The title compound, C20H19NO7, crystallizes in the space group Pna21. X-ray analysis shows the compound has the desired 3'-hydroxy and 4'-methoxy substitution pattern, as in the natural template combretastatin A-4.
Supporting information
CCDC reference: 269813
Key indicators
- Single-crystal X-ray study
- T = 295 K
- Mean (C-C) = 0.005 Å
- R factor = 0.051
- wR factor = 0.145
- Data-to-parameter ratio = 7.4
checkCIF/PLATON results
No syntax errors found
Alert level A
PLAT222_ALERT_3_A Large Non-Solvent H Ueq(max)/Ueq(min) ... 6.73 Ratio
Alert level C
RINTA01_ALERT_3_C The value of Rint is greater than 0.10
Rint given 0.135
PLAT020_ALERT_3_C The value of Rint is greater than 0.10 ......... 0.14
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) ..... 7.36
PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) ... 3.00 Ratio
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ... 5
Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
correct. If it is not, please give the correct count in the
_publ_section_exptl_refinement section of the submitted CIF.
From the CIF: _diffrn_reflns_theta_max 74.01
From the CIF: _reflns_number_total 1972
Count of symmetry unique reflns 1975
Completeness (_total/calc) 99.85%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 0
Fraction of Friedel pairs measured 0.000
Are heavy atom types Z>Si present no
1 ALERT level A = In general: serious problem
0 ALERT level B = Potentially serious problem
5 ALERT level C = Check and explain
1 ALERT level G = General alerts; check
0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
1 ALERT type 2 Indicator that the structure model may be wrong or deficient
5 ALERT type 3 Indicator that the structure quality may be low
1 ALERT type 4 Improvement, methodology, query or suggestion
Data collection: CAD-4 Software (Enraf–Nonius, 1998); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.
4-(3-hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2,5-dihydro-
1
H-pyrrole-2,5-dione
top
Crystal data top
C20H19NO7 | Dx = 1.424 Mg m−3 |
Mr = 385.22 | Melting point: 234 K |
Orthorhombic, Pna21 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2c -2n | Cell parameters from 25 reflections |
a = 14.0827 (17) Å | θ = 21–28° |
b = 17.674 (3) Å | µ = 0.92 mm−1 |
c = 7.2238 (4) Å | T = 295 K |
V = 1798.0 (4) Å3 | Needle, green yellow |
Z = 4 | 0.58 × 0.12 × 0.04 mm |
F(000) = 808 | |
Data collection top
Enraf–Nonius CAD-4 diffractometer | 1654 reflections with I > 2σ(I) |
Radiation source: rotating anode | Rint = 0.135 |
Graphite monochromator | θmax = 74.0° |
θ/2ω scans | h = −17→17 |
Absorption correction: numerical (de Meulenaer & Tompa, 1965) | k = −22→21 |
