Methyl 3,4-bis­(cyclo­propyl­meth­oxy)benzoate

Cheng, X.-C.; Hou, J.-J.; Xie, C.-Z.; Wang, R.-L.; Xu, W.-R.

doi:10.1107/S1600536811013158

organic compounds

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ISSN: 2056-9890

Volume 67| Part 5| May 2011| Page o1130

doi:10.1107/S1600536811013158

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Methyl 3,4-bis(cyclopropylmethoxy)benzoate

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

^aSchool of Pharmaceutical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China, and ^bTianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China
^*Correspondence e-mail: wangrunling@tijmu.edu.cn

(Received 2 April 2011; accepted 8 April 2011; online 13 April 2011)

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, P 2₁ 2₁ 2₁
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 F² > 2.0σ(F²)
R_int = 0.034

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 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

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
Symmetry code: (i) x+1, y, z.

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.

Supporting information

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

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

checkCIF report

Comment top

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.

Related literature top

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

Experimental top

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).

Computing details top

Data collection: CrystalClear-SM Expert (Rigaku, 2009); cell refinement: CrystalClear-SM Expert (Rigaku, 2009); data reduction: CrystalClear-SM Expert (Rigaku, 2009); 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 (Rigaku, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, with atom labels and 30% probability displacement ellipsoids, and H atoms are shown as small spheres of arbitrary radius.
	Fig. 2. The packing of the title compound, showing the one-dimensional structure,with intermolecular hydrogen bonds (dashed lines); for clarity H atoms have been omitted.

Methyl 3,4-bis(cyclopropylmethoxy)benzoate top

Crystal data top

C₁₆H₂₀O₄	F(000) = 592.00
M_r = 276.33	D_x = 1.278 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71075 Å
Hall symbol: P 2ac 2ab	Cell parameters from 6064 reflections
a = 4.9018 (8) Å	θ = 1.3–31.4°
b = 15.543 (2) Å	µ = 0.09 mm⁻¹
c = 18.846 (2) Å	T = 113 K
V = 1435.9 (3) Å³	Prism, colorless
Z = 4	0.22 × 0.20 × 0.18 mm

Data collection top

Rigaku Saturn724 CCD diffractometer	3300 reflections with F² > 2.0σ(F²)
Detector resolution: 14.222 pixels mm^-1	R_int = 0.034
ω scans	θ_max = 29.1°
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	h = −6→6
T_min = 0.891, T_max = 0.984	k = −21→21
20068 measured reflections	l = −25→25
3852 independent reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.114	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0778P)²] where P = (F_o² + 2F_c²)/3
3852 reflections	(Δ/σ)_max = 0.001
182 parameters	Δρ_max = 0.57 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³
Primary atom site location: structure-invariant direct methods

Crystal data top

C₁₆H₂₀O₄	V = 1435.9 (3) Å³
M_r = 276.33	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 4.9018 (8) Å	µ = 0.09 mm⁻¹
b = 15.543 (2) Å	T = 113 K
c = 18.846 (2) Å	0.22 × 0.20 × 0.18 mm

Data collection top

Rigaku Saturn724 CCD diffractometer	3852 independent reflections
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	3300 reflections with F² > 2.0σ(F²)
T_min = 0.891, T_max = 0.984	R_int = 0.034
20068 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.114	H-atom parameters constrained
S = 1.06	Δρ_max = 0.57 e Å⁻³
3852 reflections	Δρ_min = −0.19 e Å⁻³
182 parameters

