organic compounds
Methyl 4-(benzyloxy)-3-methoxybenzoate
aHigh Technology Research Institute of Nanjing University, Changzhou 213162, Jiangsu, People's Republic of China, and bSchool of Petrochemical Engineering, Changzhou University & High Technology Research Institute of Nanjing University, Changzhou 213164, Jiangsu, People's Republic of China
*Correspondence e-mail: wkcoool@163.com
In the title compound, C16H16O4, the aromatic rings are almost normal to one another, making a dihedral angle of 85.81 (10)°. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming chains propagating along the b-axis direction. There are also C—H⋯π interactions present which link the chains, forming two-dimensional networks lying parallel to (102).
CCDC reference: 960929
Related literature
For details of the anticancer properties of the drug Cediranib {systematic name: 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline}, for which the title compound is an important intermediate in the synthesis, see: Folkman (1996). For the synthetic procedure, see: Li & Zhang (2012). For bond-length data, see: Allen et al. (1987).
Experimental
Crystal data
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Data collection: CAD-4 Software (Enraf–Nonius, 1985); cell CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.
Supporting information
CCDC reference: 960929
10.1107/S1600536813025415/su2645sup1.cif
contains datablocks I, wang. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536813025415/su2645Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536813025415/su2645Isup3.cml
The title compound was prepared according to the procedure reported by Li & Zhang (2012). A solution of 4-(benzyloxy)-3-methoxybenzoic acid (5 g, 19.36 mmol) was added slowly to a solution of methanol and concentrated sulfuric acid (2 ml). After being stirred for 12 h at reflux, saturated sodium bicarbonate solution was added to adjust the pH to 7. Dichloromethane was added, and the mixture was then filtered and the organic phase evaporated on a rotary evaporator and to obtain the title compound. Block-like colourless crystals were obtained by dissolving (0.5 g, 1.84 mmol) of the title compound in ethanol (25 ml) and evaporating the solvent slowly at room temperature for about 7 days.
All the H atoms were positioned geometrically and constrained to ride on their parent atom: C—H = 0.93 - 0.96 Å with Uiso(H) = 1.5Ueq(C-methyl) and = 1.2Ueq(C) for other H atoms.
Data collection: CAD-4 Software (Enraf–Nonius, 1985); cell
CAD-4 Software (Enraf–Nonius, 1985); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C16H16O4 | F(000) = 576 |
Mr = 272.29 | Dx = 1.292 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 1683 reflections |
a = 5.2466 (7) Å | θ = 5.3–45.5° |
b = 17.973 (2) Å | µ = 0.09 mm−1 |
c = 14.8785 (18) Å | T = 293 K |
β = 94.018 (3)° | Block, colourless |
V = 1399.6 (3) Å3 | 0.12 × 0.12 × 0.10 mm |
Z = 4 |
Enraf–Nonius CAD-4 diffractometer | 1666 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.029 |
Graphite monochromator | θmax = 25.0°, θmin = 2.3° |
ω/2θ scans | h = −6→6 |
Absorption correction: ψ scan (North et al., 1968) | k = −21→14 |
