3-Hy­droxy-2-(4-methyl­phen­yl)-4H-chromen-4-one

Padgett, C.W.; Lynch, W.E.; Sheriff, K.; Dean, R.; Zingales, S.

doi:10.1107/S2414314618011380

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 3| Part 8| August 2018| x181138

https://doi.org/10.1107/S2414314618011380

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3-Hydroxy-2-(4-methylphenyl)-4H-chromen-4-one

Clifford W. Padgett,^a ^* Will E. Lynch,^a Kirkland Sheriff,^a Raven Dean ^a and Sarah Zingales ^a

^aGeorgia Southern University, 11935 Abercorn St., Department of Chemistry and Biochemistry, Savannah GA 31419, USA
^*Correspondence e-mail: cpadgett@georgiasouthern.edu

Edited by S. Bernès, Benemérita Universidad Autónoma de Puebla, México (Received 27 June 2018; accepted 9 August 2018; online 16 August 2018)

Our work in the area of carbon-monoxide-releasing molecules led to the synthesis and crystallization of new flavone derivatives as intermediates. Herein we report the first crystal structure of the title compound, C₁₆H₁₂O₃, a hydroxy-substituted flavone where the 2-phenyl group has been replaced by a p-tolyl group. The introduction of the 3-hydroxy group allows the formation of intermolecular O—H⋯O=C hydrogen bonds, used to build centrosymmetric R₂²(10) ring motifs in the crystal.

Keywords: crystal structure; benzopyran; flavone; hydrogen bond.

CCDC reference: 1861212

Structure description

Flavones contain the 2-phenylbenzopyran pharmacophore and are secondary metabolites of plants. They possess many biological activities, including antibiotic, anticancer, and antioxidant behavior. Recently, there has been interest in flavones as carbon-monoxide-releasing molecules (CORMs; Anderson et al., 2015 ). Our work in this area led to the synthesis and crystallization of flavones as intermediates. Herein we report the first crystal structure of a new 3-hydroxyflavone (Fig. 1), which forms a hydrogen-bonded dimer. The hydrogen bonding occurs between O atoms of the benzopyranone ring with an R(10) synthon. The hydrogen bond between O2 and O3ⁱ is characterized by an O⋯O separation of 2.721 (2) Å [symmetry code: (i) −x + 2, −y + 2, −z + 1; Table 1], and the ring motifs R₂²(10) are placed on inversion centers in the space group P2₁/n (Fig. 2). A secondary intramolecular C—H⋯O hydrogen bond (Table 1, entry 2) also involves the hydroxy O2 atom as an acceptor group, forming an S(6) motif. The centroid Cg1 of the tolyl ring (C10–C15) and the centroid Cg2 of a symmetry-related pyranone ring (C1–C4/C9/O1; symmetry code: x, y − 1, z) are separated by 3.7525 (15) Å, with both rings almost parallel. This is the only significant π–π interaction observed in the crystal. The molecule is nearly planar, with the tolyl and benzopyranone rings forming a dihedral angle of 18.27 (8)°. This is consistent with several other similar flavonoids, for example, 2-(4-chlorophenyl)-3-hydroxy-4H-chromen-4-one is nearly planar, with the phenyl ring tilted by 15.92 (8)° with respect to the benzopyranone ring (Zingales & Padgett, 2017 ), 3-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one, where the angle is 18.9 (4)° (Wera et al., 2011a ), and 3-hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one, where the corresponding angle is 12.3 (1)° (Wera et al., 2011b ). The crystal structure exhibits a classic herringbone pattern (Fig. 2) with the blocks consisting of the hydrogen-bonded dimers.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3ⁱ	0.88 (2)	1.92 (2)	2.721 (2)	151 (3)
C11—H11⋯O2	0.93	2.24	2.838 (3)	122
Symmetry code: (i) -x+2, -y+2, -z+1.

Figure 1
A view of the molecular structure of the title compound, showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
Crystal packing diagram of the title compound, viewed along the a axis. H atoms have been omitted for clarity and O⋯O bonds represent hydrogen-bonded O-atom sites.

