Crystal structures of (E)-3-(4-hy-droxy-benzyl-idene)chroman-4-one and (E)-3-(3-hy-droxy-benzyl-idene)-2-phenyl-chroman-4-one.

The synthesis and crystal structures of (E)-3-(4-hy-droxy-benzyl-idene)chroman-4-one, C16H12O3, I, and (E)-3-(3-hy-droxy-benzyl-idene)-2-phenyl-chroman-4-one, C22H16O3, II, are reported. These compounds are of inter-est with respect to biological activity. Both structures display inter-molecular C-H⋯O and O-H⋯O hydrogen bonding, forming layers in the crystal lattice. The crystal structure of compound I is consolidated by π-π inter-actions. The lipophilicity (logP) was determined as it is one of the parameters qualifying compounds as potential drugs. The logP value for compound I is associated with a larger contribution of C⋯H inter-action in the Hirshfeld surface. © Suchojad et al. 2019.

Chemical context

Chromanone (chroman-4-one) and flavanone (2-phenyl­chroman-4-one) belong to the class of heterocyclic compounds and are composed of a benzene ring fused to a 2,3-di­hydro-γ-pyran­one ring (Emami & Ghanbarimasir, 2015 ▸). 3-Aryl­idenechromanones/flavanones and their derivatives are naturally occurring homoisoflavones, and can be obtained by condensing the corresponding aryl aldehydes with chromanone/flavanone. These compounds were synthesized for the first time by Robinson in the early 1920s by the condensation reaction of chromanone or flavanone with the appropriate aryl aldehyde using a catalyst (alcohol potassium hydroxide) (Perkin et al.,1926 ▸). In 1979, Levai and Schag synthesized E-3-aryl­idenechroman-4-one using piperidine as a catalyst (Levai & Schag, 1979 ▸). Several years later, in 1993, Pijewska and coworkers (Pijewska et al., 1993 ▸) obtained the series of 3-aryl­ideneflavanones derivatives substituted by various groups using flavanones with aromatic aldehydes in the presence of piperidine. Flavonoid compounds belong to one of the largest and most inter­esting groups of chemical compounds. They are of inter­est to many scientists because they show biological properties (Nijveldt et al., 2001 ▸; Williams et al., 2004 ▸). Natural and synthetic flavonoids have a wide range of anti­oxidant, anti-allergic, anti-inflammatory, anti-microbial, anti-coagulant, anti-cholesterol or anti-cancer activities (Czaplińska et al., 2012 ▸).

Structural commentary

The mol­ecular structures of I and II are shown in Fig. 1 ▸. The main chroman skeleton of each mol­ecule consists of a benzene ring fused with a pyran ring. In position 3 of the chroman moiety, a para-hy­droxy­benzyl­idene (I) or a meta-hy­droxy­benzyl­idene (II) substituent is connected to give the E-isomer, similar to the previously mentioned structure (Kupcewicz, et al., 2013 ▸). Moreover in compound II, the chroman moiety is subsituted at position 2 by a phenyl ring. The pyran rings adopt an envelope conformation with puckering parameters Q T = 0.371 (2) Å, φ2 = 233.8 (4)°, θ2 = 120.0 (3)° for I, and Q T = 0.423 (3) Å, φ2 = 65.9 (5)°, θ2 = 58.5 (4)° for II. The dihedral angles between the hy­droxy­benzyl­idene rings and the main chroman skeleton are 47.54 (8) and 69.46 (12)°, respectively, for I and II (Fig. 2 ▸).

Figure 1

The mol­ecular structures of compounds I and II with displacement ellipsoids drawn at the 50% probability level.

Figure 2

Overlay of compound I (green) and compound II (red).

Supra­molecular features

In the crystal packing of I, mol­ecules are connected into layers parallel to the bc plane via C—H⋯O and O—H⋯O hydrogen bonds (Table 1 ▸, Fig. 3 ▸). The stability of the layers is further enhanced by π–π stacking inter­actions occurring between the benzene rings fused with the pyran rings and the aromatic rings of adjacent hy­droxy­benzyl­idene groups (Table 2 ▸). In the crystal packing of II, mol­ecules are also linked by O—H⋯O and C—H⋯O hydrogen bonds (Table 3 ▸, Fig. 4 ▸) into layers parallel to the ab plane.

Table 1

Hydrogen-bond geometry (Å, °) for I

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11⋯O3i	0.95	2.55	3.264 (2)	132
C11—H11⋯O3ii	0.95	2.52	3.194 (2)	129
O3—H3⋯O4iii	0.84	1.85	2.6852 (19)	172
C2—H2A⋯O1iv	0.99	2.53	3.397 (3)	147
C11—H11⋯O4	0.95	2.45	2.818 (2)	103

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Figure 3

Partial packing of compound I showing the O—H⋯O (blue dotted lines) and C—H⋯O (cyan dotted lines) hydrogen-bonding network.

Table 2

Geometrical parameters (Å, °) for the π–π stacking inter­actions for compound I

Cg(1) and Cg(2) are the centroids of the C5–C10 and C12–C17 rings, respectively; α refers to the dihedral angle between planes (I) and (J); β refers to the angle between the Cg(I))–Cg(J) vector and normal to plane (I); γ refers to the angle between the Cg(I))–Cg(J) vector and normal to plane (J).

