supplementary materials


hb6564 scheme

Acta Cryst. (2012). E68, o173    [ doi:10.1107/S160053681105327X ]

N-{2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethyl}phthalimide

Y. Shao, D. An, M. Zhou, L. Liu and X.-Q. Sun

Abstract top

In the title compound, C16H21N3O3, the piperazine ring adopts a chair conformation, with its N-C bonds in pseudo-equatorial orientations. In the crystal, molecules are linked by O-H...N hydrogen bonds, generating C(5) chains propagating in [101]. Weak aromatic [pi]-[pi] stacking interactions also occur [centroid-centroid separation = 3.899 (1) Å].

Comment top

Piperazine derivatives in pharmaceutical and chemical industries have a wide range of applications (Tian, et al., 2011). The title compound, which is an intermediate for our designed drug, was synthesized from 2-(2-bromoethyl)phthalimide and 2-(piperazin-1-yl)ethanol in the presence of K2CO3 as acid-acceptor (Ghosh, et al., 2010). In the molecule of the title compound (Fig. 1), the phthalimide fragment is planar, with r.m.s. deviation of 0.02 Å. The six-membered piperazine ring adopts the chair conformation. In the crystal, the crystal packing is stabilized by O—H···N hydrogen bonding interactions and ππ interactions involving the benzene ring (Fig. 2). For the O—H···N the hydrogen bonding interactions, the relevant distances and angles are: O3···H3A= 0.821 Å, H3A···N3 =1.997 Å, O3···N3[i]= 2.811 (3) Å, and O3—H3A···N3[i]= 171.3°. And for the π ···π interactions, the relevant distances are: Cg···Cg[ii] = 3.899 (1)Å [symmetry code: (i) x - 1/2, 1/2 - y, -1/2 + z; (ii) 2 - x, -y, 2 - z; Cg is the centroid of the C1–C2–C3–C4–C5–C6 ring].

Related literature top

For general background to piperazine derivatives, see: Tian et al. (2011). For the preparation, see: Ghosh et al. (2010).

Experimental top

A suspension of 2-(2-bromoethyl)phthalimide (0.63 g, 2.5 mmol), 2-(piperazin-1-yl)ethanol (0.36 g, 2.8 mmol) and K2CO3 (0.90 g, 6.5 mmol) in 15 ml acetonitrile was stirred at room temperature for 0.5 h, and then heated to reflux for 10 h. After cooling and filtration, the filter residue was washed with CH3CN. And the filtrate and washing were combined prior to removing the solvent under vacuum. A white powder (0.55 g, 1.8 mmol) was obtained after recrystallization from ethyl acetate/ petroleum ether. Colourless blocks were obtained by slow evaporation of a CH3OH solution.

