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

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ISSN: 2056-9890

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

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[Grisar, J. M., Claxton, G. P., Bare, T. M., Dage, R. C., Cheng, H. C. & Woodward, J. K. (1981). J. Med. Chem. 24, 327-336.]); Gronnow et al. (2005[Gronnow, M. J., White, R. J., Clark, J. H. & Macquarrie, D. J. (2005). Org. Process Res. Dev. 9, 516-518.]); Watanabe et al. (1984[Watanabe, M., Kawada, M., Takamoto, M., Imada, I. & Noguchi, S. (1984). Chem. Pharm. Bull. 32, 3372-3377.]).

[Scheme 1]

Experimental

Crystal data
  • C13H15BrO4

  • Mr = 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[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.459, Tmax = 0.770

  • 5055 measured reflections

  • 2418 independent reflections

  • 1255 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.58 e Å−3

  • Δρmin = −0.57 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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⋯O2iv 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[Enraf-Nonius (1989). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). (2004). 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


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.

Refinement top

H atoms were positioned geometrically and refined as riding atoms, with C—H = 0.96Å and Uiso(H) = 1.5Ueq(C) for methyl H atoms, 0.97Å and Uiso(H) = 1.2Ueq(C) for methylene H atoms, and C—H = 0.93Å and Uiso(H) = 1.2Ueq(C) for all other H atoms.

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
[Figure 1] Fig. 1. The molecular structure of (I), with atom labels and the 30% probability displacement ellipsoids for non-H atoms.
[Figure 2] Fig. 2. Layered structure generated by weak C—H···O hydrogen bonds .
Methyl 5-(2-bromoacetyl)-2-propoxybenzoate top
Crystal data top
C13H15BrO4F(000) = 640
Mr = 315.16Dx = 1.562 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 16.292 (3) ÅCell parameters from 25 reflections
b = 10.534 (2) Åθ = 10–13°
c = 7.8160 (16) ŵ = 3.07 mm1
β = 92.42 (3)°T = 293 K
V = 1340.2 (5) Å3Block, colourless
Z = 40.30 × 0.10 × 0.09 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
1255 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.038
Graphite monochromatorθmax = 25.2°, θmin = 1.3°
ω/2θ scansh = 1919
Absorption correction: ψ scan
(North et al., 1968)
k = 012
Tmin = 0.459, Tmax = 0.770l = 09
5055 measured reflections3 standard reflections every 200 reflections
2418 independent reflections intensity decay: none
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)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.163H-atom parameters constrained
S = 1.01 w = 1/[σ2(Fo2) + (0.070P)2 + 0.6P]
where P = (Fo2 + 2Fc2)/3
2418 reflections(Δ/σ)max < 0.001
163 parametersΔρmax = 0.59 e Å3
0 restraintsΔρmin = 0.57 e Å3
Crystal data top
C13H15BrO4V = 1340.2 (5) Å3
Mr = 315.16Z = 4
Monoclinic, P21/cMo Kα radiation
a = 16.292 (3) ŵ = 3.07 mm1
b = 10.534 (2) ÅT = 293 K
c = 7.8160 (16) Å0.30 × 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)
Rint = 0.038
Tmin = 0.459, Tmax = 0.7703 standard reflections every 200 reflections
5055 measured reflections intensity decay: none
2418 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0670 restraints
wR(F2) = 0.163H-atom parameters constrained
S = 1.01Δρmax = 0.59 e Å3
2418 reflectionsΔρmin = 0.57 e Å3
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
xyzUiso*/Ueq
Br0.87726 (4)0.11114 (8)0.09429 (10)0.0697 (3)
O11.0062 (3)0.0376 (4)0.2942 (6)0.0686 (13)
C10.9832 (4)0.1652 (7)0.1690 (10)0.067 (2)
H1A0.97810.24170.23680.080*
H1B1.01410.18670.06960.080*
O21.3189 (3)0.0316 (4)0.7514 (4)0.0528 (11)
C21.0319 (3)0.0665 (5)0.2757 (7)0.0404 (13)
O31.2859 (3)0.1509 (4)0.5226 (5)0.0500 (11)
C31.1118 (3)0.1133 (5)0.3539 (6)0.0358 (12)
O41.3340 (2)0.2111 (3)0.5971 (4)0.0428 (9)
C41.1620 (3)0.0215 (5)0.4371 (6)0.0362 (12)
H4A1.14520.06300.43790.043*
C51.2358 (3)0.0556 (5)0.5178 (6)0.0346 (12)
C61.2604 (3)0.1825 (5)0.5180 (6)0.0348 (12)
C71.2117 (3)0.2720 (5)0.4331 (6)0.0420 (13)
H7A1.22870.35620.43050.050*
C81.1383 (3)0.2374 (6)0.3525 (6)0.0397 (13)
H8A1.10620.29880.29630.048*
C91.3255 (5)0.2576 (7)0.6034 (8)0.069 (2)
H9A1.32210.32930.52770.104*
H9B1.38210.23760.62950.104*
H9C1.29880.27740.70730.104*
C101.2855 (3)0.0437 (6)0.6120 (7)0.0399 (13)
C111.4632 (4)0.4854 (7)0.7446 (10)0.074 (2)
H11A1.51500.48840.80770.111*
H11B1.46740.53070.63870.111*
H11C1.42160.52400.81090.111*
C121.4400 (4)0.3468 (6)0.7070 (8)0.0524 (16)
H12A1.43720.30010.81350.063*
H12B1.48150.30760.63900.063*
C131.3581 (3)0.3422 (6)0.6111 (7)0.0423 (14)
H13A1.36230.37910.49810.051*
H13B1.31760.38990.67220.051*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br0.0589 (4)0.0640 (5)0.0837 (6)0.0063 (4)0.0256 (3)0.0101 (4)
O10.069 (3)0.038 (3)0.095 (3)0.010 (3)0.035 (3)0.013 (3)
C10.063 (4)0.043 (4)0.092 (5)0.017 (3)0.027 (4)0.038 (4)
O20.075 (3)0.044 (2)0.038 (2)0.007 (2)0.019 (2)0.000 (2)
C20.048 (3)0.023 (3)0.050 (3)0.003 (3)0.007 (3)0.001 (3)
O30.077 (3)0.031 (2)0.040 (2)0.016 (2)0.0199 (19)0.0067 (19)
C30.049 (3)0.036 (3)0.022 (3)0.004 (3)0.002 (2)0.005 (2)
O40.050 (2)0.032 (2)0.045 (2)0.0014 (18)0.0100 (17)0.0032 (18)
C40.054 (3)0.027 (3)0.028 (3)0.001 (3)0.000 (2)0.007 (2)
C50.047 (3)0.034 (3)0.024 (3)0.006 (3)0.005 (2)0.008 (2)
C60.035 (2)0.035 (3)0.033 (3)0.003 (2)0.004 (2)0.003 (2)
C70.059 (3)0.024 (3)0.042 (3)0.002 (3)0.005 (3)0.001 (3)
C80.049 (3)0.036 (3)0.034 (3)0.006 (3)0.002 (2)0.005 (3)
C90.099 (5)0.047 (4)0.059 (4)0.020 (4)0.025 (4)0.004 (3)
C100.051 (3)0.034 (3)0.034 (3)0.002 (3)0.001 (3)0.001 (3)
C110.066 (4)0.064 (5)0.090 (5)0.006 (4)0.018 (4)0.014 (4)
C120.054 (3)0.050 (4)0.051 (3)0.011 (3)0.014 (3)0.002 (3)
C130.050 (3)0.034 (3)0.042 (3)0.001 (3)0.005 (3)0.005 (3)
Geometric parameters (Å, º) top
Br—C11.887 (6)C6—C71.382 (7)
O1—C21.185 (7)C7—C81.377 (7)
C1—C21.532 (8)C7—H7A0.9300
C1—H1A0.9700C8—H8A0.9300
C1—H1B0.9700C9—H9A0.9600
O2—C101.204 (6)C9—H9B0.9600
C2—C31.498 (7)C9—H9C0.9600
O3—C101.328 (7)C11—C121.534 (10)
O3—C91.430 (7)C11—H11A0.9600
C3—C81.377 (8)C11—H11B0.9600
C3—C41.408 (7)C11—H11C0.9600
O4—C61.360 (6)C12—C131.504 (7)
O4—C131.439 (7)C12—H12A0.9700
C4—C51.382 (7)C12—H12B0.9700
C4—H4A0.9300C13—H13A0.9700
C5—C61.396 (8)C13—H13B0.9700
C5—C101.498 (8)
C2—C1—Br114.2 (4)C7—C8—H8A119.5
C2—C1—H1A108.7O3—C9—H9A109.5
Br—C1—H1A108.7O3—C9—H9B109.5
C2—C1—H1B108.7H9A—C9—H9B109.5
Br—C1—H1B108.7O3—C9—H9C109.5
H1A—C1—H1B107.6H9A—C9—H9C109.5
O1—C2—C3124.0 (5)H9B—C9—H9C109.5
O1—C2—C1121.1 (5)O2—C10—O3123.7 (5)
C3—C2—C1114.8 (5)O2—C10—C5125.8 (5)
C10—O3—C9116.6 (4)O3—C10—C5110.5 (4)
C8—C3—C4118.7 (5)C12—C11—H11A109.5
C8—C3—C2125.2 (5)C12—C11—H11B109.5
C4—C3—C2116.1 (5)H11A—C11—H11B109.5
C6—O4—C13118.6 (4)C12—C11—H11C109.5
C5—C4—C3120.6 (5)H11A—C11—H11C109.5
C5—C4—H4A119.7H11B—C11—H11C109.5
C3—C4—H4A119.7C13—C12—C11109.4 (6)
C4—C5—C6119.6 (5)C13—C12—H12A109.8
C4—C5—C10119.0 (5)C11—C12—H12A109.8
C6—C5—C10121.3 (5)C13—C12—H12B109.8
O4—C6—C7123.0 (5)C11—C12—H12B109.8
O4—C6—C5117.4 (4)H12A—C12—H12B108.2
C7—C6—C5119.6 (4)O4—C13—C12107.6 (5)
C8—C7—C6120.6 (5)O4—C13—H13A110.2
C8—C7—H7A119.7C12—C13—H13A110.2
C6—C7—H7A119.7O4—C13—H13B110.2
C3—C8—C7120.9 (5)C12—C13—H13B110.2
C3—C8—H8A119.5H13A—C13—H13B108.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C1—H1A···O1i0.972.353.148 (9)139
C8—H8A···O1i0.932.593.500 (7)165
C9—H9A···O2ii0.962.613.534 (8)162
C9—H9C···O3iii0.962.593.501 (8)158
C13—H13A···O2iv0.972.593.484 (7)154
Symmetry codes: (i) x+2, y1/2, z+1/2; (ii) x, y+1/2, z1/2; (iii) x, y+1/2, z+1/2; (iv) x, y1/2, z1/2.