	Cg(I)⋯Cg(J)	Cg(I)_Perp	Cg(J)_Perp	α	β	γ
Cg(1)⋯Cg(1)i	3.8508 (13)	3.5260 (9)	−3.5259 (9)	0.03 (10)	23.7	23.7
Cg(1)⋯Cg(1)ii	3.8512 (13)	3.5260 (9)	−3.5262 (9)	0.03 (10)	23.7	23.7
Cg(2)⋯Cg(2)i	3.8510 (13)	3.3739 (8)	−3.3738 (8)	0.03 (10)	28.8	28.8
Cg(2)⋯Cg(2)ii	3.8510 (13)	3.3740 (8)	−3.3738 (8)	0.03 (10)	28.8	28.8

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

Table 3

Hydrogen-bond geometry (Å, °) for II

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O4i	0.84	1.89	2.728 (3)	172
C17—H17⋯O4i	0.95	2.49	3.184 (4)	130
C6—H6⋯O3ii	0.95	2.45	3.265 (4)	143
C11—H11⋯O4	0.95	2.43	2.807 (3)	103

Symmetry codes: (i) ; (ii) .

Figure 4

Partial packing of compound II showing the O—H⋯O (blue dotted lines) and C—H⋯O (cyan dotted lines) hydrogen-bonding network.

Database survey

A search of the Cambridge Structural Database (CSD version 5.40, last update November 2018; Groom et al., 2016 ▸) using the scheme presented in Fig. 5 ▸ found 41 chromanone (Ishikawa et al., 2013a ▸,b ▸; Zimmerman et al., 2015 ▸; Marx, Suresh et al., 2007 ▸; Katrusiak et al., 1987 ▸; Brien et al., 2012 ▸; Suresh et al., 2007 ▸; Boonsri et al., 2005 ▸; Biruntha et al., 2018 ▸; Talhi et al., 2016 ▸; Wu, Liu et al., 2011 ▸; Marx et al., 2008 ▸; Cheng et al., 2011 ▸; Valkonen et al., 2012 ▸; Lepitre et al., 2017 ▸; Gopaul, Shaikh, Koorbanally et al., 2012 ▸; Gopaul, Koorbanally et al., 2012 ▸; Marx, Manivannan et al., 2007 ▸; Suresh et al., 2007 ▸; Marx et al., 2008 ▸; Hassaine et al., 2016 ▸; Chantrapromma et al., 2006 ▸; Zhang et al., 2012 ▸; Augustine et al., 2008 ▸; Gopaul, Shaikh, Ramjugernath et al., 2012 ▸; Gopaul & Koorbanally, 2012 ▸; Zhang et al., 2013 ▸) and four flavanone structures (Zhong et al., 2013 ▸; Kupcewicz et al., 2013 ▸; Wu, Zeng et al., 2011 ▸; Monserrat et al., 2013 ▸). In the flavanone structures, the phenyl substituent at the C2 position is always nearly perpendicular to the chroman moiety, with the C(phen)—C2—C3—C4 torsion angle in the range 82.44–107.90°. In both chromanone and flavanone structures, the pyran ring adopts a slightly distorted envelope conformation. In the 41 chromanone derivatives, the bond distances and angles within the chroman moiety are in good agreement with those found in compound I.

Figure 5

Reference moiety for database survey.

Experimental and theoretical lipophilicity of compounds I and II

Lipophilicity is one of the descriptors that is currently used in the design of new drugs and in assessing the activity of medicinal substances (Jóźwiak et al., 2001 ▸). Most often, the increase in lipophilicity increases the biological activity of compounds as a result of the affinity of substances with biological membranes and better permeability (Dołowy, 2009 ▸). However, a further increase in lipophilicity results in greater affinity for lipids and hinders the transport of compound mol­ecules through the aqueous phase. That is why it is important to choose substances with optimal hydro­phobic and hydro­philic properties and partition coefficient logP (Dołowy, 2009 ▸).

The experimental lipophilicity (logP) of compounds I and II was determined using the RP–TLC method. The values of logP obtained are 2.95 and 3.98, respectively for I and II, the difference being due to the different, bulky substituent at the C2 position of the pyran ring. The theoretical values of lipophilicity (miLogP) also show the same trend, the value for compound I is lower (miLogP = 3.14) than that for compound II (miLogP = 4.70). This is in agreement with the values previously reported for similar aryl­idenochromanone/flavanone derivatives (Adamus-Grabicka et al., 2018 ▸). The theoretical values of lipophilicity were calculated using the online Molinspiration Cheminformatics software (http://www.molinspiration.com). According to the ‘rule of five’ proposed by Lipinski et al. (2001 ▸), compounds I and II may be potential anti-cancer drugs, the most important parameters according to Lipinski being the logP value (logP < 5) and molar mass (< 500 Da).

