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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 69| Part 10| October 2013| Page o1562
doi:10.1107/S1600536813025415

Methyl 4-(benz­yl­oxy)-3-meth­­oxy­benzo­ate

Kai Wang,a* ChaoFan Ju,b Jian Xiaob and Qiang Chena

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

(Received 10 September 2013; accepted 13 September 2013; online 18 September 2013)

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[Folkman, J. (1996). Sci. Am. 275, 150-154.]). For the synthetic procedure, see: Li & Zhang (2012[Li, H.-S. & Zhang, S.-X. (2012). Patent No. CN 102603718A.]). For bond-length data, see: Allen et al. (1987[Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.]).

[Scheme 1]

Experimental

Crystal data

  • C16H16O4

  • Mr = 272.29

  • Monoclinic, P 21 /c

  • a = 5.2466 (7) Å

  • b = 17.973 (2) Å

  • c = 14.8785 (18) Å

  • β = 94.018 (3)°

  • V = 1399.6 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 293 K

  • 0.12 × 0.12 × 0.10 mm
Data collection

  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.989, Tmax = 0.991

  • 7732 measured reflections

  • 2454 independent reflections

  • 1666 reflections with I > 2σ(I)

  • Rint = 0.029

  • 3 standard reflections every 120 min intensity decay: 1%
Refinement

  • R[F2 > 2σ(F2)] = 0.045

  • wR(F2) = 0.138

  • S = 0.91

  • 2454 reflections

  • 182 parameters

  • H-atom parameters constrained

  • Δρmax = 0.18 e Å−3

  • Δρmin = −0.17 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

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-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [x-1, -y-{\script{1\over 2}}, z-{\script{1\over 2}}].

Data collection: CAD-4 Software (Enraf–Nonius, 1985)[Enraf-Nonius (1985). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]; cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information

CCDC reference: 960929

Crystal structure: contains datablocks I, wang. DOI: 10.1107/S1600536813025415/su2645sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813025415/su2645Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813025415/su2645Isup3.cml

checkCIF report


Comment top

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).

Related literature top

For details concerning 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 top

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.

