1-[Bis(4-fluoro­phen­yl)meth­yl]piperazine

A S Dayananda; Grzegorz Dutkiewicz; H S Yathirajan; A R Ramesha; Maciej Kubicki

doi:10.1107/S1600536812036902

. 2012 Aug 31;68(Pt 9):o2817. doi: 10.1107/S1600536812036902

1-[Bis(4-fluorophenyl)methyl]piperazine

A S Dayananda ^a, Grzegorz Dutkiewicz ^b, H S Yathirajan ^a, A R Ramesha ^c, Maciej Kubicki ^b,^*

PMCID: PMC3435841 PMID: 22969687

Abstract

In the title molecule, C₁₇H₁₈F₂N₂, the dihedral angle between the benzene rings is 73.40 (3)°. The piperazine ring is close to an ideal chair conformation and the N—H hydrogen is in an equatorial position. In the crystal, molecules are linked via weak C—H⋯F hydrogen bonds.

Related literature

For medical applications of piperazines, see: Bogatcheva et al. (2006 ▶); Brockunier et al. (2004 ▶). For related structures, see: Betz et al. (2011a ▶,b ▶); Hu et al. (2003 ▶); Naveen et al. (2006 ▶). For asymmetry parameters, see: Duax & Norton (1975 ▶).

Experimental

Crystal data

C₁₇H₁₈F₂N₂
M _r = 288.33
Monoclinic,
a = 12.1574 (5) Å
b = 8.8559 (2) Å
c = 13.8604 (4) Å
β = 93.355 (3)°
V = 1489.72 (8) Å³
Z = 4
Cu Kα radiation
μ = 0.77 mm⁻¹
T = 130 K
0.15 × 0.08 × 0.06 mm

Data collection

Atlas SuperNova (Single source at offset) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.828, T _max = 1.000
8816 measured reflections
3006 independent reflections
2847 reflections with I > 2σ(I)
R _int = 0.010

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.096
S = 1.04
3006 reflections
262 parameters
All H-atom parameters refined
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812036902/mw2085sup1.cif

e-68-o2817-sup1.cif^{(24.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812036902/mw2085Isup2.hkl

e-68-o2817-Isup2.hkl^{(144.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812036902/mw2085Isup3.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
C25—H25⋯F24ⁱ	0.962 (14)	2.424 (14)	3.2720 (13)	146.8 (10)
C25—H25⋯F34ⁱⁱ	0.962 (14)	2.533 (14)	3.1998 (13)	126.5 (10)

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

Acknowledgments

ASD thanks the University of Mysore for research facilities and HSY thanks R. L. Fine Chem., Bengaluru, for the gift sample.

supplementary crystallographic information

Comment

Piperazine is currently the most important building block used in drug discovery with a high number of positive hits encountered in biological screens of this heterocycle and its congeners. They are found in biologically active compounds across a number of different therapeutic areas such as antifungal, antibacterial, antimalarial, antipsychotic, antidepressant and antitumour activity against colon, prostate, breast, lung and leukemia tumors (Brockunier et al., 2004; Bogatcheva et al., 2006). 1-[bis(4-fluorophenyl)methyl]piperazine is an intermediate for the preparation of flunarizine which is a calcium channel blocker. Here we report the crystal structure of the title compound (I).

Only two structures of neutral 1-benzhydrylpiperazine derivatives have been reported so far: 1-benzhydrylpiperazine itself (Naveen et al., 2006) and (R)-1-((4-chlorophenyl)phenylmethyl)piperazine (Hu et al., 2003) as well as two structures of salts of I, the trinitrophenolate (Betz et al., 2011a) and the 2-(2-phenylethyl)benzoate (Betz et al., 2011b).

The dihedral angle between the mean planes of the p-fluorophenyl rings is 73.40 (3)°. The piperazine ring is in a chair conformation and the asymmetry parameters (Duax & Norton, 1975) are quite small with the largest value for the mirror plane being 3.7° and for the twofold axis 3.0°. The N—H hydrogen atom is in an equatorial position (the C—C—N—H torsion angles are 177° and -176°). In the crystal there are only very weak C—H···F contacts and, interestingly, the shortest contacts to both F atoms are created by the same carbon atom (C25). Therefore it seems that the three-dimensional structure is mainly governed by van der Waals forces.

Experimental

The title compound obtained as a gift sample from R. L. Fine Chem., Bengaluru, India. X-ray quality crystals were grown from a 1:1 (v:v) toluene/hexane solution by slow evaporation (m.p: 360–362 K).