Tmin = 0.69, Tmax = 0.965 | l = −8→8 |
3459 measured reflections | 3 standard reflections every 60 min |
1972 independent reflections | intensity decay: 3% |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.051 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.145 | Only H-atom displacement parameters refined |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0712P)2] where P = (Fo2 + 2Fc2)/3 |
1972 reflections | (Δ/σ)max < 0.001 |
268 parameters | Δρmax = 0.44 e Å−3 |
1 restraint | Δρmin = −0.23 e Å−3 |
Special details top
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 (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.1848 (2) | −0.02928 (17) | 0.5300 (6) | 0.0277 (7) | |
C2 | 0.0906 (2) | −0.02839 (17) | 0.5627 (5) | 0.0261 (7) | |
C3 | 0.0601 (3) | −0.10821 (18) | 0.6082 (6) | 0.0286 (8) | |
C5 | 0.2188 (3) | −0.10917 (19) | 0.5518 (7) | 0.0324 (8) | |
N4 | 0.1406 (2) | −0.15187 (15) | 0.5968 (6) | 0.0332 (8) | |
H4 | 0.1471 | −0.1950 | 0.6193 | 0.031 (12)* | |
C6 | 0.2515 (2) | 0.03134 (18) | 0.4829 (6) | 0.0275 (8) | |
C7 | 0.2352 (3) | 0.07935 (18) | 0.3325 (6) | 0.0323 (8) | |
H7 | 0.1805 | 0.0742 | 0.2616 | 0.017 (9)* | |
C8 | 0.3018 (3) | 0.13503 (19) | 0.2897 (6) | 0.0320 (8) | |
C9 | 0.3825 (3) | 0.14408 (19) | 0.3977 (6) | 0.0309 (8) | |
C10 | 0.3980 (3) | 0.0965 (2) | 0.5472 (7) | 0.0374 (9) | |
C11 | 0.3332 (3) | 0.0390 (2) | 0.5867 (7) | 0.0353 (9) | |
H11 | 0.3451 | 0.0057 | 0.6836 | 0.061 (16)* | |
C12 | 0.0225 (2) | 0.03464 (17) | 0.5744 (6) | 0.0260 (7) | |
C13 | −0.0731 (3) | 0.0237 (2) | 0.5296 (6) | 0.0323 (8) | |
H13 | −0.0935 | −0.0232 | 0.4867 | 0.050 (14)* | |
C14 | −0.1375 (3) | 0.0822 (2) | 0.5486 (7) | 0.0366 (9) | |
H14 | −0.2008 | 0.0746 | 0.5171 | 0.021 (9)* | |
C15 | −0.1082 (3) | 0.1526 (2) | 0.6148 (7) | 0.0356 (9) | |
C16 | −0.0121 (3) | 0.16363 (18) | 0.6583 (6) | 0.0337 (8) | |
C17 | 0.0519 (3) | 0.10542 (19) | 0.6374 (6) | 0.0313 (8) | |
H17 | 0.1156 | 0.1134 | 0.6655 | 0.015 (8)* | |
O18 | −0.01722 (18) | −0.13021 (14) | 0.6544 (6) | 0.0396 (7) | |
O19 | 0.29849 (19) | −0.13220 (15) | 0.5328 (7) | 0.0507 (10) | |
O20 | 0.2942 (2) | 0.18510 (16) | 0.1466 (5) | 0.0492 (9) | |
C21 | 0.2285 (4) | 0.1705 (3) | 0.0040 (8) | 0.0559 (14) | |
H21A | 0.1651 | 0.1736 | 0.0525 | 0.093 (14)* | |
H21B | 0.2392 | 0.1207 | −0.0449 | 0.093 (14)* | |
H21C | 0.2362 | 0.2072 | −0.0927 | 0.093 (14)* | |
O22 | 0.4435 (2) | 0.20294 (14) | 0.3608 (5) | 0.0406 (7) | |
C23 | 0.5255 (3) | 0.1831 (3) | 0.2582 (12) | 0.0630 (17) | |
H23A | 0.5070 | 0.1649 | 0.1383 | 0.101 (15)* | |
H23B | 0.5598 | 0.1442 | 0.3225 | 0.101 (15)* | |
H23C | 0.5654 | 0.2268 | 0.2440 | 0.101 (15)* | |
