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 ▶). For related hydroxy derivatives of the title mol­ecule, see: Tao, Bin et al. (2006 ▶); Tao, Li et al. (2006 ▶).

Experimental

Crystal data

• C₁₉H₂₁NOS

• M _r = 311.43

• Monoclinic,

• a = 9.6140 (19) Å

• b = 18.578 (4) Å

• c = 9.905 (2) Å

• β = 104.53 (3)°

• V = 1712.5 (6) ų

• 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 ▶) 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

• Δρ_max = 0.45 e Å⁻³

• Δρ_min = −0.32 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1981 ▶); cell refinement: CAD-4 Software; 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.

Supplementary Material

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

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 U_iso(H) = 1.5 U_eq(carrier C) for the methyl groups and U_iso(H) = 1.2 U_eq(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

C19H21NOS	F000 = 664
Mr = 311.43	Dx = 1.208 Mg m−3
Monoclinic, P21/n	Melting point = 386–388 K
Hall symbol: -P 2yn	Mo Kα radiation λ = 0.71073 Å
a = 9.6140 (19) Å	Cell parameters from 25 reflections
b = 18.578 (4) Å	θ = 10–13º
c = 9.905 (2) Å	µ = 0.19 mm−1
β = 104.53 (3)º	T = 293 (2) K
V = 1712.5 (6) Å3	Block, brown
Z = 4	0.40 × 0.30 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.038
Radiation source: fine-focus sealed tube	θmax = 26.0º
Monochromator: graphite	θmin = 2.4º
T = 293(2) K	h = 0→11
ω/2θ scans	k = 0→22
Absorption correction: ψ scan(North et al., 1968)	l = −12→11
Tmin = 0.928, Tmax = 0.981	3 standard reflections
3550 measured reflections	every 200 reflections
3352 independent reflections	intensity decay: <1%
2009 reflections with I > 2s(I)

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.070	H-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 reflections	Δρmax = 0.45 e Å−3
199 parameters	Δρmin = −0.32 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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

