Crystal structure of {[2-hy­droxy-2-(3-meth­oxy­phen­yl)cyclo­hex­yl]meth­yl}di­methyl­ammonium benzoate

S N Sheshadri; P Nagendra; B P Siddaraju; K H Hemakumar; K Byrappa; N K Lokanath; S Madan Kumar

doi:10.1107/S2056989015019362

. 2015 Oct 17;71(Pt 11):o864–o865. doi: 10.1107/S2056989015019362

Crystal structure of {[2-hydroxy-2-(3-methoxyphenyl)cyclohexyl]methyl}dimethylammonium benzoate

S N Sheshadri ^a, P Nagendra ^b, B P Siddaraju ^c, K H Hemakumar ^d, K Byrappa ^e, N K Lokanath ^f, S Madan Kumar ^g,^*

PMCID: PMC4645060 PMID: 26594567

Abstract

The title compound, C₁₆H₂₆NO₂ ⁺·C₇H₅O₂ ⁻, is a benzoate salt of the painkiller Tramadol. The six-membered cyclohexane ring of the cation adopts a slightly distorted chair conformation and carries OH and 3-methoxyphenyl substituents at the 2-position and a protonated methylazaniumylmethyl group at the 3-position. In addition, a weak intramolecular C—H⋯O hydrogen bond is observed in the cation. In the crystal, weak O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds link the components into chains along [010]. A C—H⋯π contact is also observed.

Keywords: crystal structure, Tramadol, intermolecular hydrogen bonds

Related literature

For pharmaceutical applications of Tramadol and related analgesics, see: Scott & Perry (2000 ▸). For related structures, see: Tessler & Goldberg (2004 ▸); Arman et al. (2010 ▸); Hemamalini & Fun (2010 ▸); Siddaraju et al. (2011 ▸); Lin & Zhang (2013 ▸); Smith (2014 ▸); Jasinski et al. (2015 ▸); Sun et al. (2012 ▸). graphic file with name e-71-0o864-scheme1.jpg

Experimental

Crystal data

C₁₆H₂₆NO₂ ⁺·C₇H₅O₂ ⁻
M _r = 385.49
Triclinic,
a = 9.013 (4) Å
b = 9.767 (4) Å
c = 12.726 (6) Å
α = 75.008 (16)°
β = 89.79 (2)°
γ = 76.493 (16)°
V = 1050.3 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.55 × 0.51 × 0.3 mm

Data collection

Rigaku Saturn724+ diffractometer
Absorption correction: multi-scan (NUMABS; Rigaku 1999 ▸) T _min = 0.955, T _max = 0.975
11931 measured reflections
5660 independent reflections
3504 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.134
S = 1.03
5660 reflections
257 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrystalClear SM Expert (Rigaku, 2011 ▸); cell refinement: CrystalClear SM Expert; data reduction: CrystalClear SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▸) and Mercury (Macrae et al., 2008 ▸); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989015019362/sj5480sup1.cif

e-71-0o864-sup1.cif^{(368.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015019362/sj5480Isup2.hkl

e-71-0o864-Isup2.hkl^{(450.1KB, hkl)}

Click here for additional data file.^{(8.3KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015019362/sj5480Isup3.cml

Click here for additional data file.^{(2.1MB, tif)}

. DOI: 10.1107/S2056989015019362/sj5480fig1.tif

A view of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level and an intramolecular hydrogen bond is drawn as a dashed line.

Click here for additional data file.^{(1.3MB, tif)}

a . DOI: 10.1107/S2056989015019362/sj5480fig2.tif

A viewed along the a axis of the crystal packing of the title compound. Hydrogen bonds are drawn as a dashed lines.

CCDC reference: 1425991

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

Cg1 is the centroid of the C1C6 benzene ring.

DHA	DH	HA	D A	DHA
C6H6O10	0.93	2.42	2.775(2)	102
C14H14BO28ⁱ	0.97	2.41	3.251(2)	144
N17H17O28ⁱ	0.98	1.65	2.6120(18)	165
O10H10O27ⁱⁱ	0.82	1.94	2.7269(17)	161
C23H23Cg1ⁱⁱⁱ	0.93	2.83	3.684(3)	153

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

Acknowledgments

The authors thank DST–PURSE, Mangalore University, Mangaluru, for providing the single-crystal X-ray diffraction facility. PN thanks Bharthi College, Maddur, for research facilities.

supplementary crystallographic information

S1. Comment

2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol hydrochloride (Tramadol) is used in the treatment of disorders of the central nervous system and in treating extreme pain. This molecule is analogous to the phenanthrene alkaloid codeine and is used in the control of pre-operative pain (Scott & Perry, 2000).

There are number of crystal structures reported available related to this salt. These include Venlafaxine [(RS)-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]- cyclohexanol] (Tessler & Goldberg, 2004), benzoic acid-2-{(E)-[(E)-2-(2-pyridylmethylidene) hydrazin-1-ylidene]methyl}pyridine (2/1) (Arman et al., 2010), 2,3-diaminopyridinium benzoate benzoic acid solvate (Hemamalini & Fun, 2010), Tramadol hydrochloride-benzoic acid (1/1) (Siddaraju et al., 2011), 4-(cyclo-propane-carboxamido) benzoic acid (Sun et al., 2012), 3,5-bis[(pyridin-4-yl)meth-oxy]benzoic acid (Lin & Zhang, 2013). The hydrogen-bonded two- and three-dimensional polymeric structures of the ammonium salts of 3,5-di-nitro-benzoic acid, 4-nitro-benzoic acid and 2,4-di-chloro-benzoic acid (Smith, 2014) and 4-[1-(2-hydroxypropyl)-4,5-diphenyl-1H-imidazol-2-yl]benzoic acid (Jasinski et al., 2015) have also been reported. In the view of the importance of Tramadol, we report herein the crystal structure of the title compound 2-hydroxy-2-(3-methoxy-phenyl)-cyclohexylmethyl-dimethyl-ammonium benzoate.

In the title molecule (Fig. 1), the six membered cyclohexane ring (C9/C11–C15) adopts a slightly distorted chair conformation with ring puckering parameters Q, θ and φ of 0.5605 (16) Å, 5.06 (16)°, and 210.3 (6)°, respectively. An intramolecular C6—H6···O10 hydrogen bond (Fig 1, Table 1) is found in the cation. Bond lengths are within normal ranges.

The crystal structure is stabilized with weak intermolecular O—H···O, N—H···O and C—H···O hydrogen bonds and a weak intermolecular C23—H23···Cg1 interaction is also observed Table 1, Fig. 2.

S2. Experimental

Tramadol (3 g, 0.01 mol) and benzoic acid (1 g, 0.01 mol) were each dissolved in 10 ml of ethanol. The solutions were mixed and stirred in a beaker at 333 K for 30 minutes. The mixture was kept aside for three days at room temperature. Colourless X-ray quality crystals were formed and one was used for the data collection