Refinement top

All the H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances of 0.93–0.97 Å, and with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); 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. View of the title compound, showing 50% probability ellipsoids.
[Figure 2] Fig. 2. Perspective view of the title compound along c direction. Labels of atoms have been omitted for clarity.
(I) top
Crystal data top
C16H21N3O3F(000) = 648
Mr = 303.36Dx = 1.280 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 5733 reflections
a = 5.8109 (6) Åθ = 2.8–29.9°
b = 37.012 (4) ŵ = 0.09 mm1
c = 7.3537 (8) ÅT = 296 K
β = 95.634 (2)°Block, colorless
V = 1573.9 (3) Å30.25 × 0.22 × 0.20 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
2775 independent reflections
Radiation source: fine-focus sealed tube2537 reflections with I > 2σ(I)
graphiteRint = 0.025
φ and ω scansθmax = 25.1°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 66
Tmin = 0.978, Tmax = 0.982k = 4443
8562 measured reflectionsl = 86
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)] = 0.057H-atom parameters constrained
wR(F2) = 0.161 w = 1/[σ2(Fo2) + (0.081P)2 + 1.190P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
2775 reflectionsΔρmax = 0.53 e Å3
201 parametersΔρmin = 0.38 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: 0.024 (4)
Crystal data top
C16H21N3O3V = 1573.9 (3) Å3
Mr = 303.36Z = 4
Monoclinic, P21/nMo Kα radiation
a = 5.8109 (6) ŵ = 0.09 mm1
b = 37.012 (4) ÅT = 296 K
c = 7.3537 (8) Å0.25 × 0.22 × 0.20 mm
β = 95.634 (2)°
Data collection top
Bruker APEXII CCD
diffractometer
2775 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
2537 reflections with I > 2σ(I)
Tmin = 0.978, Tmax = 0.982Rint = 0.025
8562 measured reflectionsθmax = 25.1°
Refinement top
R[F2 > 2σ(F2)] = 0.057H-atom parameters constrained
wR(F2) = 0.161Δρmax = 0.53 e Å3
S = 1.00Δρmin = 0.38 e Å3
2775 reflectionsAbsolute structure: ?
201 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
C10.8296 (4)0.04878 (5)0.9736 (3)0.0374 (5)
C20.7865 (4)0.02500 (6)1.1105 (3)0.0471 (6)
H20.65300.01101.10240.057*
C30.9495 (5)0.02280 (7)1.2607 (3)0.0522 (6)
H30.92600.00671.35430.063*
C41.1458 (5)0.04391 (7)1.2744 (3)0.0538 (6)
H41.25180.04191.37730.065*
C51.1882 (4)0.06811 (7)1.1375 (3)0.0496 (6)
H51.31990.08251.14660.060*
C61.0265 (4)0.06991 (6)0.9870 (3)0.0389 (5)
C71.0250 (4)0.09147 (6)0.8160 (3)0.0429 (5)
C80.6974 (4)0.05594 (6)0.7936 (3)0.0414 (5)
C90.7626 (5)0.09520 (6)0.5245 (3)0.0473 (6)
H9A0.66590.07760.45580.057*
H9B0.90240.09820.46400.057*
C100.6356 (4)0.13096 (6)0.5228 (3)0.0398 (5)
H10A0.50430.12880.59400.048*
H10B0.73800.14940.57890.048*
C110.7464 (4)0.15193 (6)0.2321 (3)0.0412 (5)
H11A0.85260.13180.22900.049*
H11B0.83000.17210.29160.049*
C120.6585 (4)0.16244 (6)0.0396 (3)0.0432 (5)
H12A0.78810.16870.02800.052*
H12B0.57850.14210.02100.052*
C130.3083 (4)0.18340 (7)0.1460 (3)0.0472 (6)
H13A0.22230.16350.08650.057*
H13B0.20440.20380.15010.057*
