4-[Bis(4-fluorophenyl)methyl]piperazin-1-ium picrate

Richard Betz; Thomas Gerber; Eric Hosten; Alaloor S Dayananda; Hemmige S Yathirajan; Badiadka Narayana

doi:10.1107/S160053681103580X

. 2011 Sep 14;67(Pt 10):o2587–o2588. doi: 10.1107/S160053681103580X

4-[Bis(4-fluorophenyl)methyl]piperazin-1-ium picrate

Richard Betz ^a,^*, Thomas Gerber ^a, Eric Hosten ^a, Alaloor S Dayananda ^b, Hemmige S Yathirajan ^b, Badiadka Narayana ^c

PMCID: PMC3201484 PMID: 22064439

Abstract

The title compound {systematic name: 4-[bis(4-fluorophenyl)methyl]piperazin-1-ium 2,4,6-trinitrophenolate}, C₁₇H₁₉F₂N₂ ⁺·C₆H₂N₃O₇ ⁻, is the picrate salt of a piperazine-supported amine bearing a benzhydryl substituent on one of its N atoms. During co-crystallisation, protonation took place on the N atom of the secondary amine functionality. The non-aromatic six-membered heterocycle adopts a chair conformation. In the crystal, N—H⋯O hydrogen bonds as well as C—H⋯O contacts connect the components into a three-dimensional network.

Related literature

For background to the biological activity of piperazines, see: Brockunier et al. (2004 ▶); Bogatcheva et al. (2006 ▶). For related structures, see: Jasinski et al. (2010 ▶, 2011 ▶); Dutkiewicz et al. (2011 ▶). For graph-set analysis of hydrogen bonds, see: Etter et al. (1990 ▶); Bernstein et al. (1995 ▶). For puckering analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₇H₁₉F₂N₂ ⁺·C₆H₂N₃O₇ ⁻
M _r = 517.45
Monoclinic,
a = 8.9425 (2) Å
b = 11.8286 (2) Å
c = 23.0922 (4) Å
β = 105.720 (1)°
V = 2351.27 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 200 K
0.52 × 0.49 × 0.41 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS: Bruker, 2008 ▶) T _min = 0.928, T _max = 1.000
20823 measured reflections
5842 independent reflections
5041 reflections with I > 2σ(I)
R _int = 0.013

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.111
S = 1.03
5842 reflections
342 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.31 e Å⁻³

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2010 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681103580X/hg5090sup1.cif

e-67-o2587-sup1.cif^{(23.5KB, cif)}

Supplementary material file. DOI: 10.1107/S160053681103580X/hg5090Isup2.cdx

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681103580X/hg5090Isup3.hkl

e-67-o2587-Isup3.hkl^{(286KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681103580X/hg5090Isup4.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
N2—H721⋯O1ⁱ	0.909 (17)	1.924 (17)	2.7696 (12)	154.0 (14)
N2—H721⋯O52ⁱ	0.909 (17)	2.369 (16)	3.0018 (14)	126.7 (12)
N2—H722⋯O1ⁱⁱ	0.926 (16)	1.927 (16)	2.7402 (13)	145.4 (14)
N2—H722⋯O31ⁱⁱ	0.926 (16)	2.345 (16)	3.0791 (15)	136.0 (13)
C3—H3A⋯O52ⁱ	0.99	2.60	3.0002 (16)	104
C13—H13⋯O32ⁱⁱⁱ	0.95	2.39	3.2159 (16)	145
C23—H23⋯O42^iv	0.95	2.61	3.2827 (17)	129

Open in a new tab

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

Acknowledgments

ASD thanks the University of Mysore for research facilities.

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. 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). The crystal structures of some related salts viz., levocetirizinium dipicrate (Jasinski et al., 2010), cinnarizinium dipicrate (Jasinski et al., 2011), 1-methylpiperazine-1,4-diium dipicrate (Dutkiewicz et al., 2011), have been reported. In the course of our studies on picrates of simple organic cations and in view of the importance of piperazines, we have determined the crystal and molecular structure of the title salt.

Protonation occurred at the nitrogen atom that is part of the secondary amine functionality. The non-aromatic heterocycle adopts a chair conformation (¹C₄, ^N1C_N2) according to a conformation analysis (Cremer & Pople, 1975). The least-squares planes defined by the carbon atoms of the two fluorophenyl moieties intersect at an angle of 73.71 (4) °. The planes defined by the atoms of the nitro groups on the picrate anion enclose angles of 7.62 (14) °, 33.52 (18) ° and 37.08 (17) °, respectively with the aromatic system they are bonded to (Fig. 1).

In the crystal, hydrogen bonds of the N–H···O type as well as C–H···O contacts are present. Both classical hydrogen bonds show bifurcation between the phenolic O atom as well as one of the nitro group's O atoms. The C–H···O contacts are supported by one of the hydrogen atoms of the non-aromatic heterocycle as well as one of the hydrogen atoms in ortho position to F atom in each of the fluorophenyl moieties. Apart from one O atom of a nitro group that forms a N–O···C_g contact with a neighbouring picrate anion, all O atoms act as acceptors for hydrogen atoms. In terms of graph-set analysis (Etter et al., 1990; Bernstein et al., 1995), the descriptor for the classical hydrogen bonds is DDDD on the unitary level while the C–H···O contacts require a DD descriptor on the same level. In total, the entities of the title compound are connected to a three-dimensional network in the crystal. The shortest intercentroid distance between two centers of gravity was found at 4.0808 (7) Å and is apparent between one of the fluorophenyl moieties and the picrate anion (Fig. 2).

The packing of the title compound in the crystal structure is shown in Figure 3.

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 methanol and picric acid (2.29 g, 0.01 mol) was also dissolved in 10 ml of methanol. Both the solutions were mixed and stirred in a beaker at 333 K for 30 minutes. The mixture was kept aside for a day at room temperature. The salt formed was filtered & dried in vaccum desiccator over phosphorous pentoxide. The compound was recrystallized from a mixture of (1:1) acetone and acetonitrile by slow evaporation (m.p: 513–516 K).