2-(3,4-Di­methoxy­phenyl)-5,7-di­methoxy-3,8-di­methyl-4H-1-benzo­pyran-4-one

The crystal structure of 2-(3,4-di­methoxy­phenyl)-5,7-di­methoxy-3,8-di­methyl-4H-1-benzo­pyran-4-one (alternatively 3′,4′-di­methoxy­phenyl-5,7-di­methoxy-3,8-di­methyl­flavone),C₂₁H₂₂O₆, known to be a potent and selective inhibitor of rat heart cytosolic cyclic nucleotide phospho­diesterases, has been determined. In the benzo­pyran ring system, the pyran ring is slightly puckered. The structure is stabilized by weak C—H...O hydrogen bonds and by π–π interactions between pyran rings.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.061
• wR factor = 0.191
• Data-to-parameter ratio = 20.5

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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S1. Comment

Certain flavonoids are known to display cardiac effects (Laekeman et al., 1986; Cheav et al., 1989). Their presence, for instance, in regularly consumed foods may reduce the risk of death from coronary heart desease in elderly men (Hertog et al., 1993). In particular, the potential cardiovascular effects of luteolin may be attributed to the inhibition of phosphodiesterase (PDE) hydrolyzing the cyclic nucleotide cAMP (cyclic adenosine monophosphate) (Abdalla et al., 1994). In an investigation of the selective inhibition of rat heart cAMP phosphodiesterases by lipophilic C-methyl-2-phenyl-4H-1-benzopyran-4-ones (C-methylflavones), the inhibition effect of eight flavones was studied, seven of them being methyl ethers of mono- or di-C-methylluteolin (Gaillard et al., 1996). Two of the eight flavones were described for the first time. One of these was chosen for the present X-ray investigation, namely 5,7-dimethoxy-2-(3,4-dimethoxyphenyl)-3,8-dimethyl-4H-1-benzopyran-4-one, (I).

A perspective view of (I), together with the atom-numbering scheme, is shown in Fig. 1. In the benzopyran ring system, pyran ring C5/C6/C12/C11/C10/O3 forms an angle of 1.58 (6)° with the C1–C6 benzene ring plane. The pyran ring is slightly puckered (r.m.s. deviation of fitted atoms is 0.017 Å). The keto atom O4 and the methyl atom C13 are twisted out of the pyran ring plane by 0.068 (2) and 0.059 (3) Å, respectively. The C14–C19 benzene ring plane forms an angle of 47.13 (6)° with the pyran ring plane. Three of the four methoxy groups are situated significantly out of the respective benzene ring plane [torsion angles: C2—C1—O1—C7 - 8.9 (3)°, C2—C3—O2—C8 - 6.6 (3)°, C15—C16—O5—C20 - 10.9 (3)° and C18—C17—O6—C21 0.4 (3)°]. The structure is stabilized by weak C—H···O hydrogen bonds (Table 1 and Fig. 2). Apart from the intramolecular contact, the molecules form a chain [C1,1(9) in terms of graph-set theory (Bernstein et al., 1995)]. Moreover, there is a π–π interaction between parallel pyran rings (symmetry related by an inverse centre), see Fig. 3, with a perpendicular distance of 3.506 (2) Å.

S2. Experimental

The synthesis of (I) has been described by Gaillard et al. (1996), who also published ¹H and ¹³C NMR data for the substance. Crystals suitable for X-ray analysis were obtained from benzene (m.p. 490–491 K).

S3. Refinement

H atoms were constrained to ideal geometry using an appropriate riding model. For methyl groups, the C—H distances (0.96 Å) and C–C–H angles (109.5°) were kept fixed, while the torsion angles were allowed to refine with the starting position based on the threefold averaged circular Fourier synthesis.

Computing details

Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT and SADABS (Sheldrick, 2001); program(s) used to solve structure: SHELXTL (Bruker, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg, 2000); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The atom-numbering scheme for (I). Displacement ellipsoids are shown at the 50% probability level.
	Fig. 2. The hydrogen-bonding pattern in (I). The projection is along the b axis.
	Fig. 3. The overlap of pyran rings in perpendicular projection.