C140.3970 (4)0.17252 (6)0.3390 (3)0.0439 (5)
H14A0.47680.19280.40060.053*
H14B0.26760.16610.40640.053*
C150.4241 (5)0.20357 (6)0.1491 (3)0.0519 (6)
H15A0.32100.18500.20320.062*
H15B0.55760.20450.21840.062*
C160.3036 (6)0.23880 (8)0.1657 (4)0.0696 (8)
H16A0.14830.23670.12900.083*
H16B0.38700.25680.08920.083*
N10.8237 (3)0.08156 (5)0.7086 (2)0.0419 (5)
N20.5552 (3)0.14180 (5)0.3366 (2)0.0360 (4)
N30.5012 (3)0.19317 (5)0.0404 (2)0.0403 (5)
O10.5199 (3)0.04208 (5)0.7274 (2)0.0618 (5)
O21.1636 (3)0.11320 (5)0.7720 (3)0.0648 (6)
O30.2965 (5)0.24873 (7)0.3547 (3)0.0921 (8)
H3A0.20180.26500.37660.138*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0419 (11)0.0314 (10)0.0381 (11)0.0005 (8)0.0002 (9)0.0024 (8)
C20.0529 (14)0.0431 (12)0.0443 (12)0.0071 (10)0.0002 (10)0.0086 (10)
C30.0676 (16)0.0493 (13)0.0383 (12)0.0031 (12)0.0014 (11)0.0086 (10)
C40.0582 (15)0.0584 (15)0.0416 (13)0.0088 (12)0.0115 (11)0.0004 (11)
C50.0417 (12)0.0526 (14)0.0524 (14)0.0020 (10)0.0059 (10)0.0047 (11)
C60.0398 (11)0.0342 (10)0.0420 (12)0.0016 (8)0.0011 (9)0.0001 (9)
C70.0434 (12)0.0382 (11)0.0473 (12)0.0015 (9)0.0054 (10)0.0020 (9)
C80.0452 (12)0.0343 (11)0.0432 (12)0.0016 (9)0.0034 (9)0.0041 (9)
C90.0655 (15)0.0407 (12)0.0354 (11)0.0044 (10)0.0033 (10)0.0052 (9)
C100.0457 (12)0.0431 (12)0.0310 (10)0.0030 (9)0.0059 (9)0.0049 (8)
C110.0380 (11)0.0497 (12)0.0364 (11)0.0053 (9)0.0067 (9)0.0062 (9)
C120.0481 (12)0.0487 (13)0.0335 (11)0.0026 (10)0.0076 (9)0.0035 (9)
C130.0440 (12)0.0513 (13)0.0448 (13)0.0093 (10)0.0025 (10)0.0073 (10)
C140.0417 (12)0.0531 (13)0.0375 (12)0.0081 (10)0.0067 (9)0.0072 (10)
C150.0728 (17)0.0457 (13)0.0350 (12)0.0036 (12)0.0063 (11)0.0025 (10)
C160.098 (2)0.0624 (17)0.0448 (14)0.0265 (16)0.0084 (14)0.0069 (12)
N10.0491 (11)0.0367 (9)0.0391 (10)0.0018 (8)0.0011 (8)0.0075 (8)
N20.0373 (9)0.0403 (9)0.0307 (9)0.0014 (7)0.0046 (7)0.0047 (7)
N30.0502 (11)0.0404 (10)0.0291 (9)0.0017 (8)0.0018 (7)0.0031 (7)
O10.0588 (11)0.0610 (11)0.0604 (11)0.0196 (9)0.0195 (9)0.0150 (9)
O20.0597 (11)0.0635 (11)0.0720 (13)0.0211 (9)0.0098 (9)0.0157 (9)
O30.136 (2)0.0818 (15)0.0558 (12)0.0490 (15)0.0048 (13)0.0216 (11)
Geometric parameters (Å, °) top
C1—C21.379 (3)C11—N21.460 (3)
C1—C61.381 (3)C11—C121.508 (3)
C1—C81.487 (3)C11—H11A0.9700
C2—C31.385 (3)C11—H11B0.9700
C2—H20.9300C12—N31.460 (3)
C3—C41.378 (4)C12—H12A0.9700
C3—H30.9300C12—H12B0.9700
C4—C51.387 (4)C13—N31.470 (3)
C4—H40.9300C13—C141.516 (3)
C5—C61.381 (3)C13—H13A0.9700
C5—H50.9300C13—H13B0.9700
C6—C71.489 (3)C14—N21.463 (3)
C7—O21.204 (3)C14—H14A0.9700
C7—N11.395 (3)C14—H14B0.9700
C8—O11.210 (3)C15—N31.472 (3)
C8—N11.385 (3)C15—C161.479 (4)
C9—N11.456 (3)C15—H15A0.9700
C9—C101.515 (3)C15—H15B0.9700
C9—H9A0.9700C16—O31.435 (3)
C9—H9B0.9700C16—H16A0.9700
C10—N21.459 (3)C16—H16B0.9700
C10—H10A0.9700O3—H3A0.8200
C10—H10B0.9700
C2—C1—C6121.2 (2)H11A—C11—H11B108.1
C2—C1—C8130.4 (2)N3—C12—C11110.60 (17)
C6—C1—C8108.36 (18)N3—C12—H12A109.5
C1—C2—C3117.4 (2)C11—C12—H12A109.5
C1—C2—H2121.3N3—C12—H12B109.5
