Methyl 5-(2-bromo­acet­yl)-2-propoxybenzoate

Ke, J.; Guan-Hong, X.; Fei, L.

doi:10.1107/S1600536808016814

organic compounds

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ISSN: 2056-9890

Volume 64| Part 7| July 2008| Page o1242

doi:10.1107/S1600536808016814

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Methyl 5-(2-bromoacetyl)-2-propoxybenzoate

Jiang Ke,^a Xu Guan-Hong ^a and Li Fei ^a ^*

^aSchool of Pharmaceutical Science, Nanjing Medical University, Nanjing 210029, People's Republic of China
^*Correspondence e-mail: kldlf@163.com

(Received 16 May 2008; accepted 3 June 2008; online 7 June 2008)

The title compound, C₁₃H₁₅BrO₄, was synthesized from methyl 5-acetyl-2-hydroxybenzoate. With the exception of the ester group and some H atoms, the molecule is planar, the average deviation from planarity being 0.086 (5) Å. The dihedral angle between the phenyl ring and the ester group is 41.6 (3)°. Adjacent molecules are interconnected by C—H⋯O bonds, generating a layered structure.

Related literature

For related literature, see: Grisar et al. (1981 ); Gronnow et al. (2005 ); Watanabe et al. (1984 ).

Experimental

Crystal data

C₁₃H₁₅BrO₄
M_r = 315.16
Monoclinic, P 2₁ /c
a = 16.292 (3) Å
b = 10.534 (2) Å
c = 7.8160 (16) Å
β = 92.42 (3)°
V = 1340.2 (5) Å³
Z = 4
Mo Kα radiation
μ = 3.07 mm⁻¹
T = 293 (2) K
0.30 × 0.10 × 0.09 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan(North et al., 1986 ) T_min = 0.459, T_max = 0.770
5055 measured reflections
2418 independent reflections
1255 reflections with I > 2σ(I)
R_int = 0.038
3 standard reflections every 200 reflections intensity decay: none

Refinement

R[F² > 2σ(F²)] = 0.067
wR(F²) = 0.163
S = 1.01
2418 reflections
163 parameters
H-atom parameters constrained
Δρ_max = 0.58 e Å⁻³
Δρ_min = −0.57 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1A⋯O1ⁱ	0.97	2.35	3.148 (9)	139
C8—H8A⋯O1ⁱ	0.93	2.59	3.500 (7)	165
C9—H9A⋯O2ⁱⁱ	0.96	2.61	3.534 (8)	162
C9—H9C⋯O3ⁱⁱⁱ	0.96	2.59	3.501 (8)	158
C13—H13A⋯O2^iv	0.97	2.59	3.484 (7)	154
Symmetry codes: (i) $[-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (iii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (iv) $[x, -y-{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: 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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808016814/kp2172sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808016814/kp2172Isup2.hkl

checkCIF report

Comment top

Methyl 5-acetyl-2-hydroxybenzoate is a common chemical intermediate, which can be easily obtained (Gronnow et al., 2005). It is widely used for the design and synthesis of biological compounds. Biological activities, such as antiulcer (Watanabe et al., 1984) and antihypertensive (Grisar et al., 1981) effects of methyl 5-acetyl-2-hydroxybenzoate derivatives have been reported. In our research, the title compound, (I) (Fig. 1) is an important intermediate used to synthesize variety of compounds, which might have an inhibitive effect on PDE5. Considerable attention has been devoted to the biological activities of methyl 5-acetyl-2-hydroxybenzoate derivatives, however, the crystal structure of the title compound has not been reported, yet. In this work, we present the crystal structure of the title compound.

The molecule is planar with the average deviation from the planarity of 0.086 (5) Å. However, the ester group is out of this plane. The dihedral angle between the phenyl and the ester group is 41.65°.

Packing analysis of the crystal structure shows that molecules are intercontacted by weak C—H···O interactions generating a layered structure (Table 1, Fig. 2).