Tmin = 0.989, Tmax = 0.991 | l = −16→17 |
7732 measured reflections | 3 standard reflections every 120 min |
2454 independent reflections | intensity decay: 1% |
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)] = 0.045 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.138 | H-atom parameters constrained |
S = 0.91 | w = 1/[σ2(Fo2) + (0.0874P)2 + 0.101P] where P = (Fo2 + 2Fc2)/3 |
2454 reflections | (Δ/σ)max = 0.005 |
182 parameters | Δρmax = 0.18 e Å−3 |
0 restraints | Δρmin = −0.17 e Å−3 |
C16H16O4 | V = 1399.6 (3) Å3 |
Mr = 272.29 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 5.2466 (7) Å | µ = 0.09 mm−1 |
b = 17.973 (2) Å | T = 293 K |
c = 14.8785 (18) Å | 0.12 × 0.12 × 0.10 mm |
β = 94.018 (3)° |
Enraf–Nonius CAD-4 diffractometer | 1666 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.029 |
Tmin = 0.989, Tmax = 0.991 | 3 standard reflections every 120 min |
7732 measured reflections | intensity decay: 1% |
2454 independent reflections |
R[F2 > 2σ(F2)] = 0.045 | 0 restraints |
wR(F2) = 0.138 | H-atom parameters constrained |
S = 0.91 | Δρmax = 0.18 e Å−3 |
2454 reflections | Δρmin = −0.17 e Å−3 |
182 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.8880 (3) | 0.30300 (7) | 0.59482 (9) | 0.0538 (4) | |
O2 | 0.5720 (3) | 0.29367 (7) | 0.71794 (9) | 0.0573 (4) | |
O3 | 0.3782 (4) | 0.61921 (8) | 0.64985 (12) | 0.0841 (5) | |
O4 | 0.2344 (3) | 0.55257 (8) | 0.76146 (10) | 0.0702 (5) | |
C1 | 1.3108 (4) | 0.18726 (11) | 0.53747 (14) | 0.0585 (6) | |
H1 | 1.4248 | 0.2124 | 0.5774 | 0.070* | |
C2 | 1.3529 (5) | 0.11390 (13) | 0.51813 (17) | 0.0714 (7) | |
H2 | 1.4940 | 0.0896 | 0.5457 | 0.086* | |
C3 | 1.1895 (5) | 0.07597 (12) | 0.45856 (17) | 0.0703 (7) | |
H3 | 1.2194 | 0.0263 | 0.4453 | 0.084* | |
C4 | 0.9838 (5) | 0.11185 (14) | 0.41926 (18) | 0.0789 (7) | |
H4 | 0.8709 | 0.0866 | 0.3790 | 0.095* | |
C5 | 0.9409 (4) | 0.18540 (14) | 0.43850 (16) | 0.0682 (6) | |
H5 | 0.8002 | 0.2095 | 0.4104 | 0.082* | |
C6 | 1.1025 (4) | 0.22385 (11) | 0.49856 (13) | 0.0475 (5) | |
C7 | 1.0484 (4) | 0.30341 (11) | 0.52037 (14) | 0.0552 (5) | |
H7A | 1.2064 | 0.3297 | 0.5366 | 0.066* | |
H7B | 0.9622 | 0.3279 | 0.4687 | 0.066* | |
C8 | 0.7756 (3) | 0.36807 (10) | 0.61691 (12) | 0.0456 (5) | |
C9 | 0.6001 (3) | 0.36283 (10) | 0.68347 (12) | 0.0430 (4) | |
C10 | 0.4714 (3) | 0.42556 (10) | 0.70828 (12) | 0.0463 (5) | |
H10 | 0.3552 | 0.4222 | 0.7525 | 0.056* | |
C11 | 0.5133 (4) | 0.49364 (10) | 0.66796 (12) | 0.0481 (5) | |
C12 | 0.6864 (4) | 0.49822 (11) | 0.60332 (15) | 0.0629 (6) | |
H12 | 0.7146 | 0.5438 | 0.5760 | 0.075* | |
C13 | 0.8196 (4) | 0.43625 (11) | 0.57813 (16) | 0.0631 (6) | |
H13 | 0.9389 | 0.4404 | 0.5350 | 0.076* | |
C14 | 0.3712 (4) | 0.28318 (11) | 0.77630 (14) | 0.0581 (6) | |
H14A | 0.3996 | 0.3146 | 0.8282 | 0.087* | |
H14B | 0.3679 | 0.2321 | 0.7951 | 0.087* | |
H14C | 0.2109 | 0.2958 | 0.7450 | 0.087* | |
C15 | 0.3720 (4) | 0.56143 (11) | 0.69069 (15) | 0.0561 (5) | |
C16 | 0.0836 (5) | 0.61549 (13) | 0.78568 (19) | 0.0836 (8) | |
H16A | 0.1948 | 0.6546 | 0.8085 | 0.100* | |
H16B | −0.0272 | 0.6009 | 0.8312 | 0.100* | |
