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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

(Received 17 December 2008; accepted 6 March 2009; online 7 May 2009)

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 ππ stacking inter­actions [centroid–centroid distance = is 4.760 (2) Å].

Related literature

For the biological activity of piperazine and its derivatives, see: Berkheij (2005[Berkheij, M. (2005). Tetrahedron Lett. 46, 2369-2371.]); Upadhayaya et al. (2004[Upadhayaya, P. S., Sinha, N. & Jain, S. (2004). Bioorg. Med. Chem. 12, 2225-2238.]); Choudhary et al. (2006[Choudhary, P., Kumar, R. & Verma, K. (2006). Bioorg. Med. Chem. 14, 1819-1826.]); Vacca et al. (1994[Vacca, J. P., Dorsey, B. D., Schleif, W. A. & Levine, R. B. (1994). J. Med. Chem. 37, 3443-3451.]); Hulme (1999[Hulme, C. (1999). Tetrahedron Lett. 40, 5295-5299.]). For reference structural data, see: Drew & Leslie (1986[Drew, M. G. B. & Leslie, P. G. (1986). Acta Cryst. C42, 174-177.]).

[Scheme 1]

Experimental

Crystal data
  • C12H15ClN2O

  • Mr = 238.71

  • Monoclinic, P 21 /c

  • a = 9.4423 (19) Å

  • b = 8.5629 (17) Å

  • c = 14.506 (3) Å

  • β = 101.34 (3)°

  • V = 1149.9 (4) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.31 mm−1

  • T = 113 K

  • 0.20 × 0.18 × 0.12 mm

Data collection
  • Rigaku Saturn diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku, 2005[Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.940, Tmax = 0.964

  • 9264 measured reflections

  • 2729 independent reflections

  • 2151 reflections with I > 2σ(I)

  • Rint = 0.035

Refinement
  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.098

  • S = 1.07

  • 2729 reflections

  • 145 parameters

  • H-atom parameters constrained

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.26 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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—H8BCg2iv 0.97 3.09 4.0393 (12) 168
C12—H12ACg2iv 0.97 3.04 3.6878 125
Symmetry codes: (i) [x, -y-{\script{1\over 2}}, z+{\script{1\over 2}}]; (ii) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) [-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iv) [x, -y-{\script{1\over 2}}, z-{\script{3\over 2}}]. Cg2 is the centroid of the C1–C6 ring.

Data collection: CrystalClear (Rigaku, 2005[Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.]); cell refinement: CrystalClear; data reduction: CrystalClear; 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

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).

Related literature top

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 et al. (1999). For reference structural data, see: Drew & Leslie (1986).

.

Experimental top

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.

Refinement top

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.