Hirshfeld surface analysis and lipophilicity index versus C⋯H contact

As the Hirshfeld surface (HS) analysis may provide useful descriptors for QSAR study (Kupcewicz, et al., 2016 ▸) and the lipophilicity parameter in biologically active compounds is associated with the contribution of inter­molecular inter­actions to the Hirshfeld surface (Małecka & Budzisz, 2014 ▸), we generated the Hirshfeld surfaces (Hirshfeld, 1977 ▸; Spackman & Jayatilaka, 2009 ▸) using the CrystalExplorer program (Turner et al., 2017 ▸) for chromone and flavanone derivatives for which the lipophilicity parameters are available, i.e. compound I, II, 3-(4-chloro­benzyl­idene)-2-phenyl-2,3-di­hydro-4H-chromen-4-one (III; Kupcewicz et al., 2013 ▸), (E)-3-(4-N,N-di­ethyl­amino­benzyl­idene)chroman-4-one (IV; Adam­us-Grabicka et al., 2018 ▸) and (E)-3-(4-N,N-di­ethyl­amino­benzyl­idene)-2-phenyl­chroman-4-one (V; Adamus-Grabicka et al., 2018 ▸).

The Hirshfeld surfaces were mapped over d norm (Fig. 6 ▸). The red, white and blue regions visible on the d norm surfaces indicate contacts with distances shorter, longer and equal to the van der Waals radii. The decomposition of the HS into 2D fingerprint plots for particular contacts is presented in Fig. 7 ▸, together with the relative percentage of contributions of different contacts. The dominant inter­action in all derivatives is the H⋯H inter­action. The contribution to the Hirshfeld surface is in the range 39.2– 55.5% for III and V. Comparing the C⋯C contacts, we can observe a large spread of percentage contribution ranging from 0.3% for V to 13.1% for compound I. This is also reflected in the presence of π–π stacking inter­actions observed in compound I (Table 2 ▸).

Figure 6

View of the three-dimensional Hirshfeld surfaces of the title compounds plotted over d norm (left) and shape-index (right); first row: compound I, second row: compound II.

Figure 7

Fingerprint plots of the title compounds; full Hirshfeld surface (left) and delineated into H⋯O, H⋯C, C⋯C, and H⋯H contacts, showing the percentage contributions of the contacts to the total Hirshfeld surface area of the mol­ecules. First row: compound I; second row: compound II; third row: 3-(4-chloro­benzyl­idene)-2-phenyl-2,3-di­hydro-4H-chromen-4-one (Kupcewicz et al., 2013 ▸); fourth row: (E)-3-(4-N,N-di­ethyl­amino­benzyl­idene)chroman-4-one (Adamus-Grabicka et al., 2018 ▸); fifth row: (E)-3-(4-N,N-di­ethyl­amino­benzyl­idene)-2-phenyl­chroman-4-one (Adamus-Grabicka et al., 2018 ▸).

As in our previous studies (Małecka et al., 2014 ▸; Kupcewicz et al., 2103), we found a relationship between the logP value and the fraction of the Hirshfeld surface covered by different inter­molecular inter­actions. The increase of logP corresponds in fact to increasing the C⋯H contribution in the Hirshfeld surface. Furthermore, for compounds I–V, the contribution of the O⋯H inter­action in the Hirshfeld surface is inversely proportional to the value of logP.

Synthesis and crystallization

The synthesis of compounds I and II is based on the condensation of chromanone or flavanone with an aryl aldehyde in the presence of piperidine (Fig. 8 ▸). Compound I was prepared according to a slightly modified procedure with respect to that described in the literature (Levai & Schag, 1979 ▸). A mechanically stirred mixture of chroman-4-one (0.01 mol), p-meth­oxy­benzaldehyde (0.01 mol) and five drops of piperidine was heated at 413 K in an oil bath for four h. The progress of the synthesis was controlled by thin layer chromatography (TLC) using toluene/methanol (9:1 v/v) as eluent. After cooling the reaction mixture was left for 24 h at room temperature. The solidified product was filtered and crystallized from methanol. Compound I was obtained as a yellow powder. The isolated solid was further recrystallized by slow evaporation at room temperature of an acetone solution. Yield: 64%, M.p.: 501–502.5 K. MS (ESI+): m/z 253.3 C16H12O3 [M+H]+. IR (KBr): 3126 (O—H), 2809 (C—Haromat), 1652 (C=O), 1608, 1578 (C=C), 1164 (C–O—C), 751 (=C—H). 1 H NMR (600 MHz, DMSO-d 6) δ (ppm): 5.42 (1H, s, =CH), 6.86–7.86 (8H, m, C—H aromat), 7.87 (2H, d, J AB = 18 Hz C2—H), 10.12 (1H, s, OH). Analysis calculated for C16H12O3 (M = 252.23 g mol−1) % C: 76.18; % H: 4.81; % O: 19.01. Found % C: 75.3; % H: 5.01; % O: 19.69.

Figure 8

Scheme of the synthesis of compounds I and II. R 1 = H/Ph, R 2 = H/OH, R 3 = OH/H, respectively for compound I and II.

