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Acta Crystallogr Sect E Struct Rep Online. 2010 July 1; 66(Pt 7): o1727.
Published online 2010 June 23. doi:  10.1107/S1600536810022816
PMCID: PMC3006790

N-{2-[4-(2-Meth­oxy­phen­yl)piperazin-1-yl]eth­yl}pyridin-2-amine monohydrate

Abstract

In the title compound, C18H24N4O·H2O, the piperizine ring adopts a chair conformation and the dihedral angle between the phenyl and pyridine rings is 39.9 (3)°. The comformations of the attachment of the anisole and N-ethyl­pyridin-2-amine groups to the piperazine ring are +anti­periplanar. An intra­molecular C—H(...)O inter­action occurs. In the crystal, the water mol­ecule links the mol­ecules into chains through O—H(...)N hydrogen bonds. Weak N—H(...)O, C—H(...)N and C—H(...)O inter­actions further stabilize the crystal structure.

Related literature

For the use of the title compound in the synthesis of receptor imaging agents, see: Lebars et al. (1998 [triangle]); Zhuang et al. (1994 [triangle]).

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Object name is e-66-o1727-scheme1.jpg

Experimental

Crystal data

  • C18H24N4O·H2O
  • M r = 330.43
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1727-efi1.jpg
  • a = 13.451 (3) Å
  • b = 19.847 (4) Å
  • c = 6.8596 (15) Å
  • V = 1831.2 (7) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 153 K
  • 0.40 × 0.23 × 0.09 mm

Data collection

  • Rigaku R-AXIS Spider diffractometer
  • 14086 measured reflections
  • 2261 independent reflections
  • 1985 reflections with I > 2σ(I)
  • R int = 0.049

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.091
  • S = 1.00
  • 2261 reflections
  • 230 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.15 e Å−3

Data collection: RAPID-AUTO (Rigaku, 2004 [triangle]); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810022816/pv2288sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810022816/pv2288Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

This work was supported by the Natural Science Foundation of Jiangsu Province (BK2008112) and the Science Foundation of the Health Department of Jiangsu Province (H200624).

supplementary crystallographic information

Comment

N-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)pyridin-2-amine, (I), is an important intermediate product in the synthesis of 131I-MPPI (Zhuang et al., 1994) and 18F-MPPF (Lebars et al., 1998), serotonin(5-HT1A) receptor imaging agents (131I-MPPI = 4-(2'-methoxypheny)-1-[2'-(N-2''-pyridinyl)- p-131I-iodobenzamido]ethyl-piperazine and 18F-MPPF = 4-(2'-methoxyphenyl)-1-[2'-(N-2''-pyridinyl) -p-18F-fluorobenzamido]ethylpiperazine). We report here the crystal structure of (I).hydrate (Fig. 1). The molecule of (I) consists of an anisole and an N-ethylpyridin-2-amine arms connected to a piperazine ring. The piperazine ring adopts a chair conformation. The dihedral angle between the phenyl and pyridine rings is 39.9 (3)°. The comformation of the attachment of the anisole and N-ethylpyridin-2-amine groups to the piperazine ring are best described by the torsion angles of 168.35 (19)° and 179.45 (17)° for C12—N4—C10—C11 and C7—N3—C8—C9, respectively; i.e. they adopt +antiperiplanar conformations. The molecules are linked through hydrogen-bonding interactions of types O—H···O, N—H···O and C—H···O (Table 1).

Experimental

The title compound was synthesized according to the method reported in the literature (Zhuang et al., 1994) and crystallized from a mixed solvent composed of acetone and water (1:1); colorless block-shaped crystals were obtained after several days.

Refinement

An absolute structure could not be determined dfue to lack of sufficient dispersion effects. Therefore, Friedel pairs (1894) were merged. Positional parameters of all the H atoms bonded to C atoms were calculated geometrically and were allowed to ride on the C atoms to which they were bonded, with C—H distances of 0.95Å (CH), 0.98Å (CH3) or 0.99Å (CH2), and with Uiso(H) = 1.2Ueq of the parent atoms. The H-atoms bonded to N and O atoms were taken from a difference map and were allowed to refine freely.