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids.
[Figure 2] Fig. 2. The packing diagram of (I), viewed down the c axis, showing the intermolecular hydrogen bonds (dashed lines).
1-Chloro-2-(4-phenylpiperazin-1-yl)ethanone top
Crystal data top
C12H15ClN2OF(000) = 504
Mr = 238.71Dx = 1.379 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3260 reflections
a = 9.4423 (19) Åθ = 3.2–27.9°
b = 8.5629 (17) ŵ = 0.31 mm1
c = 14.506 (3) ÅT = 113 K
β = 101.34 (3)°Block, colourless
V = 1149.9 (4) Å30.20 × 0.18 × 0.12 mm
Z = 4
Data collection top
Rigaku Saturn
diffractometer
2729 independent reflections
Radiation source: rotating anode2151 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.035
ω scansθmax = 27.9°, θmin = 3.2°
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2005)
h = 1212
Tmin = 0.940, Tmax = 0.964k = 811
9264 measured reflectionsl = 1619
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)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.098H-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 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = 0.26 e Å3
Crystal data top
C12H15ClN2OV = 1149.9 (4) Å3
Mr = 238.71Z = 4
Monoclinic, P21/cMo Kα radiation
a = 9.4423 (19) ŵ = 0.31 mm1
b = 8.5629 (17) ÅT = 113 K
c = 14.506 (3) Å0.20 × 0.18 × 0.12 mm
β = 101.34 (3)°
Data collection top
Rigaku Saturn
diffractometer
2729 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2005)
2151 reflections with I > 2σ(I)
Tmin = 0.940, Tmax = 0.964Rint = 0.035
9264 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.098H-atom parameters constrained
S = 1.07Δρmax = 0.25 e Å3
2729 reflectionsΔρmin = 0.26 e Å3
145 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
Cl10.62862 (4)0.03256 (4)0.08928 (2)0.03631 (13)
O10.58185 (10)0.16571 (10)0.24044 (7)0.0297 (2)
N10.75320 (11)0.03812 (12)0.56187 (8)0.0237 (2)
N20.66086 (12)0.00754 (12)0.36497 (8)0.0244 (2)
C10.82553 (13)0.04592 (14)0.65699 (10)0.0230 (3)
C20.76046 (14)0.02277 (14)0.72590 (10)0.0276 (3)
H20.67240.07390.70820.033*
C30.82561 (16)0.01541 (15)0.81981 (11)0.0312 (3)
H30.78150.06270.86460.037*
C40.95649 (16)0.06196 (16)0.84812 (10)0.0311 (3)
H41.00040.06640.91130.037*
C51.02012 (14)0.13211 (15)0.78058 (10)0.0299 (3)
H51.10690.18540.79890.036*
C60.95647 (13)0.12419 (15)0.68604 (10)0.0253 (3)
H61.00130.17140.64160.030*
C70.80673 (14)0.13837 (14)0.49496 (10)0.0256 (3)
H7A0.89610.09610.48210.031*
H7B0.82630.24190.52150.031*
C80.69545 (14)0.14856 (14)0.40466 (10)0.0266 (3)
H8A0.60840.19750.41700.032*
H8B0.73250.21280.35970.032*
C90.61886 (13)0.11941 (14)0.43097 (10)0.0250 (3)
H9A0.61280.22310.40350.030*
H9B0.52420.09210.44250.030*
C100.72706 (13)0.12050 (14)0.52343 (10)0.0256 (3)
H10A0.69080.18570.56830.031*
H10B0.81740.16500.51370.031*
C110.63200 (13)0.03982 (14)0.27233 (10)0.0237 (3)
C120.66787 (14)0.08973 (15)0.20873 (9)0.0272 (3)
H12A0.76950.11580.22660.033*
H12B0.61240.18230.21690.033*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0485 (2)0.0282 (2)0.0289 (2)0.00339 (14)0.00042 (16)0.00073 (13)
O10.0291 (5)0.0214 (5)0.0375 (6)0.0028 (4)0.0034 (4)0.0060 (4)
N10.0219 (5)0.0164 (5)0.0314 (6)0.0042 (4)0.0021 (4)0.0009 (4)
N20.0241 (5)0.0174 (5)0.0309 (6)0.0036 (4)0.0033 (4)0.0005 (4)