Synthesis and crystallization

The title compound was synthesized (Fig. 3) by the aldol condensation of 2-hydroxyacetophenone and 4-methylbenzaldehyde to yield the chalcone (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one, followed by its oxidative cyclization to the flavone, as reported in the literature (Kurzwernhart et al., 2012 ). 2-Hydroxyacetophenone (4.8 g, 36 mmol) and 4-methylbenzaldehyde (4.3 g, 36 mmol) were dissolved in ethanol (90 ml). An NaOH solution (5 M, 30 ml) was added and the reaction was stirred until a precipitate formed. The reaction mixture was acidified to pH 6 with dilute acetic acid. The solids were filtered off and taken directly to the next step. (E)-1-(2-Hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one (3.5 g, 14 mmol) was then suspended in EtOH (30 ml) and cooled in an ice water bath. An NaOH solution (5 M, 5 ml) and H₂O₂ (30%, 2.2 equiv., 3 ml) were added and the reaction stirred overnight, warming to room temperature. The reaction mixture was acidified to pH 1 with HCl (6 M) and poured into cold water (400 ml). The white solid was collected by filtration and recrystallization of an MeOH solution afforded yellow crystals (1.7 g, 19% yield over two steps). The structure was confirmed to match the literature (Kurzwernhart et al., 2012). ¹H NMR (300 MHz, CDCl₃, p.p.m.): δ 8.26 (dd, J = 1.2, 8.1 Hz, 1H, Ar—H), 8.17 (d, J = 8.2 Hz, 2H, Ar—H), 7.72 (td, J = 1.7, 8.6 Hz, 1H, Ar—H), 7.6 (d, J = 8.2 Hz, 1H, Ar—H), 7.42 (t, J = 7.6 Hz, 1H, Ar—H), 7.36 (d, J = 8.2 Hz, 2H, Ar—H), 7.01 (bs, 1H, OH), 2.45 (s, 3H, CH₃).

Figure 3
Synthesis of 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	C₁₆H₁₂O₃
M_r	252.26
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	13.2958 (13), 5.1981 (4), 18.8162 (15)
β (°)	109.212 (9)
V (Å³)	1228.02 (19)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.50 × 0.20 × 0.05

Data collection
Diffractometer	Rigaku XtaLAB mini
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.]$ )
T_min, T_max	0.838, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	12529, 2252, 1394
R_int	0.056
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.054, 0.170, 1.04
No. of reflections	2252
No. of parameters	176
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.20
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.]$ ), SHELXT2018 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1861212

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314618011380/bh4039sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618011380/bh4039Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314618011380/bh4039Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO; cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXT-2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: Olex2 (Dolomanov et al., 2009); software used to prepare material for publication: Olex2.

3-Hydroxy-2-(4-methylphenyl)-4H-chromen-4-one top

Crystal data top

C₁₆H₁₂O₃	F(000) = 528
M_r = 252.26	D_x = 1.364 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 13.2958 (13) Å	Cell parameters from 1203 reflections
b = 5.1981 (4) Å	θ = 2.3–21.8°
c = 18.8162 (15) Å	µ = 0.09 mm⁻¹
β = 109.212 (9)°	T = 293 K
V = 1228.02 (19) Å³	Needle, yellow
Z = 4	0.50 × 0.20 × 0.05 mm

Data collection top

Rigaku XtaLAB mini diffractometer	2252 independent reflections
Radiation source: Sealed Tube, Rigaku (Mo) X-ray Source	1394 reflections with I > 2σ(I)
Graphite Monochromator monochromator	R_int = 0.056
Detector resolution: 13.6612 pixels mm^-1	θ_max = 25.3°, θ_min = 2.3°
profile data from ω–scans	h = −15→16
Absorption correction: multi-scan CrysAlisPro (Rigaku OD, 2018)	k = −5→6
T_min = 0.838, T_max = 1.000	l = −22→22
12529 measured reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.054	Hydrogen site location: mixed
wR(F²) = 0.170	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0872P)² + 0.0826P] where P = (F_o² + 2F_c²)/3
2252 reflections	(Δ/σ)_max < 0.001
176 parameters	Δρ_max = 0.21 e Å⁻³
1 restraint	Δρ_min = −0.19 e Å⁻³

