1-{4-[Bis(4-fluoro­phen­yl)meth­yl]piperazin-1-yl}ethanone

A S Dayananda; H S Yathirajan; Amanda C Keeley; Jerry P Jasinski

doi:10.1107/S1600536812028097

. 2012 Jun 27;68(Pt 7):o2237. doi: 10.1107/S1600536812028097

1-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}ethanone

A S Dayananda ^a, H S Yathirajan ^a, Amanda C Keeley ^b, Jerry P Jasinski ^b,^*

PMCID: PMC3394028 PMID: 22798893

Abstract

In the title compound, C₁₉H₂₀F₂N₂O, the six-membered piperazine group adopts a slightly distorted chair conformation. The dihedral angle between the mean planes of the two benzene rings is 73.4 (6)°. The mean plane of the ethanone group is twisted from the mean planes of the two benzene rings by 66.7 (8) and 86.2 (6)°. In the crystal, C—H⋯O and C—H⋯F interactions link the molecules, forming a three-dimensional structure.

Related literature

For the biological activity of piperazines, see: Bogatcheva et al. (2006 ▶); Brockunier et al. (2004 ▶). For a review of pharmacological and toxicological information for piperazine derivatives, see: Elliott (2011 ▶). For related structures, see: Betz et al. (2011a ▶,b ▶); Dai et al. (2012 ▶); Dayananda et al. (2012a ▶,b ▶); Zhong et al. (2011 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For reference bond-length data, see Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₉H₂₀F₂N₂O
M _r = 330.37
Monoclinic,
a = 10.1701 (5) Å
b = 16.5521 (5) Å
c = 11.1690 (5) Å
β = 114.690 (5)°
V = 1708.27 (14) Å³
Z = 4
Cu Kα radiation
μ = 0.79 mm⁻¹
T = 173 K
0.48 × 0.32 × 0.22 mm

Data collection

Oxford Xcalibur Eos Gemini diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.802, T _max = 1.000
10536 measured reflections
3297 independent reflections
2809 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.155
S = 1.04
3297 reflections
218 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Oxford Diffraction, 2010 ▶); 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.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812028097/zj2086sup1.cif

e-68-o2237-sup1.cif^{(19.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812028097/zj2086Isup2.hkl

e-68-o2237-Isup2.hkl^{(161.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812028097/zj2086Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13⋯O1ⁱ	0.93	2.46	3.371 (2)	167
C15—H15⋯O1ⁱ	0.93	2.55	3.351 (3)	145
C18—H18⋯F2ⁱⁱ	0.93	2.54	3.319 (3)	142

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

ASD thanks the University of Mysore for research facilities. JPJ acknowledges the NSF–MRI program (grant No. CHE1039027) for funds to purchase the X-ray diffractometer.

supplementary crystallographic information

Comment

4,4'-Difluorobenzhydryl piperazine is an intermediate for the preparation of flunarizine which is a calcium channel blocker. Piperazines are among the most important building blocks in today's drug discovery and are found in biologically active compounds across a number of different therapeutic areas (Brockunier et al., 2004; Bogatcheva et al., 2006). A review on the current pharmacological and toxicological information for piperazine derivatives is described (Elliott, 2011).

The crystal structures of 4-[bis(4-fluorophenyl)methyl]piperazin-1-ium 2-(2-phenylethyl) benzoate (Betz et al., 2011a), 4-[bis(4-fluorophenyl)methyl]piperazin-1-ium picrate (Betz et al., 2011b), (E)-1-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-3-(4-ethoxyphenyl) prop-2-en-1-one (Zhong et al., 2011), 4-[bis(4-fluorophenyl) methyl]piperazin-1-ium bis(trichloroacetate) 0.4-hydrate (Dayananda et al., 2012a), 4-[bis(4-fluorophenyl)methyl] piperazin-1-ium 2-hydroxybenzoate 2-hydroxybenzoic acid monosolvate (Dayananda et al., 2012b) and 1-[bis(4-fluorophenyl) methyl]-4-[2-(2-methylphenoxy)ethyl]piperazine (Dai et al., 2012) have been reported. In the course of our studies on the salts of piperazines and in view of the importance of piperazines, this paper reports the crystal and molecular structure of the title compound, C₁₉H₂₀F₂N₂O, (I), which was accidentally obtained by the reaction of 4,4'-difluorobenzhydryl piperazine and acetyl salicylic acid.

In the asymmetric unit of the title compound, (I), the 6-membered piperazine group (N1/C3/C4/N2/C5/C6) adopts a slightly distorted chair conformation with puckering parameters Q, θ and φ of 0.568 (9) Å, 172.2 (7)°, and 350.979 (8)° (Cremer & Pople, 1975), respectively (Fig. 1). For an ideal chair θ has a value of 0 or 180°. Bond lengths are in normal ranges (Allen et al., 1987). The dihedral angle between the mean planes of the two benzene rings is 73.4 (6)°. The mean plane of the ethanone group (C1/C2/O1/N1) is twisted from the mean planes of the two benzene rings by 66.7 (8)° and 86.2 (6)°. Weak C—H···O and C—H···F intermolecular interactions (Table 1) are observed providing increased stability with crystal packing (Fig. 2).

Experimental

4,4'-Difluorobenzhydryl piperazine was obtained from R. L. Fine Chem., Bengaluru, India. 4,4'-Difluorobenzhydryl piperazine (2.88 g, 0.01 mol) was dissolved in 10 ml of absolute ethanol and acetylsalicylic acid (1.81 g, 0.01 mol) was also dissolved in 10 ml of absolute ethanol. Both the solutions were mixed and stirred in a beaker at 333 K for 30 min. The mixture was kept aside for a day at room temperature. The compound formed was filtered and dried in a vacuum desiccator over phosphorous pentoxide. The compound was recrystallized from a mixture of toluene and dimethyl formamide by slow evaporation (m.p. 418–423 K).