Related literature top

For related literature, see: Grisar et al. (1981); Gronnow et al. (2005); Watanabe et al. (1984). PLEASE SUPPLY SCHEME

Experimental top

Methyl 5-acetyl-2-propoxybenzoate was obtained by the alkylation of methyl 5-acetyl-2-hydroxybenzoate. To a mixture of methyl 5-acetyl-2-propoxybenzoate (1 mmol), aluminium trichloride (0.15 mmol) and dichlormethane (15 mL), bromine (1.1 mmol) was added dropwise during 15 min at 273 K. The mixture was stirred at room temperature for 10 h. The resulting mixture was washed by aqueous solution of sodium thiosulfate, saturated salt solution, dried by anhydrous sodium sulfate, then the solvent was distilled off. Single crystals suitable for X-ray analysis (m.p. 379 K) were obtained by slow evaporation of solvent mixture of dichlormethane and methanol at room temperature.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); 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 molecular structure of (I), with atom labels and the 30% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Layered structure generated by weak C—H···O hydrogen bonds .

Methyl 5-(2-bromoacetyl)-2-propoxybenzoate top

Crystal data top

C₁₃H₁₅BrO₄	F(000) = 640
M_r = 315.16	D_x = 1.562 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 16.292 (3) Å	Cell parameters from 25 reflections
b = 10.534 (2) Å	θ = 10–13°
c = 7.8160 (16) Å	µ = 3.07 mm⁻¹
β = 92.42 (3)°	T = 293 K
V = 1340.2 (5) Å³	Block, colourless
Z = 4	0.30 × 0.10 × 0.09 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	1255 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.038
Graphite monochromator	θ_max = 25.2°, θ_min = 1.3°
ω/2θ scans	h = −19→19
Absorption correction: ψ scan (North et al., 1968)	k = 0→12
T_min = 0.459, T_max = 0.770	l = 0→9
5055 measured reflections	3 standard reflections every 200 reflections
2418 independent reflections	intensity decay: none

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)] = 0.067	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.163	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.070P)² + 0.6P] where P = (F_o² + 2F_c²)/3
2418 reflections	(Δ/σ)_max < 0.001
163 parameters	Δρ_max = 0.59 e Å⁻³
0 restraints	Δρ_min = −0.57 e Å⁻³

Crystal data top

C₁₃H₁₅BrO₄	V = 1340.2 (5) Å³
M_r = 315.16	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 16.292 (3) Å	µ = 3.07 mm⁻¹
b = 10.534 (2) Å	T = 293 K
c = 7.8160 (16) Å	0.30 × 0.10 × 0.09 mm
β = 92.42 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1255 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.038
T_min = 0.459, T_max = 0.770	3 standard reflections every 200 reflections
5055 measured reflections	intensity decay: none
2418 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.067	0 restraints
wR(F²) = 0.163	H-atom parameters constrained
S = 1.01	Δρ_max = 0.59 e Å⁻³
2418 reflections	Δρ_min = −0.57 e Å⁻³
163 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

