rac-Methyl 2-(2-formyl-4-nitro­phen­oxy)hexa­noate

Song, J.-S.; Wang, D.-C.; He, X.-J.; Qiu, J.-K.; Ou-yang, P.-K.

doi:10.1107/S1600536812015462

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 68| Part 5| May 2012| Page o1395

doi:10.1107/S1600536812015462

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rac-Methyl 2-(2-formyl-4-nitrophenoxy)hexanoate

Jun-Song Song,^a De-Cai Wang,^a ^* Xue-Jun He,^a Jiang-Kai Qiu ^a and Ping-Kai Ou-yang ^a

^aState Key Laboratory of Materials-Oriented Chemical Engineering, School of Pharmaceutical Sciences, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: dc_wang@hotmail.com

(Received 23 March 2012; accepted 10 April 2012; online 18 April 2012)

In the racemic title compound, C₁₄H₁₇NO₆, the plane of the ester group of the methyl hexanoate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring, while the nitro group is approximately coplanar with the benzene ring [dihedral angle = 10.3 (2)°]. In the crystal, molecules form weak aromatic C—H⋯O_nitro hydrogen-bonding interactions, giving inversion dimers [graph set R₂²(8)].

Related literature

For applications of the title compound, see: Dale & White (2007 ). For graph-set analysis, see: Etter et al. (1990 )

Experimental

Crystal data

C₁₄H₁₇NO₆
M_r = 295.29
Monoclinic, P 2₁ /n
a = 14.918 (3) Å
b = 4.922 (1) Å
c = 20.928 (4) Å
β = 103.26 (3)°
V = 1495.7 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.20 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 four-circle diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.980, T_max = 0.990
2722 measured reflections
2722 independent reflections
1228 reflections with I > 2σ(I)
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.076
wR(F²) = 0.172
S = 1.00
2722 reflections
172 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2A⋯O1ⁱ	0.93	2.52	3.442 (6)	169
Symmetry code: (i) -x, -y+2, -z+1.

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ); cell refinement: CAD-4 EXPRESS; 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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812015462/zs2196sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812015462/zs2196Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812015462/zs2196Isup3.cml

checkCIF report

Comment top

The title compound, C₁₄H₁₇NO₆ is a good organic intermediate for the synthesis of the drug dronedarone, an important drug used to treat cardiac arrhythmia (Dale & White, 2007), and its crystal structure is reported herein.

In the title compound (Fig. 1), both the nitro group and the aldehyde group are approximately coplanar with the benzene ring, as shown by the torsion angles O1—N—C3—C4 [170.9 (4)°] and C6—C5—C7—O3 [177.6 (4)°]. The plane of the ester group of the methyl hexanoate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring. In the crystal, the molecules are linked by weak intermolecular aromatic C2—H···O1_nitro hydrogen-bonding interactions (Table 1), giving centrosymmetric cyclic dimers [graph set R²₂(8) (Etter et al., 1990)]. Also present are intramolecular interactions between the aldehyde and methylene C—H groups and the ether O-atom.

Related literature top

For applications of the title compound, see: Dale & White (2007). For graph-set analysis, see: Etter et al. (1990)

Experimental top

A mixture of 5-nitrosalicylaldehyde (0.2 mol, 33.4 g), methyl 2-bromohexanoate (2-bromhexine acid methyl ester) (0.2 mol, 41.8g) and anhydrous potassium carbonate (0.2 mol, 27.6g) in DMF (400 ml) was reacted for 3.5h at 365-367 K. After the completion of the reaction, the precipitate was filtered and washed and the product (0.1 g) was crystallized from 15 ml of CH₃OH at room temperature to give colorless crystals from which a specimen was selected for X-ray data collection.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); 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

Fig. 1. The structure of the title compound, showing the atom numbering scheme. Non-H atoms are shown as 30% probability displacement ellipsoids.

rac-Methyl 2-(2-formyl-4-nitrophenoxy)hexanoate top

Crystal data top

C₁₄H₁₇NO₆	F(000) = 624
M_r = 295.29	D_x = 1.311 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 25 reflections
a = 14.918 (3) Å	θ = 9–13°
b = 4.922 (1) Å	µ = 0.10 mm⁻¹
c = 20.928 (4) Å	T = 293 K
β = 103.26 (3)°	Block, colourless
V = 1495.7 (5) Å³	0.20 × 0.10 × 0.10 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 four-circle diffractometer	1228 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.000
Graphite monochromator	θ_max = 25.4°, θ_min = 1.5°
ω–2θ scans	h = −17→17
Absorption correction: ψ scan (North et al., 1968)	k = 0→5
T_min = 0.980, T_max = 0.990	l = 0→25
2722 measured reflections	3 standard reflections every 200 reflections
2722 independent reflections	intensity decay: 1%

