2-(4-Acetyl-3,5-di­hydroxy-2-methyl­phenoxy)-4,6-di­methoxy-3-methyl­benzoic acid

In the title compound, C₁₉H₂₀O₈, the benzene rings are nearly perpendicular to each other [dihedral angle 80.2 (2)°]. The carboxy group is twisted out while both the methoxy and acetyl groups are almost coplanar with their attached benzene rings. The hydroxy group is involved in an intramolecular O-H...O hydrogen bond with the acetyl O atom and the compound is connected through an intermolecular O-H...O contact to form a dimer. The crystal structure is stabilized by intermolecular O-H...O hydrogen bonds.

S1. Comment

It has been reported that p-depsides could be readily converted into the corresponding diphenyl ether via an intramolecular Smiles rearrangement (Elix et al., 1984). A number of depsides have been prepared as intermediate compounds in the synthesis of corresponding diphenyl ether molecules. Suitable reaction conditions for an intramolecular Smiles rearrangement of the prepared depsides have also been studied extensively (Elix & Jenie, 1989; Elix et al., 1990). The crystal structure determination of the title compound, (I), was undertaken as part of structural studies on diphenyl ether derivatives. Knowledge of the three-dimensional structure of (I) could be useful for the understanding of this synthesis and predicting selectivity of (I). \scheme

It is very difficult to obtain good quality crystals for this compound. Preliminary tests also show that this compound processes anti-bacterial action against S. aureus, though not against E. coli.

The bond lengths and bond angles observed in the structure are normal and agree reasonably with the reported values (Elix et al., 1978; Allen et al., 1987; Chantrapromma et al., 1998). The benzene rings are essentially planar [the atoms having the largest deviations in the two benzene rings are C6 − 0.036 (5) Å and C9 0.017 (5) Å] and they are nearly perpendicular to each other [dihedral angle 80.2 (2)°]. The carboxy group is twisted out of the benzene plane [C7—C12—C19—O8 − 38.5 (6)°] while the two methoxy groups and the acetyl group are nearly coplanar with the benzene rings [C18—O6—C11—C10 8.6 (6)°, C17—O5—C9—C10 − 5.1 (7)° and C2—C3—C13—C14 3.9 (8)°]. The hydroxy group in the molecule is involved in an intramolecular O—H···O hydrogen bond with the acetyl O atom. The compound is connected by intermolecular O—H···O contact to form a dimer (O8—H8A···O7 in Table 2).

S2. Experimental

The title compound was synthesized according to the procedure of Elix et al. (1984). A solution of 4,6-dimethoxy-2-hydroxy-3-methylbenzoic acid (0.07 mmol) and 2,4,6-trihydroxy-3-methylacetophenone (0.07 mmol) in dry dichloromethane was added to a mixture of N,N-dimethylaminopyridine (0.01 mmol) and N,N-dicyclohexyl-carbodiimide(0.17 mmol). The reaction mixture was stirred in a nitrogen atmosphere at room temperature for 6 h. After purification, the corresponding depside (0.05 mmol) was obtained. For the Smiles rearrangement of the depside, a mixture of the depside (0.27 mmol) and anhydrous potassium carbonate (0.40 mmol) in dimethyl sulfoxide (5 ml) was stirred in a nitrogen atmosphere at room temperature for 16 h. The reaction mixture was acidified with cold diluted hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were washed with water to remove the dimethylsulfoxide. After evaporation of the solvent, the crude product was recrystallized in methanol, giving the title compound as light brown crystals, m.p. 447–449 K.

S3. Refinement

After checking their presence in the difference map, all H atoms were placed in calculated positions with O—H = 0.82 Å and C—H = 0.93–0.96 Å, and were allowed to ride on their attached atoms with U_iso = 1.5U_eq for the attached atom. Due to large fraction of weak data at higher angles, the 2θ maximum is limited to 50°.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 1990).