O24 | 0.4781 (2) | 0.11165 (18) | 0.6479 (6) | 0.0576 (11) | |
C25 | 0.5024 (4) | 0.0617 (3) | 0.7931 (11) | 0.078 (2) | |
H25A | 0.5109 | 0.0117 | 0.7443 | 0.079 (12)* | |
H25B | 0.4525 | 0.0613 | 0.8837 | 0.079 (12)* | |
H25C | 0.5604 | 0.0783 | 0.8500 | 0.079 (12)* | |
O26 | −0.1656 (2) | 0.21367 (16) | 0.6431 (5) | 0.0459 (8) | |
C27 | −0.2594 (3) | 0.2101 (3) | 0.5727 (10) | 0.0545 (13) | |
H27A | −0.2973 | 0.1783 | 0.6512 | 0.069 (10)* | |
H27B | −0.2582 | 0.1894 | 0.4498 | 0.069 (10)* | |
H27C | −0.2861 | 0.2600 | 0.5694 | 0.069 (10)* | |
O28 | 0.0205 (2) | 0.23070 (15) | 0.7287 (6) | 0.0528 (10) | |
H28 | −0.0125 | 0.2702 | 0.6782 | 0.050 (14)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0364 (18) | 0.0220 (14) | 0.0246 (19) | −0.0007 (12) | −0.0037 (17) | 0.0014 (14) |
C2 | 0.0297 (17) | 0.0267 (15) | 0.0219 (19) | −0.0020 (12) | −0.0001 (15) | −0.0011 (14) |
C3 | 0.0354 (17) | 0.0276 (15) | 0.0229 (19) | −0.0027 (13) | −0.0003 (15) | 0.0002 (13) |
C5 | 0.038 (2) | 0.0287 (16) | 0.031 (2) | 0.0013 (14) | −0.0018 (19) | 0.0017 (15) |
N4 | 0.0385 (17) | 0.0200 (13) | 0.041 (2) | 0.0008 (11) | 0.0023 (16) | 0.0031 (12) |
C6 | 0.0277 (17) | 0.0266 (15) | 0.028 (2) | 0.0014 (13) | 0.0017 (15) | 0.0014 (14) |
C7 | 0.0329 (18) | 0.0330 (17) | 0.031 (2) | −0.0043 (14) | −0.0081 (17) | 0.0056 (16) |
C8 | 0.0383 (19) | 0.0295 (16) | 0.028 (2) | −0.0049 (14) | −0.0013 (18) | 0.0027 (15) |
C9 | 0.0335 (18) | 0.0251 (15) | 0.034 (2) | −0.0059 (13) | 0.0002 (17) | −0.0020 (14) |
C10 | 0.0350 (18) | 0.0359 (18) | 0.041 (3) | −0.0058 (15) | −0.011 (2) | −0.0017 (18) |
C11 | 0.0362 (19) | 0.0349 (17) | 0.035 (2) | −0.0028 (14) | −0.0078 (18) | 0.0088 (15) |
C12 | 0.0299 (17) | 0.0251 (15) | 0.0231 (19) | 0.0005 (12) | 0.0010 (15) | 0.0037 (13) |
C13 | 0.0367 (19) | 0.0343 (17) | 0.026 (2) | −0.0025 (14) | 0.0000 (18) | 0.0011 (14) |
C14 | 0.0301 (17) | 0.047 (2) | 0.033 (2) | 0.0018 (15) | 0.0003 (18) | 0.0020 (19) |
C15 | 0.045 (2) | 0.0355 (18) | 0.026 (2) | 0.0094 (15) | 0.0057 (18) | 0.0058 (15) |
C16 | 0.048 (2) | 0.0263 (15) | 0.027 (2) | −0.0003 (14) | −0.0018 (19) | 0.0005 (16) |
C17 | 0.0334 (17) | 0.0288 (15) | 0.032 (2) | −0.0005 (13) | −0.0070 (17) | 0.0064 (15) |
O18 | 0.0328 (13) | 0.0345 (12) | 0.052 (2) | −0.0076 (10) | 0.0012 (15) | 0.0047 (13) |
O19 | 0.0332 (14) | 0.0375 (14) | 0.081 (3) | 0.0071 (11) | 0.0056 (19) | 0.0067 (17) |
O20 | 0.0585 (18) | 0.0453 (14) | 0.044 (2) | −0.0226 (13) | −0.0192 (18) | 0.0207 (15) |
C21 | 0.065 (3) | 0.065 (3) | 0.038 (3) | −0.023 (2) | −0.019 (3) | 0.022 (2) |
O22 | 0.0372 (14) | 0.0333 (13) | 0.051 (2) | −0.0125 (11) | 0.0045 (15) | −0.0029 (13) |
C23 | 0.045 (2) | 0.054 (3) | 0.090 (5) | −0.004 (2) | 0.019 (3) | 0.011 (3) |