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)] = 0.076	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.172	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.050P)²] where P = (F_o² + 2F_c²)/3
2722 reflections	(Δ/σ)_max < 0.001
172 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₄H₁₇NO₆	V = 1495.7 (5) Å³
M_r = 295.29	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 14.918 (3) Å	µ = 0.10 mm⁻¹
b = 4.922 (1) Å	T = 293 K
c = 20.928 (4) Å	0.20 × 0.10 × 0.10 mm
β = 103.26 (3)°

Data collection top

Enraf–Nonius CAD-4 four-circle diffractometer	1228 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.000
T_min = 0.980, T_max = 0.990	3 standard reflections every 200 reflections
2722 measured reflections	intensity decay: 1%
2722 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.076	0 restraints
wR(F²) = 0.172	H-atom parameters constrained
S = 1.00	Δρ_max = 0.26 e Å⁻³
2722 reflections	Δρ_min = −0.22 e Å⁻³
172 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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	U_iso*/U_eq
N	−0.0326 (2)	0.6463 (8)	0.59117 (19)	0.0672 (11)
C1	0.2020 (3)	0.5437 (8)	0.56249 (18)	0.0592 (11)
H1A	0.2389	0.6148	0.5363	0.071*
O1	−0.0535 (2)	0.8534 (7)	0.55953 (18)	0.0926 (11)
C2	0.1162 (3)	0.6501 (9)	0.55803 (19)	0.0604 (11)
H2A	0.0946	0.7942	0.5300	0.072*
O2	−0.0834 (2)	0.5218 (8)	0.61742 (19)	0.1013 (13)
C3	0.0617 (3)	0.5338 (9)	0.59740 (18)	0.0544 (10)
O3	0.16665 (19)	−0.0836 (7)	0.72916 (13)	0.0747 (10)
O4	0.31794 (16)	0.2096 (6)	0.61157 (12)	0.0598 (8)
C4	0.0913 (2)	0.3232 (7)	0.64028 (16)	0.0437 (9)
H4A	0.0533	0.2496	0.6654	0.052*
C5	0.1794 (2)	0.2243 (8)	0.64485 (17)	0.0496 (9)
O5	0.2966 (2)	0.0517 (6)	0.48813 (13)	0.0675 (9)
C6	0.2353 (3)	0.3330 (8)	0.60504 (17)	0.0529 (10)
O6	0.3773 (2)	0.3910 (8)	0.46304 (16)	0.0990 (12)
C7	0.2119 (3)	0.0063 (8)	0.69327 (17)	0.0549 (10)
H7A	0.2704	−0.0651	0.6961	0.066*
C8	0.3791 (3)	0.3212 (9)	0.5738 (2)	0.0645 (12)
H8A	0.3839	0.5183	0.5803	0.077*
C9	0.3496 (3)	0.2609 (11)	0.5030 (2)	0.0663 (12)