Compound II was synthesized according to the procedure described by Pijewska et al., (1993 ▸). A mixture of 2-phenyl­chroman-4-one (0.01 mol), 3-hy­droxy­benzaldehyde (0.01 mol) and five drops of piperidine was heated under reflux in an oil bath with mechanical stirring. The reaction proceeded at 413 K for 5 h. The progress of the reaction was controlled by TLC (eluent: toluene/methanol, 9:1 v/v). After cooling at room temperature, the mixture was dissolved in methanol. After 24 h compound II precipitated as a light-cream fine crystalline powder and was purified by crystallization from methanol. Crystal suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution at room temperature. Yield: 52.4%. M.p.: 482–483 K. MS (ESI+): m/z 329.2 C22H16O3 [M+H]+. IR (KBr): 3297 (O—H), 3054 (C—Haromat), 2351 (C—Haliph), 1663 (C=O), 1608, 1590, 1504 (C=C), 1141 (C—O—C), 757 (=C—H). 1 H NMR (600 MHz, DMSO-d 6) δ (ppm): 6.57 (1H, s, C2—H), 5.69 (1H, s, =CH), 6.89–7.91 (14H, m, CHaromat), 8.12 (1H, s, OH). Analysis calculated For C22H16O3 (M = 328.19 g mol−1) %C: 80.51; %H: 4.87; % O: 14.62. Found %C: 79.99; %H: 5.11; % O: 14.90.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4 ▸. All hydrogen atoms were fixed geometrically at calculated positions (O—H = 0.84 Å, C—H = 0.95–0.99 Å) and refined as riding model with U iso(H) = 1.5U eq(O) or 1.2U eq(C). A rotating model was used for the hy­droxy groups.

Table 4

Experimental details

	I	II
Crystal data
Chemical formula	C16H12O3	C22H16O3
M r	252.27	328.37
Crystal system, space group	Monoclinic, P21/c	Triclinic, P
Temperature (K)	120	120
a, b, c (Å)	3.8510 (2), 22.2541 (11), 13.7837 (9)	5.3969 (6), 11.6576 (16), 12.944 (2)
α, β, γ (°)	90, 96.766 (5), 90	91.992 (12), 98.282 (10), 97.568 (10)
V (Å3)	1173.04 (11)	797.68 (19)
Z	4	2
Radiation type	Mo Kα	Mo Kα
μ (mm−1)	0.10	0.09
Crystal size (mm)	0.4 × 0.2 × 0.1	0.8 × 0.2 × 0.05
Data collection
Diffractometer	STOE IPDS 2T	STOE IPDS 2T
Absorption correction	–	–
No. of measured, independent and observed [I > 2σ(I)] reflections	7027, 2413, 1618	6849, 3281, 1804
R int	0.050	0.077
(sin θ/λ)max (Å−1)	0.628	0.628
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.048, 0.115, 1.03	0.068, 0.200, 0.94
No. of reflections	2413	3281
No. of parameters	173	228
H-atom treatment	H-atom parameters constrained	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.19, −0.19	0.23, −0.29

Computer programs: X-AREA and X-RED32 (Stoe & Cie, 2002 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2014/7 (Sheldrick, 2015b ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I, II. DOI: 10.1107/S2056989019015639/rz5266sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989019015639/rz5266Isup4.hkl

Structure factors: contains datablock(s) II. DOI: 10.1107/S2056989019015639/rz5266IIsup5.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989019015639/rz5266Isup4.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989019015639/rz5266IIsup5.cml

CCDC references: 1966749, 1966750

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

C16H12O3	Dx = 1.428 Mg m−3
Mr = 252.27	Melting point: 220 K
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 3.8510 (2) Å	Cell parameters from 219 reflections
b = 22.2541 (11) Å	θ = 4.1–28.9°
c = 13.7837 (9) Å	µ = 0.10 mm−1
β = 96.766 (5)°	T = 120 K
V = 1173.04 (11) Å3	Needle, light-yellow
Z = 4	0.4 × 0.2 × 0.1 mm
F(000) = 528

STOE IPDS 2T diffractometer	1618 reflections with I > 2σ(I)
Radiation source: GeniX Mo, 0.05 x 0.05 mm2 microfocus	Rint = 0.050
Detector resolution: 6.67 pixels mm-1	θmax = 26.5°, θmin = 3.7°
rotation method, ω scans	h = −4→4
7027 measured reflections	k = −27→27
2413 independent reflections	l = −16→17

Refinement on F2	Primary atom site location: difference Fourier map
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.115	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0546P)2 + 0.2287P] where P = (Fo2 + 2Fc2)/3
2413 reflections	(Δ/σ)max < 0.001
173 parameters	Δρmax = 0.19 e Å−3
0 restraints	Δρmin = −0.19 e Å−3

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.