O24 | 0.0544 (19) | 0.0536 (16) | 0.065 (3) | −0.0221 (14) | −0.032 (2) | 0.0185 (19) |
C25 | 0.074 (4) | 0.077 (3) | 0.084 (6) | −0.025 (3) | −0.054 (4) | 0.023 (4) |
O26 | 0.0435 (16) | 0.0487 (15) | 0.046 (2) | 0.0147 (12) | −0.0006 (17) | −0.0030 (15) |
C27 | 0.044 (2) | 0.063 (3) | 0.057 (4) | 0.019 (2) | 0.002 (3) | 0.002 (3) |
O28 | 0.064 (2) | 0.0324 (14) | 0.062 (3) | 0.0063 (13) | −0.017 (2) | −0.0070 (14) |
Geometric parameters (Å, º) top
C1—C2 | 1.347 (5) | C14—C15 | 1.395 (6) |
C1—C6 | 1.466 (5) | C14—H14 | 0.9300 |
C1—C5 | 1.500 (4) | C15—O26 | 1.363 (4) |
C2—C12 | 1.472 (4) | C15—C16 | 1.404 (6) |
C2—C3 | 1.511 (4) | C16—O28 | 1.369 (4) |
C3—O18 | 1.203 (5) | C16—C17 | 1.376 (5) |
C3—N4 | 1.374 (5) | C17—H17 | 0.9300 |
C5—O19 | 1.201 (4) | O20—C21 | 1.409 (6) |
C5—N4 | 1.374 (5) | C21—H21A | 0.9600 |
N4—H4 | 0.7842 | C21—H21B | 0.9600 |
C6—C11 | 1.380 (5) | C21—H21C | 0.9600 |
C6—C7 | 1.398 (5) | O22—C23 | 1.416 (6) |
C7—C8 | 1.394 (5) | C23—H23A | 0.9600 |
C7—H7 | 0.9300 | C23—H23B | 0.9600 |
C8—O20 | 1.365 (5) | C23—H23C | 0.9600 |
C8—C9 | 1.387 (5) | O24—C25 | 1.413 (7) |
C9—O22 | 1.376 (4) | C25—H25A | 0.9600 |
C9—C10 | 1.385 (6) | C25—H25B | 0.9600 |
C10—O24 | 1.369 (5) | C25—H25C | 0.9600 |
C10—C11 | 1.395 (5) | O26—C27 | 1.417 (6) |
C11—H11 | 0.9300 | C27—H27A | 0.9600 |
C12—C17 | 1.394 (5) | C27—H27B | 0.9600 |
C12—C13 | 1.399 (5) | C27—H27C | 0.9600 |
C13—C14 | 1.382 (5) | O28—H28 | 0.9147 |
C13—H13 | 0.9300 | | |
| | | |
C2—C1—C6 | 131.6 (3) | C13—C14—H14 | 119.7 |
C2—C1—C5 | 107.9 (3) | C15—C14—H14 | 119.7 |
C6—C1—C5 | 120.5 (3) | O26—C15—C14 | 125.6 (4) |
C1—C2—C12 | 131.3 (3) | O26—C15—C16 | 115.4 (3) |
C1—C2—C3 | 107.9 (3) | C14—C15—C16 | 119.0 (3) |
C12—C2—C3 | 120.6 (3) | O28—C16—C17 | 117.9 (4) |
O18—C3—N4 | 125.6 (3) | O28—C16—C15 | 121.8 (3) |
O18—C3—C2 | 128.3 (3) | C17—C16—C15 | 120.2 (3) |
N4—C3—C2 | 106.1 (3) | C16—C17—C12 | 120.8 (3) |
O19—C5—N4 | 126.1 (3) | C16—C17—H17 | 119.6 |
O19—C5—C1 | 127.3 (3) | C12—C17—H17 | 119.6 |
N4—C5—C1 | 106.6 (3) | C8—O20—C21 | 119.1 (3) |
C3—N4—C5 | 111.5 (3) | O20—C21—H21A | 109.5 |
C3—N4—H4 | 129.0 | O20—C21—H21B | 109.5 |
C5—N4—H4 | 119.2 | H21A—C21—H21B | 109.5 |
C11—C6—C7 | 120.0 (3) | O20—C21—H21C | 109.5 |
C11—C6—C1 | 118.7 (3) | H21A—C21—H21C | 109.5 |
C7—C6—C1 | 121.2 (3) | H21B—C21—H21C | 109.5 |
C8—C7—C6 | 119.4 (4) | C9—O22—C23 | 115.1 (3) |
C8—C7—H7 | 120.3 | O22—C23—H23A | 109.5 |
C6—C7—H7 | 120.3 | O22—C23—H23B | 109.5 |
O20—C8—C9 | 114.5 (3) | H23A—C23—H23B | 109.5 |
O20—C8—C7 | 124.9 (4) | O22—C23—H23C | 109.5 |
C9—C8—C7 | 120.5 (4) | H23A—C23—H23C | 109.5 |
O22—C9—C10 | 120.7 (4) | H23B—C23—H23C | 109.5 |