Special details top

Geometry. ENTER SPECIAL DETAILS OF THE MOLECULAR GEOMETRY

Refinement. Refinement was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F². R-factor (gt) are based on F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O(1)	0.3872 (2)	0.69719 (7)	0.66936 (5)	0.0321
O(2)	0.6968 (2)	0.59026 (7)	0.66908 (5)	0.0306
O(3)	0.7825 (2)	0.48335 (5)	0.42141 (5)	0.0209
O(4)	0.4320 (2)	0.56811 (6)	0.34625 (4)	0.0250
C(1)	0.4862 (3)	0.62225 (8)	0.56094 (7)	0.0192
C(2)	0.6558 (3)	0.56094 (8)	0.52884 (7)	0.0184
C(3)	0.6319 (3)	0.54351 (8)	0.45719 (6)	0.0174
C(4)	0.4378 (3)	0.58918 (8)	0.41612 (7)	0.0193
C(5)	0.2695 (3)	0.64967 (8)	0.44863 (7)	0.0213
C(6)	0.2930 (3)	0.66574 (8)	0.52102 (7)	0.0211
C(7)	0.5139 (3)	0.64194 (8)	0.63788 (7)	0.0216
C(8)	0.7487 (4)	0.60502 (11)	0.74361 (7)	0.0406
C(9)	0.9395 (3)	0.42507 (8)	0.46452 (6)	0.0199
C(10)	1.0118 (3)	0.34763 (8)	0.42075 (7)	0.0205
C(11)	1.2662 (3)	0.29938 (9)	0.44212 (8)	0.0262
C(12)	1.2614 (3)	0.35005 (9)	0.37423 (7)	0.0246
C(13)	0.2283 (3)	0.61039 (9)	0.30217 (7)	0.0302
C(14)	0.2718 (4)	0.57919 (10)	0.22787 (7)	0.0330
C(15)	0.5052 (4)	0.61632 (12)	0.18752 (10)	0.0442
C(16)	0.2225 (4)	0.64137 (13)	0.16830 (8)	0.0428
H(2)	0.7878	0.5312	0.5565	0.022*
H(5)	0.1381	0.6800	0.4213	0.026*
H(6)	0.1765	0.7066	0.5431	0.025*
H(8A)	0.5750	0.6078	0.7693	0.049*
H(8B)	0.8469	0.6595	0.7495	0.049*
H(8C)	0.8593	0.5578	0.7626	0.049*
H(9A)	0.8319	0.4073	0.5065	0.024*
H(9B)	1.1078	0.4538	0.4813	0.024*
H(10)	0.8558	0.3120	0.4033	0.025*
H(11A)	1.3747	0.3225	0.4821	0.031*
H(11B)	1.2633	0.2358	0.4386	0.031*
H(12A)	1.2558	0.3176	0.3291	0.030*
H(12B)	1.3671	0.4043	0.3725	0.030*
H(13A)	0.2504	0.6736	0.3045	0.036*
H(13B)	0.0423	0.5955	0.3186	0.036*
H(14)	0.2271	0.5175	0.2183	0.040*
H(15A)	0.6201	0.6597	0.2118	0.053*
H(15B)	0.6047	0.5779	0.1546	0.053*
H(16A)	0.1462	0.6184	0.1235	0.051*
H(16B)	0.1615	0.7002	0.1807	0.051*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O(1)	0.0398	0.0311	0.0253	0.0080	0.0001	−0.0084
O(2)	0.0391	0.0348	0.0179	0.0103	−0.0046	−0.0070
O(3)	0.0251	0.0207	0.0170	0.0073	−0.0011	0.0001
O(4)	0.0346	0.0232	0.0170	0.0084	−0.0041	0.0008
C(1)	0.0205	0.0176	0.0194	−0.0020	0.0025	−0.0008
C(2)	0.0171	0.0187	0.0194	−0.0004	−0.0002	−0.0003
C(3)	0.0192	0.0152	0.0178	0.0006	0.0017	−0.0000
C(4)	0.0228	0.0182	0.0170	−0.0013	−0.0017	0.0020
C(5)	0.0222	0.0188	0.0229	0.0010	−0.0014	0.0024
C(6)	0.0213	0.0185	0.0235	0.0012	0.0042	−0.0012
C(7)	0.0243	0.0197	0.0208	−0.0031	0.0009	−0.0025
C(8)	0.0575	0.0441	0.0202	0.0155	−0.0122	−0.0113
C(9)	0.0213	0.0205	0.0179	0.0038	−0.0004	0.0030
C(10)	0.0189	0.0203	0.0222	0.0011	0.0009	0.0013
C(11)	0.0251	0.0244	0.0291	0.0071	0.0026	0.0046
C(12)	0.0247	0.0255	0.0236	0.0017	0.0060	0.0002
C(13)	0.0337	0.0335	0.0235	0.0069	−0.0052	0.0038
C(14)	0.0389	0.0350	0.0251	0.0013	−0.0049	0.0053
C(15)	0.0457	0.0498	0.0371	0.0028	0.0038	0.0098
C(16)	0.0510	0.0542	0.0230	0.0148	−0.0043	0.0114

Geometric parameters (Å, º) top

O(1)—C(7)	1.2143 (17)	C(15)—C(16)	1.484 (3)
O(2)—C(7)	1.3397 (11)	C(2)—H(2)	0.950
O(2)—C(8)	1.4458 (19)	C(5)—H(5)	0.950
O(3)—C(3)	1.3692 (14)	C(6)—H(6)	0.950
O(3)—C(9)	1.4397 (10)	C(8)—H(8A)	0.980
O(4)—C(4)	1.3572 (17)	C(8)—H(8B)	0.980
O(4)—C(13)	1.4558 (13)	C(8)—H(8C)	0.980
C(1)—C(2)	1.4017 (18)	C(9)—H(9A)	0.990
C(1)—C(6)	1.3856 (15)	C(9)—H(9B)	0.990
C(1)—C(7)	1.488 (3)	C(10)—H(10)	1.000
C(2)—C(3)	1.382 (3)	C(11)—H(11A)	0.990
C(3)—C(4)	1.4169 (14)	C(11)—H(11B)	0.990
C(4)—C(5)	1.3930 (18)	C(12)—H(12A)	0.990
C(5)—C(6)	1.392 (3)	C(12)—H(12B)	0.990
C(9)—C(10)	1.502 (2)	C(13)—H(13A)	0.990
C(10)—C(11)	1.5098 (14)	C(13)—H(13B)	0.990
C(10)—C(12)	1.506 (2)	C(14)—H(14)	1.000
C(11)—C(12)	1.5026 (17)	C(15)—H(15A)	0.990
C(13)—C(14)	1.497 (3)	C(15)—H(15B)	0.990
C(14)—C(15)	1.490 (3)	C(16)—H(16A)	0.990
C(14)—C(16)	1.5009 (15)	C(16)—H(16B)	0.990

