Synthesis and crystal structure of (2E)-1-[3,5-bis­­(benz­yl­oxy)phen­yl]-3-(4-eth­­oxy­phen­yl)prop-2-en-1-one

In the title compound, C₃₁H₂₈O₄, the phenyl rings of the chalcone unit subtend a dihedral angle of 26.43 (10)°. The phenyl rings of the pendant benz­yloxy groups are orientated at 75.57 (13) and 75.70 (10)° with respect to their attached ring. In the crystal, weak C—H⋯O and C—H⋯π inter­actions link the mol­ecules. The inter­molecular inter­actions were qu­anti­fied and analysed using Hirshfeld surface analysis, which showed a breakdown into H⋯H (49.8%), H⋯C/C⋯H (33.8%) and H⋯O/O⋯H (13.6%) inter­actions with other types making negligible contributions.

1. Chemical context

Chalcones incorporate an α,β-unsaturated carbonyl (enone) bridge connecting two aromatic rings. The chalcone scaffold exhibits anti-cancer efficacy on various human cancer cells (Zhuang et al., 2017; Liu et al., 2022). DrugBank lists three chalcone-based drugs namely hesperidin methyl­chalcone (DrugBank: DB15943), di­hydroxy­meth­oxy­chalcone (DB14122) and 3-(4-hy­droxy­phen­yl)prop-2-en-1-one (DB07500). In general, the anti­cancer efficacy of chalcones is enhanced by attaching different substitutents at ring A of the chalcone, which is attached to the C=O group (Mai et al., 2014). As part of our studies in this area, we have prepared and undertaken a single-crystal X-ray diffraction study of the title compound, C₃₁H₂₈O₄, (I), and the results are presented here.

2. Structural commentary

The mol­ecular structure of (I) is illustrated in Fig. 1. The C12–C17 and C19–C24 phenyl rings of the chalcone unit subtend a dihedral angle of 26.43 (10)°: the most significant twist occurs about the C11—C12 bond, as indicated by the C10—C11—C12—C13 torsion angle of −13.0 (3)°. The dihedral angles between the C19–C24 and C26–C31 pendant phenyl rings and their attached C12–C17 ring are 75.57 (13) and 75.70 (10)°, respectively. The C3—O1—C2—C1, C14—O4—C25—C26 and C16—O3—C18—C19 torsion angles of 177.2 (3), 176.21 (18) and 179.5 (2)°, respectively, indicate an anti conformation in each case.

Figure 1 The mol­ecular structure of (I) with displacement ellipsoids drawn at the 30% probability level.

3. Supra­molecular features

In the crystal of (I), the mol­ecules associate via weak C—H⋯O inter­actions (Table 1), forming C(15) chains propagating along [101] (Fig. 2). In addition, inversion-related mol­ecules are linked by pairwise weak C—H⋯π inter­actions (Fig. 3).

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C26–C31 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1A⋯O4^i	0.96	2.64	3.227 (3)	119
C25—H25B⋯Cg1^ii	0.97	2.68	3.398 (2)	132
Symmetry codes: (i) ; (ii) .

Figure 2 Detail of the packing of (I) showing C—H⋯O inter­actions as dashed lines. For clarity H atoms not involved in these hydrogen bonds have been omitted.

Figure 3 Detail of the packing of (I) showing C—H⋯π inter­actions as dashed lines.

4. Hirshfeld surface analysis

To further characterize the inter­molecular inter­actions in (I), a Hirshfeld surface analysis was performed using Crystal Explorer 21 (Spackman et al., 2021) and the associated two dimensional fingerprint plots were generated. The HS mapped over d_norm in the range −0.09 to +1.53 a.u. is illustrated in Fig. 4, using colours to indicate contacts that are shorter (red areas), equal to (white areas), or longer than (blue areas) the sum of the van der Waals radii (Ashfaq et al., 2021).

Figure 4 A view of the Hirshfeld surface mapped over dnorm for (I).

The overall two-dimensional fingerprint plot, Fig. 5a, and those delineated into H⋯H inter­actions (49.8%), H⋯C/C⋯H (33.8%), H⋯O/O⋯H (13.6%), C⋯C (1.8%) and O⋯C/C⋯O (1%) inter­actions are illustrated in Fig. 5b–f, respectively, together with their relative contributions to the HS. The most important inter­action is H⋯H, which is reflected in Fig. 5b as widely scattered points of high density due to the large hydrogen content of the mol­ecule with the tip at d_e = d_i = 1.10 Å. As a result of the presence of C—H⋯O inter­actions, the H⋯O/O⋯H contacts contribute 13.6% to the overall crystal packing, as reflected in Fig. 5d with the tips at d_e + d_i = 2.50 Å.

Figure 5 Two-dimensional fingerprint plots for (I), showing (a) all inter­actions, and delineated into (b) H⋯H, (c) H⋯C/C⋯H, (d) H⋯O/O⋯H, (e) C⋯C and (f) O⋯C/C⋯O inter­actions.

5. Synthesis and crystallization

Equimolar concentrations of 3,5-di­benzyl­oxyaceto­phenone and 4-eth­oxy­benzaldehyde were dissolved in ethanol in separate reaction flasks and then mixed. Drop by drop, utilizing a magnetic stirring device, 2 ml of 10% sodium hydroxide in water were introduced at room temperature. The course of the process was tracked using thin-layer chromatography. After the process was complete, the resulting product was placed on crushed ice. The finished product was vacuum-filtered, dried, and then recrystallized from ethanol solution to yield colourless blocks of the title compound.

IR (cm⁻¹): 3032 aromatic C—H stretch, 2934 and 2875 aliphatic C—H stretch, 1651 C=O stretch, 1568 aromatic ring C=C stretch (see table in the supporting information).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed in idealized positions and allowed to ride on their parent atoms: C—H = 0.93–0.97 Å, with U_iso(H) = 1.5U_eq(C-meth­yl) and 1.2U_eq(C) for other H atoms.

Table 2
Experimental details

Crystal data
Chemical formula	C31H28O4
Mr	464.53
Crystal system, space group	Triclinic, P
Temperature (K)	298
a, b, c (Å)	9.0494 (9), 10.0326 (11), 14.6932 (15)
α, β, γ (°)	100.153 (3), 107.292 (3), 90.789 (4)
V (Å^3)	1250.6 (2)
Z	2
Radiation type	Mo Kα
μ (mm^−1)	0.08
Crystal size (mm)	0.31 × 0.23 × 0.19
Data collection
Diffractometer	Bruker D8 Quest XRD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	30243, 5428, 3607
Rint	0.037
(sin θ/λ)max (Å^−1)	0.638
Refinement
R[F^2 > 2σ(F^2)], wR(F^2), S	0.057, 0.178, 1.05
No. of reflections	5428
No. of parameters	317
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å^−3)	0.36, −0.18
Computer programs: APEX3 and SAINT (Bruker, 2017), SHELXT2018/2 (Sheldrick, 2015a), SHELXL2019/3 (Sheldrick, 2015b), ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2020).

Footnotes

‡Additional correspondence author, e-mail: [e-mail].