H16C | −0.0171 | 0.6329 | 0.7335 | 0.100* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0645 (9) | 0.0414 (7) | 0.0585 (8) | 0.0127 (6) | 0.0255 (7) | 0.0029 (6) |
O2 | 0.0783 (10) | 0.0372 (7) | 0.0597 (8) | 0.0080 (6) | 0.0284 (7) | 0.0058 (6) |
O3 | 0.1240 (15) | 0.0404 (9) | 0.0900 (12) | 0.0199 (8) | 0.0231 (10) | 0.0051 (8) |
O4 | 0.0835 (11) | 0.0497 (9) | 0.0804 (10) | 0.0211 (7) | 0.0277 (9) | −0.0038 (7) |
C1 | 0.0590 (13) | 0.0555 (13) | 0.0617 (13) | 0.0077 (10) | 0.0084 (10) | −0.0034 (10) |
C2 | 0.0729 (15) | 0.0581 (14) | 0.0848 (17) | 0.0183 (12) | 0.0168 (13) | 0.0063 (13) |
C3 | 0.0827 (17) | 0.0462 (12) | 0.0868 (17) | −0.0010 (12) | 0.0399 (14) | −0.0076 (12) |
C4 | 0.0712 (16) | 0.0758 (18) | 0.0911 (18) | −0.0194 (13) | 0.0155 (14) | −0.0256 (14) |
C5 | 0.0511 (12) | 0.0743 (16) | 0.0796 (16) | 0.0061 (11) | 0.0058 (11) | −0.0059 (13) |
C6 | 0.0469 (11) | 0.0491 (11) | 0.0487 (11) | 0.0023 (9) | 0.0188 (9) | 0.0002 (9) |
C7 | 0.0582 (12) | 0.0511 (12) | 0.0591 (12) | 0.0094 (9) | 0.0242 (10) | 0.0056 (10) |
C8 | 0.0485 (10) | 0.0385 (10) | 0.0504 (10) | 0.0063 (8) | 0.0082 (8) | −0.0017 (8) |
C9 | 0.0503 (10) | 0.0344 (9) | 0.0448 (10) | 0.0026 (8) | 0.0062 (8) | 0.0007 (8) |
C10 | 0.0510 (11) | 0.0433 (11) | 0.0456 (10) | 0.0046 (8) | 0.0097 (8) | −0.0038 (9) |
C11 | 0.0548 (11) | 0.0358 (10) | 0.0538 (11) | 0.0039 (8) | 0.0054 (9) | −0.0034 (9) |
C12 | 0.0768 (14) | 0.0374 (10) | 0.0771 (15) | 0.0008 (10) | 0.0244 (12) | 0.0060 (10) |
C13 | 0.0676 (13) | 0.0468 (12) | 0.0786 (14) | 0.0061 (10) | 0.0323 (11) | 0.0080 (11) |
C14 | 0.0702 (14) | 0.0482 (12) | 0.0581 (12) | −0.0017 (10) | 0.0208 (10) | 0.0073 (10) |
C15 | 0.0660 (13) | 0.0408 (11) | 0.0613 (13) | 0.0066 (9) | 0.0027 (11) | −0.0086 (10) |
C16 | 0.0882 (18) | 0.0625 (15) | 0.1027 (19) | 0.0262 (13) | 0.0258 (15) | −0.0171 (14) |
O1—C8 | 1.360 (2) | C7—H7A | 0.9700 |
O1—C7 | 1.437 (2) | C7—H7B | 0.9700 |
O2—C9 | 1.357 (2) | C8—C13 | 1.381 (3) |
O2—C14 | 1.424 (2) | C8—C9 | 1.402 (3) |
O3—C15 | 1.205 (2) | C9—C10 | 1.378 (2) |
O4—C15 | 1.327 (3) | C10—C11 | 1.387 (3) |
O4—C16 | 1.440 (2) | C10—H10 | 0.9300 |
C1—C6 | 1.369 (3) | C11—C12 | 1.371 (3) |
C1—C2 | 1.371 (3) | C11—C15 | 1.477 (3) |
C1—H1 | 0.9300 | C12—C13 | 1.381 (3) |
C2—C3 | 1.371 (3) | C12—H12 | 0.9300 |
C2—H2 | 0.9300 | C13—H13 | 0.9300 |
C3—C4 | 1.354 (3) | C14—H14A | 0.9600 |
C3—H3 | 0.9300 | C14—H14B | 0.9600 |
C4—C5 | 1.374 (3) | C14—H14C | 0.9600 |
C4—H4 | 0.9300 | C16—H16A | 0.9601 |
C5—C6 | 1.374 (3) | C16—H16B | 0.9601 |
C5—H5 | 0.9300 | C16—H16C | 0.9600 |
C6—C7 | 1.498 (3) | ||
C8—O1—C7 | 117.96 (14) | O2—C9—C10 | 125.47 (16) |
C9—O2—C14 | 117.16 (14) | O2—C9—C8 | 115.00 (15) |
C15—O4—C16 | 116.30 (17) | C10—C9—C8 | 119.53 (16) |
C6—C1—C2 | 120.6 (2) | C9—C10—C11 | 120.70 (17) |
C6—C1—H1 | 119.7 | C9—C10—H10 | 119.7 |
C2—C1—H1 | 119.7 | C11—C10—H10 | 119.7 |
C1—C2—C3 | 120.8 (2) | C12—C11—C10 | 119.29 (17) |
C1—C2—H2 | 119.6 | C12—C11—C15 | 118.61 (17) |
C3—C2—H2 | 119.6 | C10—C11—C15 | 122.08 (18) |
C4—C3—C2 | 119.1 (2) | C11—C12—C13 | 120.99 (18) |
C4—C3—H3 | 120.5 | C11—C12—H12 | 119.5 |
C2—C3—H3 | 120.5 | C13—C12—H12 | 119.5 |
C3—C4—C5 | 120.3 (2) | C12—C13—C8 | 120.00 (19) |