2-(3,4-Dimethoxyphenyl)-5,7-dimethoxy-3,8-dimethyl-4H-1-benzopyran-4-one

Crystal data

C21H22O6	F(000) = 1568
Mr = 370.39	Dx = 1.339 Mg m^−3
Monoclinic, C2/c	Melting point: 490–491 K K
Hall symbol: -C 2yc	Mo Kα radiation, λ = 0.71073 Å
a = 19.3584 (2) Å	Cell parameters from 5905 reflections
b = 7.6117 (1) Å	θ = 1.6–30.5°
c = 26.1758 (4) Å	µ = 0.10 mm^−1
β = 107.700 (1)°	T = 296 K
V = 3674.43 (8) Å^3	Irregular, colorless
Z = 8	0.53 × 0.44 × 0.35 mm

Data collection

Siemens SMART CCD diffractometer	5565 independent reflections
Radiation source: fine-focus sealed tube	4109 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.037
ω scans	θmax = 30.5°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 2001)	h = −27→27
Tmin = 0.950, Tmax = 0.967	k = −10→10
23515 measured reflections	l = −37→37

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.061	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.191	H-atom parameters constrained
S = 1.02	w = 1/[σ^2(Fo^2) + (0.1046P)^2 + 2.3577P] where P = (Fo^2 + 2Fc^2)/3
5565 reflections	(Δ/σ)max < 0.001
272 parameters	Δρmax = 0.32 e Å^−3
0 restraints	Δρmin = −0.37 e Å^−3

Special details

Experimental. Data were collected at room temperature using a Siemens SMART CCD diffractometer. A full sphere of reciprocal space was scanned by 0.3° steps in ω with a crystal–to–detector distance of 3.97 cm, 30 s per frame. Preliminary orientation matrix was obtained from the first 100 frames using SMART (Siemens, 1995). The collected frames were integrated using the preliminary orientation matrix which was updated every 100 frames. Final cell parameters were obtained by refinement on the position of 5905 reflections with I>10σ(I) after integration of all the frames data using SAINT (Siemens, 1995).

