supplementary materials


lh5389 scheme

Acta Cryst. (2012). E68, o70    [ doi:10.1107/S1600536811052597 ]

2-Chloro-1-[4-(2,4-difluorobenzyl)piperazin-1-yl]ethanone

B. Zhang, G. L. V. Damu, J.-S. Lv and C.-H. Zhou

Abstract top

In the title molecule, C13H15ClF2N2O, the piperazine ring is in a chair conformation with the 2,4-difluorobenzyl and chloroacetyl substituents in equatorial positions.

Comment top

The piperazine ring is present in many clinical drugs (Cai et al., 2009). The incorporation of a piperazine moiety gernerally improves physicochemical properties, and thereby enhances biological activities (Gan, Cai & Zhou, 2009). The piperazine moiety is extensively employed to construct various bioactive molecules (Gan, Lu & Zhou, 2009). Our interest is to develop azole-containing piperazine derivatives as medicinal agents (Gan et al., 2010). Herein we report the crystal structure of the title compound (I).

In the molecular structure (Fig. 1) of (I) the piperazine ring is in a chair conformation, in which the 2,4-difluorobenzyl and chloroacetyl groups are located in equatorial positions.

Related literature top

For the synthesis, see: Gan et al. (2010). For applications of piperazine derivatives, see: Gan, Cai & Zhou (2009); Cai et al. (2009); Gan, Lu, & Zhou (2009).

Experimental top

Compound (I) was synthesized according to the procedure of Gan et al. (2010). Single crystals suitable for X-ray diffraction analysis were grown in a mixed solution petroleum ether and ethyl acetate by slow evaporation at room temperature.

Refinement top

The hydrogen atoms attached to the benzene ring were placed in calculated positions with C—H = 0.93 Å and Uiso(H) = 1.2Ueq(C). All other H atoms were refined independently with isotropic displacement parameters.