2-(4-Acetyl-3,5-dihydroxy-2-methylphenoxy)-4,6-dimethoxy-3-methylbenzoic acid

Crystal data

C19H20O8	Dx = 1.399 Mg m^−3
Mr = 376.35	Melting point = 174–176 K
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 6.0228 (3) Å	Cell parameters from 3937 reflections
b = 24.792 (1) Å	θ = 1.6–28.2°
c = 12.189 (1) Å	µ = 0.11 mm^−1
β = 100.928 (1)°	T = 293 K
V = 1787.1 (2) Å^3	Plate, light brown
Z = 4	0.34 × 0.18 × 0.10 mm
F(000) = 792

Data collection

Siemens SMART CCD area-detector diffractometer	1529 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.075
Graphite monochromator	θmax = 25.0°, θmin = 1.6°
Detector resolution: 8.33 pixels mm^-1	h = −7→6
ω scans	k = −29→29
6669 measured reflections	l = −11→14
2848 independent reflections

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)] = 0.080	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.231	H-atom parameters constrained
S = 0.96	w = 1/[σ^2(Fo^2) + (0.1483P)^2] where P = (Fo^2 + 2Fc^2)/3
2848 reflections	(Δ/σ)max < 0.001
244 parameters	Δρmax = 0.47 e Å^−3
0 restraints	Δρmin = −0.36 e Å^−3

Special details

Experimental. The data collection covered over a hemisphere of reciprocal space by a combination of three sets of exposures; each set had a different ϕ angle (0, 88 and 180°) for the crystal and each exposure of 10 s covered 0.3° in ω. The crystal-to-detector distance was 4.023 cm and the detector swing angle was −35°. Coverage of the unique set is over 90% complete. Crystal decay was monitored by repeating fifty initial frames at the end of data collection and analysing the duplicate reflections, and was found to be negligible. After checking their presence in the difference map, all H atoms were placed at the geometrically calculated positions and a riding model was used for their refinement. The isotropic displacment parameters of the hydrogen atoms were fixed at one and a half times of the U_eq value of their parent atoms.

Crystal decay was monitored by SAINT (Siemens, 1996) and was found to be negligible.