C10.0199 (6)0.0161 (6)0.0319 (7)0.0025 (4)0.0027 (5)0.0008 (5)
C20.0236 (6)0.0199 (6)0.0396 (8)0.0006 (5)0.0072 (6)0.0022 (5)
C30.0358 (7)0.0233 (7)0.0360 (8)0.0027 (6)0.0105 (6)0.0043 (6)
C40.0359 (7)0.0263 (7)0.0293 (8)0.0046 (6)0.0021 (6)0.0028 (6)
C50.0261 (7)0.0254 (7)0.0364 (8)0.0013 (5)0.0016 (6)0.0042 (6)
C60.0222 (6)0.0210 (6)0.0325 (8)0.0023 (5)0.0047 (5)0.0005 (5)
C70.0242 (6)0.0181 (6)0.0333 (8)0.0051 (5)0.0028 (5)0.0003 (5)
C80.0306 (7)0.0164 (6)0.0314 (7)0.0031 (5)0.0026 (6)0.0005 (5)
C90.0228 (6)0.0169 (6)0.0348 (8)0.0049 (5)0.0048 (5)0.0006 (5)
C100.0220 (6)0.0160 (6)0.0375 (8)0.0023 (5)0.0031 (5)0.0013 (5)
C110.0165 (6)0.0193 (6)0.0341 (7)0.0031 (5)0.0022 (5)0.0011 (5)
C120.0280 (7)0.0220 (6)0.0291 (7)0.0016 (5)0.0004 (5)0.0014 (5)
Geometric parameters (Å, º) top
Cl1—C121.7682 (14)C5—C61.386 (2)
O1—C111.2304 (15)C5—H50.9300
N1—C11.4157 (18)C6—H60.9300
N1—C71.4586 (16)C7—C81.5119 (18)
N1—C101.4705 (16)C7—H7A0.9700
N2—C111.3463 (18)C7—H7B0.9700
N2—C91.4632 (17)C8—H8A0.9700
N2—C81.4666 (15)C8—H8B0.9700
C1—C61.3965 (18)C9—C101.5177 (18)
C1—C21.4015 (19)C9—H9A0.9700
C2—C31.381 (2)C9—H9B0.9700
C2—H20.9300C10—H10A0.9700
C3—C41.391 (2)C10—H10B0.9700
C3—H30.9300C11—C121.5229 (18)
C4—C51.383 (2)C12—H12A0.9700
C4—H40.9300C12—H12B0.9700
C1—N1—C7117.19 (10)H7A—C7—H7B108.2
C1—N1—C10115.21 (10)N2—C8—C7110.53 (10)
C7—N1—C10110.21 (11)N2—C8—H8A109.5
C11—N2—C9119.41 (10)C7—C8—H8A109.5
C11—N2—C8124.38 (11)N2—C8—H8B109.5
C9—N2—C8114.07 (11)C7—C8—H8B109.5
C6—C1—C2118.20 (13)H8A—C8—H8B108.1
C6—C1—N1123.06 (12)N2—C9—C10111.12 (10)
C2—C1—N1118.70 (11)N2—C9—H9A109.4
C3—C2—C1120.76 (13)C10—C9—H9A109.4
C3—C2—H2119.6N2—C9—H9B109.4
C1—C2—H2119.6C10—C9—H9B109.4
C2—C3—C4120.68 (13)H9A—C9—H9B108.0
C2—C3—H3119.7N1—C10—C9111.28 (10)
C4—C3—H3119.7N1—C10—H10A109.4
C5—C4—C3118.83 (14)C9—C10—H10A109.4
C5—C4—H4120.6N1—C10—H10B109.4
C3—C4—H4120.6C9—C10—H10B109.4
C4—C5—C6121.01 (13)H10A—C10—H10B108.0
C4—C5—H5119.5O1—C11—N2122.85 (12)
C6—C5—H5119.5O1—C11—C12121.70 (12)
C5—C6—C1120.52 (13)N2—C11—C12115.44 (10)
C5—C6—H6119.7C11—C12—Cl1111.30 (9)
C1—C6—H6119.7C11—C12—H12A109.4
N1—C7—C8109.74 (11)Cl1—C12—H12A109.4
N1—C7—H7A109.7C11—C12—H12B109.4
C8—C7—H7A109.7Cl1—C12—H12B109.4
N1—C7—H7B109.7H12A—C12—H12B108.0
C8—C7—H7B109.7
C7—N1—C1—C610.51 (17)C11—N2—C8—C7143.92 (12)
C10—N1—C1—C6121.65 (13)C9—N2—C8—C752.87 (14)
C7—N1—C1—C2166.96 (11)N1—C7—C8—N257.54 (14)
C10—N1—C1—C260.88 (15)C11—N2—C9—C10145.88 (11)
C6—C1—C2—C31.11 (18)C8—N2—C9—C1050.00 (14)
N1—C1—C2—C3178.71 (11)C1—N1—C10—C9166.07 (10)
C1—C2—C3—C40.7 (2)C7—N1—C10—C958.57 (13)
C2—C3—C4—C50.3 (2)N2—C9—C10—N152.08 (14)
C3—C4—C5—C60.9 (2)C9—N2—C11—O16.05 (18)
C4—C5—C6—C10.5 (2)C8—N2—C11—O1168.43 (12)
C2—C1—C6—C50.48 (19)C9—N2—C11—C12174.87 (11)
N1—C1—C6—C5177.96 (11)C8—N2—C11—C1212.49 (17)
C1—N1—C7—C8164.61 (10)O1—C11—C12—Cl10.20 (15)
C10—N1—C7—C861.01 (13)N2—C11—C12—Cl1178.89 (9)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2···O1i0.932.473.1850 (16)134
C9—H9A···O10.972.382.7456 (17)102
C12—H12B···O1ii0.972.433.3426 (16)157
C5—H5···Cg2iii0.933.253.7651 (15)117
C8—H8B···Cg2iv0.973.094.0393 (12)168
C12—H12A···Cg2iv0.973.043.6878125
Symmetry codes: (i) x, y1/2, z+1/2; (ii) x+1, y+1/2, z+1/2; (iii) x+2, y1/2, z+1/2; (iv) x, y1/2, z3/2.

