3-(3,4,5-Trimethoxy­phen­yl)-1H-iso­chrom­en-1-one

The title compound, C₁₈H₁₆O₅, is a biologically active isocoumarin. The mol­ecule is almost planar. No hydrogen bonding is found in the crystal structure.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C)= 0.002 Å
• R factor = 0.044
• wR factor = 0.115
• Data-to-parameter ratio = 14.2

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S1. Comment

The isocoumarin nucleus is an abundant structural motif in natural products (Barry, 1964). Many constituents of the steadily growing class of known isocoumarins exhibit valuable biological properties such as antifungal (Meepagala et al., 2002), anti-tumor or cytotoxic, anti-inflammatory, anti-allergic (Rossi et al., 2003) and enzyme inhibitory activity (Powers et al., 2002). In view of the importance of this class of compounds, the title compound, (I), has been synthesized and its crystal structure is reported here.

In the molecule of the title compound, (I), (Fig. 1) the bond lengths and angles can be regarded as normal (Cambridge Structural Database, Version 5.28, November 2006; Allen, 2002; Mogul, Version 1.1; Bruno et al., 2004). The molecules are essentially planar (r.m.s. deviation for all non-H atoms = 0.033 Å). No hydrogen bonding is found within the crystal lattice.

Related literature

For related literature, see: Barry (1964); Meepagala et al. (2002); Powers et al. (2002); Rossi et al. (2003). For bond-length data, see: Allen (2002); Bruno et al. (2004).

S2. Experimental

A mixture of 3,4,5-trimethoxybenzoic acid (5.9 g, 28 mmol) and thionyl chloride (2.94 ml, 34 mmol) was heated for 30 min in the presence of a few drops of DMF under reflux at 343 K to give 3,4,5-trimethoyxbenzoyl chloride. Completion of reaction was indicated by the disappearance of gas evolution. Removal of excess thionyl chloride was carried out under reduced pressure to afford 3,4,5-tri- methoxybenzoyl chloride. Homophthalic acid (1.5 g, 7.2 mmol) was then added and the solution was refluxed for 6 h at 473 K with stirring. The reaction mixture was extracted with ethyl acetate (3 times 100 ml), an aqueous solution of sodium carbonate (5%, 200 ml) was added to remove the unreacted homophthalic acid. The organic layer was separated, concentrated and chromatographed on silica gel using petroleum ether (313–353 K fractions) as eluent to afford the title compound (yield; 72%; m.p. 437–438 K). Colorless single crystals suitable for X-ray analysis were obtained by slow evaporation of an ethyl acetate solution.

S3. Refinement

H atoms were positioned geometrically, with C—H = 0.95 and 0.98 Å, for aromatic and methyl H atoms, and constrained to ride on their parent atoms, with U_iso(H) = xU_eq(C), where x = 1.5 for methyl H, and x = 1.2 for all other H atoms.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1999); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The reaction scheme.
	Fig. 2. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

3-(3,4,5-trimethoxyphenyl)-1H-isochromen-1-one

Crystal data

C18H16O5	F(000) = 656
Mr = 312.31	Dx = 1.416 Mg m^−3
Monoclinic, P21/n	Melting point: 437(1) K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 9.1496 (11) Å	Cell parameters from 2460 reflections
b = 12.8426 (15) Å	θ = 2.3–26.3°
c = 12.6835 (14) Å	µ = 0.10 mm^−1
β = 100.592 (2)°	T = 100 K
V = 1465.0 (3) Å^3	Irregular, colorless
Z = 4	0.60 × 0.50 × 0.40 mm

Data collection

Bruker CCD area-detector diffractometer	2278 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.037
Graphite monochromator	θmax = 26.4°, θmin = 2.3°
φ and ω scans	h = −7→11
8307 measured reflections	k = −13→16
2994 independent reflections	l = −15→10

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.115	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0558P)^2 + 0.0317P] where P = (Fo^2 + 2Fc^2)/3
2994 reflections	(Δ/σ)max < 0.001
211 parameters	Δρmax = 0.34 e Å^−3
0 restraints	Δρmin = −0.17 e Å^−3

