3-(2,3-Di­meth­oxy­phen­yl)-2,3-di­hydro-1H-benzo[f]chromen-1-one

The crystal structure of a flavanone is reported in which C—H⋯O hydrogen bonds link the mol­ecules into chains.

Abstract

In the title compound, C₂₁H₁₈O₄, the central pyran ring is in an envelope conformation and the dihedral angle between the benzene ring and naphthalene ring system is 88.31 (1)°. The meth­oxy groups at the ortho and meta positions of the benzene ring are tilted to the ring with C—C—O—C torsion angles of 105.9 (4) and 9.5 (5)°, respectively. In the crystal, pairwise C—H⋯O hydrogen bonds form R ² ₂(14) inversion dimers, which are linked by another pair of C—H⋯O hydrogen bonds to form [210] chains in the crystal.

Structure description

Flavanones exhibit a wide range of biological properties, including anti­viral (Shi et al., 2022 ▸), anti­fungal (Emami et al. 2013 ▸) and anti­cancer activities (Bailly, 2021 ▸; Zhao et al., 2019 ▸) as well as being used in the treatment of Alzheimer’s disease (Jin et al., 2021 ▸). In continuation of our research into flavanone derivatives (Sung, 2020 ▸), the title compound was synthesized and its crystal structure was determined.

The title compound, C₂₁H₁₈O₄, was prepared in a two-step reaction. A Claisen–Schmidt condensation reaction between 2,3-dimeth­oxy-benzaldehyde and 2-hy­droxy-1-aceto­naphthone gave the corresponding benzochalcone, which was then used for an intra­molecular Michael addition reaction to provide the desired flavanone (Yong et al. 2014 ▸). The mol­ecular structure of the title compound is shown in Fig. 1 ▸. The central pyran ring (C1/C2/C3/O2/C12/C21) has an envelope conformation with atom C3 as the flap. C3 is a stereogenic centre: in the arbitrarily chosen asymmetric unit, C3 has an S configuration, but crystal symmetry generates a racemic mixture. The hydrogen atom H3 attached to C3 forms a trans diaxial conformation with atom H2B of the C2 methyl­ene group (H3—C3—C2—H2B = −179.1°) and a gauche conformation with the other H atom attached to C2 (H3—C3—C2—H2A = −60.8°). The meth­oxy group at the meta position of the benzene ring is twisted slightly from the ring [C9—C7—O4—C8 = 9.5 (5)°]. However, the meth­oxy group at the ortho position is significantly distorted from the benzene ring due to steric hindrance with the pyran ring [C4—C5—O3—C6 = 105.9 (4)°]. The C12–C21 naphthalene ring system (r.m.s. deviation = 0.036 Å) and benzene ring (C4/ C5/C7/ C11/C9/C10]; r.m.s. deviation = 0.003 Å) lie almost perpendicular to each other forming a dihedral angle of 88.31 (1)°. In the crystal, pairs of C18—H18⋯O1 hydrogen bonds form an inversion dimer with graph-set notation (14). The dimers are linked by another pair of C13—H13⋯O2 hydrogen bonds to form a [210] chain. (Table 1 ▸, Fig. 2 ▸).

Figure 1.

The mol­ecular structure of the title compound, showing the atom-labelling scheme and displacement ellipsoids drawn at the 50% probability level.

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13⋯O2i	0.95	2.52	3.454 (4)	169
C18—H18⋯O1ii	0.95	2.52	3.452 (4)	166

Symmetry codes: (i) ; (ii) .

Figure 2.

Part of the crystal structure of the title compound, showing the weak C—H⋯O hydrogen bonds forming (14) dimers as yellow lines. An additional pair of inter­molecular hydrogen bonds (blue lines) link the dimers to form a chain.

Synthesis and crystallization

A solution of 2-hy­droxy-1-aceto­naphthone (186 mg, 1 mmol) and 2,3-di­meth­oxy­benzaldehyde (166 mg, 1 mmol) was dissolved in ethanol (15 ml) and the temperature was adjusted to around 276–277 K in an ice bath. To the cooled reaction mixture was added 1.0 ml of 40% aqueous KOH solution, and the reaction mixture was stirred at room temperature for 24 h. This mixture was poured into iced water (50 ml) acidified with 6 N HCl solution. The mixture was extracted with ethyl acetate (3 × 30 ml) and the combined organic layers were dried under MgSO₄. Filtration and evaporation of the filtrate gave a solid chalcone, which was dissolved in DMSO and a catalytic amount of conc. HCl was added. After 10 h, the reaction mixture was poured into iced water to give a solid flavanone. Recrystallization from ethanol solution gave the crystals used in this X-ray diffraction study.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸.