Special details top

Refinement. All C-bound H atoms were positioned geometrically and refined as riding, with C—H = 0.93 or 0.96 Å and U_iso(H) = 1.2U_eq(C) or U_iso(H) = 1.5U_eq(C) for C(H) and CH₃ groups, respectively. H atoms involved in O—H···O hydrogen bonds were located on a difference Fourier map and refined isotropically with U_iso(H) = 1.5U_eq(O). The H2—O2 distance was restrained to a target value of 0.84 (2) Å, using a DFIX command in SHELXL (Sheldrick, 2015b).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.64822 (13)	0.5830 (3)	0.41165 (9)	0.0524 (5)
O2	0.92078 (14)	0.6646 (4)	0.53130 (10)	0.0596 (5)
H2	0.965 (2)	0.788 (5)	0.5307 (17)	0.089*
O3	0.90470 (15)	1.0256 (4)	0.42282 (10)	0.0690 (6)
C1	0.74245 (18)	0.5511 (4)	0.46966 (12)	0.0432 (6)
C2	0.82869 (18)	0.6966 (5)	0.47341 (13)	0.0454 (6)
C3	0.82503 (19)	0.8942 (5)	0.41869 (13)	0.0475 (6)
C4	0.72316 (19)	0.9250 (4)	0.35938 (13)	0.0444 (6)
C5	0.7068 (2)	1.1130 (5)	0.30258 (14)	0.0542 (7)
H5	0.761741	1.224393	0.303120	0.065*
C6	0.6103 (2)	1.1322 (5)	0.24672 (15)	0.0633 (8)
H6	0.599902	1.256239	0.209369	0.076*
C7	0.5278 (2)	0.9665 (6)	0.24576 (16)	0.0652 (8)
H7	0.462708	0.979595	0.207336	0.078*
C8	0.5412 (2)	0.7834 (5)	0.30083 (14)	0.0609 (8)
H8	0.485876	0.672806	0.300054	0.073*
C9	0.6391 (2)	0.7672 (5)	0.35765 (13)	0.0474 (6)
C10	0.73289 (19)	0.3510 (4)	0.52236 (12)	0.0448 (6)
C11	0.8214 (2)	0.2358 (5)	0.57398 (13)	0.0537 (7)
H11	0.889464	0.284054	0.575491	0.064*
C12	0.8091 (2)	0.0512 (5)	0.62279 (15)	0.0601 (7)
H12	0.869413	−0.024043	0.656593	0.072*
C13	0.7094 (2)	−0.0264 (5)	0.62317 (14)	0.0569 (7)
C14	0.6227 (2)	0.0887 (5)	0.57241 (15)	0.0641 (8)
H14	0.555015	0.041315	0.571865	0.077*
C15	0.6321 (2)	0.2730 (5)	0.52190 (15)	0.0599 (7)
H15	0.571313	0.344940	0.487657	0.072*
C16	0.6976 (3)	−0.2350 (6)	0.67638 (15)	0.0745 (9)
H16A	0.709676	−0.400200	0.657852	0.112*
H16B	0.626982	−0.229299	0.679462	0.112*
H16C	0.748656	−0.207334	0.725449	0.112*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0470 (10)	0.0573 (11)	0.0434 (10)	−0.0100 (8)	0.0021 (8)	0.0074 (8)
O2	0.0438 (11)	0.0700 (13)	0.0563 (11)	−0.0092 (9)	0.0045 (9)	0.0091 (10)
O3	0.0565 (12)	0.0855 (14)	0.0582 (12)	−0.0253 (11)	0.0099 (9)	0.0103 (10)
C1	0.0399 (14)	0.0497 (14)	0.0345 (12)	−0.0004 (11)	0.0048 (10)	−0.0002 (10)
C2	0.0389 (14)	0.0545 (15)	0.0399 (13)	−0.0022 (11)	0.0089 (11)	−0.0050 (11)
C3	0.0456 (15)	0.0565 (16)	0.0393 (13)	−0.0089 (12)	0.0123 (12)	−0.0036 (11)
C4	0.0466 (14)	0.0485 (14)	0.0374 (13)	−0.0045 (11)	0.0130 (11)	−0.0046 (10)
C5	0.0595 (17)	0.0555 (16)	0.0478 (15)	−0.0037 (13)	0.0179 (14)	0.0028 (12)
C6	0.074 (2)	0.0633 (18)	0.0525 (17)	0.0055 (15)	0.0211 (16)	0.0145 (13)
C7	0.0559 (18)	0.077 (2)	0.0538 (16)	0.0015 (15)	0.0057 (14)	0.0140 (14)
C8	0.0465 (16)	0.0712 (18)	0.0551 (16)	−0.0122 (13)	0.0032 (13)	0.0087 (14)
C9	0.0491 (15)	0.0487 (14)	0.0401 (13)	−0.0023 (12)	0.0089 (11)	0.0040 (11)
C10	0.0508 (15)	0.0422 (13)	0.0368 (13)	−0.0047 (11)	0.0082 (11)	−0.0039 (10)
C11	0.0517 (16)	0.0588 (16)	0.0445 (14)	−0.0024 (13)	0.0077 (12)	−0.0025 (12)
C12	0.0697 (19)	0.0577 (17)	0.0427 (14)	0.0055 (14)	0.0047 (13)	0.0064 (12)
C13	0.081 (2)	0.0459 (15)	0.0391 (14)	−0.0079 (14)	0.0129 (14)	−0.0024 (11)
C14	0.0619 (19)	0.0672 (18)	0.0596 (17)	−0.0179 (14)	0.0153 (15)	0.0034 (14)
C15	0.0508 (16)	0.0649 (18)	0.0542 (15)	−0.0108 (14)	0.0042 (12)	0.0100 (13)
C16	0.110 (3)	0.0560 (18)	0.0596 (18)	−0.0103 (17)	0.0310 (18)	0.0045 (14)

