organic compounds
1-Chloro-2-(4-phenylpiperazin-1-yl)ethanone
aCollege of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, People's Republic of China
*Correspondence e-mail: xuyj1960@qust.edu.cn
The title compound, C12H15ClN2O, is a piperazine derivative with the potential for use as a starting material for pharmaceutial and agrochemical applications. The structure is stabilized by C—H⋯O hydrogen bonds, C—H⋯π interactions and π–π stacking interactions [centroid–centroid distance = is 4.760 (2) Å].
Related literature
For the biological activity of piperazine and its derivatives, see: Berkheij (2005); Upadhayaya et al. (2004); Choudhary et al. (2006); Vacca et al. (1994); Hulme (1999). For reference structural data, see: Drew & Leslie (1986).
Experimental
Crystal data
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Refinement
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Data collection: CrystalClear (Rigaku, 2005); cell CrystalClear; data reduction: CrystalClear; 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
10.1107/S1600536809008216/hg2461sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536809008216/hg2461Isup2.hkl
To a solution of 1-phenylpiperazine hydrochloride (2.0 g, 10 mmol) triethylamine (2.8 ml, 2 mmol) in anhydrous dichloromethane (50 ml) was added chloroacetyl chloride (0.8 mL, 10 mmol) dropwise at 273 K. The reaction mixture was stirred at room temperature for 2 h and monitored by TLC, and then the mixture was diluted with dichloromethane (50 ml) and washed with water (200 ml). The organic phase was dride over anhydrous sodium sulfate and concentrated to yield a solid which was crystallized to obtain 2-chloro-1-(4-phenylpiperazin-1-yl)ethanone.
H atoms were placed in calculated positions and treated using a riding model, with C—H = 0.93–0.98 Å and with Uiso(H) = 1.2 Ueq(C) or 1.5 Ueq(C) for methyl H atoms.
Data collection: CrystalClear (Rigaku, 2005); cell
CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); 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).Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids. | |
Fig. 2. The packing diagram of (I), viewed down the c axis, showing the intermolecular hydrogen bonds (dashed lines). |
C12H15ClN2O | F(000) = 504 |
Mr = 238.71 | Dx = 1.379 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 3260 reflections |
a = 9.4423 (19) Å | θ = 3.2–27.9° |
b = 8.5629 (17) Å | µ = 0.31 mm−1 |
c = 14.506 (3) Å | T = 113 K |
β = 101.34 (3)° | Block, colourless |
V = 1149.9 (4) Å3 | 0.20 × 0.18 × 0.12 mm |
Z = 4 |
Rigaku Saturn diffractometer | 2729 independent reflections |
Radiation source: rotating anode | 2151 reflections with I > 2σ(I) |
Confocal monochromator | Rint = 0.035 |
ω scans | θmax = 27.9°, θmin = 3.2° |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | h = −12→12 |
Tmin = 0.940, Tmax = 0.964 | k = −8→11 |
9264 measured reflections | l = −16→19 |
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)] = 0.035 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.098 | H-atom parameters constrained |
S = 1.07 | w = 1/[σ2(Fo2) + (0.055P)2 + 0.0763P] where P = (Fo2 + 2Fc2)/3 |
2729 reflections | (Δ/σ)max = 0.001 |
145 parameters | Δρmax = 0.25 e Å−3 |
0 restraints | Δρmin = −0.26 e Å−3 |
C12H15ClN2O | V = 1149.9 (4) Å3 |
