aspect of anti-inflammatory, anti-proliferative and antiangiogenic therapies [5], [6], [7]. As an α,β-unsaturated polyphenol compound, it can be considered as one kind of chemopreventive and anticancer agent [8, 9]. Just because of the presence of a diketone group, curcumin becomes unstable at physiological pH. Rapid metabolism and deficient absorption affect its pharmacokinetics and hinder its clinical application [10]. In order to overcome the defect, it is important to modify its structure with mono ketone instead of the β-diketone group. Liu’s group synthesized novel curcumin analogues by the deletion of a methylene and the β-diketone moiety groups. Among these compounds, 5,7-dimethoxy-3-(3-(2-((1E,4E)-3-oxo-5-(pyridin-2-yl)penta-1,4-dien-1-yl)phenoxy)propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one could induce gastric cancer cells apoptosis by inhibiting the TrxR activity [11]. Li’s group reported that curcumin analogues based on a cyclohexanone moiety possess anti-inflammatory properties [12]. It was found that heterocyclic compounds often exhibit a wide range of biological activities such as antimicrobial, antitumor and antimalarial properties [13]. A piperidone ring was introduced to curcumin analogues and a set of 3,5-bis(arylidene)-4-piperidones were designed [14, 15]. Previous results indicated that fluorine-containing substituents in the aromatic rings usually imparted some distinctive properties to medicines including enhanced binding interactions, metabolic stability, and selective reactivity of compounds [16]. Additionally, it was reported that the phenylsulfonyl moiety in 3,5-bis(arylidene)-4-piperidones could significantly improve the bioactivity of anti-inflammatory [17]. As a part of our continuing study on anti-neuroinflammatory agents, one new curcumin analogue containing the piperidone ring, a fluorine atom and phenylsulfonyl moiety was synthesized by the Claisen–Schmidt condensation reaction and N-benzenesulfonylation reaction.

Single-crystal structure analysis shows that the asymmetric unit consists of a 3,5-bis(arylidene)-4-piperidinone molecule (cf. Figure). All bond lengths and bond angles were found to be consistent with the values reported in the literature [18], [19], [20], [21]. Both 4-fluorobenzylidene moieties are symmetrically arranged on the both sides of the central piperidone scaffold. In the title molecule, the torsion angles of C3–C2–C6–C7 and C3–C4–C13–C14 bonds are 179.84(19)° and 178.45(17)°, respectively. It means that the title molecule is in the E stereochemistry of the exocyclic olefinic double bonds. The piperidone ring displays a half-chair conformation with the N1 atom deviating by 0.594(2) Å from the least-squares plane through the ring. The title compound is obviously not planar with the dihedral angle between the fluorophenyl and piperidone rings being 31.97(6)° and 63.87(6)°, respectively. The dihedral angle between fluorophenyl rings is 48.21(7)°. The phenylsulfonyl moiety adopts a pseudo-axial conformation with respect to the piperidone ring, meaning that the molecule as a whole forms a “organic click” in the direction of the carbonyl group. No classic hydrogen bonds were found. Neighbouring molecules are linked via weak C–H⋯F hydrogen bonds to a two-dimensional sheet in the ab plane. Molecules containing as a group the α,β-unsaturated ketone and peripheric heteroatoms (such as O and F) may have anticancer, anti-bacterial and antifungal activities [22].


Corresponding author: Xiao-Fan Zhang, 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:

Award Identifier / Grant number: J18KA092

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

  2. Research funding: This work was supported by the Project of the Shandong Province Higher Educational Science and Technology Program (No. J18KA092).

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

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Received: 2021-07-24
Accepted: 2021-08-18
Published Online: 2021-09-02
Published in Print: 2021-12-20

© 2021 Zhong-Fei Gao 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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