	x	y	z	Uiso*/Ueq
O3	0.5127 (4)	0.21588 (6)	0.68339 (10)	0.0282 (4)
H3	0.5952	0.1823	0.6701	0.042*
O4	−0.1988 (4)	0.39218 (6)	0.15977 (10)	0.0304 (4)
O1	0.2599 (4)	0.50810 (6)	0.36926 (10)	0.0252 (4)
C9	0.1347 (5)	0.52849 (8)	0.27851 (14)	0.0217 (4)
C17	0.3626 (5)	0.25884 (8)	0.42639 (15)	0.0218 (4)
H17	0.4012	0.2441	0.3639	0.026*
C3	0.0393 (5)	0.40641 (8)	0.32620 (14)	0.0207 (4)
C14	0.2335 (5)	0.29994 (8)	0.60754 (15)	0.0216 (4)
H14	0.1846	0.3135	0.6698	0.026*
C11	0.0949 (5)	0.34735 (8)	0.34238 (15)	0.0219 (4)
H11	0.0614	0.3229	0.2856	0.026*
C10	−0.0381 (5)	0.49118 (8)	0.20685 (15)	0.0217 (4)
C12	0.1982 (5)	0.31486 (8)	0.43307 (14)	0.0200 (4)
C13	0.1298 (5)	0.33398 (8)	0.52539 (15)	0.0219 (4)
H13	0.0104	0.3709	0.5318	0.026*
C8	0.2011 (6)	0.58826 (9)	0.25768 (15)	0.0256 (5)
H8	0.3229	0.6133	0.3061	0.031*
C15	0.4089 (5)	0.24590 (8)	0.59954 (15)	0.0208 (4)
C7	0.0889 (6)	0.61086 (9)	0.16621 (16)	0.0277 (5)
H7	0.1330	0.6518	0.1523	0.033*
C4	−0.0782 (5)	0.42671 (9)	0.22612 (14)	0.0216 (4)
C2	0.0920 (6)	0.45481 (8)	0.40230 (15)	0.0227 (4)
H2A	−0.1381	0.4662	0.4220	0.027*
H2B	0.2363	0.4387	0.4607	0.027*
C6	−0.0882 (6)	0.57486 (9)	0.09380 (16)	0.0283 (5)
H6	−0.1649	0.5909	0.0311	0.034*
C5	−0.1499 (6)	0.51545 (9)	0.11493 (15)	0.0249 (5)
H5	−0.2708	0.4906	0.0661	0.030*
C16	0.4693 (5)	0.22483 (8)	0.50797 (15)	0.0217 (4)
H16	0.5830	0.1874	0.5018	0.026*

	U11	U22	U33	U12	U13	U23
O3	0.0407 (9)	0.0236 (7)	0.0200 (8)	0.0065 (7)	0.0022 (7)	0.0031 (6)
O4	0.0459 (10)	0.0235 (7)	0.0198 (8)	−0.0049 (7)	−0.0044 (7)	−0.0004 (6)
O1	0.0305 (8)	0.0209 (7)	0.0231 (8)	−0.0046 (6)	−0.0020 (6)	0.0006 (6)
C9	0.0221 (11)	0.0231 (10)	0.0200 (11)	0.0031 (8)	0.0023 (8)	0.0014 (8)
C17	0.0266 (11)	0.0229 (10)	0.0160 (10)	−0.0013 (8)	0.0025 (8)	−0.0018 (8)
C3	0.0204 (10)	0.0223 (9)	0.0190 (11)	−0.0003 (8)	0.0015 (8)	0.0008 (8)
C14	0.0257 (11)	0.0199 (9)	0.0192 (11)	−0.0036 (8)	0.0030 (8)	−0.0029 (7)
C11	0.0229 (11)	0.0242 (10)	0.0179 (11)	−0.0002 (8)	−0.0003 (8)	−0.0023 (8)
C10	0.0240 (11)	0.0200 (9)	0.0212 (11)	0.0025 (8)	0.0036 (9)	0.0006 (8)
C12	0.0205 (10)	0.0215 (9)	0.0178 (10)	−0.0019 (8)	0.0009 (8)	−0.0008 (8)
C13	0.0218 (10)	0.0192 (10)	0.0245 (11)	−0.0005 (8)	0.0015 (8)	−0.0001 (8)
C8	0.0271 (12)	0.0228 (10)	0.0276 (12)	−0.0012 (8)	0.0052 (9)	−0.0029 (8)
C15	0.0228 (10)	0.0198 (9)	0.0190 (10)	−0.0023 (8)	−0.0010 (8)	0.0035 (8)
C7	0.0345 (13)	0.0200 (10)	0.0303 (13)	0.0021 (9)	0.0111 (10)	0.0028 (8)
C4	0.0235 (11)	0.0234 (10)	0.0169 (11)	0.0013 (8)	−0.0014 (8)	−0.0001 (8)
C2	0.0280 (11)	0.0203 (9)	0.0193 (11)	−0.0016 (8)	0.0000 (9)	0.0005 (8)
C6	0.0326 (12)	0.0275 (11)	0.0256 (12)	0.0066 (9)	0.0070 (9)	0.0055 (9)
C5	0.0285 (12)	0.0250 (10)	0.0211 (11)	0.0024 (8)	0.0024 (9)	−0.0008 (8)
C16	0.0249 (11)	0.0169 (9)	0.0231 (11)	0.0006 (8)	0.0024 (9)	−0.0005 (8)