Mr = 238.71 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 9.4423 (19) Å | µ = 0.31 mm−1 |
b = 8.5629 (17) Å | T = 113 K |
c = 14.506 (3) Å | 0.20 × 0.18 × 0.12 mm |
β = 101.34 (3)° |
Rigaku Saturn diffractometer | 2729 independent reflections |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | 2151 reflections with I > 2σ(I) |
Tmin = 0.940, Tmax = 0.964 | Rint = 0.035 |
9264 measured reflections |
R[F2 > 2σ(F2)] = 0.035 | 0 restraints |
wR(F2) = 0.098 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.25 e Å−3 |
2729 reflections | Δρmin = −0.26 e Å−3 |
145 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
Cl1 | 0.62862 (4) | 0.03256 (4) | 0.08928 (2) | 0.03631 (13) | |
O1 | 0.58185 (10) | −0.16571 (10) | 0.24044 (7) | 0.0297 (2) | |
N1 | 0.75320 (11) | 0.03812 (12) | 0.56187 (8) | 0.0237 (2) | |
N2 | 0.66086 (12) | −0.00754 (12) | 0.36497 (8) | 0.0244 (2) | |
C1 | 0.82553 (13) | 0.04592 (14) | 0.65699 (10) | 0.0230 (3) | |
C2 | 0.76046 (14) | −0.02277 (14) | 0.72590 (10) | 0.0276 (3) | |
H2 | 0.6724 | −0.0739 | 0.7082 | 0.033* | |
C3 | 0.82561 (16) | −0.01541 (15) | 0.81981 (11) | 0.0312 (3) | |
H3 | 0.7815 | −0.0627 | 0.8646 | 0.037* | |
C4 | 0.95649 (16) | 0.06196 (16) | 0.84812 (10) | 0.0311 (3) | |
H4 | 1.0004 | 0.0664 | 0.9113 | 0.037* | |
C5 | 1.02012 (14) | 0.13211 (15) | 0.78058 (10) | 0.0299 (3) | |
H5 | 1.1069 | 0.1854 | 0.7989 | 0.036* | |
C6 | 0.95647 (13) | 0.12419 (15) | 0.68604 (10) | 0.0253 (3) | |
H6 | 1.0013 | 0.1714 | 0.6416 | 0.030* | |
C7 | 0.80673 (14) | 0.13837 (14) | 0.49496 (10) | 0.0256 (3) | |
H7A | 0.8961 | 0.0961 | 0.4821 | 0.031* | |
H7B | 0.8263 | 0.2419 | 0.5215 | 0.031* | |
C8 | 0.69545 (14) | 0.14856 (14) | 0.40466 (10) | 0.0266 (3) | |
H8A | 0.6084 | 0.1975 | 0.4170 | 0.032* | |
H8B | 0.7325 | 0.2128 | 0.3597 | 0.032* | |
C9 | 0.61886 (13) | −0.11941 (14) | 0.43097 (10) | 0.0250 (3) | |
H9A | 0.6128 | −0.2231 | 0.4035 | 0.030* | |
H9B | 0.5242 | −0.0921 | 0.4425 | 0.030* | |
C10 | 0.72706 (13) | −0.12050 (14) | 0.52343 (10) | 0.0256 (3) | |
H10A | 0.6908 | −0.1857 | 0.5683 | 0.031* | |
H10B | 0.8174 | −0.1650 | 0.5137 | 0.031* | |
C11 | 0.63200 (13) | −0.03982 (14) | 0.27233 (10) | 0.0237 (3) | |
C12 | 0.66787 (14) | 0.08973 (15) | 0.20873 (9) | 0.0272 (3) | |
H12A | 0.7695 | 0.1158 | 0.2266 | 0.033* | |
H12B | 0.6124 | 0.1823 | 0.2169 | 0.033* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0485 (2) | 0.0282 (2) | 0.0289 (2) | 0.00339 (14) | −0.00042 (16) | −0.00073 (13) |
O1 | 0.0291 (5) | 0.0214 (5) | 0.0375 (6) | −0.0028 (4) | 0.0034 (4) | −0.0060 (4) |
N1 | 0.0219 (5) | 0.0164 (5) | 0.0314 (6) | −0.0042 (4) | 0.0021 (4) | 0.0009 (4) |
N2 | 0.0241 (5) | 0.0174 (5) | 0.0309 (6) | −0.0036 (4) | 0.0033 (4) | −0.0005 (4) |
C1 | 0.0199 (6) | 0.0161 (6) | 0.0319 (7) | 0.0025 (4) | 0.0027 (5) | 0.0008 (5) |
C2 | 0.0236 (6) | 0.0199 (6) | 0.0396 (8) | −0.0006 (5) | 0.0072 (6) | 0.0022 (5) |
C3 | 0.0358 (7) | 0.0233 (7) | 0.0360 (8) | 0.0027 (6) | 0.0105 (6) | 0.0043 (6) |
C4 | 0.0359 (7) | 0.0263 (7) | 0.0293 (8) | 0.0046 (6) | 0.0021 (6) | −0.0028 (6) |
C5 | 0.0261 (7) | 0.0254 (7) | 0.0364 (8) | −0.0013 (5) | 0.0016 (6) | −0.0042 (6) |
C6 | 0.0222 (6) | 0.0210 (6) | 0.0325 (8) | −0.0023 (5) | 0.0047 (5) | −0.0005 (5) |
C7 | 0.0242 (6) | 0.0181 (6) | 0.0333 (8) | −0.0051 (5) | 0.0028 (5) | 0.0003 (5) |