C3—C2—H2121.3C11—C12—H12B109.5
C4—C3—C2121.5 (2)H12A—C12—H12B108.1
C4—C3—H3119.3N3—C13—C14110.70 (18)
C2—C3—H3119.3N3—C13—H13A109.5
C3—C4—C5121.1 (2)C14—C13—H13A109.5
C3—C4—H4119.4N3—C13—H13B109.5
C5—C4—H4119.4C14—C13—H13B109.5
C6—C5—C4117.2 (2)H13A—C13—H13B108.1
C6—C5—H5121.4N2—C14—C13110.55 (18)
C4—C5—H5121.4N2—C14—H14A109.5
C5—C6—C1121.6 (2)C13—C14—H14A109.5
C5—C6—C7130.5 (2)N2—C14—H14B109.5
C1—C6—C7107.87 (18)C13—C14—H14B109.5
O2—C7—N1124.7 (2)H14A—C14—H14B108.1
O2—C7—C6129.5 (2)N3—C15—C16114.0 (2)
N1—C7—C6105.80 (18)N3—C15—H15A108.8
O1—C8—N1125.2 (2)C16—C15—H15A108.8
O1—C8—C1128.9 (2)N3—C15—H15B108.8
N1—C8—C1105.84 (17)C16—C15—H15B108.8
N1—C9—C10112.62 (18)H15A—C15—H15B107.7
N1—C9—H9A109.1O3—C16—C15105.9 (2)
C10—C9—H9A109.1O3—C16—H16A110.6
N1—C9—H9B109.1C15—C16—H16A110.6
C10—C9—H9B109.1O3—C16—H16B110.6
H9A—C9—H9B107.8C15—C16—H16B110.6
N2—C10—C9111.02 (17)H16A—C16—H16B108.7
N2—C10—H10A109.4C8—N1—C7112.13 (18)
C9—C10—H10A109.4C8—N1—C9124.43 (19)
N2—C10—H10B109.4C7—N1—C9123.34 (19)
C9—C10—H10B109.4C11—N2—C10111.95 (16)
H10A—C10—H10B108.0C11—N2—C14108.56 (17)
N2—C11—C12110.79 (18)C10—N2—C14110.22 (16)
N2—C11—H11A109.5C12—N3—C13108.70 (17)
C12—C11—H11A109.5C12—N3—C15109.44 (17)
N2—C11—H11B109.5C13—N3—C15112.78 (18)
C12—C11—H11B109.5C16—O3—H3A109.5
C6—C1—C2—C30.8 (3)O1—C8—N1—C7177.6 (2)
C8—C1—C2—C3176.4 (2)C1—C8—N1—C70.3 (2)
C1—C2—C3—C41.0 (4)O1—C8—N1—C91.1 (4)
C2—C3—C4—C50.3 (4)C1—C8—N1—C9176.87 (19)
C3—C4—C5—C60.4 (4)O2—C7—N1—C8179.9 (2)
C4—C5—C6—C10.5 (3)C6—C7—N1—C80.1 (2)
C4—C5—C6—C7177.1 (2)O2—C7—N1—C93.2 (4)
C2—C1—C6—C50.1 (3)C6—C7—N1—C9176.69 (19)
C8—C1—C6—C5177.7 (2)C10—C9—N1—C897.9 (3)
C2—C1—C6—C7178.2 (2)C10—C9—N1—C785.9 (3)
C8—C1—C6—C70.4 (2)C12—C11—N2—C10179.14 (17)
C5—C6—C7—O22.3 (4)C12—C11—N2—C1459.0 (2)
C1—C6—C7—O2179.9 (2)C9—C10—N2—C1169.7 (2)
C5—C6—C7—N1177.6 (2)C9—C10—N2—C14169.38 (19)
C1—C6—C7—N10.2 (2)C13—C14—N2—C1158.3 (2)
C2—C1—C8—O10.1 (4)C13—C14—N2—C10178.72 (18)
C6—C1—C8—O1177.4 (2)C11—C12—N3—C1358.2 (2)
C2—C1—C8—N1178.0 (2)C11—C12—N3—C15178.21 (19)
C6—C1—C8—N10.4 (2)C14—C13—N3—C1257.8 (2)
N1—C9—C10—N2173.76 (18)C14—C13—N3—C15179.35 (18)
N2—C11—C12—N360.1 (2)C16—C15—N3—C12168.0 (2)
N3—C13—C14—N258.9 (3)C16—C15—N3—C1370.9 (3)
N3—C15—C16—O3165.2 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···N3i0.822.002.811 (3)171
Symmetry codes: (i) x−1/2, −y+1/2, z−1/2.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
O3—H3A···N3i0.822.002.811 (3)171
Symmetry codes: (i) x−1/2, −y+1/2, z−1/2.
Acknowledgements top

We gratefully acknowledge the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Changzhou University (ZMF10020010) for financial support.

references
References top

Bruker (2000). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

Ghosh, B., Antonio, T., Zhen, J., Kharkar, P., Reith, M. E. A. & Dutta, A. K. (2010). J. Med. Chem. 53, 1023–1037.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Tian, Z., Wei, X., Liang, J., Liu, R. & Zhang, Y. (2011). Yingyong Huagong, 40, 1648–1652.