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Acta Cryst. (2008). E64, o553    [ doi:10.1107/S1600536808003255 ]

N,N-Dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine

X. Tao, X.-Q. Zhang, L. Yuan and J.-T. Wang

Abstract top

The title compound, C19H21NOS, is an intermediate for the synthesis of duloxetine hydrochloride. In the molecular structure, the thiophene and naphthalene ring systems make a dihedral angle of 87.5°. All bond lengths and angles involving heteroatoms are as expected. In the crystal structure, no classical hydrogen bonds are found.

Comment top

The title compound, (I), an is intermediate for Duloxetine hydrochloride (Deeter et al., 1990). The crystal structure determination of (I) has been carried out in order to elucidate its molecular conformation. In the molecular structure (Fig. 1) bond lengths and angles are within normal ranges and compare well with those observed in the corresponding alcohol, 3-hydroxy-N,N-dimethyl-3-(2-thienyl)propanamine (Tao, Bin et al., 2006; Tao, Li et al., 2006). The thiophene (S/C6···C9) and naphthalene (C10···C19) rings are planar and the dihedral angle between them is 87.5°. In the crystal structure, no classic hydrogen bonds are found. It may then be assumed that dipole-dipole and van der Waals interactions are effective for the molecular packing (Fig. 2).

Related literature top

For the preparation of duloxetine see: Deeter et al. (1990). For related hydroxyl derivatives of the title molecule, see: Tao, Bin et al. (2006); Tao, Li et al. (2006).

Experimental top

N,N-Dimethyl-3-(2-thienyl)-3-hydroxylpropanamine (9.25 g, 0.05 mol) was dissolved in 30 ml of dimethylsulfoxide. Sodium hydride (60%, 1.5 g, 0.225 mol) was added to the solution with stirring at room temperature for another 15 min. Then, 1-fluoronaphthalene (8.75 g, 0.06 mol) was added, and the mixture was stirred for 8 h. at 323 K. The mixture was poured into 50 ml of ice water, and the pH was adjusted to 4–5 using acetic acid. 50 ml of hexane was added, stirred and the layers were separated. The aqueous phase was stirred with 30 ml of hexane, the pH was adjusted to 12 using 25% aqueous sodium hydroxide, 30 ml of ethyl acetate was added, stirred and the layers were separated. The aqueous phase was extracted with another 30 ml of ethyl acetate, and the organic extracts were combined, washed with 30 ml of water, dried over magnesium sulfate. The solvent was removed under vacuum to obtain (I) as a brown oil (yield: 11.3 g, 72.9%). The title compound (I) was dissolved in a mixture of ethanol and acetone (2:1). After 14 days, brown single crystals were collected.