Table 2. Experimental details.

Crystal data
Chemical formula	C21H18O4
M r	334.35
Crystal system, space group	Triclinic, P
Temperature (K)	200
a, b, c (Å)	8.3312 (14), 9.6506 (16), 11.797 (2)
α, β, γ (°)	94.261 (4), 107.335 (4), 112.326 (3)
V (Å3)	818.4 (2)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.09
Crystal size (mm)	0.34 × 0.21 × 0.16
Data collection
Diffractometer	Bruker SMART CCD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.969, 0.985
No. of measured, independent and observed [I > 2σ(I)] reflections	5181, 3202, 2136
R int	0.020
(sin θ/λ)max (Å−1)	0.618
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.057, 0.204, 1.13
No. of reflections	3202
No. of parameters	228
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.30, −0.38

Computer programs: APEX2 and SAINT (Bruker, 2012 ▸), SHELXS and SHELXTL (Sheldrick, 2008 ▸) , SHELXL2014 (Sheldrick, 2015 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 2205278

Additional supporting information: crystallographic information; 3D view; checkCIF report

full crystallographic data

Crystal data

C21H18O4	Z = 2
Mr = 334.35	F(000) = 352
Triclinic, P1	Dx = 1.357 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.3312 (14) Å	Cell parameters from 2013 reflections
b = 9.6506 (16) Å	θ = 2.7–25.9°
c = 11.797 (2) Å	µ = 0.09 mm−1
α = 94.261 (4)°	T = 200 K
β = 107.335 (4)°	Block, yellow
γ = 112.326 (3)°	0.34 × 0.21 × 0.16 mm
V = 818.4 (2) Å3

Data collection

Bruker SMART CCD diffractometer	3202 independent reflections
Radiation source: fine-focus sealed tube	2136 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.020
ω scans	θmax = 26.1°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −10→9
Tmin = 0.969, Tmax = 0.985	k = −11→11
5181 measured reflections	l = −14→13