Special details

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	0.06795 (13)	−0.09566 (8)	0.90108 (9)	0.0233 (3)
O2	−0.02138 (14)	−0.25646 (9)	0.89341 (10)	0.0318 (3)
O3	0.48183 (13)	0.05277 (9)	1.16745 (9)	0.0260 (3)
O4	0.49911 (13)	0.25376 (9)	1.12205 (9)	0.0257 (3)
O5	0.33372 (14)	0.33656 (9)	0.94506 (9)	0.0276 (3)
C1	0.07078 (19)	0.00454 (12)	0.86049 (13)	0.0219 (4)
C2	−0.02265 (19)	0.03254 (13)	0.77178 (14)	0.0242 (4)
H2	−0.0177	0.1011	0.7446	0.029*
C3	−0.13180 (19)	−0.03967 (13)	0.71586 (13)	0.0224 (4)
C4	−0.2329 (2)	−0.01390 (14)	0.62211 (14)	0.0270 (4)
H4	−0.2305	0.0535	0.5916	0.032*
C5	−0.33525 (19)	−0.08564 (14)	0.57447 (13)	0.0257 (4)
H5	−0.4019	−0.0680	0.5104	0.031*
C6	−0.34238 (19)	−0.18538 (14)	0.61976 (14)	0.0266 (4)
H6	−0.4145	−0.2343	0.5868	0.032*
C7	−0.24555 (19)	−0.21133 (13)	0.71088 (14)	0.0246 (4)
H7	−0.2511	−0.2781	0.7420	0.029*
C8	−0.13848 (19)	−0.14039 (13)	0.75854 (13)	0.0226 (4)
C9	−0.03234 (19)	−0.17074 (13)	0.85328 (14)	0.0241 (4)
C10	0.18687 (19)	0.06831 (13)	0.92672 (13)	0.0211 (4)
C11	0.27868 (19)	0.02571 (13)	1.01638 (13)	0.0222 (4)
H11	0.2680	−0.0453	1.0345	0.027*
C12	0.38595 (19)	0.08734 (13)	1.07925 (13)	0.0216 (4)
C13	0.39979 (18)	0.19212 (13)	1.05433 (13)	0.0220 (4)
C14	0.30928 (19)	0.23387 (12)	0.96341 (14)	0.0222 (4)
C15	0.20359 (19)	0.17299 (13)	0.89984 (14)	0.0232 (4)
H15	0.1425	0.2020	0.8382	0.028*
C16	0.4738 (2)	−0.05468 (13)	1.19420 (14)	0.0276 (4)
H16A	0.3743	−0.0704	1.2083	0.041*
H16B	0.5481	−0.0700	1.2584	0.041*
H16C	0.4933	−0.0975	1.1343	0.041*
C17	0.6300 (2)	0.27931 (15)	1.08026 (15)	0.0326 (5)
H17A	0.6817	0.2151	1.0669	0.049*
H17B	0.6961	0.3223	1.1324	0.049*
H17C	0.6018	0.3179	1.0129	0.049*
C18	0.2489 (2)	0.38220 (13)	0.85078 (15)	0.0319 (5)
H18A	0.2674	0.3443	0.7875	0.048*