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: PLATON (Spek, 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound showing 50% ellipsoids.
2-Chloro-1-[4-(2,4-difluorobenzyl)piperazin-1-yl]ethanone top
Crystal data top
C13H15ClF2N2OF(000) = 600
Mr = 288.72Dx = 1.435 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 4078 reflections
a = 7.895 (2) Åθ = 3.2–27.4°
b = 8.512 (2) ŵ = 0.30 mm1
c = 19.884 (5) ÅT = 296 K
V = 1336.2 (6) Å3Block, colorless
Z = 40.30 × 0.25 × 0.24 mm
Data collection top
Bruker SMART CCD
diffractometer
2324 independent reflections
Radiation source: fine-focus sealed tube2238 reflections with I > 2σ(I)
graphiteRint = 0.026
φ and ω scansθmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 98
Tmin = 0.915, Tmax = 0.931k = 810
5743 measured reflectionsl = 2123
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086 w = 1/[σ2(Fo2) + (0.0501P)2 + 0.1826P]
where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max < 0.001
2324 reflectionsΔρmax = 0.37 e Å3
220 parametersΔρmin = 0.18 e Å3
0 restraintsAbsolute structure: Flack (1983), 938 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.05 (7)
Crystal data top
C13H15ClF2N2OV = 1336.2 (6) Å3
Mr = 288.72Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.895 (2) ŵ = 0.30 mm1
b = 8.512 (2) ÅT = 296 K
c = 19.884 (5) Å0.30 × 0.25 × 0.24 mm
Data collection top
Bruker SMART CCD
diffractometer
2324 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
2238 reflections with I > 2σ(I)
Tmin = 0.915, Tmax = 0.931Rint = 0.026
5743 measured reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086Δρmax = 0.37 e Å3
S = 1.07Δρmin = 0.18 e Å3
2324 reflectionsAbsolute structure: Flack (1983), 938 Friedel pairs
220 parametersFlack parameter: 0.05 (7)
0 restraints
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
Cl10.26806 (8)1.41412 (7)0.14714 (3)0.06679 (19)
N10.53726 (18)0.88254 (16)0.14628 (8)0.0392 (3)
F10.86597 (19)0.62487 (19)0.15098 (7)0.0786 (4)
N20.25240 (19)1.04611 (18)0.20166 (8)0.0441 (4)
C70.6577 (3)0.8543 (2)0.09087 (11)0.0466 (4)
C20.1248 (2)1.1492 (2)0.19486 (9)0.0397 (4)
C40.3630 (2)0.8503 (2)0.12429 (10)0.0437 (4)
C60.5486 (2)1.0480 (2)0.16685 (11)0.0458 (4)
O10.01636 (16)1.11102 (17)0.17464 (8)0.0559 (4)
C30.2357 (3)0.8832 (2)0.17911 (11)0.0482 (4)
F20.6783 (2)0.21756 (16)0.01314 (7)0.0834 (5)
C10.1573 (3)1.3191 (2)0.21356 (10)0.0474 (4)
C130.7660 (2)0.5758 (2)0.10072 (9)0.0477 (4)
C90.5670 (3)0.6280 (2)0.01646 (10)0.0504 (5)
H90.49840.69800.00700.061*
C50.4260 (2)1.0821 (3)0.22316 (11)0.0509 (5)
C80.6638 (2)0.6844 (2)0.06941 (8)0.0416 (4)
C100.5682 (3)0.4712 (3)0.00294 (10)0.0539 (5)
H100.50050.43540.03800.065*
C110.6726 (3)0.3717 (2)0.03146 (10)0.0540 (5)
C120.7734 (3)0.4185 (2)0.08374 (10)0.0576 (5)
H120.84300.34830.10660.069*
H2M0.219 (3)1.327 (3)0.2523 (10)0.049 (6)*
H1M0.049 (3)1.374 (3)0.2171 (10)0.048 (5)*
H9M0.451 (3)1.011 (3)0.2616 (12)0.056 (6)*
H5M0.328 (2)0.920 (2)0.0833 (9)0.038 (5)*
H4M0.265 (3)0.814 (3)0.2201 (11)0.064 (6)*
H10M0.432 (3)1.185 (3)0.2347 (12)0.064 (7)*
H7M0.665 (3)1.071 (2)0.1839 (9)0.045 (5)*
H6M0.362 (3)0.745 (3)0.1093 (11)0.062 (7)*
H8M0.524 (3)1.123 (2)0.1293 (10)0.048 (5)*
H3M0.134 (3)0.868 (3)0.1630 (11)0.057 (6)*
H11M0.761 (3)0.886 (3)0.1060 (10)0.051 (5)*
H12M0.619 (3)0.919 (3)0.0531 (13)0.061 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0769 (4)0.0526 (3)0.0708 (3)0.0112 (3)0.0027 (3)0.0112 (2)
N10.0336 (7)0.0325 (7)0.0514 (8)0.0009 (6)0.0024 (6)0.0012 (6)
F10.0775 (9)0.0846 (10)0.0737 (8)0.0243 (8)0.0276 (7)0.0206 (8)
N20.0328 (7)0.0415 (8)0.0581 (8)0.0027 (7)0.0002 (7)0.0081 (7)
C70.0422 (10)0.0400 (10)0.0577 (11)0.0014 (8)0.0096 (9)0.0031 (9)
