Cinnarizinium picrate

Yanxi Song; C S Chidan Kumar; G B Nethravathi; S Naveen; Hongqi Li

doi:10.1107/S1600536812020764

. 2012 May 16;68(Pt 6):o1747. doi: 10.1107/S1600536812020764

Cinnarizinium picrate

Yanxi Song ^a, C S Chidan Kumar ^b, G B Nethravathi ^c, S Naveen ^d, Hongqi Li ^e,^*

PMCID: PMC3379334 PMID: 22719532

Abstract

In the title salt {systematic name: 4-diphenylmethyl-1-[(E)-3-phenylprop-2-en-1-yl]piperazin-1-ium 2,4,6-trinitrophenolate), C₂₆H₂₉N₂ ⁺·C₆H₂N₃O₇ ⁻, the cinnarizinium cation is protonated at the piperazine N atom connected to the styrenylmethyl group; the piperazine ring adopts a distorted chair conformaiton. In the crystal, bifurcated N—H⋯(O,O) hydrogen bonds link the components into two-ion aggregates.

Related literature

For background to the anti-histamine cinnarizine, see: Towse (1980 ▶); Barrett & Zolov (1960 ▶). For related structures, see: Mouillé et al. (1975 ▶); Bertolasi et al. (1980 ▶); Jasinski et al. (2011 ▶). For additional conformational analysis, see: Cremer & Pople (1975 ▶). graphic file with name e-68-o1747-scheme1.jpg

Experimental

Crystal data

C₂₆H₂₉N₂ ⁺·C₆H₂N₃O₇ ⁻
M _r = 597.62
Monoclinic,
a = 14.5906 (19) Å
b = 12.7720 (17) Å
c = 16.441 (2) Å
β = 103.114 (2)°
V = 2984.0 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.16 × 0.16 × 0.07 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ▶) T _min = 0.985, T _max = 0.993
15196 measured reflections
5262 independent reflections
3181 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.143
S = 1.03
5262 reflections
401 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; 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/S1600536812020764/tk5091sup1.cif

e-68-o1747-sup1.cif^{(23.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020764/tk5091Isup2.hkl

e-68-o1747-Isup2.hkl^{(257.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812020764/tk5091Isup3.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—H2A⋯O7ⁱ	0.94 (3)	2.59 (2)	3.119 (3)	116.6 (18)
N2—H2A⋯O1ⁱ	0.94 (3)	1.79 (3)	2.710 (3)	168 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported in part (ALS) by the Council for the Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO). YS and HL acknowledge financial support by the Fundamental Research Funds for the Central Universities.

supplementary crystallographic information

Comment

Cinnarizine (Stugeron, Stunarone) is an anti-histamine which is mainly used for the control of nausea and vomiting due to motion sickness. Cinnarizine could be also viewed as a nootropic drug because of its vasorelaxating abilities (due to calcium channel blockage) and as a labyrinthine sedative (Towse et al., 1980). A clinical evaluation of cinnarizine in various allergic disorders has been reported earlier (Barrett et al., 1960). Cinnarizine can be used in scuba divers without an increased risk of central nervous system oxygen toxicity. The crystal structures of some related compounds viz. cinnarizine (Mouillé et al., 1975) and cyclizine hydrochloride (Bertolasi et al., 1980) have been reported. In view of the above, and as a part of our studies on the salts of the piperazines, the title compound was synthesized and herein we report its crystal structure.

The molecular structure and atom numbering scheme of the title compound are shown in Fig 1. In the structure, the piperazine ring adopts a slightly distorted chair conformation with the puckering parameters Q, θ and φ having values of 0.584 (2)°, 174.3 (2)° and 179 (2)°, respectively (Cremer & Pople, 1975). These values slightly different from those reported earlier for cinnarizinium dipicrate (Jasinski et al., 2011). For an ideal chair conformation, θ has a value of 0 or 180°. The sum of the bond angles around the piperazine-N atoms N1 and N2 are 328.94° and 332.45°, respectively, indicating that they are sp³ hybridized. The bonds N1—C7 and N2—C18 connecting the diphenylmethyl and the phenyl-but-2-ene groups make an angle of 74.44 (14)° and 70.28 (14)°, respectively, with the Cremer and Pople (1975) plane of the piperazine ring and thus the substituents are in the equatorial plane. The dihedral angle between the piperazine ring and the phenyl ring (C21–C26) bridged by the but-2-ene group is 63.50 (12)° whereas the dihedral angles between the piperazine ring and the diphenyl methyl rings (C1–C6) and (C8–C13) are 77.63 (11)° and 89.85 (15)°, respectively. In the crystal structure, N—H···O hydrogen bonds link the ions into two ion aggregates.

Experimental

Cinnarizine (3.68 g, 0.01 mol) and picric acid (2.99 g, 0.01 mol) were dissolved separately in methanol. The solutions were mixed and stirred for a few minutes at room temperature. The precipitate was collected by filtration and purified by recrystallization from methanol. On recrystallization with DMF after 15 days, good quality single crystals were obtained; M.pt: 463–465 K.