3-Meth­oxy-2-p-tolyl-4H-chromen-4-one

Koh, D.

doi:10.1107/S2414314616020198

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 12| December 2016| x162019

https://doi.org/10.1107/S2414314616020198

Open

access

3-Methoxy-2-p-tolyl-4H-chromen-4-one

Dongsoo Koh ^a ^*

^aDepartment of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea
^*Correspondence e-mail: dskoh@dongduk.ac.kr

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 10 December 2016; accepted 20 December 2016; online 22 December 2016)

In the title compound, C₁₇H₁₄O₃, the methyl-substituted benzene ring is twisted relative to the 4H-chromenon skeleton by 51.5 (2)°. The C atom of the methoxy group of the 4H-chromenon unit is displaced from the ring plane by 1.225 (2) Å. In the crystal, C—H—O interactions connect the molecules into (001) sheets.

Keywords: crystal structure; flavonol; methylation.

CCDC reference: 1523530

Structure description

Flavonol, as shown in its name, is a class of flavonoid which has a 3-hydroxy functional group in the flavone skeleton. Various flavonols have been isolated from natural sources and synthesized(Bendaikha et al., 2014 ; Prescott et al., 2013 ) due to their wide spectrum of biological activities (Lee et al., 2014 ; Dias et al., 2013 ). Because it has been well established that the presence and position of hydroxy and methoxy substituents plays an important role in determining the biological activity of flavonoids (Burmistrova et al., 2014 ), the 3-hydroxy functional group in the title flavonol was methylated and its crystal structure was determined.

An intermediate, chalcone I, was prepared by the previously reported methods and flavonol II was obtained by oxidative cyclization of the chalcone I with H₂O₂ in alkaline methanol medium (Lee et al., 2014). Methylation of flavonol II with DMS (dimethyl sulfide) gave the desired methylated flavonol.

In the title compound (Fig. 1), the methyl-substituted benzene ring is twisted relative to the 4H-chromenone ring by 51.5 (2)°. The methoxy group of the 4H-chromenone unit is almost orthogonal to the ring [displacement = 1.225 (2) Å; C9—O3—C17 = 113.67 (14)°]. In the crystal, C—H—O interactions (Table 1) connect the molecules into (001) sheets (Figs. 2 and 3). Example structures of methylated flavonols have been published previously (e.g. Serdiuk et al., 2013 ).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4⋯O1ⁱ	0.94	2.48	3.249 (2)	138
C6—H6⋯O1ⁱⁱ	0.94	2.55	3.214 (2)	128
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]$ ; (ii) x, y-1, z.

Figure 1
The molecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level

Figure 2
Part of the crystal structure of the title compound, with C4—H4⋯O1 interactions shown as dashed lines; these generate [100] chains.

Figure 3
A partial view of the crystal structure of the title compound, with C6—H6⋯O1 interactions shown as brown dashed lines; these generate [010] chains.

Synthesis and crystallization

2-Hydroxyacetophenone (10 mmol, 1.36 g) and 4-methylbenzaldehyde (10 mmol, 1.2 g) were dissolved in 20 ml of ethanol and the temperature was adjusted to around 275–277 K in an ice bath. To the cooled reaction mixture was added 2 ml of 50% (w/v) of aqueous KOH solution and the resulting solution was stirred at room temperature for 24 h. At the end of the reaction, ice water was added to the mixture and it was then acidified with 3 N HCl (pH = 3–4). The precipitate was vacuum filtered and washed with methanol to give chalcone I. The chalcone compound I (1 mmol, 238 mg) was dissolved in 5 ml of methanol and 5 ml of THF and cooled in a water–ice bath (275–277 K). To the cold solution was added 16% sodium hydroxide (0.5 ml) and an excess of 35% H₂O₂ (2 ml). The reaction mixture was stirred for 3 h and was then acidified with 3 N HCl (pH = 4–5). The precipitatate was vacuum filtered and washed with H₂O–methanol solution to furnish flavonol II. The flavonol compound II (0.3 mmol, 75 mg) was methylated with dimethyl sulfate (DMS) (10 mmol, 1 ml) in 4 ml of 16% NaOH solution. The reaction mixture was heated at 333 K for 4–6 h. The resulting mixture was extracted with EtOAc (20 ml × 2) and washed with saturated NaHCO₃ solution (20 ml × 2). The combined organic layer was dried over MgSO₄ and filtered. The filtrate was evaporated to yield the title compound as a crude solid which was recrystallized from methanol solution (m.p. 364–365 K). The synthetic scheme is shown in Fig. 4.