Refinement top

All H atoms were included in the riding model approximation with C—H distances constrained to 0.93 (aromatic CH) 0.96 (methyl CH3), 0.97 (methylene CH2) and 0.98 Å (methine CH), and with Uiso(H) = 1.5 Ueq(carrier C) for the methyl groups and Uiso(H) = 1.2 Ueq(carrier C) otherwise.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1981); cell refinement: CAD-4 Software (Enraf–Nonius, 1981); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The structure of (I). Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. The crystal packing of (I) viewed along [100].
N,N-Dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine top
Crystal data top
C19H21NOSF000 = 664
Mr = 311.43Dx = 1.208 Mg m−3
Monoclinic, P21/nMelting point = 386–388 K
Hall symbol: -P 2ynMo Kα radiation
λ = 0.71073 Å
a = 9.6140 (19) ÅCell parameters from 25 reflections
b = 18.578 (4) Åθ = 10–13º
c = 9.905 (2) ŵ = 0.19 mm−1
β = 104.53 (3)ºT = 293 (2) K
V = 1712.5 (6) Å3Block, brown
Z = 40.40 × 0.30 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.038
Radiation source: fine-focus sealed tubeθmax = 26.0º
Monochromator: graphiteθmin = 2.4º
T = 293(2) Kh = 0→11
ω/2θ scansk = 0→22
Absorption correction: ψ scan
(North et al., 1968)		l = −12→11
Tmin = 0.928, Tmax = 0.9813 standard reflections
3550 measured reflections every 200 reflections
3352 independent reflections intensity decay: <1%
2009 reflections with I > 2s(I)
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.070H-atom parameters constrained
wR(F2) = 0.194  w = 1/[σ2(Fo2) + (0.08P)2 + 0.85P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
3352 reflectionsΔρmax = 0.45 e Å−3
199 parametersΔρmin = −0.32 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C19H21NOSV = 1712.5 (6) Å3
Mr = 311.43Z = 4
Monoclinic, P21/nMo Kα
a = 9.6140 (19) ŵ = 0.19 mm−1
b = 18.578 (4) ÅT = 293 (2) K
c = 9.905 (2) Å0.40 × 0.30 × 0.10 mm
β = 104.53 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		2009 reflections with I > 2s(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.038
Tmin = 0.928, Tmax = 0.9813 standard reflections
3550 measured reflections every 200 reflections
3352 independent reflections intensity decay: <1%
Refinement top
R[F2 > 2σ(F2)] = 0.070199 parameters
wR(F2) = 0.194H-atom parameters constrained
S = 1.04Δρmax = 0.45 e Å−3
3352 reflectionsΔρmin = −0.32 e Å−3
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S0.03342 (12)0.25309 (6)0.17997 (10)0.0561 (3)
O0.1693 (2)0.34125 (12)0.0007 (2)0.0445 (6)
N−0.1370 (3)0.47356 (16)−0.2560 (3)0.0517 (8)
C1−0.2401 (5)0.4470 (2)−0.3807 (5)0.0777 (14)
H1A−0.27770.4015−0.36070.117*
H1B−0.19290.4412−0.45470.117*
H1C−0.31730.4809−0.40860.117*
C2−0.0803 (5)0.5421 (2)−0.2843 (5)0.0753 (13)
H2A−0.01330.5593−0.20160.113*
H2B−0.15750.5760−0.31230.113*
H2C−0.03220.5367−0.35770.113*
C3−0.0227 (4)0.4218 (2)−0.2029 (4)0.0517 (10)
H3A0.05590.4461−0.13830.062*
H3B0.01310.4041−0.28000.062*
C4−0.0708 (4)0.3584 (2)−0.1295 (4)0.0506 (10)
H4A−0.10160.3758−0.04930.061*
H4B−0.15270.3357−0.19240.061*