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.204	H-atom parameters constrained
S = 1.13	w = 1/[σ2(Fo2) + (0.0727P)2 + 0.8943P] where P = (Fo2 + 2Fc2)/3
3202 reflections	(Δ/σ)max < 0.001
228 parameters	Δρmax = 0.30 e Å−3
0 restraints	Δρmin = −0.38 e Å−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.5916 (4)	0.4265 (4)	0.1200 (3)	0.0387 (7)
O1	0.7393 (3)	0.5280 (3)	0.1255 (2)	0.0534 (7)
C2	0.4897 (5)	0.4555 (4)	0.1987 (3)	0.0467 (8)
H2A	0.5804	0.5215	0.2782	0.056*
H2B	0.4162	0.5101	0.1594	0.056*
C3	0.3641 (4)	0.3088 (4)	0.2179 (3)	0.0404 (8)
H3	0.4419	0.2569	0.2588	0.048*
O2	0.2359 (3)	0.2101 (2)	0.10246 (19)	0.0406 (6)
C4	0.2501 (4)	0.3214 (4)	0.2935 (3)	0.0387 (7)
C5	0.2559 (4)	0.2556 (3)	0.3936 (3)	0.0368 (7)
O3	0.3634 (3)	0.1743 (3)	0.4229 (2)	0.0470 (6)
C6	0.5292 (5)	0.2525 (5)	0.5253 (4)	0.0649 (11)
H6A	0.6015	0.3530	0.5121	0.097*
H6B	0.6025	0.1923	0.5364	0.097*
H6C	0.4983	0.2664	0.5979	0.097*
C7	0.1468 (4)	0.2610 (4)	0.4626 (3)	0.0396 (7)
O4	0.1617 (3)	0.1893 (3)	0.5578 (2)	0.0501 (6)
C8	0.0315 (5)	0.1696 (5)	0.6180 (4)	0.0558 (10)
H8A	0.0463	0.2702	0.6546	0.084*
H8B	0.0537	0.1122	0.6816	0.084*
H8C	−0.0947	0.1128	0.5590	0.084*
C9	0.0321 (5)	0.3356 (4)	0.4296 (3)	0.0443 (8)
H9	−0.0429	0.3403	0.4753	0.053*
C10	0.0275 (5)	0.4029 (4)	0.3300 (3)	0.0474 (8)
H10	−0.0501	0.4549	0.3083	0.057*
C11	0.1337 (5)	0.3958 (4)	0.2616 (3)	0.0452 (8)
H11	0.1277	0.4416	0.1928	0.054*
C12	0.3185 (4)	0.1820 (4)	0.0248 (3)	0.0366 (7)
C13	0.2063 (4)	0.0489 (4)	−0.0672 (3)	0.0425 (8)
H13	0.0818	−0.0104	−0.0740	0.051*
C14	0.2764 (5)	0.0057 (4)	−0.1459 (3)	0.0427 (8)
H14	0.1997	−0.0838	−0.2083	0.051*
C15	0.4630 (4)	0.0918 (4)	−0.1370 (3)	0.0378 (7)
C16	0.5352 (5)	0.0391 (4)	−0.2161 (3)	0.0428 (8)
H16	0.4571	−0.0510	−0.2778	0.051*
C17	0.7169 (5)	0.1166 (4)	−0.2048 (3)	0.0482 (9)
H17	0.7653	0.0800	−0.2577	0.058*
C18	0.8306 (5)	0.2500 (4)	−0.1150 (3)	0.0474 (9)
H18	0.9572	0.3027	−0.1065	0.057*
C19	0.7633 (5)	0.3060 (4)	−0.0389 (3)	0.0438 (8)
H19	0.8427	0.3985	0.0200	0.053*
C20	0.5757 (4)	0.2274 (4)	−0.0469 (3)	0.0366 (7)
C21	0.4989 (4)	0.2770 (3)	0.0347 (3)	0.0364 (7)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0354 (17)	0.0354 (16)	0.0444 (18)	0.0114 (14)	0.0171 (14)	0.0101 (14)
O1	0.0415 (14)	0.0415 (13)	0.0690 (17)	0.0044 (11)	0.0286 (13)	0.0005 (12)
C2	0.0425 (19)	0.0418 (18)	0.053 (2)	0.0108 (15)	0.0244 (16)	−0.0009 (16)
C3	0.0327 (16)	0.0440 (18)	0.0390 (17)	0.0112 (14)	0.0130 (14)	0.0041 (14)
O2	0.0309 (11)	0.0458 (12)	0.0404 (12)	0.0101 (10)	0.0165 (10)	0.0001 (10)
C4	0.0335 (16)	0.0407 (17)	0.0353 (17)	0.0101 (14)	0.0120 (14)	0.0028 (14)
C5	0.0330 (16)	0.0334 (16)	0.0428 (18)	0.0123 (13)	0.0157 (14)	0.0027 (14)
O3	0.0464 (14)	0.0478 (13)	0.0530 (14)	0.0236 (11)	0.0217 (12)	0.0090 (11)
C6	0.048 (2)	0.087 (3)	0.055 (2)	0.034 (2)	0.0076 (19)	0.006 (2)
C7	0.0399 (18)	0.0389 (17)	0.0393 (17)	0.0124 (15)	0.0198 (15)	0.0042 (14)
O4	0.0556 (15)	0.0598 (15)	0.0489 (14)	0.0277 (13)	0.0312 (12)	0.0186 (12)
C8	0.061 (2)	0.061 (2)	0.056 (2)	0.023 (2)	0.039 (2)	0.0157 (19)
C9	0.0443 (19)	0.0452 (18)	0.0471 (19)	0.0172 (16)	0.0246 (16)	0.0045 (15)
C10	0.0438 (19)	0.050 (2)	0.053 (2)	0.0234 (17)	0.0196 (17)	0.0080 (17)
C11	0.0451 (19)	0.0470 (19)	0.0431 (19)	0.0180 (16)	0.0163 (16)	0.0131 (15)
C12	0.0325 (16)	0.0436 (17)	0.0360 (17)	0.0157 (14)	0.0158 (14)	0.0080 (14)
C13	0.0292 (16)	0.0429 (18)	0.0457 (19)	0.0065 (14)	0.0136 (14)	0.0007 (15)
C14	0.0402 (18)	0.0417 (18)	0.0411 (18)	0.0120 (15)	0.0161 (15)	0.0013 (14)
C15	0.0361 (17)	0.0385 (17)	0.0371 (17)	0.0141 (14)	0.0127 (14)	0.0084 (14)
C16	0.0433 (19)	0.0439 (18)	0.0452 (19)	0.0190 (15)	0.0208 (16)	0.0074 (15)
C17	0.054 (2)	0.050 (2)	0.053 (2)	0.0255 (18)	0.0306 (18)	0.0131 (17)
C18	0.0397 (18)	0.050 (2)	0.061 (2)	0.0178 (16)	0.0294 (17)	0.0189 (17)
C19	0.0370 (18)	0.0438 (18)	0.051 (2)	0.0136 (15)	0.0213 (16)	0.0105 (15)
C20	0.0343 (16)	0.0380 (16)	0.0404 (17)	0.0147 (14)	0.0165 (14)	0.0135 (14)
C21	0.0315 (16)	0.0371 (16)	0.0396 (17)	0.0120 (13)	0.0143 (14)	0.0080 (14)