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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
O1	0.02601 (7)	0.2857 (2)	−0.13252 (4)	0.0500 (3)
O2	0.26710 (7)	0.5218 (2)	−0.05331 (5)	0.0489 (3)
O3	0.12825 (6)	0.36546 (17)	0.05651 (4)	0.0376 (3)
O4	−0.05017 (6)	0.2213 (2)	−0.06501 (5)	0.0505 (3)
O5	0.16114 (9)	0.5776 (2)	0.24443 (5)	0.0591 (4)
O6	0.13327 (8)	0.3019 (2)	0.29255 (5)	0.0541 (4)
C1	0.08198 (8)	0.3412 (2)	−0.09004 (6)	0.0356 (3)
C2	0.14577 (8)	0.4071 (2)	−0.09608 (6)	0.0370 (3)
H2	0.1511	0.4175	−0.1301	0.047 (6)*
C3	0.20247 (8)	0.4581 (2)	−0.05061 (6)	0.0357 (3)
C4	0.19638 (8)	0.4465 (2)	0.00096 (6)	0.0342 (3)
C5	0.13115 (8)	0.3780 (2)	0.00500 (5)	0.0313 (3)
C6	0.07243 (8)	0.3248 (2)	−0.03855 (6)	0.0315 (3)
C7	0.03012 (11)	0.3202 (3)	−0.18467 (7)	0.0558 (5)
H7A	0.0384	0.4433	−0.1882	0.057 (7)*
H7B	−0.0146	0.2866	−0.2107	0.093 (9)*
H7C	0.0693	0.2541	−0.1904	0.069 (7)*
C8	0.28177 (10)	0.5211 (3)	−0.10355 (8)	0.0532 (5)
H8A	0.2777	0.4034	−0.1173	0.055 (6)*
H8B	0.3300	0.5640	−0.0987	0.073 (7)*
H8C	0.2475	0.5953	−0.1285	0.069 (7)*
C9	0.25620 (9)	0.5078 (3)	0.04922 (7)	0.0457 (4)
H9A	0.3021	0.4713	0.0460	0.114 (12)*
H9B	0.2496	0.4575	0.0810	0.095 (10)*
H9C	0.2550	0.6336	0.0514	0.124 (13)*
C10	0.06792 (8)	0.2979 (2)	0.06699 (6)	0.0336 (3)
C11	0.00769 (8)	0.2495 (2)	0.02784 (6)	0.0337 (3)
C12	0.00543 (8)	0.2621 (2)	−0.02897 (6)	0.0337 (3)
C13	−0.06062 (9)	0.1872 (3)	0.03847 (7)	0.0430 (4)
H13A	−0.0619	0.0611	0.0381	0.103 (11)*
H13B	−0.1021	0.2318	0.0112	0.069 (7)*
H13C	−0.0614	0.2291	0.0729	0.070 (7)*
C14	0.08178 (8)	0.2926 (2)	0.12599 (6)	0.0358 (3)
C15	0.11390 (9)	0.4397 (2)	0.15624 (6)	0.0399 (4)
H15	0.1241	0.5386	0.1390	0.048 (6)*
C16	0.13061 (9)	0.4390 (2)	0.21174 (6)	0.0405 (4)
C17	0.11490 (9)	0.2895 (3)	0.23781 (6)	0.0400 (4)
C18	0.08389 (10)	0.1441 (3)	0.20786 (7)	0.0435 (4)
H18	0.0740	0.0449	0.2251	0.052 (6)*
C19	0.06718 (10)	0.1443 (3)	0.15176 (6)	0.0413 (4)
H19	0.0465	0.0457	0.1320	0.045 (5)*
C20	0.18819 (16)	0.7187 (4)	0.22090 (12)	0.0722 (7)
H20A	0.2214	0.6744	0.2033	0.095 (10)*
H20B	0.2128	0.8006	0.2483	0.092 (10)*
H20C	0.1486	0.7769	0.1952	0.111 (12)*
C21	0.12001 (13)	0.1539 (4)	0.32130 (8)	0.0650 (6)
H21A	0.0691	0.1274	0.3098	0.091 (9)*
H21B	0.1354	0.1796	0.3590	0.093 (9)*
H21C	0.1466	0.0547	0.3146	0.067 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0401 (6)	0.0810 (10)	0.0253 (5)	−0.0161 (6)	0.0047 (5)	−0.0017 (5)
O2	0.0333 (6)	0.0723 (9)	0.0422 (6)	−0.0116 (6)	0.0133 (5)	0.0019 (6)
O3	0.0320 (5)	0.0548 (7)	0.0251 (5)	−0.0059 (5)	0.0075 (4)	−0.0002 (5)
O4	0.0328 (6)	0.0807 (10)	0.0334 (6)	−0.0161 (6)	0.0034 (5)	0.0002 (6)
O5	0.0696 (9)	0.0648 (9)	0.0418 (7)	−0.0186 (7)	0.0154 (6)	−0.0145 (6)
O6	0.0572 (8)	0.0766 (10)	0.0261 (5)	−0.0075 (7)	0.0089 (5)	0.0002 (6)
C1	0.0317 (7)	0.0456 (9)	0.0270 (6)	−0.0017 (6)	0.0049 (5)	0.0007 (6)
C2	0.0338 (7)	0.0489 (9)	0.0291 (7)	−0.0014 (6)	0.0107 (6)	0.0023 (6)
C3	0.0277 (7)	0.0441 (9)	0.0359 (7)	−0.0018 (6)	0.0106 (6)	0.0023 (6)
C4	0.0274 (6)	0.0415 (8)	0.0314 (7)	−0.0020 (6)	0.0056 (5)	0.0006 (6)
C5	0.0299 (7)	0.0386 (8)	0.0251 (6)	0.0003 (6)	0.0076 (5)	0.0019 (5)
C6	0.0269 (6)	0.0388 (8)	0.0275 (6)	−0.0005 (5)	0.0064 (5)	0.0017 (5)
C7	0.0461 (10)	0.0919 (17)	0.0270 (7)	−0.0098 (10)	0.0075 (7)	−0.0009 (9)
C8	0.0354 (8)	0.0801 (15)	0.0483 (10)	−0.0019 (9)	0.0190 (7)	0.0108 (10)
C9	0.0346 (8)	0.0598 (11)	0.0370 (8)	−0.0113 (8)	0.0023 (6)	−0.0029 (8)
C10	0.0315 (7)	0.0423 (8)	0.0282 (6)	0.0006 (6)	0.0108 (5)	0.0013 (6)
C11	0.0298 (7)	0.0415 (8)	0.0302 (6)	0.0002 (6)	0.0097 (5)	0.0014 (6)
C12	0.0286 (7)	0.0418 (8)	0.0292 (6)	−0.0021 (6)	0.0063 (5)	0.0016 (6)
C13	0.0322 (7)	0.0571 (11)	0.0419 (8)	−0.0012 (7)	0.0143 (7)	0.0032 (8)
C14	0.0329 (7)	0.0474 (9)	0.0271 (6)	0.0004 (6)	0.0093 (5)	0.0007 (6)
C15	0.0413 (8)	0.0473 (9)	0.0317 (7)	−0.0018 (7)	0.0120 (6)	0.0009 (6)
C16	0.0369 (8)	0.0525 (10)	0.0309 (7)	−0.0019 (7)	0.0086 (6)	−0.0051 (7)
C17	0.0336 (7)	0.0597 (10)	0.0260 (6)	0.0020 (7)	0.0079 (6)	0.0014 (6)
C18	0.0452 (9)	0.0517 (10)	0.0333 (7)	−0.0024 (8)	0.0116 (7)	0.0067 (7)
C19	0.0432 (9)	0.0488 (9)	0.0310 (7)	−0.0047 (7)	0.0099 (6)	−0.0003 (7)
C20	0.0825 (18)	0.0632 (14)	0.0759 (16)	−0.0259 (13)	0.0316 (15)	−0.0180 (13)
C21	0.0622 (13)	0.0956 (18)	0.0356 (9)	−0.0084 (12)	0.0123 (9)	0.0140 (10)