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	1.1912 (5)	0.58748 (10)	0.2336 (2)	0.0408 (8)
O2	0.5518 (6)	0.65014 (13)	−0.0280 (3)	0.0714 (12)
H2A	0.5548	0.6186	−0.0477	0.107*
O3	0.6996 (7)	0.80722 (13)	0.0786 (3)	0.0742 (12)
O4	1.0595 (7)	0.77311 (12)	0.1958 (3)	0.0718 (12)
H4A	0.9642	0.7950	0.1667	0.108*
O5	0.6954 (6)	0.48547 (12)	0.4075 (3)	0.0585 (10)
O6	1.1350 (5)	0.39835 (11)	0.1675 (3)	0.0469 (9)
O7	1.4470 (5)	0.46170 (12)	0.1015 (3)	0.0482 (9)
O8	1.2700 (6)	0.53787 (13)	0.0455 (3)	0.0613 (10)
H8A	1.3684	0.5390	0.0074	0.092*
C1	0.8631 (8)	0.61821 (17)	0.1042 (4)	0.0462 (12)
H1A	0.8223	0.5829	0.0843	0.055*
C2	0.7321 (8)	0.66010 (17)	0.0563 (4)	0.0486 (13)
C3	0.7823 (8)	0.71442 (16)	0.0875 (4)	0.0422 (12)
C4	0.9890 (8)	0.72245 (16)	0.1640 (4)	0.0442 (12)
C5	1.1305 (8)	0.68091 (16)	0.2101 (4)	0.0425 (12)
C6	1.0567 (8)	0.62856 (16)	0.1827 (4)	0.0402 (11)
C7	1.0854 (7)	0.53831 (15)	0.2480 (4)	0.0336 (10)
C8	0.9357 (7)	0.53618 (16)	0.3208 (4)	0.0400 (11)
C9	0.8464 (7)	0.48542 (17)	0.3387 (4)	0.0396 (11)
C10	0.9128 (7)	0.43905 (16)	0.2901 (4)	0.0402 (11)
H10A	0.8545	0.4057	0.3052	0.048*
C11	1.0657 (7)	0.44248 (16)	0.2190 (4)	0.0359 (10)
C12	1.1536 (7)	0.49248 (15)	0.1943 (3)	0.0323 (10)
C13	0.6371 (9)	0.76068 (18)	0.0483 (4)	0.0543 (14)
C14	0.4080 (10)	0.7549 (2)	−0.0252 (5)	0.0721 (17)
H14A	0.3408	0.7899	−0.0401	0.108*
H14B	0.3133	0.7330	0.0119	0.108*
H14C	0.4236	0.7381	−0.0943	0.108*
C15	1.3484 (9)	0.6915 (2)	0.2918 (5)	0.0708 (17)
H15A	1.3722	0.7297	0.2999	0.106*
H15B	1.4723	0.6755	0.2643	0.106*
H15C	1.3389	0.6760	0.3630	0.106*
C16	0.8672 (9)	0.58493 (18)	0.3812 (4)	0.0535 (13)
H16A	0.9421	0.6164	0.3601	0.080*
H16B	0.9095	0.5796	0.4604	0.080*
H16C	0.7064	0.5898	0.3614	0.080*
C17	0.5833 (9)	0.43585 (19)	0.4250 (5)	0.0658 (16)
H17A	0.4812	0.4420	0.4754	0.099*
H17B	0.6937	0.4094	0.4564	0.099*
H17C	0.5001	0.4230	0.3549	0.099*
C18	1.0217 (9)	0.34841 (17)	0.1762 (5)	0.0560 (14)
H18A	1.0858	0.3210	0.1362	0.084*
H18B	0.8639	0.3524	0.1449	0.084*
H18C	1.0393	0.3383	0.2534	0.084*
C19	1.3050 (8)	0.49644 (16)	0.1123 (4)	0.0384 (11)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0546 (18)	0.0297 (16)	0.038 (2)	−0.0020 (13)	0.0086 (15)	0.0020 (13)
O2	0.093 (3)	0.0396 (18)	0.070 (3)	0.0101 (18)	−0.013 (2)	−0.0040 (17)
O3	0.104 (3)	0.032 (2)	0.084 (3)	0.0077 (18)	0.011 (2)	0.0013 (18)
O4	0.100 (3)	0.0298 (18)	0.082 (3)	−0.0069 (18)	0.008 (2)	−0.0062 (17)
O5	0.079 (2)	0.047 (2)	0.061 (3)	0.0046 (17)	0.042 (2)	0.0006 (16)
O6	0.067 (2)	0.0329 (17)	0.048 (2)	0.0005 (14)	0.0296 (17)	−0.0024 (14)
O7	0.066 (2)	0.0402 (17)	0.045 (2)	0.0076 (16)	0.0263 (17)	0.0050 (14)
O8	0.084 (2)	0.054 (2)	0.057 (2)	0.0194 (18)	0.041 (2)	0.0228 (17)
C1	0.073 (3)	0.025 (2)	0.037 (3)	0.003 (2)	0.005 (3)	−0.0011 (19)
C2	0.067 (3)	0.036 (3)	0.039 (3)	−0.001 (2)	0.001 (3)	−0.002 (2)
C3	0.069 (3)	0.029 (2)	0.035 (3)	0.002 (2)	0.023 (3)	0.0003 (18)
C4	0.075 (3)	0.026 (2)	0.037 (3)	−0.009 (2)	0.022 (3)	−0.0035 (18)
C5	0.063 (3)	0.031 (2)	0.036 (3)	−0.006 (2)	0.016 (2)	−0.0018 (19)
C6	0.060 (3)	0.032 (2)	0.032 (3)	0.002 (2)	0.017 (2)	0.0013 (19)
C7	0.043 (2)	0.032 (2)	0.026 (3)	0.0014 (19)	0.005 (2)	0.0047 (17)
C8	0.056 (3)	0.031 (2)	0.034 (3)	0.006 (2)	0.013 (2)	0.0014 (19)
C9	0.051 (3)	0.042 (3)	0.032 (3)	0.010 (2)	0.023 (2)	0.0045 (19)
C10	0.056 (3)	0.032 (2)	0.036 (3)	0.000 (2)	0.019 (2)	0.0052 (19)
C11	0.052 (2)	0.034 (2)	0.025 (3)	0.0054 (19)	0.016 (2)	0.0004 (18)
C12	0.043 (2)	0.036 (2)	0.021 (3)	0.0034 (18)	0.014 (2)	0.0046 (17)
C13	0.091 (4)	0.036 (3)	0.042 (3)	0.010 (3)	0.026 (3)	0.008 (2)
C14	0.088 (4)	0.051 (3)	0.076 (4)	0.018 (3)	0.012 (3)	0.012 (3)
C15	0.079 (4)	0.054 (3)	0.076 (4)	−0.011 (3)	0.006 (3)	−0.009 (3)
C16	0.078 (3)	0.043 (3)	0.045 (3)	0.007 (2)	0.025 (3)	−0.001 (2)
C17	0.077 (4)	0.053 (3)	0.078 (4)	−0.004 (3)	0.043 (3)	0.009 (3)
C18	0.072 (3)	0.039 (3)	0.065 (4)	−0.001 (2)	0.034 (3)	−0.004 (2)
C19	0.061 (3)	0.030 (2)	0.025 (3)	−0.001 (2)	0.012 (2)	−0.0003 (19)

