Orphenadrinium dihydrogen citrate

Manpreet Kaur; Jerry P Jasinski; Amanda C Keeley; H S Yathirajan; B P Siddaraju

doi:10.1107/S1600536813001207

. 2013 Jan 19;69(Pt 2):o248. doi: 10.1107/S1600536813001207

Orphenadrinium dihydrogen citrate

Manpreet Kaur ^a, Jerry P Jasinski ^b,^*, Amanda C Keeley ^b, H S Yathirajan ^a, B P Siddaraju ^c

PMCID: PMC3569781 PMID: 23424527

Abstract

In the title salt, C₁₈H₂₄NO⁺·C₆H₇O₇ ⁻, the dihedral angle between the benzene rings in the cation is 74.2 (5)°. In the crystal, anion–anion O—H⋯O hydrogen bonds and weak O—H⋯O interactions form infinite chains along [100]. Between these chains, cation–anion N—H—O hydrogen bonds are observed, forming an alternate pattern of cation and anion layers and leading to a two-dimensional network parallel to (100).

Related literature

For a clinical and pharmacological review of the efficacy of orphenadrine, see: Hunskaar & Donnel (1991 ▶). For related structures, see: Fun et al. (2010 ▶); Glaser et al. (1992 ▶); Jasinski et al. (2011 ▶). For standard bond lengths, see Allen et al. (1987 ▶). graphic file with name e-69-0o248-scheme1.jpg

Experimental

Crystal data

C₁₈H₂₄NO⁺·C₆H₇O₇ ⁻
M _r = 461.50
Triclinic,
a = 9.9515 (8) Å
b = 10.7382 (9) Å
c = 12.625 (1) Å
α = 98.863 (7)°
β = 104.391 (7)°
γ = 111.498 (8)°
V = 1170.0 (2) Å³
Z = 2
Cu Kα radiation
μ = 0.82 mm⁻¹
T = 173 K
0.32 × 0.28 × 0.14 mm

Data collection

Agilent Xcalibur (Eos, Gemini) diffractometer
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012 ▶) T _min = 0.854, T _max = 1.000
7161 measured reflections
4471 independent reflections
3795 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.161
S = 1.03
4471 reflections
305 parameters
H-atom parameters constrained
Δρ_max = 0.67 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012 ▶); 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

Click here for additional data file.^{(31KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813001207/hg5283sup1.cif

e-69-0o248-sup1.cif^{(31KB, cif)}

Click here for additional data file.^{(219KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813001207/hg5283Isup2.hkl

e-69-0o248-Isup2.hkl^{(219KB, hkl)}

Click here for additional data file.^{(9.2KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813001207/hg5283Isup3.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
N1—H1⋯O6ⁱ	0.91	1.83	2.725 (2)	167
O4—H4A⋯O8ⁱⁱ	0.82	2.30	3.067 (2)	156
O7—H7A⋯O5ⁱⁱ	0.82	1.81	2.634 (2)	178

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

Acknowledgments

MK and HSY thank the University of Mysore for research facilities. JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

supplementary crystallographic information

Comment

Orphenadrine (systematic IUPAC name: N,N-dimethyl-2-[(2-methylphenyl) phenyl-methoxy]ethanamine) is an anticholinergic drug of the ethanolamine antihistamine class with prominent CNS and peripheral actions used to treat painful muscle spasm and other symptoms and conditions as well as some aspects of Parkinson's disease. It is closely related to diphenhydramine and therefore related to other drugs used for Parkinson's disease like benztropine and trihexyphenidyl and is also structurally related to nefopam, a centrally acting yet non-opioid analgesic. Clinical and pharmacological review of the efficacy of orphenadrine and its combination with paracetamol has been described (Hunskaar & Donnel, 1991). Orphenadrine citrate is a skeletal muscle relaxant. It acts in the central nervous system to produce its muscle relaxant effects. The orphenadrine salt used for Parkinsonism is the hydrochloride, whereas the muscle relaxant tablet is the citrate. The solid-state structure of orphenadrine hydrochloride and conformational comparisons with diphenhydramine hydrochloride and nefopam hydrochloride is reported (Glaser et al., 1992). The crystal structure of orphenadrinium picrate picric acid (Fun et al., 2010) and orphenadrinium picrate (Jasinski et al., 2011) is recently reported. In view of the importance of orphenadrine, this paper reports the crystal structure of the title salt, (I), C₁₈H₂₄NO⁺. C₆H₇O₇^-.

In the title salt, C₁₈H₂₄NO⁺. C₆H₇O₇^-, one cation-anion pair crystallizes in the asymmetric unit (Fig. 1). The cation contains a positively charged N atom with quaternary character. The anion consists of a dihydrogen citrate counterion. The dihedral angle between the two benzene rings in the cation is 74.2 (5)°. Bond lengths are in normal ranges (Allen et al., 1987). In the crystal anion-anion O—H···O hydrogen bonds and weak O—H···O intermolecular interactions form infinite chains along [100] (Table 1). In between these chains cation-anion N—H—O hydrogen bonds are observed forming an alternate pattern of cation and anion layers forming a two-dimensional network providing additional crystal stability (Fig. 2).

Experimental

The title compound was obtained as a gift sample from R. L. Fine Chem, Bengaluru. The compound was recrystallized from methanol by slow evaporation (m. p.: 410 K).