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Acta Crystallogr Sect E Struct Rep Online. 2008 March 1; 64(Pt 3): o553.
Published online 2008 February 6. doi:  10.1107/S1600536808003255
PMCID: PMC2960821

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

Abstract

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.

Related literature

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

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Object name is e-64-0o553-scheme1.jpg

Experimental

Crystal data

  • C19H21NOS
  • M r = 311.43
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o553-efi1.jpg
  • a = 9.6140 (19) Å
  • b = 18.578 (4) Å
  • c = 9.905 (2) Å
  • β = 104.53 (3)°
  • V = 1712.5 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.19 mm−1
  • T = 293 (2) K
  • 0.40 × 0.30 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.928, T max = 0.981
  • 3550 measured reflections
  • 3352 independent reflections
  • 2009 reflections with I > 2s(I)
  • R int = 0.038
  • 3 standard reflections every 200 reflections intensity decay: <1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.070
  • wR(F 2) = 0.194
  • S = 1.04
  • 3352 reflections
  • 199 parameters
  • H-atom parameters constrained
  • Δρmax = 0.45 e Å−3
  • Δρmin = −0.32 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1981 [triangle]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808003255/bh2157sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808003255/bh2157Isup2.hkl

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

Acknowledgments

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

supplementary crystallographic information

Comment

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).

Experimental

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

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.

Figures

Fig. 1.
The structure of (I). Displacement ellipsoids are drawn at the 30% probability level.
Fig. 2.
The crystal packing of (I) viewed along [100].

Crystal data

C19H21NOSF000 = 664
Mr = 311.43Dx = 1.208 Mg m3
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 mm1
β = 104.53 (3)ºT = 293 (2) K
V = 1712.5 (6) Å3Block, brown
Z = 40.40 × 0.30 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometerRint = 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

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 Å3
199 parametersΔρmin = −0.32 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

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)

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, °)

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)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BH2157).

References

  • Deeter, J., Frazier, J., Staten, G., Staszak, M. & Weigel, L. (1990). Tetrahedron Lett.31, 7101–7104.
  • Enraf–Nonius (1981). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.
  • 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. [PubMed]
  • 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.

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