Figures

Fig. 1.
A view of the title compound with the atomic numbering scheme. Displacement ellipsoids were drawn at the 50% probability level.

Crystal data

C18H24N4O·H2OF(000) = 712
Mr = 330.43Dx = 1.199 Mg m3
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 4880 reflections
a = 13.451 (3) Åθ = 3.0–27.5°
b = 19.847 (4) ŵ = 0.08 mm1
c = 6.8596 (15) ÅT = 153 K
V = 1831.2 (7) Å3Prism, colorless
Z = 40.40 × 0.23 × 0.09 mm

Data collection

Rigaku R-AXIS Spider diffractometer1985 reflections with I > 2σ(I)
Radiation source: Rotating AnodeRint = 0.049
graphiteθmax = 27.5°, θmin = 3.0°
ω scansh = −17→17
14086 measured reflectionsk = −25→22
2261 independent reflectionsl = −8→8

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.091H atoms treated by a mixture of independent and constrained refinement
S = 1.00w = 1/[σ2(Fo2) + (0.0505P)2 + 0.160P] where P = (Fo2 + 2Fc2)/3
2261 reflections(Δ/σ)max < 0.001
230 parametersΔρmax = 0.18 e Å3
1 restraintΔρmin = −0.15 e Å3

Special details

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)