O(1)···C(6)	2.875 (2)	H(6)···C(1)^viii	3.4340
O(1)···C(8)	2.6738 (14)	H(6)···C(2)^iv	3.4221
O(2)···C(2)	2.6895 (19)	H(6)···C(4)^viii	3.4694
O(3)···O(4)	2.5873 (12)	H(6)···C(5)^viii	2.9995
O(3)···C(12)	3.2546 (14)	H(6)···C(6)^viii	2.9886
O(4)···C(15)	3.1046 (16)	H(6)···H(2)^iv	3.3350
C(1)···C(4)	2.787 (3)	H(6)···H(5)^viii	3.2433
C(2)···C(5)	2.7880 (15)	H(6)···H(5)ⁱ	2.9456
C(2)···C(9)	2.804 (2)	H(6)···H(6)^viii	3.2354
C(3)···C(6)	2.7955 (18)	H(6)···H(6)ⁱ	3.2354
C(5)···C(13)	2.834 (3)	H(8A)···O(3)ⁱⁱ	3.2735
O(1)···C(13)ⁱ	3.468 (4)	H(8A)···C(10)ⁱⁱ	2.9685
O(2)···C(15)ⁱⁱ	3.545 (2)	H(8A)···C(12)ⁱⁱ	2.6574
O(3)···C(5)ⁱⁱⁱ	3.556 (2)	H(8A)···C(14)^ix	3.4558
O(3)···C(12)^iv	3.407 (2)	H(8A)···H(8C)^iv	3.5954
O(4)···C(12)^iv	3.5306 (19)	H(8A)···H(10)ⁱⁱ	2.8381
C(2)···C(6)ⁱⁱⁱ	3.526 (3)	H(8A)···H(12A)ⁱⁱ	2.2901
C(3)···C(5)ⁱⁱⁱ	3.538 (3)	H(8A)···H(12B)ⁱⁱ	2.9188
C(5)···O(3)^iv	3.556 (3)	H(8A)···H(12B)^v	3.3617
C(5)···C(3)^iv	3.538 (3)	H(8A)···H(13B)^ix	3.3436
C(6)···C(2)^iv	3.526 (3)	H(8A)···H(14)^ix	2.6278
C(8)···C(12)ⁱⁱ	3.578 (3)	H(8A)···H(16B)ⁱ	3.1585
C(8)···C(12)^v	3.509 (7)	H(8B)···O(1)ⁱⁱⁱ	3.1047
C(12)···O(3)ⁱⁱⁱ	3.407 (4)	H(8B)···C(12)^v	3.0389
C(12)···O(4)ⁱⁱⁱ	3.531 (3)	H(8B)···C(16)ⁱ	3.5151
C(12)···C(8)^vi	3.578 (5)	H(8B)···H(10)ⁱⁱ	3.0967
C(12)···C(8)^vii	3.509 (5)	H(8B)···H(12A)ⁱⁱ	3.3323
C(13)···O(1)^viii	3.468 (3)	H(8B)···H(12A)^v	2.4836
C(15)···O(2)^vi	3.545 (3)	H(8B)···H(12B)^v	2.8849
C(15)···C(16)ⁱⁱⁱ	3.556 (4)	H(8B)···H(13A)ⁱ	2.8266
C(16)···C(15)^iv	3.556 (3)	H(8B)···H(14)ⁱⁱ	3.5027
O(1)···H(6)	2.5982	H(8B)···H(15A)ⁱ	3.1979
O(1)···H(8A)	2.5145	H(8B)···H(16B)ⁱ	2.7043
O(1)···H(8B)	2.7752	H(8C)···O(3)ⁱⁱ	3.1385
O(2)···H(2)	2.3550	H(8C)···O(4)ⁱⁱ	2.7133
O(3)···H(2)	2.6517	H(8C)···C(12)^v	3.1519
O(3)···H(10)	2.7092	H(8C)···C(13)ⁱⁱ	3.3878
O(3)···H(12B)	3.2512	H(8C)···C(14)ⁱⁱ	2.8694
O(4)···H(5)	2.6652	H(8C)···C(15)ⁱⁱ	3.1254
O(4)···H(14)	2.7276	H(8C)···H(8A)ⁱⁱⁱ	3.5954
O(4)···H(15A)	3.0496	H(8C)···H(10)ⁱⁱ	3.4987
C(1)···H(5)	3.2624	H(8C)···H(12A)^v	2.9798
C(2)···H(6)	3.2736	H(8C)···H(12B)^v	2.5373
C(2)···H(9A)	2.5735	H(8C)···H(13B)^ix	3.2663
C(2)···H(9B)	2.9122	H(8C)···H(14)^ix	3.2138
C(3)···H(5)	3.2890	H(8C)···H(14)ⁱⁱ	2.4852
C(3)···H(9A)	2.5109	H(8C)···H(15A)ⁱⁱ	3.5154
C(3)···H(9B)	2.7551	H(8C)···H(15B)ⁱⁱ	2.9371
C(4)···H(2)	3.2784	H(9A)···C(11)^iv	3.4606
C(4)···H(6)	3.2707	H(9A)···C(11)^x	3.3711
C(4)···H(13A)	2.6440	H(9A)···C(15)ⁱⁱ	3.5231
C(4)···H(13B)	2.6731	H(9A)···H(11A)^iv	2.6402
C(5)···H(13A)	2.7429	H(9A)···H(11A)^x	3.5855
C(5)···H(13B)	2.8201	H(9A)···H(11B)^x	2.4769
C(6)···H(2)	3.2707	H(9A)···H(12B)^iv	3.4008
C(7)···H(2)	2.6681	H(9A)···H(15B)ⁱⁱ	2.8173
C(7)···H(6)	2.6334	H(9A)···H(16A)^ix	3.2426
C(7)···H(8A)	2.5499	H(9A)···H(16A)ⁱⁱ	3.4014
C(7)···H(8B)	2.6766	H(9B)···O(3)ⁱⁱⁱ	3.5250
C(7)···H(8C)	3.1783	H(9B)···O(4)ⁱⁱⁱ	3.4870
C(9)···H(2)	2.5055	H(9B)···C(1)ⁱⁱⁱ	3.5419
C(9)···H(11A)	2.6830	H(9B)···C(2)ⁱⁱⁱ	3.2847
C(9)···H(11B)	3.3775	H(9B)···C(3)ⁱⁱⁱ	2.9578
C(9)···H(12A)	3.4221	H(9B)···C(4)ⁱⁱⁱ	2.9243
C(9)···H(12B)	2.7392	H(9B)···C(5)ⁱⁱⁱ	3.2049
C(11)···H(9A)	2.9697	H(9B)···C(6)ⁱⁱⁱ	3.4973
C(11)···H(9B)	2.6293	H(9B)···H(15B)ⁱⁱ	3.4627
C(12)···H(9A)	3.3820	H(9B)···H(16A)ⁱⁱ	3.1460
C(12)···H(9B)	2.6912	H(10)···C(8)^vi	3.3147
C(13)···H(5)	2.5315	H(10)···C(11)^iv	2.9874
C(13)···H(15A)	2.6793	H(10)···C(11)^x	3.4165
C(13)···H(15B)	3.3759	H(10)···C(12)^iv	3.0231
C(13)···H(16A)	3.3933	H(10)···C(16)^xi	3.0002
C(13)···H(16B)	2.7007	H(10)···H(8A)^vi	2.8381
C(15)···H(13A)	2.6862	H(10)···H(8B)^vi	3.0967
C(15)···H(13B)	3.3697	H(10)···H(8C)^vi	3.4987
C(16)···H(13A)	2.6193	H(10)···H(11A)^iv	2.7913