C10	0.2656 (3)	−0.0163 (11)	0.41826 (19)	0.0806 (15)
H10A	0.2268	−0.1741	0.4135	0.121*
H10B	0.3180	−0.0529	0.4003	0.121*
H10C	0.2315	0.1337	0.3953	0.121*
C11	0.4715 (3)	0.1900 (12)	0.6028 (2)	0.0907 (17)
H11A	0.4652	−0.0034	0.5941	0.109*
H11B	0.5153	0.2588	0.5790	0.109*
C12	0.5116 (4)	0.2243 (12)	0.6721 (3)	0.107
H12A	0.4667	0.1703	0.6967	0.128*
H12B	0.5642	0.1040	0.6846	0.128*
C13	0.5406 (4)	0.4958 (13)	0.6900 (3)	0.122
H13A	0.4881	0.6034	0.6949	0.147*
H13B	0.5656	0.5768	0.6555	0.147*
C14	0.6167 (4)	0.4976 (13)	0.7569 (3)	0.123
H14A	0.6367	0.6807	0.7676	0.184*
H14B	0.6683	0.3891	0.7521	0.184*
H14C	0.5912	0.4241	0.7913	0.184*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N	0.055 (2)	0.056 (3)	0.086 (3)	0.014 (2)	0.008 (2)	−0.010 (2)
C1	0.088 (3)	0.040 (2)	0.050 (2)	−0.006 (2)	0.018 (2)	−0.0012 (19)
O1	0.079 (2)	0.073 (2)	0.122 (3)	0.031 (2)	0.016 (2)	0.010 (2)
C2	0.073 (3)	0.048 (3)	0.057 (2)	0.008 (2)	0.008 (2)	0.004 (2)
O2	0.063 (2)	0.111 (3)	0.138 (3)	0.010 (2)	0.040 (2)	0.022 (3)
C3	0.053 (2)	0.057 (3)	0.050 (2)	0.003 (2)	0.0052 (17)	−0.010 (2)
O3	0.0661 (19)	0.094 (3)	0.0691 (18)	−0.0031 (18)	0.0249 (15)	0.0283 (18)
O4	0.0533 (16)	0.074 (2)	0.0563 (16)	0.0033 (15)	0.0203 (13)	0.0139 (15)
C4	0.046 (2)	0.036 (2)	0.049 (2)	−0.0041 (17)	0.0126 (16)	0.0033 (18)
C5	0.051 (2)	0.044 (2)	0.051 (2)	−0.0027 (19)	0.0062 (18)	−0.0037 (18)
O5	0.075 (2)	0.070 (2)	0.0647 (19)	−0.0062 (17)	0.0305 (15)	0.0095 (17)
C6	0.057 (2)	0.065 (3)	0.0377 (18)	−0.003 (2)	0.0119 (18)	0.0054 (19)
O6	0.102 (3)	0.116 (3)	0.088 (2)	−0.025 (2)	0.042 (2)	0.016 (2)
C7	0.053 (2)	0.052 (3)	0.058 (2)	−0.019 (2)	0.010 (2)	−0.010 (2)
C8	0.048 (2)	0.071 (3)	0.083 (3)	−0.005 (2)	0.031 (2)	0.018 (2)
C9	0.053 (2)	0.077 (3)	0.078 (3)	0.010 (3)	0.032 (2)	0.021 (3)
C10	0.061 (3)	0.115 (4)	0.063 (3)	0.008 (3)	0.009 (2)	−0.011 (3)
C11	0.063 (3)	0.131 (5)	0.078 (3)	−0.010 (3)	0.018 (2)	0.002 (3)
C12	0.107	0.107	0.107	0.000	0.024	0.000
C13	0.122	0.122	0.122	0.000	0.028	0.000
C14	0.123	0.123	0.123	0.000	0.028	0.000

