2-(4-Chloro­phen­yl)-3-hy­droxy-4H-chromen-4-one

Zingales, S.; Padgett, C.

doi:10.1107/S2414314617009968

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 7| July 2017| x170996

https://doi.org/10.1107/S2414314617009968

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2-(4-Chlorophenyl)-3-hydroxy-4H-chromen-4-one

Sarah Zingales ^a and Clifford Padgett ^a ^*

^aArmstrong State University, Department of Chemistry and Physics, 11935 Abercorn St., Savannah, GA 31419, USA
^*Correspondence e-mail: clifford.padgett@armstrong.edu

Edited by M. Zeller, Purdue University, USA (Received 28 June 2017; accepted 5 July 2017; online 13 July 2017)

Flavones are a subclass of flavonoids, secondary metabolites of plants which contain the 2-phenylbenzopyran pharmacophore. They are of interest as they display a wide variety of biological activities, such as anticancer and antioxidant. Recently, there has been an interest in coordinating flavones to various transition metals for anticancer activity. Our work in this area led to the synthesis and crystallization of flavones as intermediates. Herein, we report the first crystal structure of 2-(4-chlorophenyl)-3-hydroxy-4H-chromen-4-one, C₁₅H₉ClO₃, a well studied compound.

Keywords: crystal structure; flavone; 2-(4-chlorophenyl)-3-hydroxy-4H-chromen-4-one.

CCDC reference: 1560427

Structure description

In the crystal structure of the title compound (Fig. 1), the molecules form hydrogen-bonded dimers (Table 1) between the molecule and an inversion-related adjacent molecule. The hydrogen-bonding occurs between oxygen atoms on the benzopyranone ring, with a classical $[R_{2}^{2}]$ (10) synthon. The O1ⁱ ⋯O3 hydrogen-bond distance is 2.698 (3) Å [symmetry code: (i) −x, −y + 2, −z + 1]. The molecule is nearly planar with the phenyl ring tilted 15.92 (8)° with respect to the benzopyranone ring. The overall structure forms a herringbone pattern (Fig. 2) with each block consisting of molecular dimers, the layers are held together with π–π interactions and π–Br interactions. The layers have a parallel displacement that results in a Br1⋯Cg1ⁱⁱ π–Br interaction with a distance of 3.623 (3) Å [symmetry code: (ii) x, y − 1, z; Cg1 is the centroid of the chlorophenyl ring] and a Cg2⋯Cg1ⁱⁱ π–π interaction with a distance of 3.688 (2) Å. (Cg2 is the centroid of the pyranone ring).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O1ⁱ	0.84 (5)	1.95 (5)	2.698 (3)	149 (4)
Symmetry code: (i) -x, -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.

Synthesis and crystallization

The title compound was synthesized from the aldol condensation of 2-hydroxyacetophenone and 4-chlorobenzaldehyde to yield the chalcone (E)-3-(4-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one followed by its oxidative cyclization to the flavone, as reported in the literature (Kurzwernhart et al., 2012 ), see Fig. 3. 2-Hydroxyacetophenone (136 mg, 1 mmol) and 4-chlorobenzaldehyde (141 mg, 1 mmol) were dissolved in ethanol (5 ml). An NaOH solution (5 M, 1 ml) was added and the reaction was stirred until a precipitate formed. The reaction mixture was cooled in an ice bath for 20 min. The solids were filtered and taken directly to the next step. (E)-3-(4-Chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one was then suspended in EtOH (5 ml) and cooled in an ice–water bath. An NaOH solution (5 M, 1 ml) and H₂O₂ (30%, 2.2 equiv, 0.25 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. The yellow solid was collected by filtration and slow evaporation of a solution of the title compound in MeOH gave yellow crystals (64 mg, 24% yield over two steps). The structure was confirmed to match the literature (Kurzwernhart et al., 2012) NMR: ¹H NMR [300 MHz, (CD₃)₂SO)] δ = 8.24 (bs, 1H), 8.22 (d, J = 8.7 Hz, 2H), 8.07 (d, J = 7.5 Hz, 1H), 7.81–7.71 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H) p.p.m..

Figure 3
Reaction sequence for the 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	C₁₅H₉ClO₃
M_r	272.67
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	173
a, b, c (Å)	13.267 (7), 5.1050 (18), 18.866 (9)
β (°)	109.67 (2)
V (Å³)	1203.2 (10)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.32
Crystal size (mm)	0.6 × 0.1 × 0.1

Data collection
Diffractometer	Rigaku XtaLab mini with hybrid CCD photon counting detector
Absorption correction	Multi-scan (REQAB; Rigaku, 1998 )
T_min, T_max	0.848, 1.00
No. of measured, independent and observed [I > 2σ(I)] reflections	12153, 2790, 1798
R_int	0.134
(sin θ/λ)_max (Å⁻¹)	0.652

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.059, 0.148, 1.03
No. of reflections	2790
No. of parameters	176
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.33
Computer programs: CrystalClear-SM Expert (Rigaku, 2011 ), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1560427