Refinement top

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.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1985); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. A view of the crystal packing of the title compound. The C—H···O hydrogen bonds are shown by dashed lines (see Table 1 for details; H atoms not involved in hydrogen bonding have been omitted for clarity).
Methyl 4-(benzyloxy)-3-methoxybenzoate top
Crystal data top
C16H16O4F(000) = 576
Mr = 272.29Dx = 1.292 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 1683 reflections
a = 5.2466 (7) Åθ = 5.3–45.5°
b = 17.973 (2) ŵ = 0.09 mm−1
c = 14.8785 (18) ÅT = 293 K
β = 94.018 (3)°Block, colourless
V = 1399.6 (3) Å30.12 × 0.12 × 0.10 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer		1666 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.029
Graphite monochromatorθmax = 25.0°, θmin = 2.3°
ω/2θ scansh = −6→6
Absorption correction: ψ scan
(North et al., 1968)		k = −21→14
Tmin = 0.989, Tmax = 0.991l = −16→17
7732 measured reflections3 standard reflections every 120 min
2454 independent reflections intensity decay: 1%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.138H-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 parametersΔρmax = 0.18 e Å−3
0 restraintsΔρmin = −0.17 e Å−3
Crystal data top
C16H16O4V = 1399.6 (3) Å3
Mr = 272.29Z = 4
Monoclinic, P21/cMo Kα radiation
a = 5.2466 (7) ŵ = 0.09 mm−1
b = 17.973 (2) ÅT = 293 K
c = 14.8785 (18) Å0.12 × 0.12 × 0.10 mm
β = 94.018 (3)°
Data collection top
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 = 0.9913 standard reflections every 120 min
7732 measured reflections intensity decay: 1%
2454 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.138H-atom parameters constrained
S = 0.91Δρmax = 0.18 e Å−3
2454 reflectionsΔρmin = −0.17 e Å−3
182 parameters
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
xyzUiso*/Ueq
O10.8880 (3)0.30300 (7)0.59482 (9)0.0538 (4)
O20.5720 (3)0.29367 (7)0.71794 (9)0.0573 (4)
O30.3782 (4)0.61921 (8)0.64985 (12)0.0841 (5)
O40.2344 (3)0.55257 (8)0.76146 (10)0.0702 (5)
C11.3108 (4)0.18726 (11)0.53747 (14)0.0585 (6)
H11.42480.21240.57740.070*
C21.3529 (5)0.11390 (13)0.51813 (17)0.0714 (7)
H21.49400.08960.54570.086*
C31.1895 (5)0.07597 (12)0.45856 (17)0.0703 (7)
H31.21940.02630.44530.084*
C40.9838 (5)0.11185 (14)0.41926 (18)0.0789 (7)
H40.87090.08660.37900.095*
C50.9409 (4)0.18540 (14)0.43850 (16)0.0682 (6)
H50.80020.20950.41040.082*
C61.1025 (4)0.22385 (11)0.49856 (13)0.0475 (5)
C71.0484 (4)0.30341 (11)0.52037 (14)0.0552 (5)
H7A1.20640.32970.53660.066*
H7B0.96220.32790.46870.066*
C80.7756 (3)0.36807 (10)0.61691 (12)0.0456 (5)
C90.6001 (3)0.36283 (10)0.68347 (12)0.0430 (4)
C100.4714 (3)0.42556 (10)0.70828 (12)0.0463 (5)
H100.35520.42220.75250.056*
C110.5133 (4)0.49364 (10)0.66796 (12)0.0481 (5)
C120.6864 (4)0.49822 (11)0.60332 (15)0.0629 (6)
H120.71460.54380.57600.075*
C130.8196 (4)0.43625 (11)0.57813 (16)0.0631 (6)
H130.93890.44040.53500.076*
C140.3712 (4)0.28318 (11)0.77630 (14)0.0581 (6)
H14A0.39960.31460.82820.087*
H14B0.36790.23210.79510.087*
H14C0.21090.29580.74500.087*
C150.3720 (4)0.56143 (11)0.69069 (15)0.0561 (5)
C160.0836 (5)0.61549 (13)0.78568 (19)0.0836 (8)
H16A0.19480.65460.80850.100*
H16B−0.02720.60090.83120.100*
H16C−0.01710.63290.73350.100*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0645 (9)0.0414 (7)0.0585 (8)0.0127 (6)0.0255 (7)0.0029 (6)
O20.0783 (10)0.0372 (7)0.0597 (8)0.0080 (6)0.0284 (7)0.0058 (6)
O30.1240 (15)0.0404 (9)0.0900 (12)0.0199 (8)0.0231 (10)0.0051 (8)
O40.0835 (11)0.0497 (9)0.0804 (10)0.0211 (7)0.0277 (9)−0.0038 (7)
C10.0590 (13)0.0555 (13)0.0617 (13)0.0077 (10)0.0084 (10)−0.0034 (10)
C20.0729 (15)0.0581 (14)0.0848 (17)0.0183 (12)0.0168 (13)0.0063 (13)
C30.0827 (17)0.0462 (12)0.0868 (17)−0.0010 (12)0.0399 (14)−0.0076 (12)
C40.0712 (16)0.0758 (18)0.0911 (18)−0.0194 (13)0.0155 (14)−0.0256 (14)
C50.0511 (12)0.0743 (16)0.0796 (16)0.0061 (11)0.0058 (11)−0.0059 (13)
C60.0469 (11)0.0491 (11)0.0487 (11)0.0023 (9)0.0188 (9)0.0002 (9)
C70.0582 (12)0.0511 (12)0.0591 (12)0.0094 (9)0.0242 (10)0.0056 (10)