Geometric parameters (Å, º)

O1—C1	1.3623 (18)	C9—H9A	0.9600
O1—C7	1.416 (2)	C9—H9B	0.9600
O2—C3	1.3635 (18)	C9—H9C	0.9600
O2—C8	1.427 (2)	C10—C11	1.349 (2)
O3—C5	1.3697 (16)	C10—C14	1.486 (2)
O3—C10	1.3779 (18)	C11—C12	1.4774 (19)
O4—C12	1.2358 (18)	C11—C13	1.508 (2)
O5—C16	1.373 (2)	C13—H13A	0.9600
O5—C20	1.415 (3)	C13—H13B	0.9600
O6—C17	1.3707 (18)	C13—H13C	0.9600
O6—C21	1.421 (3)	C14—C19	1.388 (2)
C1—C2	1.386 (2)	C14—C15	1.402 (2)
C1—C6	1.4204 (19)	C15—C16	1.389 (2)
C2—C3	1.406 (2)	C15—H15	0.9300
C2—H2	0.9300	C16—C17	1.407 (3)
C3—C4	1.393 (2)	C17—C18	1.383 (3)
C4—C5	1.400 (2)	C18—C19	1.405 (2)
C4—C9	1.505 (2)	C18—H18	0.9300
C5—C6	1.403 (2)	C19—H19	0.9300
C6—C12	1.474 (2)	C20—H20A	0.9600
C7—H7A	0.9600	C20—H20B	0.9600
C7—H7B	0.9600	C20—H20C	0.9600
C7—H7C	0.9600	C21—H21A	0.9600
C8—H8A	0.9600	C21—H21B	0.9600
C8—H8B	0.9600	C21—H21C	0.9600
C8—H8C	0.9600
C1—O1—C7	117.75 (14)	O3—C10—C14	108.72 (12)
C3—O2—C8	119.27 (14)	C10—C11—C12	120.08 (13)
C5—O3—C10	120.85 (12)	C10—C11—C13	123.34 (14)
C16—O5—C20	117.24 (16)	C12—C11—C13	116.54 (13)
C17—O6—C21	117.92 (16)	O4—C12—C6	123.97 (13)
O1—C1—C2	122.29 (13)	O4—C12—C11	120.29 (13)
O1—C1—C6	116.53 (13)	C6—C12—C11	115.73 (12)
C2—C1—C6	121.17 (13)	C11—C13—H13A	109.5
C1—C2—C3	119.79 (13)	C11—C13—H13B	109.5
C1—C2—H2	120.1	H13A—C13—H13B	109.5
C3—C2—H2	120.1	C11—C13—H13C	109.5
O2—C3—C4	114.96 (13)	H13A—C13—H13C	109.5
O2—C3—C2	123.15 (13)	H13B—C13—H13C	109.5
C4—C3—C2	121.89 (13)	C19—C14—C15	119.73 (14)
C3—C4—C5	116.16 (13)	C19—C14—C10	121.87 (15)
C3—C4—C9	121.57 (14)	C15—C14—C10	118.32 (14)
C5—C4—C9	122.25 (14)	C16—C15—C14	120.67 (16)
O3—C5—C6	120.95 (13)	C16—C15—H15	119.7
O3—C5—C4	114.09 (13)	C14—C15—H15	119.7
C6—C5—C4	124.95 (13)	O5—C16—C15	124.63 (17)
C5—C6—C1	116.03 (13)	O5—C16—C17	115.76 (14)
C5—C6—C12	119.54 (12)	C15—C16—C17	119.60 (16)
C1—C6—C12	124.41 (13)	O6—C17—C18	125.26 (16)
O1—C7—H7A	109.5	O6—C17—C16	115.20 (16)
O1—C7—H7B	109.5	C18—C17—C16	119.54 (14)
H7A—C7—H7B	109.5	C17—C18—C19	120.95 (16)
O1—C7—H7C	109.5	C17—C18—H18	119.5
H7A—C7—H7C	109.5	C19—C18—H18	119.5
H7B—C7—H7C	109.5	C14—C19—C18	119.50 (16)
O2—C8—H8A	109.5	C14—C19—H19	120.2