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314617009968/zl4017sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617009968/zl4017Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617009968/zl4017Isup3.cml

checkCIF report

Computing details top

Data collection: CrystalClear-SM Expert (Rigaku, 2011); cell refinement: CrystalClear-SM Expert (Rigaku, 2011); data reduction: CrystalClear-SM Expert (Rigaku, 2011); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

2-(4-Chlorophenyl)-3-hydroxy-4H-chromen-4-one top

Crystal data top

C₁₅H₉ClO₃	F(000) = 560
M_r = 272.67	D_x = 1.505 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 13.267 (7) Å	Cell parameters from 2168 reflections
b = 5.1050 (18) Å	θ = 2.3–27.5°
c = 18.866 (9) Å	µ = 0.32 mm⁻¹
β = 109.67 (2)°	T = 173 K
V = 1203.2 (10) Å³	Prism, colorless
Z = 4	0.6 × 0.1 × 0.1 mm

Data collection top

Rigaku XtaLab mini with hybrid CCD photon counting detector diffractometer	1798 reflections with I > 2σ(I)
ω scans	R_int = 0.134
Absorption correction: multi-scan (REQAB; Rigaku, 1998)	θ_max = 27.6°, θ_min = 1.7°
T_min = 0.848, T_max = 1.00	h = −17→17
12153 measured reflections	k = −6→6
2790 independent reflections	l = −24→24

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.059	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.148	w = 1/[σ²(F_o²) + (0.045P)² + 0.358P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
2790 reflections	Δρ_max = 0.25 e Å⁻³
176 parameters	Δρ_min = −0.33 e Å⁻³
0 restraints

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. All H atoms were positioned geometrically and refined as riding with C—H = 0.95 or 0.98 Å and U_iso(H) = 1.2U_eq(C) or U_iso(H) = 1.5U_eq(C) for C(H) and C(H,H,H) groups respectively. Positions and thermal parameters of hydroxyl H atoms were freely refined.

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

	x	y	z	U_iso*/U_eq
Cl1	0.29231 (7)	−0.28855 (15)	0.31556 (4)	0.0465 (3)
O2	0.35505 (15)	0.5852 (4)	0.58662 (10)	0.0319 (5)
O3	0.07635 (17)	0.6574 (4)	0.46991 (12)	0.0378 (5)
O1	0.09468 (17)	1.0214 (4)	0.57933 (11)	0.0434 (6)
C4	0.3655 (2)	0.7714 (5)	0.64026 (15)	0.0299 (6)
C3	0.2581 (2)	0.5458 (5)	0.53041 (14)	0.0280 (6)
C10	0.2654 (2)	0.3419 (5)	0.47707 (15)	0.0288 (6)
C1	0.1756 (2)	0.8890 (6)	0.58247 (15)	0.0315 (6)
C5	0.2797 (2)	0.9286 (6)	0.64112 (14)	0.0299 (6)
C2	0.1711 (2)	0.6911 (5)	0.52714 (15)	0.0293 (6)
C11	0.1738 (2)	0.2221 (6)	0.42686 (15)	0.0332 (7)
H11	0.1064	0.2712	0.4271	0.040*
C9	0.2971 (2)	1.1185 (6)	0.69760 (16)	0.0361 (7)
H9	0.2409	1.2249	0.6990	0.043*
C12	0.1827 (2)	0.0323 (6)	0.37722 (15)	0.0358 (7)
H12	0.1215	−0.0439	0.3437	0.043*
C13	0.2827 (3)	−0.0442 (6)	0.37737 (15)	0.0349 (7)
C15	0.3655 (2)	0.2598 (6)	0.47606 (16)	0.0355 (7)
H15	0.4272	0.3355	0.5092	0.043*
C14	0.3744 (2)	0.0684 (6)	0.42671 (16)	0.0381 (7)
H14	0.4415	0.0156	0.4267	0.046*
C6	0.4670 (2)	0.8002 (6)	0.69450 (16)	0.0371 (7)
H6	0.5235	0.6941	0.6935	0.045*
C8	0.3977 (3)	1.1489 (6)	0.75141 (16)	0.0381 (7)
H8	0.4089	1.2760	0.7886	0.046*
C7	0.4821 (3)	0.9891 (6)	0.74977 (17)	0.0408 (8)
H7	0.5493	1.0096	0.7862	0.049*
H3	0.035 (4)	0.780 (9)	0.471 (3)	0.103 (18)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0659 (6)	0.0394 (4)	0.0341 (4)	0.0075 (4)	0.0166 (4)	−0.0049 (3)
O2	0.0270 (10)	0.0373 (11)	0.0264 (10)	0.0045 (9)	0.0023 (9)	−0.0038 (8)
O3	0.0256 (11)	0.0457 (13)	0.0364 (12)	0.0028 (10)	0.0030 (9)	−0.0071 (10)
O1	0.0338 (12)	0.0591 (14)	0.0347 (12)	0.0145 (11)	0.0083 (10)	−0.0065 (10)
C4	0.0327 (16)	0.0312 (14)	0.0249 (14)	0.0001 (12)	0.0085 (13)	−0.0015 (11)
C3	0.0265 (14)	0.0325 (15)	0.0212 (13)	0.0005 (12)	0.0032 (12)	0.0031 (11)
C10	0.0309 (15)	0.0289 (15)	0.0255 (14)	0.0020 (12)	0.0080 (12)	0.0047 (11)
C1	0.0305 (16)	0.0378 (16)	0.0276 (14)	0.0031 (13)	0.0115 (13)	0.0050 (12)
C5	0.0311 (15)	0.0357 (15)	0.0244 (14)	0.0007 (13)	0.0115 (13)	0.0022 (12)
C2	0.0277 (15)	0.0337 (15)	0.0258 (14)	−0.0013 (12)	0.0078 (12)	0.0001 (12)
C11	0.0315 (16)	0.0370 (16)	0.0276 (14)	0.0013 (13)	0.0052 (13)	0.0016 (12)
C9	0.0382 (17)	0.0383 (16)	0.0317 (15)	0.0000 (13)	0.0118 (14)	−0.0019 (12)
C12	0.0408 (18)	0.0350 (16)	0.0276 (15)	−0.0005 (13)	0.0061 (14)	−0.0017 (12)
C13	0.0492 (19)	0.0299 (15)	0.0240 (14)	0.0048 (14)	0.0103 (14)	0.0031 (11)
C15	0.0277 (15)	0.0403 (17)	0.0329 (15)	0.0054 (13)	0.0027 (13)	−0.0007 (13)
C14	0.0374 (17)	0.0427 (17)	0.0354 (17)	0.0094 (14)	0.0137 (15)	−0.0005 (14)
C6	0.0321 (16)	0.0422 (17)	0.0334 (16)	0.0025 (13)	0.0063 (14)	−0.0046 (13)
C8	0.0423 (18)	0.0400 (17)	0.0301 (15)	−0.0065 (14)	0.0096 (14)	−0.0076 (13)
C7	0.0367 (18)	0.0472 (18)	0.0324 (16)	−0.0041 (15)	0.0036 (14)	−0.0055 (14)

