1-Chloro-2-(4-phenyl­piperazin-1-yl)ethanone

Xu, Y.-J.; Jing, F.

doi:10.1107/S1600536809008216

organic compounds

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Volume 65| Part 6| June 2009| Page o1211

doi:10.1107/S1600536809008216

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1-Chloro-2-(4-phenylpiperazin-1-yl)ethanone

Yong-Ji Xu ^a ^* and Fei Jing ^a

^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 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

C₁₂H₁₅ClN₂O
M_r = 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 ) T_min = 0.940, T_max = 0.964
9264 measured reflections
2729 independent reflections
2151 reflections with I > 2σ(I)
R_int = 0.035

Refinement

R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.098
S = 1.07
2729 reflections
145 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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⋯Cg2^iv	0.97	3.09	4.0393 (12)	168
C12—H12A⋯Cg2^iv	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); cell refinement: 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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809008216/hg2461sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809008216/hg2461Isup2.hkl

checkCIF report

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···C_g2, C8—H8B···C_g2 and C12—H12A···C_g2 (C_g2 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.

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

	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).

1-Chloro-2-(4-phenylpiperazin-1-yl)ethanone top

Crystal data top

C₁₂H₁₅ClN₂O	F(000) = 504
M_r = 238.71	D_x = 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

Data collection top

Rigaku Saturn diffractometer	2729 independent reflections
Radiation source: rotating anode	2151 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.035
ω scans	θ_max = 27.9°, θ_min = 3.2°
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	h = −12→12
T_min = 0.940, T_max = 0.964	k = −8→11
9264 measured reflections	l = −16→19

Refinement top

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(F_o²) + (0.055P)² + 0.0763P] where P = (F_o² + 2F_c²)/3
2729 reflections	(Δ/σ)_max = 0.001
145 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₂H₁₅ClN₂O	V = 1149.9 (4) Å³
M_r = 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)°

Data collection top

Rigaku Saturn diffractometer	2729 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	2151 reflections with I > 2σ(I)
T_min = 0.940, T_max = 0.964	R_int = 0.035
9264 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	0 restraints
wR(F²) = 0.098	H-atom parameters constrained
S = 1.07	Δρ_max = 0.25 e Å⁻³
2729 reflections	Δρ_min = −0.26 e Å⁻³
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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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···Cg2^iv	0.97	3.09	4.0393 (12)	168
C12—H12A···Cg2^iv	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
M_r	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)
T_min, T_max	0.940, 0.964
No. of measured, independent and observed [I > 2σ(I)] reflections	9264, 2729, 2151
R_int	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
Δρ_max, Δρ_min (e Å⁻³)	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···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···Cg2^iv	0.97	3.09	4.0393 (12)	168
C12—H12A···Cg2^iv	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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