	x	y	z	U_iso*/U_eq
Br	0.87726 (4)	−0.11114 (8)	0.09429 (10)	0.0697 (3)
O1	1.0062 (3)	0.0376 (4)	0.2942 (6)	0.0686 (13)
C1	0.9832 (4)	−0.1652 (7)	0.1690 (10)	0.067 (2)
H1A	0.9781	−0.2417	0.2368	0.080*
H1B	1.0141	−0.1867	0.0696	0.080*
O2	1.3189 (3)	0.0316 (4)	0.7514 (4)	0.0528 (11)
C2	1.0319 (3)	−0.0665 (5)	0.2757 (7)	0.0404 (13)
O3	1.2859 (3)	0.1509 (4)	0.5226 (5)	0.0500 (11)
C3	1.1118 (3)	−0.1133 (5)	0.3539 (6)	0.0358 (12)
O4	1.3340 (2)	−0.2111 (3)	0.5971 (4)	0.0428 (9)
C4	1.1620 (3)	−0.0215 (5)	0.4371 (6)	0.0362 (12)
H4A	1.1452	0.0630	0.4379	0.043*
C5	1.2358 (3)	−0.0556 (5)	0.5178 (6)	0.0346 (12)
C6	1.2604 (3)	−0.1825 (5)	0.5180 (6)	0.0348 (12)
C7	1.2117 (3)	−0.2720 (5)	0.4331 (6)	0.0420 (13)
H7A	1.2287	−0.3562	0.4305	0.050*
C8	1.1383 (3)	−0.2374 (6)	0.3525 (6)	0.0397 (13)
H8A	1.1062	−0.2988	0.2963	0.048*
C9	1.3255 (5)	0.2576 (7)	0.6034 (8)	0.069 (2)
H9A	1.3221	0.3293	0.5277	0.104*
H9B	1.3821	0.2376	0.6295	0.104*
H9C	1.2988	0.2774	0.7073	0.104*
C10	1.2855 (3)	0.0437 (6)	0.6120 (7)	0.0399 (13)
C11	1.4632 (4)	−0.4854 (7)	0.7446 (10)	0.074 (2)
H11A	1.5150	−0.4884	0.8077	0.111*
H11B	1.4674	−0.5307	0.6387	0.111*
H11C	1.4216	−0.5240	0.8109	0.111*
C12	1.4400 (4)	−0.3468 (6)	0.7070 (8)	0.0524 (16)
H12A	1.4372	−0.3001	0.8135	0.063*
H12B	1.4815	−0.3076	0.6390	0.063*
C13	1.3581 (3)	−0.3422 (6)	0.6111 (7)	0.0423 (14)
H13A	1.3623	−0.3791	0.4981	0.051*
H13B	1.3176	−0.3899	0.6722	0.051*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br	0.0589 (4)	0.0640 (5)	0.0837 (6)	0.0063 (4)	−0.0256 (3)	−0.0101 (4)
O1	0.069 (3)	0.038 (3)	0.095 (3)	0.010 (3)	−0.035 (3)	−0.013 (3)
C1	0.063 (4)	0.043 (4)	0.092 (5)	0.017 (3)	−0.027 (4)	−0.038 (4)
O2	0.075 (3)	0.044 (2)	0.038 (2)	−0.007 (2)	−0.019 (2)	0.000 (2)
C2	0.048 (3)	0.023 (3)	0.050 (3)	0.003 (3)	−0.007 (3)	−0.001 (3)
O3	0.077 (3)	0.031 (2)	0.040 (2)	−0.016 (2)	−0.0199 (19)	0.0067 (19)
C3	0.049 (3)	0.036 (3)	0.022 (3)	−0.004 (3)	−0.002 (2)	−0.005 (2)
O4	0.050 (2)	0.032 (2)	0.045 (2)	0.0014 (18)	−0.0100 (17)	−0.0032 (18)
C4	0.054 (3)	0.027 (3)	0.028 (3)	−0.001 (3)	0.000 (2)	−0.007 (2)
C5	0.047 (3)	0.034 (3)	0.024 (3)	−0.006 (3)	0.005 (2)	−0.008 (2)
C6	0.035 (2)	0.035 (3)	0.033 (3)	−0.003 (2)	−0.004 (2)	−0.003 (2)
C7	0.059 (3)	0.024 (3)	0.042 (3)	0.002 (3)	−0.005 (3)	0.001 (3)
C8	0.049 (3)	0.036 (3)	0.034 (3)	−0.006 (3)	−0.002 (2)	−0.005 (3)
C9	0.099 (5)	0.047 (4)	0.059 (4)	−0.020 (4)	−0.025 (4)	0.004 (3)
C10	0.051 (3)	0.034 (3)	0.034 (3)	0.002 (3)	0.001 (3)	−0.001 (3)
C11	0.066 (4)	0.064 (5)	0.090 (5)	0.006 (4)	−0.018 (4)	0.014 (4)
C12	0.054 (3)	0.050 (4)	0.051 (3)	0.011 (3)	−0.014 (3)	−0.002 (3)
C13	0.050 (3)	0.034 (3)	0.042 (3)	0.001 (3)	−0.005 (3)	−0.005 (3)

Geometric parameters (Å, º) top

Br—C1	1.887 (6)	C6—C7	1.382 (7)
O1—C2	1.185 (7)	C7—C8	1.377 (7)
C1—C2	1.532 (8)	C7—H7A	0.9300
C1—H1A	0.9700	C8—H8A	0.9300
C1—H1B	0.9700	C9—H9A	0.9600
O2—C10	1.204 (6)	C9—H9B	0.9600
C2—C3	1.498 (7)	C9—H9C	0.9600
O3—C10	1.328 (7)	C11—C12	1.534 (10)
O3—C9	1.430 (7)	C11—H11A	0.9600
C3—C8	1.377 (8)	C11—H11B	0.9600
C3—C4	1.408 (7)	C11—H11C	0.9600
O4—C6	1.360 (6)	C12—C13	1.504 (7)
O4—C13	1.439 (7)	C12—H12A	0.9700
C4—C5	1.382 (7)	C12—H12B	0.9700
C4—H4A	0.9300	C13—H13A	0.9700
C5—C6	1.396 (8)	C13—H13B	0.9700
C5—C10	1.498 (8)