C(16)···H(13B)	3.0514	H(10)···H(11A)^x	3.0070
H(2)···H(9A)	2.1545	H(10)···H(11B)^iv	3.2057
H(2)···H(9B)	2.4315	H(10)···H(11B)^x	3.1032
H(5)···H(6)	2.3396	H(10)···H(12A)^iv	3.2582
H(5)···H(13A)	2.2709	H(10)···H(12B)^iv	2.8516
H(5)···H(13B)	2.3861	H(10)···H(16A)^xi	3.0514
H(9A)···H(10)	2.4474	H(10)···H(16B)^xi	2.3527
H(9A)···H(11A)	3.0045	H(11A)···O(3)ⁱⁱⁱ	3.3990
H(9B)···H(10)	2.9237	H(11A)···C(9)ⁱⁱⁱ	3.2119
H(9B)···H(11A)	2.4243	H(11A)···C(10)ⁱⁱⁱ	3.3530
H(9B)···H(11B)	3.5652	H(11A)···C(10)^xii	3.2863
H(9B)···H(12B)	2.5324	H(11A)···C(11)^xii	3.0519
H(10)···H(11A)	2.9497	H(11A)···C(16)ⁱⁱ	3.5854
H(10)···H(11B)	2.4153	H(11A)···H(9A)ⁱⁱⁱ	2.6402
H(10)···H(12A)	2.4108	H(11A)···H(9A)^xii	3.5855
H(10)···H(12B)	2.9459	H(11A)···H(10)ⁱⁱⁱ	2.7913
H(11A)···H(12A)	2.9435	H(11A)···H(10)^xii	3.0070
H(11A)···H(12B)	2.4248	H(11A)···H(11A)^x	3.3981
H(11B)···H(12A)	2.4247	H(11A)···H(11A)^xii	3.3981
H(11B)···H(12B)	2.9436	H(11A)···H(11B)^x	3.4694
H(13A)···H(14)	2.9227	H(11A)···H(11B)^xii	2.5855
H(13A)···H(15A)	2.5272	H(11A)···H(16A)ⁱⁱ	2.8206
H(13A)···H(16A)	3.5547	H(11B)···C(9)^xii	3.2146
H(13A)···H(16B)	2.4089	H(11B)···C(10)^xii	3.1923
H(13B)···H(14)	2.4211	H(11B)···C(11)^x	3.3599
H(13B)···H(16B)	3.1209	H(11B)···C(11)^xii	3.3805
H(14)···H(15A)	2.9345	H(11B)···C(15)^xiii	3.2233
H(14)···H(15B)	2.3983	H(11B)···C(16)^xi	3.4476
H(14)···H(16A)	2.4103	H(11B)···C(16)^xiii	3.5454
H(14)···H(16B)	2.9445	H(11B)···H(9A)^xii	2.4769
H(15A)···H(16A)	2.9283	H(11B)···H(10)ⁱⁱⁱ	3.2057
H(15A)···H(16B)	2.4063	H(11B)···H(10)^xii	3.1032
H(15B)···H(16A)	2.4063	H(11B)···H(11A)^x	2.5855
H(15B)···H(16B)	2.9283	H(11B)···H(11A)^xii	3.4694
O(1)···H(5)ⁱ	2.8414	H(11B)···H(11B)^x	3.3990
O(1)···H(8B)^iv	3.1047	H(11B)···H(11B)^xii	3.3990
O(1)···H(12A)ⁱⁱ	3.0988	H(11B)···H(15A)^xiii	3.1240
O(1)···H(13A)ⁱ	2.7280	H(11B)···H(15B)^xiii	3.0867
O(1)···H(13B)ⁱ	3.3183	H(11B)···H(16A)^xi	2.9551
O(1)···H(14)^ix	3.5071	H(11B)···H(16B)^xi	3.1149
O(1)···H(15A)^viii	3.4180	H(12A)···O(1)^vi	3.0988
O(1)···H(16B)ⁱ	3.5118	H(12A)···C(8)^vi	3.1867
O(2)···H(14)^ix	2.8256	H(12A)···C(8)^vii	3.1528
O(2)···H(14)ⁱⁱ	3.4119	H(12A)···C(15)^xiii	3.3551
O(2)···H(15B)ⁱⁱ	2.8026	H(12A)···H(8A)^vi	2.2901
O(3)···H(5)ⁱⁱⁱ	3.5191	H(12A)···H(8B)^vi	3.3323
O(3)···H(8A)^vi	3.2735	H(12A)···H(8B)^vii	2.4836
O(3)···H(8C)^vi	3.1385	H(12A)···H(8C)^vii	2.9798
O(3)···H(9B)^iv	3.5250	H(12A)···H(10)ⁱⁱⁱ	3.2582
O(3)···H(11A)^iv	3.3990	H(12A)···H(15A)^xiii	2.6428
O(3)···H(12B)^iv	2.5506	H(12A)···H(16B)^xi	2.7473
O(3)···H(13B)ⁱⁱⁱ	2.9009	H(12A)···H(16B)^xiii	3.3943
O(4)···H(8C)^vi	2.7133	H(12B)···O(3)ⁱⁱⁱ	2.5506
O(4)···H(9B)^iv	3.4870	H(12B)···O(4)ⁱⁱⁱ	2.6136
O(4)···H(12B)^iv	2.6136	H(12B)···C(3)ⁱⁱⁱ	2.9854
O(4)···H(13B)ⁱⁱⁱ	3.0664	H(12B)···C(4)ⁱⁱⁱ	3.0090
C(1)···H(5)ⁱ	3.1796	H(12B)···C(8)^vii	3.0774
C(1)···H(6)ⁱ	3.4340	H(12B)···C(9)ⁱⁱⁱ	3.3140
C(1)···H(9B)^iv	3.5419	H(12B)···C(10)ⁱⁱⁱ	3.4040
C(2)···H(6)ⁱⁱⁱ	3.4221	H(12B)···C(13)ⁱⁱⁱ	3.5333
C(2)···H(9B)^iv	3.2847	H(12B)···H(8A)^vi	2.9188
C(2)···H(15B)ⁱⁱ	3.4133	H(12B)···H(8A)^vii	3.3617
C(3)···H(5)ⁱⁱⁱ	3.3346	H(12B)···H(8B)^vii	2.8849
C(3)···H(9B)^iv	2.9578	H(12B)···H(8C)^vii	2.5373
C(3)···H(12B)^iv	2.9854	H(12B)···H(9A)ⁱⁱⁱ	3.4008
C(3)···H(13B)ⁱⁱⁱ	3.3947	H(12B)···H(10)ⁱⁱⁱ	2.8516
C(4)···H(6)ⁱ	3.4694	H(12B)···H(13B)ⁱⁱⁱ	3.5216
C(4)···H(9B)^iv	2.9243	H(12B)···H(14)ⁱⁱⁱ	3.4659
C(4)···H(12B)^iv	3.0090	H(13A)···O(1)^viii	2.7280
C(4)···H(13B)ⁱⁱⁱ	3.4883	H(13A)···C(7)^viii	3.2771
C(5)···H(6)ⁱ	2.9995	H(13A)···C(8)^viii	3.5579
C(5)···H(9B)^iv	3.2049	H(13A)···H(8B)^viii	2.8266
C(6)···H(2)^iv	3.3092	H(13A)···H(15A)^iv	3.5566
C(6)···H(5)ⁱ	3.1287	H(13B)···O(1)^viii	3.3183