Figure 4
Synthetic scheme for the title compound.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₁₇H₁₄O₃
M_r	266.28
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	223
a, b, c (Å)	6.2439 (2), 7.9982 (3), 27.0113 (10)
V (Å³)	1348.94 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.22 × 0.14 × 0.07

Data collection
Diffractometer	PHOTON 100 CMOS
No. of measured, independent and observed [I > 2σ(I)] reflections	21647, 3356, 2520
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.104, 1.05
No. of reflections	3356
No. of parameters	183
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.16
Computer programs: SMART and SAINT (Bruker, 2000 ), SHELXS97, SHELXL97 and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1523530

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314616020198/hb4104sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616020198/hb4104Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314616020198/hb4104Isup3.cml

checkCIF report

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

3-Methoxy-2-p-tolyl-4H-chromen-4-one top

Crystal data top

C₁₇H₁₄O₃	F(000) = 560
M_r = 266.28	D_x = 1.311 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9141 reflections
a = 6.2439 (2) Å	θ = 2.7–27.0°
b = 7.9982 (3) Å	µ = 0.09 mm⁻¹
c = 27.0113 (10) Å	T = 223 K
V = 1348.94 (8) Å³	Block, colourless
Z = 4	0.22 × 0.14 × 0.07 mm

Data collection top

PHOTON 100 CMOS diffractometer	2520 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.049
Graphite monochromator	θ_max = 28.3°, θ_min = 2.7°
φ and ω scans	h = −8→8
21647 measured reflections	k = −10→10
3356 independent reflections	l = −36→36

Refinement top

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.104	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0451P)² + 0.2725P] where P = (F_o² + 2F_c²)/3
3356 reflections	(Δ/σ)_max = 0.001
183 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.8605 (3)	0.2938 (2)	0.91222 (6)	0.0330 (4)
O1	0.9374 (2)	0.42547 (15)	0.92802 (5)	0.0426 (3)
C2	0.9379 (3)	0.1291 (2)	0.92751 (6)	0.0326 (4)
C3	1.1101 (3)	0.1115 (2)	0.96055 (7)	0.0416 (5)
H3	1.1757	0.2070	0.9740	0.050*
C4	1.1831 (4)	−0.0452 (3)	0.97322 (7)	0.0477 (5)
H4	1.3004	−0.0564	0.9948	0.057*
C5	1.0840 (3)	−0.1870 (2)	0.95420 (7)	0.0423 (5)
H5	1.1335	−0.2934	0.9635	0.051*
C6	0.9149 (3)	−0.1736 (2)	0.92205 (6)	0.0370 (4)
H6	0.8478	−0.2695	0.9093	0.044*
C7	0.8453 (3)	−0.0147 (2)	0.90884 (6)	0.0326 (4)
O2	0.68193 (19)	−0.00843 (14)	0.87466 (4)	0.0343 (3)
C8	0.6107 (3)	0.1430 (2)	0.85826 (6)	0.0315 (4)
C9	0.6885 (3)	0.2892 (2)	0.87624 (6)	0.0319 (4)
C10	0.4456 (3)	0.1239 (2)	0.81962 (6)	0.0319 (4)
C11	0.2745 (3)	0.0167 (2)	0.82682 (7)	0.0385 (4)
H11	0.2629	−0.0433	0.8566	0.046*
C12	0.1211 (3)	−0.0028 (2)	0.79056 (7)	0.0390 (4)
H12	0.0022	−0.0717	0.7968	0.047*
C13	0.1381 (3)	0.0767 (2)	0.74513 (7)	0.0360 (4)
C14	0.3115 (3)	0.1827 (2)	0.73797 (7)	0.0376 (4)
H14	0.3268	0.2380	0.7075	0.045*
C15	0.4623 (3)	0.2085 (2)	0.77474 (6)	0.0365 (4)
H15	0.5762	0.2833	0.7694	0.044*
C16	−0.0256 (3)	0.0460 (3)	0.70531 (7)	0.0458 (5)
H16A	−0.1641	0.0869	0.7162	0.069*
H16B	−0.0349	−0.0729	0.6987	0.069*
H16C	0.0165	0.1043	0.6754	0.069*
O3	0.6097 (2)	0.43757 (14)	0.85849 (5)	0.0406 (3)
C17	0.4490 (3)	0.5098 (3)	0.88908 (8)	0.0525 (5)
H17A	0.5034	0.5214	0.9225	0.079*
H17B	0.3236	0.4382	0.8893	0.079*
H17C	0.4105	0.6190	0.8763	0.079*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0369 (9)	0.0283 (8)	0.0339 (9)	−0.0017 (8)	0.0067 (8)	−0.0018 (7)
O1	0.0476 (8)	0.0290 (6)	0.0512 (8)	−0.0034 (6)	−0.0014 (7)	−0.0076 (5)
C2	0.0385 (10)	0.0298 (8)	0.0295 (8)	−0.0004 (8)	0.0043 (7)	−0.0012 (7)
C3	0.0495 (12)	0.0367 (10)	0.0385 (10)	−0.0031 (9)	−0.0041 (9)	−0.0046 (8)
C4	0.0543 (12)	0.0468 (11)	0.0419 (11)	0.0046 (11)	−0.0117 (10)	0.0040 (9)
C5	0.0525 (12)	0.0333 (9)	0.0411 (10)	0.0063 (9)	0.0000 (9)	0.0068 (8)
C6	0.0436 (11)	0.0279 (9)	0.0395 (10)	−0.0006 (8)	0.0036 (9)	0.0037 (7)
C7	0.0354 (9)	0.0324 (9)	0.0299 (8)	0.0007 (8)	0.0029 (7)	0.0006 (7)
O2	0.0370 (7)	0.0257 (6)	0.0401 (7)	−0.0008 (6)	−0.0042 (5)	−0.0002 (5)
C8	0.0308 (9)	0.0296 (8)	0.0342 (9)	0.0011 (7)	0.0049 (8)	0.0033 (7)
C9	0.0350 (9)	0.0258 (8)	0.0348 (9)	0.0013 (8)	0.0043 (7)	0.0019 (7)
C10	0.0320 (9)	0.0288 (8)	0.0349 (9)	0.0014 (8)	0.0034 (7)	−0.0023 (7)
C11	0.0400 (10)	0.0395 (10)	0.0362 (9)	−0.0046 (9)	0.0047 (8)	0.0027 (8)
C12	0.0317 (9)	0.0402 (10)	0.0452 (10)	−0.0061 (9)	0.0032 (8)	−0.0006 (8)
C13	0.0331 (9)	0.0362 (9)	0.0387 (10)	0.0063 (8)	0.0009 (8)	−0.0047 (8)
C14	0.0392 (10)	0.0377 (10)	0.0357 (9)	0.0014 (9)	0.0041 (8)	0.0038 (7)
C15	0.0337 (9)	0.0343 (9)	0.0415 (10)	−0.0042 (9)	0.0053 (8)	0.0018 (8)
C16	0.0400 (11)	0.0518 (12)	0.0456 (11)	0.0002 (10)	−0.0041 (9)	−0.0046 (9)
O3	0.0454 (7)	0.0281 (6)	0.0483 (7)	0.0057 (6)	0.0056 (7)	0.0046 (5)
C17	0.0445 (11)	0.0524 (12)	0.0606 (13)	0.0154 (11)	0.0038 (10)	−0.0006 (10)