O22—C9—C8 | 119.3 (4) | C10—O24—C25 | 118.2 (3) |
C10—C9—C8 | 119.8 (3) | O24—C25—H25A | 109.5 |
O24—C10—C9 | 115.2 (3) | O24—C25—H25B | 109.5 |
O24—C10—C11 | 124.9 (4) | H25A—C25—H25B | 109.5 |
C9—C10—C11 | 119.9 (4) | O24—C25—H25C | 109.5 |
C6—C11—C10 | 120.4 (4) | H25A—C25—H25C | 109.5 |
C6—C11—H11 | 119.8 | H25B—C25—H25C | 109.5 |
C10—C11—H11 | 119.8 | C15—O26—C27 | 117.6 (4) |
C17—C12—C13 | 119.0 (3) | O26—C27—H27A | 109.5 |
C17—C12—C2 | 120.3 (3) | O26—C27—H27B | 109.5 |
C13—C12—C2 | 120.6 (3) | H27A—C27—H27B | 109.5 |
C14—C13—C12 | 120.3 (3) | O26—C27—H27C | 109.5 |
C14—C13—H13 | 119.8 | H27A—C27—H27C | 109.5 |
C12—C13—H13 | 119.8 | H27B—C27—H27C | 109.5 |
C13—C14—C15 | 120.5 (4) | C16—O28—H28 | 110.1 |
| | | |
C6—C1—C2—C12 | −4.5 (8) | C8—C9—C10—C11 | 1.0 (6) |
C5—C1—C2—C12 | 174.7 (4) | C7—C6—C11—C10 | 2.6 (6) |
C6—C1—C2—C3 | −179.0 (4) | C1—C6—C11—C10 | −179.4 (4) |
C5—C1—C2—C3 | 0.3 (5) | O24—C10—C11—C6 | 176.1 (4) |
C1—C2—C3—O18 | 176.0 (4) | C9—C10—C11—C6 | −2.9 (7) |
C12—C2—C3—O18 | 0.8 (7) | C1—C2—C12—C17 | −30.7 (7) |
C1—C2—C3—N4 | −0.6 (5) | C3—C2—C12—C17 | 143.2 (4) |
C12—C2—C3—N4 | −175.8 (3) | C1—C2—C12—C13 | 151.8 (4) |
C2—C1—C5—O19 | 179.7 (5) | C3—C2—C12—C13 | −34.4 (6) |
C6—C1—C5—O19 | −1.0 (7) | C17—C12—C13—C14 | −0.4 (6) |
C2—C1—C5—N4 | 0.2 (5) | C2—C12—C13—C14 | 177.2 (4) |
C6—C1—C5—N4 | 179.5 (4) | C12—C13—C14—C15 | −0.7 (7) |
O18—C3—N4—C5 | −176.0 (5) | C13—C14—C15—O26 | −178.4 (4) |
C2—C3—N4—C5 | 0.7 (5) | C13—C14—C15—C16 | 1.2 (7) |
O19—C5—N4—C3 | 179.9 (5) | O26—C15—C16—O28 | 1.6 (6) |
C1—C5—N4—C3 | −0.6 (5) | C14—C15—C16—O28 | −178.1 (5) |
C2—C1—C6—C11 | 128.1 (5) | O26—C15—C16—C17 | 179.1 (4) |
C5—C1—C6—C11 | −51.1 (5) | C14—C15—C16—C17 | −0.6 (7) |
C2—C1—C6—C7 | −53.9 (6) | O28—C16—C17—C12 | 177.1 (4) |
C5—C1—C6—C7 | 126.9 (4) | C15—C16—C17—C12 | −0.6 (7) |
C11—C6—C7—C8 | −0.4 (6) | C13—C12—C17—C16 | 1.1 (6) |
C1—C6—C7—C8 | −178.4 (4) | C2—C12—C17—C16 | −176.5 (4) |
C6—C7—C8—O20 | 179.8 (4) | C9—C8—O20—C21 | 165.2 (4) |
C6—C7—C8—C9 | −1.5 (6) | C7—C8—O20—C21 | −16.1 (7) |
O20—C8—C9—O22 | 3.5 (6) | C10—C9—O22—C23 | 83.5 (6) |
C7—C8—C9—O22 | −175.3 (4) | C8—C9—O22—C23 | −100.0 (5) |
O20—C8—C9—C10 | −180.0 (4) | C9—C10—O24—C25 | −175.0 (5) |
C7—C8—C9—C10 | 1.2 (6) | C11—C10—O24—C25 | 6.0 (8) |
O22—C9—C10—O24 | −1.6 (6) | C14—C15—O26—C27 | −10.8 (7) |
C8—C9—C10—O24 | −178.1 (4) | C16—C15—O26—C27 | 169.6 (4) |
O22—C9—C10—C11 | 177.4 (4) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···O20i | 0.78 | 2.28 | 3.045 (4) | 164 |
O28—H28···O24ii | 0.91 | 2.10 | 2.909 (4) | 146 |
O28—H28···O22ii | 0.91 | 2.42 | 3.101 (5) | 131 |
Symmetry codes: (i) −x+1/2, y−1/2, z+1/2; (ii) x−1/2, −y+1/2, z. |