	x	y	z	Uiso*/Ueq
S	0.03342 (12)	0.25309 (6)	0.17997 (10)	0.0561 (3)
O	0.1693 (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	−0.2777	0.4015	−0.3607	0.117*
H1B	−0.1929	0.4412	−0.4547	0.117*
H1C	−0.3173	0.4809	−0.4086	0.117*
C2	−0.0803 (5)	0.5421 (2)	−0.2843 (5)	0.0753 (13)
H2A	−0.0133	0.5593	−0.2016	0.113*
H2B	−0.1575	0.5760	−0.3123	0.113*
H2C	−0.0322	0.5367	−0.3577	0.113*
C3	−0.0227 (4)	0.4218 (2)	−0.2029 (4)	0.0517 (10)
H3A	0.0559	0.4461	−0.1383	0.062*
H3B	0.0131	0.4041	−0.2800	0.062*
C4	−0.0708 (4)	0.3584 (2)	−0.1295 (4)	0.0506 (10)
H4A	−0.1016	0.3758	−0.0493	0.061*
H4B	−0.1527	0.3357	−0.1924	0.061*
C5	0.0463 (4)	0.30309 (19)	−0.0816 (4)	0.0439 (9)
H5A	0.0711	0.2822	−0.1634	0.053*
C6	0.0029 (4)	0.24339 (18)	0.0033 (4)	0.0406 (8)
C7	−0.0719 (4)	0.17959 (18)	−0.0465 (4)	0.043
H7A	−0.0997	0.1649	−0.1392	0.052*
C8	−0.0976 (4)	0.1414 (2)	0.0708 (4)	0.0542 (10)
H8A	−0.1447	0.0973	0.0620	0.065*
C9	−0.0482 (4)	0.1743 (2)	0.1943 (4)	0.0510 (10)
H9A	−0.0580	0.1556	0.2785	0.061*
C10	0.3039 (4)	0.31259 (19)	0.0180 (3)	0.0403 (8)
C11	0.3328 (4)	0.2446 (2)	−0.0182 (4)	0.0498 (9)
H11A	0.2584	0.2131	−0.0572	0.060*
C12	0.4781 (5)	0.2225 (2)	0.0045 (4)	0.0574 (11)
H12A	0.4982	0.1762	−0.0211	0.069*
C13	0.5882 (5)	0.2673 (2)	0.0627 (4)	0.0603 (11)
H13A	0.6825	0.2515	0.0761	0.072*
C14	0.5612 (4)	0.3372 (2)	0.1027 (4)	0.0496 (10)
C15	0.6714 (4)	0.3854 (3)	0.1646 (4)	0.0677 (13)
H15A	0.7665	0.3704	0.1814	0.081*
C16	0.6431 (5)	0.4528 (3)	0.2002 (5)	0.0746 (13)
H16A	0.7185	0.4836	0.2397	0.089*
C17	0.5021 (5)	0.4765 (2)	0.1781 (4)	0.0655 (12)
H17A	0.4837	0.5230	0.2040	0.079*
C18	0.3900 (4)	0.4320 (2)	0.1186 (4)	0.0481 (9)
H18A	0.2961	0.4485	0.1038	0.058*
C19	0.4161 (4)	0.36147 (19)	0.0798 (3)	0.0409 (8)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
S	0.0651 (7)	0.0585 (6)	0.0425 (5)	−0.0028 (5)	0.0094 (5)	−0.0023 (5)
O	0.0335 (13)	0.0410 (14)	0.0566 (15)	−0.0007 (11)	0.0070 (11)	−0.0068 (11)
N	0.0482 (19)	0.0464 (18)	0.058 (2)	0.0008 (15)	0.0083 (15)	0.0088 (15)
C1	0.065 (3)	0.070 (3)	0.081 (3)	−0.003 (2)	−0.011 (2)	0.018 (3)
C2	0.074 (3)	0.054 (3)	0.095 (4)	−0.003 (2)	0.017 (3)	0.013 (3)
C3	0.041 (2)	0.055 (2)	0.057 (2)	−0.0018 (18)	0.0077 (18)	0.0090 (19)
C4	0.040 (2)	0.055 (2)	0.053 (2)	0.0009 (18)	0.0033 (17)	0.0086 (19)
C5	0.044 (2)	0.045 (2)	0.0414 (19)	−0.0021 (17)	0.0088 (16)	−0.0027 (16)
C6	0.0393 (19)	0.044 (2)	0.0367 (17)	0.0071 (16)	0.0068 (14)	0.0008 (16)
C7	0.043	0.043	0.043	0.000	0.011	0.000
C8	0.060 (3)	0.041 (2)	0.059 (3)	−0.0030 (19)	0.012 (2)	−0.0004 (19)
C9	0.062 (3)	0.047 (2)	0.046 (2)	0.0077 (19)	0.0170 (19)	0.0069 (18)
C10	0.0380 (19)	0.048 (2)	0.0372 (19)	0.0080 (16)	0.0127 (15)	0.0072 (16)
C11	0.055 (2)	0.050 (2)	0.048 (2)	0.0039 (19)	0.0182 (18)	0.0050 (19)
C12	0.069 (3)	0.056 (2)	0.055 (2)	0.022 (2)	0.029 (2)	0.011 (2)
C13	0.050 (2)	0.084 (3)	0.049 (2)	0.025 (2)	0.0167 (19)	0.016 (2)
C14	0.041 (2)	0.070 (3)	0.039 (2)	0.0091 (19)	0.0118 (17)	0.0115 (19)
C15	0.039 (2)	0.103 (4)	0.059 (3)	−0.002 (2)	0.008 (2)	0.005 (3)
C16	0.051 (3)	0.101 (4)	0.067 (3)	−0.019 (3)	0.004 (2)	−0.007 (3)
C17	0.064 (3)	0.060 (3)	0.069 (3)	−0.009 (2)	0.011 (2)	−0.010 (2)
C18	0.046 (2)	0.052 (2)	0.046 (2)	−0.0025 (18)	0.0120 (17)	0.0017 (18)
C19	0.0399 (19)	0.050 (2)	0.0324 (18)	0.0023 (17)	0.0085 (15)	0.0062 (16)

Geometric parameters (Å, °)

