organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

aDepartment of Applied Chemistry, College of Science, Nanjing University of Technology, Nanjing 210009, People's Republic of China, and bNanjing Huawei Medicinal Science, Development Co., Ltd., Nanjing 210036, People's Republic of China
*Correspondence e-mail: wjt@njut.edu.cn

(Received 18 December 2007; accepted 30 January 2008; online 6 February 2008)

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[Deeter, J., Frazier, J., Staten, G., Staszak, M. & Weigel, L. (1990). Tetrahedron Lett. 31, 7101-7104.]). For related hydroxy derivatives of the title mol­ecule, see: Tao, Bin et al. (2006[Tao, X., Bin, X., Zhu, H.-J., Yuan, L. & Wang, J.-T. (2006). Acta Cryst. E62, o5202-o5203.]); Tao, Li et al. (2006[Tao, M.-L., Li, A.-J., Wang, J., Ma, J. & Liu, D.-Z. (2006). Acta Cryst. E62, o1289-o1290.]).

[Scheme 1]

Experimental

Crystal data
  • C19H21NOS

  • Mr = 311.43

  • Monoclinic, P 21 /n

  • 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[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.928, Tmax = 0.981

  • 3550 measured reflections

  • 3352 independent reflections

  • 2009 reflections with I > 2s(I)

  • Rint = 0.038

  • 3 standard reflections every 200 reflections intensity decay: <1%

Refinement
  • R[F2 > 2σ(F2)] = 0.070

  • wR(F2) = 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[Enraf-Nonius (1981). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