C(6)···H(6)ⁱ	2.9886	H(13B)···O(3)^iv	2.9009
C(6)···H(9B)^iv	3.4973	H(13B)···O(4)^iv	3.0664
C(7)···H(5)ⁱ	3.0449	H(13B)···C(3)^iv	3.3947
C(7)···H(13A)ⁱ	3.2771	H(13B)···C(4)^iv	3.4883
C(7)···H(14)^ix	3.1360	H(13B)···H(8A)^xiv	3.3436
C(8)···H(10)ⁱⁱ	3.3147	H(13B)···H(8C)^xiv	3.2663
C(8)···H(12A)ⁱⁱ	3.1867	H(13B)···H(12B)^iv	3.5216
C(8)···H(12A)^v	3.1528	H(13B)···H(15A)^iv	3.0552
C(8)···H(12B)^v	3.0774	H(14)···O(1)^xiv	3.5071
C(8)···H(13A)ⁱ	3.5579	H(14)···O(2)^xiv	2.8256
C(8)···H(14)^ix	3.0483	H(14)···O(2)^vi	3.4119
C(8)···H(14)ⁱⁱ	3.2335	H(14)···C(7)^xiv	3.1360
C(8)···H(15B)ⁱⁱ	3.3790	H(14)···C(8)^xiv	3.0483
C(8)···H(16B)ⁱ	3.3736	H(14)···C(8)^vi	3.2335
C(9)···H(11A)^iv	3.2119	H(14)···H(8A)^xiv	2.6278
C(9)···H(11B)^x	3.2146	H(14)···H(8B)^vi	3.5027
C(9)···H(12B)^iv	3.3140	H(14)···H(8C)^xiv	3.2138
C(9)···H(15B)ⁱⁱ	3.5885	H(14)···H(8C)^vi	2.4852
C(10)···H(8A)^vi	2.9685	H(14)···H(12B)^iv	3.4659
C(10)···H(11A)^iv	3.3530	H(14)···H(15B)^iv	3.4109
C(10)···H(11A)^x	3.2863	H(15A)···O(1)ⁱ	3.4180
C(10)···H(11B)^x	3.1923	H(15A)···C(12)^xv	3.4231
C(10)···H(12B)^iv	3.4040	H(15A)···C(13)ⁱⁱⁱ	3.5184
C(10)···H(16B)^xi	3.1033	H(15A)···C(14)ⁱⁱⁱ	3.4443
C(11)···H(9A)ⁱⁱⁱ	3.4606	H(15A)···C(16)ⁱⁱⁱ	3.0775
C(11)···H(9A)^xii	3.3711	H(15A)···H(8B)^viii	3.1979
C(11)···H(10)ⁱⁱⁱ	2.9874	H(15A)···H(8C)^vi	3.5154
C(11)···H(10)^xii	3.4165	H(15A)···H(11B)^xv	3.1240
C(11)···H(11A)^x	3.0519	H(15A)···H(12A)^xv	2.6428
C(11)···H(11B)^x	3.3805	H(15A)···H(13A)ⁱⁱⁱ	3.5566
C(11)···H(11B)^xii	3.3599	H(15A)···H(13B)ⁱⁱⁱ	3.0552
C(11)···H(16B)^xi	3.4832	H(15A)···H(16A)ⁱⁱⁱ	3.1351
C(12)···H(8A)^vi	2.6574	H(15A)···H(16B)ⁱⁱⁱ	2.7897
C(12)···H(8B)^vii	3.0389	H(15B)···O(2)^vi	2.8026
C(12)···H(8C)^vii	3.1519	H(15B)···C(2)^vi	3.4133
C(12)···H(10)ⁱⁱⁱ	3.0231	H(15B)···C(8)^vi	3.3790
C(12)···H(15A)^xiii	3.4231	H(15B)···C(9)^vi	3.5885
C(12)···H(16B)^xi	3.2856	H(15B)···C(14)ⁱⁱⁱ	3.5496
C(13)···H(8C)^vi	3.3878	H(15B)···C(16)ⁱⁱⁱ	3.1951
C(13)···H(12B)^iv	3.5333	H(15B)···H(2)^vi	2.5642
C(13)···H(15A)^iv	3.5184	H(15B)···H(8C)^vi	2.9371
C(14)···H(8A)^xiv	3.4558	H(15B)···H(9A)^vi	2.8173
C(14)···H(8C)^vi	2.8694	H(15B)···H(9B)^vi	3.4627
C(14)···H(15A)^iv	3.4443	H(15B)···H(11B)^xv	3.0867
C(14)···H(15B)^iv	3.5496	H(15B)···H(14)ⁱⁱⁱ	3.4109
C(15)···H(2)^vi	3.5201	H(15B)···H(16A)ⁱⁱⁱ	2.7897
C(15)···H(8C)^vi	3.1254	H(15B)···H(16B)ⁱⁱⁱ	3.3623
C(15)···H(9A)^vi	3.5231	H(16A)···C(15)^iv	3.3656
C(15)···H(11B)^xv	3.2233	H(16A)···H(2)^xiv	3.3954
C(15)···H(12A)^xv	3.3551	H(16A)···H(9A)^xiv	3.2426
C(15)···H(16A)ⁱⁱⁱ	3.3656	H(16A)···H(9A)^vi	3.4014
C(15)···H(16B)ⁱⁱⁱ	3.4736	H(16A)···H(9B)^vi	3.1460
C(16)···H(8B)^viii	3.5151	H(16A)···H(10)^xvi	3.0514
C(16)···H(10)^xvi	3.0002	H(16A)···H(11A)^vi	2.8206
C(16)···H(11A)^vi	3.5854	H(16A)···H(11B)^xvi	2.9551
C(16)···H(11B)^xvi	3.4476	H(16A)···H(15A)^iv	3.1351
C(16)···H(11B)^xv	3.5454	H(16A)···H(15B)^iv	2.7897
C(16)···H(15A)^iv	3.0775	H(16B)···O(1)^viii	3.5118
C(16)···H(15B)^iv	3.1951	H(16B)···C(8)^viii	3.3736
H(2)···C(6)ⁱⁱⁱ	3.3092	H(16B)···C(10)^xvi	3.1033
H(2)···C(15)ⁱⁱ	3.5201	H(16B)···C(11)^xvi	3.4832
H(2)···H(6)ⁱⁱⁱ	3.3350	H(16B)···C(12)^xvi	3.2856
H(2)···H(15B)ⁱⁱ	2.5642	H(16B)···C(15)^iv	3.4736
H(2)···H(16A)^ix	3.3954	H(16B)···H(8A)^viii	3.1585
H(5)···O(1)^viii	2.8414	H(16B)···H(8B)^viii	2.7043
H(5)···O(3)^iv	3.5191	H(16B)···H(10)^xvi	2.3527
H(5)···C(1)^viii	3.1796	H(16B)···H(11B)^xvi	3.1149
H(5)···C(3)^iv	3.3346	H(16B)···H(12A)^xvi	2.7473
H(5)···C(6)^viii	3.1287	H(16B)···H(12A)^xv	3.3943
H(5)···C(7)^viii	3.0449	H(16B)···H(15A)^iv	2.7897
H(5)···H(6)^viii	2.9456	H(16B)···H(15B)^iv	3.3623
H(5)···H(6)ⁱ	3.2433