O3—C15	1.354 (2)	C11—H11	0.9500
O3—H3	0.8400	C10—C5	1.398 (3)
O4—C4	1.242 (2)	C10—C4	1.471 (3)
O1—C9	1.364 (2)	C12—C13	1.396 (3)
O1—C2	1.450 (2)	C13—H13	0.9500
C9—C8	1.391 (3)	C8—C7	1.379 (3)
C9—C10	1.397 (3)	C8—H8	0.9500
C17—C16	1.378 (3)	C15—C16	1.392 (3)
C17—C12	1.406 (3)	C7—C6	1.394 (3)
C17—H17	0.9500	C7—H7	0.9500
C3—C11	1.346 (3)	C2—H2A	0.9900
C3—C4	1.471 (3)	C2—H2B	0.9900
C3—C2	1.501 (3)	C6—C5	1.381 (3)
C14—C13	1.382 (3)	C6—H6	0.9500
C14—C15	1.390 (3)	C5—H5	0.9500
C14—H14	0.9500	C16—H16	0.9500
C11—C12	1.458 (3)
C15—O3—H3	109.5	C7—C8—H8	120.3
C9—O1—C2	115.95 (15)	C9—C8—H8	120.3
O1—C9—C8	116.97 (18)	O3—C15—C14	117.16 (18)
O1—C9—C10	122.55 (17)	O3—C15—C16	122.95 (18)
C8—C9—C10	120.40 (18)	C14—C15—C16	119.89 (18)
C16—C17—C12	121.80 (19)	C8—C7—C6	121.30 (19)
C16—C17—H17	119.1	C8—C7—H7	119.4
C12—C17—H17	119.1	C6—C7—H7	119.4
C11—C3—C4	118.72 (18)	O4—C4—C10	120.57 (18)
C11—C3—C2	125.41 (18)	O4—C4—C3	123.19 (18)
C4—C3—C2	115.86 (16)	C10—C4—C3	116.22 (17)
C13—C14—C15	120.37 (19)	O1—C2—C3	113.35 (16)
C13—C14—H14	119.8	O1—C2—H2A	108.9
C15—C14—H14	119.8	C3—C2—H2A	108.9
C3—C11—C12	130.40 (19)	O1—C2—H2B	108.9
C3—C11—H11	114.8	C3—C2—H2B	108.9
C12—C11—H11	114.8	H2A—C2—H2B	107.7
C5—C10—C9	118.78 (18)	C5—C6—C7	118.8 (2)
C5—C10—C4	120.86 (18)	C5—C6—H6	120.6
C9—C10—C4	120.22 (18)	C7—C6—H6	120.6
C13—C12—C17	117.70 (18)	C6—C5—C10	121.3 (2)
C13—C12—C11	124.65 (18)	C6—C5—H5	119.4
C17—C12—C11	117.57 (17)	C10—C5—H5	119.4
C14—C13—C12	120.83 (18)	C17—C16—C15	119.31 (18)
C14—C13—H13	119.6	C17—C16—H16	120.3
C12—C13—H13	119.6	C15—C16—H16	120.3
C7—C8—C9	119.48 (19)

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11···O3i	0.95	2.55	3.264 (2)	132
C11—H11···O3ii	0.95	2.52	3.194 (2)	129
O3—H3···O4iii	0.84	1.85	2.6852 (19)	172
C2—H2A···O1iv	0.99	2.53	3.397 (3)	147
C11—H11···O4	0.95	2.45	2.818 (2)	103

C22H16O3	F(000) = 344
Mr = 328.37	Dx = 1.367 Mg m−3
Triclinic, P1	Melting point: 210 K
a = 5.3969 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 11.6576 (16) Å	Cell parameters from 3650 reflections
c = 12.944 (2) Å	θ = 3.5–29.5°
α = 91.992 (12)°	µ = 0.09 mm−1
β = 98.282 (10)°	T = 120 K
γ = 97.568 (10)°	Plate, colourless
V = 797.68 (19) Å3	0.8 × 0.2 × 0.05 mm
Z = 2

STOE IPDS 2T diffractometer	1804 reflections with I > 2σ(I)
Radiation source: GeniX Mo, 0.05 x 0.05 mm2 microfocus	Rint = 0.077
Detector resolution: 6.67 pixels mm-1	θmax = 26.5°, θmin = 3.5°
rotation method, ω scans	h = −6→6
6849 measured reflections	k = −13→14
3281 independent reflections	l = −16→16

Refinement on F2	Primary atom site location: difference Fourier map
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.068	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.200	H-atom parameters constrained
S = 0.94	w = 1/[σ2(Fo2) + (0.1159P)2] where P = (Fo2 + 2Fc2)/3
3281 reflections	(Δ/σ)max < 0.001
228 parameters	Δρmax = 0.23 e Å−3
0 restraints	Δρmin = −0.29 e Å−3

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.