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
C19H21NOSF(000) = 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 = 10–13°
c = 9.905 (2) ŵ = 0.19 mm1
β = 104.53 (3)°T = 293 K
V = 1712.5 (6) Å3Block, brown
Z = 40.40 × 0.30 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
2009 reflections with I > 2s(I)
Radiation source: fine-focus sealed tubeRint = 0.038
Graphite monochromatorθmax = 26.0°, θmin = 2.4°
ω/2θ scansh = 011
Absorption correction: ψ scan
(North et al., 1968)
k = 022
Tmin = 0.928, Tmax = 0.981l = 1211
3550 measured reflections3 standard reflections every 200 reflections
3352 independent reflections intensity decay: <1%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.070Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.194H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.08P)2 + 0.85P]
where P = (Fo2 + 2Fc2)/3
3352 reflections(Δ/σ)max < 0.001
199 parametersΔρmax = 0.45 e Å3
0 restraintsΔρmin = 0.32 e Å3
Crystal data top
C19H21NOSV = 1712.5 (6) Å3
Mr = 311.43Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.6140 (19) ŵ = 0.19 mm1
b = 18.578 (4) ÅT = 293 K
c = 9.905 (2) Å0.40 × 0.30 × 0.10 mm
β = 104.53 (3)°
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 every 200 reflections
3550 measured reflections intensity decay: <1%
3352 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0700 restraints
wR(F2) = 0.194H-atom parameters constrained
S = 1.04Δρmax = 0.45 e Å3
3352 reflectionsΔρmin = 0.32 e Å3
199 parameters
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)
N0.1370 (3)0.47356 (16)0.2560 (3)0.0517 (8)
C10.2401 (5)0.4470 (2)0.3807 (5)0.0777 (14)
H1A0.27770.40150.36070.117*
H1B0.19290.44120.45470.117*
H1C0.31730.48090.40860.117*
C20.0803 (5)0.5421 (2)0.2843 (5)0.0753 (13)
H2A0.01330.55930.20160.113*
H2B0.15750.57600.31230.113*
H2C0.03220.53670.35770.113*
C30.0227 (4)0.4218 (2)0.2029 (4)0.0517 (10)
H3A0.05590.44610.13830.062*
H3B0.01310.40410.28000.062*
C40.0708 (4)0.3584 (2)0.1295 (4)0.0506 (10)
H4A0.10160.37580.04930.061*
H4B0.15270.33570.19240.061*
C50.0463 (4)0.30309 (19)0.0816 (4)0.0439 (9)
H5A0.07110.28220.16340.053*
C60.0029 (4)0.24339 (18)0.0033 (4)0.0406 (8)
C70.0719 (4)0.17959 (18)0.0465 (4)0.043
H7A0.09970.16490.13920.052*
C80.0976 (4)0.1414 (2)0.0708 (4)0.0542 (10)
H8A0.14470.09730.06200.065*
C90.0482 (4)0.1743 (2)0.1943 (4)0.0510 (10)
H9A0.05800.15560.27850.061*
C100.3039 (4)0.31259 (19)0.0180 (3)0.0403 (8)
C110.3328 (4)0.2446 (2)0.0182 (4)0.0498 (9)
H11A0.25840.21310.05720.060*
C120.4781 (5)0.2225 (2)0.0045 (4)0.0574 (11)
H12A0.49820.17620.02110.069*
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, º) 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—C120.9 (5)
C1—N—C3—C474.6 (4)C10—C11—C12—C130.7 (6)
N—C3—C4—C5176.9 (3)C11—C12—C13—C140.2 (6)
C10—O—C5—C4157.5 (3)C12—C13—C14—C15179.4 (4)
C10—O—C5—C680.0 (4)C12—C13—C14—C191.0 (6)
C3—C4—C5—O53.6 (4)C13—C14—C15—C16178.9 (4)
C3—C4—C5—C6174.6 (3)C19—C14—C15—C160.8 (6)
O—C5—C6—C7154.8 (3)C14—C15—C16—C170.9 (7)
C4—C5—C6—C786.3 (4)C15—C16—C17—C180.7 (7)
O—C5—C6—S30.0 (4)C16—C17—C18—C190.4 (6)
C4—C5—C6—S88.8 (3)C17—C18—C19—C10179.7 (3)
C9—S—C6—C70.6 (3)C17—C18—C19—C140.3 (5)
C9—S—C6—C5176.4 (3)C11—C10—C19—C18179.9 (3)
C5—C6—C7—C8176.3 (3)O—C10—C19—C180.1 (5)
S—C6—C7—C80.8 (4)C11—C10—C19—C140.2 (5)
C6—C7—C8—C90.7 (5)O—C10—C19—C14180.0 (3)
C7—C8—C9—S0.3 (4)C13—C14—C19—C18179.2 (3)
C6—S—C9—C80.2 (3)C15—C14—C19—C180.5 (5)
C5—O—C10—C1110.8 (5)C13—C14—C19—C100.8 (5)
C5—O—C10—C19169.4 (3)C15—C14—C19—C10179.6 (3)
O—C10—C11—C12179.3 (3)

Experimental details

Crystal data
Chemical formulaC19H21NOS
Mr311.43
Crystal system, space groupMonoclinic, P21/n
Temperature (K)293
a, b, c (Å)9.6140 (19), 18.578 (4), 9.905 (2)
β (°) 104.53 (3)
V3)1712.5 (6)
Z4
Radiation typeMo Kα
µ (mm1)0.19
Crystal size (mm)0.40 × 0.30 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.928, 0.981
No. of measured, independent and
observed [I > 2s(I)] reflections
3550, 3352, 2009
Rint0.038
(sin θ/λ)max1)0.616
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.070, 0.194, 1.04
No. of reflections3352
No. of parameters199
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.45, 0.32

Computer programs: CAD-4 Software (Enraf–Nonius, 1981), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Selected geometric parameters (Å, º) 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

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

References

First citationDeeter, J., Frazier, J., Staten, G., Staszak, M. & Weigel, L. (1990). Tetrahedron Lett. 31, 7101–7104.  CSD CrossRef CAS Web of Science Google Scholar
First citationEnraf–Nonius (1981). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationTao, X., Bin, X., Zhu, H.-J., Yuan, L. & Wang, J.-T. (2006). Acta Cryst. E62, o5202–o5203.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationTao, M.-L., Li, A.-J., Wang, J., Ma, J. & Liu, D.-Z. (2006). Acta Cryst. E62, o1289–o1290.  Web of Science CSD CrossRef IUCr Journals Google Scholar

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