C8 | 0.0306 (7) | 0.0164 (6) | 0.0314 (7) | −0.0031 (5) | 0.0026 (6) | −0.0005 (5) |
C9 | 0.0228 (6) | 0.0169 (6) | 0.0348 (8) | −0.0049 (5) | 0.0048 (5) | −0.0006 (5) |
C10 | 0.0220 (6) | 0.0160 (6) | 0.0375 (8) | −0.0023 (5) | 0.0031 (5) | 0.0013 (5) |
C11 | 0.0165 (6) | 0.0193 (6) | 0.0341 (7) | 0.0031 (5) | 0.0022 (5) | −0.0011 (5) |
C12 | 0.0280 (7) | 0.0220 (6) | 0.0291 (7) | 0.0016 (5) | −0.0004 (5) | −0.0014 (5) |
Cl1—C12 | 1.7682 (14) | C5—C6 | 1.386 (2) |
O1—C11 | 1.2304 (15) | C5—H5 | 0.9300 |
N1—C1 | 1.4157 (18) | C6—H6 | 0.9300 |
N1—C7 | 1.4586 (16) | C7—C8 | 1.5119 (18) |
N1—C10 | 1.4705 (16) | C7—H7A | 0.9700 |
N2—C11 | 1.3463 (18) | C7—H7B | 0.9700 |
N2—C9 | 1.4632 (17) | C8—H8A | 0.9700 |
N2—C8 | 1.4666 (15) | C8—H8B | 0.9700 |
C1—C6 | 1.3965 (18) | C9—C10 | 1.5177 (18) |
C1—C2 | 1.4015 (19) | C9—H9A | 0.9700 |
C2—C3 | 1.381 (2) | C9—H9B | 0.9700 |
C2—H2 | 0.9300 | C10—H10A | 0.9700 |
C3—C4 | 1.391 (2) | C10—H10B | 0.9700 |
C3—H3 | 0.9300 | C11—C12 | 1.5229 (18) |
C4—C5 | 1.383 (2) | C12—H12A | 0.9700 |
C4—H4 | 0.9300 | C12—H12B | 0.9700 |
C1—N1—C7 | 117.19 (10) | H7A—C7—H7B | 108.2 |
C1—N1—C10 | 115.21 (10) | N2—C8—C7 | 110.53 (10) |
C7—N1—C10 | 110.21 (11) | N2—C8—H8A | 109.5 |
C11—N2—C9 | 119.41 (10) | C7—C8—H8A | 109.5 |
C11—N2—C8 | 124.38 (11) | N2—C8—H8B | 109.5 |
C9—N2—C8 | 114.07 (11) | C7—C8—H8B | 109.5 |
C6—C1—C2 | 118.20 (13) | H8A—C8—H8B | 108.1 |
C6—C1—N1 | 123.06 (12) | N2—C9—C10 | 111.12 (10) |
C2—C1—N1 | 118.70 (11) | N2—C9—H9A | 109.4 |
C3—C2—C1 | 120.76 (13) | C10—C9—H9A | 109.4 |
C3—C2—H2 | 119.6 | N2—C9—H9B | 109.4 |
C1—C2—H2 | 119.6 | C10—C9—H9B | 109.4 |
C2—C3—C4 | 120.68 (13) | H9A—C9—H9B | 108.0 |
C2—C3—H3 | 119.7 | N1—C10—C9 | 111.28 (10) |
C4—C3—H3 | 119.7 | N1—C10—H10A | 109.4 |
C5—C4—C3 | 118.83 (14) | C9—C10—H10A | 109.4 |
C5—C4—H4 | 120.6 | N1—C10—H10B | 109.4 |
C3—C4—H4 | 120.6 | C9—C10—H10B | 109.4 |
C4—C5—C6 | 121.01 (13) | H10A—C10—H10B | 108.0 |
C4—C5—H5 | 119.5 | O1—C11—N2 | 122.85 (12) |
C6—C5—H5 | 119.5 | O1—C11—C12 | 121.70 (12) |
C5—C6—C1 | 120.52 (13) | N2—C11—C12 | 115.44 (10) |
C5—C6—H6 | 119.7 | C11—C12—Cl1 | 111.30 (9) |
C1—C6—H6 | 119.7 | C11—C12—H12A | 109.4 |
N1—C7—C8 | 109.74 (11) | Cl1—C12—H12A | 109.4 |
N1—C7—H7A | 109.7 | C11—C12—H12B | 109.4 |
C8—C7—H7A | 109.7 | Cl1—C12—H12B | 109.4 |
N1—C7—H7B | 109.7 | H12A—C12—H12B | 108.0 |
C8—C7—H7B | 109.7 | ||
C7—N1—C1—C6 | −10.51 (17) | C11—N2—C8—C7 | −143.92 (12) |
C10—N1—C1—C6 | 121.65 (13) | C9—N2—C8—C7 | 52.87 (14) |
C7—N1—C1—C2 | 166.96 (11) | N1—C7—C8—N2 | −57.54 (14) |
C10—N1—C1—C2 | −60.88 (15) | C11—N2—C9—C10 | 145.88 (11) |
C6—C1—C2—C3 | −1.11 (18) | C8—N2—C9—C10 | −50.00 (14) |
N1—C1—C2—C3 | −178.71 (11) | C1—N1—C10—C9 | 166.07 (10) |
C1—C2—C3—C4 | 0.7 (2) | C7—N1—C10—C9 | −58.57 (13) |
C2—C3—C4—C5 | 0.3 (2) | N2—C9—C10—N1 | 52.08 (14) |
C3—C4—C5—C6 | −0.9 (2) | C9—N2—C11—O1 | −6.05 (18) |
C4—C5—C6—C1 | 0.5 (2) | C8—N2—C11—O1 | −168.43 (12) |
C2—C1—C6—C5 | 0.48 (19) | C9—N2—C11—C12 | 174.87 (11) |
N1—C1—C6—C5 | 177.96 (11) | C8—N2—C11—C12 | 12.49 (17) |
C1—N1—C7—C8 | −164.61 (10) | O1—C11—C12—Cl1 | −0.20 (15) |
C10—N1—C7—C8 | 61.01 (13) | N2—C11—C12—Cl1 | 178.89 (9) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O1i | 0.93 | 2.47 | 3.1850 (16) | 134 |