	x	y	z	Uiso*/Ueq
O1	0.1107 (4)	0.13471 (17)	0.24184 (16)	0.0423 (6)
O4	0.7889 (4)	0.30522 (17)	0.39197 (16)	0.0432 (6)
O3	−0.1593 (4)	0.6939 (2)	0.44060 (17)	0.0503 (6)
H3	−0.0545	0.6964	0.4956	0.075*
C10	0.5289 (5)	0.1266 (2)	0.3391 (2)	0.0365 (7)
C17	0.1145 (5)	0.5660 (2)	0.3820 (2)	0.0390 (7)
H17	0.1940	0.5611	0.4518	0.047*
C9	0.2888 (5)	0.0736 (3)	0.2913 (2)	0.0386 (7)
C3	0.3849 (5)	0.3163 (3)	0.2945 (2)	0.0378 (7)
C7	0.3920 (6)	−0.1113 (3)	0.3446 (2)	0.0453 (8)
H7	0.3455	−0.1925	0.3474	0.054*
C5	0.6977 (6)	0.0575 (3)	0.3885 (2)	0.0405 (7)
H5	0.8608	0.0925	0.4207	0.049*
C4	0.5884 (5)	0.2528 (3)	0.3452 (2)	0.0370 (7)
C15	−0.1803 (6)	0.6487 (3)	0.2598 (2)	0.0431 (8)
H15	−0.3077	0.6973	0.2454	0.052*
C16	−0.0743 (5)	0.6358 (3)	0.3619 (2)	0.0401 (7)
C11	0.3763 (5)	0.4240 (3)	0.3311 (2)	0.0385 (7)
H11	0.5114	0.4544	0.3843	0.046*
C12	0.1891 (5)	0.5030 (2)	0.3014 (2)	0.0378 (7)
C8	0.2210 (6)	−0.0459 (3)	0.2943 (2)	0.0431 (7)
H8	0.0587	−0.0818	0.2620	0.052*
C13	0.0823 (6)	0.5165 (3)	0.1989 (3)	0.0442 (8)
H13	0.1332	0.4755	0.1427	0.053*
C14	−0.0998 (6)	0.5905 (3)	0.1791 (2)	0.0440 (8)
H14	−0.1694	0.6010	0.1090	0.053*
C2	0.2058 (5)	0.2476 (2)	0.2083 (2)	0.0376 (7)
H2	0.0587	0.2908	0.1899	0.045*
C21	0.3266 (5)	0.2321 (3)	0.1100 (2)	0.0387 (7)
C22	0.2451 (7)	0.1373 (3)	0.0408 (2)	0.0517 (9)
H22	0.1084	0.0819	0.0531	0.062*
C6	0.6322 (6)	−0.0602 (3)	0.3915 (2)	0.0440 (8)
H6	0.7491	−0.1062	0.4251	0.053*
C26	0.5228 (6)	0.3134 (3)	0.0894 (2)	0.0493 (8)
H26	0.5783	0.3797	0.1357	0.059*
C23	0.3612 (8)	0.1222 (3)	−0.0467 (3)	0.0632 (11)
H23	0.3042	0.0566	−0.0938	0.076*
C24	0.5596 (7)	0.2024 (4)	−0.0654 (3)	0.0593 (10)
H24	0.6417	0.1913	−0.1244	0.071*
C25	0.6382 (6)	0.2991 (3)	0.0022 (3)	0.0558 (9)
H25	0.7716	0.3556	−0.0114	0.067*

	U11	U22	U33	U12	U13	U23
O1	0.0412 (11)	0.0325 (12)	0.0520 (13)	0.0005 (9)	0.0064 (10)	0.0075 (10)
O4	0.0394 (11)	0.0355 (12)	0.0525 (13)	0.0035 (10)	0.0017 (10)	−0.0001 (10)
O3	0.0553 (13)	0.0463 (14)	0.0510 (13)	0.0193 (11)	0.0022 (10)	0.0025 (11)
C10	0.0432 (16)	0.0317 (17)	0.0372 (15)	0.0082 (13)	0.0115 (13)	0.0044 (12)
C17	0.0413 (16)	0.0267 (16)	0.0469 (17)	0.0024 (13)	0.0014 (13)	0.0043 (13)
C9	0.0412 (16)	0.0344 (17)	0.0416 (16)	0.0037 (13)	0.0122 (13)	0.0036 (13)
C3	0.0397 (15)	0.0375 (17)	0.0372 (16)	0.0058 (13)	0.0083 (13)	0.0043 (13)
C7	0.0550 (19)	0.0309 (17)	0.0522 (19)	0.0020 (15)	0.0195 (15)	0.0020 (14)
C5	0.0438 (16)	0.0377 (18)	0.0419 (16)	0.0075 (14)	0.0108 (13)	0.0049 (13)
C4	0.0406 (16)	0.0363 (17)	0.0343 (15)	0.0048 (14)	0.0077 (13)	−0.0015 (12)
C15	0.0397 (16)	0.0345 (17)	0.0538 (18)	0.0054 (13)	0.0007 (14)	0.0081 (14)
C16	0.0428 (16)	0.0294 (16)	0.0478 (18)	0.0044 (13)	0.0063 (14)	0.0033 (13)
C11	0.0410 (16)	0.0328 (17)	0.0426 (16)	0.0055 (13)	0.0082 (13)	0.0057 (13)
C12	0.0383 (15)	0.0275 (16)	0.0469 (17)	0.0018 (13)	0.0053 (13)	0.0053 (13)
C8	0.0455 (16)	0.0343 (18)	0.0504 (18)	0.0023 (14)	0.0134 (14)	0.0009 (14)
C13	0.0481 (17)	0.0372 (18)	0.0479 (17)	0.0061 (14)	0.0079 (14)	0.0074 (14)
C14	0.0477 (17)	0.0373 (18)	0.0473 (18)	0.0074 (14)	0.0055 (14)	0.0087 (14)
C2	0.0374 (15)	0.0285 (16)	0.0463 (17)	0.0015 (12)	0.0063 (13)	0.0070 (13)
C21	0.0391 (15)	0.0376 (17)	0.0390 (16)	0.0077 (13)	0.0016 (13)	0.0051 (13)
C22	0.064 (2)	0.041 (2)	0.0476 (19)	0.0048 (17)	0.0052 (16)	−0.0032 (15)
C6	0.0511 (18)	0.0351 (18)	0.0492 (18)	0.0124 (14)	0.0117 (15)	0.0086 (14)
C26	0.0465 (18)	0.058 (2)	0.0433 (18)	0.0043 (16)	0.0078 (15)	0.0034 (16)
C23	0.087 (3)	0.057 (2)	0.046 (2)	0.023 (2)	0.0006 (19)	−0.0052 (17)
C24	0.059 (2)	0.079 (3)	0.0456 (19)	0.032 (2)	0.0082 (17)	0.0074 (19)
C25	0.0512 (19)	0.070 (3)	0.0469 (19)	0.0052 (18)	0.0094 (15)	0.0139 (18)