H18B	0.2782	0.4552	0.8459	0.048*
H18C	0.1429	0.3785	0.8542	0.048*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0270 (7)	0.0168 (6)	0.0253 (6)	−0.0011 (5)	0.0024 (5)	0.0009 (5)
O2	0.0363 (8)	0.0227 (7)	0.0328 (7)	−0.0039 (6)	−0.0033 (6)	0.0045 (5)
O3	0.0300 (7)	0.0209 (7)	0.0266 (7)	−0.0029 (5)	0.0038 (5)	−0.0007 (5)
O4	0.0275 (7)	0.0243 (7)	0.0275 (7)	−0.0071 (5)	0.0105 (6)	−0.0039 (5)
O5	0.0334 (8)	0.0176 (6)	0.0320 (7)	−0.0035 (5)	0.0062 (6)	0.0003 (5)
C1	0.0238 (10)	0.0174 (9)	0.0270 (10)	0.0002 (7)	0.0108 (8)	−0.0006 (7)
C2	0.0266 (10)	0.0183 (9)	0.0298 (10)	0.0007 (7)	0.0104 (8)	0.0019 (7)
C3	0.0230 (9)	0.0226 (9)	0.0231 (9)	0.0026 (7)	0.0078 (7)	−0.0016 (7)
C4	0.0296 (10)	0.0246 (10)	0.0271 (10)	0.0042 (8)	0.0061 (8)	0.0014 (7)
C5	0.0223 (10)	0.0320 (10)	0.0221 (9)	0.0033 (8)	0.0024 (7)	−0.0030 (8)
C6	0.0214 (9)	0.0319 (10)	0.0273 (9)	0.0009 (8)	0.0067 (8)	−0.0077 (8)
C7	0.0250 (10)	0.0232 (10)	0.0269 (10)	0.0018 (7)	0.0086 (8)	−0.0021 (7)
C8	0.0212 (9)	0.0232 (9)	0.0247 (9)	0.0002 (7)	0.0076 (7)	−0.0032 (7)
C9	0.0229 (9)	0.0215 (10)	0.0287 (10)	−0.0013 (7)	0.0066 (8)	−0.0016 (8)
C10	0.0220 (9)	0.0196 (9)	0.0236 (9)	0.0006 (7)	0.0091 (7)	−0.0028 (7)
C11	0.0254 (10)	0.0169 (9)	0.0272 (9)	−0.0008 (7)	0.0122 (8)	−0.0021 (7)
C12	0.0235 (9)	0.0238 (10)	0.0194 (8)	0.0021 (7)	0.0086 (7)	−0.0011 (7)
C13	0.0229 (9)	0.0208 (9)	0.0244 (9)	−0.0045 (7)	0.0100 (7)	−0.0065 (7)
C14	0.0265 (10)	0.0169 (9)	0.0261 (9)	0.0008 (7)	0.0126 (8)	−0.0016 (7)
C15	0.0229 (9)	0.0221 (9)	0.0260 (9)	0.0020 (7)	0.0086 (8)	−0.0002 (7)
C16	0.0333 (11)	0.0204 (9)	0.0284 (10)	0.0005 (8)	0.0041 (8)	0.0006 (7)
C17	0.0261 (10)	0.0366 (11)	0.0364 (11)	−0.0061 (8)	0.0093 (9)	−0.0020 (8)
C18	0.0359 (11)	0.0230 (10)	0.0370 (11)	−0.0028 (8)	0.0070 (9)	0.0061 (8)