Experimental details

Crystal data
Chemical formulaC12H15ClN2O
Mr238.71
Crystal system, space groupMonoclinic, P21/c
Temperature (K)113
a, b, c (Å)9.4423 (19), 8.5629 (17), 14.506 (3)
β (°) 101.34 (3)
V3)1149.9 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.31
Crystal size (mm)0.20 × 0.18 × 0.12
Data collection
DiffractometerRigaku Saturn
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku, 2005)
Tmin, Tmax0.940, 0.964
No. of measured, independent and
observed [I > 2σ(I)] reflections
9264, 2729, 2151
Rint0.035
(sin θ/λ)max1)0.658
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.098, 1.07
No. of reflections2729
No. of parameters145
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.25, 0.26

Computer programs: CrystalClear (Rigaku, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2···O1i0.932.473.1850 (16)134.3
C9—H9A···O10.972.382.7456 (17)101.8
C12—H12B···O1ii0.972.433.3426 (16)157.3
C5—H5···Cg2iii0.933.253.7651 (15)117
C8—H8B···Cg2iv0.973.094.0393 (12)168
C12—H12A···Cg2iv0.973.043.6878125
Symmetry codes: (i) x, y1/2, z+1/2; (ii) x+1, y+1/2, z+1/2; (iii) x+2, y1/2, z+1/2; (iv) x, y1/2, z3/2.
 

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

First citationBerkheij, M. (2005). Tetrahedron Lett. 46, 2369–2371.  Web of Science CrossRef CAS Google Scholar
First citationChoudhary, P., Kumar, R. & Verma, K. (2006). Bioorg. Med. Chem. 14, 1819–1826.  Web of Science CrossRef PubMed Google Scholar
First citationDrew, M. G. B. & Leslie, P. G. (1986). Acta Cryst. C42, 174–177.  CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationHulme, C. (1999). Tetrahedron Lett. 40, 5295–5299.  Web of Science CrossRef CAS Google Scholar
First citationRigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationUpadhayaya, P. S., Sinha, N. & Jain, S. (2004). Bioorg. Med. Chem. 12, 2225–2238.  Web of Science CrossRef PubMed CAS Google Scholar
First citationVacca, J. P., Dorsey, B. D., Schleif, W. A. & Levine, R. B. (1994). J. Med. Chem. 37, 3443–3451.  PubMed Web of Science Google Scholar

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