xyzUiso*/Ueq
O10.43965 (12)0.13354 (8)0.6019 (3)0.0352 (4)
O20.35365 (13)0.46544 (8)0.6564 (3)0.0296 (4)
N10.75758 (14)0.58179 (9)0.4876 (3)0.0254 (4)
N20.69260 (15)0.52222 (10)0.7505 (3)0.0258 (4)
N30.52175 (13)0.38007 (8)0.6319 (3)0.0218 (4)
N40.44650 (13)0.25939 (8)0.4558 (3)0.0222 (4)
C10.82362 (19)0.62843 (12)0.4242 (4)0.0341 (6)
H10.82740.63640.28790.041*
C20.88518 (19)0.66487 (13)0.5425 (4)0.0357 (6)
H20.93080.69660.49000.043*
C30.87886 (17)0.65392 (12)0.7421 (4)0.0316 (6)
H30.91950.67890.82930.038*
C40.81411 (17)0.60715 (11)0.8117 (3)0.0267 (5)
H40.80950.59900.94790.032*
C50.75372 (15)0.57077 (10)0.6798 (3)0.0212 (5)
C60.62161 (16)0.48524 (10)0.6333 (3)0.0257 (5)
H6A0.64900.47760.50120.031*
H6B0.55930.51150.62040.031*
C70.60037 (17)0.41825 (11)0.7313 (3)0.0251 (5)
H7A0.66200.39100.73330.030*
H7B0.58020.42650.86810.030*
C80.55437 (16)0.35756 (11)0.4378 (3)0.0228 (5)
H8A0.61450.32910.45090.027*
H8B0.57180.39720.35720.027*
C90.47335 (16)0.31789 (10)0.3383 (3)0.0243 (5)
H9A0.41420.34690.31950.029*
H9B0.49660.30290.20840.029*
C100.41288 (17)0.28054 (11)0.6490 (3)0.0283 (5)
H10A0.39670.24040.72880.034*
H10B0.35200.30830.63670.034*
C110.49388 (19)0.32103 (11)0.7477 (3)0.0286 (5)
H11A0.47040.33590.87760.034*
H11B0.55300.29210.76710.034*
C120.38607 (15)0.21023 (10)0.3614 (3)0.0243 (5)
C130.33403 (17)0.22331 (11)0.1915 (4)0.0300 (5)
H130.33350.26780.14030.036*
C140.28283 (19)0.17297 (13)0.0947 (4)0.0394 (6)
H140.24760.1831−0.02180.047*
C150.28287 (19)0.10831 (13)0.1670 (4)0.0388 (6)
H150.24840.07360.09970.047*
C160.33326 (18)0.09392 (12)0.3380 (4)0.0338 (6)
H160.33220.04940.38890.041*
C170.38516 (16)0.14392 (11)0.4357 (4)0.0274 (5)
C180.4404 (2)0.06745 (13)0.6815 (5)0.0505 (8)
H18A0.37200.05300.70720.061*
H18B0.47820.06740.80360.061*
H18C0.47150.03640.58860.061*
H0A0.320 (2)0.4515 (15)0.757 (5)0.051 (9)*
H2N0.686 (2)0.5217 (13)0.871 (4)0.033 (7)*
H0B0.400 (2)0.4384 (17)0.647 (6)0.063 (11)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0412 (9)0.0224 (8)0.0420 (10)−0.0083 (7)−0.0081 (9)0.0084 (8)
O20.0339 (9)0.0310 (9)0.0239 (9)0.0051 (8)0.0037 (8)0.0022 (7)
N10.0265 (10)0.0241 (10)0.0257 (10)−0.0036 (8)−0.0005 (8)−0.0006 (8)
N20.0314 (10)0.0257 (9)0.0203 (10)−0.0092 (8)−0.0007 (9)−0.0035 (8)
N30.0277 (9)0.0194 (8)0.0183 (9)−0.0054 (7)0.0004 (8)0.0000 (7)
N40.0256 (9)0.0182 (8)0.0228 (9)−0.0045 (7)−0.0002 (8)−0.0013 (8)
C10.0380 (14)0.0343 (13)0.0300 (13)−0.0063 (11)0.0025 (11)0.0049 (11)
C20.0341 (13)0.0321 (13)0.0410 (15)−0.0149 (11)0.0015 (12)0.0029 (11)
C30.0253 (11)0.0277 (12)0.0418 (14)−0.0039 (10)−0.0071 (11)−0.0046 (11)
C40.0261 (11)0.0277 (11)0.0263 (12)−0.0004 (10)−0.0034 (10)−0.0037 (10)
C50.0206 (10)0.0175 (10)0.0256 (11)0.0019 (8)0.0008 (9)−0.0023 (9)
C60.0300 (11)0.0206 (10)0.0264 (12)−0.0066 (9)−0.0063 (10)0.0021 (9)
C70.0306 (11)0.0240 (11)0.0208 (11)−0.0045 (9)−0.0066 (10)−0.0002 (9)
C80.0256 (10)0.0197 (10)0.0231 (11)−0.0043 (9)0.0033 (10)0.0005 (9)
C90.0289 (11)0.0198 (10)0.0242 (11)−0.0032 (9)−0.0005 (10)−0.0014 (9)
C100.0350 (12)0.0241 (11)0.0258 (12)−0.0061 (9)0.0079 (11)−0.0004 (10)
C110.0409 (13)0.0247 (11)0.0204 (11)−0.0102 (10)−0.0004 (11)0.0019 (10)
C120.0203 (10)0.0233 (10)0.0292 (12)−0.0034 (9)0.0019 (10)−0.0044 (10)
C130.0307 (12)0.0273 (12)0.0320 (13)−0.0040 (10)−0.0009 (11)−0.0030 (10)
C140.0384 (13)0.0416 (14)0.0381 (14)−0.0114 (11)−0.0092 (13)−0.0024 (13)
C150.0379 (13)0.0358 (13)0.0427 (14)−0.0144 (11)−0.0008 (13)−0.0110 (12)
C160.0330 (13)0.0237 (11)0.0448 (15)−0.0093 (10)0.0057 (12)−0.0036 (11)
C170.0243 (11)0.0245 (11)0.0335 (13)−0.0024 (9)0.0026 (10)−0.0029 (10)
C180.0586 (18)0.0296 (13)0.063 (2)−0.0095 (12)−0.0168 (17)0.0175 (14)