C(7)—O(2)—C(8)	116.68 (12)	H(8A)—C(8)—H(8B)	109.475
C(3)—O(3)—C(9)	116.11 (9)	H(8A)—C(8)—H(8C)	109.468
C(4)—O(4)—C(13)	117.33 (10)	H(8B)—C(8)—H(8C)	109.472
C(2)—C(1)—C(6)	120.17 (12)	O(3)—C(9)—H(9A)	109.948
C(2)—C(1)—C(7)	120.42 (11)	O(3)—C(9)—H(9B)	109.953
C(6)—C(1)—C(7)	119.40 (11)	C(10)—C(9)—H(9A)	109.961
C(1)—C(2)—C(3)	120.30 (12)	C(10)—C(9)—H(9B)	109.956
O(3)—C(3)—C(2)	124.69 (11)	H(9A)—C(9)—H(9B)	108.328
O(3)—C(3)—C(4)	115.80 (10)	C(9)—C(10)—H(10)	116.366
C(2)—C(3)—C(4)	119.50 (11)	C(11)—C(10)—H(10)	116.367
O(4)—C(4)—C(3)	115.03 (11)	C(12)—C(10)—H(10)	116.375
O(4)—C(4)—C(5)	125.26 (12)	C(10)—C(11)—H(11A)	117.777
C(3)—C(4)—C(5)	119.71 (12)	C(10)—C(11)—H(11B)	117.773
C(4)—C(5)—C(6)	120.21 (12)	C(12)—C(11)—H(11A)	117.769
C(1)—C(6)—C(5)	120.09 (12)	C(12)—C(11)—H(11B)	117.772
O(1)—C(7)—O(2)	123.48 (12)	H(11A)—C(11)—H(11B)	114.909
O(1)—C(7)—C(1)	125.10 (12)	C(10)—C(12)—H(12A)	117.744
O(2)—C(7)—C(1)	111.42 (11)	C(10)—C(12)—H(12B)	117.746
O(3)—C(9)—C(10)	108.69 (9)	C(11)—C(12)—H(12A)	117.745
C(9)—C(10)—C(11)	116.52 (11)	C(11)—C(12)—H(12B)	117.747
C(9)—C(10)—C(12)	119.44 (11)	H(12A)—C(12)—H(12B)	114.871
C(11)—C(10)—C(12)	59.78 (9)	O(4)—C(13)—H(13A)	110.344
C(10)—C(11)—C(12)	59.97 (9)	O(4)—C(13)—H(13B)	110.344
C(10)—C(12)—C(11)	60.25 (9)	C(14)—C(13)—H(13A)	110.360
O(4)—C(13)—C(14)	106.85 (12)	C(14)—C(13)—H(13B)	110.358
C(13)—C(14)—C(15)	117.46 (14)	H(13A)—C(13)—H(13B)	108.585
C(13)—C(14)—C(16)	117.91 (14)	C(13)—C(14)—H(14)	116.594
C(15)—C(14)—C(16)	59.51 (12)	C(15)—C(14)—H(14)	116.598
C(14)—C(15)—C(16)	60.61 (12)	C(16)—C(14)—H(14)	116.603
C(14)—C(16)—C(15)	59.89 (12)	C(14)—C(15)—H(15A)	117.706
C(1)—C(2)—H(2)	119.856	C(14)—C(15)—H(15B)	117.711
C(3)—C(2)—H(2)	119.846	C(16)—C(15)—H(15A)	117.702
C(4)—C(5)—H(5)	119.900	C(16)—C(15)—H(15B)	117.720
C(6)—C(5)—H(5)	119.892	H(15A)—C(15)—H(15B)	114.826
C(1)—C(6)—H(6)	119.947	C(14)—C(16)—H(16A)	117.785
C(5)—C(6)—H(6)	119.960	C(14)—C(16)—H(16B)	117.794
O(2)—C(8)—H(8A)	109.469	C(15)—C(16)—H(16A)	117.781
O(2)—C(8)—H(8B)	109.474	C(15)—C(16)—H(16B)	117.788
O(2)—C(8)—H(8C)	109.470	H(16A)—C(16)—H(16B)	114.905