C9—H9A···O1 | 0.97 | 2.38 | 2.7456 (17) | 102 |
C12—H12B···O1ii | 0.97 | 2.43 | 3.3426 (16) | 157 |
C5—H5···Cg2iii | 0.93 | 3.25 | 3.7651 (15) | 117 |
C8—H8B···Cg2iv | 0.97 | 3.09 | 4.0393 (12) | 168 |
C12—H12A···Cg2iv | 0.97 | 3.04 | 3.6878 | 125 |
Symmetry codes: (i) x, −y−1/2, z+1/2; (ii) −x+1, y+1/2, −z+1/2; (iii) −x+2, y−1/2, −z+1/2; (iv) x, −y−1/2, z−3/2. |
Experimental details
Crystal data | |
Chemical formula | C12H15ClN2O |
Mr | 238.71 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 113 |
a, b, c (Å) | 9.4423 (19), 8.5629 (17), 14.506 (3) |
β (°) | 101.34 (3) |
V (Å3) | 1149.9 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.31 |
Crystal size (mm) | 0.20 × 0.18 × 0.12 |
Data collection | |
Diffractometer | Rigaku Saturn diffractometer |
Absorption correction | Multi-scan (CrystalClear; Rigaku, 2005) |
Tmin, Tmax | 0.940, 0.964 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9264, 2729, 2151 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.658 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.035, 0.098, 1.07 |
No. of reflections | 2729 |
No. of parameters | 145 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.25, −0.26 |
Computer programs: CrystalClear (Rigaku, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O1i | 0.93 | 2.47 | 3.1850 (16) | 134.3 |
C9—H9A···O1 | 0.97 | 2.38 | 2.7456 (17) | 101.8 |
C12—H12B···O1ii | 0.97 | 2.43 | 3.3426 (16) | 157.3 |
C5—H5···Cg2iii | 0.93 | 3.25 | 3.7651 (15) | 117 |
C8—H8B···Cg2iv | 0.97 | 3.09 | 4.0393 (12) | 168 |
C12—H12A···Cg2iv | 0.97 | 3.04 | 3.6878 | 125 |
Symmetry codes: (i) x, −y−1/2, z+1/2; (ii) −x+1, y+1/2, −z+1/2; (iii) −x+2, y−1/2, −z+1/2; (iv) x, −y−1/2, z−3/2. |
Acknowledgements
This work was supported by the Natural Science Foundation of Shandong Province, China (No. Y2007B50). The authors thank Professor Yong-Hong Wen for help with this paper.
References
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Piperazine and its derivatives are important pharmacores that can be found in biologically active compounds across a number of different therapeutic areas (Berkheij, 2005), such as antifungal (Upadhayaya et al., 2004), anti-bacterial, anti-malarial, anti-psychotic agents (Choudhary et al., 2006), HIV protease inhibitor (Vacca et al., 1994), anti-depressant and anti-tumour activity colon, prostate, breast, lung and leukemia tumors (Hulme et al., 1999). In an attempt to further synthesis piperazine derivatives, the title compound, 2-chloro-1-(4-phenylpiperazin-1-yl)ethanone, (I) (Fig. 1), was synthesized and its X-ray crystal structure determined.
In the structure of title compund (Fig. 1), the bond lengths and angles in the piperazine ring and the benzene ring are normal (Drew & Leslie, 1986) (Table 1). The dihedral angle between the piperazine ring N1/N2/C7—C10 and C1—C6 benzene ring is 36.8 (2)°. The molecular structure is stabilized by inter and intramolecular C—H···O interactions (Table 2). There exists π-π stacking interactions and C—H···π interactions. The π-π stacking interaction between the two phenyl rings is observed in the structure. The centroid distance between the two rings is 4.760 Å. There are three types of C—H···π interactions, C5—H5···Cg2, C8—H8B···Cg2 and C12—H12A···Cg2 (Cg2 is the C1—C6 ring centroid) (Table 2).