Geometric parameters (Å, º) top

Cl1—C13	1.742 (3)	C11—H11	0.9300
O2—C4	1.361 (3)	C11—C12	1.380 (4)
O2—C3	1.379 (3)	C9—H9	0.9300
O3—C2	1.365 (3)	C9—C8	1.387 (4)
O3—H3	0.83 (5)	C12—H12	0.9300
O1—C1	1.252 (3)	C12—C13	1.381 (4)
C4—C5	1.398 (4)	C13—C14	1.384 (4)
C4—C6	1.398 (4)	C15—H15	0.9300
C3—C10	1.473 (4)	C15—C14	1.382 (4)
C3—C2	1.356 (4)	C14—H14	0.9300
C10—C11	1.405 (4)	C6—H6	0.9300
C10—C15	1.399 (4)	C6—C7	1.384 (4)
C1—C5	1.464 (4)	C8—H8	0.9300
C1—C2	1.440 (4)	C8—C7	1.394 (4)
C5—C9	1.401 (4)	C7—H7	0.9300

C4—O2—C3	120.6 (2)	C8—C9—C5	120.4 (3)
C2—O3—H3	109 (3)	C8—C9—H9	119.8
O2—C4—C5	122.0 (2)	C11—C12—H12	120.0
O2—C4—C6	116.7 (2)	C13—C12—C11	119.9 (3)
C5—C4—C6	121.3 (3)	C13—C12—H12	120.0
O2—C3—C10	111.7 (2)	C12—C13—Cl1	119.2 (2)
C2—C3—O2	121.0 (2)	C12—C13—C14	120.7 (3)
C2—C3—C10	127.3 (2)	C14—C13—Cl1	120.1 (2)
C11—C10—C3	121.8 (3)	C10—C15—H15	119.4
C15—C10—C3	120.1 (3)	C14—C15—C10	121.2 (3)
C15—C10—C11	118.1 (3)	C14—C15—H15	119.4
O1—C1—C5	122.5 (3)	C13—C14—H14	120.3
O1—C1—C2	121.3 (3)	C15—C14—C13	119.4 (3)
C2—C1—C5	116.3 (2)	C15—C14—H14	120.3
C4—C5—C1	118.5 (2)	C4—C6—H6	120.5
C4—C5—C9	118.6 (3)	C7—C6—C4	119.0 (3)
C9—C5—C1	122.9 (3)	C7—C6—H6	120.5
O3—C2—C1	117.6 (2)	C9—C8—H8	120.0
C3—C2—O3	120.7 (3)	C9—C8—C7	120.0 (3)
C3—C2—C1	121.7 (3)	C7—C8—H8	120.0
C10—C11—H11	119.6	C6—C7—C8	120.7 (3)
C12—C11—C10	120.7 (3)	C6—C7—H7	119.7
C12—C11—H11	119.6	C8—C7—H7	119.7
C5—C9—H9	119.8

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.84 (5)	1.95 (5)	2.698 (3)	149 (4)

Symmetry code: (i) −x, −y+2, −z+1.

Acknowledgements

The authors would like to thank Armstrong State University for support of this work.

References

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