Geometric parameters (Å, º) top

C1—O1	1.233 (2)	C10—C11	1.383 (3)
C1—C9	1.449 (3)	C10—C15	1.392 (2)
C1—C2	1.463 (2)	C11—C12	1.379 (3)
C2—C7	1.382 (2)	C11—H11	0.9400
C2—C3	1.404 (3)	C12—C13	1.386 (3)
C3—C4	1.377 (3)	C12—H12	0.9400
C3—H3	0.9400	C13—C14	1.388 (3)
C4—C5	1.391 (3)	C13—C16	1.504 (3)
C4—H4	0.9400	C14—C15	1.384 (3)
C5—C6	1.371 (3)	C14—H14	0.9400
C5—H5	0.9400	C15—H15	0.9400
C6—C7	1.390 (2)	C16—H16A	0.9700
C6—H6	0.9400	C16—H16B	0.9700
C7—O2	1.377 (2)	C16—H16C	0.9700
O2—C8	1.364 (2)	O3—C17	1.422 (2)
C8—C9	1.357 (2)	C17—H17A	0.9700
C8—C10	1.475 (2)	C17—H17B	0.9700
C9—O3	1.371 (2)	C17—H17C	0.9700

O1—C1—C9	122.85 (16)	C15—C10—C8	120.88 (16)
O1—C1—C2	122.85 (17)	C12—C11—C10	120.43 (17)
C9—C1—C2	114.29 (15)	C12—C11—H11	119.8
C7—C2—C3	117.98 (17)	C10—C11—H11	119.8
C7—C2—C1	120.52 (16)	C11—C12—C13	121.59 (18)
C3—C2—C1	121.49 (17)	C11—C12—H12	119.2
C4—C3—C2	120.16 (18)	C13—C12—H12	119.2
C4—C3—H3	119.9	C12—C13—C14	117.58 (17)
C2—C3—H3	119.9	C12—C13—C16	120.41 (17)
C3—C4—C5	120.21 (19)	C14—C13—C16	122.00 (17)
C3—C4—H4	119.9	C15—C14—C13	121.45 (17)
C5—C4—H4	119.9	C15—C14—H14	119.3
C6—C5—C4	120.87 (18)	C13—C14—H14	119.3
C6—C5—H5	119.6	C14—C15—C10	120.05 (18)
C4—C5—H5	119.6	C14—C15—H15	120.0
C5—C6—C7	118.34 (17)	C10—C15—H15	120.0
C5—C6—H6	120.8	C13—C16—H16A	109.5
C7—C6—H6	120.8	C13—C16—H16B	109.5
O2—C7—C2	121.64 (16)	H16A—C16—H16B	109.5
O2—C7—C6	115.91 (15)	C13—C16—H16C	109.5
C2—C7—C6	122.43 (16)	H16A—C16—H16C	109.5
C8—O2—C7	119.44 (13)	H16B—C16—H16C	109.5
C9—C8—O2	122.18 (15)	C9—O3—C17	113.67 (14)
C9—C8—C10	126.34 (16)	O3—C17—H17A	109.5
O2—C8—C10	111.47 (14)	O3—C17—H17B	109.5
C8—C9—O3	119.52 (16)	H17A—C17—H17B	109.5
C8—C9—C1	121.84 (15)	O3—C17—H17C	109.5
O3—C9—C1	118.58 (15)	H17A—C17—H17C	109.5
C11—C10—C15	118.81 (17)	H17B—C17—H17C	109.5
C11—C10—C8	120.28 (16)