C2—C1—Br	114.2 (4)	C7—C8—H8A	119.5
C2—C1—H1A	108.7	O3—C9—H9A	109.5
Br—C1—H1A	108.7	O3—C9—H9B	109.5
C2—C1—H1B	108.7	H9A—C9—H9B	109.5
Br—C1—H1B	108.7	O3—C9—H9C	109.5
H1A—C1—H1B	107.6	H9A—C9—H9C	109.5
O1—C2—C3	124.0 (5)	H9B—C9—H9C	109.5
O1—C2—C1	121.1 (5)	O2—C10—O3	123.7 (5)
C3—C2—C1	114.8 (5)	O2—C10—C5	125.8 (5)
C10—O3—C9	116.6 (4)	O3—C10—C5	110.5 (4)
C8—C3—C4	118.7 (5)	C12—C11—H11A	109.5
C8—C3—C2	125.2 (5)	C12—C11—H11B	109.5
C4—C3—C2	116.1 (5)	H11A—C11—H11B	109.5
C6—O4—C13	118.6 (4)	C12—C11—H11C	109.5
C5—C4—C3	120.6 (5)	H11A—C11—H11C	109.5
C5—C4—H4A	119.7	H11B—C11—H11C	109.5
C3—C4—H4A	119.7	C13—C12—C11	109.4 (6)
C4—C5—C6	119.6 (5)	C13—C12—H12A	109.8
C4—C5—C10	119.0 (5)	C11—C12—H12A	109.8
C6—C5—C10	121.3 (5)	C13—C12—H12B	109.8
O4—C6—C7	123.0 (5)	C11—C12—H12B	109.8
O4—C6—C5	117.4 (4)	H12A—C12—H12B	108.2
C7—C6—C5	119.6 (4)	O4—C13—C12	107.6 (5)
C8—C7—C6	120.6 (5)	O4—C13—H13A	110.2
C8—C7—H7A	119.7	C12—C13—H13A	110.2
C6—C7—H7A	119.7	O4—C13—H13B	110.2
C3—C8—C7	120.9 (5)	C12—C13—H13B	110.2
C3—C8—H8A	119.5	H13A—C13—H13B	108.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···O1ⁱ	0.97	2.35	3.148 (9)	139
C8—H8A···O1ⁱ	0.93	2.59	3.500 (7)	165
C9—H9A···O2ⁱⁱ	0.96	2.61	3.534 (8)	162
C9—H9C···O3ⁱⁱⁱ	0.96	2.59	3.501 (8)	158
C13—H13A···O2^iv	0.97	2.59	3.484 (7)	154

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) x, −y+1/2, z−1/2; (iii) x, −y+1/2, z+1/2; (iv) x, −y−1/2, z−1/2.

Experimental details

Crystal data
Chemical formula	C₁₃H₁₅BrO₄
M_r	315.16
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	16.292 (3), 10.534 (2), 7.8160 (16)
β (°)	92.42 (3)
V (Å³)	1340.2 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	3.07
Crystal size (mm)	0.30 × 0.10 × 0.09

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.459, 0.770
No. of measured, independent and observed [I > 2σ(I)] reflections	5055, 2418, 1255
R_int	0.038
(sin θ/λ)_max (Å⁻¹)	0.599

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.067, 0.163, 1.01
No. of reflections	2418
No. of parameters	163
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.59, −0.57

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), 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
C1—H1A···O1ⁱ	0.97	2.3500	3.148 (9)	139
C8—H8A···O1ⁱ	0.93	2.5900	3.500 (7)	165
C9—H9A···O2ⁱⁱ	0.96	2.6100	3.534 (8)	162
C9—H9C···O3ⁱⁱⁱ	0.96	2.5900	3.501 (8)	158
C13—H13A···O2^iv	0.97	2.5900	3.484 (7)	154

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) x, −y+1/2, z−1/2; (iii) x, −y+1/2, z+1/2; (iv) x, −y−1/2, z−1/2.

Acknowledgements

We acknowledge staff of the Shanghai Institute of Materia Medica for their active cooperation in this work. We also thank the Instrument Analysis and Research Center of Nanjing University for the structural characterization.

References

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