Geometric parameters (Å, º) top

N—O2	1.200 (4)	C7—H7A	0.9300
N—O1	1.216 (4)	C8—C9	1.476 (6)
N—C3	1.490 (5)	C8—C11	1.517 (6)
C1—C2	1.366 (5)	C8—H8A	0.9800
C1—C6	1.383 (5)	C10—H10A	0.9600
C1—H1A	0.9300	C10—H10B	0.9600
C2—C3	1.405 (5)	C10—H10C	0.9600
C2—H2A	0.9300	C11—C12	1.447 (6)
C3—C4	1.376 (5)	C11—H11A	0.9700
O3—C7	1.204 (4)	C11—H11B	0.9700
O4—C6	1.353 (4)	C12—C13	1.428 (7)
O4—C8	1.446 (4)	C12—H12A	0.9700
C4—C5	1.385 (5)	C12—H12B	0.9700
C4—H4A	0.9300	C13—C14	1.587 (7)
C5—C6	1.412 (5)	C13—H13A	0.9700
C5—C7	1.479 (5)	C13—H13B	0.9700
O5—C9	1.291 (5)	C14—H14A	0.9600
O5—C10	1.468 (4)	C14—H14B	0.9600
O6—C9	1.200 (5)	C14—H14C	0.9600

O2—N—O1	124.6 (4)	O6—C9—C8	121.4 (5)
O2—N—C3	116.9 (4)	O5—C9—C8	115.3 (4)
O1—N—C3	118.5 (4)	O5—C10—H10A	109.5
C2—C1—C6	121.6 (4)	O5—C10—H10B	109.5
C2—C1—H1A	119.2	H10A—C10—H10B	109.5
C6—C1—H1A	119.2	O5—C10—H10C	109.5
C1—C2—C3	117.6 (4)	H10A—C10—H10C	109.5
C1—C2—H2A	121.2	H10B—C10—H10C	109.5
C3—C2—H2A	121.2	C12—C11—C8	118.7 (5)
C4—C3—C2	123.2 (4)	C12—C11—H11A	107.6
C4—C3—N	119.5 (4)	C8—C11—H11A	107.6
C2—C3—N	117.3 (4)	C12—C11—H11B	107.6
C6—O4—C8	116.7 (3)	C8—C11—H11B	107.6
C3—C4—C5	117.8 (3)	H11A—C11—H11B	107.1
C3—C4—H4A	121.1	C13—C12—C11	113.7 (6)
C5—C4—H4A	121.1	C13—C12—H12A	108.8
C4—C5—C6	120.4 (4)	C11—C12—H12A	108.8
C4—C5—C7	117.3 (3)	C13—C12—H12B	108.8
C6—C5—C7	122.3 (4)	C11—C12—H12B	108.8
C9—O5—C10	117.2 (4)	H12A—C12—H12B	107.7
O4—C6—C1	125.9 (4)	C12—C13—C14	110.4 (6)
O4—C6—C5	114.7 (3)	C12—C13—H13A	109.6
C1—C6—C5	119.4 (4)	C14—C13—H13A	109.6
O3—C7—C5	123.5 (4)	C12—C13—H13B	109.6
O3—C7—H7A	118.3	C14—C13—H13B	109.6
C5—C7—H7A	118.3	H13A—C13—H13B	108.1
O4—C8—C9	113.1 (3)	C13—C14—H14A	109.5
O4—C8—C11	104.4 (3)	C13—C14—H14B	109.5
C9—C8—C11	110.5 (4)	H14A—C14—H14B	109.5
O4—C8—H8A	109.6	C13—C14—H14C	109.5
C9—C8—H8A	109.6	H14A—C14—H14C	109.5
C11—C8—H8A	109.6	H14B—C14—H14C	109.5
O6—C9—O5	123.2 (5)

C6—C1—C2—C3	−1.3 (6)	C4—C5—C6—C1	1.5 (5)
C1—C2—C3—C4	1.0 (6)	C7—C5—C6—C1	−177.6 (3)
C1—C2—C3—N	−178.6 (3)	C4—C5—C7—O3	−1.5 (5)
O2—N—C3—C4	−10.1 (6)	C6—C5—C7—O3	177.6 (4)
O1—N—C3—C4	170.9 (4)	C6—O4—C8—C9	−72.8 (5)
O2—N—C3—C2	169.5 (4)	C6—O4—C8—C11	166.9 (4)
O1—N—C3—C2	−9.6 (5)	C10—O5—C9—O6	−3.7 (6)
C2—C3—C4—C5	0.6 (5)	C10—O5—C9—C8	−180.0 (3)
N—C3—C4—C5	−179.9 (3)	O4—C8—C9—O6	160.8 (4)
C3—C4—C5—C6	−1.8 (5)	C11—C8—C9—O6	−82.5 (6)
C3—C4—C5—C7	177.3 (3)	O4—C8—C9—O5	−22.8 (5)
C8—O4—C6—C1	4.5 (5)	C11—C8—C9—O5	93.8 (4)
C8—O4—C6—C5	−177.5 (3)	O4—C8—C11—C12	−57.5 (6)
C2—C1—C6—O4	178.0 (4)	C9—C8—C11—C12	−179.5 (5)
C2—C1—C6—C5	0.1 (6)	C8—C11—C12—C13	−68.5 (7)
C4—C5—C6—O4	−176.6 (3)	C11—C12—C13—C14	−157.4 (5)
C7—C5—C6—O4	4.3 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12A···O4	0.97	2.51	2.877 (6)	102
C7—H7A···O4	0.93	2.46	2.769 (5)	100
C2—H2A···O1ⁱ	0.93	2.52	3.442 (6)	169

Symmetry code: (i) −x, −y+2, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₇NO₆
M_r	295.29
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	14.918 (3), 4.922 (1), 20.928 (4)
β (°)	103.26 (3)
V (Å³)	1495.7 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.20 × 0.10 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 four-circle diffractometer
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.980, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections	2722, 2722, 1228
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.076, 0.172, 1.00
No. of reflections	2722
No. of parameters	172
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.22

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2A···O1ⁱ	0.93	2.52	3.442 (6)	169

Symmetry code: (i) −x, −y+2, −z+1.

Acknowledgements

The work was supported by the Center for Testing and Analysis, Nanjing University.

References

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