Opipramolium fumarate

M S Siddegowda; Jerry P Jasinski; James A Golen; H S Yathirajan; M T Swamy

doi:10.1107/S160053681103159X

. 2011 Aug 11;67(Pt 9):o2296. doi: 10.1107/S160053681103159X

Opipramolium fumarate

M S Siddegowda ^a, Jerry P Jasinski ^b,^*, James A Golen ^b, H S Yathirajan ^a, M T Swamy ^c

PMCID: PMC3200775 PMID: 22064675

Abstract

In the crystal structure of the title salt {systematic name: 4-[3-(5H-dibenz[b,f]azepin-5-yl)propyl]-1-(2-hydroxyethyl)piperazin-1-ium (2Z)-3-carboxyprop-2-enoate}, C₂₃H₃₀N₃O⁺·C₄H₃O₄ ⁻, the piperazine group in the opipramol cation is protonated at only one of the N atoms. In the cation, the dihedral angle between the two benzene rings is 53.5 (6)°. An extensive array of intermolecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds and weak intermolecular N—H⋯O, C—H⋯O and C—H⋯π interactions dominate the crystal packing.

Related literature

For the use of opipramol in the treatment of anxiety disorders, see: Moller et al. (2001 ▶). For related structures, see: Fun et al. (2011 ▶); Jasinski et al. (2010 ▶). For standard bond lengths, see Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₃H₃₀N₃O⁺·C₄H₃O₄ ⁻
M _r = 479.56
Monoclinic,
a = 8.9116 (3) Å
b = 6.7167 (3) Å
c = 20.6377 (8) Å
β = 98.685 (3)°
V = 1221.14 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.25 × 0.22 × 0.12 mm

Data collection

Oxford Diffraction Xcalibur Eos Gemini diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.978, T _max = 0.989
8285 measured reflections
3393 independent reflections
3116 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.097
S = 1.03
3393 reflections
325 parameters
4 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.19 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/S160053681103159X/bt5601sup1.cif

e-67-o2296-sup1.cif^{(24.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681103159X/bt5601Isup2.hkl

e-67-o2296-Isup2.hkl^{(166.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681103159X/bt5601Isup3.cml

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

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

Cg2 and Cg3 are the centroids of the C1–C6 and C9–C14 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O4ⁱ	0.85 (2)	1.83 (2)	2.674 (2)	171 (3)
O2—H2O⋯N2ⁱⁱ	0.87 (2)	1.79 (2)	2.649 (2)	176 (3)
N3—H3N⋯O5	0.90 (2)	1.72 (2)	2.616 (2)	179 (2)
N3—H3N⋯O4	0.90 (2)	2.59 (2)	3.167 (2)	123 (2)
C12—H12A⋯O3ⁱⁱⁱ	0.95	2.49	3.399 (3)	159
C19—H19A⋯O2^iv	0.99	2.57	3.551 (2)	170
C19—H19B⋯O1^v	0.99	2.47	3.365 (2)	151
C21—H21B⋯O5^vi	0.99	2.43	3.415 (2)	172
C22—H22B⋯O1^v	0.99	2.57	3.447 (2)	148
C2—H2A⋯Cg2^vii	0.95	2.95	3.684 (2)	135
C5—H5A⋯Cg3^viii	0.95	2.79	3.655 (2)	152

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) ; (viii) .

Acknowledgments

MSS 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

Opipramol [systematic IUPAC name: 4-[3-(5H-dibenz[b,f] azepin-5-yl)propyl]-1-piperazinethanol] is an antidepressant and anxiolytic typically used in the treatment of generalized anxiety disorder (Moller et al., 2001). Opipramol is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). The crystal structure studies of opipramol dipicrate (Jasinski et al., 2010) and opipramol (Fun et al., 2011) have been reported. In view of the importance of opipramol, the paper reports the crystal structure of the title compound, (I).

In Opipramolium fumarate, C₂₃H₃₀N₃O⁺, C₄H₃O₄^-, the piperazine group in the opipramol cation is protonated at only one of the N atoms (Fig. 1). The 6-membered piperazine group (N2/C18/C19/N3/C20/C21) adopts a slightly distorted chair conformation with puckering parameters Q, θ and φ of 0.5894 (18) Å, 2.00 (17)°, and 14 (6)°, respectively. For an ideal chair θ has a value of 0 or 180°. In the cation the dihedral angle between the two benzene rings is 53.5 (6)°. Bond distances and angles are in normal ranges (Allen et al., 1987). An extensive array of O—H···O, O—H···N and N—H···O hydrogen bonds and weak N—H···O, C—H···O, C—H···Cgπ-ring intermolecular interactions (Table 1), dominate crystal packing in the unit cell (Fig. 2).

Experimental

Opipramol base (2.0 g, 0.0055 mol) was dissolved in 10 ml of DMSO and fumaric acid (1.276 g, 0.011 mol) was added. The solution was stirred in a beaker at 348 K for 15 minutes. The mixture was kept aside for two days at room temperature. Crystals of the product formed were used as such for x-ray work (m. p.: 432–434 K).