C20.0351 (8)0.0415 (9)0.0424 (8)0.0014 (8)0.0052 (7)0.0008 (7)
C40.0375 (9)0.0323 (9)0.0611 (11)0.0029 (8)0.0004 (8)0.0060 (8)
C60.0321 (9)0.0385 (10)0.0667 (12)0.0006 (7)0.0065 (8)0.0067 (9)
O10.0328 (6)0.0533 (8)0.0815 (9)0.0013 (6)0.0034 (6)0.0032 (7)
C30.0361 (9)0.0376 (9)0.0710 (12)0.0001 (8)0.0047 (9)0.0024 (9)
F20.1251 (14)0.0440 (7)0.0812 (9)0.0043 (8)0.0120 (9)0.0143 (7)
C10.0461 (10)0.0431 (10)0.0532 (11)0.0057 (9)0.0024 (9)0.0072 (9)
C130.0456 (9)0.0524 (11)0.0451 (9)0.0064 (10)0.0002 (8)0.0044 (8)
C90.0508 (10)0.0531 (12)0.0474 (10)0.0074 (9)0.0017 (8)0.0041 (9)
C50.0394 (10)0.0492 (12)0.0643 (12)0.0064 (9)0.0108 (9)0.0151 (10)
C80.0386 (9)0.0418 (10)0.0444 (9)0.0017 (8)0.0096 (7)0.0030 (8)
C100.0562 (12)0.0567 (12)0.0487 (10)0.0027 (10)0.0024 (9)0.0083 (9)
C110.0689 (13)0.0396 (10)0.0535 (10)0.0009 (10)0.0147 (9)0.0055 (9)
C120.0688 (13)0.0498 (11)0.0542 (11)0.0208 (11)0.0009 (10)0.0031 (9)
Geometric parameters (Å, °) top
Cl1—C11.778 (2)C6—H8M1.00 (2)
N1—C41.469 (2)C3—H4M1.03 (2)
N1—C61.469 (2)C3—H3M0.88 (3)
N1—C71.475 (2)F2—C111.362 (2)
F1—C131.340 (2)C1—H2M0.91 (2)
N2—C21.343 (2)C1—H1M0.98 (2)
N2—C31.463 (2)C13—C81.376 (3)
N2—C51.468 (2)C13—C121.382 (3)
C7—C81.509 (3)C9—C81.387 (3)
C7—H11M0.91 (2)C9—C101.389 (3)
C7—H12M0.98 (3)C9—H90.9300
C2—O11.228 (2)C5—H9M1.00 (2)
C2—C11.516 (3)C5—H10M0.90 (3)
C4—C31.509 (3)C10—C111.365 (3)
C4—H5M1.046 (19)C10—H100.9300
C4—H6M0.94 (3)C11—C121.368 (3)
C6—C51.508 (3)C12—H120.9300
C6—H7M1.00 (2)
C4—N1—C6108.60 (14)H4M—C3—H3M114 (2)
C4—N1—C7110.54 (15)C2—C1—Cl1109.57 (13)
C6—N1—C7108.94 (14)C2—C1—H2M111.4 (14)
C2—N2—C3121.37 (16)Cl1—C1—H2M109.4 (13)
C2—N2—C5126.42 (16)C2—C1—H1M108.8 (13)
C3—N2—C5111.78 (15)Cl1—C1—H1M105.6 (12)
N1—C7—C8112.82 (15)H2M—C1—H1M111.9 (18)
N1—C7—H11M106.6 (13)F1—C13—C8118.23 (17)
C8—C7—H11M110.3 (14)F1—C13—C12117.35 (17)
N1—C7—H12M106.2 (14)C8—C13—C12124.42 (18)
C8—C7—H12M109.6 (14)C8—C9—C10122.64 (19)
H11M—C7—H12M111.4 (19)C8—C9—H9118.7
O1—C2—N2122.76 (17)C10—C9—H9118.7
O1—C2—C1119.10 (16)N2—C5—C6110.06 (16)
N2—C2—C1118.14 (16)N2—C5—H9M106.3 (14)
N1—C4—C3111.97 (16)C6—C5—H9M109.0 (13)
N1—C4—H5M112.1 (10)N2—C5—H10M108.9 (16)
C3—C4—H5M106.2 (10)C6—C5—H10M109.9 (16)
N1—C4—H6M106.0 (15)H9M—C5—H10M113 (2)
C3—C4—H6M113.6 (14)C13—C8—C9115.72 (18)
H5M—C4—H6M106.9 (17)C13—C8—C7122.34 (17)
N1—C6—C5110.60 (17)C9—C8—C7121.95 (17)
N1—C6—H7M109.5 (12)C11—C10—C9117.5 (2)
C5—C6—H7M107.6 (11)C11—C10—H10121.3
N1—C6—H8M112.9 (11)C9—C10—H10121.3
C5—C6—H8M107.8 (12)F2—C11—C10118.9 (2)
H7M—C6—H8M108.2 (17)F2—C11—C12117.6 (2)
N2—C3—C4109.69 (15)C10—C11—C12123.4 (2)
N2—C3—H4M106.1 (13)C11—C12—C13116.28 (19)
C4—C3—H4M108.3 (14)C11—C12—H12121.9
N2—C3—H3M109.5 (15)C13—C12—H12121.9
C4—C3—H3M108.7 (15)
C4—N1—C7—C864.7 (2)N1—C6—C5—N258.6 (2)
C6—N1—C7—C8176.09 (16)F1—C13—C8—C9178.12 (17)
C3—N2—C2—O16.0 (3)C12—C13—C8—C91.7 (3)
C5—N2—C2—O1177.8 (2)F1—C13—C8—C71.6 (3)
C3—N2—C2—C1174.52 (18)C12—C13—C8—C7178.66 (19)
C5—N2—C2—C12.7 (3)C10—C9—C8—C131.8 (3)
C6—N1—C4—C358.6 (2)C10—C9—C8—C7178.50 (18)
C7—N1—C4—C3178.10 (15)N1—C7—C8—C1385.7 (2)
C4—N1—C6—C559.1 (2)N1—C7—C8—C994.6 (2)
C7—N1—C6—C5179.51 (16)C8—C9—C10—C111.3 (3)
C2—N2—C3—C4117.63 (19)C9—C10—C11—F2179.20 (19)
C5—N2—C3—C455.3 (2)C9—C10—C11—C120.5 (3)
N1—C4—C3—N256.8 (2)F2—C11—C12—C13179.39 (19)
O1—C2—C1—Cl1101.22 (18)C10—C11—C12—C130.4 (3)
N2—C2—C1—Cl179.24 (19)F1—C13—C12—C11178.81 (18)
C2—N2—C5—C6115.8 (2)C8—C13—C12—C111.0 (3)
C3—N2—C5—C656.7 (2)
Acknowledgements top

This work was partially supported by the Natural Science Foundation of China (21172181) and the Fundamental Research Funds for the Central Universities (XDJK2011D007)

references
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