Geometric parameters (Å, º)

O1—C1	1.3880 (19)	C7—C8	1.392 (2)
O1—C9	1.391 (2)	C7—H7	0.9500
O2—C9	1.209 (2)	C8—C9	1.453 (2)
O3—C12	1.363 (2)	C10—C11	1.395 (2)
O3—C16	1.426 (2)	C10—C15	1.402 (2)
O4—C13	1.3796 (19)	C11—C12	1.392 (2)
O4—C17	1.434 (2)	C11—H11	0.9500
O5—C14	1.3648 (19)	C12—C13	1.393 (2)
O5—C18	1.426 (2)	C13—C14	1.397 (2)
C1—C2	1.331 (2)	C14—C15	1.382 (2)
C1—C10	1.475 (2)	C15—H15	0.9500
C2—C3	1.449 (2)	C16—H16A	0.9800
C2—H2	0.9500	C16—H16B	0.9800
C3—C4	1.405 (2)	C16—H16C	0.9800
C3—C8	1.408 (2)	C17—H17A	0.9800
C4—C5	1.372 (2)	C17—H17B	0.9800
C4—H4	0.9500	C17—H17C	0.9800
C5—C6	1.410 (2)	C18—H18A	0.9800
C5—H5	0.9500	C18—H18B	0.9800
C6—C7	1.362 (2)	C18—H18C	0.9800
C6—H6	0.9500
C1—O1—C9	122.47 (13)	C12—C11—C10	119.96 (15)
C12—O3—C16	117.18 (13)	C12—C11—H11	120.0
C13—O4—C17	113.61 (13)	C10—C11—H11	120.0
C14—O5—C18	117.34 (13)	O3—C12—C11	124.38 (15)
C2—C1—O1	120.73 (15)	O3—C12—C13	115.41 (15)
C2—C1—C10	127.91 (16)	C11—C12—C13	120.20 (15)
O1—C1—C10	111.35 (14)	O4—C13—C12	119.33 (15)
C1—C2—C3	121.23 (16)	O4—C13—C14	121.09 (15)
C1—C2—H2	119.4	C12—C13—C14	119.54 (15)
C3—C2—H2	119.4	O5—C14—C15	124.49 (15)
C4—C3—C8	118.25 (16)	O5—C14—C13	114.88 (15)
C4—C3—C2	123.42 (16)	C15—C14—C13	120.63 (15)
C8—C3—C2	118.33 (15)	C14—C15—C10	119.77 (16)
C5—C4—C3	120.28 (17)	C14—C15—H15	120.1
C5—C4—H4	119.9	C10—C15—H15	120.1
C3—C4—H4	119.9	O3—C16—H16A	109.5
C4—C5—C6	120.63 (16)	O3—C16—H16B	109.5
C4—C5—H5	119.7	H16A—C16—H16B	109.5
C6—C5—H5	119.7	O3—C16—H16C	109.5
C7—C6—C5	119.76 (17)	H16A—C16—H16C	109.5
C7—C6—H6	120.1	H16B—C16—H16C	109.5
C5—C6—H6	120.1	O4—C17—H17A	109.5
C6—C7—C8	120.29 (17)	O4—C17—H17B	109.5
C6—C7—H7	119.9	H17A—C17—H17B	109.5
C8—C7—H7	119.9	O4—C17—H17C	109.5
C7—C8—C3	120.75 (15)	H17A—C17—H17C	109.5
C7—C8—C9	119.59 (15)	H17B—C17—H17C	109.5
C3—C8—C9	119.66 (15)	O5—C18—H18A	109.5
O2—C9—O1	116.78 (15)	O5—C18—H18B	109.5
O2—C9—C8	125.70 (16)	H18A—C18—H18B	109.5
O1—C9—C8	117.50 (15)	O5—C18—H18C	109.5
C11—C10—C15	119.86 (16)	H18A—C18—H18C	109.5
C11—C10—C1	120.59 (15)	H18B—C18—H18C	109.5
C15—C10—C1	119.55 (15)
C9—O1—C1—C2	−1.0 (2)	C2—C1—C10—C15	2.5 (3)
C9—O1—C1—C10	179.63 (14)	O1—C1—C10—C15	−178.16 (14)
O1—C1—C2—C3	1.1 (3)	C15—C10—C11—C12	0.4 (2)
C10—C1—C2—C3	−179.65 (16)	C1—C10—C11—C12	−178.83 (15)
C1—C2—C3—C4	179.91 (17)	C16—O3—C12—C11	2.1 (2)
C1—C2—C3—C8	0.9 (3)	C16—O3—C12—C13	−178.50 (15)
C8—C3—C4—C5	0.2 (3)	C10—C11—C12—O3	−179.23 (15)
C2—C3—C4—C5	−178.76 (16)	C10—C11—C12—C13	1.4 (3)
C3—C4—C5—C6	1.2 (3)	C17—O4—C13—C12	106.40 (17)
C4—C5—C6—C7	−0.9 (3)	C17—O4—C13—C14	−75.9 (2)
C5—C6—C7—C8	−0.9 (3)	O3—C12—C13—O4	−4.2 (2)
C6—C7—C8—C3	2.3 (3)	C11—C12—C13—O4	175.20 (15)
C6—C7—C8—C9	−177.59 (16)	O3—C12—C13—C14	178.08 (15)
C4—C3—C8—C7	−2.0 (3)	C11—C12—C13—C14	−2.5 (2)
C2—C3—C8—C7	177.06 (16)	C18—O5—C14—C15	−3.2 (2)
C4—C3—C8—C9	177.94 (16)	C18—O5—C14—C13	177.38 (15)
C2—C3—C8—C9	−3.0 (2)	O4—C13—C14—O5	3.6 (2)
C1—O1—C9—O2	177.54 (15)	C12—C13—C14—O5	−178.75 (14)
C1—O1—C9—C8	−1.1 (2)	O4—C13—C14—C15	−175.88 (14)
C7—C8—C9—O2	4.5 (3)	C12—C13—C14—C15	1.8 (2)
C3—C8—C9—O2	−175.39 (17)	O5—C14—C15—C10	−179.39 (16)
C7—C8—C9—O1	−176.98 (15)	C13—C14—C15—C10	0.0 (2)
C3—C8—C9—O1	3.1 (2)	C11—C10—C15—C14	−1.1 (2)
C2—C1—C10—C11	−178.24 (17)	C1—C10—C15—C14	178.13 (15)
O1—C1—C10—C11	1.1 (2)