O1—C1—C2—C7	179.68 (17)	C10—C8—C9—C1	−176.22 (16)
C9—C1—C2—C7	−1.4 (2)	O1—C1—C9—C8	177.99 (18)
O1—C1—C2—C3	−1.6 (3)	C2—C1—C9—C8	−0.9 (2)
C9—C1—C2—C3	177.25 (16)	O1—C1—C9—O3	0.9 (3)
C7—C2—C3—C4	0.5 (3)	C2—C1—C9—O3	−178.00 (15)
C1—C2—C3—C4	−178.26 (19)	C9—C8—C10—C11	−131.6 (2)
C2—C3—C4—C5	−1.4 (3)	O2—C8—C10—C11	48.8 (2)
C3—C4—C5—C6	1.1 (3)	C9—C8—C10—C15	50.6 (3)
C4—C5—C6—C7	0.1 (3)	O2—C8—C10—C15	−128.94 (17)
C3—C2—C7—O2	−177.20 (15)	C15—C10—C11—C12	−1.5 (3)
C1—C2—C7—O2	1.5 (2)	C8—C10—C11—C12	−179.29 (17)
C3—C2—C7—C6	0.7 (3)	C10—C11—C12—C13	3.3 (3)
C1—C2—C7—C6	179.49 (17)	C11—C12—C13—C14	−2.5 (3)
C5—C6—C7—O2	177.00 (15)	C11—C12—C13—C16	176.76 (18)
C5—C6—C7—C2	−1.1 (3)	C12—C13—C14—C15	−0.1 (3)
C2—C7—O2—C8	0.8 (2)	C16—C13—C14—C15	−179.32 (17)
C6—C7—O2—C8	−177.31 (16)	C13—C14—C15—C10	1.8 (3)
C7—O2—C8—C9	−3.2 (2)	C11—C10—C15—C14	−1.0 (3)
C7—O2—C8—C10	176.35 (13)	C8—C10—C15—C14	176.76 (16)
O2—C8—C9—O3	−179.63 (15)	C8—C9—O3—C17	97.8 (2)
C10—C8—C9—O3	0.9 (3)	C1—C9—O3—C17	−85.1 (2)
O2—C8—C9—C1	3.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O1ⁱ	0.94	2.48	3.249 (2)	138
C6—H6···O1ⁱⁱ	0.94	2.55	3.214 (2)	128

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

Acknowledgements

This work was supported bya Dongduk Women's University Grant.

References

Bendaikha, S., Gadaut, M., Harakat, D. & Magid, A. (2014). Phytochemistry, 103, 129–136. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2000). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burmistrova, O., Marrero, M., Estevez, S., Welsch, I., Brouard, I., Quintana, J. & Estevez, F. (2014). Eur. J. Med. Chem. 84, 30–41. CrossRef CAS Google Scholar
Dias, T. A., Duarte, C. L., Lima, C. F., Proenca, F. & Pereira-Wilson, C. (2013). Eur. J. Med. Chem. 65, 500–510. Web of Science CrossRef CAS PubMed Google Scholar
Lee, M. S., Yong, Y., Lee, J. M., Koh, D., Shin, S. Y. & Lee, Y. H. (2014). J. Korean Soc. Appl. Biol. Chem. 57, 129–132. Web of Science CrossRef CAS Google Scholar
Prescott, T. A. K., Kite, G. C., Porter, E. A. & Veitch, N. C. (2013). Phytochemistry, 88, 85–91. Web of Science CrossRef CAS PubMed Google Scholar
Serdiuk, I. E., Wera, M., Roshal, A. D. & Błazejowski, J. (2013). Acta Cryst. E69, o895. CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.