Geometric parameters (Å, º)

C1—O1	1.227 (4)	C8—H8C	0.9800
C1—C21	1.471 (4)	C9—C10	1.381 (5)
C1—C2	1.507 (4)	C9—H9	0.9500
C2—C3	1.488 (5)	C10—C11	1.379 (5)
C2—H2A	0.9900	C10—H10	0.9500
C2—H2B	0.9900	C11—H11	0.9500
C3—O2	1.439 (4)	C12—C21	1.394 (4)
C3—C4	1.513 (4)	C12—C13	1.406 (4)
C3—H3	1.0000	C13—C14	1.352 (4)
O2—C12	1.366 (3)	C13—H13	0.9500
C4—C5	1.379 (4)	C14—C15	1.423 (4)
C4—C11	1.396 (5)	C14—H14	0.9500
C5—O3	1.389 (4)	C15—C20	1.410 (4)
C5—C7	1.400 (4)	C15—C16	1.410 (4)
O3—C6	1.419 (4)	C16—C17	1.369 (5)
C6—H6A	0.9800	C16—H16	0.9500
C6—H6B	0.9800	C17—C18	1.396 (5)
C6—H6C	0.9800	C17—H17	0.9500
C7—O4	1.362 (4)	C18—C19	1.367 (5)
C7—C9	1.388 (5)	C18—H18	0.9500
O4—C8	1.428 (4)	C19—C20	1.424 (4)
C8—H8A	0.9800	C19—H19	0.9500
C8—H8B	0.9800	C20—C21	1.449 (4)
O1—C1—C21	123.8 (3)	C10—C9—C7	119.7 (3)
O1—C1—C2	119.8 (3)	C10—C9—H9	120.1
C21—C1—C2	116.4 (3)	C7—C9—H9	120.1
C3—C2—C1	110.8 (3)	C11—C10—C9	121.1 (3)
C3—C2—H2A	109.5	C11—C10—H10	119.5
C1—C2—H2A	109.5	C9—C10—H10	119.5
C3—C2—H2B	109.5	C10—C11—C4	120.0 (3)
C1—C2—H2B	109.5	C10—C11—H11	120.0
H2A—C2—H2B	108.1	C4—C11—H11	120.0
O2—C3—C2	109.8 (3)	O2—C12—C21	123.3 (3)
O2—C3—C4	107.0 (2)	O2—C12—C13	114.5 (3)
C2—C3—C4	116.2 (3)	C21—C12—C13	122.3 (3)
O2—C3—H3	107.8	C14—C13—C12	119.7 (3)
C2—C3—H3	107.8	C14—C13—H13	120.2
C4—C3—H3	107.8	C12—C13—H13	120.2
C12—O2—C3	114.2 (2)	C13—C14—C15	121.3 (3)
C5—C4—C11	118.8 (3)	C13—C14—H14	119.4
C5—C4—C3	120.3 (3)	C15—C14—H14	119.4
C11—C4—C3	120.9 (3)	C20—C15—C16	120.5 (3)
C4—C5—O3	119.6 (3)	C20—C15—C14	119.6 (3)
C4—C5—C7	121.4 (3)	C16—C15—C14	119.9 (3)
O3—C5—C7	118.9 (3)	C17—C16—C15	120.6 (3)
C5—O3—C6	114.0 (3)	C17—C16—H16	119.7
O3—C6—H6A	109.5	C15—C16—H16	119.7
O3—C6—H6B	109.5	C16—C17—C18	119.5 (3)
H6A—C6—H6B	109.5	C16—C17—H17	120.2
O3—C6—H6C	109.5	C18—C17—H17	120.2
H6A—C6—H6C	109.5	C19—C18—C17	121.2 (3)
H6B—C6—H6C	109.5	C19—C18—H18	119.4
O4—C7—C9	125.0 (3)	C17—C18—H18	119.4
O4—C7—C5	116.0 (3)	C18—C19—C20	120.8 (3)
