Methyl 3,4-bis­(cyclo­propyl­meth­oxy)benzoate

Xian-Chao Cheng; Jing-Jing Hou; Cheng-Zhi Xie; Run-Ling Wang; Wei-Ren Xu

doi:10.1107/S1600536811013158

. 2011 Apr 13;67(Pt 5):o1130. doi: 10.1107/S1600536811013158

Methyl 3,4-bis(cyclopropylmethoxy)benzoate

Xian-Chao Cheng ^a, Jing-Jing Hou ^a, Cheng-Zhi Xie ^a, Run-Ling Wang ^a,^*, Wei-Ren Xu ^b

PMCID: PMC3089130 PMID: 21754441

Abstract

The title compound, C₁₆H₂₀O₄, was obtained unintentionally as the byproduct of an attempted synthesis of methyl 3-(cyclopropylmethoxy)-4-hydroxybenzoate. In the crystal, the molecules are linked by intermolecular C—H⋯O interactions.

Related literature

For the preparation, see: Bose et al. (2005 ▶). For a similar structure, see: Hou et al. (2010 ▶).

Experimental

Crystal data

C₁₆H₂₀O₄
M _r = 276.33
Orthorhombic,
a = 4.9018 (8) Å
b = 15.543 (2) Å
c = 18.846 (2) Å
V = 1435.9 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 113 K
0.22 × 0.20 × 0.18 mm

Data collection

Rigaku Saturn724 CCD diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998 ▶) T _min = 0.891, T _max = 0.984
20068 measured reflections
3852 independent reflections
3300 reflections with F ² > 2.0σ(F ²)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.114
S = 1.06
3852 reflections
182 parameters
H-atom parameters constrained
Δρ_max = 0.57 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: CrystalClear-SM Expert (Rigaku, 2009 ▶); cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: CrystalStructure (Rigaku, 2009 ▶); software used to prepare material for publication: CrystalStructure.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811013158/jh2279sup1.cif

e-67-o1130-sup1.cif^{(33.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811013158/jh2279Isup2.hkl

e-67-o1130-Isup2.hkl^{(188.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12B⋯O3ⁱ	0.99	2.55	3.4073 (18)	145

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Symmetry code: (i) Inline graphic .

Acknowledgments

This research was supported by the Tianjin Medical University Science Foundation (2009ky16) and a China Postdoctoral Science Foundation funded project (20100480655).

supplementary crystallographic information

Comment

Roflumilast is an effective phosphodiesterase-4 inhibitor (PDE4 inhibitor), which can be used in the treatment of asthma, inflammation, bronchitis, allergy and other disorders related to immune system, heart and kidney. During the development of our own PDE4 inhibitors, roflumilast was synthesized as the positive control in the bioactivity screening, and the title compound,methyl 3,4-bis(cyclopropylmethoxy)benzoate, was a byproduct during preparation of the intermediate methyl 3-(cyclopropylmethoxy)-4-hydroxybenzoate.The crystallographic analysis of the title compound is done to confirm the chemical structure of the title compound. In the title compound, all bond lengths and angles are normal and in a good agreement with those reported previously (Hou, et al., 2010). In the crystal structure, the hydroxy groups are involved in the formation of intermolecular C—H···O hydrogen bonds(Tab 1), which link the molecules related by translation along axis b into one-dimensional chains.

Experimental

A mixture of 3,4-dihydroxy methyl benzoate (1.68 g, 10 mmol) and potassium carbonate (2.76 g, 20 mmol) in acetone (50 ml) was added with a solution of cyclopropyl methyl bromide (1.35 g, 10 mmol) in acetone (50 ml). The reaction mixture was stirred at 40 °C for 18 h, and then was filtered. The filtrate was evaporated on a rotary evaporator to get the dried solid, which was then purified by flash column chromatography to obtain methyl 3-(cyclopropylmethoxy)-4-hydroxybenzoate, methyl 4-(cyclopropylmethoxy)-3-hydroxybenzoate, and the title compound methyl 3,4-bis(cyclopropylmethoxy)benzoate(Bose,et al.,2005).

Crystals suitable for X-ray diffraction were obtained through slow evaporation of a solution of the pure title compound in ethyl acetate/n-hexane (1/10 by volume).