C(8)—O(2)—C(7)—O(1)	−2.4 (2)	C(2)—C(3)—C(4)—O(4)	179.31 (11)
C(8)—O(2)—C(7)—C(1)	177.99 (12)	C(2)—C(3)—C(4)—C(5)	−1.41 (19)
C(3)—O(3)—C(9)—C(10)	160.99 (10)	O(4)—C(4)—C(5)—C(6)	179.71 (12)
C(9)—O(3)—C(3)—C(2)	11.35 (17)	C(3)—C(4)—C(5)—C(6)	0.5 (2)
C(9)—O(3)—C(3)—C(4)	−167.98 (11)	C(4)—C(5)—C(6)—C(1)	0.7 (2)
C(4)—O(4)—C(13)—C(14)	177.72 (12)	O(3)—C(9)—C(10)—C(11)	153.94 (11)
C(13)—O(4)—C(4)—C(3)	177.39 (11)	O(3)—C(9)—C(10)—C(12)	85.31 (14)
C(13)—O(4)—C(4)—C(5)	−1.83 (19)	C(9)—C(10)—C(11)—C(12)	−110.19 (13)
C(2)—C(1)—C(6)—C(5)	−1.01 (19)	C(9)—C(10)—C(12)—C(11)	105.34 (13)
C(6)—C(1)—C(2)—C(3)	0.09 (19)	C(11)—C(10)—C(12)—C(11)	0.0
C(2)—C(1)—C(7)—O(1)	175.66 (13)	C(12)—C(10)—C(11)—C(12)	0.0
C(2)—C(1)—C(7)—O(2)	−4.76 (17)	C(10)—C(11)—C(12)—C(10)	0.0
C(7)—C(1)—C(2)—C(3)	−179.24 (12)	O(4)—C(13)—C(14)—C(15)	−76.77 (16)
C(6)—C(1)—C(7)—O(1)	−3.7 (2)	O(4)—C(13)—C(14)—C(16)	−144.94 (14)
C(6)—C(1)—C(7)—O(2)	175.90 (12)	C(13)—C(14)—C(15)—C(16)	−107.83 (16)
C(7)—C(1)—C(6)—C(5)	178.33 (12)	C(13)—C(14)—C(16)—C(15)	107.08 (17)
C(1)—C(2)—C(3)—O(3)	−178.20 (12)	C(15)—C(14)—C(16)—C(15)	0.0
C(1)—C(2)—C(3)—C(4)	1.11 (19)	C(16)—C(14)—C(15)—C(16)	0.0
O(3)—C(3)—C(4)—O(4)	−1.31 (17)	C(14)—C(15)—C(16)—C(14)	0.0
O(3)—C(3)—C(4)—C(5)	177.96 (11)