Geometric parameters (Å, º)

O1—C6	1.374 (5)	C7—C12	1.411 (6)
O1—C7	1.402 (5)	C8—C9	1.402 (6)
O2—C2	1.369 (6)	C8—C16	1.512 (6)
O2—H2A	0.8200	C9—C10	1.387 (6)
O3—C13	1.248 (5)	C10—C11	1.381 (6)
O4—C4	1.358 (5)	C10—H10A	0.9300
O4—H4A	0.8200	C11—C12	1.403 (6)
O5—C9	1.349 (5)	C12—C19	1.478 (6)
O5—C17	1.438 (5)	C13—C14	1.503 (8)
O6—C11	1.366 (5)	C14—H14A	0.9600
O6—C18	1.427 (5)	C14—H14B	0.9600
O7—C19	1.239 (5)	C14—H14C	0.9600
O8—C19	1.303 (5)	C15—H15A	0.9600
O8—H8A	0.8200	C15—H15B	0.9600
C1—C2	1.366 (6)	C15—H15C	0.9600
C1—C6	1.385 (6)	C16—H16A	0.9600
C1—H1A	0.9300	C16—H16B	0.9600
C2—C3	1.416 (6)	C16—H16C	0.9600
C3—C4	1.421 (7)	C17—H17A	0.9600
C3—C13	1.466 (6)	C17—H17B	0.9600
C4—C5	1.386 (6)	C17—H17C	0.9600
C5—C6	1.392 (6)	C18—H18A	0.9600
C5—C15	1.512 (7)	C18—H18B	0.9600
C7—C8	1.381 (6)	C18—H18C	0.9600
C6—O1—C7	117.3 (3)	C11—C12—C7	117.2 (4)
C2—O2—H2A	109.5	C11—C12—C19	120.7 (4)
C4—O4—H4A	109.5	C7—C12—C19	122.1 (4)
C9—O5—C17	118.8 (4)	O3—C13—C3	120.0 (5)
C11—O6—C18	117.9 (3)	O3—C13—C14	117.1 (4)
C19—O8—H8A	109.5	C3—C13—C14	122.9 (4)
C2—C1—C6	119.8 (4)	C13—C14—H14A	109.5
C2—C1—H1A	120.1	C13—C14—H14B	109.5
C6—C1—H1A	120.1	H14A—C14—H14B	109.5
C1—C2—O2	119.7 (4)	C13—C14—H14C	109.5
C1—C2—C3	122.1 (4)	H14A—C14—H14C	109.5
O2—C2—C3	118.1 (4)	H14B—C14—H14C	109.5
C2—C3—C4	115.2 (4)	C5—C15—H15A	109.5
C2—C3—C13	124.9 (4)	C5—C15—H15B	109.5
C4—C3—C13	119.9 (4)	H15A—C15—H15B	109.5
O4—C4—C5	115.9 (4)	C5—C15—H15C	109.5
O4—C4—C3	120.3 (4)	H15A—C15—H15C	109.5
C5—C4—C3	123.8 (4)	H15B—C15—H15C	109.5
C4—C5—C6	116.9 (4)	C8—C16—H16A	109.5
C4—C5—C15	121.9 (4)	C8—C16—H16B	109.5
C6—C5—C15	121.2 (4)	H16A—C16—H16B	109.5
O1—C6—C1	121.5 (4)	C8—C16—H16C	109.5
O1—C6—C5	116.7 (4)	H16A—C16—H16C	109.5
C1—C6—C5	121.8 (4)	H16B—C16—H16C	109.5
C8—C7—O1	118.8 (4)	O5—C17—H17A	109.5
C8—C7—C12	123.4 (4)	O5—C17—H17B	109.5
O1—C7—C12	117.6 (4)	H17A—C17—H17B	109.5
C7—C8—C9	116.8 (4)	O5—C17—H17C	109.5
C7—C8—C16	123.6 (4)	H17A—C17—H17C	109.5