C80.0485 (10)0.0385 (10)0.0504 (10)0.0063 (8)0.0082 (8)−0.0017 (8)
C90.0503 (10)0.0344 (9)0.0448 (10)0.0026 (8)0.0062 (8)0.0007 (8)
C100.0510 (11)0.0433 (11)0.0456 (10)0.0046 (8)0.0097 (8)−0.0038 (9)
C110.0548 (11)0.0358 (10)0.0538 (11)0.0039 (8)0.0054 (9)−0.0034 (9)
C120.0768 (14)0.0374 (10)0.0771 (15)0.0008 (10)0.0244 (12)0.0060 (10)
C130.0676 (13)0.0468 (12)0.0786 (14)0.0061 (10)0.0323 (11)0.0080 (11)
C140.0702 (14)0.0482 (12)0.0581 (12)−0.0017 (10)0.0208 (10)0.0073 (10)
C150.0660 (13)0.0408 (11)0.0613 (13)0.0066 (9)0.0027 (11)−0.0086 (10)
C160.0882 (18)0.0625 (15)0.1027 (19)0.0262 (13)0.0258 (15)−0.0171 (14)
Geometric parameters (Å, º) top
O1—C81.360 (2)C7—H7A0.9700
O1—C71.437 (2)C7—H7B0.9700
O2—C91.357 (2)C8—C131.381 (3)
O2—C141.424 (2)C8—C91.402 (3)
O3—C151.205 (2)C9—C101.378 (2)
O4—C151.327 (3)C10—C111.387 (3)
O4—C161.440 (2)C10—H100.9300
C1—C61.369 (3)C11—C121.371 (3)
C1—C21.371 (3)C11—C151.477 (3)
C1—H10.9300C12—C131.381 (3)
C2—C31.371 (3)C12—H120.9300
C2—H20.9300C13—H130.9300
C3—C41.354 (3)C14—H14A0.9600
C3—H30.9300C14—H14B0.9600
C4—C51.374 (3)C14—H14C0.9600
C4—H40.9300C16—H16A0.9601
C5—C61.374 (3)C16—H16B0.9601
C5—H50.9300C16—H16C0.9600
C6—C71.498 (3)
C8—O1—C7117.96 (14)O2—C9—C10125.47 (16)
C9—O2—C14117.16 (14)O2—C9—C8115.00 (15)
C15—O4—C16116.30 (17)C10—C9—C8119.53 (16)
C6—C1—C2120.6 (2)C9—C10—C11120.70 (17)
C6—C1—H1119.7C9—C10—H10119.7
C2—C1—H1119.7C11—C10—H10119.7
C1—C2—C3120.8 (2)C12—C11—C10119.29 (17)
C1—C2—H2119.6C12—C11—C15118.61 (17)
C3—C2—H2119.6C10—C11—C15122.08 (18)
C4—C3—C2119.1 (2)C11—C12—C13120.99 (18)
C4—C3—H3120.5C11—C12—H12119.5
C2—C3—H3120.5C13—C12—H12119.5
C3—C4—C5120.3 (2)C12—C13—C8120.00 (19)
C3—C4—H4119.8C12—C13—H13120.0
C5—C4—H4119.8C8—C13—H13120.0
C4—C5—C6121.1 (2)O2—C14—H14A109.5
C4—C5—H5119.4O2—C14—H14B109.5
C6—C5—H5119.4H14A—C14—H14B109.5
C1—C6—C5118.12 (19)O2—C14—H14C109.5
C1—C6—C7121.67 (18)H14A—C14—H14C109.5
C5—C6—C7120.21 (18)H14B—C14—H14C109.5
O1—C7—C6106.99 (15)O3—C15—O4122.60 (18)
O1—C7—H7A110.3O3—C15—C11124.3 (2)
C6—C7—H7A110.3O4—C15—C11113.09 (18)
O1—C7—H7B110.3O4—C16—H16A109.5
C6—C7—H7B110.3O4—C16—H16B109.4
H7A—C7—H7B108.6H16A—C16—H16B109.5
O1—C8—C13125.04 (17)O4—C16—H16C109.5
O1—C8—C9115.48 (15)H16A—C16—H16C109.5
C13—C8—C9119.47 (16)H16B—C16—H16C109.5
C6—C1—C2—C30.9 (3)O1—C8—C9—C10−178.12 (16)
C1—C2—C3—C4−0.5 (3)C13—C8—C9—C100.9 (3)
C2—C3—C4—C50.4 (4)O2—C9—C10—C11−179.44 (17)
C3—C4—C5—C6−0.9 (4)C8—C9—C10—C110.2 (3)
C2—C1—C6—C5−1.3 (3)C9—C10—C11—C12−0.5 (3)
C2—C1—C6—C7178.4 (2)C9—C10—C11—C15177.82 (18)
C4—C5—C6—C11.3 (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—C81.3 (4)
C1—C6—C7—O1−90.8 (2)O1—C8—C13—C12177.3 (2)
C5—C6—C7—O188.9 (2)C9—C8—C13—C12−1.6 (3)
C7—O1—C8—C13−5.6 (3)C16—O4—C15—O32.0 (3)
C7—O1—C8—C9173.40 (16)C16—O4—C15—C11−177.77 (18)
C14—O2—C9—C108.2 (3)C12—C11—C15—O38.1 (3)
C14—O2—C9—C8−171.46 (16)C10—C11—C15—O3−170.3 (2)
O1—C8—C9—O21.5 (2)C12—C11—C15—O4−172.12 (18)
C13—C8—C9—O2−179.44 (18)C10—C11—C15—O49.5 (3)
Hydrogen-bond geometry (Å, º) top
Cg is the centroid of the C1–C6 ring
D—H···AD—HH···AD···AD—H···A
C14—H14B···O3i0.962.533.379 (3)147
C14—H14A···Cgii0.962.753.519 (2)137
Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x−1, −y−1/2, z−1/2.
Hydrogen-bond geometry (Å, º) top
Cg is the centroid of the C1–C6 ring
D—H···AD—HH···AD···AD—H···A
C14—H14B···O3i0.962.533.379 (3)147
C14—H14A···Cgii0.962.753.519 (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

First citationAllen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.  CrossRef Web of Science Google Scholar
 First citationEnraf–Nonius (1985). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.  Google Scholar
 First citationFolkman, J. (1996). Sci. Am. 275, 150–154.  CrossRef CAS PubMed Google Scholar
 First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
 First citationLi, H.-S. & Zhang, S.-X. (2012). Patent No. CN 102603718A.  Google Scholar
 First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 69| Part 10| October 2013| Page o1562
doi:10.1107/S1600536813025415
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