Geometric parameters (Å, °)

O1—C171.371 (3)C7—H7A0.9900
O1—C181.421 (3)C7—H7B0.9900
O2—H0A0.88 (3)C8—C91.508 (3)
O2—H0B0.83 (3)C8—H8A0.9900
N1—C51.338 (3)C8—H8B0.9900
N1—C11.354 (3)C9—H9A0.9900
N2—C51.356 (3)C9—H9B0.9900
N2—C61.448 (3)C10—C111.514 (3)
N2—H2N0.83 (3)C10—H10A0.9900
N3—C111.464 (3)C10—H10B0.9900
N3—C71.469 (3)C11—H11A0.9900
N3—C81.472 (3)C11—H11B0.9900
N4—C121.426 (3)C12—C131.384 (3)
N4—C91.459 (3)C12—C171.411 (3)
N4—C101.462 (3)C13—C141.383 (3)
C1—C21.366 (4)C13—H130.9500
C1—H10.9500C14—C151.376 (4)
C2—C31.389 (4)C14—H140.9500
C2—H20.9500C15—C161.385 (4)
C3—C41.360 (3)C15—H150.9500
C3—H30.9500C16—C171.386 (3)
C4—C51.414 (3)C16—H160.9500
C4—H40.9500C18—H18A0.9800
C6—C71.517 (3)C18—H18B0.9800
C6—H6A0.9900C18—H18C0.9800
C6—H6B0.9900
C17—O1—C18117.5 (2)H8A—C8—H8B108.1
H0A—O2—H0B105 (3)N4—C9—C8110.15 (18)
C5—N1—C1117.0 (2)N4—C9—H9A109.6
C5—N2—C6124.1 (2)C8—C9—H9A109.6
C5—N2—H2N115.1 (19)N4—C9—H9B109.6
C6—N2—H2N118.7 (19)C8—C9—H9B109.6
C11—N3—C7110.20 (17)H9A—C9—H9B108.1
C11—N3—C8108.93 (16)N4—C10—C11109.59 (18)
C7—N3—C8111.22 (17)N4—C10—H10A109.8
C12—N4—C9115.76 (18)C11—C10—H10A109.8
C12—N4—C10115.61 (17)N4—C10—H10B109.8
C9—N4—C10110.42 (16)C11—C10—H10B109.8
N1—C1—C2124.7 (2)H10A—C10—H10B108.2
N1—C1—H1117.7N3—C11—C10111.48 (19)
C2—C1—H1117.7N3—C11—H11A109.3
C1—C2—C3117.7 (2)C10—C11—H11A109.3
C1—C2—H2121.1N3—C11—H11B109.3
C3—C2—H2121.1C10—C11—H11B109.3
C4—C3—C2119.5 (2)H11A—C11—H11B108.0
C4—C3—H3120.3C13—C12—C17118.3 (2)
C2—C3—H3120.3C13—C12—N4122.9 (2)
C3—C4—C5119.5 (2)C17—C12—N4118.6 (2)
C3—C4—H4120.3C14—C13—C12121.4 (2)
C5—C4—H4120.3C14—C13—H13119.3
N1—C5—N2119.5 (2)C12—C13—H13119.3
N1—C5—C4121.7 (2)C15—C14—C13120.0 (2)
N2—C5—C4118.8 (2)C15—C14—H14120.0
N2—C6—C7108.79 (18)C13—C14—H14120.0
N2—C6—H6A109.9C14—C15—C16119.9 (2)
C7—C6—H6A109.9C14—C15—H15120.1
N2—C6—H6B109.9C16—C15—H15120.1
C7—C6—H6B109.9C15—C16—C17120.6 (2)
H6A—C6—H6B108.3C15—C16—H16119.7
N3—C7—C6112.45 (17)C17—C16—H16119.7
N3—C7—H7A109.1O1—C17—C16124.3 (2)
C6—C7—H7A109.1O1—C17—C12115.84 (19)
N3—C7—H7B109.1C16—C17—C12119.8 (2)
C6—C7—H7B109.1O1—C18—H18A109.5