O2—C8—H8B	109.5	C18—C19—H19	120.2
H8A—C8—H8B	109.5	O5—C20—H20A	109.5
O2—C8—H8C	109.5	O5—C20—H20B	109.5
H8A—C8—H8C	109.5	H20A—C20—H20B	109.5
H8B—C8—H8C	109.5	O5—C20—H20C	109.5
C4—C9—H9A	109.5	H20A—C20—H20C	109.5
C4—C9—H9B	109.5	H20B—C20—H20C	109.5
H9A—C9—H9B	109.5	O6—C21—H21A	109.5
C4—C9—H9C	109.5	O6—C21—H21B	109.5
H9A—C9—H9C	109.5	H21A—C21—H21B	109.5
H9B—C9—H9C	109.5	O6—C21—H21C	109.5
C11—C10—O3	122.68 (13)	H21A—C21—H21C	109.5
C11—C10—C14	128.59 (14)	H21B—C21—H21C	109.5
C7—O1—C1—C2	−8.9 (3)	C14—C10—C11—C13	3.4 (3)
C7—O1—C1—C6	172.34 (17)	C5—C6—C12—O4	176.11 (17)
O1—C1—C2—C3	−178.35 (16)	C1—C6—C12—O4	−1.9 (3)
C6—C1—C2—C3	0.3 (3)	C5—C6—C12—C11	−3.9 (2)
C8—O2—C3—C4	173.28 (16)	C1—C6—C12—C11	178.06 (15)
C8—O2—C3—C2	−6.6 (3)	C10—C11—C12—O4	−178.48 (17)
C1—C2—C3—O2	179.10 (16)	C13—C11—C12—O4	−0.6 (2)
C1—C2—C3—C4	−0.8 (3)	C10—C11—C12—C6	1.5 (2)
O2—C3—C4—C5	−178.68 (15)	C13—C11—C12—C6	179.41 (15)
C2—C3—C4—C5	1.2 (2)	C11—C10—C14—C19	48.6 (3)
O2—C3—C4—C9	2.5 (2)	O3—C10—C14—C19	−132.30 (16)
C2—C3—C4—C9	−177.65 (17)	C11—C10—C14—C15	−134.66 (19)
C10—O3—C5—C6	1.0 (2)	O3—C10—C14—C15	44.47 (19)
C10—O3—C5—C4	−179.00 (14)	C19—C14—C15—C16	−0.6 (3)
C3—C4—C5—O3	178.63 (14)	C10—C14—C15—C16	−177.49 (15)
C9—C4—C5—O3	−2.5 (2)	C20—O5—C16—C15	−10.9 (3)
C3—C4—C5—C6	−1.3 (2)	C20—O5—C16—C17	170.2 (2)
C9—C4—C5—C6	177.53 (16)	C14—C15—C16—O5	−179.08 (17)
O3—C5—C6—C1	−179.02 (14)	C14—C15—C16—C17	−0.2 (3)
C4—C5—C6—C1	0.9 (2)	C21—O6—C17—C18	0.4 (3)
O3—C5—C6—C12	2.8 (2)	C21—O6—C17—C16	−178.85 (18)
C4—C5—C6—C12	−177.28 (15)	O5—C16—C17—O6	−0.9 (2)
O1—C1—C6—C5	178.38 (15)	C15—C16—C17—O6	−179.86 (15)
C2—C1—C6—C5	−0.4 (2)	O5—C16—C17—C18	179.82 (16)
O1—C1—C6—C12	−3.5 (2)	C15—C16—C17—C18	0.9 (3)
C2—C1—C6—C12	177.71 (16)	O6—C17—C18—C19	−179.84 (16)
C5—O3—C10—C11	−3.5 (2)	C16—C17—C18—C19	−0.6 (3)
C5—O3—C10—C14	177.27 (13)	C15—C14—C19—C18	0.9 (3)
O3—C10—C11—C12	2.1 (2)	C10—C14—C19—C18	177.59 (15)
C14—C10—C11—C12	−178.83 (15)	C17—C18—C19—C14	−0.2 (3)
O3—C10—C11—C13	−175.59 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8B···O4^i	0.96	2.52	3.454 (2)	164
C9—H9B···O3	0.96	2.35	2.762 (2)	106

Symmetry code: (i) x+1/2, y+1/2, z.