Geometric parameters (Å, º) top

O1—C9	1.372 (3)	C8—C9	1.389 (3)
O1—C1	1.374 (3)	C8—H8	0.9300
O2—C2	1.355 (3)	C10—C11	1.391 (3)
O2—H2	0.878 (18)	C10—C15	1.398 (4)
O3—C3	1.241 (3)	C11—C12	1.375 (4)
C1—C2	1.356 (3)	C11—H11	0.9300
C1—C10	1.471 (3)	C12—C13	1.387 (4)
C2—C3	1.444 (3)	C12—H12	0.9300
C3—C4	1.453 (3)	C13—C14	1.369 (4)
C4—C9	1.378 (3)	C13—C16	1.518 (4)
C4—C5	1.411 (3)	C14—C15	1.384 (4)
C5—C6	1.368 (4)	C14—H14	0.9300
C5—H5	0.9300	C15—H15	0.9300
C6—C7	1.390 (4)	C16—H16A	0.9600
C6—H6	0.9300	C16—H16B	0.9600
C7—C8	1.375 (4)	C16—H16C	0.9600
C7—H7	0.9300

C9—O1—C1	120.49 (18)	O1—C9—C8	116.4 (2)
C2—O2—H2	110 (2)	C4—C9—C8	122.0 (2)
C2—C1—O1	120.6 (2)	C11—C10—C15	118.0 (2)
C2—C1—C10	128.2 (2)	C11—C10—C1	122.3 (2)
O1—C1—C10	111.23 (19)	C15—C10—C1	119.8 (2)
O2—C2—C1	119.9 (2)	C12—C11—C10	120.5 (3)
O2—C2—C3	118.0 (2)	C12—C11—H11	119.8
C1—C2—C3	122.0 (2)	C10—C11—H11	119.8
O3—C3—C2	121.3 (2)	C11—C12—C13	122.0 (3)
O3—C3—C4	123.3 (2)	C11—C12—H12	119.0
C2—C3—C4	115.5 (2)	C13—C12—H12	119.0
C9—C4—C5	118.2 (2)	C14—C13—C12	117.1 (2)
C9—C4—C3	119.8 (2)	C14—C13—C16	121.7 (3)
C5—C4—C3	122.0 (2)	C12—C13—C16	121.1 (3)
C6—C5—C4	120.3 (2)	C13—C14—C15	122.4 (3)
C6—C5—H5	119.9	C13—C14—H14	118.8
C4—C5—H5	119.9	C15—C14—H14	118.8
C5—C6—C7	120.1 (2)	C14—C15—C10	120.0 (3)
C5—C6—H6	120.0	C14—C15—H15	120.0
C7—C6—H6	120.0	C10—C15—H15	120.0
C8—C7—C6	120.9 (3)	C13—C16—H16A	109.5
C8—C7—H7	119.6	C13—C16—H16B	109.5
C6—C7—H7	119.6	H16A—C16—H16B	109.5
C7—C8—C9	118.6 (2)	C13—C16—H16C	109.5
C7—C8—H8	120.7	H16A—C16—H16C	109.5
C9—C8—H8	120.7	H16B—C16—H16C	109.5
O1—C9—C4	121.6 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3ⁱ	0.88 (2)	1.92 (2)	2.721 (2)	151 (3)
C11—H11···O2	0.93	2.24	2.838 (3)	122

Symmetry code: (i) −x+2, −y+2, −z+1.

Acknowledgements

The authors would like to thank Georgia Southern University for support of this work.

References

Anderson, S. N., Richards, J. M., Esquer, H. J., Benninghoff, A. D., Arif, A. M. & Berreau, L. M. (2015). ChemistryOpen, 4, 590–594. Web of Science CrossRef Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Kurzwernhart, A., Kandioller, W., Bächler, S., Bartel, C., Martic, S., Buczkowska, M., Mühlgassner, G., Jakupec, M. A., Kraatz, H.-B., Bednarski, P. J., Arion, V. B., Marko, D., Keppler, B. K. & Hartinger, C. G. (2012). J. Med. Chem. 55, 10512–10522. Web of Science CSD CrossRef CAS PubMed Google Scholar
Rigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Wera, M., Pivovarenko, V. G. & Błażejowski, J. (2011a). Acta Cryst. E67, o264–o265. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Wera, M., Serdiuk, I. E., Roshal, A. D. & Błażejowski, J. (2011b). Acta Cryst. E67, o440. Web of Science CSD CrossRef IUCr Journals Google Scholar
Zingales, S. & Padgett, C. (2017). IUCrData, 2, x170996. Google Scholar

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