Symmetry codes: (i) x+1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1, y, z; (iv) x−1, y, z; (v) −x+5/2, −y+1, z+1/2; (vi) −x+3/2, −y+1, z−1/2; (vii) −x+5/2, −y+1, z−1/2; (viii) x−1/2, −y+3/2, −z+1; (ix) −x+1/2, −y+1, z+1/2; (x) x−1/2, −y+1/2, −z+1; (xi) −x+1, y−1/2, −z+1/2; (xii) x+1/2, −y+1/2, −z+1; (xiii) −x+2, y−1/2, −z+1/2; (xiv) −x+1/2, −y+1, z−1/2; (xv) −x+2, y+1/2, −z+1/2; (xvi) −x+1, y+1/2, −z+1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12B···O3ⁱⁱⁱ	0.99	2.55	3.4073 (18)	145

Symmetry code: (iii) x+1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₆H₂₀O₄
M_r	276.33
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	113
a, b, c (Å)	4.9018 (8), 15.543 (2), 18.846 (2)
V (Å³)	1435.9 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.22 × 0.20 × 0.18

Data collection
Diffractometer	Rigaku Saturn724 CCD diffractometer
Absorption correction	Multi-scan (REQAB; Jacobson, 1998)
T_min, T_max	0.891, 0.984
No. of measured, independent and observed [F² > 2.0σ(F²)] reflections	20068, 3852, 3300
R_int	0.034
(sin θ/λ)_max (Å⁻¹)	0.684

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.114, 1.06
No. of reflections	3852
No. of parameters	182
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.57, −0.19

Computer programs: CrystalClear-SM Expert (Rigaku, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), CrystalStructure (Rigaku, 2009).

Hydrogen-bond geometry (Å, º) top

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

Symmetry code: (i) x+1, y, z.

Acknowledgements

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

References

Bose, P., Sachdeva, Y. P., Rathore, R. S. & Kumar, Y. (2005). WO Patent 2005/026095 A1. Google Scholar
Hou, J.-J., Cheng, X.-C., Wang, R.-L. & Wang, S.-Q. (2010). Acta Cryst. E66, o2004. Web of Science CSD CrossRef IUCr Journals Google Scholar
Jacobson, R. (1998). REQAB. Private communication to the Rigaku Corporation, Tokyo, Japan. Google Scholar
Rigaku. (2009). CrystalClear-SM Expert and CrystalStructure. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar