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Acta Crystallogr Sect E Struct Rep Online. 2010 June 1; 66(Pt 6): o1274.
Published online 2010 May 8. doi:  10.1107/S1600536810014996
PMCID: PMC2979402

N-Benzyl-2-(2-bromo­phen­yl)-2-(2-nitro­phen­oxy)acetamide

Abstract

The title compound, C21H17BrN2O4, a 2-phen­oxy-2-phenyl­acetamide derivative, exhibits a stereogenic center but crystallizes as a racemate as indicated by the centrosymmetric space group. In the mol­ecular structure, the nitro-substituted benzene ring is coplanar [dihedral angle = 12.9 (1)°] with the plane formed by H—N—C(=O)—C=O due to intra­molecular N—H(...)O hydrogen-bond inter­actions.

Related literature

For the synthesis and biological activity of 2-phen­oxy-2-phenyl-acetamides, see: Dorsch et al. (2002 [triangle]); Wang et al. (2010 [triangle]); Lau et al. (2003 [triangle]). For additional synthetic procedures, see: Dai & Li (2007 [triangle]).

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Object name is e-66-o1274-scheme1.jpg

Experimental

Crystal data

  • C21H17BrN2O4
  • M r = 441.28
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1274-efi1.jpg
  • a = 7.5818 (5) Å
  • b = 10.4650 (7) Å
  • c = 13.1095 (10) Å
  • α = 73.939 (6)°
  • β = 82.878 (6)°
  • γ = 74.447 (6)°
  • V = 961.56 (12) Å3
  • Z = 2
  • Cu Kα radiation
  • μ = 3.17 mm−1
  • T = 293 K
  • 0.38 × 0.26 × 0.18 mm

Data collection

  • Oxford Diffraction Xcalibur Atlas Gemini ultra diffractometer
  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 [triangle]) T min = 0.427, T max = 0.565
  • 7135 measured reflections
  • 3363 independent reflections
  • 2522 reflections with I > 2σ(I)
  • R int = 0.030

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.105
  • S = 1.03
  • 3363 reflections
  • 254 parameters
  • H-atom parameters constrained
  • Δρmax = 0.37 e Å−3
  • Δρmin = −0.39 e Å−3

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: OLEX2 (Dolomanov et al., 2009 [triangle]); software used to prepare material for publication: OLEX2.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810014996/im2196sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810014996/im2196Isup2.hkl

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

Acknowledgments

This work was supported by a research grant from the Natural Science Foundation of China (grant No. 20672092). Professor Wei-Min Dai is thanked for his valuable suggestions on this work. Mr Jiyong Liu of the X-ray crystallography facility of Zhejiang University is acknowledged for his assistance with the crystal structural analysis.

supplementary crystallographic information

Comment

The title compound, C21H17BrN2O4, is a 2-phenoxy-2-phenyl-acetamide derivative, which have been reported to deliver various biological activities such as acting as inhibitors of the coagulation factors Xa and IXa and are therefore used for the therapy of thromboembolic disorder and as safe and effective anticoagulants for myocardial infarction and ischemic disease (Dorsch, et al.; 2002, Wang et al., 2010). They are also active as glucokinase activators rendering their use for the treatment of type I and type II diabetes (Lau, et al.; 2003).

The title compound has recently been obtained during the Lewis base-catalyzed phenol-Passerini three-component reaction (phenol-P-3CR) from nitrophenols, aryl aldehydes and alkyl isocyanides (Dai & Li; 2007). We report here its crystal structure. In the molecular structure (Fig. 1), there is one benzyl group linked to the amide nitrogen atom. In addition, one 2-bromobenzene and a 2-nitrophenoxy substituents are attached to the α-carbon. The nitro-substituted benzene moiety is coplanar with the plane formed by atoms H22-N22-C8-C9-O2 due to intramolecular hydrogen bond interactions between N22-H22···O2 and N22-H22···O25.

Experimental

To a solution of 2-nitrophenol (28 mg, 0.20 mmol) in anhydrous MeCN (0.2 mL, 1.0 M) in a 2-mL tube were added 2-bromobenzaldehyde (48.0 mg, 0.26 mmol), N,N-diisopropylethylamine (0.004 mL, 0.02 mmol, 10 mol%), and benzyl isocyanide (0.037 mL, 0.30 mmol, 1.5 equiv). The resulting mixture was stirred at 352 K under a nitrogen atmosphere for 72 h. The reaction mixture was concentrated under reduced pressure and the residue was then puried by flash column chromatography (silica gel, eluted with 20% EtOAc in light petroleum ether) to afford the title compound as a yellow solid (84.0 mg, 95%). mp 418-419 K (EtOAc-hexane). Single crystals suitable for X-ray diffraction of the title compound were grown in the mixed solvent of EtOAc and hexane (v:v = 1:3) at 283 K.

Refinement

The H atoms were placed in calculated positions with C—H = 0.93-0.98 Å, and included in the refinement in riding model, with Uiso(H) = 1.2Ueq (carrier atom).

Figures

Fig. 1.
Molecular structure of (1). Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small circles of arbitary radii.

Crystal data

C21H17BrN2O4Z = 2
Mr = 441.28F(000) = 448
Triclinic, P1Dx = 1.524 Mg m3
Hall symbol: -P 1Cu Kα radiation, λ = 1.54184 Å
a = 7.5818 (5) ÅCell parameters from 3052 reflections
b = 10.4650 (7) Åθ = 3.5–66.9°
c = 13.1095 (10) ŵ = 3.17 mm1
α = 73.939 (6)°T = 293 K
β = 82.878 (6)°Block, colorless
γ = 74.447 (6)°0.38 × 0.26 × 0.18 mm
V = 961.56 (12) Å3

Data collection

Oxford Diffraction Xcalibur Atlas Gemini ultra diffractometer3363 independent reflections
Radiation source: fine-focus sealed tube2522 reflections with I > 2σ(I)
graphiteRint = 0.030
Detector resolution: 10.3592 pixels mm-1θmax = 66.6°, θmin = 3.5°
ω scansh = −9→8
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)k = −11→12
Tmin = 0.427, Tmax = 0.565l = −15→15
7135 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.105w = 1/[σ2(Fo2) + (0.0523P)2 + 0.350P] where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
3363 reflectionsΔρmax = 0.37 e Å3
254 parametersΔρmin = −0.39 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0258 (10)

Special details

Experimental. (CrysAlis Pro; Oxford Diffraction, 2009) Version 1.171.33.53 (release 17-11-2009 CrysAlis171 .NET) (compiled Nov 17 2009,16:58:22) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.
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 > 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)

xyzUiso*/Ueq
Br270.67572 (5)0.56595 (4)0.87665 (3)0.0848 (2)
O20.3651 (3)0.99683 (19)0.82814 (14)0.0599 (5)
O240.6787 (3)0.8846 (3)0.63093 (18)0.0856 (7)
O250.2519 (5)1.2538 (2)0.8109 (2)0.1010 (9)
O260.0566 (5)1.3176 (3)0.9264 (3)0.1318 (13)
N220.5004 (4)1.0913 (3)0.64616 (19)0.0712 (7)
H220.41531.13180.68460.085*
N230.1698 (4)1.2288 (3)0.8964 (2)0.0653 (7)
C10.6438 (6)1.3641 (4)0.5979 (3)0.0878 (11)
H10.51901.40280.60640.105*
C20.7724 (10)1.4280 (5)0.6178 (3)0.1174 (18)
H20.73411.50900.63950.141*
C30.9541 (11)1.3690 (8)0.6046 (4)0.126 (2)
H31.04011.41010.61820.152*
C41.0118 (7)1.2529 (7)0.5724 (4)0.1164 (18)
H41.13651.21500.56280.140*
C50.8863 (5)1.1907 (4)0.5537 (3)0.0829 (10)
H50.92671.10980.53200.099*
C60.7016 (4)1.2457 (4)0.5664 (2)0.0629 (8)
C70.5676 (6)1.1746 (5)0.5464 (3)0.0911 (13)
H7B0.46461.24240.51080.109*
H7A0.62591.11590.49980.109*
C80.5655 (4)0.9562 (4)0.6794 (2)0.0615 (8)
C90.4855 (4)0.8876 (3)0.7880 (2)0.0515 (6)
H90.58490.83960.83630.062*
C100.3835 (4)0.7874 (3)0.7772 (2)0.0477 (6)
C110.4463 (4)0.6461 (3)0.8127 (2)0.0577 (7)
C120.3448 (5)0.5585 (3)0.8030 (3)0.0745 (9)
H120.38960.46420.82710.089*
C130.1799 (5)0.6103 (4)0.7584 (3)0.0750 (9)
H130.11100.55110.75320.090*
C140.1141 (4)0.7491 (4)0.7209 (2)0.0673 (8)
H140.00170.78420.68950.081*
C150.2163 (4)0.8368 (3)0.7301 (2)0.0558 (7)
H150.17160.93090.70400.067*
C160.3115 (4)0.9775 (3)0.93255 (19)0.0460 (6)
C170.3463 (4)0.8503 (3)1.0060 (2)0.0544 (7)
H170.41340.77280.98460.065*
C180.2821 (4)0.8388 (3)1.1098 (2)0.0631 (8)
H180.30770.75341.15830.076*
C190.1805 (4)0.9514 (4)1.1434 (2)0.0698 (9)
H190.13730.94201.21400.084*
C200.1435 (4)1.0772 (3)1.0723 (2)0.0628 (8)
H200.07391.15371.09430.075*
C210.2096 (4)1.0908 (3)0.9674 (2)0.0488 (6)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Br270.0661 (3)0.0668 (3)0.1161 (4)0.00496 (17)−0.0286 (2)−0.0247 (2)
O20.0875 (14)0.0447 (10)0.0454 (10)−0.0160 (10)0.0037 (9)−0.0113 (8)
O240.0676 (14)0.124 (2)0.0680 (14)−0.0247 (14)0.0139 (12)−0.0354 (14)
O250.165 (3)0.0495 (13)0.0740 (16)−0.0125 (15)−0.0038 (18)−0.0060 (12)
O260.135 (3)0.0565 (16)0.171 (3)0.0045 (17)0.036 (2)−0.0219 (18)
N220.0792 (18)0.085 (2)0.0506 (14)−0.0405 (16)0.0013 (13)−0.0016 (13)
N230.0701 (16)0.0466 (14)0.084 (2)−0.0138 (13)−0.0136 (14)−0.0209 (13)
C10.103 (3)0.087 (3)0.062 (2)−0.022 (2)0.0102 (19)−0.0068 (19)
C20.201 (6)0.094 (3)0.068 (3)−0.065 (4)0.000 (3)−0.015 (2)
C30.175 (6)0.149 (5)0.083 (3)−0.113 (5)−0.031 (4)0.009 (3)
C40.085 (3)0.156 (5)0.099 (3)−0.057 (3)−0.020 (2)0.014 (3)
C50.081 (2)0.089 (3)0.069 (2)−0.025 (2)−0.0016 (18)−0.0021 (18)
C60.071 (2)0.078 (2)0.0367 (14)−0.0313 (17)−0.0043 (13)0.0037 (14)
C70.104 (3)0.126 (3)0.0500 (18)−0.070 (3)−0.0088 (18)0.0084 (19)
C80.0524 (17)0.088 (2)0.0523 (17)−0.0299 (17)−0.0051 (14)−0.0172 (16)
C90.0577 (16)0.0545 (15)0.0455 (14)−0.0160 (13)−0.0042 (12)−0.0152 (12)
C100.0467 (14)0.0546 (15)0.0455 (14)−0.0130 (12)0.0004 (11)−0.0192 (12)
C110.0501 (15)0.0574 (17)0.0684 (18)−0.0065 (13)−0.0058 (13)−0.0256 (14)
C120.077 (2)0.0560 (18)0.100 (3)−0.0164 (16)−0.0095 (19)−0.0330 (17)
C130.075 (2)0.079 (2)0.088 (2)−0.0344 (19)−0.0033 (18)−0.0341 (19)
C140.0490 (16)0.098 (3)0.0607 (18)−0.0223 (17)−0.0044 (14)−0.0242 (17)
C150.0513 (15)0.0632 (17)0.0507 (15)−0.0112 (14)−0.0016 (12)−0.0142 (13)
C160.0512 (14)0.0500 (14)0.0443 (14)−0.0208 (12)−0.0049 (11)−0.0148 (11)
C170.0654 (17)0.0504 (15)0.0479 (15)−0.0143 (13)−0.0077 (13)−0.0114 (12)
C180.0674 (19)0.071 (2)0.0466 (16)−0.0188 (16)−0.0079 (14)−0.0045 (14)
C190.0681 (19)0.094 (3)0.0481 (16)−0.0191 (18)−0.0003 (14)−0.0220 (17)
C200.0556 (17)0.075 (2)0.0663 (19)−0.0107 (15)−0.0044 (14)−0.0361 (16)
C210.0486 (14)0.0482 (14)0.0561 (16)−0.0161 (12)−0.0107 (12)−0.0165 (12)

Geometric parameters (Å, °)

Br27—C111.903 (3)C8—C91.538 (4)
O2—C161.354 (3)C9—C101.504 (4)
O2—C91.439 (3)C9—H90.9800
O24—C81.218 (4)C10—C151.386 (4)
O25—N231.209 (4)C10—C111.388 (4)
O26—N231.203 (4)C11—C121.384 (4)
N22—C81.331 (4)C12—C131.357 (5)
N22—C71.473 (4)C12—H120.9300
N22—H220.8600C13—C141.370 (5)
N23—C211.461 (4)C13—H130.9300
C1—C61.358 (5)C14—C151.387 (4)
C1—C21.406 (7)C14—H140.9300
C1—H10.9300C15—H150.9300
C2—C31.361 (8)C16—C171.391 (4)
C2—H20.9300C16—C211.391 (4)
C3—C41.341 (8)C17—C181.371 (4)
C3—H30.9300C17—H170.9300
C4—C51.367 (6)C18—C191.375 (5)
C4—H40.9300C18—H180.9300
C5—C61.372 (5)C19—C201.367 (5)
C5—H50.9300C19—H190.9300
C6—C71.494 (5)C20—C211.386 (4)
C7—H7B0.9700C20—H200.9300
C7—H7A0.9700
C16—O2—C9121.1 (2)C10—C9—H9109.5
C8—N22—C7122.8 (3)C8—C9—H9109.5
C8—N22—H22118.6C15—C10—C11117.2 (3)
C7—N22—H22118.6C15—C10—C9119.1 (3)
O26—N23—O25120.9 (3)C11—C10—C9123.7 (2)
O26—N23—C21118.1 (3)C12—C11—C10121.3 (3)
O25—N23—C21120.9 (3)C12—C11—Br27117.6 (2)
C6—C1—C2120.0 (4)C10—C11—Br27121.0 (2)
C6—C1—H1120.0C13—C12—C11120.1 (3)
C2—C1—H1120.0C13—C12—H12120.0
C3—C2—C1118.7 (5)C11—C12—H12120.0
C3—C2—H2120.7C12—C13—C14120.4 (3)
C1—C2—H2120.7C12—C13—H13119.8
C4—C3—C2121.5 (5)C14—C13—H13119.8
C4—C3—H3119.3C13—C14—C15119.5 (3)
C2—C3—H3119.3C13—C14—H14120.2
C3—C4—C5119.6 (5)C15—C14—H14120.2
C3—C4—H4120.2C10—C15—C14121.5 (3)
C5—C4—H4120.2C10—C15—H15119.3
C4—C5—C6121.1 (5)C14—C15—H15119.3
C4—C5—H5119.4O2—C16—C17123.9 (2)
C6—C5—H5119.4O2—C16—C21117.9 (2)
C1—C6—C5119.1 (4)C17—C16—C21118.2 (2)
C1—C6—C7121.0 (4)C18—C17—C16120.2 (3)
C5—C6—C7119.9 (4)C18—C17—H17119.9
N22—C7—C6111.5 (3)C16—C17—H17119.9
N22—C7—H7B109.3C17—C18—C19121.2 (3)
C6—C7—H7B109.3C17—C18—H18119.4
N22—C7—H7A109.3C19—C18—H18119.4
C6—C7—H7A109.3C20—C19—C18119.5 (3)
H7B—C7—H7A108.0C20—C19—H19120.2
O24—C8—N22125.8 (3)C18—C19—H19120.2
O24—C8—C9118.7 (3)C19—C20—C21120.0 (3)
N22—C8—C9115.5 (3)C19—C20—H20120.0
O2—C9—C10111.1 (2)C21—C20—H20120.0
O2—C9—C8106.1 (2)C20—C21—C16120.9 (3)
C10—C9—C8111.0 (2)C20—C21—N23117.2 (3)
O2—C9—H9109.5C16—C21—N23121.9 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N22—H22···O20.862.082.521 (3)111
N22—H22···O250.862.393.227 (4)164

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2196).

References

  • Dai, W.-M. & Li, H. (2007). Tetrahedron, 63, 12866–12876.
  • Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst.42, 339–341.
  • Dorsch, D., Mederski, W., Tsaklakidis, C., Cezanne, B., Gleitz, J. & Barnes, C. (2002). PCT Int. Appl. WO 2002057236.
  • Lau, J., Kodra, J. T., Guzel, M., Santosh, K. C., Mjalli, A. M. M., Andrews, R. C. & Polisetti, D. R. (2003). PCT Int. Appl. WO 2003055482.
  • Oxford Diffraction (2009). CrysAlis PRO Oxford Diffraction Ltd, Yarnton, England.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Wang, S., Beck, R., Burd, A., Blench, T., Marlin, F., Ayele, T., Buxton, S., Dagostin, C., Malic, M., Joshi, R., Barry, J., Sajad, M., Cheung, C., Shaikh, S., Chahwala, S., Chander, C., Baumgartner, C., Holthoff, H.-P., Murray, E., Blackney, M. & Giddings, A. (2010). J. Med. Chem.53, 1473–1482. [PubMed]

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