C9—C7—C5	119.0 (3)	C18—C19—H19	119.6
C7—O4—C8	117.8 (3)	C20—C19—H19	119.6
O4—C8—H8A	109.5	C15—C20—C19	117.4 (3)
O4—C8—H8B	109.5	C15—C20—C21	119.2 (3)
H8A—C8—H8B	109.5	C19—C20—C21	123.4 (3)
O4—C8—H8C	109.5	C12—C21—C20	117.7 (3)
H8A—C8—H8C	109.5	C12—C21—C1	117.6 (3)
H8B—C8—H8C	109.5	C20—C21—C1	124.5 (3)
O1—C1—C2—C3	−156.5 (3)	C3—O2—C12—C13	158.7 (3)
C21—C1—C2—C3	26.8 (4)	O2—C12—C13—C14	−176.9 (3)
C1—C2—C3—O2	−57.2 (4)	C21—C12—C13—C14	3.3 (5)
C1—C2—C3—C4	−178.8 (3)	C12—C13—C14—C15	0.6 (5)
C2—C3—O2—C12	55.5 (3)	C13—C14—C15—C20	−2.0 (5)
C4—C3—O2—C12	−177.5 (3)	C13—C14—C15—C16	176.4 (3)
O2—C3—C4—C5	111.0 (3)	C20—C15—C16—C17	1.6 (5)
C2—C3—C4—C5	−125.9 (3)	C14—C15—C16—C17	−176.8 (3)
O2—C3—C4—C11	−67.2 (4)	C15—C16—C17—C18	−0.8 (5)
C2—C3—C4—C11	55.9 (4)	C16—C17—C18—C19	−0.9 (5)
C11—C4—C5—O3	176.6 (3)	C17—C18—C19—C20	1.7 (5)
C3—C4—C5—O3	−1.6 (4)	C16—C15—C20—C19	−0.8 (5)
C11—C4—C5—C7	0.5 (5)	C14—C15—C20—C19	177.6 (3)
C3—C4—C5—C7	−177.7 (3)	C16—C15—C20—C21	−178.7 (3)
C4—C5—O3—C6	105.9 (4)	C14—C15—C20—C21	−0.3 (5)
C7—C5—O3—C6	−77.9 (4)	C18—C19—C20—C15	−0.9 (5)
C4—C5—C7—O4	178.7 (3)	C18—C19—C20—C21	177.0 (3)
O3—C5—C7—O4	2.6 (4)	O2—C12—C21—C20	174.8 (3)
C4—C5—C7—C9	−0.6 (5)	C13—C12—C21—C20	−5.5 (5)
O3—C5—C7—C9	−176.7 (3)	O2—C12—C21—C1	−10.3 (5)
C9—C7—O4—C8	9.5 (5)	C13—C12—C21—C1	169.4 (3)
C5—C7—O4—C8	−169.8 (3)	C15—C20—C21—C12	3.9 (4)
O4—C7—C9—C10	−179.3 (3)	C19—C20—C21—C12	−173.9 (3)
C5—C7—C9—C10	0.0 (5)	C15—C20—C21—C1	−170.6 (3)
C7—C9—C10—C11	0.7 (5)	C19—C20—C21—C1	11.6 (5)
C9—C10—C11—C4	−0.8 (5)	O1—C1—C21—C12	−170.1 (3)
C5—C4—C11—C10	0.2 (5)	C2—C1—C21—C12	6.4 (4)
C3—C4—C11—C10	178.4 (3)	O1—C1—C21—C20	4.4 (5)
C3—O2—C12—C21	−21.5 (4)	C2—C1—C21—C20	−179.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C13—H13···O2i	0.95	2.52	3.454 (4)	169
C18—H18···O1ii	0.95	2.52	3.452 (4)	166

Symmetry codes: (i) −x, −y, −z; (ii) −x+2, −y+1, −z.

Funding Statement

This work was supported by a Dongduk Women’s University grant.