O1—C9	1.369 (3)	C15—H15	0.9500
O1—C2	1.453 (3)	C11—C12	1.475 (4)
O4—C4	1.234 (3)	C11—H11	0.9500
O3—C16	1.370 (4)	C12—C13	1.391 (4)
O3—H3	0.8400	C8—H8	0.9500
C10—C5	1.397 (4)	C13—C14	1.393 (4)
C10—C9	1.405 (4)	C13—H13	0.9500
C10—C4	1.460 (4)	C14—H14	0.9500
C17—C12	1.392 (4)	C2—C21	1.526 (4)
C17—C16	1.388 (4)	C2—H2	1.0000
C17—H17	0.9500	C21—C22	1.381 (4)
C9—C8	1.396 (4)	C21—C26	1.388 (4)
C3—C11	1.335 (4)	C22—C23	1.387 (5)
C3—C4	1.492 (4)	C22—H22	0.9500
C3—C2	1.499 (4)	C6—H6	0.9500
C7—C8	1.380 (4)	C26—C25	1.381 (4)
C7—C6	1.396 (4)	C26—H26	0.9500
C7—H7	0.9500	C23—C24	1.381 (5)
C5—C6	1.374 (4)	C23—H23	0.9500
C5—H5	0.9500	C24—C25	1.383 (5)
C15—C14	1.378 (4)	C24—H24	0.9500
C15—C16	1.383 (4)	C25—H25	0.9500
C9—O1—C2	115.9 (2)	C7—C8—H8	120.3
C16—O3—H3	109.5	C9—C8—H8	120.3
C5—C10—C9	118.8 (3)	C12—C13—C14	119.7 (3)
C5—C10—C4	121.1 (3)	C12—C13—H13	120.1
C9—C10—C4	119.8 (2)	C14—C13—H13	120.1
C12—C17—C16	120.9 (3)	C15—C14—C13	121.0 (3)
C12—C17—H17	119.5	C15—C14—H14	119.5
C16—C17—H17	119.5	C13—C14—H14	119.5
O1—C9—C8	117.0 (3)	O1—C2—C3	111.0 (2)
O1—C9—C10	122.8 (3)	O1—C2—C21	109.4 (2)
C8—C9—C10	120.2 (3)	C3—C2—C21	112.3 (2)
C11—C3—C4	118.3 (3)	O1—C2—H2	108.0
C11—C3—C2	127.3 (3)	C3—C2—H2	108.0
C4—C3—C2	114.4 (2)	C21—C2—H2	108.0
C8—C7—C6	121.1 (3)	C22—C21—C26	118.9 (3)
C8—C7—H7	119.5	C22—C21—C2	121.1 (3)
C6—C7—H7	119.5	C26—C21—C2	120.1 (3)
C6—C5—C10	121.2 (3)	C21—C22—C23	120.6 (3)
C6—C5—H5	119.4	C21—C22—H22	119.7
C10—C5—H5	119.4	C23—C22—H22	119.7
O4—C4—C10	123.2 (3)	C5—C6—C7	119.3 (3)
O4—C4—C3	121.2 (3)	C5—C6—H6	120.3
C10—C4—C3	115.6 (3)	C7—C6—H6	120.3
C14—C15—C16	119.6 (3)	C25—C26—C21	120.7 (3)
C14—C15—H15	120.2	C25—C26—H26	119.6
C16—C15—H15	120.2	C21—C26—H26	119.6
O3—C16—C15	118.4 (2)	C24—C23—C22	120.1 (3)
O3—C16—C17	121.8 (3)	C24—C23—H23	120.0
C15—C16—C17	119.8 (3)	C22—C23—H23	120.0
C3—C11—C12	129.9 (3)	C23—C24—C25	119.7 (3)
C3—C11—H11	115.1	C23—C24—H24	120.2
C12—C11—H11	115.1	C25—C24—H24	120.2
C17—C12—C13	118.9 (2)	C26—C25—C24	120.0 (4)
C17—C12—C11	117.1 (3)	C26—C25—H25	120.0
C13—C12—C11	124.1 (3)	C24—C25—H25	120.0
C7—C8—C9	119.4 (3)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O4i	0.84	1.89	2.728 (3)	172
C17—H17···O4i	0.95	2.49	3.184 (4)	130
C6—H6···O3ii	0.95	2.45	3.265 (4)	143
C11—H11···O4	0.95	2.43	2.807 (3)	103