N-Benzyl-N-methyl-3-phenyl-3-[4-(tri­fluoro­meth­yl)phen­oxy]propanamine (N-benzylflouoxetine)

Nosheen Kanwal; Erum Akbar Hussain; Onur Sahin

doi:10.1107/S1600536810012699

. 2010 Apr 24;66(Pt 5):o1146. doi: 10.1107/S1600536810012699

N-Benzyl-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamine (N-benzylflouoxetine)

Nosheen Kanwal ^a,^*, Erum Akbar Hussain ^a, Onur Sahin ^b

PMCID: PMC2979243 PMID: 21579194

Abstract

In the title compound, C₂₄H₂₄F₃NO, the N-benzyl derivative of fluoxetine {N-methyl-3-[4-(trifluoromethyl)phenoxy]benzenepropanamine}, the three aromatic rings A, B and C are inclined to one another by 76.77 (12)° for A/B, 17.05 (14)° for A/C and 89.66 (14)° for B/C. In the crystal structure, molecules are linked via C—H⋯π interactions to form one-dimensional chains propagating in the [010] direction.

Related literature

For the therapeutic uses of fluoxetine, see: Benefield et al. (1986 ▶); Feighner & Boyer (1991 ▶); Markowitz et al. (1999 ▶); Wong et al. (1995 ▶); Zhu et al. (2009 ▶). For the crystal structures of various fluoxetine derivatives, see: Childs et al. (2004 ▶); Robertson et al. (1988 ▶).

Experimental

Crystal data

C₂₄H₂₄F₃NO
M _r = 399.44
Monoclinic,
a = 6.1712 (5) Å
b = 17.2900 (14) Å
c = 20.3028 (16) Å
β = 91.029 (5)°
V = 2166.0 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.31 × 0.25 × 0.22 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
24582 measured reflections
5395 independent reflections
1743 reflections with I > 2σ(I)
R _int = 0.092

Refinement

R[F ² > 2σ(F ²)] = 0.052
wR(F ²) = 0.136
S = 0.91
5395 reflections
297 parameters
8 restraints
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810012699/su2167sup1.cif

e-66-o1146-sup1.cif^{(25.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810012699/su2167Isup2.hkl

e-66-o1146-Isup2.hkl^{(258.9KB, hkl)}

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

Table 1. C—H⋯π interactions (Å, °).

Cg1 is the centroid of ring A (C1–C6), Cg2 that of ring B (C8–C13) and Cg3 that of ring C (C17–C22).

D	H	Centroid	C—H	H⋯Cg	D⋯Cg	C—H⋯Cg
C10	H10	Cg3ⁱ	0.93	2.90	3.588 (3)	132
C18	H18	Cg1ⁱⁱ	0.93	3.08	3.976 (4)	162
C19	H19	Cg2ⁱⁱ	0.93	2.94	3.719 (4)	143

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Symmetry codes: (i) −x + 1, y − Inline graphic , −z + ; (ii) −x, y + , −z + .

Acknowledgments

The authors are grateful to Professor Hoong-Kun Fun (Universiti Sains Malaysia) and Mr Zeeshan Haider (HEJ) for their kind assistance.

supplementary crystallographic information

Comment

Fluoxetine (N-methyl-3-[4-(trifluoromethyl)phenoxy]benzenepropanamine) has been approved worldwide in the therapy of major depression (Markowitz et al., 1999); Feighner & Boyer, 1991) and in the treatment of other syndromes, such as Bulimia nervosa, Panic fits and obsessive–compulsive disorder (Benefield et al., 1986; Wong et al., 1995). Recently, Zhu et al. reported that continuous Fluoxetine administration also prevents recurrence of pulmonary arterial hypertension in rats (Zhu et al., 2009). Crystal structure of Fluoxetine has been reported as the hydrochloride, hydrochloride benzoic acid, hydrochloride succinic acid and hydrochloride fumaric acid (Robertson et al., 1988; Childs et al., 2004). Herein, we report on the crystal structure of N-Benzyl Fluoxetine.

The molecular structure of the title molecule is illustrated in Fig. 1. The geometrical parameters are similar to those in the above mentioned derivatives. In the title compound the F atoms of the CF₃ groups shows disorder and were modelled with three different orientations (F1a—F3a, F1b—F2b and F2aa—F2ab—F3bb—F3ba) with occupancy factors of 0.50, 0.50 and 0.25, respectively (Fig. 1). The H7—C7—C8—C9 torsion angle is -19.2°, indicating that the monosubstituted phenyl ring (B) deviates only slightly from the plane defined by atoms C8, C7, and H7.

The relationship of this phenyl ring to the trifluoromethyl-substituted phenoxy ring (A) is defined by the torsion angles C8—C7—O1—C1 and C7—O1—C1—C6, which are 82.8 (2) and -6.9 (3)°, respectively. The three phenyl ring mean planes are approximately planar, with maximum deviations of 0.0094 (17) Å for atom C3 (ring A), 0.0032 (18) Å for atom C11 (ring B) and 0.0050 (17) Å for atom C17 (ring C).

In the crystal structure of the title compound, there are no intra- or intermolecular hydrogen-bonding interactions, only weak C—H···π interactions. These lead to the formation of a chain propagating along [010]; see Fig. 2 and Table 1.

Experimental

A mixture of Fluoxetine hydrogen chloride 0.5 g (1.45 mmol), sodium hydride 0.14 g (5.8 mmol) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 30 min, followed by the addition of benzyl chloride 0.33 ml (2.9 mmol). Stirring was continued for a period of 3 h and the contents were then poured over crushed ice. The precipitated product was isolated, washed and crystallized from methanol, giving colourless prism-like crystals, suitable for X-ray analysis.