C9—C8—C16	119.6 (4)	H17B—C17—H17C	109.5
O5—C9—C10	123.3 (4)	O6—C18—H18A	109.5
O5—C9—C8	114.8 (4)	O6—C18—H18B	109.5
C10—C9—C8	121.8 (4)	H18A—C18—H18B	109.5
C11—C10—C9	119.8 (4)	O6—C18—H18C	109.5
C11—C10—H10A	120.1	H18A—C18—H18C	109.5
C9—C10—H10A	120.1	H18B—C18—H18C	109.5
O6—C11—C10	122.5 (4)	O7—C19—O8	121.0 (4)
O6—C11—C12	116.6 (4)	O7—C19—C12	123.6 (4)
C10—C11—C12	120.8 (4)	O8—C19—C12	115.3 (4)
C6—C1—C2—O2	174.4 (4)	C17—O5—C9—C10	−5.1 (7)
C6—C1—C2—C3	−2.7 (7)	C17—O5—C9—C8	175.9 (4)
C1—C2—C3—C4	5.6 (7)	C7—C8—C9—O5	−178.0 (4)
O2—C2—C3—C4	−171.5 (4)	C16—C8—C9—O5	2.5 (6)
C1—C2—C3—C13	−173.3 (4)	C7—C8—C9—C10	3.0 (6)
O2—C2—C3—C13	9.6 (7)	C16—C8—C9—C10	−176.5 (4)
C2—C3—C4—O4	177.0 (4)	O5—C9—C10—C11	179.0 (4)
C13—C3—C4—O4	−4.1 (7)	C8—C9—C10—C11	−2.1 (7)
C2—C3—C4—C5	−2.6 (7)	C18—O6—C11—C10	8.6 (6)
C13—C3—C4—C5	176.3 (4)	C18—O6—C11—C12	−169.9 (4)
O4—C4—C5—C6	177.2 (4)	C9—C10—C11—O6	−179.1 (4)
C3—C4—C5—C6	−3.2 (7)	C9—C10—C11—C12	−0.6 (7)
O4—C4—C5—C15	0.7 (7)	O6—C11—C12—C7	−179.3 (4)
C3—C4—C5—C15	−179.7 (5)	C10—C11—C12—C7	2.2 (6)
C7—O1—C6—C1	−29.9 (6)	O6—C11—C12—C19	2.8 (6)
C7—O1—C6—C5	152.9 (4)	C10—C11—C12—C19	−175.8 (4)
C2—C1—C6—O1	179.2 (4)	C8—C7—C12—C11	−1.2 (6)
C2—C1—C6—C5	−3.8 (7)	O1—C7—C12—C11	173.1 (3)
C4—C5—C6—O1	−176.3 (4)	C8—C7—C12—C19	176.7 (4)
C15—C5—C6—O1	0.2 (7)	O1—C7—C12—C19	−9.0 (6)
C4—C5—C6—C1	6.5 (7)	C2—C3—C13—O3	−178.2 (5)
C15—C5—C6—C1	−177.0 (5)	C4—C3—C13—O3	3.0 (7)
C6—O1—C7—C8	−67.2 (5)	C2—C3—C13—C14	3.8 (8)
C6—O1—C7—C12	118.3 (4)	C4—C3—C13—C14	−175.0 (5)
O1—C7—C8—C9	−175.6 (4)	C11—C12—C19—O7	−36.4 (6)
C12—C7—C8—C9	−1.4 (6)	C7—C12—C19—O7	145.8 (4)
O1—C7—C8—C16	4.0 (6)	C11—C12—C19—O8	139.3 (4)
C12—C7—C8—C16	178.2 (4)	C7—C12—C19—O8	−38.5 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···O7^i	0.82	2.10	2.914 (4)	178
O4—H4A···O3	0.82	1.77	2.506 (6)	148
O8—H8A···O7^ii	0.82	1.89	2.697 (5)	170

Symmetry codes: (i) −x+2, −y+1, −z; (ii) −x+3, −y+1, −z.