C3—C4—H4 | 119.8 | C12—C13—H13 | 120.0 |
C5—C4—H4 | 119.8 | C8—C13—H13 | 120.0 |
C4—C5—C6 | 121.1 (2) | O2—C14—H14A | 109.5 |
C4—C5—H5 | 119.4 | O2—C14—H14B | 109.5 |
C6—C5—H5 | 119.4 | H14A—C14—H14B | 109.5 |
C1—C6—C5 | 118.12 (19) | O2—C14—H14C | 109.5 |
C1—C6—C7 | 121.67 (18) | H14A—C14—H14C | 109.5 |
C5—C6—C7 | 120.21 (18) | H14B—C14—H14C | 109.5 |
O1—C7—C6 | 106.99 (15) | O3—C15—O4 | 122.60 (18) |
O1—C7—H7A | 110.3 | O3—C15—C11 | 124.3 (2) |
C6—C7—H7A | 110.3 | O4—C15—C11 | 113.09 (18) |
O1—C7—H7B | 110.3 | O4—C16—H16A | 109.5 |
C6—C7—H7B | 110.3 | O4—C16—H16B | 109.4 |
H7A—C7—H7B | 108.6 | H16A—C16—H16B | 109.5 |
O1—C8—C13 | 125.04 (17) | O4—C16—H16C | 109.5 |
O1—C8—C9 | 115.48 (15) | H16A—C16—H16C | 109.5 |
C13—C8—C9 | 119.47 (16) | H16B—C16—H16C | 109.5 |
C6—C1—C2—C3 | 0.9 (3) | O1—C8—C9—C10 | −178.12 (16) |
C1—C2—C3—C4 | −0.5 (3) | C13—C8—C9—C10 | 0.9 (3) |
C2—C3—C4—C5 | 0.4 (4) | O2—C9—C10—C11 | −179.44 (17) |
C3—C4—C5—C6 | −0.9 (4) | C8—C9—C10—C11 | 0.2 (3) |
C2—C1—C6—C5 | −1.3 (3) | C9—C10—C11—C12 | −0.5 (3) |
C2—C1—C6—C7 | 178.4 (2) | C9—C10—C11—C15 | 177.82 (18) |
C4—C5—C6—C1 | 1.3 (3) | C10—C11—C12—C13 | −0.2 (3) |
C4—C5—C6—C7 | −178.4 (2) | C15—C11—C12—C13 | −178.6 (2) |
C8—O1—C7—C6 | −168.61 (16) | C11—C12—C13—C8 | 1.3 (4) |
C1—C6—C7—O1 | −90.8 (2) | O1—C8—C13—C12 | 177.3 (2) |
C5—C6—C7—O1 | 88.9 (2) | C9—C8—C13—C12 | −1.6 (3) |
C7—O1—C8—C13 | −5.6 (3) | C16—O4—C15—O3 | 2.0 (3) |
C7—O1—C8—C9 | 173.40 (16) | C16—O4—C15—C11 | −177.77 (18) |
C14—O2—C9—C10 | 8.2 (3) | C12—C11—C15—O3 | 8.1 (3) |
C14—O2—C9—C8 | −171.46 (16) | C10—C11—C15—O3 | −170.3 (2) |
O1—C8—C9—O2 | 1.5 (2) | C12—C11—C15—O4 | −172.12 (18) |
C13—C8—C9—O2 | −179.44 (18) | C10—C11—C15—O4 | 9.5 (3) |
Cg is the centroid of the C1–C6 ring |
D—H···A | D—H | H···A | D···A | D—H···A |
C14—H14B···O3i | 0.96 | 2.53 | 3.379 (3) | 147 |
C14—H14A···Cgii | 0.96 | 2.75 | 3.519 (2) | 137 |
Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x−1, −y−1/2, z−1/2. |
Cg is the centroid of the C1–C6 ring |
D—H···A | D—H | H···A | D···A | D—H···A |
C14—H14B···O3i | 0.96 | 2.53 | 3.379 (3) | 147 |
C14—H14A···Cgii | 0.96 | 2.75 | 3.519 (2) | 137 |
Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x−1, −y−1/2, z−1/2. |
Acknowledgements
The authors thank the Center of Testing and Analysis, Nanjing University for the data collection.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The title compound is an important organic intermediate which has been used to synthesis the antineoplastic drug Cediranib. The drug has shown promising activity against diseases which include lung and breast cancer (Folkman, 1996).
The molecular structure of the title molecule is shown in Fig. 1. The bond lengths (Allen et al., 1987) and angles are within normal ranges. In the molecule the two aromatic rings (C1-C6) and (C8-C13) are almost normal to one another with a dihedral angle of 85.81 (10) °.
In the crystal, molecules are linked by C—H···O hydrogen bonds forming chains propagating along the b axis direction (Table 1 and Fig. 2). There are also C-H···π interactions present (Table 1) linking the chains to form two-dimensional networks lying parallel to (102).