C50.0463 (4)0.30309 (19)−0.0816 (4)0.0439 (9)
H5A0.07110.2822−0.16340.053*
C60.0029 (4)0.24339 (18)0.0033 (4)0.0406 (8)
C7−0.0719 (4)0.17959 (18)−0.0465 (4)0.043
H7A−0.09970.1649−0.13920.052*
C8−0.0976 (4)0.1414 (2)0.0708 (4)0.0542 (10)
H8A−0.14470.09730.06200.065*
C9−0.0482 (4)0.1743 (2)0.1943 (4)0.0510 (10)
H9A−0.05800.15560.27850.061*
C100.3039 (4)0.31259 (19)0.0180 (3)0.0403 (8)
C110.3328 (4)0.2446 (2)−0.0182 (4)0.0498 (9)
H11A0.25840.2131−0.05720.060*
C120.4781 (5)0.2225 (2)0.0045 (4)0.0574 (11)
H12A0.49820.1762−0.02110.069*
C130.5882 (5)0.2673 (2)0.0627 (4)0.0603 (11)
H13A0.68250.25150.07610.072*
C140.5612 (4)0.3372 (2)0.1027 (4)0.0496 (10)
C150.6714 (4)0.3854 (3)0.1646 (4)0.0677 (13)
H15A0.76650.37040.18140.081*
C160.6431 (5)0.4528 (3)0.2002 (5)0.0746 (13)
H16A0.71850.48360.23970.089*
C170.5021 (5)0.4765 (2)0.1781 (4)0.0655 (12)
H17A0.48370.52300.20400.079*
C180.3900 (4)0.4320 (2)0.1186 (4)0.0481 (9)
H18A0.29610.44850.10380.058*
C190.4161 (4)0.36147 (19)0.0798 (3)0.0409 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S0.0651 (7)0.0585 (6)0.0425 (5)−0.0028 (5)0.0094 (5)−0.0023 (5)
O0.0335 (13)0.0410 (14)0.0566 (15)−0.0007 (11)0.0070 (11)−0.0068 (11)
N0.0482 (19)0.0464 (18)0.058 (2)0.0008 (15)0.0083 (15)0.0088 (15)
C10.065 (3)0.070 (3)0.081 (3)−0.003 (2)−0.011 (2)0.018 (3)
C20.074 (3)0.054 (3)0.095 (4)−0.003 (2)0.017 (3)0.013 (3)
C30.041 (2)0.055 (2)0.057 (2)−0.0018 (18)0.0077 (18)0.0090 (19)
C40.040 (2)0.055 (2)0.053 (2)0.0009 (18)0.0033 (17)0.0086 (19)
C50.044 (2)0.045 (2)0.0414 (19)−0.0021 (17)0.0088 (16)−0.0027 (16)
C60.0393 (19)0.044 (2)0.0367 (17)0.0071 (16)0.0068 (14)0.0008 (16)
C70.0430.0430.0430.0000.0110.000
C80.060 (3)0.041 (2)0.059 (3)−0.0030 (19)0.012 (2)−0.0004 (19)
C90.062 (3)0.047 (2)0.046 (2)0.0077 (19)0.0170 (19)0.0069 (18)
C100.0380 (19)0.048 (2)0.0372 (19)0.0080 (16)0.0127 (15)0.0072 (16)
C110.055 (2)0.050 (2)0.048 (2)0.0039 (19)0.0182 (18)0.0050 (19)
C120.069 (3)0.056 (2)0.055 (2)0.022 (2)0.029 (2)0.011 (2)
C130.050 (2)0.084 (3)0.049 (2)0.025 (2)0.0167 (19)0.016 (2)
C140.041 (2)0.070 (3)0.039 (2)0.0091 (19)0.0118 (17)0.0115 (19)
C150.039 (2)0.103 (4)0.059 (3)−0.002 (2)0.008 (2)0.005 (3)
C160.051 (3)0.101 (4)0.067 (3)−0.019 (3)0.004 (2)−0.007 (3)
C170.064 (3)0.060 (3)0.069 (3)−0.009 (2)0.011 (2)−0.010 (2)
C180.046 (2)0.052 (2)0.046 (2)−0.0025 (18)0.0120 (17)0.0017 (18)
C190.0399 (19)0.050 (2)0.0324 (18)0.0023 (17)0.0085 (15)0.0062 (16)
Geometric parameters (Å, °) top
S—C61.709 (3)C7—H7A0.9300
S—C91.683 (4)C8—C91.343 (5)
O—C101.370 (4)C8—H8A0.9300
O—C51.443 (4)C9—H9A0.9300
N—C21.440 (5)C10—C111.360 (5)
N—C31.455 (5)C10—C191.425 (5)
N—C11.462 (5)C11—C121.419 (5)
C1—H1A0.9600C11—H11A0.9300
C1—H1B0.9600C12—C131.357 (6)
C1—H1C0.9600C12—H12A0.9300
C2—H2A0.9600C13—C141.400 (5)
C2—H2B0.9600C13—H13A0.9300
C2—H2C0.9600C14—C151.406 (6)
C3—C41.517 (5)C14—C191.429 (5)
C3—H3A0.9700C15—C161.345 (6)
C3—H3B0.9700C15—H15A0.9300
C4—C51.511 (5)C16—C171.390 (6)
C4—H4A0.9700C16—H16A0.9300
C4—H4B0.9700C17—C181.369 (5)
C5—C61.513 (5)C17—H17A0.9300
C5—H5A0.9800C18—C191.405 (5)