Experimental details

Crystal data
Chemical formulaC13H15BrO4
Mr315.16
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)16.292 (3), 10.534 (2), 7.8160 (16)
β (°) 92.42 (3)
V3)1340.2 (5)
Z4
Radiation typeMo Kα
µ (mm1)3.07
Crystal size (mm)0.30 × 0.10 × 0.09
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.459, 0.770
No. of measured, independent and
observed [I > 2σ(I)] reflections
5055, 2418, 1255
Rint0.038
(sin θ/λ)max1)0.599
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.067, 0.163, 1.01
No. of reflections2418
No. of parameters163
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
C1—H1A···O1i0.972.35003.148 (9)139
C8—H8A···O1i0.932.59003.500 (7)165
C9—H9A···O2ii0.962.61003.534 (8)162
C9—H9C···O3iii0.962.59003.501 (8)158
C13—H13A···O2iv0.972.59003.484 (7)154
Symmetry codes: (i) x+2, y1/2, z+1/2; (ii) x, y+1/2, z1/2; (iii) x, y+1/2, z+1/2; (iv) x, y1/2, z1/2.
 

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

First citationEnraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationGrisar, J. M., Claxton, G. P., Bare, T. M., Dage, R. C., Cheng, H. C. & Woodward, J. K. (1981). J. Med. Chem. 24, 327–336.  CrossRef CAS PubMed Web of Science Google Scholar
First citationGronnow, M. J., White, R. J., Clark, J. H. & Macquarrie, D. J. (2005). Org. Process Res. Dev. 9, 516–518.  Web of Science CrossRef CAS Google Scholar
First citationHarms, K. & Wocadlo, S. (1995). (2004). XCAD4. University of Marburg, Germany.  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
First citationWatanabe, M., Kawada, M., Takamoto, M., Imada, I. & Noguchi, S. (1984). Chem. Pharm. Bull. 32, 3372–3377.  Google Scholar

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