S—C6	1.709 (3)	C7—H7A	0.9300
S—C9	1.683 (4)	C8—C9	1.343 (5)
O—C10	1.370 (4)	C8—H8A	0.9300
O—C5	1.443 (4)	C9—H9A	0.9300
N—C2	1.440 (5)	C10—C11	1.360 (5)
N—C3	1.455 (5)	C10—C19	1.425 (5)
N—C1	1.462 (5)	C11—C12	1.419 (5)
C1—H1A	0.9600	C11—H11A	0.9300
C1—H1B	0.9600	C12—C13	1.357 (6)
C1—H1C	0.9600	C12—H12A	0.9300
C2—H2A	0.9600	C13—C14	1.400 (5)
C2—H2B	0.9600	C13—H13A	0.9300
C2—H2C	0.9600	C14—C15	1.406 (6)
C3—C4	1.517 (5)	C14—C19	1.429 (5)
C3—H3A	0.9700	C15—C16	1.345 (6)
C3—H3B	0.9700	C15—H15A	0.9300
C4—C5	1.511 (5)	C16—C17	1.390 (6)
C4—H4A	0.9700	C16—H16A	0.9300
C4—H4B	0.9700	C17—C18	1.369 (5)
C5—C6	1.513 (5)	C17—H17A	0.9300
C5—H5A	0.9800	C18—C19	1.405 (5)
C6—C7	1.410 (5)	C18—H18A	0.9300
C7—C8	1.435 (5)
C9—S—C6	91.74 (18)	C6—C7—H7A	126.0
C10—O—C5	119.6 (3)	C8—C7—H7A	126.0
C2—N—C3	111.4 (3)	C9—C8—C7	114.8 (3)
C2—N—C1	110.1 (3)	C9—C8—H8A	122.6
C3—N—C1	111.9 (3)	C7—C8—H8A	122.6
N—C1—H1A	109.5	C8—C9—S	112.6 (3)
N—C1—H1B	109.5	C8—C9—H9A	123.7
H1A—C1—H1B	109.5	S—C9—H9A	123.7
N—C1—H1C	109.5	C11—C10—O	125.2 (3)
H1A—C1—H1C	109.5	C11—C10—C19	121.4 (3)
H1B—C1—H1C	109.5	O—C10—C19	113.3 (3)
N—C2—H2A	109.5	C10—C11—C12	119.1 (4)
N—C2—H2B	109.5	C10—C11—H11A	120.5
H2A—C2—H2B	109.5	C12—C11—H11A	120.5
N—C2—H2C	109.5	C13—C12—C11	121.4 (4)
H2A—C2—H2C	109.5	C13—C12—H12A	119.3
H2B—C2—H2C	109.5	C11—C12—H12A	119.3
N—C3—C4	113.1 (3)	C12—C13—C14	120.6 (4)
N—C3—H3A	109.0	C12—C13—H13A	119.7
C4—C3—H3A	109.0	C14—C13—H13A	119.7
N—C3—H3B	109.0	C13—C14—C15	122.7 (4)
C4—C3—H3B	109.0	C13—C14—C19	119.4 (4)
H3A—C3—H3B	107.8	C15—C14—C19	117.8 (4)
C5—C4—C3	112.7 (3)	C16—C15—C14	121.8 (4)
C5—C4—H4A	109.1	C16—C15—H15A	119.1
C3—C4—H4A	109.1	C14—C15—H15A	119.1
C5—C4—H4B	109.1	C15—C16—C17	120.5 (4)
C3—C4—H4B	109.1	C15—C16—H16A	119.8
H4A—C4—H4B	107.8	C17—C16—H16A	119.8
O—C5—C4	106.5 (3)	C18—C17—C16	120.5 (4)
O—C5—C6	110.3 (3)	C18—C17—H17A	119.8
C4—C5—C6	112.7 (3)	C16—C17—H17A	119.8
O—C5—H5A	109.1	C17—C18—C19	120.4 (4)
C4—C5—H5A	109.1	C17—C18—H18A	119.8
C6—C5—H5A	109.1	C19—C18—H18A	119.8
C7—C6—C5	127.5 (3)	C18—C19—C10	122.9 (3)
C7—C6—S	112.9 (3)	C18—C19—C14	119.0 (3)
C5—C6—S	119.4 (3)	C10—C19—C14	118.1 (3)
C6—C7—C8	108.0 (3)
C2—N—C3—C4	161.7 (4)	C19—C10—C11—C12	−0.9 (5)
C1—N—C3—C4	−74.6 (4)	C10—C11—C12—C13	0.7 (6)
N—C3—C4—C5	176.9 (3)	C11—C12—C13—C14	0.2 (6)
C10—O—C5—C4	−157.5 (3)	C12—C13—C14—C15	179.4 (4)
C10—O—C5—C6	80.0 (4)	C12—C13—C14—C19	−1.0 (6)
C3—C4—C5—O	53.6 (4)	C13—C14—C15—C16	178.9 (4)
C3—C4—C5—C6	174.6 (3)	C19—C14—C15—C16	−0.8 (6)
O—C5—C6—C7	−154.8 (3)	C14—C15—C16—C17	0.9 (7)
C4—C5—C6—C7	86.3 (4)	C15—C16—C17—C18	−0.7 (7)
O—C5—C6—S	30.0 (4)	C16—C17—C18—C19	0.4 (6)
C4—C5—C6—S	−88.8 (3)	C17—C18—C19—C10	179.7 (3)
C9—S—C6—C7	0.6 (3)	C17—C18—C19—C14	−0.3 (5)
C9—S—C6—C5	176.4 (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—C14	0.2 (5)
C6—C7—C8—C9	0.7 (5)	O—C10—C19—C14	180.0 (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—C18	0.5 (5)
C5—O—C10—C11	−10.8 (5)	C13—C14—C19—C10	0.8 (5)
C5—O—C10—C19	169.4 (3)	C15—C14—C19—C10	−179.6 (3)
O—C10—C11—C12	179.3 (3)