C6—C71.410 (5)C18—H18A0.9300
C7—C81.435 (5)
C9—S—C691.74 (18)C6—C7—H7A126.0
C10—O—C5119.6 (3)C8—C7—H7A126.0
C2—N—C3111.4 (3)C9—C8—C7114.8 (3)
C2—N—C1110.1 (3)C9—C8—H8A122.6
C3—N—C1111.9 (3)C7—C8—H8A122.6
N—C1—H1A109.5C8—C9—S112.6 (3)
N—C1—H1B109.5C8—C9—H9A123.7
H1A—C1—H1B109.5S—C9—H9A123.7
N—C1—H1C109.5C11—C10—O125.2 (3)
H1A—C1—H1C109.5C11—C10—C19121.4 (3)
H1B—C1—H1C109.5O—C10—C19113.3 (3)
N—C2—H2A109.5C10—C11—C12119.1 (4)
N—C2—H2B109.5C10—C11—H11A120.5
H2A—C2—H2B109.5C12—C11—H11A120.5
N—C2—H2C109.5C13—C12—C11121.4 (4)
H2A—C2—H2C109.5C13—C12—H12A119.3
H2B—C2—H2C109.5C11—C12—H12A119.3
N—C3—C4113.1 (3)C12—C13—C14120.6 (4)
N—C3—H3A109.0C12—C13—H13A119.7
C4—C3—H3A109.0C14—C13—H13A119.7
N—C3—H3B109.0C13—C14—C15122.7 (4)
C4—C3—H3B109.0C13—C14—C19119.4 (4)
H3A—C3—H3B107.8C15—C14—C19117.8 (4)
C5—C4—C3112.7 (3)C16—C15—C14121.8 (4)
C5—C4—H4A109.1C16—C15—H15A119.1
C3—C4—H4A109.1C14—C15—H15A119.1
C5—C4—H4B109.1C15—C16—C17120.5 (4)
C3—C4—H4B109.1C15—C16—H16A119.8
H4A—C4—H4B107.8C17—C16—H16A119.8
O—C5—C4106.5 (3)C18—C17—C16120.5 (4)
O—C5—C6110.3 (3)C18—C17—H17A119.8
C4—C5—C6112.7 (3)C16—C17—H17A119.8
O—C5—H5A109.1C17—C18—C19120.4 (4)
C4—C5—H5A109.1C17—C18—H18A119.8
C6—C5—H5A109.1C19—C18—H18A119.8
C7—C6—C5127.5 (3)C18—C19—C10122.9 (3)
C7—C6—S112.9 (3)C18—C19—C14119.0 (3)
C5—C6—S119.4 (3)C10—C19—C14118.1 (3)
C6—C7—C8108.0 (3)
C2—N—C3—C4161.7 (4)C19—C10—C11—C12−0.9 (5)
C1—N—C3—C4−74.6 (4)C10—C11—C12—C130.7 (6)
N—C3—C4—C5176.9 (3)C11—C12—C13—C140.2 (6)
C10—O—C5—C4−157.5 (3)C12—C13—C14—C15179.4 (4)
C10—O—C5—C680.0 (4)C12—C13—C14—C19−1.0 (6)
C3—C4—C5—O53.6 (4)C13—C14—C15—C16178.9 (4)
C3—C4—C5—C6174.6 (3)C19—C14—C15—C16−0.8 (6)
O—C5—C6—C7−154.8 (3)C14—C15—C16—C170.9 (7)
C4—C5—C6—C786.3 (4)C15—C16—C17—C18−0.7 (7)
O—C5—C6—S30.0 (4)C16—C17—C18—C190.4 (6)
C4—C5—C6—S−88.8 (3)C17—C18—C19—C10179.7 (3)
C9—S—C6—C70.6 (3)C17—C18—C19—C14−0.3 (5)
C9—S—C6—C5176.4 (3)C11—C10—C19—C18−179.9 (3)
C5—C6—C7—C8−176.3 (3)O—C10—C19—C18−0.1 (5)
S—C6—C7—C8−0.8 (4)C11—C10—C19—C140.2 (5)
C6—C7—C8—C90.7 (5)O—C10—C19—C14180.0 (3)
C7—C8—C9—S−0.3 (4)C13—C14—C19—C18−179.2 (3)
C6—S—C9—C8−0.2 (3)C15—C14—C19—C180.5 (5)
C5—O—C10—C11−10.8 (5)C13—C14—C19—C100.8 (5)
C5—O—C10—C19169.4 (3)C15—C14—C19—C10−179.6 (3)
O—C10—C11—C12179.3 (3)
Table 1
Selected geometric parameters (Å, °) top
S—C61.709 (3)N—C21.440 (5)
S—C91.683 (4)N—C31.455 (5)
O—C101.370 (4)N—C11.462 (5)
O—C51.443 (4)
C9—S—C691.74 (18)O—C5—C6110.3 (3)
C10—O—C5119.6 (3)C7—C6—S112.9 (3)
C2—N—C3111.4 (3)C5—C6—S119.4 (3)
C2—N—C1110.1 (3)C8—C9—S112.6 (3)
C3—N—C1111.9 (3)C11—C10—O125.2 (3)
N—C3—C4113.1 (3)O—C10—C19113.3 (3)
O—C5—C4106.5 (3)
Acknowledgements top

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

references
References top

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Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.

North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Tao, X., Bin, X., Zhu, H.-J., Yuan, L. & Wang, J.-T. (2006). Acta Cryst. E62, o5202–o5203.

Tao, M.-L., Li, A.-J., Wang, J., Ma, J. & Liu, D.-Z. (2006). Acta Cryst. E62, o1289–o1290.