H7A—C7—H7B107.8O1—C18—H18B109.5
N3—C8—C9110.64 (18)H18A—C18—H18B109.5
N3—C8—H8A109.5O1—C18—H18C109.5
C9—C8—H8A109.5H18A—C18—H18C109.5
N3—C8—H8B109.5H18B—C18—H18C109.5
C9—C8—H8B109.5
C5—N1—C1—C2−0.5 (4)C7—N3—C11—C10−179.99 (19)
N1—C1—C2—C3−0.8 (4)C8—N3—C11—C10−57.7 (2)
C1—C2—C3—C41.3 (4)N4—C10—C11—N358.0 (2)
C2—C3—C4—C5−0.5 (4)C9—N4—C12—C13−16.5 (3)
C1—N1—C5—N2−176.7 (2)C10—N4—C12—C13114.8 (2)
C1—N1—C5—C41.4 (3)C9—N4—C12—C17158.5 (2)
C6—N2—C5—N1−7.0 (3)C10—N4—C12—C17−70.1 (3)
C6—N2—C5—C4174.9 (2)C17—C12—C13—C14−0.6 (3)
C3—C4—C5—N1−0.9 (3)N4—C12—C13—C14174.5 (2)
C3—C4—C5—N2177.2 (2)C12—C13—C14—C150.1 (4)
C5—N2—C6—C7155.8 (2)C13—C14—C15—C160.8 (4)
C11—N3—C7—C6−171.59 (19)C14—C15—C16—C17−1.1 (4)
C8—N3—C7—C667.5 (2)C18—O1—C17—C16−1.8 (3)
N2—C6—C7—N3174.53 (18)C18—O1—C17—C12179.8 (2)
C11—N3—C8—C957.8 (2)C15—C16—C17—O1−177.7 (2)
C7—N3—C8—C9179.45 (17)C15—C16—C17—C120.6 (4)
C12—N4—C9—C8−167.51 (17)C13—C12—C17—O1178.7 (2)
C10—N4—C9—C858.7 (2)N4—C12—C17—O13.4 (3)
N3—C8—C9—N4−58.9 (2)C13—C12—C17—C160.3 (3)
C12—N4—C10—C11168.35 (19)N4—C12—C17—C16−175.0 (2)
C9—N4—C10—C11−57.8 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H0A···N1i0.87 (3)2.01 (3)2.877 (3)179 (4)
O2—H0B···N30.83 (3)2.01 (3)2.831 (2)174 (3)
N2—H2N···O2i0.83 (3)2.05 (3)2.864 (3)168 (3)
C3—H3···N4ii0.952.563.471 (3)161
C10—H10A···O10.992.362.957 (3)118
C15—H15···O2iii0.952.583.379 (3)142

Symmetry codes: (i) −x+1, −y+1, z+1/2; (ii) −x+3/2, y+1/2, z+1/2; (iii) −x+1/2, y−1/2, z−1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2288).

References

  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Lebars, D., Lemaire, C., Ginovart, N., Plenevaux, A., Aerts, J., Brihaye, C., Hassoun, W., Leviel, V., Mekhsian, P., Weissmann, D., Pujol, J. F., Luxen, A., & Comar, D. (1998). Nucl. Med. Biol. 25, 343–350. [PubMed]
  • Rigaku (2004). RAPID-AUTO Rigaku Corporation, Tokyo, Japan.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Zhuang, Z. P., Kung, M. P. & Kung, H. F. (1994). J. Med. Chem.37, 1406–1407. [PubMed]

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